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Purpose: Physical activity (PA) is associated with many health benefits. While PA has been associated with reduced mortality after breast cancer diagnosis in many studies, few studies have examined the role of PA in breast cancer survival among underserved and minority populations, including Black women. We investigated PA in association with mortality among Black predominantly low-income breast cancer survivors in the Southern Community Cohort Study (SCCS)., Methods: Study participants were women diagnosed with incident breast cancer (n = 949) in the SCCS, which is a prospective cohort study of predominantly low-income adults aged 40-79 years recruited from 12 Southeastern states between 2002 and 2009. Participants completed a detailed baseline questionnaire, with annual follow-up for mortality via registry linkages. Cox regression models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for associations of pre-diagnosis PA (measured via a validated questionnaire) with all-cause and breast cancer-specific mortality., Results: Breast cancer survivors had a mean age of 61.1 years and most (79.3%) had a household income of < $25,000. In adjusted models, higher levels of total PA (MET-hours/day) were inversely associated with all-cause mortality with HRs (95% CIs): 0.79 (0.59-1.06), 0.66 (0.49-0.90), and 0.60 (0.43-0.84), for Q2, Q3, and Q4 (reference: Q1), respectively, p trend  ≤ 0.01. A similar inverse association was found for breast cancer-specific mortality., Conclusion: Higher levels of pre-diagnosis PA were associated with improved survival among low-income Black breast cancer survivors. Resources to reduce barriers to PA participation and increase support for education and intervention efforts to promote PA among Black women are needed., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Neonatal abstinence syndrome (NAS), largely a consequence of prenatal opioid exposure, results in substantial morbidity. Population-based studies of NAS going beyond Medicaid populations and hospital discharge data (HDD) alone are limited. Using statewide Tennessee (TN) HDD and birth certificate (BC) data, we examined trends and evaluated maternal and infant factors associated with NAS., Methods: We conducted a population-based descriptive study during 2013-2017 in TN. NAS infants were identified with International Classification of Diseases (ICD)-9-Clinical Modification (CM) and ICD-10-CM codes in HDD and linked to BC data using iterative deterministic matching algorithms. Descriptive analyses were conducted for infant and maternal factors (exposures) by NAS (outcome). Multivariable logistic regression models were used to estimate adjusted ORs and 95% CIs., Results: NAS incidence increased from 13.4 to 15.4 per 1,000 live births between 2013-2017 (15% increase; p trend <0.001), but remained stable in 2017. In adjusted models, maternal factors associated with reduced odds of NAS included breastfeeding (OR:0.55, 95%CI:0.52-0.59) and prenatal care (OR:0.36, 95%CI:0.32-0.41). Smoking, preterm birth and lower birthweight were associated with increased odds of NAS., Conclusions: This study highlights the value of utilizing surveillance data to monitor trends and correlates of NAS to inform prevention efforts and targeting of public health resources., Competing Interests: Conflicts of interest: The authors’ declare they have no conflicts of interest.

Background: Despite increasing trends of nonfatal opioid overdoses in emergency departments (EDs), population-based studies comparing prescription opioid dosing patterns before and after nonfatal opioid overdoses are limited., Objectives: To evaluate characteristics of prescribing behaviors before and after nonfatal overdoses, with a focus on opioid dosage., Methods: Included were 5,395 adult residents of Tennessee discharged from hospital EDs after a first nonfatal opioid overdose (2016-2017). Patients were linked to eligible prescription records in the Tennessee Controlled Substance Monitoring Database. We estimated odds ratios (OR) and 95% confidence intervals (CI) to evaluate characteristics associated with filling opioid prescriptions 90 days before overdose and with high daily dose (≥ 90 morphine milligram equivalents) 90 days after overdose., Results: Among patients who filled a prescription both before and after an overdose, the percentage filling a low, medium, and high dose was 33.7%, 31.9%, and 34.4%, respectively, after an opioid overdose (n = 1,516). Most high-dose users before an overdose (>70%) remained high-dose users with the same prescriber after the overdose. Male gender, ages ≥ 35 years, and medium metro residence were associated with increased odds of high-dose filling after an opioid overdose. Patients filling overlapping opioid-benzodiazepine prescriptions and with > 7 days' supply had increased odds of filling high dose after an opioid overdose (OR 1.4, 95% CI 1.08-1.70 and OR 3.7, 95% CI 2.28-5.84, respectively)., Conclusions: In Tennessee, many patients treated in the ED for an overdose are still prescribed high-dose opioid analgesics after an overdose, highlighting a missed opportunity for intervention and coordination of care between ED and non-ED providers., (Copyright © 2021 Elsevier Inc. All rights reserved.)

