PGY 101: Chapter 74 Breast Breast Cancer in the US Breast Cancer is estimated to affect over 230,000 women annually in the US Based on SEER Database rates from , the cumulative lifetime risk of an average woman in the general US population is 12.3% Estimated 15,480 new cases of female breast cancer in Florida Breast Cancer in the US Greatest risk in the 5 th and 6 th decade of life Median Age at Diagnosis 61 Breast Cancer in the US Early Detection through screening Advances in Systemic Therapy Patient Education Personalized Care Percent surviving 5 years 89.2% SEER Cancer Statistics 2014 Breast Cancer What is Breast Cancer? Breast Cancer Risk Non-Modifiable Being a Woman Getting Older Family History of Cancer Menstruating Early Late Menopause Never Having Children Older Age at First Birth History of Radiation Dense Breasts History of Breast Biopsy History of Abnormal Biopsy Modifiable Hormone Therapy Obesity Unhealthy Diet Sedentary Lifestyle Drinking Alcohol Lack of Screening Education, Awareness, Action History of Breast Cancer in First degree relatives increase an individuals risk of breast cancer 2-fold increased risk in women whose sisters or mothers have had breast cancer Hereditary Breast Cancer Stratton MR. Nat Genet. 2008;40:17 Family History Known inherited alterations in genes that lead to an increased risk of developing breast cancer Genetics Approximately 5-10% of all breast cancer Lead to a 10- to 20 fold increased lifetime risk of developing breast cancer as well as many associated cancers Ovarian, Pancreas, Prostate, Melanoma, Thyroid, Colon Cancers occur at younger ages Inherited Gene Alterations BR (Breast) CA (Cancer) Susceptibility genes (BRCA 1 & BRCA 2) Approximately 80% of all hereditary breast cancers Cumulative lifetime risk of Breast Cancer: BRCA 1 65-87% BRCA 2 45-55% Cumulative lifetime risk of Ovarian Cancer: BRCA 1 39-51% BRCA 2 11-35% What if a Woman has a strong Family History but Negative for BRCA? Risk Calculators Mammography remains the only study proven to detect early breast cancer and decrease breast cancer related deaths Breast cancer mortality reduction up to 40% Screening detected cancers Smaller in size Less likely to have lymph nodes involved Less likely to receive chemotherapy Screening American Cancer Society Recommendations Yearly mammograms are recommended starting at age 40 and continuing for as long as a woman is in good health Clinical breast exam (CBE) about every 3 years for women in their 20s and 30s and every year for women 40 and over Women should know how their breasts normally look and feel and report any breast change promptly to their health care provider Breast self-exam (BSE) is an option for women starting in their 20s Recommendations vary based on risk General Population Baseline mammogram between and annual mammography starting at age 40. Start 10 years younger then your youngest 1 st degree relative diagnosed with breast cancer High Risk Population Annual mammography and MRI starting at the age of 30 BRCA 1 or 2 carriers 1 st degree relative of BRCA carriers but untested Lifetime risk of 20-25% based on family risk assessment models History of chest wall radiation Screening Diagnostic Imaging Addition of Spot Magnification Mammographic Views, Breast Ultrasound, and or MRI Mag Views Ultrasound MRI 12345 Biopsy for Diagnosis Stereotactic Ultrasound MRI Stage Tumor Size Lymph Node Involvement Spread to other Organs Tumor Proteins ER PR Her2 Neu Cancer Staging Size Nodes Metastasis Tumor Marker Profile: ER/PR/Her 2 status Breast Cancer Treatment Cure Breast Whole Body Surgical Oncologists Radiation Oncologists Plastic/Reconstructive Surgeons Medical Oncologists Anti-Estrogen Therapy Chemotherapy Targeted Therapy Surgical Treatment Breast TissueLymph Nodes Breast Saving Mastectomy Dr. William S. Halsted ( ) Halstedian Principle: Cancer spreads in an orderly, slow, and localized manner, contiguous with its site of origin The Complete Operation The result of operations for the cure of cancer of the breast performed at the Johns Hopkins Hospital from June 1889 to 1894 Skin Envelope NAC Breast Tissue Pectoralis Major and Minor Axillary Levels I-III Radical Mastectomy Surgical Evolution Radical Mastectomy Modified Radical Mastectomy Skin Sparing Mastectomy Nipple Sparing Mastectomy Partial Mastectomy