Disparities in breast cancer prognostic factors by race, insurance status, and education

Black women are more likely to be diagnosed with advanced stage and other less favorable breast cancer prognostic factors than white women. The aim of this study was to examine the extent to which markers of socioeconomic position accounts for black–white differences in these factors. Our study included 193,969 women diagnosed with invasive breast cancers during 2004–2005 from the National Cancer Database, which represents about 72% of all patients with cancer treated in the United States. Compared to white women, black women are more likely to be diagnosed with breast tumors that are less differentiated (odds ratio (OR) = 2.55, 95% confidence interval (CI) 2.44–2.66), hormone receptor negative (OR = 2.29, 95% CI 2.22–2.37), large (OR = 1.87, 95% CI 1.80–1.95), metastatic (OR = 1.89, 95% CI 1.78–2.00), and lymph node-positive (OR = 1.44, 95% CI 1.40–1.48). In multivariable analyses, adjustment for insurance and area-level educational attainment explained 31–39% of the differences in tumor size and metastasis, but only about 14% of the differences in grade and hormone receptors. After accounting for race and other covariates, uninsured women remained 3.66 (95% CI 3.30–4.07) times more likely to have metastasis and 2.37 (95% CI 2.17–2.58) times more likely to have large tumors compared to privately insured women. Similarly, the risk of having breast cancer with less favorable prognostic factors increased as area-level educational attainment decreased. Extending health insurance coverage to all women is likely to have an effect on reducing racial disparities in the development of breast cancers with poor prognostic factors.     

Radial scars and subsequent breast cancer risk: results from the Nurses’ Health Studies

Radial scars (RS) are benign proliferative lesions associated with an increased risk of subsequent breast cancer. However, it remains unclear whether RS are an independent risk factor for breast cancer or whether their association with breast cancer is due to their common occurrence with other proliferative lesions known to increase breast cancer risk. We performed an updated analysis of the association between RS and subsequent breast cancer risk in a nested case–control study among 460 cases and 1,792 controls with benign breast disease (BBD) in the Nurses’ Health Studies. Logistic regression was used to estimate associations between RS in BBD biopsy specimens and breast cancer risk, adjusted for matching factors and breast cancer risk factors, including histologic category of concurrent BBD. In multivariable models prior to adjustment for histologic category of BBD, RS were associated with a twofold increased risk of breast cancer (odds ratio (OR) = 2.0; 95 % confidence interval (95 % CI) 1.4, 2.8). This association was attenuated but still significant after adjustment for BBD histologic category (OR = 1.6; 95 % CI 1.1, 2.3). In models adjusted for BBD histologic category and other covariates, risk appeared greater among women with multiple RS (1 RS, OR = 1.5; 95 % CI 0.9, 2.3; ≥2 RS, OR = 2.7; 95 % CI 1.5, 5.0; p-heterogeneity = 0.12). There were also suggestions of a greater risk associated with RS among women age ≥50 years at biopsy (p-heterogeneity = 0.07) and for estrogen receptor-negative/progesterone receptor-negative tumors compared with other hormone receptor subtypes (p-heterogeneity = 0.19). RS appear to be an independent histologic risk factor for breast cancer. Larger studies are needed to further evaluate whether risk is increased when multiple RS are present and whether associations vary by age at biopsy or by hormone receptor status of the breast tumor.     

Vegetable protein and vegetable fat intakes in pre-adolescent and adolescent girls, and risk for benign breast disease in young women

