The relationship between body composition and response to neoadjuvant chemotherapy in women with operable breast cancer.
Del Fabbro Egidio,Parsons Henrique,Warneke Carla L,Pulivarthi Kalyan,Litton Jennifer K,Dev Rony,Palla Shana L,Brewster Abenaa,Bruera Eduardo
The oncologist
INTRODUCTION:Overweight women diagnosed with breast cancer have greater recurrence and mortality risks. Recent studies in advanced cancer showed that the combination of sarcopenia and an overweight or obese body mass index (BMI) is associated with poor clinical outcomes. OBJECTIVES:To compare pathological complete response (pCR) cases with controls and evaluate associations among a pCR, survival outcome, and sarcopenia as well as the combination of both sarcopenia and a BMI ≥25 kg/m(2). METHODS:Sixty-seven breast cancer patients with a pCR to neoadjuvant chemotherapy (NC) were matched with controls who did not have a pCR to NC. Patients were matched by age, Black's nuclear grading system, clinical cancer stage, and estrogen receptor and progesterone receptor status. Body composition was analyzed using computed tomography images taken prior to NC. RESULTS:BMI was associated with pCR. Among normal weight patients, the pCR rate was higher in sarcopenic patients and the progression-free survival (PFS) interval was significantly longer than in overweight or obese BMI patients. The death hazard was 2% higher for each unit higher skeletal muscle index and 0.6% higher for each unit higher visceral adipose tissue. CONCLUSIONS:Overweight patients treated with NC had a lower pCR rate and shorter PFS time. Among patients with a normal BMI, the pCR rate was better in sarcopenic patients. More research is required to evaluate the negative impact of sarcopenic obesity on prognosis and the contributors to better response rates in operable, normal weight breast cancer patients with sarcopenia.
10.1634/theoncologist.2012-0169
Skeletal Muscle Measures as Predictors of Toxicity, Hospitalization, and Survival in Patients with Metastatic Breast Cancer Receiving Taxane-Based Chemotherapy.
Shachar Shlomit Strulov,Deal Allison M,Weinberg Marc,Nyrop Kirsten A,Williams Grant R,Nishijima Tomohiro F,Benbow Julia M,Muss Hyman B
Clinical cancer research : an official journal of the American Association for Cancer Research
PURPOSE:Severe skeletal muscle (SM) loss (sarcopenia) is associated with poor cancer outcomes, including reduced survival and increased toxicity. This study investigates SM measures in metastatic breast cancer (MBC) patients receiving first-line taxane-based chemotherapy and evaluates associations with treatment toxicity and other outcomes. EXPERIMENTAL DESIGN:Using computerized tomography (CT) images taken for the evaluation of disease burden, skeletal muscle area (SMA), and density (SMD) were measured at the third lumbar vertebrae. Sarcopenia was defined as skeletal muscle index (SMI = SMA/height) ≤ 41. Skeletal muscle gauge (SMG) was created by multiplying SMI × SMD. Fisher exact tests, t tests, the Kaplan-Meier method, and Cox regression modeling were used. RESULTS:MBC patients (N = 40), median age 55 (range, 34-80), 58% sarcopenic, median SMG 1296 AU (SD, 522). Grade 3-4 toxicity was found in 57% of sarcopenic versus 18% of non-sarcopenic patients (P = 0.02). Toxicity-related hospitalizations were also higher in sarcopenic patients (39% vs. 0%, P = 0.005) as were any adverse events-defined as any grade 3-4 toxicities, hospitalizations, dose reductions, or dose delay-(74% vs. 35%, P = 0.02). Low SMG was associated with grade 3-4 toxicity (P = 0.04), hospitalization (P = 0.01), and time to treatment failure (for progression or toxicity; P = 0.03). Low SMG had a borderline significant association with any adverse event (P = 0.06) and overall survival (P = 0.07). CONCLUSIONS:SM measures are associated with toxicity outcomes and survival in MBC patients receiving first-line taxane-based chemotherapy. Further studies are needed to explore how routinely obtained CT scans can be used to individualize dosing and improve treatment planning. Clin Cancer Res; 23(3); 658-65. ©2016 AACR.
10.1158/1078-0432.CCR-16-0940
Low muscle attenuation is a prognostic factor for survival in metastatic breast cancer patients treated with first line palliative chemotherapy.
Rier Hánah N,Jager Agnes,Sleijfer Stefan,van Rosmalen Joost,Kock Marc C J M,Levin Mark-David
Breast (Edinburgh, Scotland)
BACKGROUND:Low muscle mass (LMM) and low muscle attenuation (LMA) reflect low muscle quantity and low muscle quality, respectively. Both are associated with a poor outcome in several types of solid malignancies. This study determined the association of skeletal muscle measures with overall survival (OS) and time to next treatment (TNT). PATIENTS AND METHODS:A skeletal muscle index (SMI) in cm/m and muscle attenuation (MA) in Hounsfield units (HU) were measured using abdominal CT-images of 166 patients before start of first-line chemotherapy for metastatic breast cancer. Low muscle mass (SMI <41 cm/m), sarcopenic obesity (LMM and BMI ≥30 kg/m) and low muscle attenuation (MA <41 HU and BMI <25 kg/m2 or MA <33 HU and BMI ≥25 kg/m2) were related to OS and TNT. RESULTS:The prevalence of LMM, sarcopenic obesity and LMA were 66.9%, 7.2% and 59.6% respectively. LMM and sarcopenic obesity showed no significant association with OS and TNT, whereas LMA was associated with both lower OS (HR 2.04, 95% CI 1.34-3.12, p = 0.001) and shorter TNT (HR 1.72, 95% CI 1.14-2.62, p = 0.010). Patients with LMA had a median OS and TNT of 15 and 8 months respectively, compared to 23 and 10 months in patients with normal MA. CONCLUSION:LMA is a prognostic factor for OS and TNT in metastatic breast cancer patients receiving first-line palliative chemotherapy, whereas LMM and sarcopenic obesity are not. Further research is needed to establish what impact LMA should have in daily clinical practice.
10.1016/j.breast.2016.10.014
Muscle mass estimation on breast magnetic resonance imaging in breast cancer patients: comparison between psoas muscle area on computer tomography and pectoralis muscle area on MRI.
Rossi Federica,Valdora Francesca,Barabino Emanuele,Calabrese Massimo,Tagliafico Alberto Stefano
European radiology
OBJECTIVES:To evaluate the correlation between psoas muscle area (TPA) on CT images and pectoralis muscle area (PMA) on MRI in breast cancer patients. METHODS:This retrospective study was institutional review board approved and women involved gave written informed consent. Twenty six patients with both body CT and breast MRI available were evaluated. Two radiologists calculated TPA on 1.25-mm and 5-mm body CT images. Two radiologists measured PMA on axial T1-weighted images. Statistical analysis included inter- and intra-reader agreement and correlation between TPA on CT and PMA on MRI. RESULTS:The Pearson r correlation coefficient was 0.70 (95% CI 0.41-0.81) and the coefficient of determination was 0.49. The inter-reader agreement was k = 0.85 and k = 0.79 for axial 1.25-mm and 5-mm CT images, respectively. The intra-reader agreement of reader 1 was k = 0.98 and k = 0.94 for 1.25-mm and 5-mm CT images, respectively. The intra-reader agreement of reader 2 was k = 0.95 and k = 0.94 for 1.25-mm and 5-mm CT images, respectively. On axial T1-weighted images, the inter-reader agreement for radiologists evaluating the PMA was k = 0.61. Intra-observer agreement of reader 1 and reader 2 for PMA estimation was good (0.62 and 0.64), respectively. CONCLUSION:The correlation between TPA on CT images and PMA on MRI was very good. Pectoralis muscle area on breast MRI could be useful to estimate muscle mass in women with breast cancer. KEY POINTS:• Pectoralis muscle area can be estimated on breast MRI • Total psoas area on CT and pectoralis muscle area on MRI are strongly correlated • Pectoralis muscle area on breast MRI could estimate the skeletal muscle mass.
