Alcohol consumption, smoking, and invasive breast cancer risk after ductal carcinoma in situ.

PURPOSE: Alcohol is an established risk factor for invasive breast cancer, and women with a prior ductal carcinoma in situ diagnosis are at higher risk of invasive breast cancer than the general population. However, for women with a prior ductal carcinoma in situ diagnosis, few studies have evaluated the association between alcohol and smoking and risk of subsequent invasive breast cancer. METHODS: Utilizing a population-based case-control design nested among women diagnosed with a ductal carcinoma in situ between 1995 and 2013, we compared 243 cases diagnosed with a subsequent invasive breast cancer and 423 individually matched controls never diagnosed with a subsequent breast cancer. RESULTS: Compared with never to occasional drinkers, drinkers consuming at least 7 alcoholic drinks per week on average at ductal carcinoma in situ diagnosis had a higher risk of invasive breast cancer that was borderline significant (OR 1.79, 95% CI 1.01-3.17, P value = 0.04). Smoking was not significantly associated with risk of developing an invasive breast cancer after adjustment for alcohol consumption. CONCLUSIONS: These findings suggest that consuming at least one alcoholic drink per day on average is positively associated with invasive breast cancer for women with a prior ductal carcinoma in situ diagnosis. If confirmed, modulating alcohol consumption could be one strategy for women with a history of ductal carcinoma in situ to impact their risk of invasive breast cancer.

Antihypertensive medications and risks of recurrence and mortality in luminal, triple-negative, and HER2-overexpressing breast cancer.

PURPOSE: Antihypertensives are commonly prescribed medications and their effect on breast cancer recurrence and mortality is not clear, particularly among specific molecular subtypes of breast cancer: luminal, triple-negative (TN), and HER2-overexpressing (H2E). METHODS: A population-based prospective cohort study of women aged 20-69 diagnosed with a first primary invasive breast cancer between 2004 and 2015 was conducted in the Seattle, Washington and Albuquerque, New Mexico greater metropolitan areas. Multivariable-adjusted Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for risks of breast cancer recurrence, breast cancer-specific mortality, and all-cause mortality associated with hypertension and antihypertensives. RESULTS: In this sample of 2,383 luminal, 1,559 TN, and 615 H2E breast cancer patients, overall median age was 52 (interquartile range, 44-60). Hypertension and current use of antihypertensives were associated with increased risks of all-cause mortality in each subtype. Current use of angiotensin-converting enzyme inhibitors was associated with increased risks of both recurrence and breast cancer-specific mortality among luminal patients (HR: 2.5; 95% CI: 1.5, 4.3 and HR: 1.9; 95% CI: 1.2, 3.0, respectively). Among H2E patients, current use of calcium channel blockers was associated with an increased risk of breast cancer-specific mortality (HR: 1.8; 95% CI: 0.6, 5.4). CONCLUSION: Our findings suggest that some antihypertensive medications may be associated with adverse breast cancer outcomes among women with certain molecular subtypes. Additional studies are needed to confirm these findings.

Reproductive and menopausal factors and risk of second primary breast cancer after in situ breast carcinoma.

PURPOSE: In situ breast cancer patients have a higher risk of developing a second primary breast cancer than women in the general population have of developing breast cancer. We have limited understanding of why some women with a previous in situ breast cancer develop second primary breast cancers while others do not. METHODS: In this population-based nested case-control study, we evaluated the association between reproductive and menopausal factors and risk of developing a second primary breast cancer among women with a previous in situ breast cancer. Using conditional logistic regression, these associations were evaluated in 552 cases and 1032 individually matched controls. RESULTS: Older age at menarche was associated with risk of second primary breast cancer among women with a previous in situ breast cancer (compared to age < 12, age 13: OR 0.60 (0.42, 0.85); age ≥ 14: OR 0.69 (0.47, 1.00); Ptrend = 0.07). Breastfeeding for > 12 months was associated with a decreased risk of developing a second primary breast cancer (OR 0.62 (0.39, 0.98)). No associations were observed for other reproductive or menopausal factors evaluated. CONCLUSIONS: Results from this study suggest that reproductive factors may play a role in development of a second primary breast cancer after diagnosis of in situ breast carcinoma.

