Breast Cancer: Key issues for the non-oncologist Primary Care - PDF document

4/7/15 ¡ Breast Cancer: Key issues for the non-oncologist Primary Care Medicine Jeffrey A. Tice, MD Associate Professor Update 2015 Department of Medicine April 2015 Department of Medicine • I have no financial disclosures • I developed and validated one of the models that will be discussed. I hold no patents and derive no financial benefit from the model. 2 1 ¡

4/7/15 ¡ OUTLINE Department of Medicine • Risk Assessment • Risk Reduction • Screening – Dr. Judith Walsh – Follow-up abnormal mammography • Tests at Diagnosis 3 Case: Maria Department of Medicine • 35 yo white woman, has 2 children ages 1 and 4. She started menstruating at age 11 and took birth control pills from age 19 to 26. • She recently had a biopsy for a breast lump which was benign (cyst) • Her mother diagnosed BC at age 69 • She is an advertising executive and drinks 2-3 glasses of wine/night. 2 ¡

4/7/15 ¡ Maria ’ s questions Department of Medicine • What is my risk for developing breast cancer? • What can I do to lower my risk? Department of Medicine Risk Assessment 6 3 ¡

4/7/15 ¡ Why risk assessment? Department of Medicine • Breast cancer is most commonly diagnosed cancer in U.S. women – 1 in 8-9 women will be diagnosed in her lifetime • 2 nd most common cause of cancer death in women – > 40,000 deaths in 2015 • Risk assessment tools are available • Risk reduction is possible Risk factors for breast cancer • Strong • Weak – Age – Age at first birth Department of Medicine – Breast density – Menarche age – Atypical hyperplasia – Height, weight, BMI – LCIS – Bone mineral density – BRCA mutation – NAF/Lavage • Moderate – SNPs – Age of diagnosis for – Family history family history – Breast biopsy – 2nd degree relatives – Race / ethnicity – Alcohol intake – Hormone therapy – Diabetes – Hormone levels (E2, T, – Physical activity IGF-1) – Breast feeding – Benign breast disease – Menopause age 4 ¡

4/7/15 ¡ Factors Considered in Department The Gail Risk Model of Medicine • Current age • Race / Ethnicity • Age at menarche • Age at first live birth • Number of 1° relatives with BC • Number of breast biopsies • Presence of ADH Gail et al . J Natl Cancer Inst 81:1879; 1989. Gail Model on NCI website Department of Medicine http://www.cancer.gov/bcrisktool/ • 5 year and lifetime estimates by race Validated for populations; but modest discriminatory value for the individual . Rockhill et al . J Natl Cancer Inst 93:358, 2001. 5 ¡

4/7/15 ¡ Case: Maria Department of Medicine • 35 yo white woman, has 2 children ages 1 and 4. She started menstruating at age 11 and took birth control pills from age 19 to 26. • She recently had a biopsy for a breast lump which was benign (cyst) • Her mother diagnosed BC at age 69 • She is an advertising executive and drinks 2-3 glasses of wine/night. What is Maria ’ s 5-year risk for BC? Department of Medicine 1. < 0.5% 2. 0.5 to 1.49% 3. 1.5 to 2.49% 4. ≥ 2.5% 6 ¡

4/7/15 ¡ Maria ’ s risk using the Gail model Department of Medicine • 5 years: 1.0% • Lifetime (to age 90): 25.8% Average 35 year old woman • 5 years: 0.3% • Lifetime (to age 90): 12.6% Risk factors not in Gail model • Weak • Strong – Age at first birth – Age Department of Medicine – Menarche age – Height, weight, – Atypical hyperplasia – Bone mineral density – LCIS – NAF/Lavage – SNPs • Moderate – Age of diagnosis for – Family history family history – Breast biopsy – 2nd degree relatives – Race / ethnicity – Diabetes – Hormone levels (E2, T, IGF-1) – Breast feeding – Benign breast disease – Menopause age 7 ¡

4/7/15 ¡ Mammographic Breast Density Department of Medicine • BI-RADS RR a Almost entirely fat 1.0 b Scattered densities 2.0 c Heterogeneously dense 2.8 d Extremely dense 4.1 • Prevalence: ~50% for BIRADS 3 and 4 density • About 10% for BIRADS 1 and 10% for BIRADS 4 Kerlikowske JNCI 2007 SB 1538: California’s New Breast Density Law Department of Medicine • For women with BIRADS c and d BD, radiologists must inform women – that they have dense breasts – that dense breasts make it harder to detect breast cancer – That dense breasts are associated with a higher risk of breast cancer • Similar laws in 21 states in the US and a national bill is before Congress 16 8 ¡

4/7/15 ¡ BCSC breast density model Department of Medicine • Age, race, BD, family history, breast biopsy https://tools.bcsc-scc.org/BC5yearRisk/ Tice, Annals IM, 2008. Maria ’ s 5-year risk comparing models Department of Medicine Gail Model 1.0% BCSC Model • Almost entirely fat .24% • Scattered densities .50% • Heterogeneously dense .77% • Extremely dense 1.0% (Average 35 yo woman’s 5 year risk is 0.3%) 9 ¡

