Weight and weight changes throughout life and postmenopausal breast cancer risk: A case-control study in France

Overweight and weight gain throughout adult life have been associated with increased risk of breast cancer after the menopause. However the role of body weight at a young age and of the timing of weight gain over the lifetime in postmenopausal breast cancer is not well documented.

Cordina-Duverger et al BMC Cancer (2016) 16:761 DOI 10.1186/s12885-016-2793-0 RESEARCH ARTICLE Open Access Weight and weight changes throughout life and postmenopausal breast cancer risk: a case-control study in France Emilie Cordina-Duverger1, Thérèse Truong1, Antoinette Anger1, Marie Sanchez1, Patrick Arveux2, Pierre Kerbrat3 and Pascal Guénel1* Abstract Background: Overweight and weight gain throughout adult life have been associated with increased risk of breast cancer after the menopause However the role of body weight at a young age and of the timing of weight gain over the lifetime in postmenopausal breast cancer is not well documented Methods: We conducted a population-based case-control study on breast cancer in France that included 739 cases and 815 population controls in postmenopausal women Height, weight at age 20, 40 and 50 as well as weight one year before diagnosis were obtained during in-person interviews Results: No association between body mass index at the age of 20 years and breast cancer after the menopause was detected However, we found that postmenopausal breast cancer was associated with weight gain between ages 40 and 50 years (OR per kg/m2 increase in BMI: 1.45 [95%ci 1.06−1.98]) The increased risk of breast cancer associated with weight gain was more consistent in leaner women at age 20, in older postmenopausal women (>65 years), and in women who did not use menopausal hormone therapy Conclusions: These findings point to the importance of controlling for weight gain in middle aged-women The role of low body weight in young adulthood in breast cancer risk after the menopause should be further scrutinized Keywords: Breast Cancer, Body Mass Index, Weight Gain, Case-control study Background With over 1.5 million new cases each year across the world, breast cancer is the leading cause of cancer among women Despite a recent decrease attributed to the reduction of menopausal hormone therapy, incidence rates of postmenopausal breast cancer in wealthy countries has grown steadily over the last decades Rising incidence rates are also observed in emerging countries as high calorie intake and sedentary life become more common, pointing to the role of overweight and lack of physical activity as major modifiable causes of breast cancer among postmenopausal women * Correspondence: pascal.guenel@inserm.fr Cancer & Environment Group, Center for Research in Epidemiology and Population Health (CESP), INSERM, University Paris-Sud, University Paris-Saclay, Villejuif, France Full list of author information is available at the end of the article The relationship between adiposity and breast cancer is complex and varies during lifetime Before menopause, adiposity reduces the risk of breast cancer This inverse association has been attributed to a decreased number of ovulations in overweight women and alteration of circulating hormone levels, which play a key role in breast cancer etiology, but other mechanisms may also account for the protective effect of high BMI before the menopause [1] After the menopause, a high BMI increases the risk of breast cancer breast cancer, and this association is explained by estradiol production in the adipose tissue [2–4] Investigating weight changes during lifetime, particularly in the period around the menopause, when the effect of BMI in breast cancer changes from a protective to a deleterious effect, is thus important to improve our understanding of the relationship between adiposity and © 2016 The Author(s) Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated Cordina-Duverger et al BMC Cancer (2016) 16:761 breast cancer However, most studies on breast cancer among postmenopausal women have only measured weight gain over long periods, usually from early adulthood to the time of cancer diagnosis, making difficult to evaluate how weight changes in specific periods of life may affect breast cancer risk [5–8] Elevated BMI during childhood or adolescence has also been associated with a decreased risk of postmenopausal breast cancer in some studies [9–11] It has been postulated that leanness in early adulthood may increase the risk of postmenopausal breast cancer due to incomplete differentiation of mammary gland cells related to insufficient mammary fat pad or progesterone deficiency [6, 12] This association, however, should be scrutinized In order to clarify the relationship between postmenopausal breast cancer risk and lifetime weight history, we used the data of a large population-based case-control study in France, focusing on the timing of weight changes over the lifetime and on the role of low weight (BMI 14 36 4.9 41 5.0 0.91 [0.57-1.45] 68.3 563 70.2 ref Tobacco (pack-years) Family history of breast cancer in first degree relatives Never No 604 81.7 715 87.7 ref Yes 135 18.3 100 12.3 1.62 [1.22-2.16] Age at menarche (years) 500 < 10 119 16.3 134 16.7 1.03 [0.77-1.36] ≥ 10 113 15.4 105 13.1 1.28 [0.95-1.74] No 269 36.8 264 32.5 ref Yes 462 63.2 548 67.5 0.83 [0.67-1.02] Physical activity ≤ 11 131 18 122 15.2 ref 12 179 24.7 172 21.4 0.98 [0.71-1.35] 13 155 21.3 174 21.6 0.82 [0.59-1.15] 14 143 19.7 165 20.5 0.81 [0.58-1.13] ≥ 15 118 16.3 172 21.4 0.63 [0.45-0.89] Nulliparous 79 10.7 50 6.1 ref FTPb 109 14.7 113 13.9 0.61 [0.39-0.95] FTP 279 37.8 270 33.1 0.65 [0.44-0.96] FTP 183 24.8 245 30.1 0.46 [0.31-0.69] ≥ FTP 89 12 137 16.8 0.41 [0.26-0.64] Parity Age at first FTP among parous women (years) < 22 185 28 252 32.9 ref 22-24 196 29.7 252 32.9 1.07 [0.82-1.40] 25-27 141 21.4 167 21.8 1.16 [0.86-1.56] > 27 138 20.9 94 12.3 2.02 [1.46-2.81] Breastfeeding among parous women (weeks) never 349 53.5 399 52.2 ref < 26 224 34.4 261 34.2 1.03 [0.82-1.31] 26-52 54 8.3 67 8.8 0.97 [0.66-1.43] > 52 25 3.8 37 4.8 0.82 [0.48-1.40] Age at menopause (years)c < 48 105 22.7 115 22.9 ref 48-50 136 29.4 157 31.2 0.85 [0.59-1.23] 51-53 133 28.8 126 25 1.03 [0.71-1.50] ≥ 54 88 19 105 20.9 0.82 [0.54-1.23] a Odds ratios adjusted for age at reference date and study area b FTP: Full-Term Pregnancy c Age at menopause unknown in 227 cases and 312 controls and 50 years of age was associated with increased risk of breast cancer (OR per kg/m2 BMI gain between ages 40 and 50: 1.32; 95 % ci 1.05–1.65) Further adjustment for current BMI did not modify this finding No association was observed with BMI gain before 40 and after 50 years of age Models were also fitted using weight changes in kg instead of BMI in kg/m2 The results are shown in Additional file 1: Table S1 and yielded similar conclusions Results of the stratification of BMI and BMI gain variables by BMI at age 20 (