10.1007/s00330-018-5663-0
Impact of body composition on outcome in patients with early breast cancer.
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer
PURPOSE:We investigated the impact of body composition on outcomes of patients with early breast cancer. Skeletal muscle mass, visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and muscle fat infiltration or inter-muscular adipose tissue areas (IMAT), obtained by computed tomography (CT), were assessed. METHODS:A total of 119 female patients who had breast cancer were included in this retrospective study. The total skeletal muscle and fat tissue areas were evaluated in two adjacent axial slices obtained at the third lumbar vertebra by CT used for disease staging. The women were assigned to either a sarcopenia or non-sarcopenia group based on their skeletal muscle index (cut-off 41.0 cm/m). They also were classified into high and low VAT/SAT ratio groups and assigned to either the high or low IMAT index group. The association of the body composition parameters and prognosis was statistically analyzed. RESULTS:Among the 119 evaluable patients, 58 were sarcopenic (48.8%), 55 (46.2%) had a high VAT/SAT ratio, and 62 (52.1%) had a high IMAT index. Median follow-up was 52.4 months. Multivariate analysis revealed sarcopenia and IMAT index as independent prognostic factors for disease-free survival (p = 0.02 and p = 0.04, respectively) and overall survival (p = 0.05 and p = 0.02, respectively). BMI was not significantly associated with disease-free survival, but a trend was observed (p = 0.09). CONCLUSIONS:Sarcopenia and IMAT index are independent prognostic factors in early breast cancer; therefore, assessing body composition could be a simple and useful approach to integrate into patient management.
10.1007/s00520-017-3902-6
Effects of Aerobic and Resistance Exercise on Metabolic Syndrome, Sarcopenic Obesity, and Circulating Biomarkers in Overweight or Obese Survivors of Breast Cancer: A Randomized Controlled Trial.
Dieli-Conwright Christina M,Courneya Kerry S,Demark-Wahnefried Wendy,Sami Nathalie,Lee Kyuwan,Buchanan Thomas A,Spicer Darcy V,Tripathy Debu,Bernstein Leslie,Mortimer Joanne E
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Purpose Metabolic syndrome is associated with an increased risk of cardiovascular disease, type 2 diabetes, and breast cancer recurrence in survivors of breast cancer. This randomized controlled trial assessed the effects of a 16-week combined aerobic and resistance exercise intervention on metabolic syndrome, sarcopenic obesity, and serum biomarkers among ethnically diverse, sedentary, overweight, or obese survivors of breast cancer. Methods Eligible survivors of breast cancer (N = 100) were randomly assigned to exercise (n = 50) or usual care (n = 50). The exercise group participated in supervised moderate-to-vigorous-65% to 85% of heart rate maximum-aerobic and resistance exercise three times per week for 16 weeks. Metabolic syndrome z-score (primary outcome), sarcopenic obesity, and serum biomarkers were measured at baseline, postintervention (4 months), and 3-month follow-up (exercise only). Results Participants were age 53 ± 10.4 years, 46% were obese, and 74% were ethnic minorities. Adherence to the intervention was 95%, and postintervention assessments were available in 91% of participants. Postintervention metabolic syndrome z-score was significantly improved in exercise versus usual care (between-group difference, -4.4; 95% CI, -5.9 to -2.7; P < .001). Sarcopenic obesity (appendicular skeletal mass index, P = .001; body mass index, P = .001) and circulating biomarkers, including insulin ( P = .002), IGF-1 ( P = .001), leptin ( P = .001), and adiponectin ( P = .001), were significantly improved postintervention compared with usual care. At 3-month follow-up, all metabolic syndrome variables remained significantly improved compared with baseline in the exercise group ( P < .01). Conclusion Combined resistance and aerobic exercise effectively attenuated metabolic syndrome, sarcopenic obesity, and relevant biomarkers in an ethnically diverse sample of sedentary, overweight, or obese survivors of breast cancer. Our findings suggest a targeted exercise prescription for improving metabolic syndrome in survivors of breast cancer and support the incorporation of supervised clinical exercise programs into breast cancer treatment and survivorship care plans.
10.1200/JCO.2017.75.7526
Relationship between Handgrip Strength and Muscle Mass in Female Survivors of Breast Cancer: A Mediation Analysis.
Benavides-Rodríguez Lorena,García-Hermoso Antonio,Rodrigues-Bezerra Diogo,Izquierdo Mikel,Correa-Bautista Jorge Enrique,Ramírez-Vélez Robinson
Nutrients
This study explored the mediating factors of sarcopenia in a group of women survivors of breast cancer in Bogotá, Colombia. This was a descriptive cross-sectional study with 98 women survivors of breast cancer, who were registered with the SIMMON (Integrated Synergies to Improve Oncological Management in Colombia) Foundation. Body weight, height, and waist circumference (WC) were measured, and body mass index (BMI) was calculated. Body composition (percentage of fat and muscle mass) was evaluated via four-pole bioelectrical impedance analysis. Sarcopenia was defined as low muscle mass plus low grip strength or low gait speed (European Working Group on Sarcopenia in Older People (EWGSOP) criteria). A "causal" mediation analysis with the Baron & Kenny procedure (PROCESS macro, Columbus, OH, USA) was used to explore variables related to sarcopenia. Analyses were performed with the IBM SPSS 21 statistical package (SPSS Inc., Chicago, IL, USA). The significance level of the results obtained in the hypothesis contrast was < 0.05. The mean age of the sample was 65.5 ± 5.9 years, with a BMI of 27.8 ± 4.7 kg/m². The prevalence of sarcopenia was 22.4%. Linear regression models suggest a partial mediation of anthropometric parameters (body mass, body mass index and waist circumference) in the association between handgrip strength and muscle mass. In conclusion, one in every five women survivors of breast cancer had sarcopenia. The findings seem to emphasize the importance of obesity prevention in women survivors of breast cancer, suggesting that high handgrip strength may not relate closely to greater muscle mass and therefore would not exclude the risk of sarcopenia.
10.3390/nu9070695
Impact of resistance and aerobic exercise on sarcopenia and dynapenia in breast cancer patients receiving adjuvant chemotherapy: a multicenter randomized controlled trial.
Adams Scott C,Segal Roanne J,McKenzie Donald C,Vallerand James R,Morielli Andria R,Mackey John R,Gelmon Karen,Friedenreich Christine M,Reid Robert D,Courneya Kerry S
Breast cancer research and treatment
The purpose of this study was to conduct an exploratory analysis of the START examining the effects of resistance exercise training (RET) and aerobic exercise training (AET) on sarcopenia, dynapenia, and associated quality of life (QoL) changes in breast cancer (BC) patients receiving adjuvant chemotherapy. Participants were randomized to usual care (UC) (n = 70), AET (n = 64), or RET (n = 66) for the duration of chemotherapy. Measures of sarcopenia [skeletal muscle index (SMI)] and dynapenia [upper extremity (UE) and lower extremity (LE) muscle dysfunction (MD)] were normalized relative to age-/sex-based clinical cut-points. QoL was assessed by the Functional Assessment of Cancer Therapy-Anemia (FACT-An) scales. At baseline, 25.5 % of BC patients were sarcopenic and 54.5 % were dynapenic with both conditions associated with poorer QoL. ANCOVAs showed significant differences favoring RET over UC for SMI (0.32 kg/m(2); p = 0.017), UE-MD (0.12 kg/kg; p < 0.001), and LE-MD (0.27 kg/kg; p < 0.001). Chi-square analyses revealed significant effects of RET, compared to UC/AET combined, on reversing sarcopenia (p = 0.039) and dynapenia (p = 0.019). The reversal of sarcopenia was associated with clinically relevant improvements in the FACT-An (11.7 points [95 % confidence interval (CI) -4.2 to 27.6]), the Trial Outcome Index-Anemia (10.0 points [95 % CI -4.0 to 24.1]), and fatigue (5.3 points [95 % CI -1.5 to 12.1]). Early-stage BC patients initiating adjuvant chemotherapy have higher than expected rates of sarcopenia and dynapenia which are associated with poorer QoL. RET during adjuvant chemotherapy resulted in the reversal of both sarcopenia and dynapenia; however, only the reversal of sarcopenia was associated with clinically meaningful improvements in QoL.
