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BREAST: anatomy, imaging techniques & clinical/radiological cases

Published by Ashley Jones Modified over 8 years ago

Presentation on theme: "BREAST: anatomy, imaging techniques & clinical/radiological cases"— Presentation transcript:

BENIGN VS MALIGNANT MASSES IN BREAST ULTRASOUND

Golan.O, Sperber.F, Shalmon.A, Weinstein.I, Gat.A

Breast Mass Linda M. Barney, MD Wright State University.

Pimp Session: Breast By James Lee, MD.

بسم الله الرحمن الرحيم.

Breast Cancer. Introduction Most common female cancer Accounts for 32% of all female cancer 211,300 new cases yearly and rising 40,000 deaths yearly.

Z. OUERGHI; N. DALI; A. MANAMANI A; A. BEN TEKAYA; I. MARZOUK; L

BREAST CANCER UPDATE DETECTION TO DIAGNOSIS

Breast Histopathology : Mammography

MCQs On Breast Imaging:

In The Nam of God.

Breast Neoplasm In this section we will be discussing breast neoplasm.

Breast Imaging Made Brief and Simple

Mammography # 1 Week 2.

Background on: Breast Cancer, X-Ray and MRI Mammography

MAMMOGRAPHY LECTURE #1 rev 2010 Positioning & Anatomy

MAMMOGRAPHY LECTURE #2 rev 2014 Positioning & Anatomy

ASSESSMENT OF BREAST SYMPTOMS/LUMPS Professor P Grantley Gill Specialists Without Borders Seminar in Surgery Rwanda, September 2010.

Elshami M.Elamin, MD Medical Oncologist Central Care Cancer Center Wichita, KS, USA

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Case Presentation on Locally Advanced breast Cancer

Related Papers

European Respiratory Journal

Annelies Rappaport

International Journal of Women's Health

Nicole Sandhu

Although much emphasis has been placed on the primary presentations of breast cancer, little focus has been placed on how systemic illnesses may affect the breast. In this article, we discuss systemic illnesses that can manifest in the breast. We summarize the clinical features, imaging, histopathology, and treatment recommendations for endocrine, vascular, systemic inflammatory, infectious, and hematologic diseases, as well as for the extramammary malignancies that can present in the breast. Despite the rarity of these manifestations of systemic disease, knowledge of these conditions is critical to the appropriate evaluation and treatment of patients presenting with breast symptoms.

Diagnostic Histopathology

Sarah Pinder

IOSR Journals

Background: Benign breast ds (BBD) are common disease affecting woman mainly. These can be diagnosed by triple assessment including clinical examination, radiological imagings, and a pathological examination. Majority of the benign lesions are not associated with an increased risk for subsequent breast cancer but some may have increased risk of malignancy like atypical hyperplasia. The main problem from women’s patient of view is fear that such a lump may be a cancer. Unlike breast cancer, benign breast diseases have often been difficult to understand, in part due to variety of names that have been used to describe the various conditions. So that clinician requires in-depth knowledge to give clear explanation about breast diseases. Making an early diagnosis and planning the treatment during initial consultations, helps in alleviating unnecessary anxiety about breast cancer and unnecessary long term follow up can be avoided. So, the need for study is to analyze the spectrum of benign breast disease. Method: A total 85 patients diagnosing as benign breast diseases under the inclusion criteria were studied during the period of Oct 2014 to March 2016; in the Dept of Surgery at People’s hospital of People’s college of medical science and research center, Bhopal. Our study objectives were A. To describe the spectrum of Benign Breast Diseases with Respect to Age of incidence, Social Demography, Duration of Symptoms, Site of lumps, Clinical features specific to conditions. B. To diagnose clinically and cytologically (FNAC) Suitable patients with benign breast disease and provide either conservative or operative treatment. C. To do histopathological examination of excised specimen for the comparisons and confirmation of cytological and clinical diagnosis. Result: Fibro adenoma was the most common benign lesion encountered (65.9%) followed by Breast Abscess 18.8% disease. Fibro adenoma was presented most often in the second and third decade (75%). Lump in the breast was the commonest presentation of BBD, Lump and Mastalgia was the second commonest symptom of BBD. There was a slight preponderance of lesions in the right breast (45.9%) as compared to left breast (44.7%), shown to be significant. Most of patients belong to middle class. 100% 0f the patients were in pre menopausal group. Majority (45.9%) of lesions were of the size 2-5 cms, 31.8% were between 6-10 cms FNAC highly reliable for fibro adenoma than for other lesions. All fibro adenomas willing for surgical procedure were managed by simple excision than follow up. All 16 cases of Breast Abscess underwent incision and drainage and simple mastectomy was done in phylloide tumors. Conclusion: In the present study BBD occupy majority of total breast diseases. Fibro adenoma was the most common benign lesion (65.9%). FNAC was highly accurate and was highly reliable for fibro adenoma than for other lesions. Triple test is a prerequisite for determining management. However all fibro adenomas willing for surgical procedure were managed by simple excision than follow up. Conservative approach is acceptable in young patients, who choose conservative management, need to be informed about the limitation of the test, advised for proper follow up, and must be assessed properly if there are symptoms and clinical changes. Breast self examination should be emphasized as a part of female adult education.

Siniša Franjić

In most women, breast pain is not severe and disappears very quickly on its own. Severe pain, which is rare, can be relieved with medication. Benign breast diseases are common in young and older women, and malignant breast diseases most commonly occur around and after menopause. Although much rarer than benign changes, breast cancers are the most common cancers in women and represent a significant health problem. When she feels pain in her breast, the woman immediately thinks she has got breast cancer. Pain is not always a symptom of cancer. This paper discusses breast cancer, as the most common type of cancer in women, but also some other breast diseases that are not so common.

The Western journal of medicine

william goodson

Sushil Kachewar

Purpose: Cystic breast lesions are a common finding in young as well as elderly females. Although, mostly benign; they can at times be malignant too. Timely diagnosis is possible with help of Fine needle aspiration cytology (FNAC). This study was carried out with the aim of studying the panorama of various cystic breast lesions on FNAC in our setup. Materials and Methods: This was a four year prospective study carried out from May 2010 to January 2014. Cystic nature of breast mass was confirmed by palpation and by sonomammography. FNAC was then performed and the smears were stained with MGG and Papanicolaou stain. Results: Out of the 72 cases that were diagnosed to be cystic breast lesions clinically or on sonomammography, 64 were found to be benign and 08 were found to be malignant on FNAC. Retrospective imaging correlation of the 08 cystic cases revealed that they were of complex cystic nature and had either thick septae(03), solid areas (04) or dense contents (01) within. This in...

Scholar Science Journals

Background: Study of pattern of benign breast disease is a challenge due to variants in occurrence and presentation in different age groups and different geographical areas. The objective is to study the clinical profile and pattern of benign breast disease and its pathological correlation. Methods: This is a prospective study of females with breast disease presenting to surgery department over a period of one year. This survey was mainly meant for studying the age distribution, to evaluate the different types of benign diseases of the breast, their mode of clinical presentation and pathology and to evaluate the various modes of management for different types of Benign Breast Diseases. Patients with obvious malignancy and males were excluded from the study. Results: A total of 100 females were included in the study. Fibroadenoma (37%) and fibroadenosis (23%) were the commonest diseases,both presenting mostly at 21-30years of age. Left side involvement was most common. The commonest presentation was breast lump which comprised 84 (84%) cases, out of which 26 (26%) had associated complaints like breast pain and nipple discharge. Conclusion: Benign breast diseases are common problems of 2nd and 3 rd decade in females and raises considerable fear of malignancy. The patients of BBDs generally present with one or more of these complaints – breast lump, breast pain or nipple discharge. All the patients with discrete breast lumps should undergo a triple assessment to make an early diagnosis.

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Disclosure of Affiliations and Significant Relationships All faculty and activity planners participating in NCCN continuing education activities are expected to disclose any conflict(s) of interest related to the content of their presentation(s) as defined by the ACCME's and ANCC's Standards for Commercial Support. All faculty presentations have been reviewed for adherence to the ACCME's Criterion 7: The provider develops activities/educational interventions independent of commercial interests (SCS 1, 2 and 6) by experts on the topics.

Anubha Bharthuar, MD

Hematology-Oncology Fellow, Roswell Park Cancer Institute, Buffalo, New York

Disclosure: Dr. Bharthuar has disclosed that she has no financial interests, arrangements, or affiliations with the manufacturer of any products or devices to be discussed in this activity or who may financially support the activity.

Case Presentation: Management of Metastatic Breast Cancer

Authors: Anubha Bharthuar, MD
THIS ACTIVITY HAS EXPIRED FOR CREDIT

Target Audience and Goal Statement

This educational activity is designed to meet the needs of physicians, nurses, and other clinical professionals who manage patients with cancer.

The goal of this program is to provide participants with increased knowledge regarding the treatment of patients with breast cancer.

Upon completion of this activity, participants should be able to:

Describe the staging work-up for each stage of breast cancer
Identify the role of prognostic markers in breast cancer
Describe the precepts of surgery and radiation in the management of stage 0, I, II, and III breast cancer
List the current recommendations for hormonal, biologic, and cytotoxic agents as adjuvant therapy for stage I, II, and III breast cancer
Define the role of preoperative therapy in stage II and III breast cancer
Differentiate agents available for the treatment of advanced or recurrent breast cancer including chemotherapy, biologic therapy, and hormonal therapy

Disclosures

Accreditation statements, for physicians.

The National Comprehensive Cancer Network (NCCN) is accredited by the Accreditation Council for Continuing Medical Education to provide continuing education for physicians.

NCCN designates this educational activity for a maximum of 2.5 AMA PRA Category 1 Credit(s)™ . Physicians should only claim credit commensurate with the extent of their participation in the activity.

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Approval as a provider refers to recognition of educational activities only and does not imply ANCC Commission on Accreditation or PA Nurses approval or endorsement of any product.

This activity is approved for 2.5 contact hours.

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Anubha Bharthuar, MD:

I am going to be presenting a clinical vignette. We are going to ask your opinion about management, and then we will see how the NCCN guidelines will apply to our patient.

We have a 63-year-old woman. She is postmenopausal. She is a hairdresser by profession and does not have any children. There is no significant family history of breast cancer. She presented earlier this year with a right breast mass measuring 10 cm into 8 cm. She also had some abdominal discomfort, anorexia, and some abdominal swelling that had been present for about a couple of weeks.

The breast mass had actually been present for about 2 years. It had been gradually increasing in size. Unfortunately, she did not have insurance and, therefore, did not seek medical attention.

On her laboratory data, there was normal complete blood count (CBC) and normal metabolic profile. Her liver function tests (LFTs) were normal, except for an elevated alkaline phosphatase and an elevated CA 27.29.

She underwent right breast biopsy. It was a Grade 1 invasive lobular carcinoma, strongly ER-positive (Allred score of 8), strongly PR-positive (Allred score of 7), and HER2-negative.

She underwent extensive imaging workup. She had CT scans of the chest, abdomen, and pelvis that showed large amount of ascites. There was evidence of peritoneal carcinomatosis. There were multiple osteolytic lesions in the thoracic and lumbar spine and the skull. The CT scan of the head also showed the skull lesions, but there was no intraparenchymal disease. The bone scan again showed multiple lesions in the right humerus, left acetabulum, right trochanter, cervical spine, and skull. She underwent an abdominal paracentesis where 7 liters of fluid were drained, and it was positive for malignant cells.

With that, we come to the question. What is the best initial management for our patient? Let me remind you, she is 63. She is postmenopausal. She has strongly ER-/PR-positive disease, peritoneal carcinomatosis, skull lesions, and multiple bone lesions.

Is the right answer, AIs with zoledronic acid? Is it tamoxifen with zoledronic acid? Cyclophosphamide plus docetaxel plus zoledronic acid? Capecitabine plus zoledronic acid? Or paclitaxel plus bevacizumab plus zoledronic acid?

As we can see, there is some variation in response. Most people chose A, which was AIs plus zoledronic acid. Some people did choose chemotherapy. The correct answer here is actually A, because, even though she has this large amount of ascites and peritoneal carcinomatosis, she does not truly qualify for a visceral crisis. She is strongly ER- and PR-positive, and she has a slow rate of growth, so AIs plus zoledronic acid is appropriate. We will go over the NCCN guidelines and see how she fits into the guidelines.

Despite the strides that we have made in early diagnosis of breast cancer, about 5% of patients still have metastatic disease at presentation. Even for those who do undergo treatment for earlier stages, depending on the stage, there is a high risk of relapse, especially in the first 5 years. However, there have been case reports of systemic relapse even up to 30 years.

The outcome is a median survival of about 28 months and a 5-year survival of 22%. One of the treatment objectives, some of which Dr. Burstein already went over, is to confirm the diagnosis, and this is where doing a biopsy is most useful. Of course, we also have to do the imaging workup, and a positron emission tomography (PET) scan is really not recommended by the NCCN front-line unless you have equivocal or suspicious findings. In those situations, again, a biopsy would probably be more useful to give you accurate staging.

Then you have to discuss the treatment goals. Our patient was a hairdresser. For her, not losing her hair was really important. What are the other comorbidities? What is their age? What is their performance status? And, of course, what is the tumor biology? Incorporating all of this is also where estimation of prognosis comes into play. There are both patient- and disease-related factors.

If you go over the guidelines, our patient has ER-/PR-positive disease that is HER2-negative. She has not had any prior endocrine therapy. She is postmenopausal and the appropriate recommendation, per NCCN, is AI or an antiestrogen.

Is one necessarily better than the other? Playing into that is the Arimidex Study Group, which was published as 2 different trials. One was a North American trial, which looked at patients in Canada and the US, and the other was the TARGET trial, which looked at patients in Europe, South America, Australia, New Zealand, etc.

The TARGET (Tamoxifen or Arimidex Randomized Group Efficacy and Tolerability) trial had 668 patients. They were followed for about 19 months. There was really no difference between the anastrozole and the tamoxifen arms as regards time to progression. There was also a similar overall response of about 32%. In the anastrozole arm, there was decreased risk of thromboembolic events and vaginal bleeding.

It is important to note here that in this study, only about 50% of the patients really had documented ER-/PR-positive disease, and, in the North American trial, almost 90% of the patients had documented ER-/PR-positive disease.

The North American trial initially was supposed to accrue again 660 patients; however, they stopped accrual once the TARGET trial had finished accrual, so they only had 353 patients in this trial. The objective response was almost similar, 21% versus 16% in the anastrozole versus tamoxifen arms, respectively. However, they found a statistically significant difference in the time to progression in the anastrozole arm of 11.1 months versus 5.6 months in the tamoxifen arm.

They published the combined results. In the overall group, there was no difference, but when they categorized according to documented ER- and PR-positivity, there was a 4-month difference between the anastrozole and tamoxifen arms.

Although anastrozole or other AIs are considered slightly superior to tamoxifen, the differences are modest. Therefore, both would be appropriate, though perhaps an AI would be slightly more appropriate for our patient.

Endocrine therapy in premenopausal women depends on what they have had before. If they are within 1 year of completion of endocrine therapy, the first choice would be ovarian suppression or ablation and then treatment as per a postmenopausal woman. If they have not had that then options include ovarian suppression, ovarian ablation, tamoxifen plus ovarian suppression, or tamoxifen alone.

For postmenopausal women, their options include AIs, both nonsteroidal and steroidal; tamoxifen; and the pure antiestrogen fulvestrant, which especially in the second-line has been proven to be equivalent to steroidal exemestane. The other options include megestrol and just pure estrogens.

