Abstract P6-09-01: Recent weight gain and increased breast cancer risk varies by receptor classification among pre and postmenopausal women
Authors: Colditz Graham A , Eliassen Heather , Toriola Adetunji T , Hankinson Susan E , Willett Walter C , Natarajan Loki , Rosner Bernard 
Published: May 2015

Abstract
Obesity is well established as a cause of postmenopausal breast cancer incidence and mortality. Furthermore, adiposity in early life – through premenopausal years reduces breast cancer incidence. However, studies using measures of adiposity at age 18 also report inverse relations with premenopausal breast cancer and for some but not all subtypes of breast cancer defined by molecular status. To assess the relations of adiposity in childhood, in late adolescence, and in adult years as well as change in weight in relation to total invasive breast cancer and subtype defined by receptor status we fit models based on the Rosner-Colditz log-incidence model of breast cancer.
The Nurses’ Health Study cohort was established in 1976 when 121,701 female US registered nurses ages 30-55 responded to a mail questionnaire inquiring about risk factors for breast cancer including reproductive factors, hormone use, anthropometric variables, benign breast disease (BBD), and family history of breast cancer. The risk factors have been updated by repeat questionnaires every 2 years. We followed a cohort of 77,232 women from 1980 to 2006 (1,445,578 person-years) documenting 4,196 incident cases of invasive breast cancer. ER and PR status were obtained from pathology reports and medical records. A total of 2,033 ER+/PR+ tumors, 595 ER-/PR- tumors, 512 ER+/PR- tumors were identified among women with complete information on breast cancer risk factors.
Overall, weight at age 18 was inversely related to incidence. The relative risk per 25 lb weight difference was 0.89 (0.85, 0.93). After controlling for weight at age 18, long-term weight change was positively related to total incident breast cancer risk among both premenopausal (RR per 25 lb weight gain since age 18=1.08; 95% CI=1.05-1.12) and postmenopausal women (RR per 25 lb weight gain since menopause=1.16; 95% CI=1.09-1.23).
In addition, we focus on the effect of short-term weight gain (over past 4 years) on breast cancer risk while controlling for weight at age 18 and long-term change in weight during premenopause and postmenopause. We found a significant effect of short-term weight change and breast cancer risk (RR=1.20; 95% CI=1.09-1.33) for a 4-year weight gain of ≥ 15 lbs vs no change (≤ 5lbs) (RR per 25 lb weight gain=1.13; 95% CI=1.06-1.21, p&lt;0.001). However, the effect was stronger for premenopausal women (≥ 15 lb weight gain vs no change, RR=1.38; 95% CI=1.13-1.69) (RR per 25 lb weight gain=1.26; 95% CI=1.08-1.48, p=0.004) than for postmenopausal women (≥ 15 lb weight gain vs no change, RR=1.10; 95% CI=0.97-1.25) (RR per 25 lb weight gain=1.08; 95% CI=1.00-1.16, p=0.063).
The effect of short-term weight gain during premenopause was stronger for ER+/PR- (RR per 25 lb weight gain=2.19; 95% CI=1.33-3.61, p=0.002) and ER-/PR- breast cancer (RR per 25 lb weight gain=1.61; 95% CI=1.09-2.38, p=0.016) than for ER+/PR+ breast cancer (RR per 25 lb weight gain=1.13; 95% CI=0.89-1.43, p=0.32).
In conclusion, adiposity in childhood has a protective lifelong relation to breast cancer risk, though mechanisms remain largely unexplained. There are long-term deleterious effects of weight change both pre- and post-menopause and deleterious effects of short-term weight gain during premenopausal years.
Citation Format: Graham A Colditz, Heather Eliassen, Adetunji T Toriola, Susan E Hankinson, Walter C Willett, Loki Natarajan, Bernard Rosner. Recent weight gain and increased breast cancer risk varies by receptor classification among pre and postmenopausal women [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-09-01.