10.1007/s10549-016-3900-2
Prevalence and prognostic effect of sarcopenia in breast cancer survivors: the HEAL Study.
Journal of cancer survivorship : research and practice
PURPOSE:This study aimed to determine the prevalence of sarcopenia and examine whether sarcopenia was associated with overall and breast-cancer-specific mortality in a cohort of women diagnosed with breast cancer (stages I-IIIA). METHODS:A total of 471 breast cancer patients from western Washington State and New Mexico who participated in the prospective Health, Eating, Activity, and Lifestyle Study were included in this study. Appendicular lean mass was measured using dual X-ray absorptiometry scans at study inception, on average, 12 months after diagnosis. Sarcopenia was defined as two standard deviations below the young healthy adult female mean of appendicular lean mass divided by height squared (<5.45 kg/m(2)). Total and breast-cancer-specific mortality data were obtained from Surveillance Epidemiology and End Results registries. Multivariable Cox proportional hazard models assessed the associations between sarcopenia and mortality. RESULTS:Median follow-up was 9.2 years; 75 women were classified as sarcopenic, and among 92 deaths, 46 were attributed to breast cancer. In multivariable models that included age, race-ethnicity/study site, treatment type, comorbidities, waist circumference, and total body fat percentage, sarcopenia was independently associated with overall mortality (hazard ratio (HR) = 2.86; 95 % CI, 1.67-4.89). Sarcopenic women had increased risk of breast-cancer-specific mortality, although the association was not statistically significant (HR = 1.95, 95 % CI, 0.87-4.35). CONCLUSION:Sarcopenia is associated with an increased risk of overall mortality in breast cancer survivors and may be associated with breast-cancer-specific mortality. The development of effective interventions to maintain and/or increase skeletal muscle mass to improve prognosis in breast cancer survivors warrants further study. IMPLICATIONS FOR CANCER SURVIVORS:Such interventions may help breast cancer patients live longer.
10.1007/s11764-012-0234-x
Association of Muscle and Adiposity Measured by Computed Tomography With Survival in Patients With Nonmetastatic Breast Cancer.
Caan Bette J,Cespedes Feliciano Elizabeth M,Prado Carla M,Alexeeff Stacey,Kroenke Candyce H,Bradshaw Patrick,Quesenberry Charles P,Weltzien Erin K,Castillo Adrienne L,Olobatuyi Taiwo A,Chen Wendy Y
JAMA oncology
Importance:Sarcopenia (low muscle mass), poor muscle quality (low muscle radiodensity), and excess adiposity derived from computed tomography (CT) has been related to higher mortality in patients with metastatic breast cancer, but the association with prognosis in patients with nonmetastatic breast cancer is unknown. Objective:To evaluate associations of all 3 body composition measures, derived from clinically acquired CT at diagnosis, with overall mortality in nonmetastatic breast cancer. Design, Setting, and Participants:This observational study included 3241 women from Kaiser Permanente of Northern California and Dana Farber Cancer Institute diagnosed from January 2000 to December 2013 with stages II or III breast cancer. We calculated hazard ratios (HRs) to evaluate the associations of all-cause mortality with sarcopenia, low muscle radiodensity, and total adipose tissue (TAT). Models were adjusted for sociodemographics, tumor characteristics, treatment, body mass index (BMI; calculated as weight in kilograms divided by height in meters squared), and other body composition measures. We also evaluated the cross-classification of categories of sarcopenia (yes/no) and tertiles of TAT, with outcomes. Main Outcomes and Measures:Overall survival time and all-cause mortality. Results:Median (range) age of 3241 women included in this study was 54 (18-80) years, and median follow-up was 6.0 years; 1086 patients (34%) presented with sarcopenia, and 1199 patients (37%) had low muscle radiodensity. Among patients with nonmetastatic breast cancer, those with sarcopenia showed higher overall mortality (HR, 1.41; 95% CI, 1.18-1.69) compared with those without sarcopenia. Patients in the highest tertile of TAT also showed higher overall mortality (HR, 1.35; 95% CI, 1.08-1.69) compared with those in the lowest tertile. Low radiodensity was not associated with survival. In analyses of sarcopenia and TAT, highest mortality was seen in patients with sarcopenia and high TAT (HR, 1.89; 95% CI, 1.30-2.73); BMI alone was not significantly related to overall mortality and did not appropriately identify patients at risk of death owing to their body composition. Conclusions and Relevance:Sarcopenia is underrecognized in nonmetastatic breast cancer and occurs in over one-third of newly diagnosed patients. Measures of both sarcopenia and adiposity from clinically acquired CT scans in nonmetastatic patients provide significant prognostic information that outperform BMI and will help to guide interventions to optimize survival outcomes.
10.1001/jamaoncol.2018.0137
Evaluation of body Computed Tomography-determined sarcopenia in breast cancer patients and clinical outcomes: A systematic review.
Rossi Federica,Valdora Francesca,Bignotti Bianca,Torri Lorenzo,Succio Giulia,Tagliafico Alberto Stefano
Cancer treatment and research communications
PURPOSE:Sarcopenia has been considered a poor prognostic factor in various malignant diseases. However, the studies that evaluated the association between CT-determined sarcopenia and outcome in breast cancer patients reported different results. Therefore, the aim of the present study is to perform a systematic review of the current literature on the evaluation of body CT-determined sarcopenia in breast cancer patients, focusing on the correlation with outcome values. METHODS:Two reviewers evaluated independently all studies dealing with CT-determined sarcopenia in breast cancer women from major medical libraries up to 24 April 2019. The keywords used for database searching were: "sarcopenia" or "muscles" or "muscle weight" or "body composition" and "breast neoplasms" or "breast cancer" and "computed tomography". Studies reporting clinical outcome values were finally compared. RESULTS:Of the n = 191 studies identified, a total of n = 15 articles were included in the systematic review. In all studies, sarcopenia was assessed at the level of the third lumbar vertebra (L3) on CT; n = 14/15 studies were retrospective. N = 13/15 studies evaluated the impact of sarcopenia on clinical outcomes. Among these studies, n = 8/13 studies concluded that sarcopenia is an important risk factor for poor prognosis in breast cancer and n = 5/13 studies concluded that body composition changes are not associated with poor prognosis. CONCLUSIONS:Most studies concluded that sarcopenia assessed on CT is an important prognostic risk factor in breast cancer patients. High-quality prospective studies to strongly confirm and assess the impact of sarcopenia evaluated on CT and breast cancer outcome are needed.
10.1016/j.ctarc.2019.100154
Muscle composition and outcomes in patients with breast cancer: meta-analysis and systematic review.
