Reproductive history,breast‐feeding and risk of triple negative breast cancer: The Breast Cancer Etiology in Minorities (BEM) study

Few risk factors have been identified for triple negative breast cancer (TNBC) which lacks expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). This more aggressive subtype disproportionately affects some racial/ethnic minorities and is associated with lower survival. We pooled data from three population‐based studies (558 TNBC and 5,111 controls) and examined associations of TNBC risk with reproductive history and breast‐feeding. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable logistic regression. For younger women, aged <50 years, TNBC risk was increased two‐fold for parous women who never breast‐fed compared to nulliparous women (OR = 2.02, 95% CI = 1.12–3.63). For younger parous women, longer duration of lifetime breast‐feeding was associated with a borderline reduced risk (≥24 vs. 0 months: OR = 0.52, 95% CI = 0.26–1.04, P_trend = 0.06). Considering the joint effect of parity and breast‐feeding, risk was increased two‐fold for women with ≥3 full‐term pregnancies (FTPs) and no or short‐term (<12 months) breast‐feeding compared to women with 1–2 FTPs and breast‐feeding ≥12 months (OR = 2.56, 95% CI = 1.22–5.35). None of these associations were observed among older women (≥50 years). Differences in reproductive patterns possibly contribute to the ethnic differences in TNBC incidence. Among controls aged <50 years, the prevalence of no or short‐term breast‐feeding and ≥3 FTPs was highest for Hispanics (22%), followed by African Americans (18%), Asian Americans (15%) and non‐Hispanic whites (6%). Breast‐feeding is a modifiable behavioral factor that may lower TNBC risk and mitigate the effect of FTPs in women under age 50 years.     

Association of female reproductive and hormonal factors with gallbladder cancer risk in Asia: A pooled analysis of the Asia Cohort Consortium

The female predominance of gallbladder cancer (GBC) has led to a hypothesis regarding the hormone-related aetiology of GBC. We aimed to investigate the association between female reproductive factors and GBC risk, considering birth cohorts of Asian women. We conducted a pooled analysis of 331,323 women from 12 cohorts across 4 countries (China, Japan, Korea, and Singapore) in the Asia Cohort Consortium. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) to assess the association between reproductive factors (age at menarche, parity, age at first delivery, breastfeeding, and age at menopause) and GBC risk. We observed that a later age at menarche was associated with an increased risk of GBC (HR 1.4, 95% CI 1.16–1.70 for 17 years and older vs. 13–14 years), especially among the cohort born in 1940 and later (HR 2.5, 95% CI 1.50–4.35). Among the cohort born before 1940, women with a later age at first delivery showed an increased risk of GBC (HR 1.56, 95% CI 1.08–2.24 for 31 years of age and older vs. 20 years of age and younger). Other reproductive factors did not show a clear association with GBC risk. Later ages at menarche and at first delivery were associated with a higher risk of GBC, and these associations varied by birth cohort.     

Associations of reproductive time events and intervals with breast cancer risk: A report from the Shanghai Breast Cancer Study

While there is clear evidence for an association between later age at first live birth and increased breast cancer risk, associations with the timing of other reproductive events are less clear. As breast tissues undergo major structural and cellular changes during pregnancy, we examined associations between reproductive time events and intervals with breast cancer risk among parous women from the population‐based Shanghai Breast Cancer Study (SBCS). Unconditional logistic regression was used to evaluate associations with breast cancer risk for 3,269 cases and 3,341 controls. In addition to later age at first live birth, later ages at first pregnancy and last pregnancy were significantly associated with increased breast cancer risk (p‐trend = 0.002, 0.015, 0.008, respectively); longer intervals from menarche to first or last live birth were also associated with increased risk (p‐trend < 0.001, =0.018, respectively). Analyses stratified by menopausal status and estrogen receptor (ER)/progesterone receptor (PR) status revealed that associations for later age at first pregnancy or live birth and longer intervals from menarche to first or last live birth occurred among premenopausal women and ER+/PR+ breast cancers, whereas the association for later age at last pregnancy occurred among postmenopausal women and women with ER+/PR? or ER?/PR+ breast cancers. Because of the high correlation with other reproductive variables, models did not include adjustment for age at first live birth; when included, the significance of all associations was attenuated. These findings suggest that while reproductive time events and intervals play an important role in breast cancer etiology, contributions may differ by menopausal status and hormone receptor status of breast cancers.     

