So much has changed. Breast Cancer Update. Terri Cusick MD FACS

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1 So much has changed. Breast Cancer Update Terri Cusick MD FACS

2 Disclosure: Myriad Genetics Speakers Beaureau

5 Biggest Changes Nipple sparing mastectomies Chemotherapy decisions based on tumor biology rather than size. Node + or... ER-, Her 2+, oncotype Z0011 trial results SLN NCCN update- pancreatic cancer, triple negative breast cancers

6 Improvements Radical Mastectomy Modified Radical Mastectomy Lumpectomy and axillary node dissection SENTINEL LYMPH NODE mastectomy or lumpectomy Oncoplastic surgery lumpectomy with local tissue rearrangement reduction lumpectomy skin and nipple sparing mastectomies

7 BI-RADS Breast Imaging Recording and Data System 0- Incomplete 1- Without lesion 2- Benign lesion 3- Lesion of low suspicion 4- Moderately suspicious lesion 5- Highly suspicious lesion

13 Specimen Mammogram

14 How a cancer SHOULD present... Left MLO

16 CORE Needle The diagnosis of breast cancer should come from a core needle biopsy -not an open biopsy -margins -timing -SLN -not a FNA -invasive vs. non invasive -ER/PR status

18 QUESTION A 42 year old woman undergoes a stereotactic core bx of a 1 cm mammographically detected lesion of her left breast that demonstrates infiltrating ductal breast CA (grade 2, ER/PR negative, HER2/neu positive). A paternal aunt had breast cancer at age 55 and a second paternal aunt had ovarian cancer at age 51. The next step in this patient s management should be... A. MRI B. Simple mastectomy and SLN C. Needle loc lumpectomy and SLN D. Genetic counseling/testing E. Neoadjuvant chemotherapy

19 Oncoplastics Combining plastic surgery and breast cancer surgery Preplanning required Team approach with plastic surgeon Some cases- cancer surgeon only

22 Mastectomy with reconstruction

23 Nipple Sparing

25 Nipple Nipple Sparing Mastectomy Specimen Nipple Sparing

28 Peau de orange

31 Basic Breast Aesthetics Nipple position and height is key The nipple needs to reside on the meridian 2/3 down the humerus, just at or above the IMF NAC to midline cm (LK example) Sternal notch to nipple 19-21cm-normal or pubescent breast cm-mature or ptotic breast

33 Breast MR Used to prove uni-focal disease Lobular breast cancer Multifocal Increased incidence of bilaterality Difficult to visualize with mammography Vague physical exam Dense Mammograms Young patients Occasionally older pts with dense mammos (look at cancer on the mammogram)

34 CHEMOTHERAPY Changes in treatment... Chemotherapy decisions are no longer based on size of tumor and lymph node status alone... Individualized to the patient! Tumor BIOLOGY...

36 Pre-Operative Chemotherapy Neo-adjuvant Chemotherapy Inflammatory Breast Cancer Chemo, mastectomy, radiation Large tumors in an attempt to close with mastectomy Large tumors in an attempt to proceed with breast conservation Note that not all cancers shrink concentrically Smaller vs. the swiss cheese effect Must place a tumor marker!!! Node Positive Patients Enlarged nodes noted at time of dx, FNA+ Suspected BRCA Allows additional time for testing to return

39 many different presentations...

40 The must not miss diagnosis- INFLAMMATORY BREAST CANCER

41 Talking to pt/family post-op Chemotherapy Node Positive ER-, her2+ Oncotype high recurrence score Oncologist preference

42 16 Cancer and 5 Reference Genes From 3 Studies Oncotype DX 21-Gene Recurrence Score (RS) Assay PROLIFERATION Ki-67 STK15 Survivin Cyclin B1 MYBL2 INVASION Stromelysin 3 Cathepsin L2 HER2 GRB7 HER2 ESTROGEN ER PR Bcl2 SCUBE2 GSTM1 CD68 REFERENCE Beta-actin GAPDH RPLPO GUS TFRC BAG1 RS = Category RS (0-100) Low risk RS <18 Int risk RS 18 and <31 High risk x HER2 Group Score x ER Group Score x Proliferation Group Score x Invasion Group Score x CD x GSTM x BAG1 RS 31

