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Body size, physical activity, and risk of triple-negative and estrogen receptor-positive breast cancer.

ABSTRACT: BACKGROUND:Triple-negative breast cancer, characterized by a lack of hormone receptor and HER2 expression, is associated with a particularly poor prognosis. Focusing on potentially modifiable breast cancer risk factors, we examined the relationship between body size, physical activity, and triple-negative disease risk. METHODS:Using data from 155,723 women enrolled in the Women's Health Initiative (median follow-up, 7.9 years), we assessed associations between baseline body mass index (BMI), BMI in earlier adulthood, waist and hip circumference, waist-hip ratio, recreational physical activity, and risk of triple-negative (n=307) and estrogen receptor-positive (ER+, n=2,610) breast cancers. RESULTS:Women in the highest versus lowest BMI quartile had 1.35-fold (95% CI, 0.92-1.99) and 1.39-fold (95% CI, 1.22-1.58) increased risks of triple-negative and ER+ breast cancers, respectively. Waist and hip circumferences were positively associated with risk of ER+ breast cancer (Ptrend=0.01 for both measures) but were not associated with triple-negative breast cancer. Compared with women who reported no recreational physical activity, women in the highest activity tertile had similarly lower risks of triple-negative and ER+ breast cancers (HR=0.77; 95% CI, 0.51-1.13; and HR=0.85; 95% CI, 0.74-0.98, respectively). CONCLUSIONS:Despite biological and clinical differences, triple-negative and ER+ breast cancers are similarly associated with BMI and recreational physical activity in postmenopausal women. The biological mechanisms underlying these similarities are uncertain and these modest associations require further investigation. IMPACT:If confirmed, these results suggest potential ways postmenopausal women might modify their risk of both ER+ and triple-negative breast cancers.

SUBMITTER: Phipps AI

PROVIDER: S-EPMC3064558 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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Body size, physical activity, and risk of triple-negative and estrogen receptor-positive breast cancer.

Phipps Amanda I AI Chlebowski Rowan T RT Prentice Ross R McTiernan Anne A Stefanick Marcia L ML Wactawski-Wende Jean J Kuller Lewis H LH Adams-Campbell Lucile L LL Lane Dorothy D Vitolins Mara M Kabat Geoffrey C GC Rohan Thomas E TE Li Christopher I CI

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20110301 3

<h4>Background</h4>Triple-negative breast cancer, characterized by a lack of hormone receptor and HER2 expression, is associated with a particularly poor prognosis. Focusing on potentially modifiable breast cancer risk factors, we examined the relationship between body size, physical activity, and triple-negative disease risk.<h4>Methods</h4>Using data from 155,723 women enrolled in the Women's Health Initiative (median follow-up, 7.9 years), we assessed associations between baseline body mass i ...[more]

PMID: 21364029

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Project description:PURPOSE:A subset of estrogen receptor-positive (ER-positive) breast cancer (BC) contains high levels of tumor-infiltrating lymphocytes (TILs), similar to triple-negative BC (TNBC). The majority of immuno-oncology trials target TNBCs because of the greater proportion of TIL-rich TNBCs. The extent to which the immune microenvironments of immune-rich ER-positive BC and TNBC differ is unknown. PATIENTS AND METHODS:RNA sequencing data from The Cancer Genome Atlas (TCGA; n = 697 ER-positive BCs; n = 191 TNBCs) were used for discovery; microarray expression data from Molecular Taxonomy of Breast Cancer International Consortium (METABRIC; n = 1,186 ER-positive BCs; n = 297 TNBCs) was used for validation. Patients in the top 25th percentile of a previously published total TIL metagene score distribution were considered immune rich. We compared expression of immune cell markers, immune function metagenes, and immuno-oncology therapeutic targets among immune-rich subtypes. RESULTS:Relative fractions of resting mast cells (TCGA P adj = .009; METABRIC P adj = 4.09E-15), CD8+ T cells (TCGA P adj = .015; METABRIC P adj = 0.390), and M2-like macrophages (TCGA P adj= 4.68E-05; METABRIC P adj = .435) were higher in immune-rich ER-positive BCs, but M0-like macrophages (TCGA P adj = 0.015; METABRIC P adj = .004) and M1-like macrophages (TCGA P adj = 9.39E-08; METABRIC P adj = 6.24E-11) were higher in immune-rich TNBCs. Ninety-one immune-related genes (eg, CXCL14, CSF3R, TGF-B3, LRRC32/GARP, TGFB-R2) and a transforming growth factor ? (TGF-?) response metagene were significantly overexpressed in immune-rich ER-positive BCs, whereas 41 immune-related genes (eg, IFNG, PD-L1, CTLA4, MAGEA4) were overexpressed in immune-rich TNBCs in both discovery and validation data sets. TGF-? pathway member genes correlated negatively with expression of immune activation markers (IFNG, granzyme-B, perforin) and positively with M2-like macrophages (IL4, IL10, and MMP9) and regulatory T-cell (FOXP3) markers in both subtypes. CONCLUSION:Different immunotherapy strategies may be optimal in immune-rich ER-positive BC and TNBC. Drugs targeting the TGF-? pathway and M2-like macrophages are promising strategies in immune-rich ER-positive BCs to augment antitumor immunity.

Dataset Information

Body size, physical activity, and risk of triple-negative and estrogen receptor-positive breast cancer.

Publications

Body size, physical activity, and risk of triple-negative and estrogen receptor-positive breast cancer.

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