A Congener-specific and Mixture Analysis of Plasma Polychlorinated Biphenyl Levels and Incident Breast Cancer.

Background: Polychlorinated biphenyls (PCBs), a diverse class of chemicals, are hypothesized mammary carcinogens. We examined plasma levels of 17 PCBs as individual congeners and as a mixture in association with breast cancer using a novel approach based on quantile g-computation.

Methods: This study included 845 White and 562 Black women who participated in the population-based, case-control Carolina Breast Cancer Study Phase I.

Plasma levels of polychlorinated biphenyls (PCBs) and breast cancer mortality: The Carolina Breast Cancer Study.

Background: It is unknown whether carcinogenic and endocrine disrupting polychlorinated biphenyls (PCBs) influence mortality following breast cancer. We examined plasma levels of 17 PCB congeners in association with mortality among women with breast cancer.

Methods: Participants included 456 white and 292 black women in North Carolina who were diagnosed with primary invasive breast cancer from 1993 to 1996, and who had PCB and lipid measurements from blood samples obtained an average of 4.

Race and delays in breast cancer treatment across the care continuum in the Carolina Breast Cancer Study.

Background: After controlling for baseline disease factors, researchers have found that black women have worse breast cancer survival, and this suggests that treatment differences may contribute to poorer outcomes. Delays in initiating and completing treatment are one proposed mechanism.

Methods: Phase 3 of the Carolina Breast Cancer Study involved a large, population-based cohort of women with incident breast cancer.

Plasma levels of dichlorodiphenyldichloroethene (DDE) and dichlorodiphenyltrichloroethane (DDT) and survival following breast cancer in the Carolina Breast Cancer Study.

Objectives: To examine plasma levels of dichlorodiphenyldichloroethene (DDE) and dichlorodiphenyltrichloroethane (DDT) in association with survival among women with breast cancer who participated in a population-based case-control study.

Methods: Participants included 456 white and 292 black women from the Carolina Breast Cancer Study Phase I who were diagnosed with primary invasive breast cancer from 1993 to 1996, and who had available DDE/DDT and lipid measurements from blood samples obtained on average 4.1 months after diagnosis.

Risk factors for Luminal A ductal carcinoma in situ (DCIS) and invasive breast cancer in the Carolina Breast Cancer Study.

Purpose: Invasive breast cancers are thought to arise from in situ lesions, but some ductal carcinoma in situ (DCIS) are indolent with low likelihood of progressing to invasive carcinoma. Comparison of risk factor associations between DCIS and invasive disease may elucidate which factors influence early versus late stages of carcinogenesis. Therefore, we determined whether there were differences in risk factor profiles for screen-detected DCIS and invasive breast cancer among Luminal A lesions.

Lifestyle Patterns and Survival Following Breast Cancer in the Carolina Breast Cancer Study.

Background: Few studies have examined the impact of lifestyle patterns on survival following breast cancer. We aimed to identify distinct lifestyle patterns based on five behavior/dietary exposures among a population-based sample of women diagnosed with breast cancer and to examine their association with subsequent survival.

Methods: In the Carolina Breast Cancer Study Phases I/II, we interviewed 1,808 women 20-74 years of age following diagnosis of invasive breast cancer.

Endocrine Therapy Nonadherence and Discontinuation in Black and White Women.

Background: Differential use of endocrine therapy (ET) by race may contribute to breast cancer outcome disparities, but racial differences in ET behaviors are poorly understood.

Methods: Women aged 20-74 years with a first primary, stage I-III, hormone receptor-positive (HR+) breast cancer were included. At 2 years postdiagnosis, we assessed nonadherence, defined as not taking ET every day or missing more than two pills in the past 14 days, discontinuation, and a composite measure of underuse, defined as either missing pills or discontinuing completely.

PAM50 and Risk of Recurrence Scores for Interval Breast Cancers.

Breast cancers detected after a negative breast screening examination and prior to the next screening are referred to as interval cancers. These cancers generally have poor clinical characteristics compared with screen-detected cancers, but associations between interval cancer and genomic cancer characteristics are not well understood. Mammographically screened women diagnosed with primary invasive breast cancer from 1993 to 2013 ( = 370) were identified by linking the Carolina Breast Cancer Study and the Carolina Mammography Registry.

Reproductive risk factor associations with lobular and ductal carcinoma in the Carolina Breast Cancer Study.

Background: Invasive lobular breast tumors display unique reproductive risk factor profiles. Lobular tumors are predominantly Luminal A subtype, and it is unclear whether reported risk factor associations are independent of molecular subtype.

