At the 2025 San Antonio Breast Cancer Symposium, we presented an exploratory analysis of the ALTTO trial, looking at adjuvant endocrine therapy in patients with hormone receptor positive or HER2 positive disease. The ALTTO trial was a large study that included more than 8,000 patients that were randomized to four anti-HER2 treatment arms, Trastuzumab, Lapatinib, their sequence or their combination...
At the 2025 San Antonio Breast Cancer Symposium, we presented an exploratory analysis of the ALTTO trial, looking at adjuvant endocrine therapy in patients with hormone receptor positive or HER2 positive disease. The ALTTO trial was a large study that included more than 8,000 patients that were randomized to four anti-HER2 treatment arms, Trastuzumab, Lapatinib, their sequence or their combination. In this specific analysis, we included 2,651 patients out of the 8,300 that were included in the ALTO trial. So we excluded those who received Lapatinib alone with hormonal receptor negative disease, with hormonal receptor positive disease that did not receive adjuvant endocrine therapy or receive ovarian functional suppression alone as adjuvant endocrine therapy. And also those patients that switched from one endocrine therapy to the other during the follow-up. So by including these 2,651 patients, we looked into the comparison between AI, aromatase inhibitors, and tamoxifen. At a 10-year follow-up in this large cohort, we observed that patients who received aromatase inhibitor experienced significantly improved disease-free survival as compared to those who received tamoxifen, tamoxifen alone. There was a 3.6% absolute difference in disease-free survival in an adjusted hazard ratio of 0.65. So apparently, the benefit of an AI over tamoxifen is quite consistent. And this was observed regardless of patient tumor treatment characteristics, meaning that also, for example, premenopausal women, there is still benefit of AI together with ovarian function suppression as compared to tamoxifen. It’s probably the best endocrine therapy that we can offer also to patients with hormone receptor positive or HER2 positive disease. Then we also observed a significant improvement for the DFS, for the AI group for time to first recurrence, 2.6% absolute difference, adjusted hazard ratio again 0.65. However, there was no improvement in overall survival. So our final take on these results, with all the limitations of this binary and exploratory analysis, but still of a large phase trial with centrally tested hormone receptor status and HER2 status, I think these results are suggesting that probably the preferred endocrine therapy also in patients with HER2 positive disease should be considered aromatase inhibitor-based therapy, so together with OFS if we talk about premenopausal women, which is something that was not very clear. We know AI is superior to tamoxifen in general in patients with hormone receptor positive disease and particularly those with HER2 negative disease. Here these data are adding on top of this evidence also the efficacy of AI versus Tamoxifen in this specific and special cohort of patients with hormone receptor positive or HER2 positive disease.