Association of mammographic density with hormone receptors in invasive breast cancers: Results from a case-only study

For many breast cancer (BC) risk factors, there is growing evidence concerning molecular subtypes for which the risk factor is specific. With regard to mammographic density (MD), there are inconsistent data concerning its association with estrogen receptor (ER) and progesterone receptor (PR) expression. The aim of our study was to analyze the association between ER and PR expression and MD. In our case-only study, data on BC risk factors, hormone receptor expression and MD were available for 2,410 patients with incident BC. MD was assessed as percent MD (PMD) using a semiautomated method by two readers for every patient. The association of ER/PR and PMD was studied with multifactorial analyses of covariance with PMD as the target variable and including well-known factors that are also associated with MD, such as age, parity, use of hormone replacement therapy, and body mass index (BMI). In addition to the commonly known associations between PMD and age, parity, BMI and hormone replacement therapy, a significant inverse association was found between PMD and ER expression levels. Patients with ER-negative tumors had an average PMD of 38%, whereas patients with high ER expression had a PMD of 35%. A statistical trend toward a positive association between PMD and PR expression was also seen. PMD appears to be inversely associated with ER expression and may correlate positively with PR expression. These effects were independent of other risk factors such as age, BMI, parity, and hormone replacement therapy, possibly suggesting other pathways that mediate this effect.     

Progesterone receptor status modifies the association between body mass index and prognosis in women diagnosed with estrogen receptor positive breast cancer

The role of progesterone receptor (PR) status on the association between obesity and prognosis of estrogen receptor positive (ER+) breast cancer (BC) remains poorly understood. We aim to examine whether this association varies according to the tumor PR status. Data for 3,747 women diagnosed with nonmetastatic ER+ invasive BC between 1995 and 2010 were analyzed. Women were classified according to their body mass index (BMI) (<18.5, 18.5–24.9, 25.0–29.9 or ≥30.0 kg/m²). Tumor PR status (PR−, PR+) was evaluated by immunohistochemistry. Hazard ratios (HR) for survival outcomes were estimated using multivariable Cox regression models. Effect modification was assessed on both additive and multiplicative scales using relative excess risk due to interaction and ratio of HRs, respectively. After a median follow-up of 5.9 years (range: 3.4–9.2), women with PR− tumors and underweight (HR = 2.76, 95% CI: 1.40–4.91), overweight (HR = 2.02, 95% CI: 1.43–2.81) or obese (HR = 2.51, 95% CI: 1.67–3.65) had increased risk of all-cause mortality, when compared to normal weight women with PR+ tumors. A similar pattern of associations was observed for BC-specific mortality. In contrast, women with PR+ tumors had similar risks for both mortality outcomes, regardless of BMI. On the additive scale, all-cause mortality was modified by PR status for overweight and obese women, whereas for BC-specific mortality, it was only modified for underweight women. The same observations were found on the multiplicative scale. These results suggest that poorer survival associated with low and high BMI among women diagnosed with ER+ BC may depend on the tumor PR status.     

The efficacy of lymphaticovenular anastomosis in breast cancer-related lymphedema

Background

U.S. Hispanic women have high rates of parity, breastfeeding, and obesity. It is unclear whether these reproductive factors are associated with breast cancer (BC) mortality. We examined the associations between breastfeeding, parity, adiposity and BC-specific and overall mortality in Hispanic and non-Hispanic white (NHW) BC cases.