Aleixo G F P,Williams G R,Nyrop K A,Muss H B,Shachar S S
Breast cancer research and treatment
PURPOSE:Breast cancer is the most common cancer and leading cause of cancer death in women. Body composition parameters, especially those related to muscle, have become a growing focus of cancer research. In this review, we summarize the literature on breast cancer and muscle parameters as well as combine their outcomes for overall survival (OS), time to tumor progression (TTP), and chemotherapy toxicity in a meta-analysis. METHODS:A systematic search of the literature for randomized controlled trials and observational studies was conducted on MEDLINE, Cochrane CENTRAL, and EMBASE through May 1, 2019. Two reviewers independently searched and selected. Meta-analysis was conducted using a random-effects model. The risk of bias was evaluated using the Newcastle-Ottawa quality assessment for cohorts and GRADE summary of findings tool from Cochrane. RESULTS:A total of 754 articles were screened from which 6 articles and one abstract were selected. Using skeletal muscle index (SMI), patients classified as sarcopenic had a 68% greater mortality risk compared to non-sarcopenic patients (HR 1.68 95% CI 1.09-2.59, 5 studies) (p = .02) (i = 70%). Low muscle density was not predictive of OS (HR 1.44 95% CI 0.77-2.68, 2 studies) (p = .25) (i = 87%). Patients with sarcopenia (56%) had more grade 3-5 toxicity compared to non-sarcopenic (25%) (RR 2.17 95% CI 1.4-3.34, 3 studies) (p = .0005) (i = 0%). TTP was nearly 71 days longer in advanced/metastatic patients classified as non-sarcopenic compared to patients with sarcopenia (MD - 70.75 95% CI - 122.32 to - 19.18) (p = .007) (i = 0%). CONCLUSION:Our synthesis of the literature shows that patients with sarcopenia have more severe chemotherapy toxicity as well as shorter OS and TTP, and that low muscle density is prognostic of OS for women with metastatic breast cancer. Our findings suggest that in clinical practice, body composition assessment is valuable as a prognostic parameter in breast cancer.
10.1007/s10549-019-05352-3
Sarcopenia in Ovarian Cancer Patients, Oncologic Outcomes Revealing the Importance of Clinical Nutrition: Review of Literature.
Cianci Stefano,Rumolo Valerio,Rosati Andrea,Scaletta Giuseppe,Alletti Salvatore Gueli,Cerentini Taís Marques,Sleiman Zaki,Lordelo Patricia,Angerame Daniela,Garganese Giorgia,Uccella Stefano,Tarascio Mattia,Scambia Giovanni
Current pharmaceutical design
INTRODUCTION:Ovarian cancer is the leading cause of death among gynecological malignancies. Its usual clinical manifestation is at advanced stages, with nutritional impairment, weight loss, and a consequent decline in skeletal muscle mass and strength (defined as sarcopenia). The relationship between sarcopenia and decreased survival was demonstrated not only in ovarian cancer but also in other cancer types, such as hepatocellular, pancreatic, lung, colon, cervical, metastatic breast, and renal cancer. The aim of this study is to review the current evidence regarding the relationship between sarcopenia and the surgical and oncological outcomes in ovarian cancer patients. METHODS:The systematic search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRSIMA) statement. The terms "SARCOPENIA" AND "OVARIAN CANCER" were systematically used to search PubMed and Scopus databases. Original reports in English language were identified, with the purpose to include all relevant papers regarding the role of sarcopenia and indicators of skeletal muscle quality assessment in gynecological ovarian cancer. RESULTS:A total of 9 studies were considered eligible for the present review. The strength of recommendation was moderate and the level of evidence was low in all selected articles. No prospective studies were conducted and most of the papers were case-control series comparing ovarian cancer sarcopenic population vs. non sarcopenic population. CONCLUSIONS:Sarcopenia appears to have an important role in oncological outcomes of ovarian cancer patients. However, sarcopenia occurrence during disease history and mechanisms underlying the possible impairment in prognosis should be better investigated. Prospective trials are awaited in order to obtain a better insight in this topic.
10.2174/1381612825666190722112808
Prognostic significance of the skeletal muscle index and an inflammation biomarker in patients with breast cancer who underwent postoperative adjuvant radiotherapy.
Hua Xin,Deng Jia-Peng,Long Zhi-Qing,Zhang Wen-Wen,Huang Xin,Wen Wen,Guo Ling,He Zhen-Yu,Lin Huan-Xin
Current problems in cancer
BACKGROUND:Given the growing evidence that sarcopenia and inflammation influence the survival of patients with cancer, we evaluated the prognostic significance of the skeletal muscle index (SMI) combined with an inflammation marker in patients with breast cancer who underwent postoperative adjuvant radiotherapy. METHODS:We conducted a retrospective analysis of 301 patients with breast cancer who received postoperative adjuvant radiotherapy between 2010 and 2012. The SMI was measured using preradiotherapy computed tomography (CT) simulation images at the level of the fourth thoracic vertebra (T4). Receiver operating characteristic curve analyses were used to determine the optimal cutoff values for the SMI and inflammatory marker. Patients were divided into 2 groups (high SMI and low SMI), based on the SMI cutoff of 10.57 cm/m. RESULTS:Patients in the high-SMI group had a median overall survival (OS) of 62.4 months, which was significantly shorter than those in the low-SMI group, with a median OS of 68.5 months (P = 0.025). Patients in the high-SMI group had a median recurrence-free survival (RFS) of 62.3 months, which was shorter but not significantly than the median RFS of 65.2 months of the low-SMI group (P = 0.159). Univariate and multivariate survival analyses revealed SMI was an independent predictor of OS (P = 0.044). The SMI-MLR combination was found to be an independent predictor of OS (P = 0.006) and RFS (P = 0.009). CONCLUSIONS:The current findings support the SMI as a promising indicator for predicting clinical outcomes in patients with breast cancer receiving postoperative adjuvant radiotherapy. A high SMI accompanied by systemic inflammation was significantly associated with reduced OS and RFS.
10.1016/j.currproblcancer.2019.100513
Prognostic Value of Skeletal Muscle Depletion Measured on Computed Tomography for Overall Survival in Patients with Non-Metastatic Breast Cancer.
Journal of breast cancer
PURPOSE:The purpose of this study was to evaluate the prognostic value of skeletal muscle depletion measured on computed tomography (CT) in patients with non-metastatic invasive breast cancer. METHODS:This retrospective study included 577 consecutive women (mean age ± standard deviation: 48.9 ± 10.2 years with breast cancer who underwent a preoperative positron-emission tomography (PET)/CT scan and curative surgery between January 2012 and August 2014. The total abdominal muscle area (TAMA), subcutaneous fat area (SFA), and visceral fat area (VFA) were measured on CT images at the L3 vertebral level. Univariate and multivariate Cox proportional-hazard regression analyses were performed to evaluate whether there was an association between sarcopenia and overall survival (OS) outcome. RESULTS:Of the 577 women, 49 (8.5%) died after a mean of 46 months. The best TAMA threshold for predicting OS was 83.7 cm. The multivariate Cox proportional-hazard analysis revealed that sarcopenia (TAMA ≤ 83.70 cm) was a strong prognostic biomarker (hazard ratio [HR], 1.951; 95% confidence interval [CI], 1.061-3.586), along with large tumor size, axillary lymph node metastasis, high nuclear grade, estrogen receptor status, and adjuvant radiation therapy. In the subgroup analysis of patients aged ≥ 50 years, TAMA (≤ 77.14 cm) was a significant independent factor (HR, 2.856; 95% CI, 1.218-6.695). CONCLUSION:Skeletal muscle depletion measured on CT was associated with worse OS outcome in patients with non-metastatic breast cancer.
10.4048/jbc.2020.23.e8
Impact of sarcopenia on the prognosis and treatment toxicities in patients diagnosed with cancer.
Antoun Sami,Borget Isabelle,Lanoy Emilie
Current opinion in supportive and palliative care
PURPOSE OF REVIEW:High-resolution computed tomography (CT) imaging routinely performed for cancer follow-up provides valuable information on body composition. The influence of body composition on outcomes and the occurrence of toxicities can therefore be explored in cancer patients. This review describes recent findings regarding the prognostic impact of skeletal muscle mass (SMM) on chemotherapy toxicity. RECENT FINDINGS:The higher risk of toxicity associated with low SMM (i.e. sarcopenia) was first described for 5-fluorouracil-based chemotherapy toxicity in colon cancer patients before being increasingly studied, not only in the case of body surface area-adapted chemotherapy in breast cancer but also in various cancers treated with targeted therapies. The underlying mechanisms are still being debated; sarcopenia could act on pharmacokinetic parameters and/or sarcopenic patients could be more susceptible to adverse medical events including chemotherapy toxicity. SUMMARY:Evidence for a strong link between sarcopenia and chemotherapy toxicity is increasing. SMM may not be the only body composition parameter involved. Muscle function assessed by measuring muscle density and the BMI could be of interest. The ultimate purpose is to better identify patients at higher risk of toxicity and to reduce toxicity through body composition-based dosing.
