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Introduction: We explored characteristics and clinical outcomes of HER2‐negative and HER2‐low metastatic breast cancers using real‐world data. Methods: We queried the National Cancer Database to identify MBC patients that were HER2‐low or HER2‐negative per immunohistochemical staining. A binomial regression analysis identified demographic and clinical correlates of each subtype. A Cox multivariable regression analysis (MVA) and propensity‐match analysis were performed to identify correlates of survival. Results: Excluding missing data, 24,636 MBC patients diagnosed between 2008 and 2015 were identified; 27.9% were HER2‐negative and 72.1% were HER2‐low. There were no relevant demographic differences between the groups. HER2‐low tumors were half as likely to have concomitant hormone receptor‐positive status (p < 0.01). The 3‐year survival rate among hormone receptor‐negative patients was 33.8% for HER2‐low and 32.2% for HER2‐negative (p < 0.05), and 60.9% and 55.6% in HER2‐low and HER2‐negative cases among hormone receptor‐positive patients (p < 0.05), respectively. HER2‐low cases were associated with better survival on MVA (HR =0.95, 95% CI 0.91–0.99) and remained superior with propensity‐matching (HR = 0.92, 95% CI 0.89–0.96). In a subset analysis isolated to hormone receptor‐positive cases, HER2‐low remained correlated with improved survival (HR = 0.93, 95% CI 0.89–0.98) with propensity‐matched MVA. Correlates of worse survival include older age as a continuous variable (HR = 1.02, 95% CI 1.02–1.02) and Black race (HR = 1.26, 95% CI 1.20–1.32) [all p < 0.01]. Conclusions: In the largest such analysis performed to date, our study demonstrates a small but statistically significant association with improved survival for HER2‐low tumors compared to HER2‐negative tumors in MBC. [ABSTRACT FROM AUTHOR]

Per‐ and polyfluoroalkyl substances (PFAS) are highly persistent endocrine‐disrupting chemicals that may contribute to breast cancer development; however, epidemiologic evidence is limited. We investigated associations between prediagnostic serum levels of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) and postmenopausal breast cancer risk, overall and by hormone receptor status, in a nested case‐control study of 621 cases and 621 matched controls in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. PFOS and PFOA levels were determined based on serum metabolomic profiling performed using ultraperformance liquid chromatography‐tandem mass spectrometry. We used multivariable conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between each PFAS and breast cancer risk, overall, by estrogen receptor (ER) or progesterone receptor (PR) status, and by joint ER/PR status. We found little evidence of association between PFOS or PFOA and breast cancer risk overall. However, in subtype‐specific analyses, we observed statistically significant increased risks of ER+, PR+, and ER+/PR+ tumors for the third vs lowest quartile of serum PFOS (ORs [95% CIs] = 1.59 [1.01‐2.50], 2.34 [1.29‐4.23], and 2.19 [1.21‐3.98], respectively) and elevated but nonstatistically significant ORs for the fourth quartile. Conversely, for PFOA, modest positive associations with ER−, PR−, ER+/PR−, and ER−/PR− tumors were generally seen in the upper quartiles. Our findings contribute evidence supporting positive associations between serum PFOS and hormone receptor‐positive tumors, and possibly between PFOA and receptor‐negative tumors. Future prospective studies incorporating tumor hormone receptor status are needed to better understand the role of PFAS in breast cancer etiology. [ABSTRACT FROM AUTHOR]

Exposure to bisphenol A (BPA), triclosan and parabens is widespread but their impact on breast cancer risk remains unclear. This nested case‐control study investigated endocrine‐disrupting chemicals (EDCs) and breast cancer risk within the Multiethnic Cohort (MEC). We measured prediagnostic urinary BPA, triclosan and parabens in 1032 postmenopausal women with breast cancer (48 African American, 77 Latino, 155 Native Hawaiian, 478 Japanese American and 274 White) and 1030 individually matched controls, using a sensitive and validated liquid chromatography mass spectrometry assay. Conditional logistic regression was used to examine risk with these EDCs with adjustment for creatinine and potential confounders. In all women, breast cancer risk was not associated with BPA (Ptrend = 0.53) and was inversely associated with triclosan (ORT3 vs T1 = 0.83, 95% CI: 0.66‐1.04, Ptrend = 0.045) and total parabens (ORT3 vs T1 = 0.77, 95% CI: 0.62‐0.97, Ptrend = 0.03). While risk of hormone receptor positive (HR+) cancer was 20% to 23% lower among women in the upper two tertiles of paraben exposure (Ptrend = 0.02), risk of HR negative (HR−) was reduced 27% but only among those in the upper tertile of exposure. Although risk associations did not differ significantly by ethnicity or by body mass index (BMI), the inverse association with triclosan was observed mainly among overweight/obese women (ORT3 vs T1 = 0.76, 95% CI: 0.56‐1.02, Ptrend = 0.02). In summary, breast cancer risk in a multiethnic population was unrelated to BPA and was weakly inversely associated with triclosan and paraben exposures. Studies with multiple urine samples collected before breast cancer diagnosis are needed to further investigate these EDCs and breast cancer risk. [ABSTRACT FROM AUTHOR]