A point to remember here is that most patients who have hormone-sensitive disease will have a longer disease-free survival and a slower rate of progression. They are likely to have fewer metastatic sites and less likelihood of having visceral disease. Those that relapse within 12 months off prior adjuvant therapy, of course, are not going to follow this path, and they are going to do poorly.

Another important point here is that 5% to 10% of patients who receive tamoxifen therapy can have a tumor flare, where there is increased bone pain, hypercalcemia, and maybe a slight increase in size of tumor. It is important to remember that these should actually subside in the next couple of weeks, and these are actually the patients who are going to have a prolonged remission on endocrine therapy.

As regards going from first-line to second-line therapy, it depends on what they have had before. Once they have progressed beyond 3 lines of therapy, they kind of become endocrine-resistant, and that is the time to look at the chemotherapeutic options.

For patients who have hormone-refractory metastatic breast cancer and for those who have ER-/PR-negative metastatic breast cancer, there are preferred single agents and, of course, preferred combination agents that I will show you in these slides. They include anthracyclines, taxanes, antimetabolites, and other microtubule inhibitors such as vinorelbine. There are other single agents; and the preferred agent with bevacizumab is paclitaxel.

The preferred chemotherapy combination regimens are listed here. The one that you will choose for your patient will depend on the therapy she has had before and how long she has had this therapy, because, obviously, if you have already given anthracyclines and paclitaxel to your patient in the adjuvant setting, you are less likely to use that when they have metastatic disease.

Other combinations are ixabepilone plus capecitabine. For patients who have HER2-positive disease, you are going to use trastuzumab with the following combinations. Most recommended is paclitaxel with or without carboplatin. If they have had exposure to trastuzumab before, options include lapatinib, capecitabine, trastuzumab with other first-line agents, and trastuzumab with capecitabine or trastuzumab plus lapatinib.

The question that comes up is, is combination chemotherapy really better than single-agent chemotherapy?

There was a Cochrane database review published in 2005 that looked at 28 trials with almost 6000 women. The combination chemotherapy did prove superior in terms of overall survival and time to progression; however, there was statistically significantly higher toxicities in the patients who received combination chemotherapy that included anorexia, nausea/vomiting, leukopenia, and hair loss.

Another point that comes up with the Cochrane database review is that most of these trials did not include quality of life. They did not look at sequential single-agent chemotherapy as compared with combination therapy. Therefore, the guidelines still state that it is preferable to use single-agent chemotherapy, unless you are looking for rapid symptom control or rapid disease control. Furthermore, when you use single-agent chemotherapy, it is easier to dose adjust, depending on the side effects that the patient experiences.

It is important to remember that chemotherapy here is palliative. We are not going for a cure, so it is important to use those options that will provide the best quality of life to your patient.

The next point that comes up is that our patient had extensive bone disease. About two-thirds to three-fourths of your patients with metastatic breast cancer are going to have bone disease. Between 50% and 75% of them are going to have a skeletal-related event that includes pain, surgical intervention for the skeletal lesions, radiation therapy for the skeletal lesions, or a cord compression. Therefore, the recommendation is to use a bisphosphonate, and this would apply regardless of what their ER/PR status or their HER2 status is.

Our patient did get zoledronic acid. The other agent that is approved here in the US is pamidronate. The zoledronic acid is 4 mg given IV given every 3 weeks. The pamidronate is 90 mg IV given over 2 hours. In European countries, ibandronate and clodronate have been approved; however, they are not available in the United States.

There are certain considerations for older women with metastatic breast cancer. Most of them have more indolent tumors; therefore, endocrine therapy is preferred. It is important to remember that older patients are going to be at a higher risk for toxicities, because they have decreased bone marrow tolerance, a higher rate of mucositis and diarrhea, and are especially at increased risk for cardiac toxicity.

These patients are also more likely to have other comorbid conditions. They may have evidence of hepatic insufficiency or renal insufficiency that will require dose reductions, depending on which drug you are deciding to use.

Single agents that have been successfully given to older women include capecitabine, vinorelbine, and taxanes. Usually, one is a little bit more reluctant to use an anthracycline because of the risk for cardiac toxicity. Targeted agents include trastuzumab and lapatinib if they have HER2-positive disease, and bevacizumab can be successfully used without increased risk of toxicities. Bisphosphonates are strongly recommended if they have evidence of skeletal lesions.

What’s new on the horizon? There are the PARP inhibitors that were shown by Dr. Burstein: the oral olaparib in BRCA1 and BRCA2 disease, and BSI-201 that was used in combination with gemcitabine and carboplatin and showed significant response in patients with triple-negative breast cancer.

Another thing that is being looked at in certain clinical trials currently is circulating tumor cells, because it is hypothesized that they may be an earlier marker of activity than traditional imaging; therefore, if we incorporate these into our management practices, will it make a difference in clinical outcome? It may be a predictor of progression-free or overall survival.

There are certain novel agents that are being looked at for bone disease. The ones that are being actively pursued are the RANK ligand inhibitors, and more specifically denosumab. As you know, at ASCO 2009, they showed results of patients with different solid tumors and multiple myeloma who, despite bisphosphonate therapy, had an elevated urinary N telopeptide. Urinary N telopeptide is a marker of bone marrow turnover and increased bone marrow resorption, and that is what is most striking in patients who have skeletal disease. With the use of denosumab, it was shown that, even for those who had already received bisphosphonate therapy and had an elevated urinary N telopeptide, this marker had become normalized.

More recently, in September at the ESMO meeting, they showed a phase III clinical trial where denosumab was compared with zoledronic acid. There was a 5-month difference in the first skeletal-related event, showing that this is probably going to be more important in the future.

There are a lot of exciting things that are going to come up, and it is possible that the guidelines are going to change. But what is important here is that there is no fixed clinical pathway that you are going to follow for patients with metastatic breast cancer. You can legitimately pursue different treatment options. You just have to take into account the clinical scenario and your patient’s preferences.

As an aside, our patient actually did not do very well with endocrine therapy. About 6 months into endocrine therapy, she developed liver lesions as well as lesions in the lung and had to be started on chemotherapy. The choice then was gemcitabine.

Disclaimer The material presented here does not necessarily reflect the views of MedscapeCME or companies that support educational programming on www.medscapecme.com. These materials may discuss therapeutic products that have not been approved by the US Food and Drug Administration and off-label uses of approved products. A qualified healthcare professional should be consulted before using any therapeutic product discussed. Readers should verify all information and data before treating patients or employing any therapies described in this educational activity.

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Breast cancer.

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Last Update: February 25, 2024 .

Continuing Education Activity

Breast cancer is the most common cancer diagnosed in women, accounting for more than 1 in 10 new cancer diagnoses annually, and is the second most common cause of cancer death among women worldwide. The risk factors for breast cancer are well established, and risk reduction plays a vital role in reducing the incidence of breast cancer. Breast cancer typically evolves silently, usually discovered on routine screening in the Western world. Without screening, breast cancer is often detected as a palpable breast mass. Surgery, radiation, chemotherapy, and immunotherapy are used in combination to treat breast cancer, depending on the stage and type of tumor. Improvements in these treatment modalities have resulted in significant improvements in overall survival and patient-reported outcomes.

This activity for healthcare professionals is designed to enhance the learner's competence when managing breast cancer, equipping them with updated knowledge, skills, and strategies for timely identification, effective interventions, and improved coordination of care, leading to better outcomes for patients outcomes and reduced morbidity.

Identify the risk factors for breast cancer.
Differentiate the various types of breast cancer.
Compare the recommended treatment options for breast cancer.
Strategize with interprofessional team members to improve patient care and optimize outcomes for patients affected by breast cancer.
Introduction

Breast cancer is the most common cancer diagnosed in women and the second most common cause of death from cancer among women worldwide. [1] The breasts are paired glands of variable size and density that lie superficial to the pectoralis major muscle. They contain milk-producing cells arranged in lobules; multiple lobules are aggregated into lobes with interspersed fat. Milk and other secretions are produced in acini and extruded through lactiferous ducts that exit at the nipple. Breasts are anchored to the underlying muscular fascia by Cooper ligaments, which support the breast. [2]

Breast cancer most commonly arises in the ductal epithelium (ie, ductal carcinoma) but can also develop in the breast lobules (ie, lobular carcinoma). Several risk factors for breast cancer have been well described. In Western countries, screening programs have succeeded in identifying most breast cancers through screening rather than due to symptoms. However, in much of the developing world, a breast mass or abnormal nipple discharge is often the presenting symptom. [3] Breast cancer is diagnosed through physical examination, breast imaging, and tissue biopsy. Treatment options include surgery, chemotherapy, radiation, hormonal therapy, and, more recently, immunotherapy. Factors such as histology, stage, tumor markers, and genetic abnormalities guide individualized treatment decisions. [1]

Breast Cancer Risk Factors

Identifying factors associated with an increased incidence of breast cancer development is important in general health screening for women. Risk factors for breast cancer include: [4] [5] (see Image. Breast Cancer Risk Factors)

Age : The age-adjusted incidence of breast cancer continues to increase with the advancing age of the female population.

Gender : Most breast cancers occur in women.

Personal history : A history of cancer in one breast increases the likelihood of a second primary cancer in the contralateral breast.

Histologic : Histologic abnormalities diagnosed by breast biopsy constitute an essential category of breast cancer risk factors. These abnormalities include lobular carcinoma in situ (LCIS) and proliferative changes with atypia.

Family history and genetic mutations : First-degree relatives of patients with breast cancer have a 2-fold to 3-fold excess risk for the development of the disease. Genetic factors cause 5% to 10% of all breast cancer cases but may account for 25% of cases in women younger than 30 years. BRCA1 and BRCA2 are the most important genes responsible for increased breast cancer susceptibility.

Reproductive : Reproductive milestones that increase a woman’s lifetime estrogen exposure are thought to increase breast cancer risk. These include the onset of menarche before age 12, first live childbirth after age 30 years, nulliparity, and menopause after the age of 55.

Exogenous hormone use : Therapeutic or supplemental estrogen and progesterone are taken for various conditions, with the most common scenarios being contraception in premenopausal women and hormone replacement therapy in postmenopausal women.

Other : Radiation, environmental exposures, obesity, and excessive alcohol consumption are some other factors that are associated with an increased risk of breast cancer.

Epidemiology

Invasive breast cancer remains the most common cancer among women worldwide, accounting for approximately 11.7% of new cases in 2020. [6] In the US, 1 in 8 women and 1 in 1000 men will develop breast cancer during their lifetime. [7] [8] [9] The incidence rate of breast cancer increases with age, from 1.5 cases per 100,000 in women aged 20 to 24 to a peak of 421.3 cases per 100,000 in women aged 75 to 79; 95% of new cases occur in women aged 40 years or older. The median age of women at the time of breast cancer diagnosis is 61 years.

A rapid increase in the incidence of breast cancer was noted until 2000, after which the incidence began to decline. More significant decreases occur in women younger than 50 years. With early detection and significant advances in treatment, breast cancer death rates have decreased over the past 25 years in North America and parts of Europe. In the US, breast cancer-related mortality dropped by 43% from 1980 to 2020. However, in many African and Asian countries (eg, Uganda, South Korea, and India), breast cancer incidence and death rates continue to rise. [6] Even within the US, marked disparity exists in detection and survival rates based on socioeconomic status and race. Although the incidence is highest among non-Hispanic whites, the mortality rate is significantly higher among African Americans. According to the American Cancer Society (ACS), breast cancer rates among women from various racial and ethnic groups are as follows: [10]

Non-Hispanic white: 128.1 in 100,000
African American: 124.3 in 100,000
Hispanic/Latina: 91.0 in 100,000
American Indian/Alaska Native: 91.9 in 100,000
Asian American/Pacific Islander: 88.3 in 100,000
Pathophysiology

Most breast cancer is sporadic (90%-95%), with only 5% to 10% of patients having an identifiable genetic mutation. [11] BRCA 1 and 2 are the most common associated genetic conditions. Invasive ductal and invasive lobular carcinoma are the most common pathologic forms of invasive breast cancer. Carcinogenesis occurs due to a complex interplay of genetic and environmental risk factors, hormonal influences, and patient-related factors. The pathogenesis, treatment, and prognosis are closely associated with the following molecular subtypes of breast cancer:

Luminal A : Hormone receptor-positive, human epidermal growth factor receptor (HER)-2 negative
Luminal B : Hormone receptor-positive, HER-2 positive
Basal-like : Hormone receptor and HER-2 negative
HER-enriched : HER-2 positive, hormone receptor-negative

Hormone receptor-positive tumors (ie, luminal A and B) tend to be less aggressive, with improved survival rates. [12] HER-2 enriched tumors are more aggressive, with a poor prognosis without targeted therapy. In the era of targeted anti-HER therapy (eg, trastuzumab), the paradigm has shifted. [13] Basal-like tumors are negative for the molecular markers and tend to have a worse prognosis with poor survival rates. [14]

Histopathology

Invasive breast cancer is characterized by the invasion of neoplastic cells beyond the basement membrane that can be morphologically varied, with several subtypes described. All specimens should be tested for hormone receptors (ie, estrogen and progesterone) and HER-2 receptors. (see Image. Breast Estrogen Receptor Staining) Other critical components assessed on the histopathologic exam include tumor grade, pleiomorphism, Ki-67 index, morphology, tumor necrosis, multifocality, and precancerous lesions. The following are the most common histologic types of invasive breast cancer.

Ductal adenocarcinoma : This histologic type comprises 50% to 75% of all invasive breast cancers. Clinically, these tumors are often felt as a breast mass secondary to a significant fibrotic reaction. Microscopically, the lesion arises in the terminal duct-lobular unit with abnormal epithelial cells with varying degrees of atypia. These cells invade the basement membrane. However, there are no pathognomonic histologic features of invasive ductal carcinoma. [1] (see Image. Invasive Ductal Carcinoma).

Lobular carcinoma : Invasive lobular cancer makes up 10% to 15% of breast cancer and tends to permeate the breast in a single-file nature. This results in tumors that typically remain clinically occult, escaping detection on mammography or physical examination until the disease becomes extensive. A discrete mass is seldom palpated. Multifocal tumors and bilateral disease are more common with invasive lobular carcinoma. Characteristically, these tumors stain negative for E-cadherin. [15] (see Image. Pleomorphic Lobular Breast Carcinoma).