We performed a statewide evaluation of prescribing patterns of controlled substances (CS) before and after an overdose, using Tennessee's Hospital Discharge Data System and the Controlled Substance Monitoring Database (CSMD). Adults' first non-fatal overdose discharges either from the emergency department (ED) or inpatient (IP) stay occurring between 2013 and 2016 were linked to prescriptions in the CSMD. The difference in the proportion of patients filling a prescription before versus after an overdose was calculated. Included were 49,398 patients with an overdose and a prescription record; most (60.5%) were treated in the ED. Among any drug type overdose the percentage of patients who filled a CS prescription within a year of experiencing an overdose was as follows: opioid analgesics: 59.1%, benzodiazepines: 37.3%, stimulants: 5.0%, muscle relaxants: 3.4%, concurrent opioid-benzodiazepines: 24.0% with the percent difference from before to after similar in both settings. Among patients treated for an opioid overdose, this represented a decrease in opioid analgesics filled by 9.7% (95%CI: -11.2, -8.3) among those treated in the ED, and by 7.1% (95% CI: -8.3, -5.9) among treated inpatients. Among patients treated for a heroin overdose, 12.2% (95%CI: -15.2, -9.3) fewer of those treated in the ED and 8.8% (95%CI: -15.0, -2.7%) fewer of treated inpatients filled a CS prescription in that year. The most common opioid analgesics included hydrocodone and oxycodone. The number of patients filling buprenorphine for treatment increased in the year after overdoses associated with any drug or opioids but decreased among those treated for a heroin overdose., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Opioid overdose deaths have continued to rise in Tennessee (TN) with fentanyl emerging as a major contributor. Current data are needed to identify at-risk populations to guide prevention strategies. We conducted a large statewide observational study among TN adult decedents (2013-2016) to evaluate the association of sociodemographic factors and prescribing patterns with opioid overdose deaths., Methods: Among drug overdose decedents identified using death certificate data (n = 5483), we used logistic regression to estimate adjusted odds ratios and 95% confidence intervals for characteristics associated with prescription opioid (PO) (excluding fentanyl), fentanyl, and heroin alone overdoses. Among decedents linked to TN's Prescription Drug Monitoring Database using deterministic algorithms, we obtained prescription history in the year before death (n = 3971), which was evaluated by type of overdose using descriptive statistics., Results: Younger, non-White decedents had lower odds of PO overdose, while females and benzodiazepines as a contributing cause were associated with increased odds of PO overdose. Younger age, Non-Hispanic Black race/ethnicity, greater than high school education, and cocaine/other stimulants as a contributing cause were associated with increased odds of fentanyl or heroin overdoses. Over 55% of PO, 39.2% of fentanyl, and 20.7% of heroin overdoses had an active opioid prescription at death. For PO, fentanyl, and heroin decedents, respectively, 46.0%, 30.5%, and 26.2% had an active prescription for benzodiazepines at death., Conclusions: Prescription opioid overdose deaths were associated with different sociodemographic profiles and prescribing history compared to fentanyl and heroin overdose deaths in TN. Data can guide prevention strategies to reduce opioid overdose mortality., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Oxidative stress may play an important role in both initiation and progression of breast cancer. We conducted the first systematic epidemiologic review to summarize the published literature on oxidative stress biomarkers and breast cancer., Materials and Methods: We implemented systematic search strategies to identify published studies of oxidative stress biomarkers and (1) risk of developing breast cancer and (2) breast cancer prognosis using the PRISMA statement guidelines., Results: We identified eleven case-control studies of oxidative stress biomarkers and breast cancer. Biomarkers utilized varied and menopausal status was a key modifying factor. Across three nested case-control studies with biomarkers measured before diagnosis, one reported increased risk of postmenopausal breast cancer in association with 8-oxodG (DNA damage biomarker), while two (one of F 2 -isoprostanes and one of fluorescent oxidation products) reported inverse associations for premenopausal breast cancer only. We identified eight prognostic studies. Two reported associations for lipid peroxidation and breast cancer prognosis; results for other studies were null., Conclusions: DNA damage may increase risk of breast cancer among postmenopausal women, while lipid peroxidation may be inversely associated with premenopausal breast cancer. Lipid peroxidation may be associated with survival after breast cancer diagnosis; however, results require evaluation in large, prospective cohort studies.

