Breast Cancer Coverage from Every Angle

Association of Prognosis in Early Breast Cancer With Somatic Driver Alterations

By: Sarah Campen, PharmD
Posted: Tuesday, August 14, 2018

In women with estrogen receptor–positive, HER2-negative early breast cancer, certain somatic driver alterations seem to be associated with a significantly increased risk of distant recurrence, found Sherene Loi, MD, PhD, of the Peter MacCallum Cancer Centre, University of Melbourne, Australia, and colleagues. Amplifications on 11q13 and 8p11, as well as an increasing number of driver alterations, were linked to distant recurrence. The study, a secondary analysis of the Breast International Group 1-98 randomized clinical trial, was published in JAMA Oncology.

“Classification of somatic driver alterations based on DNA analysis provides valuable prognostic information that may aid treatment decision-making in the adjuvant setting,” concluded the researchers.

Driver alterations were characterized using next-generation sequencing in primary tumors from 764 postmenopausal patients with estrogen receptor–positive, HER2-negative early-stage breast cancer. As part of the original trial, participants were assigned to receive monotherapy with letrozole, tamoxifen, or a sequential strategy for 5 years.

In all, 538 samples (70.4%) were successfully sequenced, including 140 distant recurrence events. The most common alteration was PIK3CA mutation (49%), which was significantly associated with reduction in the risk for distant recurrence. TP53 mutations, amplifications on 11q13 and 8p11, and an increasing number of driver alterations were found to be linked to a significantly greater risk of distant recurrence.

Additionally, they discovered that patients with tumors that harbored PIK3CA mutations had a significantly greater benefit from letrozole over tamoxifen than did those whose tumors did not harbor those mutations (P = .002). Considered a “novel finding,” researchers noted that the exact mechanisms underlying this observation are yet unknown.

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