Alcohol, smoking, and risk of Her2-overexpressing and triple-negative breast cancer relative to estrogen receptor-positive breast cancer.

Epidemiological evidence is limited on how alcohol consumption and smoking are associated with risk of different subtypes of breast cancer, such as triple-negative (TN) and human epidermal growth factor receptor 2-overexpressing (H2E) breast cancers, which may have different etiologies from more common luminal (estrogen receptor [ER+]) breast cancers. In this population-based case-case study, we evaluated the association between alcohol, smoking, and risk of H2E and TN breast cancer, compared with ER+ breast cancers, among women aged 20-69 years. Using polytomous regression, associations between alcohol consumption, smoking, and breast cancer risk were evaluated in 909 ER+, 1,290 TN, and 489 H2E breast cancer patients, with ER+ breast cancer patients as the reference group. Current alcohol consumption at diagnosis was associated with a lower risk of H2E breast cancer (odds ratio = 0.74, 95% confidence interval: 0.58-0.92) relative to ER+ cancers. No difference in association was observed by menopausal status. No association between alcohol consumption and TN breast cancer relative to ER+ breast cancer was observed. Women who smoked did not have an altered risk of TN or H2E breast cancer, relative to ER+ cancer. Our results suggest that alcohol is associated with lower risk of H2E breast cancer relative to ER+ breast cancer. This study adds to the body of epidemiologic evidence that breast cancer etiology differs by breast cancer subtype.

Body mass index and risk of luminal, HER2-overexpressing, and triple negative breast cancer.

Triple negative (TN, tumors that do not express estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2 (HER2)) and HER2-overexpressing (H2E, ER-/HER2+) tumors are two particularly aggressive subtypes of breast cancer. There is a lack of knowledge regarding the etiologies of these cancers and in particular how anthropometric factors are related to risk. We conducted a population-based case-case study consisting of 2659 women aged 20-69 years diagnosed with invasive breast cancer from 2004 to 2012. Four case groups defined based on joint ER/PR/HER2 status were included: TN, H2E, luminal A (ER+/HER2-), and luminal B (ER+/HER2+). Polytomous logistic regression was used to estimate odds ratios (ORs) and associated 95 % confidence intervals (CIs) where luminal A patients served as the reference group. Obese premenopausal women [body mass index (BMI) ≥30 kg/m(2)] had an 82 % (95 % CI 1.32-2.51) increased risk of TN breast cancer compared to women whose BMI <25 kg/m(2), and those in the highest weight quartile (quartiles were categorized based on the distribution among luminal A patients) had a 79 % (95 % CI 1.23-2.64) increased risk of TN disease compared to those in the lowest quartile. Among postmenopausal women obesity was associated with reduced risks of both TN (OR = 0.74, 95 % CI 0.54-1.00) and H2E (OR = 0.47, 95 % CI 0.32-0.69) cancers. Our results suggest obesity has divergent impacts on risk of aggressive subtypes of breast cancer in premenopausal versus postmenopausal women, which may contribute to the higher incidence rates of TN cancers observed among younger African American and Hispanic women.

Active smoking and the risk of estrogen receptor-positive and triple-negative breast cancer among women ages 20 to 44 years.

BACKGROUND: Evidence regarding the correlation between smoking and breast cancer among young women is mixed, and previous studies have not assessed whether smoking is associated differentially with risks of the major breast cancer subtypes. METHODS: This was a population-based, case-control study of 778 women with estrogen receptor (ER)-positive breast cancers and 182 women with ER-negative, progesterone receptor-negative, and human epidermal growth factor receptor 2-negative (triple-negative [TN]), invasive breast cancers ages 20 to 44 years who were diagnosed from 2004 to 2010 in the Seattle-Puget Sound metropolitan area. A control group of 938 cancer-free women also was included. Associations between various aspects of smoking history and the risks of ER-positive and TN breast cancer were assessed using polytomous logistic regression. RESULTS: Ever-smokers had a 1.3-fold increased risk (95% confidence interval [CI], 1.1-fold to 1.7-fold increased risk) of breast cancer overall; and, when stratified by cancer subtype, they had a 1.4-fold increased risk (95% CI, 1.1-fold to 1.8-fold increased risk) of ER-positive breast cancer, but there was no elevation in their risk of TN disease (odds ratio, 1.1; 95% CI, 0.7-1.6). Current/recent smokers with a ≥10 pack-year history of smoking had a 1.6-fold increased risk (95% CI, 1.1-fold to 2.4-fold increased risk) of ER-positive breast cancer but had no increase in their risk of TN breast cancer (odds ratio, 1.0; 95% CI, 0.5-1.9). CONCLUSIONS: The current results suggested that young women who are current/recent smokers with high pack-year histories may have an increased risk of ER-positive breast cancer but not TN breast cancer. Although this association was modest, the findings suggest that an increased risk of ER-positive breast cancer may be another health risk incurred by young women who smoke.

