BIG predictors.

Sure, we have Oncotype DX to guide us on optimal chemo use for women with estrogen receptor (ER)-positive, HER2(-) breast cancer. But when are we going to get genomic guidance on optimal endocrine therapy? Enter this secondary analysis of the BIG 1-98 trial—you know, the big one that back in 2005 established a benefit with aromatase inhibition (AI) over tamoxifen in postmenopausal women with ER(+), HER2(-) breast cancer. Adequate tissue for next-generation sequencing (NGS) was available from roughly 2700 of the 8000 enrollees. From these, all 350 with distant recurrence plus a random sampling of those without underwent NGS with successful testing completion on a total of 538 samples. Among these, PI3K mutations were associated with lower rates of recurrence, and those with specific mutations in PI3K derived the biggest benefit from AI over tamoxifen. On the other hand, TP53 mutations, 11q13 and 8p11 amplifications, and increasing number of driver alterations were associated with higher rates of distant recurrence. TBL: Put your hand calcs away because a comprehensive genomic test predicting benefit with various endocrine therapies is coming to a lab near you. | Luen, JAMA Oncol 2018