43 nnals of Surgery: eptember Volume Issue 3 - pp oi: /SLA.0b013e3181f08f32 riginal Articles ocoregional Recurrence After Sentinel Lymph Node Dissection With or Without Axillary issection in Patients With Sentinel Lymph Node Metastases: The American College of urgeons Oncology Group Z0011 Randomized Trial iuliano, Armando E. MD*; McCall, Linda MS ; Beitsch, Peter MD ; Whitworth, Pat W. MD ; Blumencranz, Peter MD ; Leitch, A. Marilyn MD ; Saha, Sukamal MD**; Hunt, elly K. MD ; Morrow, Monica MD ; Ballman, Karla PhD

44 Z0011 Trial September 2010 American College of Surgeons Oncology Group Prospective, randomized trial. SLND (446) vs. SLND and ALND (445) 6.3 yr F/U= no difference in local or regional recurrence Despite the potential for residual disease, SLND without ALND may be reasonable management for selected patients with early stage breast cancer treated with breast conserving therapy and adjuvant systemic therapy.

45 Z0011 Trial September 2010 What does this mean for our mastectomy patients? What does this mean for our neoadjuvant chemotherapy patients? Z1071 trial- SLN and ALND

48 The Great Mammogram Debate -Patrick Borgen -There will never be a randomized controlled study for mammograms. (Should we do a randomized controlled study to determine if we should put parachutes in airplanes? -The cure rate for screening detected mammograms is so high -In a screening study, symptomatic people must be excluded from the trial. Women with palpable masses and palpable LN were placed in the screening arm of the study. -Some portable Xray machines were repurposed for mammography. - 2 trial advisors resigned in protest over design

54 BRCA 1. <=45yo or <60 and triple negative yo two cancers (breast, ovarian) 3. >50 need 3 cancers

55 Updated NCCN Guidelines HBOC V For Women with Cancer Early onset breast cancer(s) Ovarian cancer (epithelial ovarian/fallopian tube) Breast and ovarian cancer in the same woman Bilateral breast cancer (2 primaries) Male breast cancer Ashkenazi Jewish heritage alone BrCa <50 with limited family structure Pancreatic cancer + family history of BrCa Triple Negative BrCa <60 Jennifer Klemp, PhD, MPH

Updated Triple-Negative NCCN Guidelines TNBC accounts for ~15% of all BrCa, but as much as 60-90% of BRCA1 carriers Several studies have indicated that

56 Updated Triple-Negative NCCN Guidelines TNBC accounts for ~15% of all BrCa, but as much as 60-90% of BRCA1 carriers Several studies have indicated that triple negative BrCa are more likely to have a BRCA mutation and treatment response made be determined by tumor characteristics Jennifer Klemp, PhD, MPH

58 BRCA Up to 87% lifetime risk of developing breast CA 27-44% lifetime risk of developing ovarian CA

60 Timing of oophorectomy important if placing mesh... ovaries?

62 Surgeon s Lounge

72 Post-Mastectomy Radiation Classic Indications Tumor larger than 5 cm 4 or more +LN Involved margins/chest wall Inflammatory Breast Cancer Possible Indications nodes in pre-menopausal pt

73 Post Mastectomy Radiation Attempt to predict preoperatively who will need postmastectomy radiation Place muscle flaps AFTER radiation TRAM flaps Latissimus flaps These flaps may be used to reconstruct AFTER radiation Does Alloderm help decrease capsular contraction? Consider fully expanding PRIOR to radiation Place implant vs. flap

74 2006 ASCO Recommendations As part of education and informed consent prior to cancer therapy, oncologists should address the possibility of infertility with patients treated during their reproductive years and be prepared to discuss possible fertility preservation options or refer appropriate and interested patients to reproductive specialists. Clinician judgment should be employed in the timing of raising this issue, but discussion at the earliest possible opportunity is encouraged. Sperm and embryo cryopreservation are considered standard practice and widely available; other available fertility preservation methods should be considered investigational and be performed in centers with the necessary expertise. Lee SJ, et al. J Clin Oncol 2006;24(18):1-16

76 Lawrence J. Schneiderman, MD Chair Emeritus Keynote Lecture: Wrong Medicine: Why Do We Pursue Futile and Costly Overtreatment? Does your hospital have a medical futility policy? We control how patients die. Give them a good death. Provide 100% pain control. 50% of US bankrupties are due to medical costs.

77 Hot Flashes Citalopram 20 mg/d (better than Effexor) not with Tamoxifen Vaginal Estrogen Ring Gabapentin Amitriptyline 10mg/d Megace 20 mg/d x 2-3 months (flares of hotflashes intense x 1 week)

78 Dr. Jennifer Klemp

79 Breast Cancer Risk Factors Relative Risk Jennifer Klemp, PhD, MPH

80 The Supreme Court unanimously ruled that although naturally isolated DNA is not patentable, synthetically created exon-only strands of nucleotides complementary (c)dna is patentable.