Height, body mass index (BMI), BMI change, and the risk of estrogen receptor-positive, HER2-positive, and triple-negative breast cancer among women ages 20 to 44 years.

BACKGROUND: The evidence regarding correlations between various anthropometric characteristics and breast cancer risk among young women is mixed, and few studies have assessed these associations by subtype. METHODS: This was a population-based, case-control study of 779 women with estrogen receptor (ER)-positive breast cancer; 182 women with ER-negative/human epidermal growth factor-2 (HER2)-negative/progesterone receptor-negative (triple-negative [TN]) breast cancer; and 60 women with ER-negative/HER2-overexpressing, invasive breast cancer ages 20 to 44 years who were diagnosed from 2004 to 2010 in the Seattle-Puget Sound metropolitan area; as well as 939 cancer-free controls. Associations between height and body mass index (BMI) at different time points in relation to breast cancer risk were assessed using polytomous logistic regression. RESULTS: Height, BMI at age 18 years, and BMI at the reference date were not related to the risks of ER-positive, TN, or HER2-overexpressing breast cancer. Changes in BMI from age 18 years to the reference date were not related to the risk of either ER-positive or HER2-overexpressing breast cancer. However, compared with women who had a BMI change from 0 to 4.9 kg/m(2) from age 18 years to the reference date, those who experienced a BMI increase ≥10 kg/m(2) during the same interval had a 2.0-fold (95% confidence interval, 1.2-fold to 3.3-fold increase) increased risk of TN breast cancer. For women with ER-positive disease, there was some evidence that parity modified the effect of BMI change (Pinteraction = .002), because a BMI increase of ≥10 kg/m(2) was associated with a reduced risk of ER-positive disease only among nulliparous women (odds ratio, 0.3; 95% confidence interval, 0.2-0.6). CONCLUSIONS: The correlations appear to differ substantially between BMI change and the risks of TN breast cancer and ER-positive breast cancer.

Alcohol, Smoking, and Risks of Breast Cancer Recurrence and Mortality among Women with Luminal, Triple-Negative, and HER2-Overexpressing Breast Cancer.

BACKGROUND: This study evaluates the relationship between smoking, alcohol, and breast cancer outcomes according to molecular subtype. METHODS: This population-based prospective cohort consisted of 3,876 women ages 20 to 69 diagnosed with a first primary invasive breast cancer from 2004 to 2015 in the Seattle-Puget Sound region. Breast cancer was categorized into three subtypes based on estrogen receptor (ER), progesterone receptor (PR), and HER2 expressions: luminal (ER+), triple-negative (TN; ER-/PR-/HER2-), and HER2-overexpressing (H2E; ER-/HER2+). We fit Cox proportional hazards models to assess the association between alcohol consumption and smoking status at diagnosis and risks of recurrence, breast cancer-specific mortality, and all-cause mortality. RESULTS: Histories of ever smoking [HR, 1.33; 95% confidence interval (CI), 1.01-1.74] and current smoking (HR, 1.59; 95% CI, 1.07-2.35) were associated with greater risk of breast cancer recurrence among TN cases. Smoking was also associated with greater risk of recurrence to bone among all cases and among luminal cases. Elevated risks of breast cancer-specific and all-cause mortality were observed among current smokers across all subtypes. Alcohol use was not positively associated with risk of recurrence or mortality overall; however, TN patients who drank four or more drinks per week had a decreased risk of recurrence (HR, 0.71; 95% CI, 0.51-0.98) and breast cancer-specific mortality (HR, 0.73; 95% CI, 0.55-0.97) compared with non-current drinkers. CONCLUSIONS: Patients with breast cancer with a history of smoking at diagnosis have elevated risks of recurrence and mortality. IMPACT: These findings underscore the need to prioritize smoking cessation among women diagnosed with breast cancer.

