During the trial, the treatment was generally well tolerated, with only a small proportion of serious adverse events reported. Three adverse effects—fatigue, somnolence, and diarrhea—occurred more frequently in the treatment group than the placebo group. Fatigue and somnolence affected about 10% of patients, and diarrhea was observed in approximately 5%. Despite these occurrences, the overall tolerability profile of the treatment was considered acceptable, with most patients managing adverse effects without needing to discontinue therapy.
However, the study does have important limitations. One key limitation is the lack of data on long-term breast cancer outcomes, such as recurrence and survival. This omission is due to the nature of hormone receptor–positive, HER2-negative breast cancer, which tends to relapse later, often beyond the 5-year mark. Since the full trial including the optional extension phase spans just over 2 years, it is too soon to assess any impact on recurrence rates or mortality. As of now, no increase in early recurrence has been observed, which is encouraging, but insufficient to draw definitive conclusions.
Future research will be necessary to determine the long-term safety and impact of these therapies. Data from the extended follow-up phase of the trial, as well as from real-world evidence, will be crucial. It will also be important to monitor any potential long-term risks, particularly in women at high risk of developing breast cancer who are using these drugs preventively. While the mechanism of action does not suggest an increased cancer risk, long-term surveillance will be essential to confirm the drugs’ safety and ensure that symptom relief does not come at the expense of increased recurrence or cancer incidence over time.