Erin Weltzien

Epidemiology of breast cancer subtypes in two prospective cohort studies of breast cancer survivors

IntroductionThe aim of this study was to describe breast tumor subtypes by common breast cancer risk factors and to determine correlates of subtypes using baseline data from two pooled prospective breast cancer studies within a large health maintenance organization.MethodsTumor data on 2544 invasive breast cancer cases subtyped by estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (Her2) status were obtained (1868 luminal A tumors, 294 luminal B tumors, 288 triple-negative tumors and 94 Her2-overexpressing tumors). Demographic, reproductive and lifestyle information was collected either in person or by mailed questionnaires. Case-only odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression, adjusting for age at diagnosis, race/ethnicity, and study origin.ResultsCompared with luminal A cases, luminal B cases were more likely to be younger at diagnosis (P = 0.0001) and were less likely to consume alcohol (OR = 0.74, 95% CI = 0.56 to 0.98), use hormone replacement therapy (HRT) (OR = 0.66, 95% CI = 0.46 to 0.94), and oral contraceptives (OR = 0.73, 95% CI = 0.55 to 0.96). Compared with luminal A cases, triple-negative cases tended to be younger at diagnosis (P ≤ 0.0001) and African American (OR = 3.14, 95% CI = 2.12 to 4.16), were more likely to have not breastfed if they had parity greater than or equal to three (OR = 1.68, 95% CI = 1.00 to 2.81), and were more likely to be overweight (OR = 1.82, 95% CI = 1.03 to 3.24) or obese (OR = 1.97, 95% CI = 1.03 to 3.77) if premenopausal. Her2-overexpressing cases were more likely to be younger at diagnosis (P = 0.03) and Hispanic (OR = 2.19, 95% CI = 1.16 to 4.13) or Asian (OR = 2.02, 95% CI = 1.05 to 3.88), and less likely to use HRT (OR = 0.45, 95% CI = 0.26 to 0.79).ConclusionsThese observations suggest that investigators should consider tumor heterogeneity in associations with traditional breast cancer risk factors. Important modifiable lifestyle factors that may be related to the development of a specific tumor subtype, but not all subtypes, include obesity, breastfeeding, and alcohol consumption. Future work that will further categorize triple-negative cases into basal and non-basal tumors may help to elucidate these associations further.

Physical Activity and Risk of Recurrence and Mortality in Breast Cancer Survivors: Findings from the LACE Study

Introduction: Identifying modifiable factors that reduce the risk of recurrence and improve survival in breast cancer survivors is a pressing concern. The purpose of this study was to examine the association of physical activity following diagnosis and treatment with the risk of breast cancer recurrence and mortality and all-cause mortality in women with early-stage breast cancer. Materials and Methods: The sample consisted of 1,970 women from the Life After Cancer Epidemiology study, a prospective investigation of behavioral risk factors and health outcomes. Self-reported frequency and duration of work-related, household and caregiving, recreational, and transportation-related activities during the six months prior to enrollment were assessed. Outcomes were ascertained from electronic or paper medical charts. Hazard ratios and 95% confidence intervals were estimated from delayed entry Cox proportional hazards models. Results: Although age-adjusted results suggested that higher levels of physical activity were associated with reduced risk of recurrence and breast cancer mortality (P for trend = 0.05 and 0.07, respectively for highest versus lowest level of hours per week of moderate physical activity), these associations were attenuated after adjustment for prognostic factors and other confounding variables (P for trend = 0.36 and 0.26). In contrast, a statistically significant protective association between physical activity and all-cause mortality remained in multivariable analyses (hazard ratio, 0.66; 95% confidence interval, 0.42-1.03; P for trend = 0.04). Conclusions: These findings do not support a protective effect of physical activity on breast cancer recurrence or mortality but do suggest that regular physical activity is beneficial for breast cancer survivors in terms of total mortality. (Cancer Epidemiol Biomarkers Prev 2009;18(1):87–95)

Alcohol Consumption and Breast Cancer Recurrence and Survival Among Women With Early-Stage Breast Cancer: The Life After Cancer Epidemiology Study