Previous investigations, of adolescent diet recalled in adulthood, found lower risk for benign breast disease (BBD) with higher intakes of vegetable fat and nuts during high school. We investigate whether vegetable protein and fat, derived from diets reported during pre-adolescence and adolescence, are associated with subsequent risk for BBD in young women. The Growing Up Today Study includes 9,039 females, 9–15 years in 1996, who completed questionnaires annually through 2001, and then in 2003, 2005, 2007, and 2010. Food frequency questionnaires (1996–2001) obtained intake data on a variety of foods. Beginning in 2005, women (18–30 years) reported whether they had ever been diagnosed with BBD that was confirmed by breast biopsy (n = 112 cases). Logistic regression estimated associations between intakes of vegetable protein and fat and biopsy-confirmed BBD. Those individual foods that were the largest contributors of protein and fat in this cohort were also investigated. In analyses of intakes from 1996 through 1998, when our cohort was youngest, vegetable fat (OR = 0.72/(10 gm/day), 95 % CI 0.53–0.98; p = 0.04) was inversely associated with BBD risk. The greatest sources of vegetable fat and protein in these girls were peanut butter, peanuts, nuts, beans (beans, lentils, and soybeans), and corn. A daily serving of any one of these was associated with lower risk (OR = 0.32/(serv/day), 95 % CI 0.13–0.79; p = 0.01). Peanut butter (and nuts) at age 11 years was inversely associated with risk (p = 0.01). In analyses of intakes at age 14 years, vegetable protein was associated with lower BBD risk (OR = 0.64/(10 gm/day), 95 % CI 0.43–0.95; p = 0.03). A daily serving at 14 years of any one of the foods was associated with lower risk (OR = 0.34, 95 % CI 0.16–0.75; p = 0.01), as was peanut butter (and nuts) (p = 0.02). Girls with a family history of breast cancer had significantly lower risk if they consumed these foods or vegetable fat. In conclusion, consumption of vegetable protein, fat, peanut butter, or nuts by older girls may help reduce their risk of BBD as young women.     

Pretreatment levels of circulating Th1 and Th2 cytokines, and their ratios, are associated with ER-negative and triple negative breast cancers

Immune signatures in breast tumors differ by estrogen receptor (ER) status. The purpose of this study was to assess associations between ER phenotypes and circulating levels of cytokines that co-ordinate cell-mediated [T-helper type 1 (Th1)] and humoral [T-helper type 2 (Th2)] immunity. We conducted a case–case comparison of 523 women with newly diagnosed breast cancer to evaluate associations between 27 circulating cytokines, measured using Luminex XMap technology, and breast cancer phenotypes [ER^? vs. ER⁺; triple negative breast cancer (TNBC) vs. luminal A (LumA)]. Ratios of Th1 to Th2 cytokines were also evaluated. Levels of interleukin (IL)-5, a Th-2 cytokine, were higher in ER^? than in ER⁺ tumors. The highest tertile of IL-5 was more strongly associated with ER^? (OR = 2.33, 95 % CI 1.40–3.90) and TNBCs (OR = 2.78, 95 % CI 1.53–5.06) compared to ER⁺ and LumA cancers, respectively, particularly among premenopausal women (OR = 4.17, 95 % CI 1.86–9.34, ER^? vs. ER⁺; OR = 5.60, 95 % CI 2.09–15.01, TNBC vs. LumA). Elevated Th1 cytokines were also detected in women with ER^? and TNBCs, with women in the highest tertile of interferon α2 (OR = 2.39, 95 % CI 1.31–4.35) or tumor necrosis factor-α (OR = 2.27, 95 % CI 1.21–4.26) being twice as likely to have TNBC versus LumA cancer. When cytokine ratios were examined, women with the highest ratios of Th1 cytokines to IL-5 levels were least likely to have ER^? or TNBCs compared to ER⁺ or LumA cancers, respectively. The strongest associations were in premenopausal women, who were up to 80 % less likely to have TNBC than LumA cancers (IL-12p40/IL-5, OR = 0.19, 95 % CI 0.07–0.56). These findings indicate that immune function is associated with ER^? and TNBC and may be most relevant among younger women, who are likely to be diagnosed with these aggressive phenotypes.     

Legume intake and the risk of cancer: a multisite case–control study in Uruguay

Background

Previous studies have suggested that a high intake of legumes may decrease the risk of stomach and prostate cancer and some other cancers. However, the evidence is still limited. To further explore the association between legume intake and cancer risk we conducted a case–control study of 11 cancer sites in Uruguay between 1996 and 2004, including 3,539 cancer cases and 2,032 hospital controls.

