medwireNews: A retrospective analysis points to the utility of intra-tumor copy number heterogeneity (CNH) to identify patients with node-negative, estrogen receptor-positive breast cancer who may be able to forgo adjuvant endocrine therapy (ET).
Daniël Miedema (Amsterdam University Medical Centers, the Netherlands) and study colleagues report in the British Journal of Cancer that individuals classified as low risk on the basis of CNH did not appear to derive a recurrence-free survival (RFS) or disease-specific survival (DSS) benefit from adjuvant ET.
Indeed, use of adjuvant ET in these patients appeared to be significantly associated with an increased risk for death, they add.
The researchers caution, however, that this effect on overall survival (OS) could be “a statistical error due to the relatively small number of patients with CNH low in the current study.”
And they continue: “[F]ollow-up studies to determine the precise effect of endocrine therapy in CNH-low patients is warranted before conclusions can be drawn on a possible negative effect of adjuvant endocrine therapy.”
The study included data on 708 participants of the METABRIC cohort who had not received neoadjuvant or adjuvant chemotherapy for node-negative, estrogen receptor-positive disease and had available copy number data. Just over half (54.5%) of the patients had received adjuvant ET, most commonly tamoxifen, while the remaining 45.5% had not.
Participants were categorized as having low (<0.03), medium (≥0.03, <0.076), or high (≥0.076) risk for recurrence based on the CNH, which “was inferred from a single bulk measurement of copy-number variants,” explain the authors.
Using inverse probability of treatment weighting to balance baseline characteristics between treatment groups, they found no significant RFS or DSS benefit of adjuvant ET in the CNH low-risk subgroup, with a nonsignificant hazard ratio (HR) for recurrence or death of 0.88 and for disease-specific mortality of 1.31, respectively, with use versus nonuse of adjuvant ET.
Conversely, OS was significantly worse for low-risk patients who did versus did not receive adjuvant ET, with an HR for death of 1.62.
In the CNH high-risk subgroup, use of adjuvant ET was associated with significantly improved RFS and DSS (HRs=0.55 and 0.61, respectively), and there was a trend toward improved OS that did not quite reach statistical significance (HR=0.71).
For patients with medium risk, the observed HRs “were between those of patients with high CNH and low CNH for all outcomes,” note Miedema et al.
They also highlight that in multivariable analysis “[t]he interaction between CNH and endocrine therapy was negative for all outcomes, but only significant for OS,” with an HR of 0.77.
The study findings “suggest that patients with high genetic risk defined by CNH benefit from adjuvant endocrine treatment, while for patients with low genetic risk adjuvant endocrine therapy might be omitted,” summarize the researchers.
And they conclude: “To verify these potentially clinically impactful results, further analysis of patients randomised for adjuvant treatment with endocrine therapy or not is warranted.”
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