The purpose of this study was to examine post-diagnosis BMI, very low physical activity, and comorbidities, as predictors of breast cancer-specific and all-cause mortality. Data from three female US breast cancer survivor cohorts were harmonized in the After Breast Cancer Pooling Project (n = 9513). Delayed entry Cox proportional hazards models were used to examine the impact of three post-diagnosis lifestyle factors: body mass index (BMI), select comorbidities (diabetes only, hypertension only, or both), and very low physical activity (defined as physical activity <1.5 MET h/week) in individual models and together in multivariate models for breast cancer and all-cause mortality. For breast cancer mortality, the individual lifestyle models demonstrated a significant association with very low physical activity but not with the selected comorbidities or BMI. In the model that included all three lifestyle variables, very low physical activity was associated with a 22 % increased risk of breast cancer mortality (HR 1.22, 95 % CI 1.05, 1.42). For all-cause mortality, the three individual models demonstrated significant associations for all three lifestyle predictors. In the combined model, the strength and significance of the association of comorbidities (both hypertension and diabetes versus neither: HR 2.16, 95 % CI 1.79, 2.60) and very low physical activity (HR 1.35, 95 % CI 1.22, 1.51) remained unchanged, but the association with obesity was completely attenuated. These data indicate that after active treatment, very low physical activity, consistent with a sedentary lifestyle (and comorbidities for all-cause mortality), may account for the increased risk of mortality, with higher BMI, that is seen in other studies.

Background: Little is known regarding the role of early-life exercise, a potentially modifiable factor, in long-term adult morbidity and mortality. We utilized the Shanghai Women's Health Study (SWHS) to investigate adolescent exercise in association with cancer, cardiovascular disease (CVD), and all-cause mortality among middle-aged and older women., Methods: The SWHS is a prospective cohort of 74,941 Chinese women ages 40 to 70 years recruited from 1996 to 2000. In-person interviews at enrollment assessed adolescent and adult exercise history, medical and reproductive history, and other lifestyle and socioeconomic (SES) factors. Mortality follow-up occurs via annual linkage to the Shanghai Vital Statistics Registry. Adjusted hazard ratios (HR) and 95% confidence intervals (CI) were derived from Cox regression models., Results: Adjusting for birth year and other adolescent factors, adolescent exercise was associated with reduced risk of cancer, CVD, and total mortality [HRs (95% CI), 0.83 (0.72-0.95), 0.83 (0.70-0.98), and 0.78 (0.71-0.85), respectively for ≤1.33 hours (h)/week, and 0.83 (0.74-0.93), 0.62 (0.53-0.72), and 0.71 (0.66-0.77), respectively for >1.33 h/week (reference = none)]. Results were attenuated after adjustment for adult SES and lifestyle factors. Participation in sports teams was inversely associated with cancer mortality [HR (95% CI), 0.86 (0.76-0.97)]. Joint adolescent and adult exercise was associated with reduced risk of all-cause, CVD, and cancer mortality [HRs (95% CIs), 0.80 (0.72-0.89), 0.83 (0.69-1.00), and 0.87 (0.74-1.01), respectively], adjusting for adult/adolescent factors, and adolescence exercise only was inversely associated with cancer mortality [HR (95% CI), 0.84 (0.71-0.98)]., Conclusions: Adolescent exercise participation, independent of adult exercise, was associated with reduced risk of cancer, CVD, and all-cause mortality., Impact: Results support promotion of exercise in adolescence to reduce mortality in later life., (©2015 American Association for Cancer Research.)

