Associations of breast cancer risk factors with tumor subtypes: a pooled analysis from the Breast Cancer Association Consortium studies.

By Xiaohong R. Yang, J. Chang-Claude, Ellen L. Goode, F. Couch, H. Nevanlinna, R. Milne, M. Gaudet, M. Schmidt, A. Broeks, A. Cox and 164 more. Journal of the National Cancer Institute, 2011

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BACKGROUND Previous studies have suggested that breast cancer risk factors are associated with estrogen receptor (ER) and progesterone receptor (PR) expression status of the tumors. METHODS We pooled tumor marker and epidemiological risk factor data from 35,568 invasive breast cancer case patients from 34 studies participating in the Breast Cancer Association Consortium. Logistic regression models were used in case-case analyses to estimate associations between epidemiological risk factors and tumor subtypes, and case-control analyses to estimate associations between epidemiological risk factors and the risk of developing specific tumor subtypes in 12 population-based studies. All statistical tests were two-sided. RESULTS In case-case analyses, of the epidemiological risk factors examined, early age at menarche (≤12 years) was less frequent in case patients with PR(-) than PR(+) tumors (P = .001). Nulliparity (P = 3 × 10(-6)) and increasing age at first birth (P = 2 × 10(-9)) were less frequent in ER(-) than in ER(+) tumors. Obesity (body mass index [BMI] ≥ 30 kg/m(2)) in younger women (≤50 years) was more frequent in ER(-)/PR(-) than in ER(+)/PR(+) tumors (P = 1 × 10(-7)), whereas obesity in older women (>50 years) was less frequent in PR(-) than in PR(+) tumors (P = 6 × 10(-4)). The triple-negative (ER(-)/PR(-)/HER2(-)) or core basal phenotype (CBP; triple-negative and cytokeratins [CK]5/6(+) and/or epidermal growth factor receptor [EGFR](+)) accounted for much of the heterogeneity in parity-related variables and BMI in younger women. Case-control analyses showed that nulliparity, increasing age at first birth, and obesity in younger women showed the expected associations with the risk of ER(+) or PR(+) tumors but not triple-negative (nulliparity vs parity, odds ratio [OR] = 0.94, 95% confidence interval [CI] = 0.75 to 1.19, P = .61; 5-year increase in age at first full-term birth, OR = 0.95, 95% CI = 0.86 to 1.05, P = .34; obesity in younger women, OR = 1.36, 95% CI = 0.95 to 1.94, P = .09) or CBP tumors. CONCLUSIONS This study shows that reproductive factors and BMI are most clearly associated with hormone receptor-positive tumors and suggest that triple-negative or CBP tumors may have distinct etiology.

Subfields: Cancer Research, Oncology, Pathology and Forensic Medicine

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Citations in the corpus

• Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. (2011, result): “%) of TNBCs stained positive for the basal cytokeratins CK5/6 (Supplemental Table 10).”
• An overview of triple-negative breast cancer (2016, background): “However, obesity (particularly, central adiposity) might be associated with increased levels of insulin and related growth factors, which could increase the risk specifically for some breast tumor subtypes, possibly including the triple-negative/ basal-like group [40].”
• Obesity and adverse breast cancer risk and outcome: mechanistic insights and strategies for intervention (2017, background): “Two meta-analyses, which included 6106 and 2486 premenopausal women with ER-positive breast cancer, respectively, demonstrated an inverse association between BMI and ER-positive breast cancer before menopause.(27,28) These observations appear to apply to both the Hispanic and nonHispanic white popul”
• Breast cancer statistics, 2013 (2014, background): “There is a growing body of evidence that breast cancer risk factors for ER1 and ER- breast cancers are distinct.(24,32) It has recently been hypothesized that the divergent trends by ER status may be reflective of increasing trends in obesity and changes in reproductive patterns, factors that studie”