Methods

The study population included 2921 parous women (1477 Hispanics, 1444 NHWs) from the Breast Cancer Health Disparities Study with invasive BC diagnosed between 1995 and 2004. Information on reproductive history and lifestyle factors was collected by in-person interview. Overall and stratified Cox proportional hazard regression models by ethnicity, parity, and body mass index (BMI) at age 30 years were used to calculate hazard ratios (HR) and 95% confidence intervals (CI).

Results

After a median follow-up time of 11.2 years, a total of 679 deaths occurred. Pre-diagnostic breastfeeding was associated with a 16% reduction in mortality (HR 0.84; 95% 0.72–0.99) irrespective of ethnicity. Parity significantly modified the association between breastfeeding duration and mortality (p interaction = 0.05), with longer breastfeeding duration associated with lower risk among women who had ≤2 births (p trend = 0.02). Breastfeeding duration was associated with reduced risk of both BC-specific and overall mortality among women with BMI <25 kg/m², while positive associations were observed among women with BMI ≥25 kg/m² (p interactions <0.01).

Conclusion

Pre-diagnostic breastfeeding was inversely associated with risk of mortality after BC, particularly in women of low parity or normal BMI. These results provide another reason to encourage breastfeeding and weight management among young women.

     

Reproductive risk factors and breast cancer subtypes: a review of the literature

Aside from age, sex, and family history, risk of developing breast cancer is largely linked to reproductive factors, which characterize exposure to sex hormones. Given that, molecular testing at the tumor level is currently possible, clinical characterization of tumor subtypes is routinely conducted to guide treatment decisions. However, despite the vast amount of published data from observational studies on reproductive factor associations and breast cancer risk, relatively fewer reports have been published on associations specific to breast tumor subtypes. We conducted a review of the literature and summarized the results of associations between reproductive factors and risk or odds of three distinct tumor subtypes: estrogen receptor/progesterone receptor positive (hormone receptor positive, HR+ tumors), tumors overexpressing the human epidermal receptor 2 protein (HER2+), and triple negative breast cancer (TNBC), which lacks the three markers. Results show that the most consistent evidence for associations with reproductive risk factors exists for HR+ breast cancers, with nulliparity, current use of menopausal hormone therapy, and prolonged interval between menarche and age at first birth being the strongest risk factors; increased age at first birth and decreased age at menarche were fairly consistently associated with HR+ cancers; and though less consistent, older age at menopause was also positively associated, while lactation was inversely associated with HR+ tumors. Fewer consistent associations have been reported for TNBC. The single protective factor most consistently associated with TNBC was longer duration of breastfeeding. Increased parity, younger age at first birth, older age at menarche, and oral contraceptive use were less consistently shown to be associated with TNBC. No remarkable associations for HER2+ breast cancers were evident, although this was based on relatively scarce data. Findings suggest heterogeneity in reproductive risk factors for the distinct subtypes of breast tumors, which may have implications for recommended prevention strategies.     

Reproductive history and risk of second primary breast cancer: the WECARE study.

BACKGROUND: Women with an initial breast cancer diagnosis are at elevated risk of developing subsequent cancer in the contralateral breast. Studies of reproductive factors and contralateral breast cancer (CBC) have provided inconsistent results. METHODS: We employed a case-control study nested within five population-based cancer registries in the United States and Denmark to examine associations between reproductive history and CBC risk. Cases were women with asynchronous CBC who had their first primary invasive breast cancer before age 55 years. Two controls, who had only one primary breast cancer diagnosis, were individually matched to each case on age and year of diagnosis, race, and registry. A total of 694 case-control triplets and 11 case-control pairs were enrolled. Information regarding possible CBC risk factors was obtained via telephone interviews. Multivariable conditional logistic regression was used to estimate rate ratios (RR) and 95% confidence intervals (95% CI) associated with risk factors of interest. RESULTS: Increasing number of full-term pregnancies (FTP) was inversely associated with CBC risk (P trend, 0.001). Women who reported menarche before age 13 years had an increased risk of CBC (RR, 1.26; 95% CI, 1.01-1.58). Age at first FTP, breastfeeding history, and age at menopause were not significantly associated with CBC risk. CONCLUSIONS: These results suggest age at menarche and parity, which are established risk factors for first primary breast cancer, are associated with CBC, whereas other reproductive risk factors associated with first primary breast cancer, such as age at first FTP, are less important factors in the development of CBC.     

