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Obesity as risk factor for subtypes of breast cancer: results from a prospective cohort study.

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.

SUBMITTER: Nattenmuller CJ

PROVIDER: S-EPMC5984403 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Obesity as risk factor for subtypes of breast cancer: results from a prospective cohort study.

Nattenmüller Cina J CJ Kriegsmann Mark M Sookthai Disorn D Fortner Renée Turzanski RT Steffen Annika A Walter Britta B Johnson Theron T Kneisel Jutta J Katzke Verena V Bergmann Manuela M Sinn Hans Peter HP Schirmacher Peter P Herpel Esther E Boeing Heiner H Kaaks Rudolf R Kühn Tilman T

BMC cancer 20180531 1

<h4>Background</h4>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).<h4>Method ...[more]

PMID: 29855282

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Project description:The aim of this study was to describe breast tumor subtypes by common breast cancer risk factors and to determine correlates of subtypes using baseline data from two pooled prospective breast cancer studies within a large health maintenance organization.Tumor data on 2544 invasive breast cancer cases subtyped by estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (Her2) status were obtained (1868 luminal A tumors, 294 luminal B tumors, 288 triple-negative tumors and 94 Her2-overexpressing tumors). Demographic, reproductive and lifestyle information was collected either in person or by mailed questionnaires. Case-only odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression, adjusting for age at diagnosis, race/ethnicity, and study origin.Compared with luminal A cases, luminal B cases were more likely to be younger at diagnosis (P = 0.0001) and were less likely to consume alcohol (OR = 0.74, 95% CI = 0.56 to 0.98), use hormone replacement therapy (HRT) (OR = 0.66, 95% CI = 0.46 to 0.94), and oral contraceptives (OR = 0.73, 95% CI = 0.55 to 0.96). Compared with luminal A cases, triple-negative cases tended to be younger at diagnosis (P < or = 0.0001) and African American (OR = 3.14, 95% CI = 2.12 to 4.16), were more likely to have not breastfed if they had parity greater than or equal to three (OR = 1.68, 95% CI = 1.00 to 2.81), and were more likely to be overweight (OR = 1.82, 95% CI = 1.03 to 3.24) or obese (OR = 1.97, 95% CI = 1.03 to 3.77) if premenopausal. Her2-overexpressing cases were more likely to be younger at diagnosis (P = 0.03) and Hispanic (OR = 2.19, 95% CI = 1.16 to 4.13) or Asian (OR = 2.02, 95% CI = 1.05 to 3.88), and less likely to use HRT (OR = 0.45, 95% CI = 0.26 to 0.79).These observations suggest that investigators should consider tumor heterogeneity in associations with traditional breast cancer risk factors. Important modifiable lifestyle factors that may be related to the development of a specific tumor subtype, but not all subtypes, include obesity, breastfeeding, and alcohol consumption. Future work that will further categorize triple-negative cases into basal and non-basal tumors may help to elucidate these associations further.

Project description:Identification of blood biomarkers that prospectively predict progression of Mycobacterium tuberculosis infection to tuberculosis disease might lead to interventions that combat the tuberculosis epidemic. We aimed to assess whether global gene expression measured in whole blood of healthy people allowed identification of prospective signatures of risk of active tuberculosis disease. RESULTS:Between July 6, 2005, and April 23, 2007, we enrolled 6363 from the ACS study and 4466 from independent South African and Gambian cohorts. 46 progressors and 107 matched controls were identified in the ACS cohort. A 16 gene signature of risk was identified. The signature predicted tuberculosis progression with a sensitivity of 66Â·1% (95% CI 63Â·2â68Â·9) and a specificity of 80Â·6% (79Â·2â82Â·0) in the 12 months preceding tuberculosis diagnosis. The risk signature was validated in an untouched group of adolescents (p=0Â·018 for RNA sequencing and p=0Â·0095 for qRT-PCR) and in the independent South African and Gambian cohorts (p values <0Â·0001 by qRT-PCR) with a sensitivity of 53Â·7% (42Â·6â64Â·3) and a specificity of 82Â·8% (76Â·7â86) in 12 months preceding tuberculosis. Interpretation: The whole blood tuberculosis risk signature prospectively identified people at risk of developing active tuberculosis, opening the possibility for targeted intervention to prevent the disease. In this prospective cohort study, we followed up healthy, South African adolescents aged 12â18 years from the adolescent cohort study (ACS) who were infected with M tuberculosis for 2 years. We collected blood samples from study participants every 6 months and monitored the adolescents for progression to tuberculosis disease. A prospective signature of risk was derived from whole blood RNA sequencing data by comparing participants who developed active tuberculosis disease (progressors) with those who remained healthy (matched controls). After adaptation to multiplex qRT-PCR, the signature was used to predict tuberculosis disease in untouched adolescent samples and in samples from independent cohorts of South African and Gambian adult progressors and controls. Participants of the independent cohorts were household contacts of adults with active pulmonary tuberculosis disease.

Dataset Information

Obesity as risk factor for subtypes of breast cancer: results from a prospective cohort study.

Publications

Obesity as risk factor for subtypes of breast cancer: results from a prospective cohort study.

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