Background The objective of this study was to evaluate the role of a 12‐month exercise intervention on endocrine‐related quality of life (QOL) and overall QOL among breast cancer survivors with aromatase inhibitor (AI)‐induced arthralgia in the Hormones and Physical Exercise (HOPE) Study. Methods This was a randomized controlled trial of 121 breast cancer survivors who were currently receiving AIs and experiencing at least mild arthralgia. QOL was assessed using the Functional Assessment of Cancer Therapy (FACT) questionnaires and the 36‐Item Short Form Survey (SF‐36) at baseline, 6 months, and 12 months. Participants were randomized to either a 1‐year gym‐based, supervised exercise intervention group (150 minutes of aerobic exercise and 2 strength‐training sessions each week) or a usual care group. Effects of the intervention on QOL were assessed using mixed‐model, repeated‐measures analysis. Results At 12 months, the exercise group had greater improvement in the overall QOL measures as well as the breast cancer‐specific (scores, 2.2 vs 0.7; P = .02), endocrine‐specific (scores, 5.6 vs 1.6; P < .001), and fatigue‐specific (score, 5.8 vs 0.5; P < .001) subscales compared with the usual care group. The results indicated a stronger effect at 12 months versus 6 months after the intervention. Conclusions Combined aerobic and resistance exercise, such as treadmill walking and strength training, improved endocrine‐related and overall QOL among breast cancer survivors who were experiencing adverse side effects from AIs. Because adverse side effects associated with AI use are quite common and this is the main reason for treatment discontinuation, this nonpharmacologic intervention could benefit many breast cancer survivors and increase successful adherence to AIs in breast cancer treatment.

Soy-food intake has previously been associated with reduced breast cancer risk. Epidemiological evidence for subgroups of breast cancer, particularly by menopausal and hormone receptor status, is less consistent. To evaluate the role of hormone receptor and menopausal status on the association between soy-food intake and breast cancer risk, we measured usual soy-food intake in adolescence and adulthood via food frequency questionnaire in 70,578 Chinese women, aged 40-70 years, recruited to the Shanghai Women’s Health Study (1996-2000). After a median follow-up of 13.2 years (range:0.01-15.0), 1,034 incident breast cancer cases were identified. Using Cox models, we found that adult soy intake was inversely associated with breast cancer risk (hazard ratio-HR) for fifth versus first quintile soy protein intake=0.78; 95% confidence interval (CI):0.63-0.97). The association was predominantly seen in premenopausal women (HR=0.46; 95% CI:0.29-0.74). Analyses further stratified by hormone receptor status showed that adult soy intake was associated with significantly decreased risk of ER+/PR+ breast cancer in postmenopausal women (HR=0.72; 95% CI:0.53-0.96) and decreased risk of ER−/PR− breast cancer in premenopausal women (HR=0.46; 95% CI:0.22-0.97). The soy association did not vary by HER2 status. Furthermore, we found that high soy intake during adulthood and adolescence was associated with reduced premenopausal breast cancer risk (HR=0.53; 95% CI:0.32-0.88; comparing third versus first tertile) while high adulthood soy intake was associated with postmenopausal breast cancer only when adolescent intake was low (HR=0.63; 95% CI:0.43-0.91). Our study suggests that hormonal status, menopausal status, and time window of exposure are important factors influencing the soy-breast cancer association.

Purpose Triple-negative breast cancer (TNBC) is an aggressive cancer with limited treatment options. Dual specificity phosphatase 4 (DUSP4) has recently been suggested as a potential marker of chemotherapy resistance for TNBC. Methods DUSP4 gene expression levels were measured in breast cancer tissue from 469 TNBC patients aged 20 to 75 years who participated in the Shanghai Breast Cancer Survival Study and their association with recurrence/breast cancer mortality and total mortality was evaluated. Information on breast cancer diagnosis, treatment, and disease progression was collected via medical chart review and multiple in-person follow-up surveys. A Cox regression model was applied in the data analyses. Results Over a median follow-up of 5.3 years (range: 0.7-8.9 years), 100 deaths and 92 recurrences/breast cancer deaths were documented. Expression levels of transcript variant 1 (NM_001394) and transcript variant 2 (NM_057158) of the DUSP4 gene were studied and were highly correlated (r=0.76). Low DUSP4 expression levels, particularly of variant 1, were associated with both increased recurrence/breast cancer mortality and increased overall mortality. Hazard ratios with adjustment for age at diagnosis and TNM stage associated with below versus above the median expression level were 1.97 (95% confidence interval (CI): 1.27-3.05) for recurrence/breast cancer mortality and 2.09 (95% CI: 1.38-3.17) for overall mortality. Additional adjustment for expression levels of MKI67 and TP53, common treatment types, breast cancer subtype, and grade did not materially alter the observed associations. Conclusions Low DUSP4 expression levels predict recurrence and mortality in TNBC patients independently from known clinical and molecular predictors.

Metformin was associated with improved survival among colorectal cancer cases, while insulin use was associated with worse survival among patients of four major cancers. Further investigation on the topic is needed given the potential translational impact of these findings.

ALDH1 is a crucial element in the retinoic acid signaling pathway regulating the self-renewal and differentiation of normal stem cells, and may play an important role in cancer progression. However, research on ALDH1 gene expressionand breast cancer prognosis has yielded conflicting results. We evaluated the association between tumor tissue ALDH1A1/ALDH1A3 mRNA expression and triple-negative breast cancer (TNBC) prognosis in the Shanghai Breast Cancer Survival Study (SBCSS, N=463), Nashville Breast Health Study (NBHS, N=86), and Southern Community Cohort Study (SCCS, N=47). Gene expression was measured in RNA isolated from breast cancer tissues. In the SBCSS, higher ALDH1A1 mRNA level was associated with improved disease-free (HR=0.87, 95% CI: 0.80-0.95, per log unit change) and overall survival (HR=0.85, 95% CI: 0.78-0.93 per log unit change) independent of age at diagnosis, TNM stage and treatment. We replicated the findings for overall survival in the NBHS and SCCS (HR = 0.27, 95% CI: 0.10-0.73) and for disease-free survival by a meta-analysis of four publicly-available gene expression datasets (HR = 0.86, 95% CI: 0.76-0.97). No significant association was found for ALDH1A3. Our study suggests high expression of ALDH1A1 mRNA in tumor tissues may be an independent predictor of a favorable TNBC outcome.