10.1097/SPC.0000000000000011
Lean body mass wasting and toxicity in early breast cancer patients receiving anthracyclines.
Mazzuca Federica,Onesti Concetta Elisa,Roberto Michela,Di Girolamo Marco,Botticelli Andrea,Begini Paola,Strigari Lidia,Marchetti Paolo,Muscaritoli Maurizio
Oncotarget
BACKGROUND:Sarcopenia refers to the reduction of both volume and number of skeletal muscle fibers. Lean body mass loss is associated with survival, quality of life and tolerance to treatment in cancer patients. The aim of our study is to analyse the association between toxicities and sarcopenia in early breast cancer patients receiving adjuvant treatment. MATERIALS AND METHODS:Breast cancer patients who have received anthracycline-based adjuvant treatment were retrospectively enrolled. CT scan images performed before, during and after adjuvant chemotherapy were used to evaluate lean body mass at third lumbar vertebra level with the software Slice Omatic V 5.0. RESULTS:21 stage I-III breast cancer patients were enrolled. According to the skeletal muscle index at third lumbar vertebra cut-off ≤38.5 cm/m, 8 patients (38.1%) were classified as sarcopenic before starting treatment, while 10 patients (47.6%) were sarcopenic at the end of treatment. A lower baseline L3 skeletal muscle index is associated with G3-4 vs G0-2 toxicities (33.4 cm/m (31.1-39.9) 40.5 cm/m (33.4-52.0), = 0.028). Similarly skeletal muscle cross sectional area was significantly lower in patients with G3-4 toxicities (86.7 cm (82.6-104.7) 109.0 cm (83.3-143.9), = 0.017). L3 skeletal muscle index is an independent predictor of severe toxicity ( = 0.0282) in multivariate analysis. CONCLUSION:Lean body mass loss is associated with higher grade of toxicity in early breast cancer patients receiving adjuvant chemotherapy.
10.18632/oncotarget.25394
Presence of early stage cancer does not impair the early protein metabolic response to major surgery.
Engelen Mariëlle P K J,Klimberg V Suzanne,Allasia Arianna,Deutz Nicolaas Ep
Journal of cachexia, sarcopenia and muscle
BACKGROUND:Combined bilateral mastectomy and reconstruction is a common major surgical procedure in women with breast cancer and in those with a family history of breast cancer. As this large surgical procedure induces muscle protein loss, a preserved anabolic response to nutrition is warranted for optimal recovery. It is unclear whether the presence of early stage cancer negatively affects the protein metabolic response to major surgery as this would mandate perioperative nutritional support. METHODS:In nine women with early stage (Stage II) breast malignancy and nine healthy women with a genetic predisposition to breast cancer undergoing the same large surgical procedure, we examined whether surgery influences the catabolic response to overnight fasting and the anabolic response to nutrition differently. Prior to and within 24 h after combined bilateral mastectomy and reconstruction surgery, whole body protein synthesis and breakdown rates were assessed after overnight fasting and after meal intake by stable isotope methodology to enable the calculation of net protein catabolism in the post-absorptive state and net protein anabolic response to a meal. RESULTS:Major surgery resulted in an up-regulation of post-absorptive protein synthesis and breakdown rates (P < 0.001) and lower net protein catabolism (P < 0.05) and was associated with insulin resistance and increased systemic inflammation (P < 0.01). Net anabolic response to the meal was reduced after surgery (P < 0.05) but higher in cancer (P < 0.05) indicative of a more preserved meal efficiency. The significant relationship between net protein anabolism and the amount of amino acids available in the circulation (R = 0.85, P < 0.001) was independent of the presence of non-cachectic early stage breast cancer or surgery. CONCLUSIONS:The presence of early stage breast cancer does not enhance the normal catabolic response to major surgery or further attenuates the anabolic response to meal intake within 24 h after major surgery in patients with non-cachectic breast cancer. This indicates that the acute anabolic potential to conventional feeding is maintained in non-cachectic early stage breast cancer after major surgery.
10.1002/jcsm.12173
Disentangling the body weight-bone mineral density association among breast cancer survivors: an examination of the independent roles of lean mass and fat mass.
George Stephanie M,McTiernan Anne,Villaseñor Adriana,Alfano Catherine M,Irwin Melinda L,Neuhouser Marian L,Baumgartner Richard N,Baumgartner Kathy B,Bernstein Leslie,Smith Ashley W,Ballard-Barbash Rachel
BMC cancer
BACKGROUND:Bone mineral density (BMD) and lean mass (LM) may both decrease in breast cancer survivors, thereby increasing risk of falls and fractures. Research is needed to determine whether lean mass (LM) and fat mass (FM) independently relate to BMD in this patient group. METHODS:The Health, Eating, Activity, and Lifestyle Study participants included 599 women, ages 29-87 years, diagnosed from 1995-1999 with stage 0-IIIA breast cancer, who underwent dual-energy X-ray absorptiometry scans approximately 6-months postdiagnosis. We calculated adjusted geometric means of total body BMD within quartiles (Q) of LM and FM. We also stratified LM-BMD associations by a fat mass index threshold that tracks with obesity (lower body fat: ≤ 12.9 kg/m2; higher body fat: >12.9 kg/m2) and stratified FM-BMD associations by appendicular lean mass index level corresponding with sarcopenia (non-sarcopenic: ≥ 5.45 kg/m2 and sarcopenic: < 5.45 kg/m2). RESULTS:Higher LM (Q4 vs. Q1) was associated with higher total body BMD overall (1.12 g/cm2 vs. 1.07 g/cm2, p-trend < 0.0001), and among survivors with lower body fat (1.13 g/cm2 vs. 1.07 g/cm2, p-trend < 0.0001) and higher body fat (1.15 g/cm2 vs. 1.08 g/cm2, p-trend = 0.004). Higher FM (Q4 vs. Q1) was associated with higher total body BMD overall (1.12 g/cm2 vs. 1.07 g/cm2, p-trend < 0.0001) and among non-sarcopenic survivors (1.15 g/cm2 vs. 1.08 g/cm2, p < 0.0001), but the association was not significant among sarcopenic survivors (1.09 g/cm2 vs. 1.04 g/cm2, p-trend = 0.18). CONCLUSION:Among breast cancer survivors, higher LM and FM were independently related to higher total body BMD. Future exercise interventions to prevent bone loss among survivors should consider the potential relevance of increasing and preserving LM.
10.1186/1471-2407-13-497
Clinical implications of low skeletal muscle mass in early-stage breast and colorectal cancer.
The Proceedings of the Nutrition Society
Although obesity has now been widely accepted to be an important risk factor for cancer survival, the associations between BMI and cancer mortality have not been consistently linear. Although morbid obesity has clearly been associated with worse survival, some studies have suggested a U-shaped association with no adverse association with overweight or lower levels of obesity. This 'obesity paradox' may be due to the fact that BMI likely incompletely captures key measures of body composition, including distribution of skeletal muscle and adipose tissue. Fat and lean body mass can be measured using clinically acquired computed tomography scans. Many of the earlier studies focused on patients with metastatic cancer. However, skeletal muscle loss in the metastatic setting may reflect end-stage disease processes. Therefore, this article focuses on the clinical implication of low skeletal muscle mass in early-stage non-metastatic breast and colorectal cancer where measures of body composition have been shown to be strong predictors of disease-free survival and overall survival and also chemotherapy toxicity and operative risk.
