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.

Nathalie Quenel-Tueux , Marc Debled (1) , Justine Rudewicz (2, 3, 4) , Gaetan Macgrogan (2) , Marina Pulido (5, 6) , Louis Mauriac (7) , Florence Dalenc (8) , Thomas Bachelot (9, 10) , Lortal Barbara , Christelle Breton-Callu , Nicolas Madranges , Christine Tunon de Lara (11) , Marion Fournier , Hervé Bonnefoi (2) , Hayssam Soueidan (12, 4) , Macha Nikolski (4, 3) , Audrey Gros (2) , Daly Catherine , Wood Henry , Rabbitts Pamela , Richard Iggo (2)

1 Service d'Oncologie Médicale
2 VINCO - Validation et identification de nouvelles cibles en oncologie
3 LaBRI - Laboratoire Bordelais de Recherche en Informatique
4 CBIB - Centre de Bioinformatique de Bordeaux
5 Unité de recherche clinique et épidémiologique
6 Centre d'investigation clinique - épidémiologie clinique
7 Plateforme de génétique moléculaire des cancers d'Aquitaine
8 INSERM U563 - CNRS UMR1037 - Centre de Physiopathologie de Toulouse-Purpan
9 Oncogénèse et progression tumorale
10 Département de Médecine Nucléaire
11 Service de Chirurgie
12 Biothérapies des maladies génétiques et cancers

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.British Journal of Cancer advance online publication 14 July 2015; doi:10.1038/bjc.2015.247 www.bjcancer.com.

Mots clés: anastrozole; endocrine treatment; fulvestrant; hormone-receptor-positive cancer; large operable or locally advanced breast cancer; neo-adjuvant

Domaines: Cancer

Nathalie Quenel-Tueux, Marc Debled, Justine Rudewicz, Gaetan Macgrogan, Marina Pulido, et al.. 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.. British Journal of Cancer, 2015, pp.bjc.2015.247. ⟨10.1038/bjc.2015.247⟩. ⟨hal-01180992⟩