No difference in Survival Fisher B, Anderson S, Bryant J et al. N Engl J Med. 2002;347: NASBP B06 Breast Conservation Fisher B, Anderson S, Bryant J et al. N Engl J Med. 2002;347: NSABP B06 Breast Conservation Breast Conservation Candidacy Focality of Disease Tumor Location PMH/Genetic Prior Radiation Cosmetic Outcome Reconstructive Surgery Womens Health and Cancer Rights Act of 1998 Mandated that all health plans include breast and nipple reconstruction as well as contralateral breast symmetry procedures to all mastectomy patients Surgical Evolution Levels I, II, III Levels I, II Sentinel Lymph Node Biopsy Giuliano AE. Ann Surg. 1994;220: Sentinel Lymph Node Biopsy Penile Squamous Cell Cancer Cabanas Penile Squamous Cell Cancer Cabanas Breast Cancer Giuliano Breast Cancer Giuliano Melanoma Morton Melanoma Morton Cabanas RM. Cancer. 1977;39: Morton DL. Surg Oncol Clin North Am. 1992;1: Giuliano AE. Ann Surg. 1994;220: Cabanas RM. Cancer. 1977;39: Morton DL. Surg Oncol Clin North Am. 1992;1: Giuliano AE. Ann Surg. 1994;220: StudyYear(n)IdentificationAccuracyNegative Predictive Value SensitivityFalse Negative Rate Giuliano Sentinel lymph node biopsy is an accurate method of axillary lymph node staging in women with early stage clinically node negative breast cancer Giuliano AE. Ann Surg. 1994;220: Randomized Controlled Trials StudyYear(n)Identification Rate (%) Accuracy (%) Negative Predictive Value (%) Sensitivity (%) False Negative Rate (%) Veronesi Krag Zavagno Veronesi U. N Engl J Med. 2003;349: Krag DN. Lancet Oncol. 2007;8: Zavagno G. Ann Surg. 2008;247: Randomized Controlled Trials StudyYear(n)LocalRegional Overall Survival Disease Free Survival ALNDSLNBALNDSLNBALNDSLNBALNDSLNB Veronesi Krag Zavagno Veronesi U. Ann Surg. 2010;251: Krag DN. Lancet Oncol. 2010;11: Zavagno G. Ann Surg. 2008;247: ACOSOG Z0011 Clinical T1-T2, N0, M0 undergoing BCT + XRT (n=856) Clinical T1-T2, N0, M0 undergoing BCT + XRT (n=856) + ALND (n=420) + ALND (n=420) Endpoints: Locoregional Recurrence Overall Survival Endpoints: Locoregional Recurrence Overall Survival No ALND (n=436) No ALND (n=436) Giuliano AE, McCall L, Beitsch et al. Ann Surg. 2010;252: Patient with 2 SLNB ACOSOG Z0011 Giuliano AE, Hunt K, Ballman KV et al. JAMA. 2011;305: % 91.8% 83.9% 82.2% ACOSOG Z0011 Giuliano AE, McCall L, Beitsch et al. Ann Surg. 2010;252: SLNB + ALNDSLNB Local Recurrence Regional Recurrence ACOSOG Z0011 At 6.3 year follow-up, women with clinically node-negative early stage breast cancer with < 3 positive sentinel nodes, who underwent breast conservation surgery demonstrated: No Benefit in Locoregional control following ALND No Benefit in Overall or Disease-free survival following ALND Breast Cancer Treatment Cure Breast Whole Body Surgical Oncologists Radiation Oncologists Plastic/Reconstructive Surgeons Medical Oncologists Anti-Estrogen Therapy Chemotherapy Targeted Therapy Adjuvant Therapy Whole Breast Radiation All Breast Conservation Locally Advanced Mastectomy Nodal Disease Close Margins Inflammatory Partial Breast Radiation Selected Early Stage Radiation Therapy Chemotherapy Endocrine Therapy Tamoxifen Aromatase Inhibitors Targeted Therapy Additional Therapy Systemic Therapy Clinical Stage Biology of the Tumor Tumor Marker Profile Oncotype Endocrine Therapy (Anti Estrogen Therapy) Any ER or PR + patient > 1% Premenopausal/DCIS: Tamoxifen, Postmenopausal: Aromatase Inhibitors Chemotherapy ER/PR/Her2 negative Any Her2 + +/- ER/PR + Her2 negative Node + disease Targeted Therapy: Herceptin Her 2 + Adjuvant Therapy Systemic Therapy Genomic Profiling of Tumors Oncotype DX Clinical Practice Guidelines NCCN GuidelinesConsider use in >0.5cm, HR+, HER 2 negative disease, pT1-3 and pN0 or pN1mic ASCO GuidelinesNewly diagnosed patients with node-negative, ER+ breast cancer who will receive tamoxifen Oncotype DX Proliferation Ki-67 STK15 Survivin Cyclin B1 MYBL2 Invasion Stromelysin 3 Cathepsin L2 HER 2 GRB7 HER2 Reference Ki-67 GAPDH RPLPO GUS TFRC Other GSTM1 CD68 BAG1 Estrogen ER PR Bcl-2 SCUBE2 16 Cancer Genes 5 Reference Genes Paik S et al. NEJM. 2004;351:2817 RS 30 NSABP B-14: Recurrence Score as Predictor of 10 yr Distant Recurrence (n=675) Oncotype DX Paik S et al. NEJM. 2004;351: yr Rate of Distant Recurrence 6.8% 14.3% 30.5% 95% CI (4-9.6%) (8-20.3%) ( %) Women with Node-negative, HR+ Breast Cancer Oncotype DX Low RSIntermediate RSHigh RS Endocrine + chemo Endocrine + chemo Treatment Algorithm Classic Treatment Design: Surgery +/- Chemo +/- XRT +/- Endocrine Neoadjuvant therapy: Chemo Surgery +/- XRT +/- Endocrine Inflammatory Breast Cancer: Chemo +/- Surgery, XRT, Endocrine Neoadjuvant Chemotherapy Surgical: Treat locally advanced cancers Convert mastectomy candidates into breast conservation candidates Improve cosmesis in patients undergoing breast conservation Medical: Use primary tumor and nodal response to tailor locoregional and systemic therapy Identify better predictors of complete response Pre- Neoadjuvant Post- Neoadjuvant pCR Pre- Neoadjuvant Post- Neoadjuvant Loco-Regional Endpoints In Breast pCR: 25-30% w/ anthracyclines/taxanes 40-50% w/ chemo + trastuzamab in HER-2+ 50-60% w/ chemo + two anti-HER-2 agents Axillary pCR: 30% w/ anthracyclines Up to 40% w/ anthracyclines/taxanes > 50% w/ chemo + anti-HER-2 therapies True or False: 97% of the lymphatic drainage of the breast drains to the internal mammary lymph node basin. True or False: Axillary Node Levels are based on the pectoralis major muscle When performing a modified radical mastectomy, what levels of axillary nodes are removed? 1.Level I 2.Level II 3.Level III 4.All of the above 5.Only A & B Which is the only screening modality that has shown to decrease mortality from breast cancer in woman over the age of 50? 1.Breast Ultrasound 2.Breast Mammography 3.Breast MRI 4.Breast Thermography A 24 you woman undergoes a breast ultrasound for a self-palpated left breast mass. You order a breast ultrasound which is demonstrated below. What Bi-Rad classification is this lesion? 1.Bi-Rads 0 2.Bi-Rads 1 3.Bi-Rads 2 4.Bi-Rads 4 A 63 you woman undergoes a breast ultrasound for a self-palpated left breast mass. Her diagnostic breast ultrasound is demonstrated below. What Bi-Rad classification is this lesion? 1.Bi-Rads 0 2.Bi-Rads 1 3.Bi-Rads 2 4.Bi-Rads 5 Which Bi-Rads classification recommends 6 month short term follow up imaging? 1.Bi-Rads 0 2.Bi-Rads 2 3.Bi-Rads 3 4.Bi-Rads 4 True or False: Breast cancer affects 1 in 8 women in the United States. Indications for genetic testing in a patient diagnosed with breast cancer are? 1.A woman diagnosed prior to the age of 45 2.A woman diagnosed at any age, who has two family members with breast, ovarian or pancreatic cancer 3.Any man diagnosed with breast cancer 4.All of the above True or False: Survival is improved in patients undergoing mastectomy for a Stage II and Stage III breast cancer as compared to breast conservation surgery. 55 yo postmenopausal woman presents to you for a high risk evaluation. You perform quantitative risk assessment on her using the GAIL risk assessment model. Her 5 year risk is 4.2% as compared to 1.8% of the general population, and her lifetime risk is 42% as compared to 16% of the general population. Your talk to her about chemoprevention. Which medications would you use for chemoprevention? 1.Raloxifene 2.Tamoxifen 3.Exemestane 4.All of the above 5.1 & 3 True or False: A 48 yo woman presents to your office for evaluation of newly diagnosed Triple negative inflammatory breast cancer. You explain that your treatment algorithm includes modified radical mastectomy followed by adjuvant chemotherapy and radiation therapy. A 72 yo old undergoes her screening mammogram. She is called back for compression views of her left breast which is demonstrated below. What is the next step in management? 1.Ultrasound guided percutaneous biopsy 2.Stereotactic percutaneous biopsy 3.Wire localized excisional biopsy 4.Short term follow up diagnostic breast imaging in 6 mo Your patient undergoes a stereotactic biopsy. Her pathology demonstrates grade 2 DCIS ER 0%, PR 24%. The area of calcifications spans 2 cm. What is not a treatment option for your patient? 1.Surgery 2.Tamoxifen 3.Radiation Therapy 4.Chemotherapy True or False: Radiation therapy decreases risk of local recurrence by at least 50%. True or False: Approximately 20% of all breast cancers are associated with genetic mutation. True or False: Male breast cancer is higher in BRCA 1 gene mutation carriers. A 62 yo woman is diagnosed with a new screen-detected left breast cancer. On clinical exam her tumor measures 3 cm in size. What is her T stage? 