Impact of mutational profiles on response of primary oestrogen receptor-positive breast cancers to oestrogen deprivation

Pre-surgical studies allow study of the relationship between mutations and response of oestrogen receptor-positive (ER+) breast cancer to aromatase inhibitors (AIs) but have been limited to small biopsies. Here in phase I of this study, we perform exome sequencing on baseline, surgical core-cuts and blood from 60 patients (40 AI treated, 20 controls). In poor responders (based on Ki67 change), we find significantly more somatic mutations than good responders. Subclones exclusive to baseline or surgical cores occur in ∼30% of tumours. In phase II, we combine targeted sequencing on another 28 treated patients with phase I. We find six genes frequently mutated: PIK3CA, TP53, CDH1, MLL3, ABCA13 and FLG with 71% concordance between paired cores. TP53 mutations are associated with poor response. We conclude that multiple biopsies are essential for confident mutational profiling of ER+ breast cancer and TP53 mutations are associated with resistance to oestrogen deprivation therapy

Accelerated Partial Breast Irradiation (APBI): A review of available techniques

Breast conservation therapy (BCT) is the procedure of choice for the management of the early stage breast cancer. However, its utilization has not been maximized because of logistics issues associated with the protracted treatment involved with the radiation treatment. Accelerated Partial Breast Irradiation (APBI) is an approach that treats only the lumpectomy bed plus a 1-2 cm margin, rather than the whole breast. Hence because of the small volume of irradiation a higher dose can be delivered in a shorter period of time. There has been growing interest for APBI and various approaches have been developed under phase I-III clinical studies; these include multicatheter interstitial brachytherapy, balloon catheter brachytherapy, conformal external beam radiation therapy and intra-operative radiation therapy (IORT). Balloon-based brachytherapy approaches include Mammosite, Axxent electronic brachytherapy and Contura, Hybrid brachytherapy devices include SAVI and ClearPath. This paper reviews the different techniques, identifying the weaknesses and strength of each approach and proposes a direction for future research and development. It is evident that APBI will play a role in the management of a selected group of early breast cancer. However, the relative role of the different techniques is yet to be clearly identified