10.1017/S0029665118000423
Sarcopenia in patients with malignant pleural effusion: impact on symptoms, health status, and response to hospitalization.
Rodríguez-Torres Janet,López-López Laura,Cabrera-Martos Irene,Valenza-Demet Gerald,Cahalin Lawrence P,Valenza Marie Carmen
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer
BACKGROUND:Malignant pleural effusion (MPE) refers to the presence of neoplastic cells in the pleural fluid and was previously associated with lung cancer, breast cancer, and lymphoma. Patients with MPE effusion have significant symptoms, diminishing their overall quality of life but little is known about the influence sarcopenia may have on their clinical presentation. PURPOSE:To examine the prevalence of sarcopenia in patients with MPE and its relationship with symptoms, health status, and the response to hospitalization. METHODS:Seventy-four patients with MPE underwent measurements of symptoms, health-related quality of life, and functional status upon admission, discharge, and 3 months after hospital discharge. RESULTS:Patients with MPE and sarcopenia were symptomatic during hospitalization and at discharge. Additionally, health-related quality of life and functional status were worse in patients with MPE and sarcopenia. All measures of patients with MPE and sarcopenia were significantly poorer 3 months after hospital discharge. CONCLUSIONS:Sarcopenia is a clinical characteristic with substantial negative effects in patients with MPE. Specific interventions may need to be provided, designed, and offered in the clinical setting.
10.1007/s00520-019-04779-0
Effect of physical activity on bone strength and body composition in breast cancer premenopausal women during endocrine therapy.
Hojan K,Milecki P,Molińska-Glura M,Roszak A,Leszczyński P
European journal of physical and rehabilitation medicine
BACKGROUND:Breast cancer endocrine therapy (ET) is one of the most basic therapeutic methods in oncology. Well-balanced physical activity exerts positive influence on bone strength (BS) and body composition (BC), which has been confirmed by the clinical research regarding osteoporosis, prevention and treatment alike. Accordingly, in the following study, an attempt was made to assess the selected parameters of young, premenopausal women's clinical state under the influence of breast cancer ET, as well as to define the influence of physical activity on the studied parameters. AIM:The assessment of the influence of aerobic and resistance training (AT and RT) on BS and BC in premenopausal women during breast cancer ET. DESIGN:This was a nonrandomized, prospective clinical study. SETTING AND POPULATION:The study was performed in 41 outpatients in the Greater Poland Cancer Centre. METHODS:The examinations were made with the anthropometric and dual energy X-ray absorptiometry measurements. The examinations were conducted according to the schedule: at the baseline, II-after 6 months of ET, III-after 6 months of AT (in 12 months of ET), IV- after following 6 months AT and RT (18 months of ET). RESULTS:After 6 months of the ET without physical activity the bone mineral density (BMD) in all regions and the hip structure parameters were lower in comparison to the baseline and there was a significant increase in fatty tissue. After 6 months of AT the BMD of all regions was lower than in 6 months ET. An introduction of RT caused the analyzed values of BS parameters to increase. Also a significant growth of lean body mass and free fat body mass was observed and so was an insignificant fall in fat. CONCLUSION:The breast cancer ET is related to the changes in BS and BC in premenopausal women. The introduction of AT caused a slowdown in negative changes in bones, and body fat was reduced. The introduction of RT reversed an adverse tendency for BS and sarcopenia. CLINICAL REHABILITATION IMPACT:The study results show that mixed type physical activity (AT and RT) during breast cancer ET could prevent negative changes, of this treatment, in body build in premenopausal women.
Sarcopenia as a determinant of chemotherapy toxicity and time to tumor progression in metastatic breast cancer patients receiving capecitabine treatment.
Prado Carla M M,Baracos Vickie E,McCargar Linda J,Reiman Tony,Mourtzakis Marina,Tonkin Katia,Mackey John R,Koski Sheryl,Pituskin Edith,Sawyer Michael B
Clinical cancer research : an official journal of the American Association for Cancer Research
PURPOSE:Body composition has emerged as an important prognostic factor in cancer patients. Severe depletion of skeletal muscle (sarcopenia) and, hence, of overall lean body mass may represent an occult condition in individuals with normal or even high body weight. Sarcopenia has been associated with poor performance status, 5-fluorouracil toxicity, and shortened survival in cancer patients. Here, we prospectively studied patients with metastatic breast cancer receiving capecitabine treatment in order to determine if sarcopenia was associated with a higher incidence of toxicity and a shorter time to tumor progression (TTP). EXPERIMENTAL DESIGN:Fifty-five women with metastatic breast cancer resistant to anthracycline and/or taxane treatment were included. Skeletal muscle cross-sectional area at the third lumbar vertebra was measured by computerized tomography, and sarcopenia was defined using a previously published cutoff point. Toxicity was assessed after cycle 1 of treatment, and TTP was determined prospectively. RESULTS:Approximately 25% of patients were classified as sarcopenic, and this feature was seen in normal weight, overweight, and obese individuals. Toxicity was present in 50% of sarcopenic patients, compared with only 20% of nonsarcopenic patients (P = 0.03), and TTP was shorter in sarcopenic patients (101.4 days; confidence interval, 59.8-142.9) versus nonsarcopenic patients (173.3 days; confidence interval, 126.1-220.5; P = 0.05). CONCLUSION:Sarcopenia is a significant predictor of toxicity and TTP in metastatic breast cancer patients treated with capecitabine. Our results raise the potential use of body composition assessment to predict toxicity and individualize chemotherapy dosing.
10.1158/1078-0432.CCR-08-2242
Pharmacological Dual Inhibition of Tumor and Tumor-Induced Functional Limitations in a Transgenic Model of Breast Cancer.
Wang Ruizhong,Bhat-Nakshatri Poornima,Padua Maria B,Prasad Mayuri S,Anjanappa Manjushree,Jacobson Max,Finnearty Courtney,Sefcsik Victoria,McElyea Kyle,Redmond Rachael,Sandusky George,Penthala Narsimha,Crooks Peter A,Liu Jianguo,Zimmers Teresa,Nakshatri Harikrishna
Molecular cancer therapeutics
Breast cancer progression is associated with systemic effects, including functional limitations and sarcopenia without the appearance of overt cachexia. Autocrine/paracrine actions of cytokines/chemokines produced by cancer cells mediate cancer progression and functional limitations. The cytokine-inducible transcription factor NF-κB could be central to this process, as it displays oncogenic functions and is integral to the Pax7:MyoD:Pgc-1β:miR-486 myogenesis axis. We tested this possibility using the MMTV-PyMT transgenic mammary tumor model and the NF-κB inhibitor dimethylaminoparthenolide (DMAPT). We observed deteriorating physical and functional conditions in PyMT mice with disease progression. Compared with wild-type mice, tumor-bearing PyMT mice showed decreased fat mass, impaired rotarod performance, and reduced grip strength as well as increased extracellular matrix (ECM) deposition in muscle. Contrary to acute cachexia models described in the literature, mammary tumor progression was associated with reduction in skeletal muscle stem/satellite-specific transcription factor Pax7. Additionally, we observed tumor-induced reduction in Pgc-1β in muscle, which controls mitochondrial biogenesis. DMAPT treatment starting at 6 to 8 weeks age prior to mammary tumor occurrence delayed mammary tumor onset and tumor growth rates without affecting metastasis. DMAPT overcame cancer-induced functional limitations and improved survival, which was accompanied with restoration of Pax7, Pgc-1β, and mitochondria levels and reduced ECM levels in skeletal muscles. In addition, DMAPT restored circulating levels of 6 out of 13 cancer-associated cytokines/chemokines changes to levels seen in healthy animals. These results reveal a pharmacological approach for overcoming cancer-induced functional limitations, and the above-noted cancer/drug-induced changes in muscle gene expression could be utilized as biomarkers of functional limitations. .