Disparities in Risk of Advanced-Stage Liver Cancer and Mortality by Race and Ethnicity.

BACKGROUND: In the United States, liver cancer is the fifth and seventh most common cause of cancer-related death among men and women, respectively. Compared with other racial or ethnic groups in the United States, Asian and Pacific Islander populations experience the highest incidence rates of liver cancer, but little is known about disparities in risk of advanced-stage disease or risk of liver cancer mortality across these heterogenous populations. METHODS: In a population-based cohort of 60 146 patients aged 20-79 years diagnosed with liver cancer from 2004 to 2018 identified through the Surveillance, Epidemiology, and End Results Program, we examined associations between race or ethnicity, including specific Asian and Pacific Islander subgroups, and risk of advanced-stage liver cancer and liver cancer-specific mortality. RESULTS: Compared with non-Hispanic White patients, non-Hispanic Black, Filipino, and Laotian patients had 30%-85% elevated odds of being diagnosed with stage IV liver cancer, whereas Hispanic, Vietnamese, and Chinese patients had 7%-33% lower odds of being diagnosed with stage IV liver cancer (all P <.05). Additionally, non-Hispanic Black, Kampuchean, and Laotian patients had 6%-22% elevated hazards of liver cancer-specific mortality, and Hispanic, Vietnamese, Chinese, and Korean patients had 3%-27% lower hazards of liver cancer-specific mortality (all P <.05). All statistical tests were 2-sided. CONCLUSIONS: Substantial variations in risk of advanced-stage liver cancer and risk of liver cancer mortality were observed by race and ethnicity, including considerable heterogeneity across individuals broadly defined as Asians and Pacific Islanders. Further efforts to understand the contributors to these disparities are needed to inform potential targeted screening and treatment interventions.

Relationship between diabetes and risk of second primary contralateral breast cancer.

Breast cancer survivors have a substantially higher risk of developing a second primary contralateral breast cancer (CBC) compared to the risk of breast cancer among women in the general population. While data regarding the relationship between diabetes and breast cancer incidence are inconsistent, diabetes is more clearly linked to an elevated risk of all-cause mortality among breast cancer survivors. However, no prior studies have assessed its impact on CBC risk. We assessed the relationship between diabetes, and CBC risk in a population-based nested case-control study consisting of women 40-79 years of age diagnosed with a first primary ER-positive invasive breast cancer. It included 322 women who developed a second primary CBC and 616-matched control women diagnosed only with a first breast cancer. We used conditional logistic regression to quantify associations between diabetes and CBC risk. Compared to women without a history of diabetes, diabetics had a 2.2-fold [95% confidence interval (CI) 1.3-3.6] increased risk of CBC. This risk was more pronounced among women diagnosed with their first breast cancer before age 60 years (odds ratio, OR = 11.5, 95% CI 2.4-54.5), compared to those diagnosed at age 60 years or older (OR = 1.5, 95% CI 0.8-2.7, P for interaction = 0.011). Diabetics diagnosed with breast cancer appear to have an elevated risk of CBC. This is the first study to report this relationship, but if confirmed efforts to insure that diabetic breast cancer survivors are carefully screened for second breast cancers may be warranted.

Determinants of Guideline-Discordant Breast Cancer Care.

