NEW YORK (Reuters Health) – Longer-term follow-up data from the MINDACT trial confirm the clinical utility of the 70-gene MammaPrint assay to help guide chemotherapy decisions in women with early breast cancer, but also suggests that age may be a factor.
“With a more mature follow-up approaching 9 years, the 70-gene signature shows an intact ability of identifying among women with high clinical risk, a subgroup, namely patients with a low genomic risk, with an excellent distant metastasis-free survival when treated with endocrine therapy alone,” the study team reports in Lancet Oncology.
“However, in an underpowered exploratory analysis this benefit appears to be age-dependent, as it is only seen in women younger than 50 years,” report Dr. Martine Piccart of the Jules Bordet Institute, in Brussels, and colleagues.
The European multicenter MINDACT trial enrolled 6,693 women with early-stage breast cancer and up to three positive lymph nodes.
Women determined to have low clinical and low genomic risk (based on MammaPrint) did not receive chemotherapy, while those at high clinical and high genomic risk did receive chemotherapy. Women with discordant risk results (high clinical risk but low genomic risk or low clinical risk but high genomic risk) were randomly assigned to receive chemotherapy or not based on either the clinical risk or the genomic risk.
The updated distant-metastasis-free survival (DMFS) rate at five years in women with high clinical risk and low genomic risk who skipped chemotherapy was 95.1%, which is above the predefined non-inferiority boundary of 92%, “supporting the previous analysis and proving MINDAT as a positive de-escalation trial,” the authors say.
The eight-year estimates overall point to a slightly larger DMFS benefit with than without chemotherapy for patients with high clinical risk and low genomic risk (92.0% vs. 89.4%; hazard ratio 0.66; 95% CI 0.48 to 0.92).
However, the magnitude of the benefit from adding chemotherapy to endocrine therapy “remains small (2.6 percentage points) and is not enhanced by nodal positivity,” the authors note.
Now, with the longer follow-up period (median 8.7 years), a “potentially clinically relevant difference” has emerged in the hormone receptor-positive, HER2-negative women according to age, they note.
For women with high clinical and low genomic risk older than age 50, there was no significant difference in DMFS between women who received chemotherapy and those who did not (with an absolute survival gain of just 0.2 percentage points with chemotherapy), indicating that these women can safely avoid chemotherapy and achieve the same outcome, the authors say.
However, in women younger than age 50, “a potentially clinically relevant chemotherapy benefit of about 5 percentage points is observed at longer follow-up, which might be in part related to chemotherapy-induced ovarian function suppression,” they report.
“It is important to acknowledge that this subgroup analysis was exploratory, limited to the 1,358 women at high clinical and low genomic risk with hormone receptor-positive, HER2-negative tumors,” the authors write.
Summing up, they say, for older women, “a strong message from the mature results from MINDACT and TAILORx is that multigene signatures guiding omission of chemotherapy, in the presence of a high clinical risk, are robust decision aids.”
“MINDACT confirms what has been learned in the past decade: namely that clinical and genomic risk assessments provide independent prognostic information and should both be integrated into treatment decisions about adjuvant chemotherapy in breast cancer. MINDACT also shows that the inclusion of genomic information contributes to the much-needed personalized oncology component of clinical care,” they conclude.
The study was funded by grants from the European Commission Sixth Framework Programme. Several authors report financial ties to Agendia, which markets the MammaPrint test.
SOURCE: https://bit.ly/2PLUbKh Lancet Oncology, online March 12, 2021.
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