Reproductive and hormonal risk factors for postmenopausal luminal, HER‐2‐overexpressing, and triple‐negative breast cancer

Abstract

BACKGROUND.Molecular profiling studies have identified subtypes of breast cancer that can be approximately classified by estrogen receptor (ER), progesterone receptor (PR), and HER‐2/neu (HER‐2) expression. These molecular subtypes are prognostically significant, but to the authors' knowledge, differences in their etiologic profiles have not been established. Reproductive factors may plausibly be differentially correlated with the risk of different breast cancer subtypes because these factors are presumed to impact exposure to endogenous sex hormones.METHODS.The authors pooled 2 population‐based, case–control studies of breast cancer in women ages 55 to 79 years for an analysis including 1476 controls and 1023 cases of luminal breast cancer, 39 cases of HER‐2‐overexpressing breast cancer, and 78 cases of triple‐negative breast cancer. Polytomous logistic regression was used to compare each case group with controls.RESULTS.Associations varied by molecular subtype. Early age at menarche was only found to be associated with risk of HER‐2‐overexpressing disease (odds ratio [OR] of 2.7; 95% confidence interval [95% CI], 1.4‐5.5), whereas breastfeeding for ≥6 months was only found to be protective for luminal and triple‐negative disease (OR of 0.8 [95% CI, 0.6‐1.0] and OR of 0.5 [95% CI, 0.3‐0.9], respectively). Both late age at menopause and the use of estrogen plus progestin hormone therapy were only found to be associated with risk of luminal disease (OR of 1.6 [95% CI, 1.1‐2.2] and OR of 1.7 [95% CI, 1.3‐2.1], respectively). No differences in risks associated with parity or age at first live birth were observed by subtype.CONCLUSIONS.Certain reproductive factors may have a greater impact on the risk of certain molecular subtypes of disease compared with others. Future studies that further define the etiology of breast cancer subtypes will add to the biologic understanding of this disease. Cancer 2008. © 2008 American Cancer Society.

Relation of Alcohol/Tobacco use with Metastasis, Hormonal (Estrogen and Progesterone) Receptor Status and c-erbB2 Protein in Mammary Ductal Carcinoma

“…It is known that the double RH-are less responsive to hormonal treatments and that, together with triple negative tumors, are more aggressive and have a graver prognosis (Phipps et al, 2008b;2008a;Reis-Filho and Tutt, 2008;Rakha and Ellis, 2009;Islam et al, 2012). Contrarily, the double RH+ respond better (Gonzalez-Angulo et al, 2007).…”

“…Later, there was a boom in triple negative studies (Phipps et al, 2008b;2008a;Reis-Filho and Tutt, 2008;Rakha and Ellis, 2009;Li et al, 2013) that aimed to associate breast cancer with stress and the use of tobacco and alcohol (Tan et al, 2009b;Kabat et al, 2011;Islam et al, 2012).…”

Molecular Subtypes of Breast Cancer: Long-term Incidence Trends and Prognostic Differences

“…This ensured that the observed incidence differences were not caused The impact of risk factors seems to differ between molecular subtypes, and it is possible that the higher incidence of HER2 negative luminal tumours among women born in 1929 or later may also be explained by differences in reproductive and lifestyle factors, such as age at menarche, age at first birth, parity, age at menopause, and body mass index (39,40,46,47).…”

Reply to reproductive and hormonal risk factors for postmenopausal luminal, HER‐2‐overexpressing, and triple‐negative breast cancer

“…However, the pathologic similarities suggest that BRCA1 or associated pathways can become inactivated in triple-negative tumors via other mechanisms, such as gene promoter methylation. 4 We previously reported a positive association between oral contraceptive use and triple-negative breast cancer. Although we did not take into consideration the menopausal status of the patients, the frequency of oral contraceptive use in our small cohort was found to be higher in patients with the triple-negative subtype compared with patients with other subtypes of breast cancer (35.3% vs 12.2%; P ¼ .02).…”

“…However, the majority of the literature indicates that any association between oral contraceptive use and breast cancer risk is likely restricted to young, premenopausal women. 3 Because our study examining risk factors for triple-negative, HER-2-overexpressing, and luminal breast cancers was restricted to women aged 55 years, 4 we did not expect to observe any associations with oral contraceptive use. In reexamining our data, we found a higher prevalence of ever-use of oral contraceptives in our triple-negative case group (48%) compared with cancer-free controls (38%); however, these differences were not found to be statistically significant, and after accounting for differences in age we observed no association between oral contraceptive use and the risk of triple-negative breast cancer (odds ratio of 0.9).…”