BACKGROUND: Evidence-based breast cancer treatment guidelines recommend the most appropriate course of therapy based on tumor characteristics and extent of disease. Evaluating the multilevel factors associated with guideline discordance is critical to identifying strategies to eliminate breast cancer survival disparities. METHODS: We identified females diagnosed with a first primary, stage I-III breast cancer between the ages of 20-69 years of age from the population-based Seattle-Puget Sound Surveillance, Epidemiology, and End Results registry. Participants completed a survey about social support, utilization of patient support services, hypothesized barriers to care, and initiation of breast cancer treatment. We used logistic regression to estimate odds ratios and 95% confidence intervals (CI). RESULTS: Among 1,390 participants, 10% reported guideline-discordant care. In analyses adjusted for patient-level sociodemographic factors, individuals who did not have someone to go with them to appointments or drive them home (OR 1.96; 95% CI, 1.09-3.59) and those who had problems talking to their doctors or their staff (OR 2.03; 95% CI, 1.13-3.64) were more likely to be guideline discordant than those with social support or without such problems, respectively. Use of patient support services was associated with a 43% lower odds of guideline discordance (OR 0.57; 95% CI, 0.36-0.88). CONCLUSIONS: Although guideline discordance in this cohort of early-stage breast cancer survivors diagnosed <70 years of age was low, instrumental social support, patient support services, and communication with doctors and their staff emerged as potential multilevel intervention targets for improving breast cancer care delivery. IMPACT: This study supports extending the reach of interventions designed to improve guideline concordance.

Bisphosphonate Use and Breast Cancer Risk among Women with Ductal Carcinoma In Situ.

Women with a history of ductal carcinoma in situ (DCIS) have an elevated risk of a subsequent invasive breast cancer, but there are few established potentially modifiable factors known to lower this risk. Bisphosphonates are a commonly used treatment for patients with osteoporosis and have been shown to lower risks of recurrence and mortality in patients with invasive breast cancer; however, their use has not previously been investigated within the context of DCIS. Utilizing a population-based nested case-control design, we compared 301 cases of women diagnosed with DCIS and a subsequent breast cancer and 587 individually matched controls (on age, DCIS diagnosis year, primary treatment, histology, grade, and disease-free survival time) who were diagnosed with DCIS but never a subsequent breast cancer. Information on recency and duration of bisphosphonate use was ascertained from patient interviews and medical record reviews. Current users of bisphosphonates had a reduced risk of developing an invasive breast cancer compared with never users [OR = 0.50; 95% confidence interval (CI): 0.26-0.99]. Users of bisphosphonates for ≥48 months had a similar reduction in risk (OR = 0.45; 95% CI, 0.24-1.06). This is the first study to document that bisphosphonate use is associated with a lower risk of subsequent invasive breast cancer among women with a history of DCIS. This finding is consistent with the protective effect of bisphosphonates observed in other breast cancer settings. If validated by others, bisphosphonates may be an effective risk-reducing approach with the potential added benefits of its positive impacts on bone health and fracture risk. SIGNIFICANCE: This study finds that bisphosphonate use among women with a history of DCIS is associated with lower risk of subsequent invasive breast cancer, providing a potential preventative approach for this high-risk population.

Cancer Cell Intrinsic and Immunologic Phenotypes Determine Clinical Outcomes in Basal-like Breast Cancer.

PURPOSE: Basal-like breast cancer (BLBC) is a particularly aggressive intrinsic molecular subtype of breast cancer that lacks targeted therapies. There is also no clinically useful test to risk stratify patients with BLBC. We hypothesized that a transcriptome-based phenotypic characterization of BLBC tumors and their microenvironments may overcome these challenges. EXPERIMENTAL DESIGN: We conducted a retrospective correlative genomic sequencing study using a matched pairs design with validation in five independent cohorts. The study was conducted on a large population-based prospective cohort of the major molecular subtypes of breast cancer conducted in the greater Seattle-Puget Sound metropolitan area. Cases consisted of women 20-69 years of age first diagnosed with invasive breast cancer identified through the population-based Surveillance Epidemiology and End Results program. Patients for this analysis (n = 949) were identified from the 1,408 patients with stage I-III triple-negative breast cancer [estrogen receptor-negative (ER-), progesterone receptor-negative (PR-), HER2-]. Of the 949 women, 248 developed a recurrence after their initial diagnosis. A matched set of 67 recurrent and nonrecurrent BLBC tumors was subjected to transcriptome sequencing. Through RNA sequencing of the matched sets of recurrent and nonrecurrent BLBC tumors, we aimed to identify prognostic phenotypes.To identify nonredundant and uncorrelated prognostic genes, we used an ensemble of variable selection algorithms, which resulted in a ranking of genes on the basis of their expected utility in classification. Using leave-one-out cross-validation, we trained a random forest classifier on the basis of the top 21 genes (BRAVO-DX). Validations were performed in five independent triple-negative or BLBC cohorts, and biomarker robustness and transferability were demonstrated by employing real-time PCR. RESULTS: We found that cancer cell intrinsic and immunologic phenotypes are independent predictors of recurrence. By simultaneously interrogating the tumor and its microenvironment, we developed a compound risk model that stratified patients into low-, medium-, and high-risk groups, with a 14%/56%/74% chance of recurrence, respectively. Biologically, the primary tumors of patients who developed a recurrence had increased growth factor signaling and stem-like features, while nonrecurrent tumors showed high lymphocyte infiltration with clonal expansion of T and B cells, as well as antitumor polarization of macrophages. We validated our model in five independent cohorts, including three large cohorts, where BRAVO-DX was highly informative in identifying patients with disease recurrence [HR, 6.79 (95% confidence interval (CI), 1.89-24.37); HR, 3.45 (95% CI, 2.41-4.93); and HR, 1.69 (95% CI, 1.17-2.46)]. A smaller gene set focused on the tumor immunophenotype, BRAVO-IMMUNE, was highly prognostic in all five cohorts. CONCLUSIONS: Together, these results indicate that phenotypic characteristics of BLBCs and their microenvironment are associated with recurrence-free survival and demonstrate the utility of intrinsic and extrinsic phenotypes as independent prognostic biomarkers in BLBC. Pending further evaluation and validation, our prognostic model has the potential to inform clinical decision-making for patients with BLBC as it identifies those at high risk of rapidly progressing on standard chemotherapy, as well as those who may benefit from alternative first-line therapies.

