Bevacizumab plus neoadjuvant chemotherapy in patients with HER2-negative inflammatory breast cancer (BEVERLY-1): a multicentre, single-arm, phase 2 study.

BACKGROUND: Addition of bevacizumab to standard chemotherapy in the neoadjuvant setting in patients with HER2-negative metastatic breast cancer improves progression-free survival and the proportion of patients achieving pathological complete response. In the BEVERLY-1 (UCBG-0802) trial we aimed to assess the addition of bevacizumab to neoadjuvant and adjuvant chemotherapy in the treatment of patients with HER2-negative inflammatory breast cancer. METHODS: We did this phase 2, single-arm trial at 20 hospitals in France. We enrolled women aged 18 years or older who had non-metastatic HER2-negative inflammatory breast cancer. Patients underwent 3-week treatment cycles, receiving neoadjuvant intravenous fluorouracil (500 mg/m(2)), epirubicin (100 mg/m(2)), cyclophosphamide (500 mg/m(2)), and bevacizumab (15 mg/kg) during cycles 1-4, then docetaxel (100 mg/m(2)) and bevacizumab during cycles 5-8. 2-4 weeks after surgery, patients received adjuvant radiotherapy, hormone therapy (if they had a hormone receptor-positive tumour), and adjuvant intravenous bevacizumab. The primary endpoint was pathological complete response in breast and axillary lymph nodes after neoadjuvant treatment, determined after centralised review in accordance with Sataloff classification and assessed in the intention-to-treat population. Our analysis of toxic effects included all patients who received at least one dose of bevacizumab. The trial is complete and follow-up is ongoing. This study is registered with ClinicalTrials.gov, number NCT00820547. FINDINGS: Between Jan 16, 2009, and Sept 8, 2010, we enrolled 101 patients, one of whom withdrew consent before treatment, leaving 100 patients in the primary endpoint analysis. After neoadjuvant therapy, 19 (19% [95% CI 12-28]; p=0·16) of 100 patients achieved a pathological complete response according to centralised review. The most frequent grade 3-4 events during the neoadjuvant phase were neutropenia (89 [89%] of 100 patients), febrile neutropenia (37 [37%]), and mucositis (23 [23%]) and during the adjuvant phase the most frequent grade 3-4 adverse event was proteinuria (5 [7%] of 75 patients). One (1%) patient died of thrombotic microangiopathy after cycle 1, which was thought to be related to bevacizumab. Two patients (3%) developed transitory heart failure. 48 (48%) patients had serious adverse events, the most frequent of which was febrile neutropenia (28 [28%]). INTERPRETATION: Our results suggest that the addition of bevacizumab to neoadjuvant and adjuvant chemotherapy does not provide clinical benefit to patients with non-metastatic HER2-negative inflammatory breast cancer. Longer follow-up and correlative studies to identify patients who might benefit from bevacizumab are needed. FUNDING: Roche, La Ligue Nationale contre le Cancer, UNICANCER, and Chugai Pharma.

[Molecular signatures of breast cancer: What clinical utility?]. / Les signatures moléculaires commerciales: quelle utilité clinique ?

The role of molecular signatures in the adjuvant management of breast cancer remains a debated topic. Discussions should take into account the level of scientific validation, the impact on practice, the expected benefits and financing issues. This article presents the key points for a rational use of commercial molecular signatures.

[Use of guidelines and heterogeneity of decision making for adjuvant chemotherapy in hormone-receptor positive, HER2-negative, early breast cancer: results of a French national survey]. / Utilisation de référentiels et hétérogénéité décisionnelle des indications de chimiothérapie adjuvante dans les cancers du sein exprimant les récepteurs hormonaux, HER2-négatifs : résultats d'un sondage national en France.

Adjuvant chemotherapy for localised breast cancer aims at reducing the risk of relapse and at increasing overall survival. Decision criteria include tumour burden and biological profile. It appears currently difficult to evaluate the benefit/risk ratio in certain borderline cases, which are more and more frequent. We have evaluated through an anonymous web survey conducted as part of the 2013 Annual Saint-Paul-de-Vence breast conference, the chemotherapy decisions, use of guidelines and level of certainty with decisions in this type of situation through four clinical cases. The survey was proposed to 1,190 French physicians who are directly in charge of breast cancer care, whatever their specialty. Three hundred and fifty-three of them replied, of whom 67 % were oncologists and 15 % surgeons. A significantly heterogeneous decision was observed for two out of four cases, in which 52 and 69 % of the physicians opted for adjuvant chemotherapy, versus 48 and 21 % for abstention respectively. Eighty seven percent of responding physicians used guidelines to guide their decision. These guidelines were regional for 63 %, national for 36 %, local in 21 % and international in 16 % of the cases. The level of certainty varied with clinical cases but not with the physician's specialty, nor type of decision.