Reproductive factors and risk of breast cancer by tumor subtypes among Ghanaian women: A population-based case–control study

Higher proportions of early-onset and estrogen receptor (ER) negative cancers are observed in women of African ancestry than in women of European ancestry. Differences in risk factor distributions and associations by age at diagnosis and ER status may explain this disparity. We analyzed data from 1,126 cases (aged 18–74 years) with invasive breast cancer and 2,106 controls recruited from a population-based case–control study in Ghana. Odds ratios (OR) and 95% confidence intervals (CI) were estimated for menstrual and reproductive factors using polytomous logistic regression models adjusted for potential confounders. Among controls, medians for age at menarche, parity, age at first birth, and breastfeeding/pregnancy were 15 years, 4 births, 20 years and 18 months, respectively. For women ≥50 years, parity and extended breastfeeding were associated with decreased risks: >5 births vs. nulliparous, OR 0.40 (95% CI 0.20–0.83) and 0.71 (95% CI 0.51–0.98) for ≥19 vs. <13 breastfeeding months/pregnancy, which did not differ by ER. In contrast, for earlier onset cases (<50 years) parity was associated with increased risk for ER-negative tumors (p-heterogeneity by ER = 0.02), which was offset by extended breastfeeding. Similar associations were observed by intrinsic-like subtypes. Less consistent relationships were observed with ages at menarche and first birth. Reproductive risk factor distributions are different from European populations but exhibited etiologic heterogeneity by age at diagnosis and ER status similar to other populations. Differences in reproductive patterns and subtype heterogeneity are consistent with racial disparities in subtype distributions.     

Association between chronological change of reproductive factors and breast cancer risk defined by hormone receptor status: results from the Seoul Breast Cancer Study

Lifestyle factors have been chronologically changed into western style ones, which could result in the rapid increase of breast cancer incidence in Korea. It is plausible that reproductive factors through hormonal mechanisms are differentially related to the risk of breast cancer subtypes. We investigated the association of reproductive risk factors on breast cancer by birth year groups and also evaluated the differential associations on the hormone receptor-defined subtypes. Using the data from the Seoul Breast Cancer Study (SeBCS), a multicenter case–control study, 3,332 breast cancer patients and 3,620 control subjects were analyzed. The distribution of subtypes among cases was as follows: 61.0 % estrogen receptor (ER)-positive, 51.9 % progesterone receptor (PR)-positive, and 43.4 % both ER/PR-positive status, respectively. Polytomous logistic regression and Wald tests for heterogeneity have been used across the subtypes. The frequencies of reproductive-related risk factors including early age at menarche, nulligravid, age at first full-term pregnancy (FFTP), duration of estrogen exposure before FFTP (EEBF), less number of children, never breastfeeding, and short duration of breastfeeding has increased as women were born later in both cases and controls, respectively (p _trend < 0.0001. Among breast cancer patients, either ER- or PR-positive subtypes were increased in women born in 1960s compared to women born in 1940s. Early age at menarche increased the risk of breast cancer regardless of the subtypes while nulligravid, late age at FFTP, and longer duration of EEBP were associated with hormone receptor-positive cancer risk only (p _{heterogeneity} < 0.05), which associations were stronger among women born later. Our results suggest that the associations of age at menarche, parity, age at FFTP, and duration of EEBF with breast cancer risk were different based on the hormone receptor status and birth year groups in Korea.     