Background: There is controversy on whether former smokers have increased risk for breast cancer recurrence or all-cause mortality, regardless of how much they smoked., Methods: Data were from three US cohorts in the After Breast Cancer Pooling Project, with detailed information on smoking among 9975 breast cancer survivors. Smoking was assessed an average of 2 years after diagnosis. Delayed entry Cox proportional hazards models were used to examine the relationships of smoking status, cigarettes per day, years of smoking, and pack years with breast cancer prognosis. Endpoints included breast cancer recurrence (n = 1727), breast cancer mortality (n = 1059), and overall mortality (n = 1803)., Results: Compared with never smokers, former smokers with less than 20 pack-years of exposure had no increased risk of any outcome. However, former smokers with 20 to less than 34.9 pack-years of exposure had a 22% increased risk of breast cancer recurrence (hazard ratio [HR] = 1.22; 95% confidence interval [CI] = 1.01 to 1.48) and a 26% increased risk of all-cause mortality (HR = 1.26; 95% CI = 1.07 to 1.48). For former smokers with 35 or more pack-years of exposure, the probability of recurrence increased by 37% (HR = 1.37; 95% CI = 1.13 to 1.66), breast cancer mortality increased by 54% (HR = 1.54; 95% CI = 1.24 to 1.91), and all-cause mortality increased by 68% (HR = 1.68; 95% CI = 1.44 to 1.96). Current smoking increased the probability of recurrence by 41% (HR = 1.41; 95% CI = 1.16 to 1.71), increased breast cancer mortality by 60% (HR = 1.61; 95% CI = 1.28 to 2.03), and doubled the risk of all-cause mortality (HR = 2.17; 95% CI = 1.85 to 2.54)., Conclusions: Lifetime cigarette smoking was statistically significantly associated with a poor prognosis among women diagnosed with breast cancer, dose-dependent increased risks of recurrence, and breast cancer and all-cause mortality.

Vitamin supplement use after breast cancer diagnosis is common, but little is known about long-term effects on recurrence and survival. We examined postdiagnosis supplement use and risk of death or recurrence in the After Breast Cancer Pooling Project, a consortium of four cohorts of 12,019 breast cancer survivors from the United States and China. Post-treatment supplement use (vitamins A, B, C, D, E, and multivitamins) was assessed 1-5 years postdiagnosis. Associations with risk of recurrence, breast cancer-specific mortality, or total mortality were analyzed in Cox proportional hazards models separately by cohort. Individual cohort results were combined using random effects meta-analysis. Interactions with smoking, treatment, and hormonal status were examined. In multivariate models, vitamin E was associated with a decreased risk of recurrence (RR: 0.88; 95 % CI 0.79-0.99), and vitamin C with decreased risk of death (RR: 0.81; 95 % CI 0.72-0.92). However, when supplements were mutually adjusted, all associations were attenuated. There were no statistically significant associations with breast cancer mortality. The use of antioxidant supplements (multivitamins, vitamin C, or E) was not associated with recurrence, but was associated with a 16 % decreased risk of death (95 % CI 0.72-0.99). In addition, vitamin D was associated with decreased risk of recurrence among ER positive, but not ER negative tumors (p-interaction = 0.01). In this large consortium of breast cancer survivors, post-treatment use of vitamin supplements was not associated with increased risk of recurrence or death. Post-treatment use of antioxidant supplements was associated with improved survival, but the associations with individual supplement were difficult to determine. Stratification by ER status and considering antioxidants as a group may be more clinically relevant when evaluating associations with cancer risk and mortality.

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.

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 individual's medical history., (©2012 AACR.)

