An exploratory analysis of the MINDACT trial indicates that chemotherapy does not significantly improve survival outcomes for patients with small (≤1 cm), node-negative, hormone receptor-positive (HR+), HER2-negative breast tumors that are genomically classified as high-risk. The study, published in Nature, found no clear differences in survival at 8 years compared to those with genomic low-risk tumors. These findings challenge conventional treatment strategies for this specific patient subgroup.
The analysis revealed that patients with small, genomic high-risk tumors who received chemotherapy did not show a statistically significant improvement in distant metastasis-free survival (DMFS) compared to those who did not receive chemotherapy (89.2% vs. 94.1% at 8 years). This suggests that the potential benefits of chemotherapy may be limited in this population. The results echo the overall MINDACT study findings, where patients with clinically low-risk/genomic high-risk tumors seemed to derive no benefit from chemotherapy (8-year DMFS 92.3% vs. 90.8% for chemotherapy and no chemotherapy, respectively).
Endocrine Therapy Benefits
For patients with low-risk tumors, endocrine therapy was associated with improved outcomes. The 8-year DFS was 89.3% in those treated with endocrine therapy compared to 79.4% in those treated without it. This highlights the importance of endocrine therapy in preventing disease recurrence, even in small, low-risk breast tumors. The majority of this effect was attributed to a difference in the development of second primary breast cancers (1.1% vs. 6.3%).
Implications for Clinical Practice
The study's findings suggest a potential shift in treatment strategies for patients with T1ab, HR+, HER2-, genomic high-risk tumors. According to the study, "long-term outcome for MINDACT patients with a genomic high-risk, HR+, HER2-, T1abN0 tumor was similar to that patients with a genomic low-risk tumor." Given the lack of apparent benefit from chemotherapy and the observed benefits of endocrine therapy, clinicians may consider de-escalating treatment in this specific subgroup. Further research is needed to determine if alternative treatment strategies, such as extended endocrine therapy or CDK4/6 inhibitors, might be more beneficial.
Study Limitations
The authors acknowledge several limitations, including the small number of events due to the generally good prognosis of patients with small, HR+, HER2- breast tumors. This limited the study's power to detect smaller treatment effects and assess outcomes for T1a tumors separately. Additionally, the study could not exclude the possibility that other prognostic gene expression signatures might identify a subgroup of patients with T1ab tumors who benefit from chemotherapy treatment. The study also acknowledges that even with a median follow-up of 8.8 years, not all disease recurrences were captured, as HR+ breast cancer can recur up to 20 years after initial diagnosis. Finally, the study was non-randomized for endocrine therapy, potentially introducing confounding by indication.