A case–control study of reproductive factors associated with subtypes of breast cancer in Northeast China

Based on the expression of estrogen receptor (ER), progesterone receptor (PR) and HER2/neu (HER2), breast cancer is classified into several subtypes: luminal A (ER+ and/or PR+, HER2?), luminal B (ER+ and/or PR+, HER2+), HER2-overexpressing (ER?, PR?, and HER2+) and triple-negative (ER?, PR?, and HER2?). The aim of this case–control study is to determine reproductive factors associated with breast cancer subtypes in Chinese women. A total of 1,417 patients diagnosed with breast cancer in the First Affiliated Hospital, China Medical University, Shenyang, China between 2001 and 2009 and 1,587 matched controls without a prior breast cancer were enrolled. Personal interviews were conducted to obtain information on reproductive characteristics and clinical history. Relationships between the factors and the subtypes of breast cancer were examined using logistic regression to compute odds ratios (OR) and 95% confidence intervals (CI). Notably, luminal A (50.0%) was the most prevalent subtype relative to luminal B (15.10%), HER2-overexpressing (10.87%) and triple-negative (23.08%). Menarche at an early age was associated with a reduced risk of luminal A (OR, 2.35; 95% CI, 1.45–3.81). Breastfeeding protected parous women from any subtype of breast cancer. Postmenopause and spontaneous abortion were inversely associated with the risk of luminal tumors. By contrast, multiparity, family history of breast cancer and induced abortion increased the risk of breast cancer. Collectively, our findings suggest that reproductive factors such as age at menarche, parity, breastfeeding, menopausal status and abortion history have different effects on the subtypes of breast cancer in Chinese women.     

Higher population-based incidence rates of triple-negative breast cancer among young African-American women : Implications for breast cancer screening recommendations

BACKGROUND:

Differences in the breast cancer burden of African‐American women compared with white American women are well documented. Recent controversies have emerged regarding age‐appropriate mammographic screening guidelines, and these surveillance recommendations may influence future breast cancer disparities. The objective of the current study was to evaluate age‐specific breast cancer stage distributions and incidence rates of triple‐negative breast cancer (TNBC) in a population‐based tumor registry.

METHODS:

The authors analyzed breast cancers from the California Cancer Registry (CCR) that were diagnosed between 1988 and 2006. The results were stratified by age and race/ethnicity, with white Americans identified as non‐Hispanic whites (NHWs) and African Americans identified as non‐Hispanic blacks (NHBs). Breast cancer stage distributions and TNBC incidence rates also were analyzed.

RESULTS:

In total, 375,761 invasive breast cancers were evaluated (including 276,938 in NHWs and 21,681 in NHBs). NHBs and Hispanics tended to be younger than NHWs (median ages 57 years, 54 years, and 64 years, respectively). Lifetime incidence rates were higher for NHWs compared with NHBs and Hispanics; however, for women aged <44 years, incidence was highest among NHBs. NHBs also had higher incidence rates of stage III and IV disease and a higher incidence of TNBC in all age categories.

CONCLUSIONS:

Population‐based data demonstrated that African‐American women had a more advanced stage distribution for breast cancer compared with white American women and higher incidence rates for TNBC. These patterns were observed for women ages 40 to 49 years and for older women, and they suggest that mammographic screening for the early detection of breast cancer will be particularly relevant for younger African‐American women. Cancer 2011. © 2011 American Cancer Society.     

Reproductive factors and breast cancer risk according to joint estrogen and progesterone receptor status: a meta-analysis of epidemiological studies

Introduction  

Although reproductive factors have been known for decades to be associated with breast cancer risk, it is unclear to what extent these associations differ by estrogen and progesterone receptor (ER/PR) status. This report presents the first meta-analysis of results from epidemiological studies that have investigated parity, age at first birth, breastfeeding, and age at menarche in relation to ER⁺PR⁺ and ER^-PR^- cancer risk.     