Results

The highest versus the lowest tertile of legume intake was associated with a significant decrease in the risk of cancers of the oral cavity and pharynx (OR = 0.48, 95% CI: 0.34–0.68), esophagus (OR = 0.54, 95% CI: 0.38–0.77), larynx (OR = 0.55, 95% CI: 0.40–0.77), upper aerodigestive tract (OR = 0.50, 95% CI: 0.40–0.63), stomach (OR = 0.69, 95% CI: 0.49–0.97), colorectum (OR = 0.43, 95% CI: 0.32–0.59), kidney (OR = 0.41, 95% CI: 0.24–0.71), and all sites combined (OR = 0.68, 95% CI: 0.59–0.78). No significant association was observed between legume intake and cancers of the lung (OR = 1.03, 95% CI: 0.83–1.27), breast (OR = 0.89, 95% CI: 0.65–1.20), prostate (OR = 0.87, 95% CI: 0.64–1.18) or bladder (OR = 0.82, 95% CI: 0.57–1.17). Similar results were found for both beans and lentils.

Conclusion

Higher intake of legumes was associated with a decreased risk of several cancers including those of the upper aerodigestive tract, stomach, colorectum, and kidney, but not lung, breast, prostate or bladder. Further investigations of these associations in prospective cohort studies are warranted.     

Do reproductive and hormonal risk factors for breast cancer associate with attendance at mammography screening?

Purpose

To determine whether reproductive and hormonal risk factors for breast cancer associate with mammography attendance.

Methods

We linked data from the Malmö Diet and Cancer Study to the Malmö mammography register (Sweden, 1992–2009). We analyzed 11,409 women (age 44–72) who were free of breast cancer at study entry and a total of 69,746 screening invitations. Generalized Estimating Equations were used to account for repeated measures within subjects. Models were adjusted for age and other sociodemographic factors.

Results

In this study cohort, mammography screening attendance ranged from 87.6 to 94.5 % between calendar years, with an average attendance of 92 %. Higher attendance was found among women who had given birth to fewer than three children (ORs ranging between 1.15 and 1.37) and had used oral contraceptives (OC) within the last decade (OR = 1.22, 95 % CI 1.07–1.38) and for a longer period (OR = 1.13, 95 % CI 1.01–1.27). A lower odds of attendance was found among post-menopausal women (OR = 0.86, 95 % CI 0.77–0.96). Age <13 at menarche, age ≥30 at first childbirth, age ≥55 at menopause, age <20 at first OC use, nulliparity, breastfeeding, and hormone replacement therapy were not associated with mammography attendance.

Conclusion

Reproductive and hormonal risk factors for breast cancer have little effect on mammography screening attendance. This may indicate a potential for under-screening of some women at higher risk.     

Racial disparities in red meat and poultry intake and breast cancer risk

Purpose

Research on the role of red meat and poultry consumption in breast carcinogenesis is inconclusive, but the evidence in African-American (AA) women is lacking. The association between consuming meat and breast cancer risk was examined in the Women’s Circle of Health Study involving 803 AA cases, 889 AA controls, 755 Caucasian cases, and 701 Caucasian controls.

Methods

Dietary information was collected using a Food Frequency Questionnaire. Odds ratios (OR) and 95 % confidence intervals (CI) were obtained from logistic regression models adjusting for potential covariates.

Results

Comparing the fourth versus the first quartiles, among Caucasian women, processed meat (OR = 1.48; 95 % CI 1.07–2.04), unprocessed red meat (OR = 1.40; 95 % CI 1.01–1.94), and poultry intakes (OR = 1.42; 95 % CI 1.01–1.99) increased breast cancer risk. Risk associated with poultry intake was more dominant in premenopausal women (OR = 2.33; 95 % CI 1.44–3.77) and for women with ER? tumors (OR = 2.55; 95 % CI 1.29–5.03) in the Caucasian group. Associations in AA women were mostly null except for a significant increased risk trend with processed meat consumption for ER+ tumors (OR = 1.36; 95 % CI 0.94–1.97, p trend = 0.04).

Conclusions

Overall, associations between breast cancer risk and consumption of red meat and poultry were of different magnitude in AA and Caucasian women, with further differences noted by menopausal and hormone receptor status in Caucasian women. This is the first study to examine racial differences in meat and breast cancer risk and represents some of the first evidence in AA women.     