Methods: Polytomous logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for the associations between risk factors and histologic subtype [ductal (n = 2,856), lobular (n = 326), and mixed ductal-lobular (n = 473)] in the Carolina Breast Cancer Study (1993-2013).

Racial Differences in PAM50 Subtypes in the Carolina Breast Cancer Study.

Background: African American breast cancer patients have lower frequency of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 (HER2)-negative disease and higher subtype-specific mortality. Racial differences in molecular subtype within clinically defined subgroups are not well understood.

Methods: Using data and biospecimens from the population-based Carolina Breast Cancer Study (CBCS) Phase 3 (2008-2013), we classified 980 invasive breast cancers using RNA expression-based PAM50 subtype and recurrence (ROR) score that reflects proliferation and tumor size.

Active smoking and survival following breast cancer among African American and non-African American women in the Carolina Breast Cancer Study.

Purpose: To examine racial differences in smoking rates at the time of breast cancer diagnosis and subsequent survival among African American and non-African American women in the Carolina Breast Cancer Study (Phases I/II), a large population-based North Carolina study.

Methods: We interviewed 788 African American and 1,020 Caucasian/non-African American women diagnosed with invasive breast cancer from 1993 to 2000, to assess smoking history. After a median follow-up of 13.

Race, Menopausal Hormone Therapy, and Invasive Breast Cancer in the Carolina Breast Cancer Study.

Purpose: The use of combined estrogen-progestin menopausal hormone therapy (MHT) has been shown to increase the risk of breast cancer, however, recent observational studies have suggested that the association between MHT and breast cancer may be modified by race. The objective of this study was to investigate the association between MHT use and incidence of invasive breast cancer in Black and White women aged ≥40 years at diagnosis after accounting for racial differences in patterns of MHT use and formulation.

Methods: Data from the Carolina Breast Cancer Study, a population-based case-control study of Black and White women in North Carolina conducted between 1993 and 2001, was used to analyze 1474 invasive breast cancer cases and 1339 controls using unconditional logistic regression.

Breast tumor DNA methylation patterns associated with smoking in the Carolina Breast Cancer Study.

Purpose: Tobacco smoking is a risk factor in several cancers, yet its roles as a putative etiologic exposure or poor prognostic factor in breast cancer are less clear. Altered DNA methylation contributes to breast cancer development and may provide a mechanistic link between smoking and gene expression changes leading to cancer development or progression.

Methods: Using a cancer-focused array, we examined methylation at 933 CpGs in 517 invasive breast tumors in the Carolina Breast Cancer Study to determine whether methylation patterns differ by exposure to tobacco smoke.

Associations of Premenopausal Hysterectomy and Oophorectomy With Breast Cancer Among Black and White Women: The Carolina Breast Cancer Study, 1993-2001.

Black women experience higher rates of hysterectomy than other women in the United States. Although research indicates that premenopausal hysterectomy with bilateral oophorectomy decreases the risk of breast cancer in black women, it remains unclear how hysterectomy without ovary removal affects risk, whether menopausal hormone therapy use attenuates inverse associations, and whether associations vary by cancer subtype. In the population-based, case-control Carolina Breast Cancer Study of invasive breast cancer in 1,391 black (725 cases, 666 controls) and 1,727 white (939 cases, 788 controls) women in North Carolina (1993-2001), we investigated the associations of premenopausal hysterectomy and oophorectomy with breast cancer risk.

Breast cancer biologic and etiologic heterogeneity by young age and menopausal status in the Carolina Breast Cancer Study: a case-control study.

Background: Young-onset breast cancer (<40 years) is associated with worse prognosis and higher mortality. Breast cancer risk factors may contribute to distinct tumor biology and distinct age at onset, but understanding of these relationships has been hampered by limited representation of young women in epidemiologic studies and may be confounded by menopausal status.

Methods: We examined tumor characteristics and epidemiologic risk factors associated with premenopausal women's and young women's breast cancer in phases I-III of the Carolina Breast Cancer Study (5309 cases, 2022 control subjects).

Active smoking and risk of Luminal and Basal-like breast cancer subtypes in the Carolina Breast Cancer Study.

Purpose: Growing evidence suggests an association between active cigarette smoking and increased breast cancer risk. However, the weak magnitude of association and conflicting results have yielded uncertainty and it is unknown whether associations differ by breast cancer subtype.

Methods: Using population-based case-control data from phases I and II of the Carolina Breast Cancer Study, we examined associations between self-reported measures of smoking and risk of Luminal and Basal-like breast cancers.

