Wendy Y. Chen

PURPOSE: To determine whether weight prior to diagnosis and weight gain after diagnosis are predictive of breast cancer survival. METHODS: Patients included 5,204 Nurses' Health Study participants diagnosed with incident, invasive, nonmetastatic breast cancer between 1976 and 2000; 860 total deaths, 533 breast cancer deaths, and 681 recurrences (defined as secondary lung, brain, bone, or liver cancer, and death from breast cancer) accrued to 2002. We computed the change in body mass index (BMI) from before to the first BMI reported > or = 12 months after the date of diagnosis. Cox proportional hazards models were used to evaluate associations of categories of BMI before diagnosis and of BMI change with time to event. We stratified by smoking, menopausal status, and breast cancer-related variables. RESULTS: In multivariate-adjusted analyses, weight before diagnosis was positively associated with breast cancer recurrence and death, but this was apparent only in never smokers. Similarly, among never-smoking women, those who gained between 0.5 and 2.0 kg/m(2) (median gain, 6.0 lb; relative risk [RR], 1.35; 95% CI, 0.93 to 1.95) or more than 2.0 kg/m(2) (median gain, 17.0 lb; RR, 1.64; 95% CI, 1.07 to 2.51) after diagnosis had an elevated risk of breast cancer death during follow-up (median, 9 years), compared with women who maintained their weight (test for linear trend, P = .03). Associations with weight were stronger in premenopausal than in postmenopausal women. Similar findings were noted for breast cancer recurrence and all-cause mortality. CONCLUSION: Weight and weight gain were related to higher rates of breast cancer recurrence and mortality, but associations were most apparent in never-smoking women.

Importance: Sarcopenia (low muscle mass), poor muscle quality (low muscle radiodensity), and excess adiposity derived from computed tomography (CT) has been related to higher mortality in patients with metastatic breast cancer, but the association with prognosis in patients with nonmetastatic breast cancer is unknown. Objective: To evaluate associations of all 3 body composition measures, derived from clinically acquired CT at diagnosis, with overall mortality in nonmetastatic breast cancer. Design, Setting, and Participants: This observational study included 3241 women from Kaiser Permanente of Northern California and Dana Farber Cancer Institute diagnosed from January 2000 to December 2013 with stages II or III breast cancer. We calculated hazard ratios (HRs) to evaluate the associations of all-cause mortality with sarcopenia, low muscle radiodensity, and total adipose tissue (TAT). Models were adjusted for sociodemographics, tumor characteristics, treatment, body mass index (BMI; calculated as weight in kilograms divided by height in meters squared), and other body composition measures. We also evaluated the cross-classification of categories of sarcopenia (yes/no) and tertiles of TAT, with outcomes. Main Outcomes and Measures: Overall survival time and all-cause mortality. Results: Median (range) age of 3241 women included in this study was 54 (18-80) years, and median follow-up was 6.0 years; 1086 patients (34%) presented with sarcopenia, and 1199 patients (37%) had low muscle radiodensity. Among patients with nonmetastatic breast cancer, those with sarcopenia showed higher overall mortality (HR, 1.41; 95% CI, 1.18-1.69) compared with those without sarcopenia. Patients in the highest tertile of TAT also showed higher overall mortality (HR, 1.35; 95% CI, 1.08-1.69) compared with those in the lowest tertile. Low radiodensity was not associated with survival. In analyses of sarcopenia and TAT, highest mortality was seen in patients with sarcopenia and high TAT (HR, 1.89; 95% CI, 1.30-2.73); BMI alone was not significantly related to overall mortality and did not appropriately identify patients at risk of death owing to their body composition. Conclusions and Relevance: Sarcopenia is underrecognized in nonmetastatic breast cancer and occurs in over one-third of newly diagnosed patients. Measures of both sarcopenia and adiposity from clinically acquired CT scans in nonmetastatic patients provide significant prognostic information that outperform BMI and will help to guide interventions to optimize survival outcomes.

