Breast Cancer Updates Risks, Genetics, DCIS For Fellows November 2016

American Cancer Society, 2015 Statistics

Risk Factors Female Age: median 57-62 Family history Previous biopsies Atypical changes BRCA positive Hormone replacement Alcohol use Obesity North European No pregnancies Late in life pregnancies Dense breasts Chest wall irradiation Oral contraceptives: ?long term use

Risk Factors for Breast Cancer Female Age Age of first delivery Age of menarche First degree family members affected Atypical hyperplasia Genetic (BRCA1/2) Increased density Obesity/body fat Physical inactivity Alcohol Hormone replacement Chest radiation therapy ? Oral contraceptive ? Tobacco use

Not Risk Factors Bras—no increased risk with underwire Trauma Deodorant Abortions Pesticides Electrical power lines ? Oral contraceptives Many dietary concerns without proof (yet)

Reducing the Risk of Breast Cancer For Those with Increased Risk Bilateral mastectomies: drastic, 95% effective Bilateral oophorectomies: reduces the risk in BRCA positive women, by 50% Tamoxifen or Raloxifene daily for 5 years based on data from P1 and P2 trials Exemestane daily for 5 years Not yet approved for this use in the U.S. One published European study

Breast Cancer Prevention / Risk Reduction NSABP P-1 and P-2 (STAR) P1 Tamoxifen vs Placebo in high risk women 1992 Risk is 1.66% using the Gail Model Over 35 minimum age, included ADH 13,388 women in USA and Canada with 69 months follow up Reduces risk of recurrence up to 50% for ER positive breast cancers No reduction in cancer mortality

P2 Study of Tamoxifen and Raloxifene 1999 Around 13,647 women with 1.66% risk level of higher Both essentially equal for invasive cancer risk reduction Slightly better reduction in DCIS with tamoxifen Endometrial cancer slightly higher with tamoxifen Only reduces risk of estrogen positive cancers

So why are not more women on these medications? Side effects No impact on cancer mortality Is there really enough risk reduction to justify the side effects? Taking the time to do the calculation Understanding that most women who get breast cancer are not going to die of it ???

Ductal Carcinoma in Situ Non invasive breast cancer (?) Test for ER/PR Usefulness of HER 2 to be determined; trials have been slow to accrue Graded Current treatment Segmental mastectomy with radiation therapy or mastectomy (if extensive) Hormonal therapy to be considered if ER positive

But there is more to talk about High grade DCIS Consider doing sentinel node since may find microscopic invasive disease Low grade DCIS Surgery without radiation therapy

Hormonal Therapy Is it treatment or risk reduction Tamoxifen vs placebo 2% vs 4% for invasive cancer 4% vs 5% for noninvasive cancer NSABP/NRGY B 35 Tamoxifen vs Anastrazole Equal with maybe a little benefit of AI in the 50 year olds IBIS II DCIS Anastrazole vs Tamoxifen Noninferiority Lancet 2016

European Studies IBIS II High risk arm Exemestane vs Placebo Anastrazole vs placebo Exemestane vs Placebo About 4500 women A little over 3 year in follow up Saw reduction in 21 cancer events out of 2280 women

Assessing the Risk Family genetics BRCA 1 and 2 (also ovary, male breast cancer, prostate, colon ca, pancreas) P53 (Li Fraumeni) (also brain, adrenal ca, sarcoma, leukemia) PTEN (Cowden’s) (also thryoid ca., hamartomas, prostate ca) Ataxia telangectasia-life time risks increased for heterozygotes (autosomal recessive) Lynch Syndrome-usually associated with colon but can also have breast cancer

Genetic Testing Only 5% of all diagnosed women are positive for the BRCA 1 /BRCA2 gene Risk factors include early age, heritage, family history of breast, ovarian, prostate, pancreatic, history of second breast cancer Genetic testing should be accompanied by genetic counseling to understand when should the test be done and what to do with the information Women who are positive or at high risk due to history need to have informed discussions about their options

Changes in Genetic Testing Myriad had a monopoly on testing for years Now there are several companies doing testing Panels have broadened Consider retesting if tested years ago Consider retesting if only had the “Jewish”panel done