Background: Soy isoflavones have antiestrogenic and anticancer properties but also possess estrogen-like properties, which has raised concern about soy food consumption among breast cancer survivors., Objective: We prospectively evaluated the association between postdiagnosis soy food consumption and breast cancer outcomes among US and Chinese women by using data from the After Breast Cancer Pooling Project., Design: The analysis included 9514 breast cancer survivors with a diagnosis of invasive breast cancer between 1991 and 2006 from 2 US cohorts and 1 Chinese cohort. Soy isoflavone intake (mg/d) was measured with validated food-frequency questionnaires. HRs and 95% CIs were estimated by using delayed-entry Cox regression models, adjusted for sociodemographic, clinical, and lifestyle factors., Results: After a mean follow-up of 7.4 y, we identified 1171 total deaths (881 from breast cancer) and 1348 recurrences. Despite large differences in soy isoflavone intake by country, isoflavone consumption was inversely associated with recurrence among both US and Chinese women, regardless of whether data were analyzed separately by country or combined. No heterogeneity was observed. In the pooled analysis, consumption of ≥10 mg isoflavones/d was associated with a nonsignificant reduced risk of all-cause (HR: 0.87; 95% CI: 0.70, 1.10) and breast cancer-specific (HR: 0.83; 95% CI: 0.64, 1.07) mortality and a statistically significant reduced risk of recurrence (HR: 0.75; 95% CI: 0.61, 0.92)., Conclusion: In this large study of combined data on US and Chinese women, postdiagnosis soy food consumption of ≥10 mg isoflavones/d was associated with a nonsignificant reduced risk of breast cancer-specific mortality and a statistically significant reduced risk of recurrence.

Obese and underweight women who develop breast cancer may have poorer survival compared with normal-weight women. However, the optimal weight for best prognosis is still under study. We conducted a prospective investigation of pre-diagnosis body mass index (BMI) and mortality among 14,948 breast cancer patients in the After Breast Cancer Pooling Project. Breast cancer patients diagnosed from 1990 to 2006 with AJCC Stage I-III breast tumors were drawn from four prospective cohorts. Hazard ratios (HR) and 95% confidence intervals (CI) representing the associations of BMI categories (World Health Organization international classifications) with recurrence and mortality were estimated using delayed entry Cox proportional hazards models. Obese (30 to < 35 kg/m(2)), severely obese (35 to < 40 kg/m(2)), and morbidly obese (≥ 40 kg/m(2)) were examined. After a mean follow-up of 7.8 years, 2,140 deaths and 2,065 recurrences were documented. Both underweight (HR = 1.59; 95% CI: 1.18, 2.13) and morbidly obese women (HR = 1.81; 95% CI: 1.42, 2.32) had the greatest risk of overall mortality compared with normal weight (18.5-24.9 kg/m(2)) women. Severe obesity (HR = 1.09; 95% CI: 0.88, 1.36) and obesity (HR = 1.11; 95% CI: 0.97, 1.27) were related to small non-significant increased risks. Overweight (25.0-29.9 kg/m(2)) was not associated with any excess risk compared with normal weight. Similar associations were found for breast cancer death and non-breast cancer death but not recurrence. Women who were underweight and morbidly obese before breast cancer diagnosis were at the greatest risk of all-cause mortality. Morbidly obese women were also at increased risk of death from breast cancer. These results suggest that degree of obesity confers differential risk on survival.

The 2008 Physical Activity (PA) Guidelines recommend engaging in at least 2.5 h (10 MET-hours/week) of moderate intensity PA per week (defined as 4 METs) to reduce risk of morbidity and mortality. This analysis was conducted to investigate whether this recommendation can be extended to breast cancer survivors. Data from four studies of breast cancer survivors measuring recreational PA from semi-quantitative questionnaires a median of 23 months post-diagnosis (interquartile range 18-32 months) were pooled in the After Breast Cancer Pooling Project (n = 13,302). Delayed entry Cox proportional hazards models were applied in data analysis with adjustment for age, post-diagnosis body mass index, race/ethnicity, menopausal status, TNM stage, cancer treatment, and smoking history. Engaging in at least 10 MET-hours/week of PA was associated with a 27% reduction in all-cause mortality (n = 1,468 events, Hazard Ratio (HR) = 0.73, 95% CI, 0.66-0.82) and a 25% reduction in breast cancer mortality (n = 971 events, HR = 0.75, 95% CI 0.65-0.85) compared with women who did not meet the PA Guidelines (<10 MET-hours/week). Risk of breast cancer recurrence (n = 1,421 events) was not associated with meeting the PA Guidelines (HR = 0.96, 95% CI, 0.86-1.06). These data suggest that adhering to the PA guidelines may be an important intervention target for reducing mortality among breast cancer survivors.