Chronic long-term exposure to cadmium air pollution and breast cancer risk in the French E3N cohort

Cadmium, due to its estrogen-like activity, has been suspected to increase the risk of breast cancer; however, epidemiological studies have reported inconsistent findings. We conducted a case–control study (4,059 cases and 4,059 matched controls) nested within the E3N French cohort study to estimate the risk of breast cancer associated with long-term exposure to airborne cadmium pollution, and its effect according to molecular subtype of breast cancer (estrogen receptor negative/positive [ER−/ER+] and progesterone receptor negative/positive [PR−/PR+]). Atmospheric exposure to cadmium was assessed using a Geographic Information System-based metric, which included subject's residence-to-cadmium source distance, wind direction, exposure duration and stack height. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression. Overall, there was no significant association between cumulative dose of airborne cadmium exposure and the risk of overall, premenopausal and postmenopausal breast cancer. However, by ER and PR status, inverse associations were observed for ER− (OR_{Q5 vs. Q1} = 0.63; 95% CI: 0.41–0.95, p_trend = 0.043) and for ER−/PR− breast tumors (OR_{Q4 vs. Q1} = 0.62; 95% CI: 0.40–0.95, OR_{Q5 vs. Q1} = 0.68; 95% CI: 0.42–1.07, p_trend = 0.088). Our study provides no evidence of an association between exposure to cadmium and risk of breast cancer overall but suggests that cadmium might be related to a decreased risk of ER− and ER−/PR− breast tumors. These observations and other possible effects linked to hormone receptor status warrant further investigations.     

Perfluorinated alkylated substances serum concentration and breast cancer risk: Evidence from a nested case-control study in the French E3N cohort

Endocrine-disrupting chemicals are proposed to increase breast cancer (BC) incidence. Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), two perfluorinated alkylated substances (PFASs), are suspected to be ubiquitously present in the blood of human population worldwide. We investigated the associations between serum concentrations of these substances and BC risk. Etude Epidémiologique auprès de femmes de l'Education Nationale is a cohort of 98,995 French women born in 1925–1950 and followed up since 1990. We sampled 194 BC cases and 194 controls from women with available blood samples. Serum concentrations of PFASs were measured by liquid chromatography coupled to tandem mass spectrometry (LC–MS/MS). Adjusted conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). All statistical tests were two sided. While PFASs concentrations were not associated with BC risk overall, we found positively linear associations between PFOS concentrations and the risk of ER+ (3rd quartile: OR = 2.22 [CI = 1.05–4.69]; 4th quartile: OR = 2.33 [CI = 1.11–4.90]); P_trend = 0.04) and PR+ tumors (3rd quartile: OR = 2.47 [CI = 1.07–5.65]; 4th quartile: OR = 2.76 [CI = 1.21–6.30]; P_trend = 0.02). When considering receptor-negative tumors, only the 2nd quartile of PFOS was associated with risk (ER−: OR = 15.40 [CI = 1.84–129.19]; PR−: OR = 3.47 [CI = 1.29–9.15]). While there was no association between PFOA and receptor-positive BC risk, the 2nd quartile of PFOA was positively associated with the risk of receptor-negative tumors (ER−: OR = 7.73 [CI = 1.46–41.08]; PR−: OR = 3.44 [CI = 1.30–9.10]). PFAS circulating levels were differentially associated with BC risk. While PFOS concentration was linearly associated with receptor-positive tumors, only low concentrations of PFOS and PFOA were associated with receptor-negative tumors. Our findings highlight the importance of considering exposure to PFASs as a potential risk factor for BC.     

Risk factors for breast cancer in a black population--the Barbados National Cancer Study

The Barbados National Cancer Study (BNCS) is a nationwide case-control study investigating environmental and genetic factors for breast cancer (BC) in a predominantly African-origin population with similar ancestry as African-Americans. This report evaluates associations of incident BC in the BNCS to various factors, including demographic, anthropometric, reproductive and family history variables, not investigated previously in this population. The BNCS included 241 incident BC cases and 481 age-matched female controls, with mean ages of 57 and 56 years, respectively. In addition to a reported family history of BC in a close relative [odds ratios (OR) = 3.74, 95% CI (1.41, 9.90) in a parent; OR = 3.26 (1.47, 7.21) in a sibling], other factors associated with BC were older age at first full-term pregnancy [OR = 1.04 (1.00, 1.07)] and having a history of benign breast disease [OR = 1.88 (1.19, 2.99)]. Increased parity reduced the risk of BC [OR = 0.34 (0.15, 0.77) among those with >or=3 children]. The reproductive patterns of African-Barbadian (AB) women tended to differ from those of African-American (AA) women (later age of menarche, earlier age at first pregnancy, higher frequency of lactation and infrequent use of exogenous hormones) and could help to explain their considerably lower postmenopausal incidence of BC. The relationship between reported family history and BC, combined with the associations noted for several reproductive and other variables, supports the genetic and environmental contributions to BC, which may vary in populations across the African diaspora. Further investigations of other populations may clarify these issues.     

