#278 ‒ Breast cancer: how to catch, treat, and survive breast cancer | Harold Burstein, M.D., Ph.D.
Dr. Harold Burstein, Professor of Medicine at Harvard Medical School and a leading breast cancer expert, provides a comprehensive overview of breast cancer. He discusses its anatomy, three main subtypes (ER+, HER2+, triple-negative), various screening methods, and advanced treatment strategies including surgery, radiation, and systemic therapies. The episode also delves into genetic predispositions like BRCA mutations and the critical role of multidisciplinary care.
Deep Dive Analysis
18 Topic Outline
Introduction to Breast Cancer and Dr. Burstein's Background
Prevalence and Mortality Rates of Breast Cancer
Breast Anatomy and Development Throughout a Woman's Life
Environmental and Lifestyle Factors Influencing Breast Cancer Risk
Three Major Subtypes of Breast Cancer
Breast Density and its Relationship to Cancer Risk
Evaluating Breast Lumps and Benign Findings
Ductal Carcinoma In Situ (DCIS) and Lobular Carcinoma In Situ (LCIS)
Screening Methods: Mammography, Ultrasound, and MRI
Staging of Invasive Breast Cancer and Prognostic Factors
Arguments for Aggressive Breast Cancer Screening
Adjuvant and Neoadjuvant Therapies for Breast Cancer
Distinction Between Chemotherapy and Targeted Therapies
Hormone Replacement Therapy Post-Breast Cancer Diagnosis
Genetics of Breast Cancer: BRCA1/2 and Other Mutations
Importance of Multidisciplinary Cancer Care
Male Breast Cancer: Incidence and Treatment Principles
Concluding Thoughts on Progress in Breast Cancer Treatment
7 Key Concepts
Three Major Flavors of Breast Cancer
Breast cancers are broadly categorized into three main types based on receptor status: Estrogen Receptor (ER) positive/HER2 negative (most common, peak incidence around age 65, often found on mammography), Triple Negative (lacking ER, Progesterone Receptor, and HER2; earlier onset, more common in younger and African-American women, more virulent), and HER2 positive (amplification of HER2 oncogene, historically aggressive but now highly treatable with targeted therapies).
Ductal Carcinoma In Situ (DCIS)
DCIS is a pre-cancerous lesion where abnormal cells accumulate within the breast ducts but have not yet penetrated the surrounding breast tissue. It is considered Stage 0 breast cancer, analogous to a colon polyp, and is typically identified via calcifications on a mammogram.
Lobular Carcinoma In Situ (LCIS)
LCIS is another pre-cancerous lesion, often considered a 'field risk marker,' indicating a woman is at a slightly increased risk for developing invasive breast cancer in either breast. Unlike DCIS, it is not typically treated with surgery and radiation, but rather with close monitoring and sometimes anti-estrogen therapy.
Adjuvant Therapy
Adjuvant therapy refers to treatments given after the primary surgery for cancer, aiming to prevent recurrence by eliminating any microscopic disease that might remain in the body. This can include radiation, chemotherapy, anti-estrogen therapy, or targeted drugs.
Neoadjuvant Therapy
Neoadjuvant therapy involves giving systemic drug treatment (like chemotherapy or targeted therapy) before surgery. This approach is used for larger tumors to shrink them, potentially allowing for less extensive surgery, and provides valuable information on how well the tumor responds to treatment, which can guide subsequent therapy.
Genomic Tests (e.g., Oncotype DX)
These are tests performed on tumor tissue that analyze patterns of gene expression to assess the risk of cancer recurrence and predict the benefit of chemotherapy, particularly in ER-positive breast cancers. They help oncologists determine which patients can safely avoid chemotherapy.
Pathologic Complete Response (pCR)
A pCR occurs when, after neoadjuvant therapy, a pathologist examines the surgically removed tissue and finds no residual cancer cells. This is a highly favorable prognostic finding, indicating a very good response to treatment and placing the patient in a lower risk category.
