medwireNews: A post-hoc analysis of the BIG 1–98 trial has identified genetic variants associated with the risk for recurrence after 5 years of adjuvant endocrine therapy in postmenopausal women with estrogen receptor (ER)-positive, HER2-negative, early-stage breast cancer.
Sherene Loi (Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia) and team hope that characterizing oncogenic driver alterations in this setting “may assist clinicians in balancing the potential benefits and risks for the use of extended endocrine therapy, as well as provide potential new drug targets.”
They therefore analyzed data pertaining to 538 participants of the phase 3 BIG 1–98 trial that evaluated adjuvant endocrine monotherapy with letrozole or tamoxifen versus a sequential strategy involving both agents.
Over a median follow-up of 8.1 years, distant recurrences occurred in 140 patients, of which 52 events were considered late as they occurred at least 5 years from randomization.
PIK3CA mutations were observed in more than half (58.8%) of the participants and were significantly associated with a reduced risk for late distant relapse in univariate (hazard ratio [HR]=0.40), but not multivariate analysis, after adjusting for clinicopathological factors.
Analysis by mutation subtype showed that PIK3CA kinase domain mutations were associated with a significantly reduced late recurrence risk versus the wild-type gene, in multivariate analysis (HR=0.22).
By contrast, chromosome 8p11 amplifications and BRCA2 mutations, which occurred in a respective 10.9% and 2.3% of patients, correlated significantly with an increased risk for late distant recurrence in multivariate analysis (HR=3.03 and 4.20, respectively).
Loi et al propose that “tumor PIK3CA status could potentially serve as a useful adjunctive biomarker to clinicopathological variables for determining if a patient has sufficiently low risk to be unlikely to derive a significant benefit from extended endocrine therapy.”
But they emphasize that the results “should be interpreted with caution given the low number of patients and events,” and highlight the need for “confirmation in larger studies.”
The team writes in the Annals of Oncology: “It is likely that prognostic estimates for patients can be refined by incorporating clinical scores such as CTS5 in conjunction with molecular information.
“Further studies will be required to best integrate clinicopathological, gene expression-based, and DNA-based molecular variables for optimal risk stratification.”
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