BRCA1 and BRCA2 families and the risk of skin cancer

BRCA1 and BRCA2 mutation carriers have elevated risks of breast and ovarian cancers. The risks for cancers at other sites remain unclear. Melanoma has been associated with BRCA2 mutations in some studies, however, few surveys have included non-melanoma skin cancer. We followed 2729 women with a BRCA1 or BRCA2 mutation for an average of 5.0 years. These women were asked to report new cases of cancer diagnosed in themselves or in their family. The risks of skin cancer were compared for probands with BRCA1 and BRCA2 mutations. Of 1779 women with a BRCA1 mutation, 29 developed skin cancer in the follow-up period (1.6%). Of the 950 women with a BRCA2 mutation, 28 developed skin cancer (3.0%) (OR = 1.83 for BRCA2 versus BRCA1; 95% CI 1.08–3.10; P = 0.02). The odds ratio for basal cell carcinoma was higher (OR = 3.8; 95% CI 1.5–9.4; P = 0.002). BRCA2 mutation carriers are at increased risk for skin cancer, compared with BRCA1 carriers, in particular for basal cell carcinoma.     

Adequacy of risk-reducing gynaecologic surgery in BRCA1 or BRCA2 mutation carriers and other women at high risk of pelvic serous cancer

The aim of this study was to describe the type of risk-reducing gynaecologic surgery (RRGS) and the extent of pathological evaluation being undertaken for Australasian women at high familial risk of pelvic serous cancer. Surgical and pathology reports were reviewed for women with BRCA1/BRCA2 mutations, or a family history of breast and ovarian cancer, who underwent RRGS between 1998 and 2008. “Adequate” surgery was defined as complete removal of all ovarian and extra-uterine fallopian tube tissue. “Adequate” pathology was defined as paraffin embedding of all removed ovarian and tubal tissue. Predictors of adequacy were assessed using logistic regression. There were 201 women, including 173 mutation carriers, who underwent RRGS. Of these, 91% had adequate surgery and 23% had adequate pathology. Independent predictors of adequate surgery were surgeon type (OR = 20; 95% CI 2–167; P = 0.005 for gynaecologic oncologists versus general gynaecologists), more recent surgery (OR = 1.33/year; 95% CI 1.07–1.67; P = 0.012) and younger patient age (OR = 0.93/year of age; 95% CI 0.87–0.99; P = 0.028). Independent predictors of adequate pathology were more recent surgery (OR = 1.26/year; 95% CI 1.06–1.49; P = 0.008) and surgeon type (OR = 3.1; 95% CI 1.4–6.7; P = 0.004 for gynaecologic oncologists versus general gynaecologists). Four serous ovarian cancers and one endometrioid endometrial cancer were detected during surgery or pathological examination. In conclusion Australasian women attending a specialist gynaecologic oncologist for RRGS are most likely to have adequate surgery and pathological examination. Additional education of clinicians and consumers is needed to ensure optimal surgery and pathology in these women.     

A case–control study of lifetime occupational sitting and likelihood of breast cancer

Purpose

Sedentary behavior may be a unique risk factor for some cancers, including breast cancer. The objective of this study was to determine the association between lifetime occupational sitting and likelihood of breast cancer.

Methods

A case–control study of 2,452 women was conducted in Alberta, Canada, between 1995 and 1997. A comprehensive measure of lifetime physical activity assessed frequency and duration of sedentary jobs. Logistic regression estimated the odds of being diagnosed with breast cancer across quartiles of lifetime occupational sitting, by menopausal status and family history of breast cancer, and within body mass index categories and physical activity quartiles.

Results

There was no association between occupational sitting and breast cancer among pre-menopausal women and women with a family history of breast cancer. Unexpectedly, higher amounts of occupational sitting were associated with lower odds of breast cancer in post-menopausal women (top versus bottom categories of occupational sitting OR = 0.71, 95 % CI 0.52, 0.97), women without a family history of breast cancer (OR = 0.77, 95 % CI 0.60, 1.00), and women in the third highest quartile of total lifetime physical activity (OR = 0.57, 95 % CI 0.33, 0.97).

Conclusion

Occupational sitting levels were lower than would be expected in a contemporary study. Exposures may have been insufficient to make a determinable contribution to breast cancer risk.     