12 Questions Answered
American women have approximately a one in eight, or 12%, lifetime risk of developing breast cancer.
Roughly 15% to 18% of women diagnosed with breast cancer are at jeopardy for recurrence and death, meaning 80% to 85% are cured.
Breast size itself does not fundamentally affect breast cancer risk, as all women generally have a similar amount of glandular tissue, though extreme breast size can correlate with obesity, which is a weak risk factor.
If a core biopsy diagnoses DCIS, the first step is usually an excisional biopsy to surgically remove the affected tissue and check for any underlying invasive cancer.
Treating DCIS has not been shown to affect mortality because the diagnosis is made so early that there is likely no survival benefit from intervention.
Modern radiation techniques use tangential field radiation, careful anatomical mapping, specific blocks, and breath-holding techniques to spare the heart and lungs, making the risk of coronary artery disease incredibly low.
Mammography is the most important screening tool for breast cancer for most individuals, supplemented by self-awareness of one's body.
Prognosis is primarily determined by tumor size, lymph node involvement (nodal status), and the biological features or subtype of the tumor (ER/PR/HER2 status, grade, genomic tests).
The median survival for stage 4 metastatic breast cancer is approximately 5 years, though this varies significantly depending on the subtype of breast cancer.
For most breast cancer patients, particularly those with ER-positive tumors, oral HRT is avoided due to systemic estrogen exposure. Non-hormonal options or localized estrogen preparations (like vaginal creams) are preferred to manage symptoms.
Roughly 8% to 10% of all breast cancer diagnoses are related to a specific hereditary gene mutation, with BRCA1 and BRCA2 accounting for about half of these.
Multidisciplinary care brings together specialists like surgeons, radiation oncologists, medical oncologists, pathologists, and genetic counselors to collaborate, ensuring a coordinated and comprehensive treatment plan, which is crucial for effective cancer management.
26 Actionable Insights
1. Prioritize Early Breast Cancer Detection
Actively pursue early detection methods for breast cancer, as catching tumors when they are small (2 cm or less with no lymph node involvement) significantly increases the chance of cure (90-95% 10-year remission). This is your best bet for a positive outcome.
2. Practice Breast Self-Awareness
Be aware of your body and breast tissue, understanding what feels normal, and seek medical evaluation immediately if you feel anything different, suspicious, or concerning. This approach, rather than rigid self-exams, has been shown to change mortality by allowing early detection.
3. Regular Mammography Screening
Regularly undergo screening mammograms as recommended by your doctor, as it is the most important screening tool for breast cancer. Supplement this with personal breast awareness.
4. Use MRI for High-Risk Screening
If you are at very high risk for breast cancer (e.g., strong family history, BRCA1/2 mutation), incorporate annual MRI screening, often staggered with mammograms, into your detection plan. This is a crucial tool for early detection in high-risk populations.
5. Seek Multidisciplinary Cancer Care
When diagnosed with breast cancer, seek care from a multidisciplinary team that includes surgeons, radiation oncologists, medical oncologists, pathologists, genetic counselors, and imaging specialists. This collaborative approach ensures comprehensive and coordinated treatment.
6. Assess Cancer Care Team Collaboration
When choosing a cancer care facility, evaluate whether the providers (surgeons, oncologists, radiologists, pathologists) regularly communicate and function as a unified team, potentially through monthly tumor boards. A lack of such collaboration might indicate a need to seek care elsewhere.
7. Obtain Second Pathology Opinion
Always consider getting a second opinion on your pathology slides, especially if there’s any ambiguity or if your local center is less experienced. You have the right to request a section of your tissue specimen be sent to another pathologist for review.
8. Undergo Genetic Testing Post-Diagnosis
Following a breast cancer diagnosis, pursue genetic testing to identify any hereditary gene mutations (e.g., BRCA1/2, PALB2, CHEK2, ATM). This information is crucial for tailoring your treatment, surveillance, and prevention strategies, and for informing family members.