The association of soy food consumption with the risk of subtype of breast cancers defined by hormone receptor and HER2 status

Soy food intake has previously been associated with reduced breast cancer risk. Epidemiological evidence for subgroups of breast cancer, particularly by menopausal and hormone receptor status, is less consistent. To evaluate the role of hormone receptor and menopausal status on the association between soy food intake and breast cancer risk, we measured usual soy food intake in adolescence and adulthood via food frequency questionnaire in 70,578 Chinese women, aged 40–70 years, recruited to the Shanghai Women's Health Study (1996–2000). After a median follow‐up of 13.2 years (range: 0.01–15.0), 1,034 incident breast cancer cases were identified. Using Cox models, we found that adult soy intake was inversely associated with breast cancer risk [hazard ratio (HR) for fifth versus first quintile soy protein intake = 0.78; 95% confidence interval (CI):0.63–0.97]. The association was predominantly seen in premenopausal women (HR = 0.46; 95% CI:0.29‐0.74). Analyses further stratified by hormone receptor status showed that adult soy intake was associated with significantly decreased risk of estrogen receptor (ER)+/progesterone receptor (PR)+ breast cancer in postmenopausal women (HR = 0.72; 95% CI:0.53–0.96) and decreased risk of ER?/PR? breast cancer in premenopausal women (HR = 0.46; 95% CI:0.22–0.97). The soy association did not vary by human epidermal growth factor‐2 (HER2) status. Furthermore, we found that high soy intake during adulthood and adolescence was associated with reduced premenopausal breast cancer risk (HR = 0.53; 95% CI: 0.32–0.88; comparing third vs. first tertile) while high adulthood soy intake was associated with postmenopausal breast cancer only when adolescent intake was low (HR = 0.63; 95% CI: 0.43–0.91). Our study suggests that hormonal status, menopausal status and time window of exposure are important factors influencing the soy‐breast cancer association.     

Pubertal growth and adult height in relation to breast cancer risk in African American women

Adult height has been positively associated with breast cancer risk. The timing of pubertal growth—as measured by age at menarche and age at attained height—may also influence risk. We evaluated associations of adult height, age at attained height, and age at menarche with incidence of invasive breast cancer in 55,687 African American women in the prospective Black Women's Health Study. Over 20 years, 1,826 invasive breast cancers [1,015 estrogen receptor (ER) positive; 542 ER negative] accrued. We used multivariable Cox proportional hazards regression to estimate hazards ratios (HRs) and 95% confidence intervals (CIs) for associations with breast cancer overall and by ER status, mutually adjusted for the three factors of interest. Adult height was associated with increased risk of ER+ breast cancer (HR for ≥70 inches vs ≤63 inches: 1.44; 95% CI: 1.09, 1.89) but not ER? (corresponding HR: 1.16; 95% CI: 0.78, 1.71) (p heterogeneity = 0.34). HRs for attained height before age 13 versus age >17 were 1.30 (95% CI: 0.96, 1.76) for ER+ and 1.25 (95% CI: 0.80, 1.96) for ER? breast cancer. Results for age at menarche (≤11 vs ≥14 years) were similar for ER+ and ER? breast cancer (HR for breast cancer overall: 1.30; 95% CI: 1.12, 1.50). We confirmed height as a strong risk factor for ER+ breast cancer in African American women and identified early age at attained height as a risk factor for both ER+ and ER? breast cancer, albeit without statistical significance of the latter associations. While adult height and timing of pubertal growth are inter‐related, our findings suggest that they may be independent risk factors for breast cancer.     