10.1158/1535-7163.MCT-17-0717
The influence of different muscle mass measurements on the diagnosis of cancer cachexia.
Blauwhoff-Buskermolen Susanne,Langius Jacqueline A E,Becker Annemarie,Verheul Henk M W,de van der Schueren Marian A E
Journal of cachexia, sarcopenia and muscle
BACKGROUND:Progressive loss of muscle mass is a major characteristic of cancer cachexia. Consensus definitions for cachexia provide different options to measure muscle mass. This study describes the effect of different methods to determine muscle mass on the diagnosis of cancer cachexia. In addition, the association of cachexia with other features of cachexia, quality of life, and survival was explored. METHODS:Prior to chemotherapy, cachexia was assessed by weight loss, body mass index, and muscle mass measurements, the latter by mid-upper arm muscle area (MUAMA), computed tomography (CT) scans, and bio-electrical impedance analysis (BIA). In addition, appetite, inflammation, muscle strength, fatigue, quality of life, and survival were measured, and associations with cachexia were explored. RESULTS:Included were 241 patients with advanced cancer of the lung (36%), colon/rectum (31%), prostate (18%), or breast (15%). Mean age was 64 ± 10 years; 54% was male. Prevalence of low muscle mass was as follows: 13% with MUAMA, 59% with CT, and 93% with BIA. In turn, the prevalence of cachexia was 37, 43, and 48%, whereby weight loss >5% was the most prominent component of being defined cachectic. Irrespective of type of muscle measurement, patients with cachexia presented more often with anorexia, inflammation, low muscle strength, and fatigue and had lower quality of life. Patients with cachexia had worse overall survival compared with patients without cachexia: HRs 2.00 (1.42-2.83) with MUAMA, 1.64 (1.15-2.34) with CT, and 1.50 (1.05-2.14) with BIA. CONCLUSIONS:Although the prevalence of low muscle mass in patients with cancer depended largely on the type of muscle measurement, this had little influence on the diagnosis of cancer cachexia (as the majority of patients was already defined cachectic based on weight loss). New studies are warranted to further elucidate the additional role of muscle measurements in the diagnosis of cachexia and the association with clinical outcomes.
10.1002/jcsm.12200
Injection of testosterone may be safer and more effective than transdermal administration for combating loss of muscle and bone in older men.
American journal of physiology. Endocrinology and metabolism
The value of testosterone replacement therapy (TRT) for older men is currently a topic of intense debate. While US testosterone prescriptions have tripled in the past decade (9), debate continues over the risks and benefits of TRT. TRT is currently prescribed for older men with either low serum testosterone (T) or low T plus accompanying symptoms of hypogonadism. The normal range for serum testosterone is 300 to 1,000 ng/dl. Serum T ≤ 300 ng/dl is considered to be low, and T ≤ 250 is considered to be frank hypogonadism. Most experts support TRT for older men with frank hypogonadism and symptoms. Treatment for men who simply have low T remains somewhat controversial. TRT is most frequently administered by intramuscular (im) injection of long-acting T esters or transdermally via patch or gel preparations and infrequently via oral administration. TRT produces a number of established benefits in hypogonadal men, including increased muscle mass and strength, decreased fat mass, increased bone mineral density, and improved sexual function, and in some cases those benefits are dose dependent. For example, doses of TRT administered by im injection are typically higher than those administered transdermally, which results in greater musculoskeletal benefits. TRT also produces known risks including development of polycythemia (Hct > 50) in 6% of those treated, decrease in HDL, breast tenderness and enlargement, prostate enlargement, increases in serum PSA, and prostate-related events and may cause suppression of the hypothalamic-pituitary-gonadal axis. Importantly, TRT does not increase the risk of prostate cancer. Putative risks include edema and worsening of sleep apnea. Several recent reports have also indicated that TRT may produce cardiovascular (CV) risks, while others report no risk or even benefit. To address the potential CV risks of TRT, we have recently reported via meta-analysis that oral TRT increases CV risk and suggested that the CV risk profile for im TRT may be better than that for oral or transdermal TRT.
10.1152/ajpendo.00111.2015
Effectiveness of bisphosphonate combined with activated vitamin D in patients with aromatase inhibitor-induced osteoporosis after breast cancer operation.
Tanaka Mizue,Itoh Soichiro,Takeuchi Yasuhiro
Osteoporosis and sarcopenia
OBJECTIVES:We compared the effectiveness of bisphosphonates combined with activated vitamin D administered for therapy of aromatase inhibitor-induced osteoporosis after a breast cancer operation and primary postmenopausal osteoporosis through propensity score matching. METHODS:Forty-eight postmenopausal patients with estrogen receptor-positive early breast cancer, who had postoperative adjuvant treatment with aromatase inhibitors and whose T-score of bone mineral density (BMD) decreased below -2.5 (AI group), and 48 patients of primary postmenopausal osteoporosis (PO group) enrolled in this retrospective observational study. They were administered monthly risedronate or minodronate, and daily alfacalcitol or eldecalcitol were combined. Their BMD (L2-4, L-BMD), serum-corrected calcium, serum phosphate, tartrate-resistant acid phosphatase 5b (TRACP-5b), bone alkaline phosphatase (BAP), estimated glomerular filtration rate, urine calcium/creatinine ratio, intact-parathyroid hormone, and 25-hydroxy vitamin D were measured before treatment and until 24 months. RESULTS:L-BMD values increased with time compared with the baseline values in each group, and there was no significant difference in the groups. Percentage value of TRACP-5b decreased rapidly after 6 months and maintained low level until 24 months in both groups. Percentage value of BAP in the AI group decreased continuously until 24 months. In contrast, the percentage change in the PO group plateaued after 6 months. CONCLUSIONS:It is suggested that monthly oral bisphosphonate combined with activated Vitamin D is an effective therapy to increase BMD in the aromatase inhibitor-induced osteoporosis after breast cancer operation. Monitoring of kidney function and concentration of Ca in blood and urine may be necessary.
10.1016/j.afos.2018.08.002
Sarcopenia Predicts Overall Survival in Patients with Lung, Breast, Prostate, or Myeloma Spine Metastases Undergoing Stereotactic Body Radiation Therapy (SBRT), Independent of Histology.
Zakaria Hesham Mostafa,Llaniguez Jeremy T,Telemi Edvin,Chuang Matthew,Abouelleil Mohamed,Wilkinson Brandon,Chandra Ankush,Boyce-Fappiano David,Elibe Erinma,Schultz Lonni,Siddiqui Farzan,Griffith Brent,Kalkanis Steven N,Lee Ian Yu,Chang Victor
Neurosurgery
BACKGROUND:Predicting survival of patients with spinal metastases would help stratify treatments from aggressive to palliation. OBJECTIVE:To evaluate whether sarcopenia predicts survival in patients with lung, breast, prostate, or multiple myeloma spinal metastases. METHODS:Psoas muscle measurements in patients with spinal metastasis were taken from computed tomography scans at 2 time points: at first episode of stereotactic body radiation therapy (SBRT) and from the most recent scan available. Overall survival and hazard ratios were calculated with multivariate cox proportional hazards regression analyses. RESULTS:In 417 patients with spinal metastases, 40% had lung cancer, 27% breast, 21% prostate, and 11% myeloma. Overall survival was not associated with age, sex, ethnicity, levels treated, or SBRT volume. Multivariate analysis showed patients in the lowest psoas tertile had shorter survival (222 d, 95% CI = 185-323 d) as compared to the largest tertile (579 d, 95% CI = 405-815 d), (HR1.54, P = .005). Median psoas size as a cutoff value was also strongly predictive for survival (HR1.48, P = .002). Survival was independent of tumor histology. The psoas/vertebral body ratio was also successful in predicting overall survival independent of tumor histology and gender (HR1.52, P < .01). Kaplan-Meier survival curves visually represent survival (P = .0005). CONCLUSION:In patients with spine metastases, psoas muscle size as a hallmark of frailty/sarcopenia is an objective, simple, and effective way to identify patients who are at risk for shorter survival, regardless of tumor histology. This information can be used to help with surgical decision making in patients with advanced cancer, as patients with small psoas sizes are at higher risk of death.