Social networks, social support mechanisms, and quality of life after breast cancer diagnosis

We examined mechanisms through which social relationships influence quality of life (QOL) in breast cancer survivors. This study included 3,139 women from the Pathways Study who were diagnosed with breast cancer from 2006 to 2011 and provided data on social networks (the presence of a spouse or intimate partner, religious/social ties, volunteering, and numbers of close friends and relatives), social support (tangible support, emotional/informational support, affection, positive social interaction), and QOL, measured by the FACT-B, approximately 2 months post diagnosis. We used logistic models to evaluate associations between social network size, social support, and lower versus higher than median QOL scores. We further stratified by stage at diagnosis and treatment. In multivariate-adjusted analyses, women who were characterized as socially isolated had significantly lower FACT-B (OR = 2.18, 95 % CI: 1.72–2.77), physical well-being (WB) (OR = 1.61, 95 % CI: 1.27–2.03), functional WB (OR = 2.08, 95 % CI: 1.65–2.63), social WB (OR = 3.46, 95 % CI: 2.73–4.39), and emotional WB (OR = 1.67, 95 % CI: 1.33–2.11) scores and higher breast cancer symptoms (OR = 1.48, 95 % CI: 1.18–1.87) compared with socially integrated women. Each social network member independently predicted higher QOL. Simultaneous adjustment for social networks and social support partially attenuated associations between social networks and QOL. The strongest mediator and type of social support that was most predictive of QOL outcomes was “positive social interaction.” However, each type of support was important depending on outcome, stage, and treatment status. Larger social networks and greater social support were related to higher QOL after a diagnosis of breast cancer. Effective social support interventions need to evolve beyond social-emotional interventions and need to account for disease severity and treatment status.     

Three novel functional polymorphisms in the promoter of FGFR2 gene and breast cancer risk: a HuGE review and meta-analysis

Published data on the association between three novel functional polymorphisms (rs11200014, rs2981579, and rs2981578) in the promoter of FGFR2 gene and breast cancer risk are inconclusive. The aim of this human genome epidemiology review and meta-analysis was to derive a more precise estimation of the relationship. A literature search of Pubmed, Embase, Web of science, and CBM databases from inception through July 2012 was conducted. Seventeen studies were included with a total of 21,742 breast cancer cases and 31,125 healthy controls. Crude odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the strength of association in allele model, dominant model, recessive model, homozygous model, and heterozygous model. When all the eligible studies were pooled into the meta-analysis, remarkable associations between the rs11200014 (A>G) polymorphism and breast cancer risk were detected in Caucasians (G vs. A: OR = 1.28, 95 % CI: 1.21–1.35; GG/AG vs. AA: OR = 1.32, 95 % CI: 1.18–1.48), but not in Asians and Africans. In addition, there were statistically significant associations between the rs2981579 (G>A) polymorphism and increased risk of breast cancer risk in all ethnicities (A vs. G: OR = 1.20, 95 % CI: 1.11–1.29; AA/GA vs. GG: OR = 1.32, 95 % CI: 1.18–1.48; AA vs. GG: OR = 1.67, 95 % CI: 1.55–1.81), including Caucasians, Asians, and Africans. However, the TT genotype of rs2981578 (C>T) polymorphism might decrease breast cancer risk (TT vs. CC/CT: OR = 0.55, 95 % CI: 0.38–0.79; TT vs. CC: OR = 0.51, 95 % CI: 0.35–0.76; TT vs. CT: OR = 0.58, 95 % CI: 0.40–0.85), especially among Asians. Results from the current meta-analysis indicates that three novel functional polymorphisms (rs11200014, rs2981579, and rs2981578) in the promoter of FGFR2 gene are associated with breast cancer susceptibility and might be a potential biomarkers for breast cancer risk.     

Adolescent physical activity and inactivity: a prospective study of risk of benign breast disease in young women