Mucinous carcinoma : Also known as colloid carcinomas, these tumors, which make up 2% to 5% of breast cancers, are well-demarcated in older women, typically characterized by mucin production. [16]

Tubular carcinoma : Microscopically characterized by infiltrating cells with minimal atypia that form small glands and tubules, 1% to 2% of breast cancers are among this subtype. [16]

Medullary carcinoma : These aggressive tumors are poorly differentiated and seen more commonly in BRCA mutant and younger patients. [17]

History and Physical

A periodic review of patient history for breast cancer risk assessment is recommended by the American College of Obstetricians and Gynecologists (ACOG). [18] Clinicians can use online assessment tools to help calculate a patient's breast cancer risk. Most breast cancer patients are asymptomatic, and lesions are discovered during routine breast examination or screening mammography. With increasing size, the patient may notice a palpable lump. Breast pain is an unusual symptom that happens 5% of the time. [19] More advanced disease may present with symptoms including peau d'orange, frank ulceration, axillary lymphadenopathy, or signs of distant metastasis. Inflammatory breast cancer, an advanced form of breast cancer, may have clinical features similar to breast abscess (eg, swelling, redness, and other local signs of inflammation). [20] (see Image. Breast Cancer Axillary Lymphadenopathy)

A thorough physical exam is a vital part of the clinical assessment for breast cancer. Both breasts must be examined in the sitting, standing, and supine positions, with the arm abducted, extended, and externally rotated. Palpation Overlying skin changes, nipple discharge, edema, peau d'orange, and ulceration should be noted. (see Image. Clinical Signs of Breast Carcinoma). Careful palpation of the regional lymph node basins for lymphadenopathy is also essential. Although some societies (eg, American Cancer Society) no longer recommend routine clinical breast examinations in asymptomatic, low-risk women as it has not been found to have a significant benefit, ACOG states that routine clinical breast examinations may be offered to these women, though not required. Furthermore, ACOG recommends an interval of every 1 to 3 years for women aged 25 to 39 years, and every year for women >40 years is appropriate if a screening breast examination is performed. However, a clinical breast examination should always be done for high-risk women and symptomatic women. [18] See StatPearls' companion topic, "Breast Examination Techniques," for additional information on clinical breast exams. [21]

Diagnostic Breast Imaging

Mammography is the most commonly used modality for screening and diagnosis of breast cancer. [22] Abnormal findings on mammography include mass lesions, calcifications, or architectural distortion. When identified on screening mammography, diagnostic mammography, which utilizes higher quality imaging with several views, is indicated. Mammography is of limited utility in patients with dense breasts, in younger patients, and in those who cannot tolerate the breast compression that is required. Breast ultrasound or magnetic resonance imaging (MRI) with contrast may be utilized in such cases. Breast ultrasound is similar in sensitivity to mammography and can be used to obtain image-guided biopsy. Though MRI is the most sensitive imaging study, it is time-consuming, has limited availability, and is expensive. [23] Indications for MRI include axillary lymph node disease and an occult primary malignancy, Paget disease, multifocal or bilateral cancers, neoadjuvant chemotherapy treatment response assessment, and high-risk patient screening. [24] (see Image. Breast Mammogram)

Breast imaging findings are classified by their Breast Imaging Reporting and Data System (BI-RADS) category, which correlates imaging findings with their probability of underlying malignancy and recommends a broad treatment strategy. The BI-RADS categories range from 0 to 6. [25]

Tissue Biopsy

Once a suspicious lesion is identified, tissue biopsy with stereotactic core needle biopsy is performed with imaging guidance. [26] [27] [28] Core needle biopsy is superior to fine needle aspiration and should be performed whenever possible. [29] In patients with clinically positive regional lymph nodes, an ultrasound-guided core needle biopsy is performed. Radiographically identifiable markers should be placed during the biopsy to mark the site in both the primary cancer and the lymph node basin to help identify and localize the lesion later. Breast tissue must be sent for a pathologic exam, including hormonal and Herceptin receptor testing.

Staging Imaging

Routine laboratory investigations and imaging for systemic disease are not recommended for operable breast cancer in the absence of symptoms. If associated symptoms are present, an MRI brain, chest CT scan, bone scan, or CT of the abdomen and pelvis may be performed as indicated. Baseline complete blood count and comprehensive metabolic panel, including liver function tests, are indicated if neoadjuvant chemotherapy is planned. For clinically advanced breast carcinoma (eg, inflammatory breast cancer, chest wall or skin involvement, and bulky axillary lymphadenopathy), a chest, abdomen, and pelvis CT along with a bone scan or an FDG-PET scan is often used. [30]

Treatment / Management

Breast cancer treatment is nuanced and based on various factors, including the disease stage, pathology, patient preference, and available resources. In general, breast cancer management approaches are divided into early breast cancer, locally advanced breast cancer, and metastatic breast cancer treatment. [30]

Early Breast Cancer

Early breast cancer includes tumors <5 cm in size without clinically positive lymph nodes. Treatment involves surgery, chemotherapy, radiation, and hormonal therapy, depending on the stage and molecular profile. [30] The modalities used include:

Surgical treatment : Options to excise the primary tumor include breast conservation surgery (eg, partial mastectomy or lumpectomy) or a total mastectomy.
Axillary lymph node management : Sentinel lymph node biopsy is performed during the operation. Without extranodal extension, no further axillary surgery is required if 2 to 3 axillary lymph nodes are microscopically positive. A completion axillary dissection or axillary radiation is indicated in patients with >3 positive lymph nodes or extranodal extension.
In hormone receptor-positive tumors, the decision to initiate chemotherapy is based on risk stratification using genomic analysis of the primary using commercially available kits (eg, Oncotype Dx). High-risk patients benefit from chemotherapy in addition to hormonal therapy.
All HER2-positive patients with tumors >1 cm should receive anti-HER2-directed therapy.
All triple-negative patients with tumors > 1 cm should receive systemic chemotherapy.
Radiation : Patients undergoing breast conservation surgery (BCS) must receive radiation to the breast with a boost to the tumor bed to reduce local recurrence. Patients who undergo mastectomy do not need breast radiation, except in certain circumstances (eg, >5 cm tumor, chest wall invasion, skin involvement, multifocal tumor, ≥4 positive nodes).
Hormonal therapy : Anti-estrogen or aromatase inhibitor therapy is indicated in all hormone receptor-positive patients.

Up-front chemotherapy (ie, neoadjuvant therapy) has been increasingly used in early-stage triple-negative and HER2-positive tumors. Delivering the chemotherapy up-front has several advantages, including allowing response assessment, a greater likelihood of completing chemotherapy, and an increased likelihood of breast conservation therapy; therefore, clinicians will likely use this strategy more extensively. [31] [32]

Locally Advanced Breast Cancer (LABC)

Locally advanced breast cancer (LABC) primarily consists of tumors larger than 5 cm or those with clinically positive lymph nodes. Most patients with LABC will receive some form of neoadjuvant therapy, with adjunct surgery and radiation therapy. Patients with LABC typically undergo a breast MRI at baseline. The primary tumor and the involved lymph nodes must have radiographically detectable markers placed before initiation of chemotherapy, as tumors can shrink and disappear after therapy. [30]

Chemotherapy regimens vary based on the tumor pathology (eg, hormone receptor-positive, HER2-positive, or triple-negative), the patient's age and physical status, and locally available resources. The goals of upfront chemotherapy are to reduce the size of the primary, eradicate micrometastatic disease, and assess disease biology based on the responsiveness of the tumor to chemotherapy. After completion of the chemotherapy regimen, breast and axillary imaging are repeated to assess response to chemotherapy and determine further management, including:

Surgical treatment : Options to excise the primary tumor include BCS or a total mastectomy. Contraindications to BCS include large tumors, chest wall or skin involvement, multifocal disease, inability to receive radiation, and large tumor size to breast size ratio.
Axillary lymph node management : In patients with a clinically positive axilla at diagnosis, an axillary dissection is always performed, regardless of the response of the tumor to neoadjuvant chemotherapy. In patients with a clinically negative axilla, sentinel lymph node biopsy is performed at the time of surgery. At least 3 lymph nodes should be harvested using a dual-tracer technique. Patients with residual disease should undergo a completion axillary dissection or axillary radiation.
Systemic chemotherapy : Patients with residual disease after systemic chemotherapy may benefit from additional chemotherapy based on the molecular characteristics.
Radiation therapy : The indications for radiation are similar to BCS.
Hormonal therapy : Anti-estrogen or aromatase inhibitor therapy is indicated in all hormone receptor-positive patients.

Metastatic Breast Cancer

Metastatic breast cancer is managed primarily with systemic therapy. Chemotherapy, targeted therapy, immunotherapy, and hormonal therapy are all options, depending on the molecular profile and patient fitness. Palliative radiation may be used in controlling bulky primary disease and metastases to the brain, bone, and lung. Surgery is not recommended except for symptom control and palliative therapy. [33]

Differential Diagnosis

The differential diagnosis for breast cancer includes the following:

Mastitis or breast abscess: Mastitis can be confused with inflammatory breast cancer. Inflammation or cellulitis that does not respond to antibiotics should be evaluated further.
Fat necrosis: Traumatic fat necrosis can harden and present as a mass that mimics breast cancer.
Fibroadenoma: Fibroadenomas >2 cm are typically excised to rule out coexisting breast cancer.
Surgical Oncology

Surgery plays a central role in managing breast cancer. [30] With the increased use of highly effective chemotherapy and targeted therapy, operations have become less extensive and morbid, while survival has improved. In current practice, surgery helps manage the primary tumor and provides essential staging information. BCS can be performed in most patients with tumors <5 cm, provided that the breast is large enough for a cosmetic result. Mastectomy is indicated in large primary tumors, tumors invading the skin or chest wall, multifocal cancers, inflammatory breast cancer, and in patients who are unable to have radiation. Sentinel lymph node biopsy is a vital staging procedure in patients with a clinically negative axilla. Those with 1 to 3 positive lymph nodes on sentinel node biopsy and without gross extranodal extension can safely avoid axillary lymph node dissection. Patients with clinically positive axillary nodes typically require an axillary lymph node dissection. [34] The following are the primary operations performed for breast cancer and in the axilla.

Partial Mastectomy or Lumpectomy

Partial mastectomy or lumpectomy involves the excision of a portion of the breast tissue with a margin of healthy tissue. [35] The incision can vary based on the location of the tumor and the desired cosmesis. Typically incisions are circumareolar, radial, or along the breast skin crease. Partial mastectomy is the centerpiece of BCS, allowing for the conservation of most of the breast. The cosmetic results depend on the amount of breast tissue removed compared to the remaining breast tissue and the nipple preservation. For nonpalpable lesions, the lesion must be localized preoperatively, usually with a wire or radioactive seed, to ensure the removal of the entire tumor.

Simple Mastectomy and Nipple-sparing Mastectomy

Simple mastectomy involves excision of the entire breast and nipple-areola complex. [34] The underlying pectoralis major fascia is removed as well. The amount of skin preserved can vary based on whether reconstruction is planned and on the type of reconstruction. A nipple-sparing mastectomy is a relatively recent modification of the simple mastectomy in which the nipple-areolar complex is spared, and the breast tissue is excised through a small circumareolar incision. The cosmetic results of reconstruction are superior to a conventional mastectomy, with a slightly increased but acceptably poorer oncologic outcome.

Modified Radical Mastectomy

Modified radical mastectomy combines the simple mastectomy technique with axillary lymph node dissection. The mastectomy incision is usually extended for the axillary contents to be removed. Radical mastectomy, which includes the removal of the pectoral muscles and sacrifice of the nerves, is seldom performed.

Axillary Sentinel Lymph Node Biopsy and Axillary Lymph Node Dissection

The axillary lymph nodes drain much of the ipsilateral breast and are divided into 3 levels by the pectoralis minor muscle. A radiotracer or blue dye is injected near the primary, and 1 to 3 lymph nodes in the axilla that have the highest uptake of radiotracer or are blue are excised. When done with a lumpectomy, the same incision can sometimes be used, or a separate incision at the axillary hairline may be required. Axillary lymph node dissection involves the removal of all the fibrofatty and lymphoid tissue in levels 2 and 3, with preservation of the long thoracic nerve and thoracodorsal nerve. [36] [37]

Radiation Oncology

Radiation therapy has a significant role in local disease control, primarily in the adjuvant setting, but may also be used for palliative therapy. In early-stage breast cancer, adjuvant radiotherapy has been shown to reduce the risk of breast recurrent disease by approximately 50%. [38] [39] While adjuvant radiotherapy in early-stage breast cancer has not been shown to improve overall survival, it is an essential part of the breast conservation approach as radiotherapy reduces the risk of recurrence and the need for additional surgery. Modalities to deliver adjuvant radiotherapy include external beam radiation, brachytherapy, or a combination. [40] [41]

Radiation Therapy Delivery Techniques

Accelerated Partial Breast Irradiation

A select number of patients may qualify for Accelerated Partial Breast Irradiation (APBI). The American Society of Radiation Oncologists (ASTRO) appropriateness guidelines consist of suitable, cautionary, and unsuitable candidates for this treatment. [42] APBI may be delivered using surgically implantable single or multi-channel channel catheter devices. These implants rely on an Ir-192 HDR afterloader to deliver conformal radiotherapy via brachytherapy. (See StatPearls' companion topic, "Brachytherapy," for additional information.) Alternatively, APBI may be delivered using external beam radiotherapy. In this case, an implantable device is unnecessary, but surgical clips, coils, or 3D implantable markers may be used to delineate the surgical cavity for external beam radiotherapy planning. The dosing is 34 to 38.5 over 10 fractions delivered twice a day. The advantage of APBI is that it can be delivered over 1 week as opposed to 3 to 6 weeks with whole breast radiation. However, if the patient opts for APBI delivered via catheter, there may be additional delays as the patient would likely need to return for further surgery. In terms of outcomes, the 10-year cumulative incidence of breast cancer recurrence for patients treated with APBI was 4.6%. [43]

Whole Breast Radiation

Whole breast radiotherapy (WBRT) is a well-studied technique employed in patients with early-stage breast cancer and continues to be the mainstay treatment for many patients. WBRT is delivered in the adjuvant setting either after breast-conserving surgery or after the completion of chemotherapy. The treatment technique is designed to cover all visible breast tissue on CT simulation. This can be safely planned and delivered using a 3D conformal plan. The ipsilateral lung and heart doses are the most important to consider when planning these cases. Dosing varies from 40.05 to 50.4 Gy in 15 to 25 fractions. The 10-year ipsilateral breast recurrence rate in these patients is approximately 3.9%. [43]

An additional radiation dose, a boost, may be given to the surgical cavity upon completion of whole breast radiation. Several randomized trials have demonstrated an improvement with local control. Early-stage breast cancer patients who received a 10 Gy boost to the surgical cavity after whole breast radiation had a 5-year local recurrence rate of 3.6% compared to 4.5% without a boost. The EORTC demonstrated a 10-year local control rate of 6% versus 10% without a boost. [44] The benefit of a radiation boost appears to be confined to younger women aged <60 years. [44] The dosing ranges from 10 to 16 Gy. The boost is not without a cost, as there is a risk of breast fibrosis that may impact cosmesis. The EORTC trial found a 4.4% rate of severe fibrosis in patients receiving a boost compared to 1.6%. [44]

Post-Mastectomy Radiation

Post-mastectomy radiation (PMRT) is indicated in patients with nodal disease after axillary staging, positive margins, and in patients with primary breast tumors >5 cm. PMRT may also be considered in patients with high-risk pathologic features, including central or medial tumors ≥2 cm with either lymphovascular invasion, grade 3, or hormone receptor-negative. Coverage includes the chest wall with or without regional lymphatics. PMRT has been extensively studied in several prospective trials. The Danish 82bc trials investigated the benefit of PMRT in premenopausal and postmenopausal high-risk patients (ie, >5 cm, locally invasive, or node-positive). The study demonstrated long-term breast cancer mortality, locoregional recurrence, and overall survival benefits. [45] The 30-year follow-up data continues to show overall survival (19% versus 14%), breast cancer mortality (56% versus 67%), and locoregional recurrence (9% versus 37%) benefits. [45]

Comprehensive Nodal Irradiation

Comprehensive nodal radiation (CNI) covers all lymphatics draining the breast and chest wall, which consists of the levels I to III axilla, supraclavicular nodes, and internal mammary nodes. CNI can be incorporated into WBRT or PMRT and is indicated in node-positive patients, either from a sentinel node biopsy or axillary dissection. In patients undergoing an axillary dissection, the radiotherapy typically includes undissected areas and areas at risk for nodal involvement. CNI is technically more challenging than WBRT alone, requiring additional fields (ie, 3 or 4 field plans). CNI also increases the dose to uninvolved structures such as the lungs and heart. Meeting heart constraints may become especially challenging when treating the left breast. Certain techniques such as deep inspiratory breath hold (DIBH) or intensity-modulated radiation therapy (IMRT) may be helpful in these circumstances to minimize the amount of dose received by these structures. CNI has been prospectively compared to axillary dissections in patients with 1 to 3 nodes positive and was found to have similar rates of axillary control (0.93% versus 1.82%). [46] In addition, CNI has also been shown to improve 10-year disease-free survival (77% versus 82%) without an improvement in overall survival in high-risk patients. [47] Using CNI may also increase the risk of lymphedema as the regional lymphatics are radiated, making it more difficult to drain the breast and upper extremity. The additional dose to the lung may also increase the risk of radiation pneumonitis.