PURPOSE To examine the association of alcohol consumption after breast cancer diagnosis with recurrence and mortality among early-stage breast cancer survivors. PATIENTS AND METHODS Patients included 1,897 LACE study participants diagnosed with early-stage breast cancer between 1997 and 2000 and recruited on average 2 years postdiagnosis, primarily from the Kaiser Permanente Northern California Cancer Registry. Alcohol consumption (ie, wine, beer, and liquor) was assessed at cohort entry using a food frequency questionnaire. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% CI with adjustment for known prognostic factors. RESULTS Two hundred ninety-three breast cancer recurrences and 273 overall deaths were ascertained after an average follow-up of 7.4 years. Nine hundred fifty-eight women (51%) were considered drinkers (> 0.5 g/d of alcohol), and the majority drank wine (89%). Drinking ≥ 6 g/d of alcohol compared with no drinking was associated with an increased risk of breast cancer recurrence (HR, 1.35; 95% CI, 1.00 to 1.83) and death due to breast cancer (HR, 1.51; 95% CI, 1.00 to 2.29). The increased risk of recurrence appeared to be greater among postmenopausal (HR, 1.51; 95% CI, 1.05 to 2.19) and overweight and obese women (HR, 1.60; 95% CI, 1.08 to 2.38). Alcohol intake was not associated with all-cause death and possibly associated with decreased risk of non-breast cancer death. CONCLUSION Consuming three to four alcoholic drinks or more per week after a breast cancer diagnosis may increase risk of breast cancer recurrence, particularly among postmenopausal and overweight/obese women, yet the cardioprotective effects of alcohol on non-breast cancer death were suggested.

Long-term Prognostic Role of Functional Limitations Among Women With Breast Cancer

BACKGROUND The long-term prognostic role of functional limitations among women with breast cancer is poorly understood. METHODS We studied a cohort of 2202 women with breast cancer at two sites in the United States, who provided complete information on body functions involving endurance, strength, muscular range of motion, and small muscle dexterity following initial adjuvant treatment. Associations of baseline functional limitations with survival were evaluated in delayed entry Cox proportional hazards models, with adjustment for baseline sociodemographic factors, body mass index, smoking, physical activity, comorbidity, tumor characteristics, and treatment. Difference in covariates between women with and without limitations was assessed with Pearson χ(2) and Student t tests. All statistical tests were two-sided. RESULTS During the median follow-up of 9 years, 112 deaths were attributable to competing causes (5% of the cohort) and 157 were attributable to breast cancer causes (7% of the cohort). At least one functional limitation was present in 39% of study participants. Proportionately, more breast cancer patients with functional limitations after initial adjuvant treatment were older, less educated, and obese (P < .001). In multivariable models, functional limitations were associated with a statistically significantly increased risk of death from all causes (hazard ratio [HR] = 1.40, 95% confidence interval [CI] = 1.03 to 1.92) and from competing causes (HR = 2.60, 95% CI = 1.69 to 3.98) but not from breast cancer (HR = 0.90, 95% CI = 0.64 to 1.26). The relationship between functional limitations and overall survival differed by tumor stage (among women with stage I and stage III breast cancer, HR = 2.02, 95% CI = 1.23 to 3.32 and HR = 0.74, 95% CI = 0.42 to 1.30, respectively). CONCLUSION In this prospective cohort study, functional limitations following initial breast cancer treatment were associated with an important reduction in all-cause and competing-cause survival, irrespective of clinical, lifestyle, and sociodemographic factors.

Weight Change and Survival after Breast Cancer in the After Breast Cancer Pooling Project

Background: Weight change after a breast cancer diagnosis has been linked to lower survival. To further understand effects of postdiagnostic weight variation on survival, we examined the relationship by comorbid status and initial body mass index (BMI). Methods: The current analysis included 12,915 patients with breast cancer diagnosed between 1990 and 2006 with stage I–III tumors from four prospective cohorts in the United States and China. HRs and 95% confidence intervals (CI) representing the associations of five weight change categories [within <5% (reference); 5%–<10% and ≥10% loss and gain] with mortality were estimated using Cox proportional hazards models. Results: Mean weight change was 1.6 kg. About 14.7% women lost and 34.7% gained weight. Weight stability in the early years postdiagnosis was associated with the lowest overall mortality risk. Weight loss ≥10% was related to a 40% increased risk of death (HR, 1.41; 95% CI, 1.14–1.75) in the United States and over three times the risk of death (HR, 3.25; 95% CI: 2.24, 4.73) in Shanghai. This association varied by prediagnosis BMI, and in the United States, lower survival was seen for women who lost weight and had comorbid conditions. Weight gain ≥10% was associated with a nonsignificant increased risk of death. Conclusions: Prevention of excessive weight gain is a valid public health goal for breast cancer survivors. Although intentionality of weight loss could not be determined, women with comorbid conditions may be particularly at risk of weight loss and mortality. Impact: Weight control strategies for breast cancer survivors should be personalized to the individuals medical history. Cancer Epidemiol Biomarkers Prev; 21(8); 1260–71. ©2012 AACR.

