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

2. American Cancer Society, 2015 Statistics

3. 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

4. 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

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

6. 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

7. 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

8. 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

9. 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
???

10. 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

11. 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

12. 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

13. 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

14. 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

15. 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

16. 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