Intensity-Modulated Radiation Therapy

Breast intensity-modulated radiation therapy (IMRT) may be used as an alternative to conventional 3D planning in certain circumstances, such as failure to meet heart dose constraints, which is common, especially in patients with left-sided disease. Several prospective randomized trials have compared 3D or 2D planning to IMRT. They have consistently demonstrated that grade 2 or higher radiation dermatitis was significantly lower with IMRT than with 3D. [48] [49] No differences in recurrence or survival were noted.

Radiation Therapy Complications

Cardiac toxicity

The risk of major coronary events as a long-term complication of breast irradiation has been well documented. Exposure of the coronary arteries may lead to accelerated atherosclerosis of the vessel, resulting in significant coronary events years after radiotherapy. A population case-control study demonstrated that the risk increases linearly with the dose to the heart, increasing the relative risk by 7.4% per gray without an apparent threshold. [50] Women with preexisting cardiac risk factors may have an even higher risk. [50]

Pneumonitis

The development of radiation pneumonitis in patients receiving adjuvant radiotherapy for breast cancer ranges from 0.8% to 2.9%. [51] Radiation pneumonitis has been documented in patients up to 1-year post-radiation and can require steroid treatment, oxygen therapy, and, in severe cases, intubation. The risk of pneumonitis increases with the volume of lung irradiated. Patients receiving comprehensive nodal RT are known to have higher rates of pneumonitis. The MA.20 study reported pneumonitis in 1.2% of their patients receiving regional nodal RT versus 0.2% in those treated to the breast only. [47] Concurrent use of taxanes such as paclitaxel, common in modern breast cancer chemotherapy regimens, may substantially increase the risk of pneumonitis in patients receiving radiation. [52] The most effective preventative measure is meticulous radiation planning and adherence to published lung dose constraints.

Breast fibrosis

Fibrotic changes in the breast are relatively common among patients receiving adjuvant radiotherapy. Onset is typically 4 to 12 months posttreatment, and the symptoms include breast shrinkage, hardening, pain, and poor wound healing. These changes can significantly affect cosmesis. The incidence in the literature ranges from 10% to 15%. [53] However, this risk of moderate to severe fibrosis may be influenced by several risk factors such as whole breast radiation dose, beam energy, dose heterogeneity, boost to the surgical cavity, and chemotherapy. A nomogram was developed using the data from the "Boost Versus No Boost" EORTC 22881-10882 trial to predict the risk of moderate to severe fibrosis in patients receiving whole breast radiation. [54] Preventative measures included weighing the risks and benefits of a breast boost, lowering beam energies, and limiting hot spots to <107% of the prescribed dose. In addition, patients at high risk for fibrosis may also take pentoxifylline with vitamin E for 6 months after radiation. This regimen has been shown in small randomized trials to reduce the risk of radiation fibrosis measured by a tissue compliance meter. [55] Unfortunately, once a patient has developed breast fibrosis, these changes are mostly irreversible. Management of patients with breast fibrosis consists mainly of symptomatic treatment, including NSAIDs, SNRIs, and anticonvulsants such as gabapentin.

Progressive swelling of the upper extremity may occur in patients treated 6 months after radiation. The patient may notice increasing arm girth, swelling, heaviness, poor wound healing, and infection. The risk of developing lymphedema depends on the disruption to the regional lymphatics. The risk factors include the number of lymph nodes removed, body mass index, and amount of irradiated lymphatics. [56] A nomogram developed by Gross et al in 2019 may help quantify this risk. [56] Patients undergoing a sentinel node biopsy have a 5.6% risk of developing lymphedema compared with a 19.9% risk in those undergoing a full axillary dissection. [57] The AMAROS trial had a 5-year lymphedema rate of 25% in patients receiving an axillary dissection versus 12% in those receiving regional nodal radiation alone. [58] Patients receiving axillary dissection and regional nodal RT would be at the highest risk of developing lymphedema. Evidence for prevention is sparse but includes weight-bearing exercise and maintaining appropriate body weight. Patients with lymphedema may be managed with fitted compression garments, arm elevation, and exercise.

Brachial plexopathy

The brachial plexus trunks may be exposed to radiation doses in patients requiring regional nodal radiation. Symptoms include hand and arm paresthesia, weakness, and pain in the affected arm and shoulder. Onset is typically 8 to 12 months after treatment. Fortunately, this rare complication only affects approximately 1% of all patients. The risk may be increased in patients who have received chemotherapy or doses of radiation exceeding 50 Gy. [59] Primary prevention consists of limiting radiation doses to <50 Gy. Patients with brachial plexopathy may be managed with gabapentin and physical therapy.

Rib fracture

Rib fractures are another rare complication of breast radiotherapy, ranging from 0.3% to 1.8% of patients. [59] [60] The median time to onset is approximately 12 months. The risk is associated with lower energies and higher doses of radiation. Treatment is generally conservative.

Secondary malignancy

Radiotherapy can induce DNA damage in both cancerous as well as normal tissues, which can lead to the development of radiation-induced malignancies years after treatment. Large meta-analyses have shown that patients receiving radiotherapy for breast cancer have an increased risk of non-breast cancers, including sarcomas, lung, and esophageal cancers. [61] However, the absolute risk of developing a secondary malignancy is low at 1% to 2% at 10 years. [62] Risk factors include age, gender, radiation field size, and radiation dose. [63]

Medical Oncology

Chemotherapy, hormone therapy, immunotherapy, and targeted therapy are the systemic therapies used in breast cancer management and are described below.

Cytotoxic Chemotherapy

Cytotoxic chemotherapy is used in the neoadjuvant and adjuvant setting. Chemotherapy is most effective in high-grade, poorly differentiated tumors that have a high cell turnover rate, such as triple-negative and HER2-positive tumors. The chemotherapy regimen depends on tumor characteristics, the patient's ability to tolerate chemotherapy, and the degree of potential benefit. [64]

Adjuvant chemotherapy is associated with improved overall survival, disease-free survival, and reduced local recurrence. [65] Cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) combination was one of the early regimens used in the adjuvant treatment of breast cancer. More modern regimens use anthracyclines (eg, doxorubicin or epirubicin) and taxanes in regimens such as TAC (ie, docetaxel, adriamycin, and cyclophosphamide). Adjuvant chemotherapy is recommended for most patients with triple-negative and HER2-positive tumors that are >T1 stage. Treatment recommendations for HR-positive tumors are more nuanced and are guided by commercially available genetic analysis kits (eg, Oncotype Dx, Mammaprint). [66] [67] Neoadjuvant chemotherapy is increasingly used for triple-negative and HER2-positive tumors, which leads to increased compliance and tumor downstaging and allows assessment of the tumor's biological response. [68] [69]

Targeted Therapy

Anti-HER2 therapy is indicated in 17% of breast cancers that overproduce the growth-promoting protein HER2/neu. Trastuzumab, the first approved drug, is a monoclonal antibody directly targeting the HER2 protein. It reduces the risk of recurrence and death by 52% and 33%, respectively, if combined with chemotherapy in HER2-positive early breast cancer if compared to chemotherapy alone. [70] [71] More recent data advocates for dual HER2 blockade with trastuzumab and pertuzumab, which improves response rates.
PARP inhibitors (eg, olaparib and talazoparib) are monoclonal antibodies that prevent the activation of PARP, which are DNA repair enzymes. They are indicated in the adjuvant setting in individuals with BRCA mutations and HER2-negative breast cancer. [72]
CDK4/6 inhibitors (palbociclib, target the CDK4/6 proteins, which promote cell division. Inhibition of this pathway promotes tumor lytic activity in HR-positive HER2-negative tumors. They are indicated in metastatic HR-positive, HER2-negative tumors and selected patients with early HR-positive tumors. [73]
Immune checkpoint inhibitors (pembrolizumab, nivolumab) act on the PD-1, PD-L1 pathway to activate the host immune system. They are currently indicated in triple-negative breast cancer and the metastatic setting. [74]

Hormonal Treatment

Selective estrogen receptor modulators (eg, tamoxifen) or aromatase inhibitors (eg, exemestane and letrozole) are indicated in HR-positive breast cancers. Estrogen receptor modulators are especially indicated in premenopausal women, while both drugs can be used postmenopausal. Hormonal therapy reduces the risk of breast cancer recurrence and mortality and is indicated from 5 to 10 years. [69] [31] Premenopausal women may also benefit from oophorectomy or chemical suppression of the ovaries (eg, GnRH antagonists), which are the primary source of estrogen before menopause. [75]

Breast cancer staging is determined clinically and histologically. Clinical breast cancer staging is based on physical examination and imaging studies before treatment. Histopathologic breast cancer staging is determined by pathologic examination of the primary tumor and regional lymph nodes after definitive surgical treatment. Staging is performed to group patients into risk categories that define prognosis and guide treatment recommendations for patients with a similar prognosis. Breast cancer is classified with the TNM classification system, which groups patients into 4 stage categories based on the primary tumor size (T), the regional lymph nodes status (N), and if there is any distant metastasis (M). [30] The most widely used TNM system is that of the American Joint Committee on Cancer.

Primary Tumor (T)

Tis: Carcinoma in-situ, Paget Disease With no Tumor

T1 : <2 cmT1a: 0.1 to 0.5 cmT1b: 0.5 to 1.0 cmT1c: 1.0 to 2.0 cm
T2 : 2 to 5 cm
T3 : >5 cm
T4 T4a: Chest wall involvementT4b: Skin involvementT4c: Both 4a and 4bT4d: Inflammatory ca

Regional Lymph Nodes (N)

N1 : Mobile ipsilateral axillary nodes
N2 : Fixed/matted ipsilateral axillary nodes
N3 N3a: Ipsilateral infraclavicular nodesN3b: Ipsilateral mammary nodesN3c: Ipsilateral supraclavicular nodes

Distant Metastases (M)

M1 : Distant metastases

Breast Cancer Staging

Stage 0 comprises ductal carcinoma in situ (DCIS) and noninvasive breast cancer. Early invasive cancer includes stages I, IIa, and IIb. Stages IIIa, IIIb, and IIIc primarily involve locally advanced disease. Stage IV is all metastatic breast cancer. [68] (see Image. Breast Cancer Metastasis Sites)

The prognosis of breast cancer depends on the stage. Stage 0 and Stage I both have a 100% 5-year survival rate. The 5-year survival rate of Stage II and Stage III breast cancer is about 93% and 72%, respectively. When the disease spreads systemically, its prognosis worsens dramatically. Only 22% of Stage IV breast cancer patients will survive their next 5 years. [30]

Complications

Complications can arise from the treatment, whether chemotherapy, radiation, hormonal therapy, or surgery.

Cosmetic issues
Permanent scarring
Alteration or loss of sensation in the chest area and reconstructed breasts

Chemotherapy

Nausea/vomiting and diarrhea
Memory loss "chemo brain"
Vaginal dryness
Menopausal symptoms/fertility issues

Hormonal Therapy

Hot flashes
Vaginal discharge dryness
Impotence in males with breast cancer
Pain and skin changes
Chronic heart and lung issues
Neuropathyy [76] [30]
Deterrence and Patient Education

Breast cancer is the most commonly diagnosed cancer in women. Addressing the environmental and personal factors that increase the risk of breast cancer is vital in reducing breast cancer incidence. Screening helps detect premalignant lesions and breast cancer before it is clinically evident. Early detection leads to improved survival. Identifying patients at high risk for breast cancer is also crucial, as these individuals need to be monitored closely. Mammography, ultrasound, and MRI may be used for screening and diagnosis. A biopsy with histopathology and molecular markers should be performed on all patients. Early breast cancer is typically treated with breast conservation surgery, radiation, chemotherapy, or hormonal therapy. More advanced tumors require a mix of different modalities to obtain the best outcome. Long-term surveillance and compliance with therapy help improve survival.

Enhancing Healthcare Team Outcomes

Patient-centered care for individuals with breast requires collaboration among healthcare professionals, including physicians, advanced practice clinicians, nurses, pharmacists, and others. These neoplasms are often discovered during screening. The necessary skills involve interpreting radiological findings, identifying potential complications, effectively communicating these findings to the patient and their care team, and understanding the intricacies of breasts. Medical oncology, interventional radiology, pathology, general surgery, plastic surgery, and primary care practitioners typically play a role in coordinating and delivering care to patients with breast cancer. The entire healthcare team also plays a crucial role in ensuring that patients continue on surveillance pathways.

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Published: 14 August 2024

Sociodemographic inequalities in breast cancer screening attendance in Germany following the implementation of an Organized Screening Program: Scoping Review

Núria Pedrós Barnils ORCID: orcid.org/0000-0002-6687-3600 1 ,
Victoria Härtling 1 ,
Himal Singh 1 &
Benjamin Schüz 1

BMC Public Health volume 24 , Article number: 2211 ( 2024 ) Cite this article

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Organized breast cancer screening (BCS) programs are effective measures among women aged 50–69 for preventing the sixth cause of death in Germany. Although the implementation of the national screening program started in 2005, participation rates have not yet reached EU standards. It is unclear which and how sociodemographic factors are related to BCS attendance. This scoping review aims to identify sociodemographic inequalities in BCS attendance among 50-69-year-old women following the implementation of the Organized Screening Program in Germany.

Following PRISMA guidelines, we searched the Web of Science, Scopus, MEDLINE, PsycINFO, and CINAHL following the PCC (Population, Concept and Context) criteria. We included primary studies with a quantitative study design and reviews examining BCS attendance among women aged 50–69 with data from 2005 onwards in Germany. Harvest plots depicting effect size direction for the different identified sociodemographic inequalities and last two years or less BCS attendance and lifetime BCS attendance were developed.

We screened 476 titles and abstracts and 33 full texts. In total, 27 records were analysed, 14 were national reports, and 13 peer-reviewed articles. Eight sociodemographic variables were identified and summarised in harvest plots: age, education, income, migration status, type of district, employment status, partnership cohabitation and health insurance. Older women with lower incomes and migration backgrounds who live in rural areas and lack private insurance respond more favourably to BCS invitations. However, from a lifetime perspective, these associations only hold for migration background, are reversed for income and urban residency, and are complemented by partner cohabitation. Finally, women living in the former East German states of Saxony, Mecklenburg-Western Pomerania, Saxony-Anhalt, and Thuringia, as well as in the former West German state of Lower Saxony, showed higher BCS attendance rates in the last two years.