4/7/15 ¡ The future of risk prediction Department of Medicine • The combination of common SNPs are the single most important risk factor not included in current models – Each individual SNP contributes little information – 76 SNPs combined are more powerful than any other risk factor • Genetic testing is becoming less expensive since the Supreme Court invalidated the patents on BRCA1 and BRCA2 19 Department of Medicine Risk Reduction 20 10 ¡

4/7/15 ¡ Which of these will NOT decrease Maria ’ s risk for breast cancer? Department of Medicine 1. Eating more fruits and vegetables 2. Brisk walking 30 minutes/day 3. Losing 10 kg (to BMI of 24 kg/m 2 ) 4. Cutting back on alcohol Which of these will NOT decrease Maria ’ s risk for breast cancer? Department of Medicine 1. Eating more fruits and vegetables 2. Brisk walking 30 minutes/day 3. Losing 10 kg (to BMI of 24 kg/m 2 ) 4. Cutting back on alcohol 11 ¡

4/7/15 ¡ LIFESTYLE Department of Medicine 23 No association with breast cancer • Fruits & vegetables Department of Medicine – Smith-Warner, JAMA, 2001 – Pooled prospective studies – 7377 cases in 351,825 women • Carotenoids; Vitamins A, C, E • Selenium Mixed results on dietary fat intake – the jury is still out Obesity • Premenopausal – small decreased risk • Postmenopausal – increased risk 12 ¡

4/7/15 ¡ Alcohol and breast cancer risk: 
 Meta-analysis 2.5 Multivariate Relative Risk 2.0 1.5 1.0 7% increase in risk per drink per day Smith-Warner, 1998 0 0 10 20 30 40 50 60 Total Alcohol Intake g/d Exercise and risk of breast cancer Department WHI Observational Cohort of Medicine (n=74,171; 1780 cancers) • Overall 30-40% decreased risk 1.2 • Greatest in 1 thinner women 0.8 • Lifetime exercise RR 0.6 matters 0.4 • 4 hours per week 0.2 0 0 ≤ 5 5 to >40 10 MET-h/week McTiernan, JAMA, 2003. 13 ¡

4/7/15 ¡ Hormone Therapy Department Women’s Health Initiative of Medicine • E + P 1.24 (1.01-1.54) ITT 1.49 (as treated) • E 0.77 (0.62-0.95) • Risk with E+P dropped to baseline within 2 years of stopping therapy Chlebowski,; NEJM 2009; Anderson, Lancet Onc, 2012. CHEMOPREVENTION Department of Medicine 28 14 ¡

4/7/15 ¡ SERMs prevent breast cancer: MA 5 years treatment = 10+ benefit Department of Medicine Cuzick, Lancet, 2013 29 10-year meta-analysis SERMs Department of Medicine • All invasive BC 38% reduction (31-44%) • ER+ 51% reduction (42-57%) • DCIS 31% reduction (10-47%) • IBIS trial: 5 years of tamoxifen; 16+ years FU – Risk reduction years 10+ equal to years 1-10 Cuzick, Lancet, 2013: Cuzick, Lancet Onc, 2015 15 ¡

4/7/15 ¡ Adverse Events From Prevention Trials of Tamoxifen & Raloxifene Department of Medicine • DVT/PE: 1.9 (1.4-2.6) • Endometrial cancer 2.4 (1.5-4.0) • ↑ risk fatal stroke • ↑ risk cataracts • ↑ risk hot flashes ** Majority of adverse events in women ≥ 50 years during 5 years active treat. Fisher JNCI ,1998; Cuzick Lancet, 2003; Barrett-Conner, NEJM, 2006. USPSTF Recommendation Department of Medicine • “ … clinicians engage in shared decision-making with women at increased risk of breast cancer regarding medications to reduce their risk. For women who are at increased risk for breast cancer and at low risk for adverse medication effects, clinicians should offer to prescribe risk- reducing medications such as tamoxifen or raloxifene.” • “In general, women with an estimated 5-year breast cancer risk of 3% or greater are more likely to benefit from tamoxifen or raloxifene” http://www.uspreventiveservicestaskforce.org/ 32 16 ¡

4/7/15 ¡ Raloxifene vs. Tamoxifen Department of Medicine • Pro raloxifene – Equivalent reduction in IBC – Less thromboembolism, uterine cancer, and cataracts – Primary care comfort with therapy • Con raloxifene – Less reduction in DCIS/LCIS: long-term follow- up concerns – Post-menopausal women only Case: Ana Department of Medicine • 34 year old woman born in Mexico • My mother ’ s fine and I don ’ t have a sister. • But my dad had 4 sisters, 2 of whom developed breast cancer and my paternal grandmother also had breast cancer • 5-year Gail risk = .31% 17 ¡