Nan Chen, MD, on Impact of Anthracyclines in High Genomic Risk Node-Negative HR-Positive/HER2-Negative Breast Cancer

In patients with early-stage, node-negative, HR-positive, HER2-negative breast cancer, there are a couple of different chemotherapy regimens that we use, primarily a taxane-based one and an anthracycline and taxane-based one. We really wanted to understand what the benefit of the additional anthracycline was, and we wanted to relate that to a recurrence score and think about whether there was a certain group of higher-risk patients that may benefit from additional therapy. So, what we did is we performed a post hoc analysis of the TAILORx study, and we included all patients with a recurrence score greater than 11 who received chemotherapy either with TC (taxane-based) or TAC (taxane and anthracycline-based). Ultimately, we ended up with a little over 2,500 patients for this analysis. What we saw was that patients who received TAC were generally younger. They tended to be more likely to be premenopausal, have larger tumors, and be more likely to have progesterone receptor-negative disease. They also tended to have a higher recurrence score compared to patients who received TC as well. This may be reflective of physician prescribing patterns since this wasn’t randomized. Our primary endpoint was looking at distant recurrence-free interval at 5 years. What we saw is that for patients with a recurrence score of less than 31, there was really no benefit to giving additional anthracycline (TAC versus TC). However, in patients with a recurrence score of 31 or above, we saw a statistically significant benefit in giving additional anthracycline to these patients. For secondary survival outcomes, we evaluated a few different things. Distant recurrence-free survival was also statistically significant. There was a trend toward improvement in overall survival, but this wasn’t significant. Additionally, we noted that the benefit of anthracyclines actually increases with increasing recurrence score. For patients with recurrence scores well above 31, in the 40s and 50s, the benefit of anthracyclines was greater than for someone with a recurrence score close to 31. We looked at this in a few different groups, such as premenopausal and postmenopausal women. We saw that the benefit of anthracyclines was somewhat similar in both of these groups. We also conducted unadjusted subgroup analyses categorizing patients by age, tumor size, and tumor grade. In our primary endpoint of distant recurrence-free interval, all subgroups had a benefit with anthracyclines, again in patients with a recurrence score of 31 or greater. In secondary survival outcomes, we found that this benefit was primarily limited to tumors that were greater than 2 cm in size. Ultimately, I think our study shows that there is a relationship between the recurrence score and the benefit of anthracyclines. In this patient population of HR-positive, HER2-negative, node-negative patients, anthracyclines should really be considered. We want to keep in mind that there are limitations to this study, including the fact that this was a post hoc analysis and that the initial study was not designed to evaluate this endpoint. Additionally, there are some late effects of anthracycline usage, such as an increased risk of hematologic malignancy, that may not be accounted for in the follow-up period of our study. These factors should all be discussed with the patient when developing individualized treatment plans. We hope that this data can help guide decisions and help evaluate the benefits and risks of anthracyclines in this patient population.