Intrinsic Subtypes from PAM50 Gene Expression Assay in a Population-Based Breast Cancer Cohort: Differences by Age, Race, and Tumor Characteristics

Background: Data are lacking to describe gene expression–based breast cancer intrinsic subtype patterns for population-based patient groups. Methods: We studied a diverse cohort of women with breast cancer from the Life After Cancer Epidemiology and Pathways studies. RNA was extracted from 1 mm punches from fixed tumor tissue. Quantitative reverse-transcriptase PCR was conducted for the 50 genes that comprise the PAM50 intrinsic subtype classifier. Results: In a subcohort of 1,319 women, the overall subtype distribution based on PAM50 was 53.1% luminal A, 20.5% luminal B, 13.0% HER2-enriched, 9.8% basal-like, and 3.6% normal-like. Among low-risk endocrine-positive tumors (i.e., estrogen and progesterone receptor positive by immunohistochemistry, HER2 negative, and low histologic grade), only 76.5% were categorized as luminal A by PAM50. Continuous-scale luminal A, luminal B, HER2-enriched, and normal-like scores from PAM50 were mutually positively correlated. Basal-like score was inversely correlated with other subtypes. The proportion with non-luminal A subtype decreased with older age at diagnosis, PTrend < 0.0001. Compared with non-Hispanic Whites, African American women were more likely to have basal-like tumors, age-adjusted OR = 4.4 [95% confidence intervals (CI), 2.3–8.4], whereas Asian and Pacific Islander women had reduced odds of basal-like subtype, OR = 0.5 (95% CI, 0.3–0.9). Conclusions: Our data indicate that over 50% of breast cancers treated in the community have luminal A subtype. Gene expression–based classification shifted some tumors categorized as low risk by surrogate clinicopathologic criteria to higher-risk subtypes. Impact: Subtyping in a population-based cohort revealed distinct profiles by age and race. Cancer Epidemiol Biomarkers Prev; 23(5); 714–24. ©2014 AACR.

Antioxidant supplement use after breast cancer diagnosis and mortality in the Life After Cancer Epidemiology (LACE) cohort

There is concern that antioxidant supplement use during chemotherapy and radiation therapy may decrease treatment effects, yet the effects of such supplements on recurrence and survival are largely unknown.

Postdiagnosis Alcohol Consumption and Breast Cancer Prognosis in the After Breast Cancer Pooling Project

Background: Alcohol consumption is an established risk factor for incident breast cancer. However, its role in breast cancer prognosis remains unclear. Methods: We conducted an investigation of postdiagnosis alcohol consumption with recurrence and mortality among 9,329 breast cancer patients in the After Breast Cancer Pooling Project. Women were diagnosed from 1990 to 2006 with AJCC Stage I-III breast tumors from three prospective US cohorts. Alcohol intake was assessed at cohort entry (mean 2.1 years postdiagnosis) using a food frequency questionnaire. HR and 95% confidence intervals (CI) were estimated using delayed entry Cox proportional hazards models with adjustment for known prognostic factors. Results: After a mean follow-up of 10.3 years, 1,646 recurrences and 1,543 deaths were ascertained. 5,422 women (58%) were considered drinkers (≥0.36 g/day of alcohol, ≥0.25 drinks/week) with a median of 5.3 g/day. Overall, compared with nondrinking, regular alcohol intake (≥6.0 g/day) was not associated with risk of recurrence (HR for 6 to less than 12 g/day, 1.03; 95% CI, 0.86–1.24; HR for 12 to less than 24 g/day, 1.12; 95% CI, 0.93–1.34; HR for ≥24 g/day, 1.04; 95% CI, 0.84–1.31). However, risk varied significantly by menopausal status (P for interaction < 0.05). Postmenopausal women who regularly consumed alcohol (≥6.0 g/day) had increased risk of recurrence (HR, 1.19; 95% CI, 1.01–1.40). Alcohol intake was not associated with mortality. Conclusions: Regular alcohol consumption was not associated with breast cancer recurrence and total mortality overall, yet recurrence risk was only elevated in postmenopausal women. Impact: The association between alcohol intake and recurrence may depend on menopausal status at breast cancer diagnosis. Cancer Epidemiol Biomarkers Prev; 22(1); 32–41. ©2012 AACR.