In previous investigations of adolescent activity recalled in adulthood, modest reductions in risk of benign breast disease (BBD) and premenopausal breast cancer were seen with moderate-strenuous activity during high school. We therefore investigated physical activity, walking, and recreational inactivity (watching TV-videos, playing computer-videogames) reported by adolescent girls in relation to their subsequent risk for BBD as young women. The Growing Up Today Study includes 9,039 females, 9–15 years at study initiation (1996), who completed questionnaires annually through 2001, then in 2003, 2005, 2007, 2010 and 2013. Annual surveys (1996–2001) obtained data on physical and sedentary activities during the past year. Beginning in 2005, women (≥18 years) reported whether they had ever been diagnosed with BBD confirmed by breast biopsy (n = 133 cases, to 11/01/2013). Logistic regression (adjusted for baseline adiposity and age; additional factors in multivariable-adjusted models) estimated associations between adolescent activities (moderate-vigorous, walking, METS, inactivity) and biopsy-confirmed BBD in young women. Girls who walked the most had significantly lower risk of BBD (multivariable-adjusted OR = 0.61, ≥30 vs ≤15 min/day; p = .049). We observed no evidence that inactivity (≥3 vs <2 h/day OR = 1.02, p = .92) or METS (top vs bottom tertile OR = 1.19, p = .42) were associated with BBD. Accounting for factors including family history, childhood adiposity, and other activities and inactivities, adolescent girls who walked the most were at lower risk for BBD. We found no evidence that high moderate-vigorous activity might reduce risk, nor did we observe any association with inactivity. Continued follow-up will re-evaluate these findings as more BBD cases, and ultimately breast cancer, are diagnosed.     

Survival of patients with BRCA1-associated breast cancer diagnosed in an MRI-based surveillance program

We report the 5- and 10-year survival rate of women diagnosed with breast cancer in the context of an annual MRI-based surveillance program. In 2001, as part of a national initiative, women in Norway with a BRCA1 mutation were offered annual screening with breast MRI in addition to mammography. 802 women with a BRCA1 mutation were screened one or more times and followed for a mean of 4.2 years. As of December 2011, 68 of 802 women in the screening program were diagnosed with DCIS or invasive breast cancer (8.5 %), including eight prevalent, 50 incident screen-detected and eight interval cancers. Two latent cancers were detected at prophylactic mastectomy. Sixty-three of the cancers were invasive and five were in situ. The mean tumour size was 1.4 cm (range 0.2–4.5 cm), and 85 % of the patients were node-negative. Ten of the 68 patients died of cancer in the follow-up period. The 5-year breast cancer-specific survival for women with cancer was 75 % (95 % CI 56–86 %) and the 10-year survival was 69 % (95 % CI: 48–83 %). The 5-year survival for women with Stage 1 breast cancer was 82 % compared to 98 % in the population. The 5- and 10-year survival of women with a BRCA1-associated breast cancer detected in a national MRI-based screening program in BRCA1 mutation carriers Norway was less than anticipated. The benefit of annual MRI surveillance on reducing breast cancer mortality in BRCA1 mutation carriers remains to be proven.     

Mammographic screening detects low-risk tumor biology breast cancers

Overdiagnosis of breast cancer, i.e. the detection of slow-growing tumors that would never have caused symptoms or death, became more prevalent with the implementation of population-based screening. Only rough estimates have been made of the proportion of patients that are overdiagnosed and identification of those patients is difficult. Therefore, the aim of this study is to evaluate whether tumor biology can help identify patients with screen-detected tumors at such a low risk of recurrence that they are likely to be overdiagnosed. Furthermore, we wish to evaluate the impact of the transition from film-screen mammography (FSM) to the more sensitive full-field digital mammography (FFDM) on the biology of the tumors detected by each screening-modality. All Dutch breast cancer patients enrolled in the MINDACT trial (EORTC-10041) accrued 2007–2011, who participated in the national screening program (biennial screening ages 50–75) were included (n = 1,165). We calculated the proportions of high-, low- and among those the ultralow-risk tumors according to the 70-gene signature for patients with screen-detected (n = 775) and interval (n = 390) cancers for FSM and FFDM. Screen-detected cancers had significantly more often a low-risk tumor biology (68 %) of which 54 % even an ultralow-risk compared to interval cancers (53 % low-, of which 45 % ultralow-risk (p = 0.001) with an OR of 2.33 (p < 0.0001; 95 % CI 1.73–3.15). FFDM detected significantly more high-risk tumors (35 %) compared to FSM (27 %) (p = 0.011). Aside from favorable clinico-pathological factors, screen-detected cancers were also more likely to have a biologically low-risk or even ultralow-risk tumor. Especially for patients with screen-detected cancers the use of tools, such as the 70-gene signature, to differentiate breast cancers by risk of recurrence may minimize overtreatment. The recent transition in screening-modalities led to an increase in the detection of biologically high-risk cancers using FFDM.     

