Association between oral contraceptive use as a risk factor and triple-negative breast cancer: A systematic review and meta-analysis

Abstract

Abstract. Triple-negative breast cancer (TNBC), a unique subtype of breast cancer, which is resistant to endocrine and targeted therapy, usually relapses early, progresses rapidly and is associated with a poor prognosis. Epidemiological investigations focusing on the association between risk factors and the onset of TNBC demonstrated that the incidence of TNBC exhibits a significant correlation with anthropometric, geographical and demographic parameters. The aim of the present systematic review and meta-analysis was to evaluate the strength of the association between the use of oral contraceptives (OCs) and TNBC. Two databases (PubMed Central/PubMed, Web of Science) and secondary references were searched to identify studies meeting the priorly established inclusion criteria. Case-control studies published between January, 2005 and March, 2016 were searched using the key words (triple-negative breast cancer OR basal-like) AND (oral contraceptives). Finally, 9 eligible articles using as control other subtypes of invasive breast cancer and 7 articles using a healthy population as control were incorporated in the meta-analysis. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using fixed-or random-effects models according to the heterogeneity between studies. The case-control comparison using other subtypes of breast cancer as the control arm exhibited a significant association between OC use and TNBC (OR = 1.31, 95% CI = 1.18-1.45; Z=5.26, P<0.00001). These results were further confirmed by the case-control comparison using the healthy population as the control arm (OR = 1.21, 95% CI = 1.01-1.46; Z=2.04, P=0.04). The present meta-analysis indicated that women who use OCs have a greater risk of TNBC compared with women who do not. This conclusion prompts that women who used OCs should be examined more closely in population screenings of breast cancer, as they may benefit from prevention and early detection strategies.

The Effects of Low HER2/neu Expression on the Clinicopathological Characteristics of Triple-Negative Breast Cancer Patients

“…resulting in shorter survival (Wang et al, 2015;Li et al, 2017) TNBC diagnosis was made possible by the negative expression of hormone receptors and human epidermal growth factor receptor 2 (HER2) neu, which was reported to account for 10-20% of all BC cases (Denkert et al, 2017) TNBC is categorized by the absence of three main biomarkers, i.e. estrogen and progesterone receptors, low expression of HER2 by immunohistochemistry (IHC), and lack of amplification by fluorescence in situ hybridization (FISH) test.…”

“…The absence of these features means that the hormonal agents and anti-HER2 treatment methods cannot be successful in treating TNBC (Kim et al, 2018;Collignon et al, 2016). The epidermal growth factor receptor (EGFR) activation stimulates cell proliferation and provide protection against apoptosis by activating protein kinase pathways (Li et al, 2017;Kim et al, 2017) Several methods, such as IHC, chromogenic in situ hybridization (CISH) and FISH are now available to quantify HER2/neu expression. (Goud et al, 2012) Hence, the aim of this study was to compare three groups of TNBCs, namely complete negative HER2 expression by IHC, minimal HER2 (1+) expression, and moderate HER2 (2+) expression by IHC and the negative FISH test for HER2 amplification.…”

Recent Use of Oral Contraceptives and Risk of Luminal B, Triple-Negative, and HER2-Overexpressing Breast Cancer

“…Few studies have evaluated the relationship between OC use and risk of molecular subtypes of breast cancer. Some of these found that OC use is associated with increased risks of TN [3,[5][6][7] [3,6,9], ER- [4], luminal A [8,10], luminal B [8,10], TN [8,10], and H2E [3,6,8,10] breast cancers. However, three did not restrict analyses to premenopausal women [5,8,9].…”

“…First, our study used a case-case study design, as did two others [11,12], where luminal A cases served as our reference outcome. While this study design is a limitation of the present study, as it prevented comparison with cancer-free controls as many other studies have done [3][4][5][6][7][8][9][10]22,23], it allowed us to examine the heterogeneity in the established association between OC use and breast cancer risk, by molecular subtype. We also restricted analyses to younger, premenopausal women, while others did not [5,8,9,11,12] which may explain inconsistencies with previous findings.…”

“…The subtypes differ in etiology, treatment options, and prognosis [2]. Some studies have shown an increased risk of TN breast cancer associated with OC use [3,[5][6][7], but others have not [8][9][10][11][12], and the association with other subtypes is less clear [3][4][5][6][7][8][9][10][11][12]. Recency [3,5,6], duration of use [3][4][5][6], and the dosage and type of hormones in OCs [3,4] have been shown to influence the association.…”