1.Tis 2.T1 3.T2 4.T3 5.T4 A 65 yo woman presents with a 6 week history of eczematoid changes to her right nipple. She has tried every over the counter moisturizer and lose dose steroid cream without relief. She states that her recent mammogram was just prior to the onset of symptoms which was negative. You punch biopsy the skin and it is diagnostic for paget cells within the dermis. What is the next step in management? 1.Central lumpectomy with sentinel lymph node biopsy 2.Simple mastectomy with sentinel lymph node biopsy 3.Breast MRI 4.Modified Radical Mastecotmy Pagets Disease 1-3% of all breast cancers Eczematoid changes of the nipple: itching, erythema, nipple discharge Dx: Biopsy demonstrates Paget cells in the dermis (in-situ disease) Typically underlying malignancy therefore get diagnostic imaging, if negative include MRI Tx: Classically mastectomy, but depending in- breast disease central lumpectomy + XRT A 57 yo woman presents to your office with complaints of a 1 month history of breast erythema, induration, and edema. She was prescribed antibiotic therapy by her PCP which did not help with her symptoms. Due to persistence in symptoms, her PCP referred her to you for evaluation. What is pathognomonic for her disease process? 1.Dermal lymphatic invasion 2.Pagetoid cells within the dermis 3.Lymphovascular invasion 4.All of the above What is the mainstay of treatment for the above patient? 1.Modified Radical mastectomy 2.Chemotherapy 3.Radiation therapy 4.Central lumpectomy A 62 you woman is recently diagnosed with a screen-detected right breast invasive ductal carcinoma. She undergoes wire localized segmental mastectomy with sentinel lymph node biopsy. Her final pathology demonstrates a 2 cm invasive ductal carcinoma, ER/PR positive, Her 2 neu negative with clear margins and negative lymph nodes. What adjuvant therapy does she need? 1.Chemotherapy because her tumor is > 1 cm in size plus radiation therapy and an aromatase inhibitor 2.No chemotherapy because her lymph nodes were negative, therefore only radiation therapy and an aromatase inhibitor 3.Send an Oncotype score to determine need for chemotherapy, then proceed with radiation therapy followed by an aromatase inhibitor 4.Only Tamoxifen What if the above patients Oncotype returned as 12? 1.No chemotherapy, but radiation therapy followed by an aromatase inhibitor 2.Chemotherapy followed by radiation therapy and an aromastase inhibitor 3.Radiation therapy alone 4.None of the above True or False: All woman undergoing breast conservation therapy who have a positive sentinel lymph node require completion axillary dissection. Benign Breast Disease Fibrocystic Changes Generic term used to describe symptoms related to the aberration of normal development and involution of the breast Encompasses: Cyclical Change Cyst formation Fibroadenoma formation Duct ectasia Sclerosing Adenosis Benign Nodular breast tissue Cysts Fluid filled round structures derived from the terminal duct lobular unit Common in Perimenopausal women Fluctuate in relation to the menstrual cycle and hormonal milieu Cysts Exam: Firm or Rubbery, well defined Imaging: US (Anechoic) Mammography Treatment: Asymptomatic:Observation Symptomatic: Aspiration Recurrent or Bloody: Excision A 21 yo old woman presents for evaluation of a self- palpated right breast lump. You order an ultrasound which is demonstrated below. What is the next step in management? 1.Reassure her that it is benign and tell her to follow as needed 2.Reassure her that it is benign and have her follow up in 6 months with repeat ultrasound 3.Explain that it is likely benign however recommend surgical excisional biopsy 4.Explain that you are concerned that it is malignant and move forward with an ultrasound guided biopsy Fibroadenomas Fibroepithelial Lesion Solid round structures arise from the epithelium of the terminal duct lobular unit Most common breast mass in adolescent women Occur from teens through 70s Fibroadenoma Exam: Painless well circumscribed mass 10-20% are multiple or bilateral Imaging: US (Isoechoic, wider than tall, gently lobulated/elliptical) Mammography Treatment: Observation Surgical Giant Juvenile Enlarging Symptomatic: Painful Fibroadenoma A 34 yo uninsured woman presents to your office with a neglected left breast mass. She cannot fit in the mammography unit, therefore you order a breast ultrasound, for which a representative image is demonstrated below. You order an ultrasound guided biopsy. Her pathology is also provided. What is her most likely diagnosis? 