medwireNews: The use of adjuvant chemotherapy in patients with hormone receptor (HR)-positive, HER2-negative early breast cancer (EBC) and up to three positive lymph nodes (LNs) could be guided by the 21-gene recurrence score (RS) and response to preoperative endocrine therapy (ET), research suggests.
Nadia Harbeck (LMU University Hospital, Munich, Germany) and fellow WSG-ADAPT trial investigators say that this approach could “spare [chemotherapy] for more than half of patients with high clinical risk and up to three involved LNs who are candidates for [chemotherapy] by conventional clinicopathologic criteria.”
The endocrine subtrial of the phase 2/3 umbrella study included 2290 EBC patients with pN0–N1 disease who were given a 3-week course of tamoxifen (mostly premenopausal patients) or aromatase inhibitors (mostly postmenopausal patients) before surgery and had their RS assessed using the Oncotype DX assay (Exact Sciences, Redwood City, California, USA).
Patients who had a low RS of 11 points or less were assigned to the control arm of the study (n=868), while those with an intermediate RS of 12–25 and a response to ET, defined as a central Ki67 score of 10% or below, were assigned to the experimental arm (n=1422). Both these groups were treated with adjuvant ET alone, the researchers explain.
A third group of patients (n=694), namely those with an intermediate RS and no ET response, were assigned to receive dose-dense chemotherapy followed by adjuvant ET as part of the chemotherapy subtrial, the team says.
Analysis showed that patients given aromatase inhibitors were significantly more likely to respond than those given tamoxifen (78.1 vs 41.1%), and that ET response was significantly more common in patients with an RS 0–11 than their counterparts with an RS of 12–25 or greater than 25 (78.8 vs 62.2 and 32.7%, respectively).
Overall, the 5-year rate of invasive disease-free survival (DFS) was “excellent” in the experimental arm at 92.6% versus 93.9% in the control arm, report Harbeck et al. The lower limit of the 95% confidence interval of the between-group difference equaled the noninferiority margin of –3.3 percentage points, therefore providing “borderline” evidence of noninferiority for the experimental arm, they write in the Journal of Clinical Oncology.
The experimental and control arms also had comparable outcomes with regard to 5-year rates of distant DFS (95.6 vs 96.3%) and overall survival (OS; 97.3 vs 98.0%).
For patients given chemotherapy, the 5-year rates of invasive DFS, distant DFS, and OS were 90.3%, 92.8%, and 96.7%, respectively.
Of note, there were no significant differences in invasive or distant DFS between the experimental and control arms by nodal status (pN0 vs pN1) or by age (>50 vs ≤50 years), and the researchers say that multivariable analysis “further supported equivalence of [invasive] DFS and [distant] DFS in the endocrine arms.”
Discussing the findings, Harbeck et al write that ET response is likely to be a “key latent variable influencing efficacy of ET” in this EBC patient population, related to type of treatment and, in turn, menopausal status.
“In view of our results, future application of short preoperative ET in premenopausal patients should involve ovarian suppression to maximize their probability for ET response,” they suggest.
Commenting on the study in a linked editorial, Mitch Dowsett (Royal Marsden Hospital, London, UK) says that the WSG-ADAPT study findings show that “short-term presurgical therapy provides an excellent scenario for discovery of biomarkers of resistance to ET.”
“These studies have the potential to identify resistance mechanisms in those patients with high Ki67 [post-ET] and to guide the selection of agents targeted to the respective mechanisms alongside their adjuvant endocrine treatment.”
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J Clin Oncol 2022; doi:10.1200/JCO.21.02759
J Clin Oncol 2022; doi: 10.1200/JCO.22.00214