Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer.
ABSTRACT Bevacizumab, a monoclonal antibody against vascular endothelial growth factor A, has shown clinical efficacy in patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer. We evaluated the efficacy, measured according to the rate of pathological complete response (absence of invasive and intraductal disease in the breast and the axillary lymph nodes), and the safety of adding bevacizumab to neoadjuvant chemotherapy in patients with early-stage breast cancer.
We randomly assigned 1948 patients with a median tumor size of 40 mm on palpation to receive neoadjuvant epirubicin and cyclophosphamide followed by docetaxel, with or without concomitant bevacizumab. Patients with untreated HER2-negative breast cancer were eligible if they had large tumors, hormone-receptor-negative disease, or hormone-receptor-positive disease with palpable nodes or positive findings on sentinel-node biopsy, and no increased cardiovascular or bleeding risk.
Overall, the rates of pathological complete response were 14.9% with epirubicin and cyclophosphamide followed by docetaxel and 18.4% with epirubicin and cyclophosphamide followed by docetaxel plus bevacizumab (odds ratio with addition of bevacizumab, 1.29; 95% confidence interval, 1.02 to 1.65; P=0.04); the corresponding rates of pathological complete response were 27.9% and 39.3% among 663 patients with triple-negative tumors (P=0.003) and 7.8% and 7.7% among 1262 patients with hormone-receptor-positive tumors (P=1.00). Breast-conserving surgery was possible in 66.6% of the patients in both groups. The addition of bevacizumab, as compared with neoadjuvant therapy alone, was associated with a higher incidence of grade 3 or 4 toxic effects (febrile neutropenia, mucositis, the hand-foot syndrome, infection, and hypertension) but with a similar incidence of surgical complications.
The addition of bevacizumab to neoadjuvant chemotherapy significantly increased the rate of pathological complete response among patients with HER2-negative early-stage breast cancer. Efficacy was restricted primarily to patients with triple-negative tumors, in whom the pathological complete response is considered to be a reliable predictor of long-term outcome. (Funded by Sanofi-Aventis and Roche, Germany; ClinicalTrials.gov number, NCT00567554.).
SourceAvailable from: Caterina Fontanella[Show abstract] [Hide abstract]
ABSTRACT: Obesity is associated with an increased risk of breast cancer (BC) and poorer outcome. We assessed the impact of body mass index (BMI) on pathological complete response (pCR), disease-free (DFS), and overall survival (OS), according to BC subtypes in patients with primary BC treated with neoadjuvant chemotherapy. 8,872 patients with primary BC from eight neoadjuvant trials were categorized according to BMI: underweight (<18.5 kg/m(2)), normal weight (18.5 to <25 kg/m(2)), overweight (25 to <30 kg/m(2)), obese (30 to <40 kg/m(2)), and very obese (≥40 kg/m(2)). BC subtypes were defined as luminal-like (ER/PgR-positive and HER2-negative), HER2/luminal (ER/PgR-positive and HER2-positive), HER2-like (ER/PgR-negative and HER2-positive), and triple-negative (TNBC; ER/PgR- and HER2-negative). pCR rate was higher in normal weight patients compared with all other BMI groups (P = 0.003). Mean DFS and OS were shorter in obese (87.3 months, P = 0.014 and 94.9 months, P = 0.001, respectively) and very obese (66.6 months, P < 0.001 and 75.3 months, P < 0.001, respectively) compared with normal weight patients (91.5 and 98.8 months, respectively) which was confirmed by subpopulation treatment effect pattern plot analyses and was consistent in luminal-like and TNBC. No interaction was observed between BMI and pCR. Normal weight patients experienced less non-hematological adverse events (P = 0.002) and were more likely to receive full taxane doses (P < 0.001) compared with all other BMI groups. In multivariable analysis, the dose of taxanes was predictive for pCR (P < 0.001). Higher BMI was associated with lower pCR and a detrimental impact on survival. Normal weight patients had the best compliance to chemotherapy and received the highest taxane doses, which seems to be related with treatment outcomes.Breast Cancer Research and Treatment 02/2015; 150(1). DOI:10.1007/s10549-015-3287-5 · 4.20 Impact Factor
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ABSTRACT: Locally advanced breast cancer (LABC) constitutes a heterogeneous entity that includes advanced-stage primary tumours, cancers with extensive nodal involvement and inflammatory breast carcinomas. Although the definition of LABC can be broadened to include some large operable breast tumours, we use this term to strictly refer to inoperable cancers that are included in the above-mentioned categories. The prognosis of such tumours is often unfavourable; despite aggressive treatment, many patients eventually develop distant metastases and die from the disease. Advances in systemic therapy, including radiation treatment, surgical techniques and the development of new targeted agents have significantly improved clinical outcomes for patients with this disease. Notwithstanding these advances, LABC remains an important clinical problem, particularly in developing countries and those without widely adapted breast cancer awareness programmes. The optimal management of LABC requires a multidisciplinary approach, a well-coordinated treatment schedule and close cooperation between medical, surgical and radiation oncologists. In this Review, we discuss the current state of the art and possible future treatment strategies for patients with LABC.Nature Reviews Clinical Oncology 02/2015; DOI:10.1038/nrclinonc.2015.13 · 15.70 Impact Factor
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ABSTRACT: Under pathophysiological conditions in adults, endothelial cells (ECs) sprout from pre-existing blood vessels to form new ones by a process termed angiogenesis. During embryonic development, Apelin (APLN) is robustly expressed in vascular ECs. In adult mice, however, APLN expression in the vasculature is significantly reduced. Here we show that APLN expression is reactivated in adult ECs after ischaemia insults. In models of both injury ischaemia and tumor angiogenesis, we find that Apln-CreER genetically labels sprouting but not quiescent vasculature. By leveraging this specific activity, we demonstrate that abolishment of the VEGF-VEGFR2 signalling pathway as well as ablation of sprouting ECs diminished tumour vascularization and growth without compromising vascular homeostasis in other organs. Collectively, we show that Apln-CreER distinguishes sprouting vessels from stabilized vessels in multiple pathological settings. The Apln-CreER line described here will greatly aid future mechanistic studies in both vascular developmental biology and adult vascular diseases.Nature Communications 01/2015; 6:6020. DOI:10.1038/ncomms7020 · 10.74 Impact Factor