Enhanced Surveillance vs. Risk Reducing Mastectomy for BRCA+ Patients with Advanced Ovarian Cancer: Surgical Futility or Valuable Prevention?

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1 Enhanced Surveillance vs. Risk Reducing Mastectomy for BRCA+ Patients with Advanced Ovarian Cancer: Surgical Futility or Valuable Prevention? Gina Westhoff, MD LMG Gynecologic Oncologist

2 The level of risk is different for every patient 64 year-old with BRCA2 mutation 24 year-old with BRCA1 mutation 41 year-old with BRCA1 mutation and advanced ovarian cancer The psychosocial context is different for each patient November 15, 2017 LEGACY HEALTH 2

3 Cumulative risk estimated for breast cancer by age 80 > 70% for BRCA1 > 75% for BRCA2 When known DCIS was excluded > 68% BRCA1 > 63% BRCA2 11/15/2017 LEGACY HEALTH 3

4 Incidence per 1000 Person-Years Age-Related Breast Cancer Incidence in BRCA1 and BRCA2 Carriers 35 Breast Cancer Incidence per 1000 Person-Years BRCA1 BRCA < Age During Follow-up Adapted from 11/15/2017 LEGACY HEALTH 4

5 Other factors that influence breast cancer risk in mutation carriers BRCA mutation position in gene 1,2 First degree relatives with younger-age breast cancer (BRCA2 patients) 3 Number of relatives with breast or ovarian cancer 2 Geographic Location 4 Physical Activity 5 Breast Feeding 6 [1] Kuchenbaecker KB. JAMA 317(23) [2] Antonioua A. Am. J. Hum. Genet. 72: [3] Semple S. Breast Cancer Res Treat Nov;154(1): [4] Moller P. Clin Genet 83: [5] Pettapiece-Phillips R. Cancer Causes Control. 26(3): [6] Jemostrom H. J Natl Cancer Inst. Jul 21;96(14): /15/2017 LEGACY HEALTH 5

6 NCCN Recommendations for Enhanced Screening Women with a known mutation begin Breast Awareness at 19 y/o Semi-annual breast exams beginning at 25 y/o Between 25-29: Annual MRI with contrast > Done on days 7-15 of menstrual cycle After age 30, alternating Mammogram and MRI every six months along with clinical breast exam 11/15/2017 LEGACY HEALTH 6

7 Enhanced Screening Pros Mammography has robust data as the standard screening modality 1 > Decrease in breast cancer mortality for general population MRI + Mammogram screened patients have a better prognosis when diagnosed 2 > Decreased tumor size (0.9 vs. 1.9) > Decreased number of lymph node positive patients > More Stage1 IDC, and more DCIS identified Preserves sexual function, body image and ability to breast feed [1] Berg WA. J. Clin. Onc. 32: [2] Chiarelli AM. J Clin Oncol 32: , /15/2017 LEGACY HEALTH 7

8 Enhanced Screening Cons : False Positives Mammogram false positives rate 1 > 10% of women are called back each year > Cancer in only % of women screened > Tomosynthesis (3-D Mammography) and second look ultrasound decreases false positives of mammography MRI also has high rate of false positives 2 > MRI has higher sensitivity (77-94%) compared to Mammography (22-59%) > Up to 18% of high risk MRI screened women undergo biopsy, while only 1.2% ultimately have breast cancer diagnosed Contributes to significant anxiety, expense [1] Padamsee TJ. Breast Cancer Research. 19: [2] Wendie AB. Journal Clin. Onc. 32: /15/2017 LEGACY HEALTH 8

9 Enhanced Screening Cons MRI limited utility in patients who are > Claustrophobic > Have metal > Mobility issues > Estimated 18.5% of women are unable to tolerate MRI 1 Costly to patients and the medical system Mutation carriers still develop interval cancers 2 > As high as 32% in BRCA1 carriers > 6.3% in BRCA2 carriers Not a cancer prevention tool [1] Berg WA. Radiology 254:79-87,2010 [2] Rijnsburger AJ. J Clin Oncol 28: , /15/2017 LEGACY HEALTH 9

10 Risk Reducing Bilateral Mastectomy Pros Goal is cancer prevention Reduction in breast cancer incidence % 1,2 > Risk of developing breast cancer after surgery is around 1% Reduction in risk of death from breast cancer 81-94% Women are satisfied with their decision 2 > Would recommend it to other patients Women have significantly decreased cancerassociated anxiety after surgery 3 [1] Ludwig KK. Am J. of Surg. 212: [2] Lostumbo L. Prophylactic mastectomy for the prevention of breast cancer Cochrane Review [3] Josephson U. Eur. J. Surg. Oncol. 26(4): /15/2017 LEGACY HEALTH 10

