Increased Risk of Breast Cancer: Screening and Prevention Elizabeth Pritchard, MD 4/5/2017
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Defining Risk
Risk Factors Modifiable Lifestyle obesity physical activity alcohol consumption breast feeding Exogenous hormone exposure
Risk Factors Non - Modifiable Increasing age Family history Precancerous breast lesions Breast density Reproductive factors early menarche/late menopause nulliparity late parity
Risk Factors Average 12% lifetime risk no family history no high risk biopsies no HRT
Risk Factors High risk 1 st degree relative at age <50 history atypical hyperplasia history LCIS increased density Gail model 1.7 IBIS/Tyler Cuzick 20
Gail Model www.cancer.gov/bcrisktool/
IBIS/Tyler Cuzick Risk Calculator Downloaded
Risk Factors Very high risk BRCA mutation History thoracic radiation age 10-30
Pruthi, et al, Annals Surgical Oncology, 2015
Atypical Ductal Hyperplasia Relative risk: 4 cumulative risk at 25 yrs of 30% increases linearly over time increased with positive FH Features of breast cancer 78% ductal 88% ER positive Not included on ACS MRI recommendation Hartmann, et al, NEJM, 2015
Atypical Ductal Hyperplasia Core biopsy ADH upgrade 15 30% increased number of foci increased risk of cancer Hartmann, et al, NEJM, 2015
LCIS Relative risk: 8-10 lifetime risk 30-40% Features of breast cancer mostly ductal either breast Not on ACS list for MRI, but others recommend annual MRI and mammogram
Thoracic Radiation Most common Hodgkin s lymphoma Non Hodgkin s lymphoma Wilms tumor bone tumors neuroblastoma soft tissue sarcoma
Thoracic Radiation Factors affecting risk total dose 20 40 Gy time since treatment increases at 8 years median time 15 years age at treatment highest for puberty to 30yo
Thoracic Radiation Increased incidence bilateral cancer Pathology no different Survival no different stage by stage Cumulative incidence - 20% by 40-45yo
Thoracic Radiation Screening CBE annually from puberty to 25 q 6 months after Mammogram/MRI annually from age 25 or 8 yrs after XRT
Thoracic Radiation Prevention No trial with SERM, but should be considered Surgery can be considered
Enhanced Screening
ACS Recommendations for High Risk Screening Mammogram and MRI annually Lifetime risk of breast cancer 20 25% Known BRCA 1 or BRCA2 mutation or other mutations First degree relative with a mutation in pt who has not had testing Radiation therapy to the chest between ages 10 and 30
NCCN Guidelines BRCA Mutation Positive Screening Age 25 29: annual MRI screening individualized if cancer at <30 mammogram if MRI not available Age 30 75: annual mammogram and MRI Age > 75: individualized
Chemoprevention
NSABP P1 Randomized to tamoxifen vs placebo Gail risk 1.7% 5 year risk Tamoxifen decreased risk by 49% AH 86% LCIS - 56% (small sample size) At 7 year f/u, benefits persist after stopping Fisher, et al, JCNI, 1998
NSABP P2 STAR trial Randomized to tamoxifen vs raloxifene Raloxifen equivalent in reducing risk in postmenopausal women Updated in 2010, median f/u 81 months Benefits greater with tamoxifen Risks less with raloxifene no increased uterine cancer slightly lower VTE Vogel, et al, JAMA, 2006
National Cancer Institute of Canada MAP.3 trial Randomized to exemestane vs placebo 35 month followup Exemestane reduced risk by 65% Not FDA approved Goss, et al, NEJM, 2011
Goss, et alnejm, 2011
IBIS II trial Randomized to anastrozole vs placebo 5 year median followup Anastrozole reduced risk by 53% Not FDA approved Cuzick, et al, Lancet, 2014
Tamoxifen Risks and Side Effects Annual Risks (Placebo) VTE, stroke 1.45 (0.92) per 1000 PE 0.69 (0.23) per 1000 more common in older women endometrial cancer 2.3 (0.93) per 1000 lower in premenopausal vasomotor symptoms67 117 per 1000
Risks and Side Effects Aromatase inhibitors Not associated with risk of thromboembolic or cardiovascular events Worse age-related bone loss in spite of Ca and vit D Vasomotor symptoms Musculoskeletal symptoms
Barriers to Usage Physician lack of information time constraints Patient fear of side effects lack of understanding of cancer risk
54% of women at increased risk accept recommendation for prevention. 40% of those don t complete 5 years because of side effects.
Prophylactic Surgery
Bilateral mastectomy Genetic mutation Previous thoracic radiation LCIS ADH
Bilateral mastectomy Always discuss reconstruction Consider nipple sparing Not 100% preventative 90 97%
Lifestyle modification
Obesity Nurses Health Study 121,000 women enrolled from 1976 95% followup in 2002 evaluated weight changes since age 18 and since menopause average weight gain since 18yo 12 kg average weight gain since menopause (8 yrs) 3 kg Eliassen, et al, JAMA, 2006
Obesity Relative risk of breast cancer Since 18yo gain 25kg or more 1.45 gain of 20 25kg 1.18 Since menopause gain 10 kg or more 1.18 loss 10 kg or more 0.77 no HRT 0.63 Eliassen, et al, JAMA, 2006
Conclusion: Obesity Over 5 years in 100,000 women not on HRT : 1145 who maintained weight would develop breast cancer 2267 who gained 10 pounds would develop breast cancer Eliassen, et al, JAMA, 2006
Obesity Mechanisms of increased risk adipose is source of estrogen by aromatization of adrenal androgens possibly hyperinsulinemia associated with obesity
Physical Activity Compared women with <1 hr per wk walking and 1 hour per day brisk walking Breast cancer - HR 0.85 10 30 % lower risk comparing highest level of activity to lowest ER/PR positive and ER/PR negative Eliassen, et al, Archives Int Med, 2010
Physical Activity Decreases circulating estrogen and androgen May improve insulin sensitivity decrease circulating insulin levels enhance immune activity decrease chronic inflammation Eliassen, et al, Archives Int Med, 2010
Alcohol Consumption 2 or more drinks per day RR 1.3 1.4 compared to none
Tamini, et al, Am JlEpidemiology, 2016
Exogenous estrogen Estrogen/progestin therapy RR 1.3 1.4 risk of death higher increases within first 2-3yrs goes back to average after stopping increased with longer duration of therapy and higher dose Estrogen alone therapy increases risk after 10 years
Conclusions Patients at increased risk for breast cancer can benefit from enhanced screening and education about risk modification. Chemoprevention provides a significant decrease in the risk of breast cancer. Lifestyle modifications also provide a real decrease in the risk of breast cancer.