Shlomit S. Shachar

Body Composition as a Predictor of Toxicity in Patients Receiving Anthracycline and Taxane Based Chemotherapy for Early Stage Breast Cancer.

Purpose: Poor body composition metrics (BCM) are associated with inferior cancer outcomes; however, in early breast cancer (EBC), there is a paucity of evidence regarding the impact of BCM on toxicities. This study investigates associations between BCM and treatment-related toxicity in patients with EBC receiving anthracyclines and taxane–based chemotherapy. Experimental Design: Pretreatment computerized tomographic (CT) images were evaluated for skeletal muscle area (SMA), skeletal muscle density (SMD), and fat tissue at the third lumbar vertebrae. Skeletal muscle index (SMI = SMA/height2) and skeletal muscle gauge (SMG = SMI × SMD) were also calculated. Relative risks (RR) are reported for associations between body composition measures and toxicity outcomes, after adjustment for age and body surface area (BSA). Results: BCM were calculated for 151 patients with EBC (median age, 49 years; range, 23–75 years). Fifty patients (33%) developed grade 3/4 toxicity, which was significantly higher in those with low SMI (RR, 1.29; P = 0.002), low SMG (RR, 1.09; P = 0.01), and low lean body mass (RR, 1.48; P = 0.002). Receiver operating characteristic analysis showed the SMG measure to be the best predictor of grade 3/4 toxicity. Dividing SMG into tertiles showed toxicity rates of 46% and 22% for lowest versus highest tertile, respectively (P = 0.005). After adjusting for age and BSA, low SMG (<1,475 units) was significantly associated with hematologic (RR, 2.12; P = 0.02), gastrointestinal grade 3/4 toxicities (RR, 6.49; P = 0.02), and hospitalizations (RR, 1.91; P = 0.05). Conclusions: Poor BCMs are significantly associated with increased treatment-related toxicities. Further studies are needed to investigate how these metrics can be used to more precisely dose chemotherapy to reduce treatment-related toxicity while maintaining efficacy. Clin Cancer Res; 23(14); 3537–43. ©2017 AACR.

Weight gain during adjuvant endocrine treatment for early-stage breast cancer: What is the evidence?

Most breast cancer (BC) tumors are early stage and hormone receptor positive, where treatment generally includes adjuvant endocrine treatment (ET). Oncology providers and women about to start ET want to know about side effects, including potential weight gain. The aim of this study was a literature review to identify the independent effect of ET on post-diagnosis weight gain. Weight gain is of concern with regard to potential associations with BC recurrence, mortality, and quality of life in survivorship. We conducted a targeted review of the literature. Thirty-eight studies met our inclusion criteria. Patient-reported weight gain ranged widely from 18 to 52xa0% of patients in Year 1 and from 7 to 55xa0% in Year 5. Some studies reported categories of weight change: lost weight (9–17xa0%), stable weight (47–64xa0%), and gained weight (27–36xa0%). Most studies comparing ET with placebo or tamoxifen with AI reported no significant difference between the two groups. Wide-ranging and inconsistent results point to the need for further research to clarify annual weight change (loss, gain, stability) from BC diagnosis through 5xa0years of ET and beyond. There is also a need to explore weight change by type of ET and to explore risk factors for weight gain in women on ET, including tumor type, sociodemographic characteristics, and health behaviors. More specific information is needed to identify high-risk BC patients who could be targeted for weight management interventions.

Changing Natural History of HER2–Positive Breast Cancer Metastatic to the Brain in the Era of New Targeted Therapies

Micro‐Abstract Patients with breast cancer brain metastases historically have a poor prognosis. In this single‐institution cohort study of patients with human epidermal growth factor receptor 2 (HER2)‐positive breast cancer brain metastases, we found no improvement in survival after brain recurrence over time despite wide adoption of HER2–targeted therapies. This highlights the importance of continued development of novel brain penetrant therapies for patients with HER2–positive metastatic disease to extend survival and improve quality of life. Background: Given the wide adoption of human epidermal growth factor receptor 2 (HER2)‐targeted therapies for advanced HER2–positive breast cancer, we studied the natural history of patients with HER2–positive breast cancer brain metastases (BCBM) over time. Patients and Methods: Patients with HER2–positive BCBM identified from a prospectively maintained database at the University of North Carolina were divided into 3 cohorts by year of BCBM diagnosis. Cohorts were selected by year of HER2–targeted therapy US Food and Drug Administration approval. Overall survival (OS), time to first metastasis, time to BCBM, and BCBM survival were estimated by the Kaplan‐Meier method. Associations between OS after BCBM and clinical variables were assessed by Cox proportional hazards regression models. Results: One hundred twenty‐three patients were identified. Median age was 51 years, and 58% were white and 31% African American. OS from initial breast cancer diagnosis improved over time: 3.6 years (95% confidence interval [CI], 2.8‐6.1) in the 1998‐2007 cohort, 6.6 years (95% CI, 4.5‐8.6) in the 2008‐2012 cohort, and 7.6 years (95% CI, 4.4‐9.6) in the 2013‐2015 cohort (P = .05). While time from initial diagnosis to first metastasis did not differ (P = .12), time to BCBM increased over time (2.6 years [95% CI, 1.3‐3.5] for 1998‐2007; 2.6 years [95% CI, 2.1‐4.3] for 2008‐2012, and 3.3 years [95% CI, 2.2‐6] for 2013‐2015; P = .05). Although OS from BCBM did not significantly differ by cohort, patients who received HER2–targeted therapy after BCBM had a prolonged OS (2.1 years [95% CI, 1.6‐2.6] vs. 0.65 years [95% CI, 0.4‐1.3]; P = .001). Conclusion: OS from initial breast cancer diagnosis significantly improved over time for patients with HER2–positive breast cancer who develop BCBM, now exceeding 7 years; survival from BCBM diagnosis may now exceed 2 years.