Relationship between Diabetes and Diabetes Medications and Risk of Different Molecular Subtypes of Breast Cancer.

BACKGROUND: Type II diabetes and certain diabetes treatments have been observed to impact breast cancer risk. However, their associations with different breast cancer molecular subtype defined by estrogen receptor (ER)/progesterone receptor (PR)/HER2 status are unclear. METHODS: We conducted a retrospective multi-center population-based case-case study consisting of 4,557 breast cancer cases to evaluate the impact of type II diabetes and diabetes medications on the risk of different breast cancer molecular subtypes [ER+/HER2-, ER+/HER2+, triple negative (ER-/PR-/HER2-), and HER2 overexpressing (H2E, ER-/PR-/HER2+)]. Using ER+/HER2- cases as the reference group, we estimated ORs and corresponding 95% confidence intervals (CI) for each subtype using polytomous logistic regression. RESULTS: Compared with those without a diabetes history, women with type II diabetes had a 38% (95% CI, 1.01-1.89) increased odds of triple-negative breast cancer (TNBC). Current and longer term recent metformin use (13-24 months of treatment within the 24-month period prior to breast cancer diagnosis) was associated with elevated odds of TNBC (OR = 1.54; 95% CI, 1.07-2.22 and OR = 1.80; 95% CI, 1.13-2.85, respectively). CONCLUSIONS: The odds of having a triple-negative rather than ER+/HER2- breast cancer is greater for women with type II diabetes, and particularly for those who were users of metformin. This finding is supported by some preclinical data suggesting that diabetes may be more strongly associated with risk of triple-negative disease. IMPACT: Our study provides novel evidence regarding potential differential effects of type II diabetes and metformin use on risk of different molecular subtypes of breast cancer.

Recent Use of Oral Contraceptives and Risk of Luminal B, Triple-Negative, and HER2-Overexpressing Breast Cancer.

Oral contraceptive use is a well-established risk factor for breast cancer and is common among reproductive-aged women in the USA. Its relationship with less common, more aggressive, molecular subtypes is less clear. A population-based case-case analysis was conducted comparing three less common molecular subtypes to luminal A breast cancer among 1701 premenopausal cases aged 21-49 diagnosed with a first primary invasive breast cancer between 2004 and 2015. Medical record reviews and structured interviewer-administered questionnaires were used to collect data on oral contraceptive use. Multinomial logistic regression was used to estimate odds ratios (OR) and corresponding 95% confidence intervals (95% CI) for recency of oral contraceptive use for each subtype of breast cancer. Current use of oral contraceptives and use within 5 years before diagnosis was associated with lower odds of H2E tumors compared with luminal A tumors [OR = 0.5, 95% CI: 0.3, 0.9 and OR = 0.5, 95% CI: 0.4, 0.8, respectively] with increasing duration associated with decreasing odds (p for trend < 0.05). Oral contraceptive use was not associated with risks of TN or luminal B breast cancer. Oral contraceptive use may be more strongly positively associated with risks of luminal A, luminal B, and TN breast cancer than with risk of H2E tumors. These findings contribute to the etiological understanding of different molecular subtypes of breast cancer.