High-quality research is needed to identify women at higher risk of not attending BCS in Germany to address the existing research’s high heterogeneity, particularly since the overall attendance rate still falls below European standards.

Protocol registration

https://osf.io/x79tq/ .

Peer Review reports

Breast cancer is currently the fifth leading cause of death among women in Germany, with 18,900 deaths in 2022 [ 1 ]. Socioeconomic inequalities in breast cancer (BC) survival are recognised in Europe [ 2 ] and in Germany [ 3 ]. In a phenomenon known as the “breast cancer paradox”, women with lower socioeconomic status experience higher mortality rates compared to women with higher socioeconomic status, despite lower incidence in this group [ 4 ]. Several explanations have been proposed for this paradox. Higher incidence among women with high socioeconomic status women is related to nulliparity [ 5 ], having children at an older age [ 6 ], the use of oral combined contraceptives [ 7 ], and higher screening attendance [ 8 ]. On the other hand, higher mortality and case fatality rates in women from lower socioeconomic backgrounds are linked to unhealthier lifestyles (e.g., smoking, diet) [ 9 ] and reduced screening attendance [ 10 ]. The same pattern was found between Black and Asian minority ethnic women and Caucasian women in the US [ 11 ]. Lower screening attendance leads to delayed initiation of treatment and the manifestation of more advanced tumours.

In 2003, the European Commission (EC) requested Member States to implement Organized Screening Programs (OSP), which would systematically invite women aged 50 to 69 years for bi-annual breast cancer screening (BCS), ensuring equitable access for all [ 12 ]. Germany started implementing OSP in 2005, reaching full country-wide implementation in 2009. The program is coordinated by the Kooperationsgemeinschaft Mammographie (Mammography Cooperation Group), with 14 regional invitation centres and 94 screening units. Registered targeted women who did not explicitly objected to be invited to screenings are bi-annually invited to take a mammography at no cost at their reference screening unit. Every screening unit, in sparsely populated areas mobile screening unit, covers an area with 800,000 to 1,000,000 inhabitants, and is headed by one or two coordinating doctors. Diagnosed breast cancers are then treated in certified breast centres [ 13 ]. Attendance rates have increased since implementation from 49 to 57% among targeted women since but are still well below the 70% EU recommendation [ 14 ]. Nevertheless, and possibly overshadowing OSP participation rates, it is important to consider the existence of grey screening in the country. This refers to mammography conducted outside the national program (i.e., via self-invitation) and thus not registered by the screening units, leading to an underestimation of the number of women undergoing screening [ 15 ].

Attendance to BCS is not uniform among eligible populations in Germany [ 16 ] or worldwide [ 10 ]. Several characteristics have been associated with BCS attendance, such as sociodemographic factors, health behaviours, health status, accessibility and logistics, attitudes, knowledge, and beliefs [ 17 , 18 , 19 ]. Several studies have investigated the presence of BCS sociodemographic inequalities in Germany. Missinne (2015) found a positive correlation between self-reported BCS attendance and income but no association with education [ 20 ]. Also, Heinig (2023) found no significant correlation between education and BCS attendance based on data from health insurances (claims data, onward) [ 15 ]. Regarding income differences, Lemke (2015) identified high income and lower education as predictive factors for higher BCS attendance based on screening units register-based data [ 21 ].

This suggests considerable heterogeneity in the research evidence concerning sociodemographic inequalities, and a review of socioeconomic correlates of BCS attendance in Germany is lacking. As such, a scoping review that encompasses this heterogeneity and summarises research evidence available on sociodemographic inequalities on BCS attendance in the country since the implementation of OSP could facilitate a comprehensive picture and lay the foundation for evidence-based screening interventions to increase screening participation in eligible women. The present scoping review, therefore, aims to identify sociodemographic inequalities in BCS attendance among women aged 50–69 years since the OSP implementation by answering the following questions:

1) What are the existing sociodemographic inequalities in breast cancer screening participation among targeted women following the implementation of an Organized Screening Program in Germany?

2) What are the effect sizes of the sociodemographic inequalities on breast cancer screening attendance among targeted women following the implementation of an Organized Screening Program in Germany?

We conducted the scoping review in line with the PRISMA-ScR guidelines for scoping reviews [ 22 ], and following the five-steps methodological framework proposed by Arksey & O’Malley’s in 2005 [ 23 ]. The review protocol, including the search strategy, was registered at the Centre for Open Science (OSF) [ 24 ] and is provided as Supplementary File 1.

Eligibility criteria

Following the recommendation for scoping reviews, we employed the PCC (Population, Concept and Context) criteria, where BCS is the concept, Germany is the context and women aged 50–69 years old are the population, as they represent the eligible screening group.

At the screening stage, studies with qualitative designs or non-primary studies, studies reporting data earlier than 2005 (i.e., date for OSP implementation) or not focused on breast cancer screening participation (e.g., focus on the program’s effectiveness), and studies that did not report information on sociodemographic variables (e.g., only general population screening attendance) were excluded. Finally, only studies published in English or German were included.

Information sources and literature search

On January 26, 2024, the following bibliographic databases were searched for the period from January 2005 to January 2024: Web of Science, Scopus, MEDLINE (via PubMed), PsycINFO (via Ovid), and CINAHL (via EBSCO).

The search terms, developed iteratively by the research team, included descriptors of BCS, such as “mammography” or “breast cancer screening”, combined with descriptors of Germany “Germany” and the time frame 2005 onwards. All search strategies are provided as a supplementary file (Supplementary File 2). For those included articles, backward snowballing was performed using the guidelines for snowballing [ 29 ]. Furthermore, a manual search of the reference lists of the included systematic or scoping reviews was performed by one researcher (NPB) to identify further relevant articles. To identify grey literature relevant to the scoping review, two team members (NPB and VH) conducted independent searches on the websites of pertinent national public health institutions (e.g., Bundesgesundheitsblatt , Bericht zum Krebsgeschehen in Deutschland , etc.,).

Selection of the sources of evidence

After performing the systematic search of all electronic databases, articles were retrieved, duplicates were removed, and references were imported in Rayyan [ 25 ]. Two authors, NPB and VH, independently screened the titles and abstracts and later the full texts of the studies in the next stage. Discrepancies between the researchers were discussed until a consensus was reached.

Data items and data charting process

The data from the eligible studies were extracted in an Excel sheet that was developed, calibrated, tested and refined a priori before three researchers (NPB, VH and HS) charted the data independently. Discrepancies that arose were resolved through discussion. We charted bibliographic information (first author, year of publication, type of publication, study title, setting, aim of the study, funding sources/conflict of interest), methods (type of study, sample size of the analysis, methods of analysis, period coverage, method of reporting data, type of screening), and results (attendance rates, sociodemographic variables, other reported exposure variables, effect sizes, direction of effect sizes, p-values). When articles developed univariate and multivariate models, information from relevant variables was extracted from univariate models for further data synthesis.

Critical Appraisal of the individual sources of evidence

The included studies were critically appraised using the National Institutes of Health (NIH) Quality Assessment Tool [ 26 ]. Two team members (NPB and VH) assessed the included studies independently, and discrepancies were discussed until a consensus was achieved.

Synthesis of the results

Results were synthesised depending on available information. Effect sizes of sociodemographic variables were extracted from 13 peer-reviewed articles. Given the heterogeneity of study designs, we used harvest plots to summarise the data. These plots are agnostic to the outcomes and measures used and are flexible enough to include any dimension considered relevant (e.g. sample size, study design, etc.) [ 27 ]. Sociodemographic information presented in the 14 national reports was synthesised narratively. All analyses were performed with R (version 4.2.3).

From the 476 titles and abstracts screened, 33 articles were included in the full-text screening. Eleven articles met the eligibility criteria and were included in the scoping review. Reasons for excluding full-text articles were not reporting breast screening attendance ( n = 10), information on sociodemographic variables missing ( n = 6), study before 2005 ( n = 2), outside Germany ( n = 1), and no quantitative or review design ( n = 1). Two systematic reviews were identified during the full-text screening, and their reference list was checked for potential articles [ 4 , 28 ]. Also, backward snowballing from included articles identified 16 further relevant records (14 national reports and 2 articles) bringing the total number of included records to 27 (Fig. 1 ). Grey literature identified 3,797 relevant records, from which none were finally added to the final review (details in Supplementary File 3).

PRISMA flow chart of the search process

Study characteristics

The scoping review included 27 records, 13 peer-reviewed articles and 14 national reports. Supplementary File 4 reports the characteristics and summary of findings of the 27 sources. Most of the records ( n = 20, [ 13 , 14 , 15 , 16 , 20 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ]) utilised nationwide or nationally representative data, while seven records drew upon data from specific regions within Germany ( n = 7, [ 21 , 44 , 45 , 46 , 47 , 48 , 49 ]). Publication dates span from 2009 to 2023, with the highest concentration of published articles falling within the 2013–2016 timeframe ( n = 10, [ 13 , 20 , 31 , 32 , 33 , 34 , 41 , 43 , 45 , 46 ]), closely followed by 2020–2023 ( n = 8, [ 14 , 15 , 21 , 38 , 39 , 40 , 48 , 49 ]). The reported data covered a broader period, ranging from 2005 to 2021. Specifically, three articles ( n = 3, [ 20 , 42 , 47 ]) and two national reports ( n = 2, [ 29 , 30 ]) pertain to the OSP implementation phase spanning 2005–2009. The remaining records ( n = 22, [ 13 , 14 , 15 , 16 , 21 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 43 , 44 , 45 , 46 , 48 , 49 ]) report data from 2009 onwards, when the OSP was fully implemented. Four included articles ( n = 4, [ 15 , 21 , 44 , 45 ]) had a cohort study design, nine articles ( n = 9 [ 16 , 20 , 41 , 42 , 43 , 46 , 47 , 48 , 49 ]), and all national reports ( n = 14, [ 13 , 14 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ]) had a cross-sectional design. The sample sizes of the records ranged from n = 237 [ 42 ] to n = 1,151,000 [ 44 ] for peer-reviewed articles and n = 4,864,574 [ 31 ] to n = 5,887,028 for national reports [ 14 ]. Peer-reviewed articles reported three methods for collecting data: self-reported data ( n = 7, [ 16 , 20 , 21 , 42 , 43 , 47 , 49 ]), claims data ( n = 2, [ 15 , 41 ]), screening units register-based data ( n = 3, [ 45 , 46 , 48 ]). One article used claims and register-based data ( n = 1, [ 44 ]). All national reports reported screening units register-based data ( n = 14, [ 13 , 14 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ]).

Three articles reported BCS attendance for the last year ( n = 3, [ 41 , 42 , 44 ]), five reported attendance in the last two years ( n = 5, [ 16 , 43 , 45 , 46 , 47 ]) and five reported never having attended to BCS ( n = 5, [ 15 , 20 , 21 , 48 , 49 ]). All national reports reported attendance in the last two years.

Critical appraisal of included sources of evidence

The methodological quality of all included records was rated following the NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies given its suitability for the research designs of the included records [ 26 ]. All 14 national reports were rated as good, five peer-reviewed articles were rated as good ( n = 5, [ 15 , 21 , 43 , 45 , 46 ]), five as fair ( n = 5, [ 16 , 20 , 41 , 42 , 44 ]) and three as poor ( n = 3, [ 47 , 48 , 49 ]). A study was considered to be good if all the applicable criteria were met, fair if one was not met and poor if two or more were not met. The overall rating of different aspects considered is represented in Fig. 2 , and the reasons behind each record’s rating are in Supplementary File 5.

Critical Appraisal of 27 included records (NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies)

Breast cancer screening attendance rates across studies

Cross-sectional studies reported an average attendance rate of 55.10% (SD = 9.85), cohort studies reported 74.67% (SD = 17.94). The average attendance rate of all records was 57.42% (SD = 12.40). Average lifetime attendance rate was 72.54% (SD = 16.32), attendance in last two years was 53.83% (SD = 8.15), attendance in the last year was 52.3% (SD = 8.34). Two articles did not report overall BCS attendance rates ( n = 2, [ 41 , 45 ]).

Studies with self-reported attendance reported an average attendance rate of 63.84% (SD = 20.27), those based on claims and screening units register-based data showed an average attendance of 54.97% (SD = 6.99).

OSP implementation phase (2005–2009) and the full OSP implementation (2009 onwards) also showed different participation rates: 47.94% (SD = 6.87) and 59.19% (SD = 12.47), respectively. There was an increase in the lifetime attendance rate from 72.54% (SD = 16.32) to 78.48% (SD = 10.22) ( n = 4, [ 15 , 21 , 48 , 49 ]) when only assessing studies carried since the full OSP implementation.

Evaluation reports of the German mammography screening programme

Fourteen of the included sources are national evaluation reports of the German Mammography Screening Programme, initiated in 2005 and conducted by the Kooperationsgemeinschaft Mammographie [ 50 ]. The reports graphically presented participation rates per federal state based on the screening units register-based data, and, as such, have the potential to detect regional inequalities in attendance. No federal state has yet reached the EU recommended rate of > 70% participation of the target population. Still, Lower Saxony, Saxony, Mecklenburg-Western Pomerania, Saxony-Anhalt and Thuringia have had the highest participation rates over the last five years [ 14 ].

Sociodemographic inequalities in breast cancer screening participation

Sociodemographic inequalities in BCS participation were examined by harvest plots based on vote counting for sociodemographic variables reported in at least two articles: age, education, income, migration status, type of district, employment status, partnership cohabitation and health insurance. Two harvest plots were plotted for the distinct reported outcomes: Attendance during the last one or two years (Fig. 3 ) and lifetime BCS attendance (Fig. 4 ). Details on the harvest plots can be found in Supplementary File 6.

Each bar represents a study and illustrates five characteristics of the study: the height of the bars indicates the sample size of the study, the width of the bars reflects the study quality based on the NIH critical appraisal tool, colour denotes the study type (blue: cohort; yellow: cross-sectional), and filling pattern indicates sociodemographic data level source (black: individual; white: regional).

Harvest plot displaying correlations between sociodemographic variables and last one-two years BCS attendance in Germany

Harvest plot displaying correlations between sociodemographic variables and lifetime BCS attendance in Germany

Age (6 effects)

Among those reporting attendance in the last one/two years, 4/5 suggested higher attendance in older women [ 16 , 43 , 44 , 46 ], and one suggested no correlation [ 47 ]. One study found no significant relationship between age and lifetime BCS attendance [ 21 ].

Education (11 effects)

Two studies (three effects) suggested higher attendance in the last one/two years with higher education [ 42 , 44 ], and three studies suggested the opposite [ 16 , 41 , 47 ]. Two studies revealed a negative correlation [ 48 , 49 ], and three studies found no relationship [ 15 , 20 , 21 ] for lifetime BCS attendance.

Income (4 effects)

Three studies found a negative correlation between income and attendance in the last one/two years [ 41 , 43 , 47 ], and one study found no correlation [ 44 ]. One study found no correlation between lifetime BCS [ 20 ], and one study found a positive correlation [ 21 ].

Migration status (7 effects)

4/7 studies identified higher lifetime BCS attendance in those with migration status (2 lifetime [ 21 , 49 ]; 2 last two years [ 44 , 46 ]). Three studies found no correlation [ 21 , 45 , 48 ]. Here, two effects from the same study illustrated a positive correlation between first-generation migrants and locals, but there was no correlation when estimating second-generation migrants versus locals [ 21 ].