Performance of Three-Biomarker Immunohistochemistry for Intrinsic Breast Cancer Subtyping in the AMBER Consortium.

Background: Classification of breast cancer into intrinsic subtypes has clinical and epidemiologic importance. To examine accuracy of IHC-based methods for identifying intrinsic subtypes, a three-biomarker IHC panel was compared with the clinical record and RNA-based intrinsic (PAM50) subtypes.

Methods: Automated scoring of estrogen receptor (ER), progesterone receptor (PR), and HER2 was performed on IHC-stained tissue microarrays comprising 1,920 cases from the African American Breast Cancer Epidemiology and Risk (AMBER) consortium.

Association of Parity and Time since Last Birth with Breast Cancer Prognosis by Intrinsic Subtype.

Background: Parity and time since last birth influence breast cancer risk and vary by intrinsic tumor subtype, but the independent effects of these factors on prognosis have received limited attention.

Methods: Study participants were 1,140 invasive breast cancer patients from phases I and II of the population-based Carolina Breast Cancer Study, with tissue blocks available for subtyping using immunohistochemical markers. Breast cancer risk factors, including pregnancy history, were collected via in-person interviews administered shortly after diagnosis.

Racial variation in breast tumor promoter methylation in the Carolina Breast Cancer Study.

Background: African American (AA) women are diagnosed with more advanced breast cancers and have worse survival than white women, but a comprehensive understanding of the basis for this disparity remains unclear. Analysis of DNA methylation, an epigenetic mechanism that can regulate gene expression, could help to explain racial differences in breast tumor clinical biology and outcomes.

Methods: DNA methylation was evaluated at 1,287 CpGs in the promoters of cancer-related genes in 517 breast tumors of AA (n = 216) or non-AA (n = 301) cases in the Carolina Breast Cancer Study (CBCS).

DNA methylation profiling in the Carolina Breast Cancer Study defines cancer subclasses differing in clinicopathologic characteristics and survival.

Introduction: Breast cancer is a heterogeneous disease, with several intrinsic subtypes differing by hormone receptor (HR) status, molecular profiles, and prognosis. However, the role of DNA methylation in breast cancer development and progression and its relationship with the intrinsic tumor subtypes are not fully understood.

Methods: A microarray targeting promoters of cancer-related genes was used to evaluate DNA methylation at 935 CpG sites in 517 breast tumors from the Carolina Breast Cancer Study, a population-based study of invasive breast cancer.

Body size across the life course and risk of premenopausal and postmenopausal breast cancer in Black women, the Carolina Breast Cancer Study, 1993-2001.

Background: It is believed that greater adiposity is associated with reduced risk of breast cancer in premenopausal but increased risk in postmenopausal women. However, few studies have evaluated these relationships among Black women or examined anthropometric measures other than near-diagnosis body mass index (BMI).

Purpose: This study investigated associations between measures of body size across the life course and breast cancer risk among Black and White women living in the US South.

Racial differences in physical activity among breast cancer survivors: implications for breast cancer care.

Background: Physical activity after breast cancer diagnosis is associated with improved survival. The current study examined levels of and changes in physical activity after breast cancer diagnosis, overall and by race.

Methods: Phase 3 of the Carolina Breast Cancer Study assessed both pre- and postdiagnosis physical activity levels in a cohort of 1735 women aged 20 years to 74 years who were diagnosed with invasive breast cancer between 2008 and 2011 in 44 counties of North Carolina.

Determinants of breast cancer treatment delay differ for African American and White women.

Background: Timeliness of care may contribute to racial disparities in breast cancer mortality. African American women experience greater treatment delay than White women in most, but not all studies. Understanding these disparities is challenging as many studies lack patient-reported data and use administrative data sources that collect limited types of information.

Association of germline microRNA SNPs in pre-miRNA flanking region and breast cancer risk and survival: the Carolina Breast Cancer Study.

Purpose: Common germline variation in the 5' region proximal to precursor (pre-) miRNA gene sequences is evaluated for association with breast cancer risk and survival among African Americans and Caucasians.

Methods: We genotyped nine single nucleotide polymorphisms (SNPs) within six miRNA gene regions previously associated with breast cancer, in 1,972 cases and 1,776 controls. In a race-stratified analysis using unconditional logistic regression, odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated to evaluate SNP association with breast cancer risk.

The case-only independence assumption: associations between genetic polymorphisms and smoking among controls in two population-based studies.

The independence assumption for a case-only analysis of statistical interaction, i. e. that genetic (G) and environmental exposures (E) are not associated in the source population, is often checked in surrogate populations.