Examination of ancestral informative markers and self-reported race with tumor characteristics of breast cancer among black and white women

African American (AA) women have a higher mortality from breast cancer (BC) compared to European American (EA) women. This may be due to the higher proportion of AA women with tumors that are diagnosed at more advanced stages and are characterized as being estrogen receptor negative (ER-)/progesterone receptor negative (PR-). Our study sought to determine whether self-reported race and percent African ancestry were associated with BC tumor characteristics. In a multi-center, population-based case-control study of BC, we determined percent African ancestry using ancestry informative markers (AIM) among women self-reporting race as AA or Black. BC tumor characteristics were associated with self-reported race (including a 30 % reduction in ER+/PR+ tumors [95 % confidence interval [CI]: 0.6-0.9] and a 1.5-fold increased risk of high grade [95 % CI: 1.2-1.9] for AA women compared to EA women). AIMs among AA women were not associated with BC tumor characteristics (AA women with ≥95 % versus <80 % African ancestry, odds ratio [OR] = 1.0 for ER+/PR+ [95 % CI: 0.6-1.8] and OR = 0.9 for high-grade tumors [95 % CI: 0.6-1.4]). Similar findings were observed for BC stage. While BC subtypes were associated with self-reported race, BC subtypes were not associated with percent African ancestry. These study results suggest that subtle differences in percent African ancestry are less important than the overall presence of African ancestry in relation to BC tumor characteristics.     

Variation in breast cancer risk associated with factors related to pregnancies according to truncating mutation location, in the French National BRCA1 and BRCA2 mutations carrier cohort (GENEPSO)

ABSTRACT: INTRODUCTION: Mutations in BRCA1 and BRCA2 confer a high risk of breast cancer (BC), but the magnitude of this risk seems to vary according to the study and various factors. Although controversial, there are data to support the hypothesis of allelic risk heterogeneity. METHODS: We assessed variation in BC risk according to factors related to pregnancies by location of mutation in the homogeneous risk region of BRCA1 and BRCA2 in 990 women in the French study GENEPSO by using a weighted Cox regression model. RESULTS: Our results confirm the existence of the protective effect of an increasing number of full-term pregnancies (FTPs) toward BC among BRCA1 and BRCA2 mutation carriers (≥3 versus 0 FTPs: hazard ratio (HR) = 0.51, 95% confidence interval (CI) = 0.33 to 0.81). Additionally, the HR shows an association between incomplete pregnancies and a higher BC risk, which reached 2.39 (95% CI = 1.28 to 4.45) among women who had at least three incomplete pregnancies when compared with women with zero incomplete pregnancies. This increased risk appeared to be restricted to incomplete pregnancies occurring before the first FTP (HR = 1.77, 95% CI = 1.19 to 2.63). We defined the TMAP score (defined as the Time of Breast Mitotic Activity during Pregnancies) to take into account simultaneously the opposite effect of full-term and interrupted pregnancies. Compared with women with a TMAP score of less than 0.35, an increasing TMAP score was associated with a statistically significant increase in the risk of BC (P trend = 0.02) which reached 1.97 (95% CI = 1.19 to 3.29) for a TMAP score >0.5 (versus TMAP ≤0.35). All these results appeared to be similar in BRCA1 and BRCA2. Nevertheless, our results suggest a variation in BC risk associated with parity according to the location of the mutation in BRCA1. Indeed, parity seems to be associated with a significantly decreased risk of BC only among women with a mutation in the central region of BRCA1 (low-risk region) (≥1 versus 0 FTP: HR = 0.27, 95% CI = 0.13 to 0.55) (Pinteraction <10-3). CONCLUSIONS: Our findings show that, taking into account environmental and lifestyle modifiers, mutation position might be important for the clinical management of BRCA1 and BRCA2 mutation carriers and could also be helpful in understanding how BRCA1 and BRCA2 genes are involved in BC.