Reproductive History and Oral Contraceptive Use in Relation to Risk of Triple-Negative Breast Cancer

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
Journal of the National Cancer Institute (Impact Factor: 12.58). 02/2011; 103(6):470-7. DOI: 10.1093/jnci/djr030
Source: PubMed


Triple-negative (ie, estrogen receptor [ER], progesterone receptor, and HER2 negative) breast cancer occurs disproportionately among African American women compared with white women and is associated with a worse prognosis than ER-positive (ER+) breast cancer. Hormonally mediated risk factors may be differentially related to risk of triple-negative and ER+ breast cancers.
Using data from 155,723 women enrolled in the Women's Health Initiative, we assessed associations between reproductive and menstrual history, breastfeeding, oral contraceptive use, and subtype-specific breast cancer risk. We used Cox regression to evaluate associations with triple-negative (N = 307) and ER+ (N = 2610) breast cancers and used partial likelihood methods to test for differences in subtype-specific hazard ratios (HRs).
Reproductive history was differentially associated with risk of triple-negative and ER+ breast cancers. Nulliparity was associated with decreased risk of triple-negative breast cancer (HR = 0.61, 95% confidence interval [CI] = 0.37 to 0.97) but increased risk of ER+ breast cancer (HR = 1.35, 95% CI = 1.20 to 1.52). Age-adjusted absolute rates of triple-negative breast cancer were 2.71 and 1.54 per 10,000 person-years in parous and nulliparous women, respectively; by comparison, rates of ER+ breast cancer were 21.10 and 28.16 per 10,000 person-years in the same two groups. Among parous women, the number of births was positively associated with risk of triple-negative disease (HR for three births or more vs one birth = 1.46, 95% CI = 0.82 to 2.63) and inversely associated with risk of ER+ disease (HR = 0.88, 95% CI = 0.74 to 1.04). Ages at menarche and menopause were modestly associated with risk of ER+ but not triple-negative breast cancer; breastfeeding and oral contraceptive use were not associated with either subtype.
The association between parity and breast cancer risk differs appreciably for ER+ and triple-negative breast cancers. These findings require further confirmation because the biological mechanisms underlying these differences are uncertain.

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    • "In contrast, these factors showed either a lack of association or associations in the opposite direction for ER-negative (non-luminal) tumours. For example, parity and premenopausal obesity were protective for luminal cancers but associated with increased risk for non-luminal tumours, particularly triple-negative breast cancer (TNBC: ER À /PR À /HER2 À ; Millikan et al, 2008; Phipps et al, 2011). We have previously shown that risk factor associations differed most strikingly between luminal A (ER þ or PR þ /HER2 À ) and core-basal phenotype (CBP: TNBC expressing (CK5 or CK5/6) or EGFR), suggesting that these two subtypes may develop from etiologically different pathways (Yang et al, 2011). "
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    ABSTRACT: Background: Luminal A breast cancer defined as hormone receptor positive and human epidermal growth factor receptor 2 (HER2) negative is known to be heterogeneous. Previous study showed that luminal A tumours with the expression of basal markers ((cytokeratin (CK) 5 or CK5/6) or epidermal growth factor receptor (EGFR)) were associated with poorer prognosis compared with those that stained negative for basal markers. Prompted by this study, we assessed whether tumour characteristics and risk factors differed by basal marker status within luminal A tumours. Methods: We pooled 5040 luminal A cases defined by immunohistochemistry (4490 basal-negative ((CK5 (or CK5/6))- and EGFR-) and 550 basal-positive ((CK5 (or CK5/6+)) or EGFR+)) from eight studies participating in the Breast Cancer Association Consortium. Case-case comparison was performed using unconditional logistic regression. Results: Tumour characteristics and risk factors did not vary significantly by the expression of basal markers, although results suggested that basal-positive luminal tumours tended to be smaller and node negative, and were more common in women with a positive family history and lower body mass index. Conclusions: Most established breast cancer risk factors were similar in basal-positive and basal-negative luminal A tumours. The non-significant but suggestive differences in tumour features and family history warrant further investigations.British Journal of Cancer advance online publication, 17 December 2015; doi:10.1038/bjc.2015.437
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    • "Hormonal contraceptive use is a risk factor for breast cancer, but the magnitude of the risk is unclear. Other possible risk factors include age,4 body mass index,5,6 family history of breast cancer,7 early menarche and late menopause,8 age at first childbirth,9 and shorter lifetime duration of breastfeeding in premenopausal women.10 A meta-analysis of case-control studies reported that oral hormonal contraceptive use increased the risk of premenopausal breast cancer.11 "
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    • "They also affirmed that history of recent birth and obesity as being risk factors for these cancers [18]. Phipps AL et al. suggested nulliparity as a protective factor for triple negative breast cancer, although they didn’t find a significant association with breast feeding and oral contraceptive usage [19]. Risk factors for basal like cancers were also explored in Carolina breast cancer study. "
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