Obesity and risk of breast cancer in the WHI clinical trial MS 1895; accepted by JAMA-Oncology

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1 Obesity and risk of breast cancer in the WHI clinical trial MS 1895; accepted by JAMA-Oncology Marian L Neuhouser, PhD, RD WHI Clinical Coordinating Center Fred Hutchinson Cancer Research Center WHI 2015 Investigator Meeting May 7, 2015

2 MS 1895 Writing Group Marian Neuhouser, Aaron Aragaki, Ross Prentice, JoAnn Manson, Rowan Chlebowski, Cara Carty, Heather Ochs-Balcom, Cynthia Thomson, Bette Caan, Lesley Tinker, Rachel Peragallo Urrutia, Jennifer Knudtson, Garnet Anderson Fred Hutchinson Cancer Research Center 1

3 Background on obesity and postmenopausal breast cancer * 2010 WCRF/AICR Continuous Update Project on Food, Nutrition, Physical Activity and Breast Cancer Prevention Body fatness Convincing - risk Abdominal fatness, adult weight gain Probable - risk * 2012 Annual Report to the Nation (Eheman, 2012) BMI vs. <25 kg/m 2 - RR=1.13 BMI > 30 vs. <25 kg/m 2 - RR=1.25 Fred Hutchinson Cancer Research Center 2

4 2009 Meta-analysis of 6 case-control and 4 cohort studies Consistent increased risk for high vs. low body weight and ER+/PR+ breast cancers; no association for ER- (not shown) Suzuki et al

5 Not all studies support strong association NSABP P-1 and STAR Trials (Cecchini et al 2012) BMI vs. <25 kg/m 2 - RR=1.07 ( ) BMI > 30 vs. <25 kg/m 2 - RR=1.14 ( ) Black Women s Health Study (Palmer et al 2007) BMI vs. <25 kg/m 2 - RR=0.80 ( ) BMI > 30 vs. <25 kg/m 2 - RR=0.88 ( ) Several others show weak or no associations Fred Hutchinson Cancer Research Center 4

6 How can WHI contribute to the science? WHI CT Design Measured height & weight Measured body circumferences Mammography as part of the protocol Annually for HT CT Biennial for DM CT Minimizes ascertainment bias Physician-adjudicated endpoints Very little missing data Fred Hutchinson Cancer Research Center 5

7 Objectives Primary Aim: To examine associations of overweight and obesity with postmenopausal breast cancer risk in a setting where measured weights and mammography were part of the trial protocol (restricted to CT) Secondary Aims: To examine whether associations differed by breast cancer characteristics, age, race/ethnicity and HT use. Fred Hutchinson Cancer Research Center 6

8 Methods * n= 67,142 women in the CT * BMI - from baseline height and weight * Weight change (%) = [(annual visit weight - baseline weight)]/ baseline weight x 100]. Time dependent variable updated with annual weights: * weight stable (± 2% of baseline weight) (ref) * 2%-5% weight gain * >5% weight gain * 2%-5% weight loss * >5% weight loss Fred Hutchinson Cancer Research Center 7

9 Methods Cox Proportional Hazards Models Interaction Tests: Interactions of BMI with HT use (current, never, past) Race/ethnicity Age Fred Hutchinson Cancer Research Center 8

10 Associations of BMI with breast cancer in the WHI CT (total and by cancer characteristics; referent = BMI<25 kg/m 2 ) Fred Hutchinson Cancer Research Center 9

11 Subgroup analyses by baseline age, race/ethnicity and HT use Fred Hutchinson Cancer Research Center 10

12 Associations of weight change with invasive breast cancer risk Compared to women who remained weight stable No main effect of weight gain Gain of 2-5% of baseline weight- HR =1.09 ( ) Gain of >5% of baseline weight- HR=1.12 ( ) No main effect of weight loss Loss of 2-5% of baseline weight HR=1.07 ( ) Loss of >5% of baseline weight HR=1.00 ( ) Fred Hutchinson Cancer Research Center 11

13 Associations of weight change with invasive breast cancer risk Interactions with baseline weight Women with normal BMI at baseline (<25.0 kg/m 2 ) who gained >5% of baseline weight HR= 1.36 (1.11,1.65) compared to weight stability P-interaction =0.05 No other significant or meaningful interactions Including no interaction of weight loss with baseline weight (ie, overweight and obese women who lost weight no associations) Fred Hutchinson Cancer Research Center 12

14 Summary and Conclusions *BMI was associated with an increased risk of invasive breast cancer. Risk progressively increased across the BMI categories (for grade 2+3 obesity HR=1.58) *Risk was strongest for ER+ tumors (RR=1.86) *Obesity was associated with breast cancer characteristics such larger tumor size, positive lymph nodes, moderate/poor differentiation and regional/distant stage Fred Hutchinson Cancer Research Center 13

15 Summary and Conclusions * No effect modification by HT * Risk stayed the same across HT use * No change in risk for weight loss * Normal weight women who gained weight was associated with increased risk * No further information when examining waist circumference (not shown) Fred Hutchinson Cancer Research Center 14

16 Next steps for WHI? *What are additional questions we can address in WHI regarding obesity and breast cancer risk? *Waist-hip provided no additional information, but are there other measures of body composition? DXA cohort manuscript proposal forthcoming *We found no interactions of race/ethnicity with breast cancer; are there other approaches? *Other subgroups to examine in more detail? Fred Hutchinson Cancer Research Center 15