1.Locally advanced Invasive ductal carcinoma 2.Inflammatory breast cancer 3.Locally advanced invasive lobular carcinoma 4.Borderline malignant phyllodes tumor Phyllodes Tumor Fibroepithelial Lesion 50 Treatment: Excisional biopsy Mastalgia Common complaint Typically no histologic difference in women with or without mastalgia Treatment is reassurance rule out malignancy if age appropriate Evening primrose oil, and vitamin E have been studied in randomized controlled trials The most common cause of bloody nipple discharge is? 1.Duct ectasia 2.Intraductal papilloma 3.DCIS 4.Invasive ductal carcinoma A 45 yo woman presents for evaluation of bloody nipple discharge. She states that it is unilateral, single duct, and spontaneous. She underwent diagnostic mammogram last week which was normal. What is your next step in management? 1.Repeat mammogram 2.Breast MRI 3.Retroareolar ultrasound 4.Ductogram 5.3&4 Your previous patient undergoes an ultrasound and ductogram which is demonstrated below. What is your diagnosis? 1.Ductal carcinoma in situ 2.Invasive ductal carcinoma 3.Duct ectasia 4.Intraductal papilloma Nipple Discharge Accounts for 3-8% of all breast clinic referrals Typically associated with a benign cause 2/3 rd of non-lactating women have a small amount of fluid on manual expression Risk of cancer increases with age: < 40 3% 1% > 60 32% Divided into Surgical and Non surgical nipple discharge Surgical: Papillomas, DCIS, Cancer Nonsurgical: Physiologic, endocrine, pharmacologic, idiopathic Nipple Discharge Exam: Number of ducts Laterality Color Spontaneity Imaging: Mammo Ultrasound (retroareolar) Ductogram Treatment: Duct excision selected or terminal duct excision Ductogram Duct Ectasia Dilation of the subareolar duct in peri and post-menopausal women Typically asymptomatic May present with cheesy, viscous, toothpaste like discharge or have nipple retraction Observation, unless discharge is persistent or repeated bouts of periductal mastitis/abscess Papilloma Typically arise from central/subareolar ducts Most common in women 30 to 50 years of life 50% are single lesions 30% present with bloody nipple discharge Treatment is surgical excision because of upgrade rates: DCIS 10.5% ADH 14.5% Papilloma Terminal Duct Excision A 34 yo woman presents for evaluation of a new right breast mass. She states that it is associated with fevers, chills, and has been progressively worsening over the past 24 hours. What is your plan in treatment? 1.Systemic chemotherapy followed by surgery if good response 2.Antibiotic therapy and surveillance 3.Ultrasound guided biopsy 4.Incision and drainage with antibiotic therapy Breast Infection Lactational MCO: Staph Aureus First 6 wks or during weaning Either from mouth of baby or skin of nipple Related to blockage of lactiferous ducts stagnate milk bacterial overgrowth Diagnosis: Clinical exam and breast ultrasound Tx: Aspiration/Drainage/Abx Non-lactational (Periductal Infection) MCO: Staph Aureus Young smokers Associated with duct ectasia Secretions become stagnate in dilated ducts bacterial overgrowth Diagnosis: Clinical exam and breast ultrasound Tx: Aspiration/Drainage/Abx or Fistulotomy Which of the below is not an indication for surgical excision? 1.Atypical ductal hyperplasia 2.Radial scar 3.Flat epithelial atypia 4.Discordance between pathology and radiographic imaging 5.Pseudoangiomatous Stromal Hyperplasia 6.All of the above are indications for excision Pseudoangiomatous Stromal Hyperplasia (PASH) Myofibroblasts that proliferate in response to hormonal stimuli Affects women from teens to 50s Presents as discrete painless mass Imaging: focal asymmetry or well circumscribed mass Treatment: Observation (some studies suggest excision) Increase risk of recurrence up to 22% Fibromatosis Desmoid tumor of the breast Affects women from teens to 80s Typically presents as firm unilateral painless mass Microscopically the tumor is composed of spindle cells Margins are infiltrative and typically invade around normal structures Proper treatment is wide local excision The role of adjuvant radiation and chemo is investigational