Type of district (3 effects)

Two studies found that living in a rural area favours last one/two years BCS attendance ( n = 2, [ 44 , 47 ]), whereas one found no correlation for lifetime BCS attendance ( n = 1, [ 21 ]).

Employment status (7 effects)

Lemke (2015) contributed 5/7 effects, showing a contextual negative association in two and no relationship in three cases [ 45 ]. Two more studies also found no relationship with BCS attendance [ 21 , 47 ]. Conversely, one study identified a positive correlation between employment status and BCS attendance in the last year [ 44 ].

Partnership cohabitation (2 effects)

One study found a positive relationship between cohabitating and lifetime BCS [ 21 ], and another found no relationship for BCS in the last two years [ 47 ].

Health insurance (2 effects)

One study observed no correlation between health insurance and lifetime BCS [ 21 ]. Still, another study identified that compulsory insurance (as opposed to private insurance) was associated with BCS in the last two years [ 47 ].

This scoping review aimed to identify sociodemographic inequalities in BCS attendance in Germany following the implementation of the OSP. Eight sociodemographic variables were identified: age, education, income, migration status, type of district, federal state, employment status, partnership cohabitation, and health insurance.

Women are more likely to attend BCS following invitation letters within two years or less as they age, have lower incomes, have a migration background, reside in rural areas, live in certain federal states such as Lower Saxony, Saxony, Mecklenburg-Western Pomerania, Saxony-Anhalt, and Thuringia, and are insured within the compulsory health insurance system (i.e., do not hold private health insurance; based on one study only). Lifetime BCS attendance is more likely in women with higher incomes, migration backgrounds, urban residency (based on one study only), and cohabitating status with a partner (based on one study only).

Our finding regarding age is similar to a scoping review in Spain [ 51 ]. However, the lifetime impact on overall BCS attendance requires further investigation, as in our scoping review, there is a substantial imbalance in research outputs- only one study focused on lifetime attendance [ 21 ].

The size and direction of the impact of educational attainment on attending BCS within two years or less remains unclear, as we identified studies reporting opposing results. Considering the quality of the assessed studies, those suggesting higher education as a protective factor yielded higher quality. In this line, Damiani’s (2015) international systematic review found that highly educated women were the most likely to undergo BCS after invitation [ 52 ]. Studies examining lifetime BCS attendance found different results, showing that in over half of the studies with high quality, there was no correlation, and in less than half with lower quality, there was a negative correlation between educational attainment and BCS attendance. There were also heterogeneous results concerning the association between income and BCS attendance. Lower income women depicted higher short-term BCS attendance rates and higher income women higher long-term BCS attendance rates.

These findings challenge the breast cancer screening paradox whereby women with higher socioeconomic status are more likely to engage in BCS. In our scoping review, there was no straightforward relationship identified between higher educational attainment or income and higher participation rates. A comparable pattern was identified by a recent international systematic review [ 10 ], which indicated that women with higher levels of education or income were no more likely to attend BCS than those with intermediate levels of education or income. It is hypothesised that high SES women utilise alternative screening services, such as grey screening, to a greater extent, and could also have larger concerns about the overall benefits of screenings [ 53 ]. Indeed, Berens (2015) exposed that women with higher educational attainment were more likely to make informed choices than those with lower educational attainments in Germany [ 54 ].

Moreover, in the context of Germany, a considerable proportion of women with high income may have a private health insurance, often as a result of their employment status as civil servants [ 55 ]. For those citizens with private health insurance, the utilisation of any preventive service can be initially borne by the individual and subsequently reimbursed, unless the overall out-of-pocket expenditure in a given year does not exceed a specified threshold (e.g., 500€), potentially jeopardising the use of these services [ 56 ]. Indeed, in our review one study suggests that holding private health insurance is associated with lower BCS attendance in the last two years . In line with this finding , private health insurance in Spain also negatively correlates with last two years BCS attendance [ 57 ].

Women with migrant backgrounds appear more likely to attend BCS in the short and long term. Over half the studies with fair to good quality support this trend. Contrarily, several studies assessing BCS attendance in other high-income countries [ 58 , 59 , 60 ] or assessing general cancer screening attendance in Germany [ 61 , 62 ] found the inverse tendency.

Furthermore, attending BCS within the last two years or less was positively correlated with living in rural areas. Analogously, Serral (2018) found the same association [ 57 ]. In the reviewed studies, BCS attendance was higher in Lower Saxony, Saxony, Mecklenburg-Western Pomerania, Saxony-Anhalt, and Thuringia. Except for Lower Saxony, all these states conform are former East German states. Großmann (2023) also noted higher BCS attendance rates in former East German states and suggested that the former centralised healthcare and prevention systems, perceived as state tasks, contributed to women viewing participation as a social responsibility [ 63 ].

About two-thirds of the included records found no significant difference between regions with higher and lower unemployment levels, while the remaining third suggested a slightly higher short term BCS attendance in regions with higher unemployment levels. These results are in accordance with Serral (2016), who showed, after adjusting by age, a positive relationship between not working and BCS attendance in Spain [ 57 ], while Jensen (2012) found the opposite relationship in Denmark [ 64 ].

Partnership cohabitation was positively associated with lifetime BCS but not with last two years or less BCS attendance. The study with a positive relation had a more robust design and better-quality assessment. Similarly, Jolidon (2022) found significantly higher attendance rates among married women compared to unmarried women in Switzerland [ 65 ]. Lastly, no study included women with disabilities in their analysis. Andiwijaya’s (2022) systematic review revealed that having a disability was negatively associated with BCS attendance [ 66 ].

Strengths and limitations

To our knowledge this is the first scoping review to identify sociodemographic inequalities in BCS attendance among women aged 50–69 years since the implementation of the OSP in Germany. In accordance with the PRISMA-ScR guidelines, the search and the screening process was conducted in a transparent and reproducible manner, and the results were visually summarised using harvest plots.

The scoping review identified heterogeneous study designs, which corresponded with the mixed findings: cross-sectional studies indicated nearly 20% lower participation rates than cohort studies. Similarly, there was almost a 20% difference between the average participation rates over the past one or two years and lifetime participation rates (i.e., being lifetime participation higher). Slightly minor differences were found with the data collection method. Here, claims or screening units register-based data reported a 9% higher prevalence than self-reported participation. Finally, BCS participation prevalence during the OSP implementation phase (2005–2009) was 12% lower than after total implementation, and was reported as a compound of formal OSP participation and self-invited participation (i.e., grey screening) [ 29 , 30 , 47 ]. The varied BCS prevalence across study characteristics might align with our scoping review’s mixed findings in sociodemographic inequalities.

Lastly, given the heterogeneity of study designs, it is impossible to distinguish correlation from causation. Accordingly, more cohort studies with objective data sources, such as claims and screening units register-based data, are needed.

Conclusions and implications

This scoping review shows considerable heterogeneity in sociodemographic inequalities in BCS attendance following the implementation of the OSP in Germany. Older women, women with lower incomes, women with migration background, women living in rural areas, women living in former East Germany states and women who are insured in the statutory insurance system respond more favourably to BCS invitations. Regarding lifetime BCS attendance, these associations only hold for migration background, are reversed for income and urban residency, and are complemented by partner cohabitation.

Given that overall attendance is well below European standards, specific sociodemographic groups should be targeted in BCS participation campaigns. At the same time, more high-quality research is needed to identify women at higher risk of not attending BCS in Germany to provide better evidence.

Data availability

All data generated or analysed during this study are included in this published article and its supplementary files.

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Pedrós Barnils, N., Härtling, V., Singh, H. et al. Sociodemographic inequalities in breast cancer screening attendance in Germany following the implementation of an Organized Screening Program: Scoping Review. BMC Public Health 24 , 2211 (2024). https://doi.org/10.1186/s12889-024-19673-6

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Weight-loss drugs like wegovy may help stave off some cancers.

Yuki Noguchi

Obesity, Cancer, and GLP1s

GLP-1 drugs, like Wegovy and Ozempic, may not be good only for diabetes and weight-loss. They are also showing promise for preventing some cancers. UCG/Universal Images Group/Getty Images hide caption

Drugs like Ozempic, Wegovy and Zepbound have transformed treatment for obesity and diabetes. Now researchers are excited about their potential impact on other conditions, including addiction and sleep apnea — and even cancer.

Scientists see this class of drugs, called GLP-1 agonists, as a breakthrough because of how they act on the brain to regulate the body’s hormones, slow digestion, and tamp down hunger. And in several recent studies, they show early promise in preventing many common cancers — including breast, colon, liver, and ovarian — known to be driven by obesity and excess weight.

“It's a hopeful story, which is, frankly, what people need,” says Arif Kamal, an oncologist specializing in breast cancer as well as chief patient officer at the American Cancer Society.

Though research on GLP-1 drugs is still in its relative infancy, so far studies fairly consistently show their benefit in staving off certain cancers. One research letter published in JAMA Oncology last year, for example, suggests GLP-1 drugs might reduce the risk of colon cancer , even among people who are not overweight. A more recent analysis in JAMA Network Open suggests GLP-1s provide far more protection against cancer for diabetic patients than insulin treatments.

Another recent study presented at the American Society of Clinical Oncologists meeting in June, showed both bariatric surgery and GLP-1 medications dramatically reduce the risk of the 13 obesity-related cancers . Among those who had bariatric surgery, that risk declined by 22% over 10 years compared to those who received no treatment. But among those taking GLP1 medications, risk dropped by a whopping 39%.

“And I think a 39% risk reduction is one of the most impactful risk reductions we've ever really seen,” says Kamal.

GLP-1 agonist drugs were originally developed to treat diabetes nearly two decades ago. Over the past decade, regulators started approving them as treatments for weight loss – first as liraglutide, sold under the brand Saxenda and, more recently, in the form of semaglutide or tirzepatide, under brands like Wegovy and Zepbound.

When it comes to cancer prevention, scientists are finding the link between obesity in cancer is complex and intertwined; the obesity-related cancers are heavily concentrated among organs involved in digestion and metabolism, like the liver and pancreas, for example, as well as among gynecologic cancers, including breast and uterus. Reproductive organs are highly sensitive to the hormone estrogen, which plays a role in allowing cells to grow rapidly during pregnancy, for example.

But Kamal says there’s also an especially close relationship between estrogen and cancer. “What we do know is that estrogen in particular — and possibly some other hormones, but estrogen for sure — drives the growth of many cancers,” he says. And fat cells increase production of estrogen.

That means women today are increasingly susceptible to cancer. Historically, men faced a much higher risk of developing cancers — in large part because they were more likely to engage in high-risk behaviors like smoking or drinking, Kamal says. But in recent years, the high prevalence of obesity among both men and women is closing that gender gap.

Obesity is also likely the most significant driver behind increasing cancer rates among younger adults , he says, just as tobacco was in generations past.

“Unhealthy weight is the smoking of our generation,” Kamal says.

That’s why indications that GLP-1 drugs may help slash that risk is so significant.

What’s more, that ASCO study suggests that GLP-1 drugs have a notable impact on cancer risk, even when patients don’t lose a lot of weight as a result of taking them. In other words, the medications seem to act on a number of the body’s mechanisms to reduce vulnerabilities to cancer.

“We think the protective effects of GLP-1s are probably multifactorial,” says Cindy Lin, resident physician at Case Western Reserve and co-author of the June ASCO study. “Part of it is weight [loss], but other factors may be contributing as well — better glycemic controls, anti-inflammatory effects.”

More research is necessary and inevitable — especially studies looking at the newer weight-loss formulations of GLP-1 medications, says Benjamin Liu, another resident physician at Case Western and co-author of the ASCO study.

He says he’s encouraged by the data so far. “It's very exciting to have, especially since it's more of a noninvasive strategy compared to bariatric surgery, and a lot more patients will be open to it.”

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Dots represent ratio; whiskers, 95% CI. Ratios below the dotted line indicate underrepresentation in oncology study enrollment.

eFigure 1. Precision Oncology Studies by Race/Ethnicity Reporting Over Time

eFigure 2. Meta-Analysis of NHW Participant Representation in Precision Oncology Trials Compared With US Cancer Incidence

eFigure 3. Meta-Analysis of Asian Participant Representation in Precision Oncology Trials Compared With US Cancer Incidence

eFigure 4. Meta-Analysis of Black Participant Representation in Precision Oncology Trials Compared With US Cancer Incidence

eFigure 5. Meta-Analysis of Hispanic Participant Representation in Precision Oncology Trials Compared With US Cancer Incidence

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Aldrighetti CM , Niemierko A , Van Allen E , Willers H , Kamran SC. Racial and Ethnic Disparities Among Participants in Precision Oncology Clinical Studies. JAMA Netw Open. 2021;4(11):e2133205. doi:10.1001/jamanetworkopen.2021.33205

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Racial and Ethnic Disparities Among Participants in Precision Oncology Clinical Studies

1 Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston
2 Dana-Farber Cancer Institute, Boston, Massachusetts
3 Broad Institute of Harvard and MIT, Cambridge, Massachusetts
4 Center for Cancer Precision Medicine, Dana-Farber Cancer Institute, Boston, Massachusetts

Question What is the representation of racial and ethnic minority populations in studies incorporating precision oncology objectives in the US?

Findings This cross-sectional analysis evaluates breast, prostate, lung, and colorectal cancer studies in the Clinicaltrials.gov registry with precision medicine objectives and reporting race and ethnicity—a total of 93 studies with 5867 total enrollees. An underrepresentation of minority racial groups and an overrepresentation of non-Hispanic White participants relative to their incidence in the US cancer population was found in precision oncology studies.

Meaning These findings demonstrate an urgent need to increase enrollment of participants from diverse racial and ethnic backgrounds onto precision oncology studies, so that meaningful precision data can be collected and stratified to traditionally underrepresented participants.

Importance Precision oncology is revolutionizing cancer care, allowing for personalized treatments to improve outcomes. Cancer research has benefitted from well-designed studies incorporating precision medicine objectives, but it is unclear if these studies are representative of the diverse cancer population.

Objective To evaluate racial and ethnic representation in breast, prostate, lung, and colorectal cancer studies incorporating precision oncology objectives in the Clinicaltrials.gov registry and compare with the incidence of these cancer types in racial and ethnic minority groups in the US population.

Design, Setting, and Participants This cross-sectional study identified US-based breast, prostate, lung, and colorectal cancer studies incorporating precision oncology objectives for reporting of race and ethnicity. The Surveillance, Epidemiology, and End Results and US Census databases were used to determine cancer incidence by race and ethnicity, linked with cancer type and median year of enrollment for each trial. Data were collected and analyzed between December 2020 and April 2021.

Main Outcomes and Measures The expected number of participants per study by each racial and ethnic group was calculated based on the corresponding US-based proportion. Under- and overrepresentation was defined as the ratio of the actual number of enrolled cases to the expected number of cases for each trial by cancer type. Ratios above 1 indicated overrepresentation while a ratio below 1 indicated underrepresentation. Random-effects meta-analysis of representation ratios of individual trials was performed to weigh each individual study.

Results Of 93 studies encompassing 5867 enrollees with race and ethnicity data; 4826 participants (82.3%) were non-Hispanic White, 587 (10.0%) were Black, and 238 (4.1%) were Asian. Per observed-to-expected ratios, White participants were overrepresented in all studies, with a ratio of 1.35 (95% CI, 1.30-1.37), as well as Asian participants, with a ratio of 1.46 (95% CI, 1.28-1.66), while Black participants (ratio, 0.49; 95% CI, 0.45-0.54), Hispanic participants (ratio, 0.24; 95% CI, 0.20-0.28), and American Indian and Alaskan Native participants (ratio, 0.43; 95% CI, 0.24-0.78) were underrepresented. By individual cancer site, White participants were consistently overrepresented in all studies, while Black and Hispanic participants were underrepresented.

