Background: Adjuvant TH is a standard therapy for patients (pts) with Stage I HER2+ eBC.Administering this de-escalated chemotherapy regimen in the neoadjuvant setting, with or without pertuzumab, in pts with cT1N0 disease might allow tailoring post-neoadjuvant treatment, particularly by de-escalating endocrine therapy in pts achieving a pathological complete response (pCR).We evaluated the pCR rate and EFS in pts with small, clinically node-negative HER2+ eBC treated with TH or THP at a single institution. Methods:We retrospectively identified all consecutive pts with cT 3 cm, cN0, HER2+ eBC who received neoadjuvant weekly paclitaxel for 12 cycles with trastuzumab (TH) or trastuzumab/pertuzumab (THP) at San Raffaele Hospital between 2020 and 2025.Clinico-pathological data were collected including pCR (defined as ypT0/TisN0) and local, locoregional and distant recurrence.Differences between subgroups were assessed using the chi-square test.Results: We included 28 pts, 82.1% (n=23) and 17.9% (n=5) treated with TH and THP, respectively.50.0%(n=14) were premenopausal.Median follow up was 36,2 months.In pts receiving TH, 69.6% (n=16) and 30.4% (n=7) had HR-positive (HR+) and HR-negative tumors, respectively.Among these pts, 4.3% (n=1) had cT1b, 82.6% (n=19) cT1c, and 13.1% (n=3) cT2 disease.All pts receiving THP had cT1c, HR+ tumors.In the TH group, the overall pCR rate was 43.5% (10/23), 85.7% (6/7) in HRand 25.0% (4/16) in HR+ (p=0.019).In the THP group, the pCR rate was 80.0% (4/5).Among HR+ premenopausal pts (n=12), those achieving pCR (66.7%) received tamoxifen alone, whereas those with residual disease (33.3%) received ovarian suppression plus tamoxifen or an aromatase inhibitor.No recurrences were observed, corresponding to a 3-years EFS of 100%. Conclusions:In small HER2+ eBC treated with neoadjuvant therapy, in HR+ pts the THP regimen may be preferred over TH when the intent is to use pCR to guide endocrine therapy de-escalation (e.g.avoiding ovarian function suppression in premenopausal pts).The pCR rate appeared high also with TH regimen.Larger, independent datasets are required to validate these exploratory findings.
Martínez et al. (Fri,) studied this question.