81 Rare changes in other genes associated with breast cancer. GENE ATM P53 or TP53 CHEK2 PTEN CHD1 PALB2 DESCRIPTION Helps repair damaged DNA. Linked to increased risk of BrCa Provides instructions for making a protein to stop tumor growth. Causes Li-Fraumeni syndrome and increases soft tissue cancer at young ages and higher risk of BrCa, leukemia, brain tumors, and sarcomas. Provides instructions for making a protein to stop tumor growth. Causes Li-Fraumeni syndrome and can double breast cancer risk. Helps regulate cell growth. Causes Cowden syndrome leading to higher risk of both benign and cancerous tumors in the breast, digestive tract, thyroid, uterus, and ovaries. Supports protein growth that helps cell adherence and tissue formation. Increased risk of lobular BrCa and rare, early onset stomach cancer. Supports protein growth that works with the BRCA2 protein to repair damaged DNA and stop tumor growth. Doubles BrCa Risk. Inheriting 2 abnormal PALB2 genes causes Fanconi anemia, higher risk of cancer, including kidney cancer and brain cancer

82 Li-Fraumeni Syndrome

83 Cowden Syndrome

84 Assists with surgical management decisions Surgery: Breast Lumpectomy vs. Mastectomy +/- Prophylactic mastectomy risk by up to 90-95% Ovaries Risk Reducing Salpingo-oophorectomy + fallopian tubes +/- uterus ( risk by >95%) risk of breast cancer by 50-70% risk of ovarian cancer by > 95% 15% Survival Advantage Probable for BRCA1/2 Carriers Jennifer Klemp, PhD, MPH Cost Effective

cancer 20%-60% Ovarian cancer 15-45% Possible increased risk

85 BRCA1-Associated Cancers: Risk by age 70 Breast cancer 50-85% (often early age at onset) Second primary breast cancer 20%-60% Ovarian cancer 15-45% Possible increased risk of other cancers Jennifer Klemp, PhD, MPH JCO 2004;22: ; NCI 2005

86 BRCA2-Associated Cancers: Risk by age 70 Breast cancer (50-85%) Breast cancer (6%) Second primary breast cancer (20-60%) Ovarian cancer (10-27%) Prostate (20%) Increased risk of pancreatic cancer and melanoma Jennifer Klemp, PhD, MPH JCO 2004;22: ; NCI 2005

87 Additional Recommendations Intervention Chemoprevention Average Risk Not indicated High Risk BRCA 1/2 Mutation Consider Tamoxifen or Raloxifene or Aromasin or Clinical Trials Consider Tamoxifen or Raloxifene or Aromasin or Clinical Trials Prophylactic Surgery Not indicated Possibly, but not common Consider, significant risk reduction + survival benefit Weight Control YES YES YES Increase Physical Activity YES YES YES Limit EtOH intake YES YES YES Jennifer Klemp, PhD, MPH

Relative Risk Associated with Family History Varies by Age of Onset and Numbers of Close Relatives Number of close relatives 1 relative: doubling of relative risk 2 relatives or bilateral BrCa:

88 Relative Risk Associated with Family History Varies by Age of Onset and Numbers of Close Relatives Number of close relatives 1 relative: doubling of relative risk 2 relatives or bilateral BrCa: tripling of relative risk 3 relatives: quadruples relative risk By Age at diagnosis Under 40 : tripling of relative risk : doubling of relative risk Jennifer Klemp, PhD, MPH Cuzick Breast Cancer 2008; 10 :S13

89 Summary Differences Between Models GAIL Only use if >35 5-yr and lifetime risk No calculation BRCA1/2 mutation risk Considers bx as risk even with no precancer Validated in US screening population Tyrer-Cuzick Can use < 35 yrs of age 10 year and lifetime risk (remaining risk) Calculates BRCA1/2 risk Biopsies without precancer no risk Validated in European high risk clinic Considers major & minor factors Jennifer Klemp, PhD, MPH Tyrer Stat Med ; 23 : 1111

90 Web Resources NCI: NCI Gail Risk Calculator: Myriad Risk Calculator: Tyrer Cuzick Model: Claus: Jennifer Klemp, PhD, MPH e.showsoftware&prodid=29820

Breast Cancer: Current Approaches to Diagnosis and Treatment

Breast Cancer: Current Approaches to Diagnosis and Treatment Barbara L. Smith, MD, Ph.D. Massachusetts General Hospital Division of Surgical Oncology No Disclosures Incidence of Breast Cancer USA 2018