9. Consult Genetic Counselor for Family History
If you have a strong family history of cancer, consult with a genetic counselor or a cancer center specialist to discuss genetic testing options. This ensures appropriate testing and interpretation of results for personalized risk assessment.
10. Get Suspicious Lumps Evaluated
If a breast change or lump is appreciated by you or a clinician, ensure you get appropriate imaging (mammography, ultrasound, MRI) and, if necessary, a tissue biopsy to understand what is happening. This is crucial for accurate diagnosis and timely intervention.
11. Understand Adjuvant Therapy’s Role
If diagnosed with early-stage breast cancer, understand that adjuvant therapy (radiation, drug therapy) is crucial after surgery to target and eliminate any microscopic cancer cells that may have spread, thereby preventing recurrence.
12. Consider Neoadjuvant Therapy
If you have a larger breast tumor, discuss neoadjuvant therapy (drug therapy before surgery) with your team. This approach can shrink the tumor, potentially allowing for less extensive surgery, and provides valuable prognostic information based on the tumor’s response.
13. Utilize Genomic Tests for Chemotherapy
For ER-positive, HER2-negative breast cancer, discuss genomic tests like Oncotype DX with your oncologist. These tests help determine your tumor’s risk and can often help you avoid unnecessary chemotherapy if your score indicates low risk.
14. Modern Radiation Minimizes Heart Risk
Be aware that modern radiation therapy techniques for breast cancer, such as tangential field radiation and breath-holding, are designed to minimize risk to the heart and lungs. Discuss these advancements with your radiation oncologist to understand the significantly reduced risks compared to older methods.
15. Inquire About Shorter Radiation Courses
Ask your radiation oncologist about the possibility of shorter radiation treatment courses, as the standard has decreased from 25 fractions to 16, with even shorter 5-day options being explored. This can reduce the overall time commitment for treatment.
16. Actively Manage Anti-Estrogen Side Effects
Be proactive in discussing and managing side effects from anti-estrogen therapies (like hot flashes, vaginal dryness, bone issues) with your oncology team. Many non-hormonal or localized hormonal options exist to alleviate discomfort and maintain quality of life.
17. Re-evaluate Treatment for Severe Side Effects
If you are experiencing severe or life-altering side effects from a long-term medication, such as tamoxifen, do not hesitate to revisit the discussion with your oncologist. It is important to communicate your quality of life concerns and explore alternative strategies.
18. Avoid Systemic HRT Post-Cancer
If you have a history of breast cancer, generally avoid oral hormone replacement therapy (HRT) due to systemic estrogen exposure. Instead, explore non-hormonal or localized hormonal treatments for menopausal symptoms that do not result in significant systemic absorption.
19. Undergo Excisional Biopsy for DCIS
If diagnosed with DCIS via core biopsy, typically undergo an excisional biopsy to surgically remove the affected breast tissue. This removes the DCIS and helps detect if there’s an underlying invasive cancer component (which occurs in 15-20% of cases).
20. Consider Radiation After DCIS Lumpectomy
If you are a younger, healthy woman (70 or younger) diagnosed with DCIS and have had a lumpectomy, strongly consider a course of radiation therapy to the breast. This is a standard approach to significantly lower the risk of DCIS or new invasive breast cancer recurrence in the breast.
21. Discuss Anti-Estrogen Therapy for DCIS
Discuss with your doctor whether to add anti-estrogen therapy (like tamoxifen or aromatase inhibitors) after DCIS treatment, understanding it offers a modest 3-5% reduction in recurrence risk over a decade. Weigh this benefit against potential long-term side effects and personal preferences.
22. Closely Monitor LCIS
If diagnosed with LCIS, engage in very close medical monitoring and consider anti-estrogen therapy to lower your risk of developing breast cancer. Note that LCIS is typically managed with surveillance and medication, not surgery or radiation.