BACKGROUND: Evaluations of epidemiologic risk factors in relation to breast cancer classified jointly by estrogen receptor (ER) and progesterone receptor (PR) status have been inconsistent. To address this issue, we conducted a prospective evaluation of risk factors for breast cancer classified according to receptor status. METHODS: During 1 029 414 person-years of follow-up of 66 145 women participating in the Nurses' Health Study from 1980 through 2000, we identified 2096 incident cases of breast cancer for which information on ER/PR status was available: 1281 were ER+/PR+, 318 were ER+/PR-, 80 were ER-/PR+, and 417 were ER-/PR-. We fit a log-incidence model of breast cancer and used polychotomous logistic regression to compare coefficients for breast cancer risk factors in patients with different ER/PR status. To test for differences in risk factor odds ratios based on marginal ER/PR categories, we evaluated ER status controlling for PR status and vice versa. The predictive ability of our log-incidence model to discriminate between women who would develop ER+/PR+ breast cancer and those who would not (and similarly for ER-/PR- breast cancer) was evaluated by using receiver operator characteristic curve analysis. All statistical tests were two-sided. RESULTS: We observed statistically significant heterogeneity among the four ER/PR categories for some risk factors (age, menopausal status, body mass index [BMI] after menopause, the one-time adverse effect of first pregnancy, and past use of postmenopausal hormones) but not for others (benign breast disease, family history of breast cancer, alcohol use, and height). The one-time adverse association of first pregnancy with incidence was present for PR- but not for PR+ tumors after controlling for ER status (P =.007). However, the association of BMI after menopause with incidence was present for PR+ but not PR- tumors (P =.005). Statistically significant differences in the incidence of ER+ and ER- tumors were seen with age, both before and after menopause (P =.003), and with past use of postmenopausal hormones (P =.01). Area under the receiver operator characteristic curve, adjusted for age, was 0.64 (95% confidence interval [CI] = 0.63 to 0.66) for ER+/PR+ tumors and 0.61 (95% CI = 0.58 to 0.64) for ER-/PR- tumors. CONCLUSIONS: Incidence rates and risk factors for breast cancer differ according to ER and PR status. Thus, to accurately estimate breast cancer risk, breast cancer cases should be divided according to the ER and PR status of the tumor.

CONTEXT: Multiple studies have linked alcohol consumption to breast cancer risk, but the risk of lower levels of consumption has not been well quantified. In addition, the role of drinking patterns (ie, frequency of drinking and "binge" drinking) and consumption at different times of adult life are not well understood. OBJECTIVE: To evaluate the association of breast cancer with alcohol consumption during adult life, including quantity, frequency, and age at consumption. DESIGN, SETTING, AND PARTICIPANTS: Prospective observational study of 105,986 women enrolled in the Nurses' Health Study followed up from 1980 until 2008 with an early adult alcohol assessment and 8 updated alcohol assessments. MAIN OUTCOME MEASURES: Relative risks of developing invasive breast cancer. RESULTS: During 2.4 million person-years of follow-up, 7690 cases of invasive breast cancer were diagnosed. Increasing alcohol consumption was associated with increased breast cancer risk that was statistically significant at levels as low as 5.0 to 9.9 g per day, equivalent to 3 to 6 drinks per week (relative risk, 1.15; 95% CI, 1.06-1.24; 333 cases/100,000 person-years). Binge drinking, but not frequency of drinking, was associated with breast cancer risk after controlling for cumulative alcohol intake. Alcohol intake both earlier and later in adult life was independently associated with risk. CONCLUSIONS: Low levels of alcohol consumption were associated with a small increase in breast cancer risk, with the most consistent measure being cumulative alcohol intake throughout adult life. Alcohol intake both earlier and later in adult life was independently associated with risk.

PURPOSE: Animal and in vitro studies suggest that aspirin may inhibit breast cancer metastasis. We studied whether aspirin use among women with breast cancer decreased their risk of death from breast cancer. METHODS: This was a prospective observational study based on responses from 4,164 female registered nurses in the Nurses' Health Study who were diagnosed with stages I, II, or III breast cancer between 1976 and 2002 and were observed until death or June 2006, whichever came first. The main outcome was breast cancer mortality risk according to number of days per week of aspirin use (0, 1, 2 to 5, or 6 to 7 days) first assessed at least 12 months after diagnosis and updated. RESULTS: There were 341 breast cancer deaths. Aspirin use was associated with a decreased risk of breast cancer death. The adjusted relative risks (RRs) for 1, 2 to 5, and 6 to 7 days of aspirin use per week compared with no use were 1.07 (95% CI, 0.70 to 1.63), 0.29 (95% CI, 0.16 to 0.52), and 0.36 (95% CI, 0.24 to 0.54), respectively (test for linear trend, P < .001). This association did not differ appreciably by stage, menopausal status, body mass index, or estrogen receptor status. Results were similar for distant recurrence. The adjusted RRs were 0.91 (95% CI, 0.62 to 1.33), 0.40 (95% CI, 0.24 to 0.65), and 0.57 (95% CI, 0.39 to 0.82; test for trend, P = .03) for 1, 2 to 5, and 6 to 7 days of aspirin use, respectively. CONCLUSION: Among women living at least 1 year after a breast cancer diagnosis, aspirin use was associated with a decreased risk of distant recurrence and breast cancer death.