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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Available from: Geoffrey C Kabat, Oct 05, 2015
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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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    ABSTRACT: Background Breast cancer is the most common cancer in women worldwide. We investigated the association of hormonal contraceptive use and breast cancer in Thai women. Methods A cohort study was conducted in Khon Kaen, Thailand. There were 70 cases of histologically confirmed breast cancer among 11 414 women aged 30 to 69 years who were recruited as participants in the cohort study during the period from 1990 through 2001. The study population was followed-up until December 31, 2011. To identify factors associated with incidence of breast cancer, hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using a Cox proportional hazards model. Results The 11 414 women provided a total observation time of 157 200 person-years. Breast cancer risk among women with a history of hormonal contraceptive use was 1.31 times that of women without such a history, but the difference was not statistically significant (95% CI, 0.65–2.65). No type of hormonal contraceptive was associated with a significant increase in breast cancer risk as compared with women who had never used hormonal contraceptives (oral contraception: HR = 1.35, 95% CI, 0.65–2.78; injection contraception: HR = 1.25, 95% CI, 0.56–2.80), and there was no relationship between duration of hormonal contraceptive use and breast cancer. Conclusions There was no association between hormonal contraceptive use and breast cancer; however, this finding should be viewed with caution due to the small number of cases.
    Journal of Epidemiology 03/2014; 24(3). DOI:10.2188/jea.JE20130121 · 3.02 Impact Factor
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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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    ABSTRACT: Young age breast cancers are quite prevalent in our setup, a significant number of which exhibit triple negative phenotype. These cancers behave in an aggressive fashion and unresponsive to targeted adjuvant therapy. We aimed to evaluate clinical and histopathologic features of triple negative cancers in our population. We retrospectively evaluated 1104 cases of primary breast cancers. Immunohistochemical studies for ER, PR and Her2neu followed by Her2neu gene amplification by FISH testing were done to identify 205 (18.6%) cases of triple negative breast cancers. Mean age for triple negative breast cancer patients was 48.4 years (+/-12.3) and 60% of patients were diagnosed at less than 50 years of age. Although ductal carcinoma was the most frequent histologic type, a meaningful number of cases exhibited metaplastic and medullary like features (10.7% and 5.9% respectively). Similarly geographic necrosis involving more than 40% of tumor and extensive lymphocytic infiltration was a considerable finding. Mean Ki67 index was 45.2% (+/-25.2) and as a reflection of tumor grade, a significantly higher proportion of cases (66.3%) were under high risk Ki67 category (>30%). Triple negative breast cancers typify high grade breast cancers with a higher frequency of atypical medullary and metaplastic histologies. Their prevailing occurrence at a younger age raises question of under lying BRCA mutations in our population. Therefore, we suggest that risk factors including BRCA 1 mutations should be uncovered in reproductive age group breast cancers especially those disclosing basal like phenotype.Virtual slides: The virtual slide(s) for this article can be found here:
    Diagnostic Pathology 02/2014; 9(1):43. DOI:10.1186/1746-1596-9-43 · 2.60 Impact Factor
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    • "Previous prospective studies investigating the association of reproductive factors with HR-positive breast cancer have shown relatively consistent inverse risk associations with increasing menarcheal age, ever having a full-term childbirth and particularly a full-term childbirth at an early age [3,9,14,25]. However, consensus on the associations with HR-negative tumors has not been reached because previous prospective studies have lacked sufficient sample sizes [3,9,26] and because of the heterogeneous nature of HR-negative subtypes [1]. "
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    ABSTRACT: The association of reproductive factors with hormone receptor (HR)-negative breast tumors remains uncertain. Within the EPIC cohort, Cox proportional hazards models were used to describe the relationships of reproductive factors (menarcheal age, time between menarche and first pregnancy, parity, number of children, age at first and last pregnancies, time since last full-term childbirth, breastfeeding, age at menopause, ever having an abortion and use of oral contraceptives [OC]) with risk of ER-PR- (n = 998) and ER+PR+ (n = 3,567) breast tumors. A later first full-term childbirth was associated with increased risk of ER+PR+ tumors but not with risk of ER-PR- tumors (>=35 vs. <=19 years HR: 1.47 [95%CI 1.15-1.88] ptrend < 0.001 for ER+PR+ tumors; >=35 vs. <=19 years HR: 0.93 [95%CI 0.53-1.65] ptrend = 0.96 for ER-PR- tumors; Phet = 0.03). The risk associations of menarcheal age, and time period between menarche and first full-term childbirth with ER-PR-tumors were in the similar direction with risk of ER+PR+ tumors (phet = 0.50), although weaker in magnitude and statistically only borderline significant. Other parity related factors such as ever a full-term birth, number of births, age- and time since last birth were associated only with ER+PR+ malignancies, however no statistical heterogeneity between breast cancer subtypes was observed. Breastfeeding and OC use were generally not associated with breast cancer subtype risk. Our study provides possible evidence that age at menarche, and time between menarche and first full-term childbirth may be associated with the etiology of both HR-negative and HR-positive malignancies, although the associations with HR-negative breast cancer were only borderline significant.
    BMC Cancer 12/2013; 13(1):584. DOI:10.1186/1471-2407-13-584 · 3.36 Impact Factor
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