23. Evaluate Absolute Risk Reduction
When considering preventative therapies like tamoxifen for conditions like LCIS, understand that while relative risk reduction can be significant, the absolute risk reduction might be modest (e.g., a few percentage points). Weigh this carefully against potential side effects and your personal motivation.
24. Expect and Manage Radiation Skin Effects
Anticipate that radiation treatment can cause skin irritation similar to a severe sunburn, leading to redness, soreness, and swelling. Be prepared to manage this discomfort, knowing that these acute side effects typically resolve over time as the skin heals.
25. Men, Be Aware of Breast Changes
Men should be aware that they can develop breast cancer and should seek medical evaluation for any changes or nodularity in their breast tissue. Early detection in men, as in women, improves prognosis.
26. Understand Individual vs. Population Risk
Understand the difference between population-level cancer risk and your individual risk when evaluating personal health factors. This helps prevent undue alarm or complacency based on general statistics.
5 Key Quotes
The good news is that only a small fraction of those will be fatal. The fatality or the mortality associated with breast cancer depends on the stage at which it is caught, and it also depends on the subtype of breast cancer because we have different treatment programs for each of the different subtypes of breast cancer.
Harold Burstein
Breast cancers largely arise from the ductal or the glandular tissue. And in this respect, breast cancer shares its origins with almost all common cancers, prostate cancer, colon cancer, lung cancer, where it is the glandular part of the organ from which arises the malignant cell.
Harold Burstein
The most important thing is if a patient does appreciate a change in the breast or a lump in the breast, certainly if a physician or other clinician provider feels something suspicious, it is very important to get appropriate imaging and, if necessary, a tissue biopsy to make sure we understand exactly what's going on.
Harold Burstein
The anti-estrogen medicines, which are very common, remember 80 plus percent of tumors are estrogen receptor positive and nearly all those patients would be advised to have anti-estrogen medications. So the side effects all relate to the estrogen deprivation, hot flashes, night sweats, bone and joint stiffness and achiness, hair thinning, not hair loss, but thinning finer hair, somewhat of a receding hairline, vaginal dryness and sexual health issues or frequent urinary tract infections related to changes in the epithelial of the genital tract, osteoporosis, all these things are related to the loss of estrogen.
Harold Burstein
The quality of pathology is the foundation for all of cancer care. And again, breast cancer, very common, usually begins in the breast. It's usually not so mysterious, but oftentimes a pathology review is vital importance.
Harold Burstein
3 Protocols
DCIS Treatment Following Core Biopsy
Harold Burstein- Perform an excisional biopsy (surgical removal of the affected tissue) to remove the DCIS and check for any invasive cancer.
- For women who had a lumpectomy (not mastectomy), strongly consider radiation therapy to the breast to lower the risk of in-breast recurrence.
- Discuss adding anti-estrogen therapy (e.g., tamoxifen or aromatase inhibitors) to further lower the risk of in-breast recurrence or developing invasive cancer, considering the small absolute benefit and side effects.
Management of LCIS (Lobular Carcinoma In Situ)
Harold Burstein- Provide very close monitoring (e.g., annual mammography).
- Consider anti-estrogen therapy (e.g., tamoxifen) to lower the risk of developing invasive breast cancer.
Genetic Testing and Management for Hereditary Breast Cancer Risk
Harold Burstein- Conduct genetic testing for BRCA1, BRCA2, PALB2, CHEK2, ATM, and other relevant gene mutations, especially after a breast cancer diagnosis or with a strong family history.
- For individuals with BRCA1/2 mutations, consider prophylactic mastectomy due to the risk of a second breast cancer.
- For individuals with BRCA1/2 mutations, consider prophylactic oophorectomy (ovary removal) after childbearing to lower ovarian cancer risk, as there is no good screening tool for ovarian cancer.
- Offer more intensive screening (e.g., annual MRI staggered with annual mammogram) for women with high-risk mutations who choose to retain their breasts.
- Advise extended family members about their potential risk and genetic testing options.