Explaining the Obesity Paradox: The Association between Body Composition and Colorectal Cancer Survival (C-SCANS Study)

Background: Body composition may partially explain the U-shaped association between body mass index (BMI) and colorectal cancer survival. Methods: Muscle and adiposity at colorectal cancer diagnosis and survival were examined in a retrospective cohort using Kaplan–Meier curves, multivariable Cox regression, and restricted cubic splines in 3,262 early-stage (I–III) male (50%) and female (50%) patients. Sarcopenia was defined using optimal stratification and sex- and BMI-specific cut points. High adiposity was defined as the highest tertile of sex-specific total adipose tissue (TAT). Primary outcomes were overall mortality and colorectal cancer–specific mortality (CRCsM). Results: Slightly over 42% patients were sarcopenic. During 5.8 years of follow-up, 788 deaths occurred, including 433 from colorectal cancer. Sarcopenic patients had a 27% [HR, 1.27; 95% confidence interval (CI), 1.09–1.48] higher risk of overall mortality than those who were not sarcopenic. Females with both low muscle and high adiposity had a 64% higher risk of overall mortality (HR, 1.64; 95% CI, 1.05–2.57) than females with adequate muscle and lower adiposity. The lowest risk of overall mortality was seen in patients with a BMI between 25 and <30 kg/m2, a range associated with the greatest number of patients (58.6%) who were not at increased risk of overall mortality due to either low muscle or high adiposity. Conclusions: Sarcopenia is prevalent among patients with non-metastatic colorectal cancer, and should, along with adiposity be a standard oncological marker. Impact: Our findings suggest a biologic explanation for the obesity paradox in colorectal cancer and refute the notion that the association between overweight and lower mortality is due solely to methodologic biases. Cancer Epidemiol Biomarkers Prev; 26(7); 1008–15. ©2017 AACR.

Exercise and Risk of Cardiovascular Events in Women With Nonmetastatic Breast Cancer

PURPOSE Cardiovascular disease (CVD) is a leading cause of death among women with nonmetastatic breast cancer. Whether exercise is associated with reductions in CVD risk in patients with breast cancer with an elevated CVD risk phenotype is not known. METHODS Using a prospective design, women (n = 2,973; mean age, 57 years) diagnosed with nonmetastatic breast cancer participating in two registry-based, regional cohort studies, completed a questionnaire that assessed leisure-time recreational physical activity (metabolic equivalent task [MET]-h/wk). The primary end point was the first occurrence of any of the following: new diagnosis of coronary artery disease, heart failure, valve abnormality, arrhythmia, stroke, or CVD death, occurring after study enrollment. RESULTS Median follow-up was 8.6 years (range, 0.2 to 14.8 years). In multivariable analysis, the incidence of cardiovascular events decreased across increasing total MET-h/wk categories (Ptrend < .001). Compared with < 2 MET-h/wk, the adjusted hazard ratio was 0.91 (95% CI, 0.76 to 1.09) for 2 to 10.9 MET-h/wk, 0.79 (95% CI, 0.66 to 0.96) for 11 to 24.5 MET-h/wk, and 0.65 (95% CI, 0.53 to 0.80) for ≥ 24.5 MET-h/wk. Similar trends were observed for the incidence of coronary artery disease and heart failure (P values < .05). Adherence to national exercise guidelines for adult patients with cancer (ie, ≥ 9 MET-h/wk) was associated with an adjusted 23% reduction in the risk of cardiovascular events in comparison with not meeting the guidelines (< 9 MET-h/wk; P < .001). The association with exercise did not differ according to age, CVD risk factors, menopausal status, or anticancer treatment. CONCLUSION Exercise is associated with substantial, graded reductions in the incidence of cardiovascular events in women with nonmetastatic breast cancer.