C. Breton-Callu

Clinical and genomic analysis of a randomised phase II study evaluating anastrozole and fulvestrant in postmenopausal patients treated for large operable or locally advanced hormone-receptor-positive breast cancer

Background:The aim of this study was to assess the efficacy of neoadjuvant anastrozole and fulvestrant treatment of large operable or locally advanced hormone-receptor-positive breast cancer not eligible for initial breast-conserving surgery, and to identify genomic changes occurring after treatment.Methods:One hundred and twenty post-menopausal patients were randomised to receive 1 mg anastrozole (61 patients) or 500 mg fulvestrant (59 patients) for 6 months. Genomic DNA copy number profiles were generated for a subgroup of 20 patients before and after treatment.Results:A total of 108 patients were evaluable for efficacy and 118 for toxicity. The objective response rate determined by clinical palpation was 58.9% (95% CI=45.0–71.9) in the anastrozole arm and 53.8% (95% CI=39.5–67.8) in the fulvestrant arm. The breast-conserving surgery rate was 58.9% (95% CI=45.0–71.9) in the anastrozole arm and 50.0% (95% CI=35.8–64.2) in the fulvestrant arm. Pathological responses >50% occurred in 24 patients (42.9%) in the anastrozole arm and 13 (25.0%) in the fulvestrant arm. The Ki-67 score fell after treatment but there was no significant difference between the reduction in the two arms (anastrozole 16.7% (95% CI=13.3–21.0) before, 3.2% (95% CI=1.9–5.5) after, n=43; fulvestrant 17.1% (95%CI=13.1–22.5) before, 3.2% (95% CI=1.8–5.7) after, n=38) or between the reduction in Ki-67 in clinical responders and non-responders. Genomic analysis appeared to show a reduction of clonal diversity following treatment with selection of some clones with simpler copy number profiles.Conclusions:Both anastrozole and fulvestrant were effective and well-tolerated, enabling breast-conserving surgery in over 50% of patients. Clonal changes consistent with clonal selection by the treatment were seen in a subgroup of patients.

Abstract P5-16-23: Rapid germline BRCA screening for locally advanced breast cancer changes surgical procedure after neoadjuvant chemotherapy

Introduction Neoadjuvant chemotherapy (NAC) is proposed in case of locally advanced breast cancer (LABC) to improve breast conservative treatment (BCT). In the case of germline BRCA mutated (gBRCAm) patients, risk-reducing prophylactic surgical strategies in France are mastectomy for pre-symptomatic. On the other hand, BCT is proposed to all patients after NAC according to clinical response, regardless their gBRCAm status. Moreover, in the case of BRCA mutation, local recurrence risk at 15 years is higher in the BCT group (23%) vs mastectomy (5%) (Pierce 2010). The aim of this retrospective one-institution analysis is to evaluate if the knowledge of gBRCAm status impact surgical decision. Patients and methods All patients who underwent BRCA genetic testing during NAC for ≥ 3cm breast cancer between 2012 and 2015 were included. BRCA testing was decided with each patient based on age, familial history of breast or ovarian cancer and histological characteristics of the tumor. Rapid germline BRCA mutation screening was performed through targeted next generation sequencing with a 25-genes panel including full coding sequence of BRCA1 & 2. Deleterious mutations were detected using MiSeq reporter and confirmed by Sanger sequencing before giving the results to the clinical geneticist, and finally used for the choice of surgical strategy. At the end of NAC (6 three-weeks cycles in our center), a shared-decision making for surgical procedure was performed, based on pre and post-NAC clinical and radiological features, and results of the genetic testing. Results A total of 25 patients (including three with bilateral cancer) were tested during NAC: mean age 38 years (26-64); mean clinical size 46 mm (20-130mm); histological types: triple negative (n=14), HER-2 positive (n=7), luminal (n=7). A germline BRCA mutation was detected in 10 patients (40%) : 8 BRCA1 and 2 BRCA2, including 8 patients among the 14 patients with a Manchester score > 20 (6 BRCA1 & 2 BRCA2). Two patients were secondarily excluded (one being metastatic and one died during NAC), one of them having a gBRCAm status. All the 23 patients evaluable for the surgical procedure after NAC could be eligible for a BCT. All the 9 patients with gBRCAm status choose mastectomy in the shared-decision making procedure while a BCT was performed in 12 of the 14 remaining patients without BRCA mutation. Discussion In this highly selected subgroup of patients, gBRCAm rate is higher (40%) than the usual rate for BRCA testing (17% in our center). Regarding the rationale for BCT or mastectomy procedure in LABC or pre-symptomatic gBRCAm patients, the duration of NAC allows rapid germline BRCA screening that looks very useful considering the high incidence of mutation we observed and the impact on surgical final decision. Furthermore, in the group of high Manchester score (>20), patients without BRCA mutation harbored incidental mutation, currently under analysis, especially on other genes involved in hereditary breast cancer, that could also be used as a compelling argument for mastectomy. Citation Format: Tunon de Lara C, Bonnet F, Debled M, Lafon D, Breton-Callu C, Rarouk-Simonet E, Fournier M, Petit A, Bubien V, Quenel-Tueux N, Lagarde P, Longy M, Macgrogan G, Sevenet N. Rapid germline BRCA screening for locally advanced breast cancer changes surgical procedure after neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-16-23.

Apport d’un scanner dosimétrique pré-thérapeutique pour la délinéation du lit tumoral des cancers du sein traités par chimiothérapie néoadjuvante

Le role du complement de dose du lit operatoire (boost) dans les carcinomes mammaires invasifs est soutenu par deux etudes randomisees [1], [2]. La pose de clips au niveau du lit operatoire ameliore le reperage de la cavite operatoire et diminue la variabilite interobservateur [3]. Neanmoins, la delineation de ce volume cible en radiotherapie externe peut etre delicate specialement en cas de larges tumeurs, requerant des techniques oncoplastiques.

Score prédictif de l’envahissement de la chaîne mammaire interne et/ou sus-claviculaire dans les cancers du sein des quadrants internes N0 : aide à la décision pour la radiothérapie

Bien que rarement consideree, la localisation interne des cancers du sein est associee a un risque accru de rechute systemique et de deces par cancer du sein [1], [2], particulierement en l’absence d’atteinte ganglionnaire axillaire [3]. Cette valeur pronostique negative independante indique un drainage lymphatique direct dans le relais mammaire interne et/ou sus-claviculaire. L’irradiation des chaines ganglionnaires internes (CGI) (chaine mammaire interne (CMI) et/ou chaine sus-claviculaire) reste cependant controversee et aucun standard n’existe.