Conclusions and Relevance This analysis found that precision oncology studies for breast, lung, prostate, and colorectal cancers vastly underrepresent racial and ethnic minority populations relative to their cancer incidence in the US population. It is imperative to increase diversity among enrollees so that all individuals may benefit from cancer research breakthroughs and personalized treatments.

Precision medicine has revolutionized oncology in the past 2 decades and is expected to continue to transform cancer management. The principle of personalized cancer therapy incorporates a multi-omic (eg, genomic, transcriptomic, metabolomic, proteomic, epigenetic) approach along with other tumor- and patient-specific factors. The identification of biomarkers facilitates stratifying patients and guiding treatment individualization, leading to improved outcomes. 1 Much biomarker discovery and translational research that contribute to personalized treatments come from well-designed studies that incorporate precision medicine principles. Additionally, knowledge learned from studies that are designed to collect translational data can be used as part of discovery for predictive and prognostic biomarkers, which then can be applied to personalized therapeutic regimens.

Several targetable biomarkers have been found to have racial and ethnic differences in incidence for different cancer types such as epidermal growth factor receptor variants in lung cancer associating with East Asian ethnicity 2 as well as Native American ancestry. 3 Separately, growing evidence suggests underlying tumor genomic differences between African American vs White men with prostate cancer. 4 , 5 This information can lead to additional study and discovery as well as novel treatment options for those who harbor the specific tumor alteration or biomarker. However, the use of race and ethnicity in such analyses has multiple limitations. Race and ethnicity must be understood as social constructs. We also recognize that the traditionally broad racial and ethnic categories do not capture the heterogeneity that exists within each group. 6 Consequently, even the aforementioned findings should be further explained and contextualized in terms of other social determinants of health, such as health insurance status, zip code, socioeconomic status, environment, and other characteristics. The intersection of social, environmental, and genomic and/or biologic factors and the resultant influence on disease is poorly understood, with calls to action to capture these data points more robustly in all future precision medicine studies to evaluate and understand these interactions. 7 , 8

The use of genetic ancestry has been lauded as a tool that can better differentiate populations in the study of biology and genomics. 8 - 10 However, genetic ancestry data are not yet readily available for clinical practice or for use in clinical studies, nor have that data been historically captured. 11 The historical static groupings of individuals by race and ethnicity with regards to reported health data over time have led to the acceptance and use of these categories in biomedical research. 7 Stratification by various racial and ethnic groupings has identified several important differences in disease risk as well as response to certain treatments. 11 In addition, the historical use of race and ethnicity as currently defined to differentiate patients in the study of disease has led to the emergence and recognition of medically underserved and underrepresented minority populations. 12 Thus, although imperfect, understanding disparities by racial and ethnic groupings is of value, particularly pertaining to the study of precision medicine, as it is important to understand from which populations we are collecting our biologic and biomarker data for use in the general cancer population.

Despite rapid diversification of the US cancer population, 13 , 14 enrollment of a diverse patient population into cancer clinical trials lags behind, including for racial and ethnic minority groups. 15 - 17 As more clinical studies specifically incorporate precision oncology principles into their design, it is unknown whether ethnic and racial minority populations are adequately represented, an important consideration when one critical question is whether precision oncology discoveries in clinical trials are broadly applicable to the general cancer population. Is precision oncology research missing crucial findings that could be benefiting traditionally marginalized groups, thus further widening inequality and contributing to disparities in cancer care? Moreover, any identifiable differences between groups in a single or across a collection of studies must be further evaluated, particularly if personalization of a therapeutic is identified for 1 group vs another, as sample sizes would be too small to gather appropriate safety data. Both prespecified analyses in postapproval settings as well as the use of real-world study would be necessary to interrogate safety and efficacy data. 18 However, the opportunity to look for differences between various racial and ethnic groupings requires a concerted effort towards recruitment of underserved populations to these studies in their initial stages. Therefore, we sought to understand how well precision oncology studies are representative of the diverse US cancer population. Focusing on the top causes of new cancer cases in the US (ie, breast, colorectal, lung, and prostate cancers), 19 we evaluated clinical studies with precision medicine objectives for their reporting of race and ethnicity, and asked whether these study demographics were representative of the diverse US cancer population.

In this cross-sectional study, the Clinicaltrials.gov registry was queried for completed US-based clinical studies by cancer type (breast, colorectal, lung, and prostate) with results incorporating precision medicine objectives based on a set of precision oncology search terms: immunohistochemistry , histopathologic , DNA , RNA , DNA sequencing , RNA sequencing , sequencing , proteomics , tumor mutational burden , tumor biomarkers , biomarkers , tumor analysis , mutation testing , mutational analysis , microarray , whole exome , molecular analysis , genomics , genetics , gene expression , expression , signatures , genetic testing , and prognostic testing . Studies were excluded if they included site locations outside the US, did not include diagnosis of cancer (eg, precancerous), or did not incorporate precision oncology measures. Eligible studies were evaluated for reporting of racial and ethnic demographic data. Additional data gathered included type of clinical study (eg, phase 1) and type of funding (National Institutes of Health [NIH] vs other). Participant demographics were obtained from Clinicaltrials.gov if present and corroborated with primary report journal articles or abstract and/or presentation if unpublished (per availability). Racial and ethnic groupings were mutually exclusive as follows: American Indian/Alaskan Native, Asian, Black, Hispanic, and Non-Hispanic White participants. Participants with race and ethnicity not reported or unknown were removed from the analysis. Overall, these individuals made up less than 3% of the total enrollees per each cancer type (eg, overall, 126 of 5993 participants [2.1%]). Clinicaltrials.gov was queried in December 2020 with an update of the query and analysis in April 2021.

Cancer incidence by race and ethnicity within the US cancer population, correlated with cancer type and median year of enrollment for each study, was collected from the National Cancer Institute Surveillance, Epidemiology, and End Result (SEER) database. 20 Age-standardized incidence rates adjusted to the 2000 standard US population by race and ethnicity were used to calculate cancer cases as a measure of proportion of cancer burden by race and ethnicity using US Census Bureau tables. 21 , 22 This study was determined to be exempt from human participant research guidelines because it was a secondary analysis of publicly available published reports and data by the Mass General Brigham institutional review board. We followed the Strengthening the Reporting of Observational Studies in Epidemiology ( STROBE ) reporting guideline for cross-sectional studies and the Preferred Reporting Items for Systematic Reviews and Meta-analyses ( PRISMA ) reporting guideline.

For each trial, the expected number of participants of each of the 5 racial and ethnic groups was calculated by multiplying the total number of participants in a trial with the US-based proportion of each group for a given cancer type and median year of enrollment. We defined underrepresentation and overrepresentation as the ratio of the actual number of enrolled cases and the expected number of cases for each trial and per cancer type, with 95% exact binomial CIs estimated. A ratio greater than 1 indicated overrepresentation, while a ratio smaller than 1 indicated underrepresentation. Since the expected number of participants for groups other than non-Hispanic White is small, especially for smaller trials, we calculated totals of expected to enrolled ratios in all precision studies and per cancer type.

Separately, we also performed random-effects meta-analysis of underrepresentation and overrepresentation ratios of individual trials (still relative to the US-based proportion of racial and ethnic groups for a given cancer type and median year of enrollment), with the exclusion of trials with no enrolled participants of a given racial or ethnic group. Therefore, the weighted average of underrepresentation and overrepresentation effect sizes from the meta-analysis might be biased for minority populations with small numbers of enrolled participants (eg, Asian). Results are presented using forest plots (eFigures 2-5 in the Supplement ) showing study-specific effect sizes, and overall effect size for each cancer type and racial and ethnic group, with respective 95% CIs. Test statistics for the pooled data and estimates for between-trial heterogeneity statistics are also shown. Data were analyzed using Stata version 16 (StataCorp). To evaluate funding source and racial and ethnic reporting or distribution, Pearson χ 2 and 2-sample Wilcoxon rank-sum tests were performed, respectively; P ≤ .05 was considered significant in 2-sided tests.

Overall, 1500 studies were queried among the 4 cancer types and 1303 were excluded ( Figure 1 ). There were 197 clinical studies that met precision oncology measures that were assessed for race and ethnicity analysis. When evaluating for racial and ethnic reporting, 93 studies (47.2%) had appropriate data, while 104 studies (52.8%) did not report any information about race or ethnicity. Over time, the proportion of precision oncology studies reporting race and ethnicity has increased (eFigure 1 in the Supplement ). The median enrollment year for the included studies spanned from 2004 to 2017. Characteristics surrounding study phase and funding for studies (both included and excluded on basis of racial and ethnic group reporting) are shown in Table 1 . There was no statistical association between source of funding (NIH vs other) and reporting of race and ethnicity.

Of the 93 studies encompassing 5867 enrollees with recorded race and ethnicity data, most participants were non-Hispanic White (4826 [82.3%]), followed by Black participants (587 [10.0%]), Asian participants (238 [4.1%]), Hispanic participants (200 [3.4%]), with the lowest representation of American Indian/Alaskan Native participants (16 [0.3%]). By cancer type, lung cancer studies had the highest proportion of White (2054 of 2399 [85.6%]) and Asian (116 [4.8%]) participants, and the lowest proportion of Black (199 [8.3%]), Hispanic (26 [1.1%]), and American Indian/Alaskan Native (4 [0.2%]) participants. Colorectal cancer studies had the highest proportion of Hispanic participants (59 of 999 [5.9%]). Prostate cancer studies had the highest proportion of Black participants (67 of 596 [11.2%]) and American Indian/Alaskan Native participants (5 of 596 [0.8%]), and the lowest proportion of Asian participants (6 of 596 [1.0%]). When evaluating racial and ethnic distribution by funding type, Asian individuals were statistically overrepresented on studies with NIH funding.

When evaluating observed-to-expected ratios by race and ethnicity in all precision oncology studies, White and Asian participants were overrepresented with a ratio of 1.35 (95% CI, 1.30-1.37; 4826 observed vs 3582 expected) and 1.46 (95% CI, 1.28-1.66; 233 observed vs 160 expected), respectively ( Figure 2 ). The other racial groups were substantially underrepresented: Black participants with a ratio of 0.49 (95% CI, 0.45-0.53; 587 observed vs 1181 expected), Hispanic participants with a 0.24 ratio (95% CI, 0.20-0.27; 200 observed vs 845 expected), and American Indian/Alaskan Native participants with a 0.43 ratio (95% CI, 0.25-0.70; 16 observed vs 37 expected). When evaluating ratios by cancer type, White participants were consistently overrepresented, while Asian participants were overrepresented in lung, colorectal, and breast cancer studies. Black and Hispanic participants were underrepresented in all cancer type studies. American Indian/Alaskan Native participants are not shown by cancer type because they are represented in very small numbers.

In the meta-analysis, which weighs individual studies, White participants remained overrepresented overall with a ratio of 1.34 (95% CI, 1.29-1.39) and by cancer type ( Table 2 ; eFigure 2 in the Supplement ). Overrepresentation ranged from 22% (colorectal cancer) to 40% (prostate and lung cancer). Asian participants were overrepresented in all studies with a ratio of 1.89 (95% CI, 1.46-2.32) (eFigure 3 in the Supplement ). Cancer type–specific overrepresentation ranged from 29% (colorectal cancer) to 196% (lung cancer). Black participants remained underrepresented among all cancer types with a ratio of 0.51 (95% CI, 0.43-0.60) (eFigure 4 in the Supplement ). Among each cancer type, underrepresentation ranged from 38% (breast cancer) to 68% (lung cancer). Similarly, Hispanic participants were underrepresented among all cancer types per meta-analysis (ratio, 0.51; 95% CI, 0.37-0.66) (eFigure 5 in the Supplement ). Cancer type–specific underrepresentation ranged from 36% (breast cancer) to 69% (lung cancer). Numbers for American Indian/Alaskan Native participants were too small for accurate meta-analysis performance.

The underrepresentation of racial and ethnic minority populations in clinical trials relative to their cancer burden in the US has been previously reported. 13 , 15 There is an urgent need to increase equitable recruitment of diverse participants to cancer clinical trials, as well as to understand racial and ethnic differences in treatment outcomes. However, the field of oncology has been moving toward personalized treatments based on presence of tumor molecular markers as well as genetic and genomic variation. Despite this, there is limited knowledge of underlying cancer biology in racial and ethnic minority groups. Current personalized treatments that are broadly generalized to all individuals based on the presence or absence of a biomarker without fully studying the implications of such treatment in racial and ethnic minority populations may not be appropriate. Even if biological differences are discovered that are unique to certain racial or ethnic minority subgroups, these must be further validated and evaluated for safety and efficacy. Similarly, large biorepositories from which to study precision omics are disproportionately dominated by individuals of European ancestry. 10 , 23 , 24 This is a well-documented issue with genomewide association studies, 10 particularly for cancer research, with European-ancestry groups making up 96% of participants, while 0.11%, 0%, and 0.5% of subjects are from African, African American and Afro-Caribbean, and Hispanic and Latin American groups in studies at the initial discovery phase in 2019, 25 prompting the call for more inclusive samples and inclusive research communities. Thus, it is insufficient to take our current understanding of tumor biomarkers and biology and generalize findings to the entire diverse cancer population. Although race and ethnicity have been used historically to stratify populations, to fully understand any biological findings that differ by these social constructs, it is critical that future studies prospectively capture additional data that accounts for social determinants that influence disease, as well as data incorporating the use of genetic ancestry. 8 , 9 , 11

As contemporary clinical studies specifically incorporate precision oncology principles, it is unknown whether racial and ethnic minority populations are adequately represented overall and by cancer type relative to their cancer incidence in the US cancer population. By focusing on the most common cancer types in the US (breast, prostate, lung, and colorectal cancers), we found that most precision oncology studies do not report the race and ethnicity of participants. Of those studies with racial and ethnic reporting, we demonstrated an underrepresentation of minority racial groups and an overrepresentation of Non-Hispanic White participants in precision oncology studies. Black and Hispanic participants were the most underrepresented on lung cancer studies by 68% and 69% per meta-analysis, respectively. On the other hand, Asian individuals were overrepresented in lung cancer studies by 196%, consistent with the prominent role of targetable oncogene drivers in this population. There is likely underlying genetic susceptibility for these alterations among the Asian population in addition to the epidemiologic association with nonsmoking status. 26 - 29 Yet, data now demonstrate differential biology (as it relates to somatic driver mutations) among Hispanic participants with lung adenocarcinoma, underscoring the importance of their increased representation on precision oncology lung trials, as well as capturing of social determinants of disease to analyze these associations further. Separately, Hispanic individuals also had poor representation in prostate cancer studies (by 67%). Overall, our findings data highlight the need to increase enrollment of these groups into future clinical studies. All individuals deserve to benefit from cancer research breakthroughs and deep understanding of the underlying tumor biology not only in the context of race and ethnicity, but in the context of social determinants of health as well.

