P4-06-05: Prognostic Impact of Disseminated and Circulating Tumor Cells in Patients Treated for Locally Advanced Breast Cancer.

Purpose Vascular endothelial growth factor (VEGF) is a potent molecule that mediates tumor angiogenesis primarily through VEGF receptor 2 (VEGFR2). Bevacizumab, a recombinant humanized monoclonal antibody to VEGF, was administered to previously untreated patients to evaluate parameters of angiogenesis. Patients and Methods Twenty-one patients with inflammatory and locally advanced breast cancer were treated with bevacizumab for cycle 1 (15 mg/kg on day 1) followed by six cycles of bevacizumab with doxorubicin (50 mg/m2) and docetaxel (75 mg/m2) every 3 weeks. After locoregional therapy, patients received eight cycles of bevacizumab alone, and hormonal therapy when indicated. Tumor biopsies and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) were obtained at baseline, and after cycles 1, 4, and 7. Results A median decrease of 66.7% in phosphorylated VEGFR2 (Y951) in tumor cells (P = .004) and median increase of 128.9% in tumor apoptosis (P = .0008) were seen after bevacizumab alone. These changes persisted with the addition of chemotherapy. There were no significant changes in microvessel density or VEGF-A expression. On DCE-MRI, parameters reflecting reduced angiogenesis, a median decrease of 34.4% in the inflow transfer rate constant (P = .003), 15.0% in the backflow extravascular- extracellular rate constant (P = .0007) and 14.3% in extravascular-extracellular volume fraction (P = .002) were seen after bevacizumab alone. Conclusion Bevacizumab has inhibitory effects on VEGF receptor activation and vascular permeability, and induces apoptosis in tumor cells.

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O78: SARCOPENIA IN LOCALLY ADVANCED BREAST CANCER: PREVALENCE, AND IMPACT ON CLINICAL AND ONCOLOGIC OUTCOMES

British Journal of Surgery ◽

10.1093/bjs/znab117.078 ◽

2021 ◽

Vol 108 (Supplement_1) ◽

Author(s):

PM Collins ◽

JA Elliott ◽

MJ Brennan ◽

M McNamara ◽

E O'Malley ◽

...

Keyword(s):

Breast Cancer ◽

Advanced Breast Cancer ◽

Locally Advanced Breast Cancer ◽

Performance Status ◽

Locally Advanced ◽

Advanced Breast ◽

Prognostic Impact ◽

Disease Specific Survival ◽

Pathologic Features ◽

Disease Specific

Abstract Introduction Sarcopenia in cancer may confer negative outcomes, but its prevalence and impact in the modern multimodal management of locally advanced breast cancer have not been systematically studied. Method Patients undergoing neoadjuvant therapy and surgery for locally advanced breast cancer between 2010 and 2015 were studied. Skeletal muscle index (SMI) and lean body mass (LBM) were determined. Sarcopenia was defined by computed tomography (CT) at L3 as SMI<38.5cm2/m2. Multivariable linear, logistic, and Cox regression analysis was undertaken to determine the independent impact of sarcopenia on clinical and oncologic outcome. Result 258 patients were studied. Sarcopenia was present in 23.0%, 7.8% and 0.0% of patients with normal weight, overweight and obesity, respectively (P=0.001). Sarcopenia was not associated with baseline cT and cN stage, tumour grade, histologic type or receptor status. Patients with sarcopenia exhibited equivalent indices of neoadjuvant therapy response including ypT and ypN stage, pathologic complete response and Sataloff grade following surgical resection. Postoperatively, sarcopenia was not independently associated with comprehensive complications index (P=0.242), length of stay (P=0.716) or overall morbidity (P=0.365). However, on multivariable analysis, lower LBM independently predicted reduced invasive disease-free (P=0.049,HR0.93[95%CI0.87-1.00]) and overall (P=0.028,HR0.92[0.85-0.99]), but not disease-specific survival (P=0.070). Conclusion Consistent with a lack of association with baseline and post-treatment pathologic features, sarcopenia in locally advanced breast cancer is associated with reduced overall, but not disease-specific, survival. These data indicate that the prognostic impact of sarcopenia may be mediated by impaired performance status and increased non-cancer mortality. Take-home message Consistent with a lack of association with baseline and post-treatment pathologic features, sarcopenia in locally advanced breast cancer is associated with reduced overall, but not disease-specific, survival. These data indicate that the prognostic impact of sarcopenia may be mediated by impaired performance status and increased non-cancer mortality.

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