Relationship Between Anthropometric Factors and Risk of Second Breast Cancer Among Women With a History of Ductal Carcinoma In Situ.

BACKGROUND: Women with ductal carcinoma in situ (DCIS) have an elevated risk of a second breast cancer, but few data are available regarding the impact of modifiable lifestyle factors on this risk. METHODS: In a population-based case-control patient study of women with a history of DCIS in western Washington diagnosed between 1996 and 2013, 497 patients diagnosed with DCIS and a second ipsilateral or contralateral invasive or in situ breast cancer were enrolled. There were 965 matched control patients with one DCIS diagnosis. Associations between anthropometric factors and risk of an invasive or in situ second breast cancer event were evaluated using conditional logistic regression. Statistical tests were two-sided. RESULTS: Obesity (body mass index [BMI] ≥ 30 kg/m2) at initial DCIS diagnosis was associated with a 1.6-fold (95% confidence interval [CI] = 1.2 to 2.2) increased risk of any second breast cancer and a 2.2-fold increased risk of a contralateral second breast cancer (95% CI = 1.4 to 3.3) compared with normal weight women (BMI < 25 kg/m2). BMI and weight, both at initial DCIS diagnosis and at the time of the second breast cancer diagnosis, were positively associated with risk of any second and second invasive breast cancers (odds ratio = 1.01-1.04, all P ≤ .03). CONCLUSIONS: Although additional confirmatory studies are needed, obesity appears to be an important contributor to the risk of second breast cancers within the growing population of women with DCIS. This has potential clinical relevance with respect to identifying which women with a history of DCIS may require more careful monitoring and who may benefit from lifestyle modifications.

Family History and Risk of Second Primary Breast Cancer after In Situ Breast Carcinoma.

Background: Incidence rates of in situ breast carcinomas have increased due to widespread adoption of mammography. Very little is known about why some women with in situ breast cancer later develop second primary breast cancers.Methods: In this population-based nested case-control study among in situ breast cancer survivors, including 539 cases with a second primary breast cancer and 994 matched controls, we evaluated the association between first-degree family history of breast cancer and risk of developing a second primary breast cancer.Results: First-degree family history of breast cancer was associated with an increased risk of developing a second primary breast cancer among women with a previous in situ breast cancer [odds ratio (OR) = 1.33, 95% confidence interval (CI), 1.05-1.69] and those with two or more affected first-degree relatives had an even higher risk (OR = 1.94; 95% CI, 1.15-3.28). Those whose relative was diagnosed at less than 50 years old were more likely to develop a second primary breast cancer (OR = 1.78; 95% CI, 1.24-2.57). No difference in risks associated with number or age of affected relatives was observed by menopausal status.Conclusions: Results from this study suggest that first-degree family history of breast cancer may be an important risk factor for development of a second primary breast cancer among women with a previous in situ breast cancer.Impact: Given the growing population of in situ breast cancer survivors, a better understanding of risk factors associated with development of a second primary breast cancer is needed to further understand risk. Cancer Epidemiol Biomarkers Prev; 27(3); 315-20. ©2018 AACR.

Alcohol Intake and Risk of Breast Cancer by Histologic Subtype and Estrogen Receptor Status Among Women Aged 55 to 74 Years.