Association of the BRCA1 promoter polymorphism rs11655505 with the risk of familial breast and/or ovarian cancer

Germline mutations in the BRCA1 tumor suppressor gene predispose affected individuals to breast cancer; however, incomplete cancer penetrance and the presence of phenocopies in BRCA1 families also indicate genetic and environmental modifiers of breast cancer risk. In this study, we have tested the single nucleotide polymorphism rs1655505 of the BRCA1 promoter, as candidate for the modifier of breast cancer risk. The polymorphic variants were genotyped in BRCA1-negative (729), familial breast and/or ovarian cancer cases (FBOC), including cases with a reported maternal history (154), nonfamilal (sporadic) cases (600), hereditary breast/ovarian cases with BRCA1 mutations (190) and population controls (1,590) from Central Poland. An association with the risk of FBOC was observed for the minor (T) allele and (TT) genotype (T: p = 0.006, OR = 1.40, 95 % CI = 1.10–1.79; TT: p = 0.001, OR = 2.23, 95 % CI = 1.37–3.62) in female cases with a reported maternal history, specifically in women with the onset of disease after 50 years of age (T: p = 0.004, OR = 1.77, 95 % CI = 1.20–2.62; TT: p = 0.001, OR = 3.7, 95 % CI = 1.62–8.46). The presented evidence suggests a need to conduct larger studies on the association between genetic variations at the BRCA1 promoter and the breast cancer risk, according to maternal/paternal lineage.     

Contribution of clinical and socioeconomic factors to differences in breast cancer subtype and mortality between Hispanic and non-Hispanic white women

Purpose

To assess tumor subtype distribution and the relative contribution of clinical and sociodemographic factors on breast cancer survival between Hispanic and non-Hispanic whites (NHWs).

Methods

We analyzed data from the California Cancer Registry, which included 29,626 Hispanic and 99,862 NHW female invasive breast cancer cases diagnosed from 2004 to 2014. Logistic regression was used to assess ethnic differences in tumor subtype, and Cox proportional hazard modeling to assess differences in breast cancer survival.

Results

Hispanics compared to NHWs had higher odds of having triple-negative (OR = 1.29; 95% CI 1.23–1.35) and HER2-overexpressing tumors (OR = 1.19; 95% CI 1.14–1.25 [HR?] and OR = 1.39; 95% CI 1.31–1.48 [HR+]). In adjusted models, Hispanic women had a higher risk of breast cancer mortality than NHW women (mortality rate ratio [MRR] = 1.24; 95% CI 1.19–1.28). Clinical factors accounted for most of the mortality difference (MRR = 1.05; 95% CI 1.01–1.09); however, neighborhood socioeconomic status (SES) and health insurance together accounted for all of the mortality difference (MRR = 1.01; 95% CI 0.97–1.05).

Conclusions

Addressing SES disparities, including increasing access to health care, may be critical to overcoming poorer breast cancer outcomes in Hispanics.

     

Serum insulin-like growth factor (IGF)-1 and IGF binding protein-3 in relation to breast cancer among Hispanic and white, non-Hispanic women in the US Southwest

Insulin-like growth factor 1 (IGF-1) and IGF binding protein 3 (IGFBP-3) have been positively associated with breast cancer, especially among premenopausal women. Hispanic women have lower levels of IGF-1 and IGFBP-3 than non-Hispanic white (NHW) women, although no studies have adequately assessed the relationship among IGF-1, IGFBP-3, and breast cancer in Hispanic women. We investigated the association among IGF-1, IGFBP-3, and breast cancer within a subset of participants (n = 184 cases, 522 controls) of a population-based case–control study of women living in the U.S. Southwest. Serum levels of IGF-1 and IGFBP-3 were measured in fasting blood samples, and associations among IGF-1, IGFBP-3, and breast cancer were calculated using logistic regression, adjusting for age, study center, ethnicity, education, recent hormone exposure, body mass index, parity, total energy expenditure, total calories, and cholesterol. Both IGF-1 and IGFBP-3 were statistically significantly associated with breast cancer overall (highest vs. lowest quartile (Q4 vs. Q1) for IGF-1: odds ratio (OR) = 1.92, 95% confidence interval (CI) = 1.07–3.43); for IGFBP-3: OR = 3.04, 95% CI = 1.63–5.67). Positive associations were observed for both premenopausal breast cancer and postmenopausal breast cancer. IGF-1 was associated with breast cancer in NHW women (Q4 vs. Q1: OR = 2.82, 95% CI = 1.36–5.83), but not in Hispanic women (Q4 vs. Q1: OR = 0.81, 95% CI = 0.29–2.27). IGFBP-3 was associated with breast cancer in both ethnic groups (Q4 vs. Q1 for NHW: OR = 3.32, 95% CI = 1.45–7.60; Q4 vs. Q1 for Hispanics: OR = 2.15, 95% CI = 0.76–6.04). In conclusion, the association between IGF-1 and breast cancer differed by ethnicity, while no ethnic differences were observed in IGFBP-3-associated breast cancer.     