10.1093/neuros/nyz216
Obesity Does Not Influence Management of Advanced Breast Cancer in the Elderly.
Tangalakis Laurel L,Cortina Chandler S,Son Jennifer D,Poirier Jennifer,Madrigrano Andrea
Clinical breast cancer
BACKGROUND:Obesity is becoming increasingly common in the elderly population, and it adds to the complexity of treatment decisions in this population. We aimed to investigate whether body mass index (BMI) affects care in this subset of patients. PATIENTS AND METHODS:We performed a retrospective chart review on 118 patients over the age of 70 years diagnosed with breast cancer and pathologically proven axillary disease over an 8-year period at an urban academic hospital and compared BMI to treatment received, clinical stage, and hormone receptor status. RESULTS:Performance of radiation therapy, axillary surgery, and chemotherapy was compared in the elderly population over lower and higher BMI, and no significant difference was detected. Although there was a trend for increasing clinical stage to be associated with a lower BMI, this was not statistically significant (P = .06). CONCLUSION:Obesity does not appear to influence treatment decisions in patients over the age of 70 years. Breast cancer providers should turn to other patient and clinical factors when deciding treatment plans in this patient population. Further investigation is needed to examine how obesity influences tumor biology, diagnosis, and treatment decisions.
10.1016/j.clbc.2018.12.020
Muscle strength in breast cancer patients receiving different treatment regimes.
Klassen Oliver,Schmidt Martina E,Ulrich Cornelia M,Schneeweiss Andreas,Potthoff Karin,Steindorf Karen,Wiskemann Joachim
Journal of cachexia, sarcopenia and muscle
BACKGROUND:Muscle dysfunction and sarcopenia have been associated with poor performance status, an increased mortality risk, and greater side effects in oncologic patients. However, little is known about how performance is affected by cancer therapy. We investigated muscle strength in breast cancer patients in different adjuvant treatment settings and also compared it with data from healthy individuals. METHODS:Breast cancer patients (N = 255) from two randomized controlled exercise trials, staged 0-III and aged 54.4 ± 9.4 years, were categorized into four groups according to their treatment status. In a cross-sectional design, muscle function was assessed bilaterally by isokinetic dynamometry (0°, 60°, 180°/s) as maximal voluntary isometric contraction (MVIC) and maximal isokinetic peak torque (MIPT) in shoulder rotators and knee flexors and extensors. Additionally, muscular fatigue index (FI%) and shoulder flexibility were evaluated. Healthy women (N = 26), aged 53.3 ± 9.8 years, were tested using the same method. Analysis of covariance was used to estimate the impact of different cancer treatments on skeletal muscle function with adjustment for various clinical and socio-demographic factors. RESULTS:Consistently, lower muscle strength was measured in shoulder and knee strength in patients after chemotherapy. On average, patients had up to 25% lower strength in lower extremities and 12-16% in upper extremities in MVIC and MIPT during cancer treatment compared with healthy women. No substantial difference between patient groups in shoulder strength, but significantly lower shoulder flexibility in patients with radical mastectomy was measured. Chemotherapy-treated patients had consistently higher FI%. No serious adverse events were reported. CONCLUSIONS:Breast cancer patients showed markedly impaired muscle strength and joint dysfunctions before and after anticancer treatment. The significant differences between patients and healthy individuals underline the need of exercise therapy as early as possible in order to prevent or counteract the loss of muscle function after curative surgery as well as the consequences of neo-/adjuvant chemotherapy.
10.1002/jcsm.12165
Sarcopenia as a predictor of mortality in women with breast cancer: a meta-analysis and systematic review.
BMC cancer
BACKGROUND:Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death in women worldwide. Recently, studies have been published with inconsistent findings regarding whether sarcopenia is a risk factor for mortality in breast cancer patients. Therefore, the aim of this systematic review and meta-analysis was to systematically assess and quantify sarcopenia as a risk factor for mortality in breast cancer patients. METHODS:In a systematic literature review of PubMed, EMBASE, and the Cochrane CENTRAL Library, we searched for observational studies written in English (from database inception until April 30, 2019) that reported an association between sarcopenia and breast cancer in women who were 18 years or older. RESULTS:A total of six studies (5497 participants) were included in this meta-analysis. Breast cancer patients with sarcopenia were associated with a significantly higher risk of mortality, compared to breast cancer patients without sarcopenia (pooled HR-hazard ratio = 1.71, 95% CI: 1.25-2.33, I = 59.1%). In addition, the results of age subgroup analysis showed that participants younger than 55 years with sarcopenia had a lower risk of mortality than participants aged 55 years and older with sarcopenia (pooled HR = 1.46, 95% CI: 1.24-1.72 versus pooled HR = 1.99, 95% CI: 1.05-3.78), whereas both have an increased risk of mortality compared to non-sarcopenic patients. Subgroup analyses regarding stage at diagnosis revealed an increased risk of mortality in non-metastatic patients compared to participants without sarcopenia (pooled HR = 1.91, 95% CI: 1.32-2.78), whereas the association was not significant in metastatic breast cancer patients. Other subgroup analyses were performed using different follow-up periods (> 5 years versus ≤5 years) and the results were different (pooled HR = 1.81, 95% CI: 1.23-2.65 versus pooled HR = 1.70, 95% CI: 0.80-3.62). CONCLUSIONS:The present study found that sarcopenia is a risk factor for mortality among female early breast cancer patients. It is imperative that more research into specific interventions aimed at treating sarcopenia be conducted in the near future in order to provide evidence which could lead to decreased mortality rates in breast cancer patients.
10.1186/s12885-020-6645-6
Beyond sarcopenia: Characterization and integration of skeletal muscle quantity and radiodensity in a curable breast cancer population.
Weinberg Marc S,Shachar Shlomit S,Muss Hyman B,Deal Allison M,Popuri Karteek,Yu Hyeon,Nyrop Kirsten A,Alston Shani M,Williams Grant R
The breast journal
Skeletal muscle loss, commonly known as sarcopenia, is highly prevalent and prognostic of adverse outcomes in oncology. However, there is limited information on adults with early breast cancer and examination of other skeletal muscle indices, despite the potential prognostic importance. This study characterizes and examines age-related changes in body composition of adults with early breast cancer and describes the creation of a novel integrated muscle measure. Female patients diagnosed with stage I-III breast cancer with abdominal computerized tomography (CT) scans within 12 weeks from diagnosis were identified from local tumor registry (N = 241). Skeletal muscle index (muscle area per height [cm /m ]), skeletal muscle density, and subcutaneous and visceral adipose tissue areas, were determined from CT L3 lumbar segments. We calculated a novel integrated skeletal measure, skeletal muscle gauge, which combines skeletal muscle index and density (SMI × SMD). 241 patients were identified with available CT imaging. Median age 52 years and range of 23-87. Skeletal muscle index and density significantly decreased with age. Using literature based cut-points, older adults (≥65 years) had significantly higher proportions of sarcopenia (63 vs 28%) and myosteatosis (90 vs 11%) compared to younger adults (<50 years). Body mass index was positively correlated with skeletal muscle index and negatively correlated with muscle density. Skeletal muscle gauge correlated better with increasing age (ρ = 0.52) than with either skeletal muscle index (ρ = 0.20) or density (ρ = 0.46). Wide variations and age-related changes in body composition metrics were found using routinely obtained abdominal CT imaging. Skeletal muscle index and density provide independent, complementary information, and the product of the two metrics, skeletal muscle gauge, requires further research to explore its impact on outcomes in women with curable breast cancer.
10.1111/tbj.12952