Obesity And Risk Of Postmenopausal Breast Cancer By Subtype Meta-Analysis Of Prospective Studies

Doris CHAN, School of Public Health, Imperial College London, United Kingdom
VINGELIENE S. 1 , AUNE D. 1,2 , POLEMITI E. 1 , ABAR L. 1 , VIEIRA R. 1 , GREENWOOD D. 3 , NORAT T. 1

1 Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom
2 Department of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim, Norway
3 Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, United Kingdom

Purpose
To systematically review the findings from prospective studies on the association of obesity with risk of breast cancer, overall and by hormone receptor subtypes, in postmenopausal women.

Methods
Relevant publications from prospective studies on obesity, as measured by body mass index (BMI), and breast cancer risk were searched in PubMed up to May 2015, as part of the WCRF Continuous Update Project. Random-effects dose-response meta-analyses were conducted to calculate the summary relative risks (RRs) for each 5 kg/m2 increase in BMI and postmenopausal breast cancer and its subtypes.

Results
Fifty-six studies (80 404 cases) could be included in the meta-analysis. The summary RR per 5 kg/m2 was 1.12 (95% confidence interval (CI)=1.09–1.15) for postmenopausal breast cancer, which confirmed the positive association that is well-established in the past reviews.
There was evidence of high heterogeneity between studies (I2=75%, P<0.001). Further analyses showed that the significant increased risk was only observed in menopausal hormone therapy (MHT) never users (RR=1.16, 95% CI=1.10–1.23) (15 studies) and not ever users (RR=1.01, 95% CI=0.96–1.06) (13 studies), and in women with oestrogen receptor (ER) positive (RR=1.17, 95% CI=1.09–1.25) (14 studies), progesterone receptor (PR) positive (RR=1.47, 95% CI=1.36–1.60) (5 studies), and joint ER+PR+ breast cancers only (RR=1.29, 95% CI=1.19–1.40) (9 studies); which could partly explain the different associations between the studies, although high heterogeneity remained in most of the subgroups.

Conclusions
Our results show an increase in risk of obesity with hormone sensitive breast cancer in postmenopausal women and support the purposed hormonal pathway that underlies the relationship. Further studies should limit the analysis to MHT never users to avoid the masking of the association by hormone use.

Funding source
This study was funded by the World Cancer Research Fund (WCRF) International (Grant number: 2007/SP01).