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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
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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
• 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
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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