Previous studies suggest that alcohol consumption and risk of breast cancer may differ by histologic subtype and hormone receptor status, though results are not entirely consistent. In this population-based case-control study, we evaluated the association between alcohol consumption and risk of invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and invasive ductal-lobular carcinoma (IDLC) overall and by estrogen receptor (ER) status, among women aged 55-74 years of age. Using polytomous regression, associations between current alcohol consumption, overall and by type of alcohol, and breast cancer risk were evaluated in 891 controls and 905 IDC, 567 ILC, and 489 IDLC cases. Current alcohol use was moderately associated with risk of ILC (odds ratio = 1.25, 95% confidence interval 0.99, 1.58) with a positive dose-response relationship based on average number of drinks per week consumed (P trend = 0.0005). When further stratified by ER status, alcohol use was positively associated with risk of ER+ ILC (P trend = 0.002) and ER+ IDC (P trend = 0.02), but inversely associated with risk of ER-IDC (P trend = 0.01). No association between alcohol and risk of IDLC tumors was observed. While the link between alcohol consumption and breast cancer risk is well established, our results suggest that the increased risk associated with alcohol is largely limited to ER+ ILC and ER+ IDC. Thus, avoiding or moderating alcohol consumption may be one way that women can lower their risks of these forms of breast cancer.

Reproductive Factors and Risk of Luminal, HER2-Overexpressing, and Triple-Negative Breast Cancer Among Multiethnic Women.

BACKGROUND: Reproductive factors are among the most well-established risk factors for breast cancer. However, their associations with different breast cancer subtypes defined by joint estrogen receptor (ER)/progesterone receptor (PR)/HER2 status remain unclear. METHODS: We assessed relationships between reproductive factors and risks of luminal A (ER(+)/HER2(-)), luminal B (ER(+)/HER2(+)), triple-negative (TN; ER(-)/PR(-)/HER2(-)), and HER2-overexpressing (H2E; ER(-)/HER2(+)) breast cancers in a population-based case-case study consisting of 2,710 women ages 20-69 years diagnosed between 2004 and 2012. ORs and 95% confidence intervals (CI) were estimated with luminal A cases serving as the reference group using polytomous logistic regression. RESULTS: Earlier age at first full-term pregnancy and age at menopause were positively associated with odds of TN breast cancer (Ptrend: 0.003 and 0.024, respectively). Parity was associated with a 43% (95% CI, 1.08-1.89) elevated odds of H2E breast cancer, and women who had ≥3 full-term pregnancies had a 63% (95% CI, 1.16-2.29, Ptrend = 0.013) increased odds of this subtype compared with nulliparous women. Breast feeding for ≥36 months was associated with a 49% (OR 0.51; 95% CI, 0.27-0.99) lower odds of TN breast cancer. CONCLUSION: Our results suggest that reproductive factors contribute differently to risks of the major molecular subtypes of breast cancer. IMPACT: African American and Hispanic women have higher incidence rates of the more aggressive TN and H2E breast cancers and their younger average age at first pregnancy, higher parity, and less frequent breast feeding could in part contribute to this disparity. Cancer Epidemiol Biomarkers Prev; 25(9); 1297-304. ©2016 AACR.

The relationship between alcohol use and risk of breast cancer by histology and hormone receptor status among women 65-79 years of age.

Alcohol consumption is associated with a moderate increase in breast cancer risk, possibly because alcohol increases estrogen levels in blood. Certain types of breast carcinomas are more hormonally responsive than others, including those that have a lobular histology or are hormone receptor positive, but few studies evaluating alcohol use and breast cancer risk have stratified results by histology or estrogen receptor (ER)/progesterone receptor (PR) status. We conducted a population-based case-control study of women 65-79 years of age in western Washington State. Women (975) diagnosed with invasive breast cancer during 1997-1999 were compared with 1007 controls. Ever-use of alcohol over the past 20 years was associated with a 1.3-fold [95% confidence interval (CI), 1.0-1.5] increased risk of breast cancer, although this increase was primarily limited to women who consumed > or =30.0 g/day of alcohol [odds ratio (OR), 1.7; 95% CI, 1.1-2.6]. Differences in risk by histology were observed: ever-use of alcohol was associated with a 1.8-fold (95% CI, 1.3-2.5) increased risk of lobular cancer but only a 1.2-fold (95% CI, 0.9-1.4) increased risk of ductal cancer. Ever-users of alcohol had an increase in risk of ER+/PR+ tumors (OR, 1.3; 95% CI, 1.1-1.7), but no change in their risks of ER+/PR- or ER-/PR- tumors. Alcohol use appears to be more strongly associated with risk of lobular carcinomas and hormone receptor-positive tumors than it is with other types of breast cancer. These results are consistent with there being an underlying hormonal basis for the known association between alcohol use and breast cancer incidence.