Recent therapeutic trends and promising targets in triple negative breast cancer.

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.

/pdf/association-of-obesity-with-breast-cancer-outcome-in-1vk5ntjxh6.pdf

Association of Obesity With Breast Cancer Outcome in Relation to Cancer Subtypes: A Meta-Analysis.

Background
Obesity may negatively affect survival in breast cancer (BC), but studies are conflicting, and associations may vary by tumor subtypes and race/ethnicity groups.

/pdf/obesity-and-survival-in-the-neoadjuvant-breast-cancer-75xgjyxz1h.pdf

Obesity and survival in the neoadjuvant breast cancer setting: role of tumor subtype in an ethnically diverse population.

Previous evidence on postdiagnosis body fatness and mortality after breast cancer was graded as limited‐suggestive. To evaluate the evidence on body mass index (BMI), waist circumference, waist‐hip‐ratio and weight change in relation to breast cancer prognosis, an updated systematic review was conducted. PubMed and Embase were searched for relevant studies published up to 31 October, 2021. Random‐effects meta‐analyses were conducted to estimate summary relative risks (RRs). The evidence was judged by an independent Expert Panel using pre‐defined grading criteria. One randomized controlled trial and 225 observational studies were reviewed (220 publications). There was strong evidence (likelihood of causality: probable) that higher postdiagnosis BMI was associated with increased all‐cause mortality (64 studies, 32 507 deaths), breast cancer‐specific mortality (39 studies, 14 106 deaths) and second primary breast cancer (11 studies, 5248 events). The respective summary RRs and 95% confidence intervals per 5 kg/m2 BMI were 1.07 (1.05‐1.10), 1.10 (1.06‐1.14) and 1.14 (1.04‐1.26), with high between‐study heterogeneity (I2 = 56%, 60%, 66%), but generally consistent positive associations. Positive associations were also observed for waist circumference, waist‐hip‐ratio and all‐cause and breast cancer‐specific mortality. There was limited‐suggestive evidence that postdiagnosis BMI was associated with higher risk of recurrence, nonbreast cancer deaths and cardiovascular deaths. The evidence for postdiagnosis (unexplained) weight or BMI change and all outcomes was graded as limited‐no conclusion. The RCT showed potential beneficial effect of intentional weight loss on disease‐free‐survival, but more intervention trials and well‐designed observational studies in diverse populations are needed to elucidate the impact of body composition and their changes on breast cancer outcomes.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ijc.34322

Postdiagnosis body fatness, weight change and breast cancer prognosis: Global Cancer Update Program (CUP global) systematic literature review and meta‐analysis

Neoadjuvant chemotherapy (NAC) of breast cancer (BC) improves outcomes, especially in patients with locally advanced and inflammatory cancer. Further insight into clinic-pathological factors influencing outcomes is essential to define the optimal therapeutic strategy for each category of patients and to predict the response to the treatment. In total, 117 patients with BC were treated with NAC with or without trastuzumab between 2010 and 2015. The histologic response to NAC was defined as a pathological complete response (pCR) when there was no evidence of residual invasive tumor in the breast or axillary lymph nodes. Relapse-free survival (RFS) was estimated using the Kaplan-Meier method and compared using log rank analysis. P-value <0.05 was considered statistically significant. The median age of the 117 patients enrolled in the present study was 52 years (age range, 35-85 years). The overall response rate (complete and partial responses) assessed by radiological and pathological evaluation were 76 and 72%, respectively. pCR was achieved in 35 out of 117 patients (~30%). In total, 6 patients (5%) developed progressive disease during chemotherapy. The RFS was 85 months (SE=3; 95% CI 79-91). The median was not reached and the mean follow-up time was 55 months (median 52 months; range 11-100 months). In this time, 20 patients (17%) experienced tumor recurrence. From the univariate analysis, the pathological response was significantly associated with receptor-based subtype, menopausal status and T-stage. From the multivariate analysis by using linear multiple regression and including receptor- menopausal status and T-stage, the model was not significant (P=0.062). However, by using the multiple logistic regression, and including age, pCR was significantly associated with ER+ HER2neg (P=0.006), T2 (P=0.043) and T3 (P=0.018). T-stage, menopausal status and receptor status are significantly associated with the pathological response in patients with inoperable BC treated with NAC.

/pdf/clinical-and-pathological-factors-predictive-of-response-to-4iljf2dya3.pdf

Clinical and pathological factors predictive of response to neoadjuvant chemotherapy in breast cancer: A single center experience

Capecitabine has been studied as a radiosensitizer, and our study seeks to examine the association of concurrent capecitabine/radiation therapy (RT) on event-free- (EFS) and overall survival (OS) in women with breast cancer (BC) with residual disease after neoadjuvant chemotherapy (NAC). In a retrospective study of women with BC who received adriamycin/taxane-based NAC from 2004–2016, we identified 21 women administered concurrent capecitabine/RT. To assess differences in survival, we selected a clinical control cohort (n = 57) based on criteria used to select patients for capecitabine/RT. We also created a matched cohort (2:1), matching on tumor subtype, pathological stage and age (< 50 or 50+ years). Differences in EFS, using STEEP criteria, and OS, using all-cause mortality, between those who received capecitabine/RT and controls were assessed. Of the 21 women who received capecitabine/RT, median age was 52 years. The majority were pathologic stage III (n = 15) and hormone receptor-positive/HER2-negative BC (n = 20). In those receiving capecitabine/RT, there were 9 events, compared with 14 events in clinical and 10 events in matched controls. Capecitabine/RT was associated with worse OS in clinical (HR 3.83 95% CI 1.12–13.11, p = 0.03) and matched controls (HR 3.71 95% CI 1.04–13.18, p = 0.04), after adjusting for clinical size, pathological stage and lymphovascular invasion. Capecitabine/RT was also associated with a trend towards worse EFS in clinical (HR 2.41 95% CI 0.86–6.74, p = 0.09) and matched controls (HR 2.68 95% CI 0.91–7.90, p = 0.07) after adjustment. Concurrent capecitabine/RT after NAC is associated with worse survival and should be carefully considered in BC.

Concurrent use of capecitabine with radiation therapy and survival in breast cancer (BC) after neoadjuvant chemotherapy

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Obesity and survival in the neoadjuvant breast cancer setting: role of tumor subtype in an ethnically diverse population.

Concurrent use of capecitabine with radiation therapy and survival in breast cancer (BC) after neoadjuvant chemotherapy