1. Obesity as risk factor for subtypes of breast cancer: results from a prospective cohort study
- Author
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Hans-Peter Sinn, Britta Walter, Annika Steffen, Manuela M. Bergmann, Theron Johnson, Disorn Sookthai, Rudolf Kaaks, Peter Schirmacher, Verena Katzke, Renée T. Fortner, Jutta Kneisel, Esther Herpel, Heiner Boeing, Tilman Kühn, Mark Kriegsmann, and Cina J. Nattenmüller
- Subjects
0301 basic medicine ,Oncology ,p53 ,Cancer Research ,Body Mass Index ,0302 clinical medicine ,Breast cancer ,610 Medical sciences Medicine ,Surgical oncology ,Risk Factors ,Germany ,Estrogen receptor ,Breast ,Prospective Studies ,Prospective cohort study ,biology ,Incidence ,Estrogen Replacement Therapy ,Age Factors ,Middle Aged ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,030220 oncology & carcinogenesis ,Ki-67 ,Female ,Research Article ,Adult ,medicine.medical_specialty ,Breast Neoplasms ,Lower risk ,Tumor subtypes ,lcsh:RC254-282 ,03 medical and health sciences ,Internal medicine ,Genetics ,medicine ,Biomarkers, Tumor ,Humans ,Bcl-2 ,Obesity ,Risk factor ,Proportional hazards model ,business.industry ,medicine.disease ,030104 developmental biology ,Premenopause ,biology.protein ,business ,Body mass index - Abstract
Background Earlier epidemiological studies indicate that associations between obesity and breast cancer risk may not only depend on menopausal status and use of exogenous hormones, but might also differ by tumor subtype. Here, we evaluated whether obesity is differentially associated with the risk of breast tumor subtypes, as defined by 6 immunohistochemical markers (ER, PR, HER2, Ki67, Bcl-2 and p53, separately and combined), in the prospective EPIC-Germany Study (n = 27,012). Methods Formalin-fixed and paraffin-embedded (FFPE) tumor tissues of 657 incident breast cancer cases were used for histopathological analyses. Associations between BMI and breast cancer risk across subtypes were evaluated by multivariable Cox regression models stratified by menopausal status and hormone therapy (HT) use. Results Among postmenopausal non-users of HT, higher BMI was significantly associated with an increased risk of less aggressive, i.e. ER+, PR+, HER2-, Ki67low, Bcl-2+ and p53- tumors (HR per 5 kg/m2: 1.44 [1.10, 1.90], p = 0.009), but not with risk of more aggressive tumor subtypes. Among postmenopausal users of HT, BMI was significantly inversely associated with less aggressive tumors (HR per 5 kg/m2: 0.68 [0.50, 0.94], p = 0.018). Finally, among pre- and perimenopausal women, Cox regression models did not reveal significant linear associations between BMI and risk of any tumor subtype, although analyses by BMI tertiles showed a significantly lower risk of less aggressive tumors for women in the highest tertile (HR: 0.55 [0.33, 0.93]). Conclusion Overall, our results suggest that obesity is related to risk of breast tumors with lower aggressiveness, a finding that requires replication in larger-scale analyses of pooled prospective data. Electronic supplementary material The online version of this article (10.1186/s12885-018-4548-6) contains supplementary material, which is available to authorized users.
- Published
- 2018