11 Risk Reducing Bilateral Mastectomy Cons ~30% of BRCA patients are getting an unnecessary operation > Higher in patients diagnosed with OvCa Patients are less satisfied with their cosmetic outcome > 36% of women report diminished satisfaction with their physical appearance 1 > 53% did not feel that their new breasts were a part of the own body [1] Josephson U. Eur. J. Surg. Oncol. 26(4): /15/2017 LEGACY HEALTH 11

12 Risk Reducing Bilateral Mastectomy Cons Sensory Changes > Numbness > Partial sensation was maintained in only 57% following surgery 1 Impact on Sexual Function > 74% reported significant loss of pleasurable sensation Chronic Pain > 10-30% of mastectomy patients Unanticipated revisions > Up to 57% of patients undergo unexpected revisions 2 > Most common revisions were implant exchange or capsulotomy and breast scar revision [1] Khan A. Eur J. Oncol. 42: [2] Donovan CA. Ann Surg. Oncol /15/2017 LEGACY HEALTH 12

13 What should BRCA1/2 patients with advanced ovarian cancer do? 11/15/2017 LEGACY HEALTH 13

14 Risk/benefit ratio changes when diagnosed with ovarian cancer BRCA1/2 patients with ovarian cancer live LONGER 1 > 5yr OS: 36% BRCAwt, 44% BRCA1, 52% BRCA2 > BRCA1 HR 0.76 ( ); BRCA HR 0.58 ( ) Breast cancer risk after a diagnosis of ovarian cancer may be LOWER than expected 2 > 5 year risk of breast cancer: BRCA1/2: 6% General population: 16% Breast cancer free survival is excellent 3 : > 97% at 5yrs and 91% at 10 years > All deaths in this cohort were due to ovarian cancer [1] Bolton et al. JAMA 2012 and Zhong et al. Clin Can Res 2015 [2] Venken et al. Cancer 2013 [3] Domcek et al. Cancer 2013

15 Goals for BRCA carriers diagnosed with ovarian cancer: 1. Identify the likelihood of surviving ovarian cancer (disease free at 12yrs) 2. Determine probability of being diagnosed with breast cancer 3. Estimate effects of RRM v MRI on survival to age 80 when diagnosed with ovarian cancer by age 50 (Bernoulli models)

16 Risk of dying from ovarian cancer decreases each year from diagnosis 50% risk of death by 4 yrs Probability of surviving OvCa: At diagnosis: 26% 11 year survivors: 98%

17 Absolute reduction in all-cause mortality by age 80: MRI v. RRM (%) MRI RRM 1 0 No cancer, age 50 Stage III-IV, Dx age 50 Stage III-IV, wait 5yrs Staeg III-IV, wait 10yrs Stage I-II, Dx age 50 11/15/

18 Absolute risk of breast cancer and benefits from either RRM and MRI are LOW Risk of breast cancer at 10 years: 3.8% Stage I/II: > RRM or MRI at completion of tx Stage III/IV: > RRM or MRI if dx age <50 and survive 10 years

19 Goals, for BRCA carriers with Stage II-IV ovarian cancer: 1. Determine if RRM or MRI/mammo is most cost effective strategy 2. Estimate survival benefit of RRM and MRI/mammo

20 RRM cost-effective for with OvCa diagnosed at early age When to get RRM after diagnosis of OvCa > BRCA1: Age 40: 4 years later Age 50: 5 years later Age 60:? > BRCA2: Age 40: 5 years later Age 50: 8-10 year later? Age 60:??

21 What is the survival benefit? If you model sensitivity analysis that oophorectomy decreases breast cancer incidence by 50%, then RRM is never cost effective.

22 Summary: BRCA patients with ovarian cancer Must individualize for each patient > Family history > Anxiety > Were they getting breast cancer surveillance before OvCa Dx? For Stage I/II patients: > start enhanced surveillance or discuss RRM at time of diagnosis For Stage III/IV patients: > Data suggests very limited survival benefit with RRM > Consider waiting on enhanced surveillance until 2 year mark (or longer) > Use RRM selectively. If considering RRM, wait 4-5 years after diagnosis for BRCA1 and longer for BRCA2

23 Thank you!