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Importance: Metformin, a biguanide commonly used to treat type 2 diabetes, has been associated with potential beneficial effects across breast cancer subtypes in observational and preclinical studies.Objective: To determine whether the administration of adjuvant metformin (vs placebo) to patients with breast cancer without diabetes improves outcomes.Design, Setting, and Participants: MA.32, a phase 3 randomized, placebo-controlled, double-blind trial, conducted in Canada, Switzerland, US, and UK, enrolled 3649 patients with high-risk nonmetastatic breast cancer receiving standard therapy between August 2010 and March 2013, with follow-up to October 2020.Interventions: Patients were randomized (stratified for hormone receptor [estrogen receptor and/or progesterone receptor {ER/PgR}] status, positive vs negative; body mass index, ≤30 vs >30; human epidermal growth factor receptor 2 [ERBB2, formerly HER2 or HER2/neu], positive vs negative; and any vs no chemotherapy) to 850 mg of oral metformin twice a day (n = 1824) or oral placebo twice a day (n = 1825) for 5 years.Main Outcomes and Measures: The primary outcome was invasive disease-free survival in hormone receptor-positive breast cancer. Of the 8 secondary outcomes, overall survival, distant relapse-free survival, and breast cancer-free interval were analyzed.Results: Of the 3649 randomized patients (mean age, 52.4 years; 3643 women [99.8%]), all (100%) were included in analyses. After a second interim analysis, futility was declared for patients who were ER/PgR-, so the primary analysis was conducted for 2533 patients who were ER/PgR+. The median duration of follow-up in the ER/PgR+ group was 96.2 months (range, 0.2-121 months). Invasive disease-free survival events occurred in 465 patients who were ER/PgR+. The incidence rates for invasive disease-free survival events were 2.78 per 100 patient-years in the metformin group vs 2.74 per 100 patient-years in the placebo group (hazard ratio [HR], 1.01; 95% CI, 0.84-1.21; P = .93), and the incidence rates for death were 1.46 per 100 patient-years in the metformin group vs 1.32 per 100 patient-years in the placebo group (HR, 1.10; 95% CI, 0.86-1.41; P = .47). Among patients who were ER/PgR-, followed up for a median of 94.1 months, incidence of invasive disease-free survival events was 3.58 vs 3.60 per 100 patient-years, respectively (HR, 1.01; 95% CI, 0.79-1.30; P = .92). None of the 3 secondary outcomes analyzed in the ER/PgR+ group had statistically significant differences. Grade 3 nonhematological toxic events occurred more frequently in patients taking metformin than in patients taking placebo (21.5% vs 17.5%, respectively, P = .003). The most common grade 3 or higher adverse events in the metformin vs placebo groups were hypertension (2.4% vs 1.9%), irregular menses (1.5% vs 1.4%), and diarrhea (1.9% vs 7.0%).Conclusions and Relevance: Among patients with high-risk operable breast cancer without diabetes, the addition of metformin vs placebo to standard breast cancer treatment did not significantly improve invasive disease-free survival.Trial Registration: ClinicalTrials.gov Identifier: NCT01101438. [ABSTRACT FROM AUTHOR]

Background: Obesity at breast cancer (BC) diagnosis has been associated with poor outcome, although the magnitude of effect in different BC subtypes is uncertain. We report on the association of obesity or overweight at diagnosis of nonmetastatic BC with disease-free (DFS) and overall survival (OS) in the following defined subtypes: hormone receptor positive/HER2 negative (HR+HER2-), HER2 positive (HER2+), and triple negative (TNBC).Methods: We searched MEDLINE, EMBASE, and COCHRANE databases up to January 1, 2019. Study eligibility was performed independently by 2 authors. Studies reporting hazard ratios (HRs) of OS and/or DFS for obesity or overweight in BC subtypes were included. The pooled hazard ratio was computed and weighted using generic inverse variance and random effects models.Results: Twenty-seven studies were included. Obese compared with nonobese women had worse DFS in all subtypes: the hazard ratios were 1.26 (95% confidence interval [CI] = 1.13 to 1.41, P < .001) for HR+HER2- BC, 1.16 (95% CI = 1.06 to 1.26, P < .001) for HER2+ BC, and 1.17 (95% CI = 1.06 to 1.29, P = .001) for TNBC. OS was also worse in obese vs nonobese women (HR+HER2- BC HR = 1.39, 95% CI = 1.20 to 1.62, P < .001; HER2+ BC HR = 1.18, 95% CI = 1.05 to 1.33, P = .006; and TNBC HR = 1.32, 95% CI = 1.13 to 1.53, P < .001). As opposed to obesity, overweight was not associated with either DFS or OS in HER2+ BC (HR = 1.02, 95% CI = 0.81 to 1.28, P = .85; and HR = 0.96, 95% CI = 0.76 to 1.21, P = .99, respectively) or TNBC (HR = 1.04, 95% CI = 0.93 to 1.18, P = .49; and HR = 1.08, 95% CI = 0.81 to 1.44, P = .17), respectively. In HR+HER2- BC, being overweight was associated with worse OS (HR = 1.14, 95% CI = 1.07 to 1.22, P < .001).Conclusions: Obesity was associated with modestly worse DFS and OS in all BC subtypes. [ABSTRACT FROM AUTHOR]

Abstract: A number of validated and objectively based prognostic models are available for use in cancer care. The quest for additional prognostic factors continues in order to increase their accuracy. To date, none has considered the effect that wounds may contribute to assessing survival. This study serves to demonstrate that certain wound classes affecting cancer patients carry associations with survival. As a prospective observational study, based on a sequential case series of 418 advanced cancer patients, all cutaneous and wound issues were documented and monitored. Three hundred and seventy seven patients were followed until their deaths. Univariate and multivariate survival analyses were performed using hazard ratios (HRs) derived from Cox-proportional hazard models. Forty-four percent of patients presented with at least one wound at referral. Patients with wounds displayed worse overall survival than those without wounds (p ⩽0.0001). A significant interaction was seen between pressure ulcers (PU’s) and sex (p =0.0005). After controlling for the co-occurrence of wounds, age, sex, Charlson comorbidity index and PPSv2, statistically significant increased risk of death was observed for female patients with PU’s (HR 2.00, p =0.0002), but not for males with PU’s (HR 0.83, p =0.328). Malignant wounds were not associated with decreased survival (HR 1.17, p =0.285). The presence of all other wounds was associated with decreased survival (HR 1.48, p =0.002). In summary, the presence of PU’s in female cancer patients and ‘other’ wounds in all cancer patients correlates with reduced survival. Therefore, this data should be incorporated into existing prognostic models or used in conjunction with them in order to enhance prognostic accuracy. [Copyright &y& Elsevier]