Timing of oral contraceptive use and the risk of breast cancer in BRCA1 mutation carriers

It is not clear if early oral contraceptive use increases the risk of breast cancer among young women with a breast cancer susceptibility gene 1 (BRCA1) mutation. Given the benefit of oral contraceptives for the prevention of ovarian cancer, estimating age-specific risk ratios for oral contraceptive use and breast cancer is important. We conducted a case–control study of 2,492 matched pairs of women with a deleterious BRCA1 mutation. Breast cancer cases and unaffected controls were matched on year of birth and country of residence. Detailed information about oral contraceptive use was collected from a routinely administered questionnaire. Conditional logistic regression was used to estimate the odds ratios (OR) and 95 % confidence intervals (CI) for the association between oral contraceptive and breast cancer, by age at first use and by age at diagnosis. Among BRCA1 mutation carriers, oral contraceptive use was significantly associated with an increased risk of breast cancer for women who started the pill prior to age 20 (OR 1.45; 95 % CI 1.20–1.75; P = 0.0001) and possibly between ages 20 and 25 as well (OR 1.19; 95 % CI 0.99–1.42; P = 0.06). The effect was limited to breast cancers diagnosed before age 40 (OR 1.40; 95 % CI 1.14–1.70; P = 0.001); the risk of early-onset breast cancer increased by 11 % with each additional year of pill use when initiated prior to age 20 (OR 1.11; 95 % CI 1.03–1.20; P = 0.008). There was no observed increase for women diagnosed at or after the age of 40 (OR 0.97; 95 % CI 0.79–1.20; P = 0.81). Oral contraceptive use before age 25 increases the risk of early-onset breast cancer among women with a BRCA1 mutation and the risk increases with duration of use. Caution should be taken when advising women with a BRCA1 mutation to take an oral contraceptive prior to age 25.     

Total energy intake and breast cancer risk in sisters: the Breast Cancer Family Registry

Energy restriction inhibits mammary tumor development in animal models. Epidemiologic studies in humans generally do not support an association between dietary energy intake and breast cancer risk, although some studies suggest a more complex interplay between measures of energy intake, physical activity, and body size. We examined the association between total energy intake jointly with physical activity and body mass index (BMI) and the risk of breast cancer among 1,775 women diagnosed with breast cancer between 1995 and 2006 and 2,529 of their unaffected sisters, enrolled in the Breast Cancer Family Registry. We collected dietary data using the Hawaii–Los Angeles Multiethnic Cohort food frequency questionnaire. Using conditional logistic regression to estimate the odds ratios (OR) and 95 % confidence intervals (CI) associated with total energy intake, we observed an overall 60–70 % increased risk of breast cancer among women in the highest quartile of total energy intake compared to those in the lowest quartile (Q4 vs. Q1: OR = 1.6, 95 % CI: 1.3–2.0; P _trend < 0.0001); these associations were limited to pre-menopausal women or women with hormone receptor-positive cancers. Although the associations were slightly stronger among women with a higher BMI or lower level of average lifetime physical activity, we observed a positive association between total energy intake and breast cancer risk across different strata of physical activity and BMI. Our results suggest that within sisters, high energy intake may increase the risk of breast cancer independent of physical activity and body size. If replicated in prospective studies, then these findings suggest that reductions in total energy intake may help in modifying breast cancer risk.