The After Breast Cancer Pooling Project was established to examine the role of physical activity, adiposity, dietary factors, supplement use, and quality of life (QOL) in breast cancer prognosis. This paper presents pooled and harmonized data on post-diagnosis lifestyle factors, clinical prognostic factors, and breast cancer outcomes from four prospective cohorts of breast cancer survivors (three US-based and one from Shanghai, China) for 18,314 invasive breast cancer cases diagnosed between 1976 and 2006. Most participants were diagnosed with stage I-II breast cancer (84.7%). About 60% of breast tumors were estrogen receptor (ER)+/progesterone receptor (PR)+; 21% were ER-/PR-. Among 8,118 participants with information on HER-2 tumor status, 74.8% were HER-2- and 18.5% were HER-2+. At 1-2 years post-diagnosis (on average), 17.9% of participants were obese (BMI ≥ 30 kg/m2), 32.6% were overweight (BMI 25-29 kg/m2), and 59.9% met the 2008 Physical Activity Guidelines for Americans (≥ 2.5 h per week of moderate activity). During follow-up (mean = 8.4 years), 3,736 deaths (2,614 from breast cancer) and 3,564 recurrences have been documented. After accounting for differences in year of diagnosis and timing of post-diagnosis enrollment, five-year overall survival estimates were similar across cohorts. This pooling project of 18,000 breast cancer survivors enables the evaluation of associations of post-diagnosis lifestyle factors, QOL, and breast cancer outcomes with an adequate sample size for investigation of heterogeneity by hormone receptor status and other clinical predictors. The project sets the stage for international collaborations for the investigation of modifiable predictors for breast cancer outcomes.

Background: Although cigarette smoking, excessive alcohol drinking, obesity, and several other well-studied unhealthy lifestyle-related factors each have been linked to the risk of multiple chronic diseases and premature death, little is known about the combined impact on mortality outcomes, in particular among Chinese and other non-Western populations. The objective of this study was to quantify the overall impact of lifestyle-related factors beyond that of active cigarette smoking and alcohol consumption on all-cause and cause-specific mortality in Chinese women., Methods and Findings: We used data from the Shanghai Women's Health Study, an ongoing population-based prospective cohort study in China. Participants included 71,243 women aged 40 to 70 years enrolled during 1996-2000 who never smoked or drank alcohol regularly. A healthy lifestyle score was created on the basis of five lifestyle-related factors shown to be independently associated with mortality outcomes (normal weight, lower waist-hip ratio, daily exercise, never exposed to spouse's smoking, higher daily fruit and vegetable intake). The score ranged from zero (least healthy) to five (most healthy) points. During an average follow-up of 9 years, 2,860 deaths occurred, including 775 from cardiovascular disease (CVD) and 1,351 from cancer. Adjusted hazard ratios for mortality decreased progressively with an increasing number of healthy lifestyle factors. Compared to women with a score of zero, hazard ratios (95% confidence intervals) for women with four to five factors were 0.57 (0.44-0.74) for total mortality, 0.29 (0.16-0.54) for CVD mortality, and 0.76 (0.54-1.06) for cancer mortality. The inverse association between the healthy lifestyle score and mortality was seen consistently regardless of chronic disease status at baseline. The population attributable risks for not having 4-5 healthy lifestyle factors were 33% for total deaths, 59% for CVD deaths, and 19% for cancer deaths., Conclusions: In this first study, to our knowledge, to quantify the combined impact of lifestyle-related factors on mortality outcomes in Chinese women, a healthier lifestyle pattern-including being of normal weight, lower central adiposity, participation in physical activity, nonexposure to spousal smoking, and higher fruit and vegetable intake-was associated with reductions in total and cause-specific mortality among lifetime nonsmoking and nondrinking women, supporting the importance of overall lifestyle modification in disease prevention. Please see later in the article for the Editors' Summary.