Background: This study was aimed at examining the risks of subsequent primary cancers (SPCs) among breast cancer survivors by hormone receptor (HR) status and age at diagnosis. Methods: Data from 12 Surveillance, Epidemiology, and End Results registries were used to identify 431,222 breast cancer survivors (at least 1 year) diagnosed between the ages of 20 and 84 years from 1992 to 2015. Risks of SPCs were measured as the standardized incidence ratio (SIR) and the excess absolute risk (EAR) per 10,000 person‐years. Poisson regression was used to test the difference in SIRs by HR status. Results: In comparison with the general population, the risk of new cancer diagnoses among survivors was 20% higher for those with HR‐positive cancers (SIR, 1.20; 95% confidence interval [CI], 1.19‐1.21; EAR, 23.3/10,000 person‐years) and 44% higher for those with HR‐negative cancers (SIR, 1.44; 95% CI, 1.41‐1.47; EAR, 45.2/10,000 person‐years), with the risk difference between HR statuses statistically significant. The higher risk after HR‐negative cancer was driven by acute nonlymphocytic leukemia and breast, ovarian, peritoneal, and lung cancers. By age at diagnosis, the total EAR per 10,000 person‐years ranged from 15.8 (95% CI, 14.1‐17.5; SIR, 1.11) among late‐onset (age, 50‐84 years) HR‐positive survivors to 69.4 (95% CI, 65.1‐73.7; SIR, 2.24) among early‐onset (age, 20‐49 years) HR‐negative survivors, with subsequent breast cancer representing 73% to 80% of the total EAR. After breast cancer, the greatest EARs were for ovarian cancer among early‐onset HR‐negative survivors, lung cancer among early‐ and late‐onset HR‐negative survivors, and uterine corpus cancer among late‐onset HR‐positive survivors. Conclusions: Risks of SPCs after breast cancer differ substantially by subtype and age. This suggests that more targeted approaches for cancer prevention and early‐detection strategies are needed in survivorship care planning. The overall risk of subsequent primary cancers among breast cancer survivors versus the cancer risk in the general population is higher among both hormone receptor (HR)–positive and HR‐negative cancer survivors, although the risk is considerably greater among HR‐negative cancer survivors; this is driven by higher risks for acute nonlymphocytic leukemia and breast, ovarian, peritoneal, and lung cancers. With respect to the age at diagnosis of first breast cancer, the largest excess risk of subsequent primary cancers in both absolute and relative terms occurs among survivors of early‐onset (age, 20‐49 years) HR‐negative breast cancer despite lower cancer incidence rates among younger survivors. [ABSTRACT FROM AUTHOR]

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− (ORQ5 vs. Q1 = 0.63; 95% CI: 0.41–0.95, ptrend = 0.043) and for ER−/PR− breast tumors (ORQ4 vs. Q1 = 0.62; 95% CI: 0.40–0.95, ORQ5 vs. Q1 = 0.68; 95% CI: 0.42–1.07, ptrend = 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. What's new? Cadmium is a common environmental contaminant that exerts estrogen‐like activity in human cells. While this activity suggests that cadmium might influence breast cancer risk, the relationship between cadmium exposure and breast cancer remains unclear. In this study, the authors employed a Geographic Information System (GIS)‐based metric to assess atmospheric cadmium exposure in women in France. No significant association was found between airborne cadmium and overall breast cancer risk. Risk varied, however, according to menopausal status and tumor hormone receptor status. Significant inverse associations were indicated for estrogen receptor‐negative breast cancers. Additional research is needed to assess cadmium exposure‐associated cancer risks. [ABSTRACT FROM AUTHOR]