There is a long history surrounding underrepresentation of medically underserved participants on trials. 12 , 18 There are multiple factors at play, including medical mistrust. 30 Prior work has found that individuals from underrepresented racial and ethnic groups’ willingness to participate in research stems from perceived trustworthiness of the researchers, the institutions conducting the research, and the information provided about the applicable research studies. 31 There may be more mistrust surrounding genetic and biological studies—for example, genetic counseling participation is low among Black women for BRCA1/2 testing. 32 This finding was exacerbated among women with higher rates of medical mistrust, 32 fear of discrimination by insurance companies if considered high-risk, 33 and fear of carrying the mutation. 34 A targeted study evaluating African American and Hispanic perspectives on the prospect of precision medicine found that, although groups believed that precision medicine can improve health outcomes, both groups were concerned that current barriers to health care would prevent their communities from benefiting from precision medicine. 35

Multiple strategies must be implemented to increase diverse enrollment onto precision oncology trials, including patient navigation programs, patient education about multi-omic studies, patient education about genetics and genetic counseling, unique trial designs, education for all researchers or members involved to combat bias, and other educational resources to address barriers to enrollment for trial participation. More research is needed to fully understand all barriers and fears surrounding research recruitment. An increase in racial and ethnic diversity among scientists, biomedical researchers, physicians, and clinical trialists can help to increase trust among patients from minoritized groups. 11 , 36 Finally, precision oncology studies should increase the reporting of race and ethnicity of participants so that improvements in diversity and representation can be observed over time, and this analysis can serve as a benchmark with which to compare future progress.

Limitations to this analysis include those associated with use of Clinicaltrials.gov. We queried studies with reported results, which could miss noncompliant and incompletely accrued studies. Our search criteria could have missed slow-accruing precision oncology studies, or those that remained open after reaching their primary end point. We may be missing crucial precision oncology studies that were not identified with the search terms used, as well as studies that did not prespecify these analyses and were instead performed post hoc. Second, no information about race and ethnicity assessment was provided—it is important to emphasize that the racial and ethnic categories as reported do not capture the cultural heterogeneity within these groups. Third, there is no information on multiracial or multiethnic patients, which fails to capture patients who might identify as more than 1 racial or ethnic group. We recognize that this is imperfect, particularly given that in the latest 2020 US Census, over 33.8 million Americans identified themselves as being multiracial, resulting in an increase of nearly 276% since the 2010 census. 14 This highlights the opportunity for future studies or trials to capture these critical nuances in the future, along with demographic, social, environmental, and other determinants of health, to create fully annotated databases to enhance the study of biology and multi-omic research with a broader lens to understand the interaction of these multiple factors.

Increased emphasis on equitable recruitment and enrollment for precision oncology studies is essential, as resulting discoveries are used to personalize treatments, and it is unclear whether current precision medicine breakthroughs can be broadly applicable to, or safe for, our diverse cancer population. We demonstrate that precision oncology studies for breast, lung, prostate, and colorectal cancers underrepresent racial and ethnic minority populations relative to their cancer incidence in the US population. All relevant stakeholders should implement strategies to increase diverse clinical study enrollment to address this disparity. A continued lack of diversity among trial enrollees may further leave behind undeserved minority populations in the era of precision oncology.

Accepted for Publication: September 3, 2021.

Published: November 8, 2021. doi:10.1001/jamanetworkopen.2021.33205

Corresponding Author: Sophia C. Kamran, MD, Department of Radiation Oncology, Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114 ( [email protected] ).

Author Contributions : Mr Aldrighetti and Dr Kamran had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Aldrighetti, Van Allen, Kamran.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Aldrighetti, Niemierko, Kamran.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Aldrighetti, Niemierko, Kamran.

Supervision: Van Allen, Kamran.

Conflict of Interest Disclosures: Dr Kamran reported having a spouse who is employed by Sanofi Genzyme. Dr Van Allen reported advisory and consulting work for Tango Therapeutics, Genome Medical, Invitae, Enara Bio, Janssen, Manifold Bio, and Monte Rosa; he reported research support from Novartis, BMS; he reported equity in Tango Therapeutics, Genome Medical, Syapse, Enara Bio, Manifold Bio, Microsoft, and Monte Rosa; he received travel reimbursement from Roche/Genentech; and he filed institutional patents on chromatin mutations and immunotherapy response and methods for clinical interpretation outside the submitted work. No other disclosures were reported.

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SYSTEMIC MANAGEMENT OF BREAST CANCER

Mar 18, 2019

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SYSTEMIC MANAGEMENT OF BREAST CANCER. Dr Alice Musibi Medical Oncologist KENYATTA NATIONAL HOSPITAL. BREAST CANCER. INTRODUCTION Is one of the deadliest and most common cancers ailing women all over the world In Australia 1 in 13 women will develop ca breast at sometime in her life

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SYSTEMIC MANAGEMENT OF BREAST CANCER Dr Alice Musibi Medical Oncologist KENYATTA NATIONAL HOSPITAL

BREAST CANCER INTRODUCTION • Is one of the deadliest and most common cancers ailing women all over the world • In Australia 1 in 13 women will develop ca breast at sometime in her life • In USA 215,990 women will be found to have invasive ca breast in 2004 • More common in older than younger women with average age of diagnosis of 64 years

CANCER IN NAIROBI (KENYA) • A total of 2,716 cases were registered, comprising of 1246 men and 1470 women between 2000-2003 • Breast cancer was leading with 22.9% followed by cervical cancer with 19.3% • The mean age of diagnosis was 45 years

BREAST CANCER TREND IN NAIROBI

Treatment • Local management • 18th century – Louis Petit of France - total mastectomy and excision of axillary's lymph nodes • 1895 - William Halstead - popularized radical mastectomy • Harvey Cushing - extended radical - internal mammary chain excised after splitting the mediastinum • 1923-1937 - local excision and radium needles. • Conventional radiotherapy

Out-come • Poor overall results of survival • Frequent local recurrence and distant metastases • Treatment worse than disease • Concept of quality life • Women’s insistence for breast preservation

Treatment • Multidisciplinary • Surgery • Chemotherapy, hormonal therapy, immunotherapy • Radiation therapy • Palliative therapy • Occupational/physiotherapy • Lymph edema therapy • etc

Types Primary induction therapy Neo-adjuvant chemotherapy Adjuvant chemotherapy Palliative Associated with a decrease in the death rate prolonged relapse-free survivals Acute and chronic side effects Systemic therapy

Systemic therapy- combination • Maximum cell kill • Tolerable range of toxicity for each drug • Broader range of interaction between drugs and tumor cells • Less chance of developing cellular drug resistance

For patients at risk of disease recurrence after treatment of primary tumior Known tumor or maximum bulk should be removed Chemotherapy started as soon as possible post op Effective chemotherapy must be used at maximally tolerated doses Usually for a period (6-8 cycles) Milan CMF trial (overview)- CMF vs. surgery alone Relapse free survival- median 19.4 benefits in pre-menopausal patients (Bonnadona G et al N Engl. J Med 1995;332;901) Adjuvant systemic therapy

Neo-adjuvant chemotherapy • Systemic therapy given preoperatively • Advantage • Early exposure to micro-metastasis • Tumor response measurable • Reduce tumor bulk so less extensive surgery • Disadvantage • May delay surgery in tumors which may turn out to be chemo-resistant • May obscure real extent of disease

Depends on prognostic factors for recurrence/survival Age tumour size, nodal status histologic grade, hormone receptors, ??Her-2/neu over-expression (about 40% of breast cancers) ?Lymphatic/vascular invasion) Estimated benefit of therapy in terms of absolute risk reduction of relapse and death. Estimation of the toxicity associated with therapy [COST] Choice of treatment regime

Prognosis • Five year relative survival is dependent on the stage of breast cancer at diagnosis Stage Survival rate 0 100% I 98% IIA 88% IIB 76% IIIA 56% IIIB 49% IV 16% *(Overview American Cancer Society –2003)*

Post-surgical Mx of breast cancer (KNH) [1989-2000] • Surgery - 374 patients • Chemotherapy • Adjuvant - 22 (5.8%) • Metastatic -21 • Radiotherapy • Adjuvant - 46 (12.4%) • Palliation - 53 • Hormone therapy (tamoxifen) - 126 (33.7%) • East African Medical Journal: 2002 79(3): 156-162

Metastatic breast cancer (MBC) • MBC is considered an incurable disease. • majority of patients with MBCdo not survive beyond 5 years after diagnosis. • Treatmentusuallyis palliative with systemic therapyincluding • chemotherapy • hormonal treatment • biologic therapy (e.g. Trastuzumab) • Pain control

MBC -2 • The surgery of breast tumors with distant metastases has been indicatedto • prevent local complications (toilet surgery) • Removal of the metastatic lesions in selectedpatients (single brain, liver, bone or pulmonary lesions). • Surgery of the primary tumor can actually improvesurvival of metastatic breast cancer. • especially in patients with only bone metastases • (JCO, Vol 24, No 18 (June 20), 2006: pp. 2743-2749)

Many of our women are presenting like this!!

Language Lack of medical insurance Poverty Fears False beliefs Fatalism Lack of information Knowledge Attitude Behavior

Risk factors • Normal lifetime risk of developing breast cancer in white women is 1 in 8 or 9 • There is no family history in over 75% of patients • Most women with breast cancer do not have any identifiable risk factors

Age Ethnicity – more cancer in white women but more mortality in blacks Family history of breast cancer Previous history of personal breast cancer gives 1-2% risk of contralateral breast cancer/year Previous history of ovarian or endometrial cancers Prolonged estrogen exposure Early menarche (under age 12)/late menopause (after age 50) Late first pregnancy/nulliparous/no full-term pregnancy (1.5 times higher incidence) Hormone replacement therapy especially high estrogen based pills but more so the combined pills Genetic predisposition BRCA1 (85%) BRCA2 p53 gene – 1% in women with cancer of breast below 40 years Lifestyle factors Dietary factors – particularly increased fat consumption Obesity Lack of exercise Alcohol consumption Smoking (???) Prior Radiation therapy Atypical epithelial hyperplasia of the breast Fibrocystic disease with proliferative changes Lobular carcinoma in situ (LCIS) Risk factors

Recommendations

Recommendations • Clinical breast examination • U/S • Mammography • MRI scans of breast • Genetic mapping

Recommendations • Facilities • Cancer centres – 1 (KNH) • Laboratories • ordinary histopathology • immunohistochemical studies • KEMRI mainly research purposes • Private hosp (Nbi, AKUH) – all send the specimens to SA or Italy • Radiotherapy units – 2

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This educational activity is designed to meet the needs of physicians, nurses, and other clinical professionals who manage patients with cancer. The goal of this program is to provide participants with increased knowledge regarding the treatment of patients with breast cancer. Upon completion of this activity, participants should be able to:
Breast Cancer
Breast cancer is the most common cancer diagnosed in women and the second most common cause of death from cancer among women worldwide.[1] The breasts are paired glands of variable size and density that lie superficial to the pectoralis major muscle. They contain milk-producing cells arranged in lobules; multiple lobules are aggregated into lobes with interspersed fat.
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A clinical case presentation with pink colors and health-related fill icons. Includes 1000+ icons and Flaticon's extension for customizing your slides. Designed to be used in Google Slides, Canva, and Microsoft PowerPoint. 16:9 widescreen format suitable for all types of screens. Includes information about fonts, colors, and credits of the ...
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2. Click on the button below the presentation features that says 'Download Breast Cancer Case as a Free PowerPoint template'. 3. Once done it will start downloading a .pptx file that you can edit in PowerPoint. 4. If we do not have the powerpoint file we will direct you to the original source so you can download it. 5.
Establishment of Prognostic Nomogram for Male Breast Cancer Patients: A
Male breast cancer (MBC) represents a rare subtype of breast cancer, with limited prognostic factor studies available. The purpose of this research was to develop a unique nomogram for predicting MBC patient overall survival (OS) and breast cancer-specific survival (BCSS).
Sociodemographic inequalities in breast cancer screening attendance in
Background Organized breast cancer screening (BCS) programs are effective measures among women aged 50-69 for preventing the sixth cause of death in Germany. Although the implementation of the national screening program started in 2005, participation rates have not yet reached EU standards. It is unclear which and how sociodemographic factors are related to BCS attendance. This scoping ...
Drugs like Wegovy and Ozempic may help prevent cancer : Shots
Several new studies find promising evidence that the GLP-1 class of drugs may have a cancer-preventive effect, especially for cancers linked to obesity. ... an oncologist specializing in breast ...
PPT
Breast Cancer Detection • United States Preventive Services Task Force • Mammogram every 1-2 years for female age 40-49 (average risk) • Age > 50 annual mammography and clinical exam • Age > 70 debatable Mammography detects only 85% of biopsy proven breast cancer hence not a substitute for tissue sampling of palpable mass.
Racial and Ethnic Disparities Among Participants in Precision Oncology
Key Points. Question What is the representation of racial and ethnic minority populations in studies incorporating precision oncology objectives in the US?. Findings This cross-sectional analysis evaluates breast, prostate, lung, and colorectal cancer studies in the Clinicaltrials.gov registry with precision medicine objectives and reporting race and ethnicity—a total of 93 studies with 5867 ...
SYSTEMIC MANAGEMENT OF BREAST CANCER
BREAST CANCER INTRODUCTION • Is one of the deadliest and most common cancers ailing women all over the world • In Australia 1 in 13 women will develop ca breast at sometime in her life • In USA 215,990 women will be found to have invasive ca breast in 2004 • More common in older than younger women with average age of diagnosis of 64 years.
Prospective metabolome-wide association study suggests environmental
BACKGROUND AND AIM[|]DDT and perfluorinated alkyl substances (PFAS) are environmental chemicals linked to breast cancer in the Child Health and Development Studies (CHDS) pregnancy cohort. In earlier metabolome-wide association studies (MWAS) of CHDS women, we found serum amino acid metabolism varied in association with DDT and PFAS. The aim of the present study was to determine whether ...
Wavelength-resolved measures of outdoor artificial light-at-night and
BACKGROUND AND AIM[|]Evidence from studies of outdoor artificial light-at-night (ALAN) and cancer risk has been mixed, which may be attributable to inadequate consideration of confounding by other built environment factors and a focus on measures of light intensity. The primary mechanism thought to underlie ALAN carcinogenicity involves melatonin suppression, which is wavelength and intensity ...

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BREAST: anatomy, imaging techniques & clinical/radiological cases

Presentation on theme: "BREAST: anatomy, imaging techniques & clinical/radiological cases"— Presentation transcript:

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Case Presentation on Locally Advanced breast Cancer

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Anubha Bharthuar, MD

Case Presentation: Management of Metastatic Breast Cancer

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Sociodemographic inequalities in breast cancer screening attendance in Germany following the implementation of an Organized Screening Program: Scoping Review

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Information sources and literature search

Selection of the sources of evidence

Data items and data charting process

Critical Appraisal of the individual sources of evidence

Synthesis of the results

Study characteristics

Critical appraisal of included sources of evidence

Breast cancer screening attendance rates across studies

Evaluation reports of the German mammography screening programme

Sociodemographic inequalities in breast cancer screening participation

Age (6 effects)

Education (11 effects)

Income (4 effects)

Migration status (7 effects)

Type of district (3 effects)

Employment status (7 effects)

Partnership cohabitation (2 effects)

Health insurance (2 effects)

Strengths and limitations

Conclusions and implications

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Supplementary Material 1

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Racial and Ethnic Disparities Among Participants in Precision Oncology Clinical Studies

SYSTEMIC MANAGEMENT OF BREAST CANCER

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