Reduced risk of breast cancer associated with recreational physical activity varies by HER2 status.
Convincing epidemiologic evidence indicates that physical activity is inversely associated with breast cancer risk. Whether this association varies by the tumor protein expression status of the estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), or p53 is unclear. We evaluated the effects of recreational physical activity on risk of invasive breast cancer classified by the four biomarkers, fitting multivariable unconditional logistic regression models to data from 1195 case and 2012 control participants in the population-based Women's Contraceptive and Reproductive Experiences Study. Self-reported recreational physical activity at different life periods was measured as average annual metabolic equivalents of energy expenditure [MET]-hours per week. Our biomarker-specific analyses showed that lifetime recreational physical activity was negatively associated with the risks of ER-positive (ER+) and of HER2-negative (HER2-) subtypes (both Ptrend  ≤ 0.04), but not with other subtypes (all Ptrend  > 0.10). Analyses using combinations of biomarkers indicated that risk of invasive breast cancer varied only by HER2 status. Risk of HER2-breast cancer decreased with increasing number of MET-hours of recreational physical activity in each specific life period examined, although some trend tests were only marginally statistically significant (all Ptrend  ≤ 0.06). The test for homogeneity of trends (HER2- vs. HER2+ ) reached statistical significance only when evaluating physical activity during the first 10 years after menarche (Phomogeneity  = 0.03). Our data suggest that physical activity reduces risk of invasive breast cancers that lack HER2 overexpression, increasing our understanding of the biological mechanisms by which physical activity acts.
Division of Cancer Etiology, Department of Population Sciences, Beckman Research Institute, City of Hope, Duarte, California, 91010.
Huiyan
H
Ma
Division of Cancer Etiology, Department of Population Sciences, Beckman Research Institute, City of Hope, Duarte, California, 91010.
Xinxin
X
Xu
Cancer Registry of Norway, PB 5313 Majorstuen, 0304, Oslo, Norway.|Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.|Department of Preventive Medicine, University of Southern California, Los Angeles, California, 90033.
Giske
G
Ursin
Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, 48201.
Michael S
MS
Simon
Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia, 30333.
Polly A
PA
Marchbanks
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, 98109.
Kathleen E
KE
Malone
Division of Cancer Etiology, Department of Population Sciences, Beckman Research Institute, City of Hope, Duarte, California, 91010.
Yani
Y
Lu
College of Health and Social Services, New Mexico State University, Las Cruces, New Mexico, 88003.
Jill A
JA
McDonald
Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia, 30333.
Suzanne G
SG
Folger
Cancer Centers Branch, National Cancer Institute, Bethesda, Maryland, 20850.
Linda K
LK
Weiss
Division of Cancer Etiology, Department of Population Sciences, Beckman Research Institute, City of Hope, Duarte, California, 91010.
Jane
J
Sullivan-Halley
Department of Preventive Medicine, University of Southern California, Los Angeles, California, 90033.
Dennis M
DM
Deapen
Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California, 90033.
Michael F
MF
Press
Division of Cancer Etiology, Department of Population Sciences, Beckman Research Institute, City of Hope, Duarte, California, 91010.
Leslie
L
Bernstein
D000328:Adult; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000209:etiology* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008875:Middle Aged; D009043:Motor Activity; D009367:Neoplasm Staging; D016017:Odds Ratio; D011159:Population Surveillance; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D012306:Risk
D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases
Breast cancer; ER; HER2; PR; Triple-negative breast cancer; luminal A breast cancer; p53; physical activity