Frailty and skeletal muscle in older adults with cancer

OBJECTIVEnComputerized tomography (CT) imaging is routine in oncologic care and can be used to measure muscle quantity and composition that may improve prognostic assessment of older patients. This study examines the association of single-slice CT-assessed muscle measurements with a frailty index in older adults with cancer.nnnMATERIALS AND METHODSnUsing the Carolina Senior Registry, we identified patients with CT imaging within 60days ± of geriatric assessment (GA). A 36-item Carolina Frailty Index was calculated. Cross-sectional skeletal muscle area (SMA) and Skeletal Muscle Density (SMD) were analyzed from CT scan L3 lumbar segments. SMA and patient height (m2) were used to calculate skeletal muscle index (SMI). Skeletal Muscle Gauge (SMG) was calculated by multiplying SMI×SMD.nnnRESULTSnOf the 162 patients, mean age 73, 53% were robust, 27% pre-frail, and 21% frail. Significant differences were found between robust and frail patients for SMD (29.4 vs 24.1 HU, p<0.001) and SMG (1188 vs 922AU, p=0.003), but not SMI (41.9 vs 39.5cm2/m2, p=0.29). After controlling for age and gender, for every 5 unit decrease in SMD, the prevalence ratio of frailty increased by 20% (PR=1.20 [1.09, 1.32]) while the prevalence of frailty did not differ based on SMI.nnnCONCLUSIONSnMuscle mass (measured as SMI) was poorly associated with a GA-based frailty index. Muscle density, which reflects muscle lipid content, was more associated with frailty. Although frailty and loss of muscle mass are both age-related conditions that are predictive of adverse outcomes, our results suggest they are separate entities.

Letter to the Editor: Integrating Skeletal Muscle Mass and Radiodensity Improves Outcome Prediction and Correlation in Oncologic Studies

JNCCN is committed to providing a forum to enhance collaboration between academic medicine and the community physician. We welcome comments about the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines), articles published in the journal, or any other topic relating to cancer prevention, detection, treatment, supportive care, or survivorship. Please send correspondence to JNCCN.edmgr.com or to JNCCN@nccn.org.

Weight gain in hormone receptor-positive (HR+) early-stage breast cancer: is it menopausal status or something else?

PurposeThis study investigates weight trajectories in pre- versus postmenopausal breast cancer (BC) survivors diagnosed with hormone receptor-positive tumors, with a specific focus on discerning menopausal status and type of endocrine treatment (ET) as risk factors for weight gain during ET.MethodsWe conducted a retrospective review of electronic medical records. Descriptive statistics and Chi-squared and t tests were used to compare pre- and postmenopausal women. Chi-squared tests and ANOVA were used for within-group associations between patient characteristics and weight trajectories. Log-binomial regression models were used to estimate relative risk for weight gain.ResultsThe final sample was 32% premenopausal (nxa0=xa0140) and 68% postmenopausal (nxa0=xa0298). Relative risk (RR) for weight gain during ET was highest in women who were premenopausal (RRxa0=xa01.29, 1.03–1.52) and had Stage 3 BC (RRxa0=xa02.12, 1.59–2.82), mastectomy (RRxa0=xa01.49, 1.19–1.88), axillary node dissection (RRxa0=xa01.39, 1.11–1.73), and chemotherapy (RRxa0=xa01.80, 1.37–2.36). For each kg of weight gained between BC diagnosis and start of ET, and for each additional year of age, RR of gaining weight during ET decreased (RRxa0=xa00.98, 0.97–0.99, and RRxa0=xa00.99, 0.98–0.99, respectively). Menopausal status and type of ET were not significant predictors of weight gain. In multivariable analysis, only weight loss between BC diagnosis and start of ET was significant.ConclusionThe association of weight loss prior to ET and subsequent substantial weight gain during ET warrants further investigation.