Epidemiological studies have reported inconsistent findings for the association between B vitamins and breast cancer (BC) risk. We investigated the relationship between biomarkers of folate and vitamin B12 and the risk of BC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Plasma concentrations of folate and vitamin B12 were determined in 2,491 BC cases individually matched to 2,521 controls among women who provided baseline blood samples. Multivariable logistic regression models were used to estimate odds ratios by quartiles of either plasma B vitamin. Subgroup analyses by menopausal status, hormone receptor status of breast tumors (estrogen receptor [ER], progesterone receptor [PR] and human epidermal growth factor receptor 2 [HER2]), alcohol intake and MTHFR polymorphisms (677C > T and 1298A > C) were also performed. Plasma levels of folate and vitamin B12 were not significantly associated with the overall risk of BC or by hormone receptor status. A marginally positive association was found between vitamin B12 status and BC risk in women consuming above the median level of alcohol (ORQ4-Q1 = 1.26; 95% CI 1.00-1.58; Ptrend = 0.05). Vitamin B12 status was also positively associated with BC risk in women with plasma folate levels below the median value (ORQ4-Q1 = 1.29; 95% CI 1.02-1.62; Ptrend = 0.03). Overall, folate and vitamin B12 status was not clearly associated with BC risk in this prospective cohort study. However, potential interactions between vitamin B12 and alcohol or folate on the risk of BC deserve further investigation. [ABSTRACT FROM AUTHOR]

In this paper, we propose a Bayesian method to address misclassification errors in both independent and dependent variables. Our work is motivated by a study of women who have experienced new breast cancers on two separate occasions. We call both cancers primary, because the second is usually not considered as the result of a metastasis spreading from the first. Hormone receptors (HRs) are important in breast cancer biology, and it is well recognized that the measurement of HR status is subject to errors. This discordance in HR status for two primary breast cancers is of concern and might be an important reason for treatment failure. To sort out the information on true concordance rate from the observed concordance rate, we consider a logistic regression model for the association between the HR status of the two cancers and introduce the misclassification parameters (i.e., sensitivity and specificity) accounting for the misclassification in HR status. The prior distribution for sensitivity and specificity is based on how HR status is actually assessed in laboratory procedures. To account for the nonlinear effect of one error-free covariate, we introduce the B-spline terms in the logistic regression model. Our findings indicate that the true concordance rate of HR status between two primary cancers is greater than the observed value. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

BACKGROUND: The effect of contralateral prophylactic mastectomy (CPM) on the survival of patients with early-stage breast cancer remains controversial. The objective of this study was to evaluate the benefits of CPM using a propensity scoring approach that reduces selection bias from the nonrandom assignment of patients in observational studies. METHODS: A total of 3889 female patients with stage I to III breast cancer were identified who were treated at The University of Texas MD Anderson Cancer Center from 1997 to 2009. We assessed the association between CPM and disease-free (DFS) and overall survival (OS), by using Cox proportional hazards models to estimate hazard ratios (HRs), and by matching patients in the CPM and no-CPM groups using propensity scores (n = 497 pairs). RESULTS: With a median follow-up time of 4.5 years, CPM was associated with improved DFS (HR, 0.75; 95% confidence interval [CI], 0.59-0.97) and OS (HR, 0.74; 95% CI, 0.56-0.99), adjusted for prognostic factors. The improved DFS was seen predominantly among hormone receptor-negative (HR, 0.60; 95% CI, 0.38-0.95) compared with hormone receptor-positive patients (HR, 0.80; 95% CI, 0.58-1.10). For the matched patient cohort, stratified survival analysis also showed an improvement in DFS with CPM (HR, 0.48; 95% CI, 0.22-1.01) in hormone receptor-negative patients that was nearly statistically significant. CONCLUSIONS: CPM was associated with improved DFS for some patients with hormone receptor-negative breast cancer, after reducing selection bias. Identifying subsets of patients most likely to benefit from CPM may have important implications for a more personalized approach to treatment decisions about CPM. Cancer 2012. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

The article provides information on a study which determined the presence of elevated levels of plasma tissue inhibitors of metalloproteinase (TIMP)-1 detected by an enzyme-linked immunoabsorbent assay (ELISA) and explored any clinically relevant associations in patients with metastatic breast cancer. Materials and methods of the study are discussed, which includes information about the patient population, study design, efficacy assessments, plasma preparation and measurement of plasma TIMP-1 levels. Results of the study are presented, as well.

The article discusses a study which aimed to compare the characteristics and outcome of patients with male breast cancer (MBC) and patients with female breast cancer (FBC) who were treated and diagnosed in the Veterans Affairs (VA) medical centers throughout the U.S. Study findings suggest the presence of differences in the biology, pathology, presentation, ethnicity, and survival between patients with MBC and patients with FBC in the VA population.