347eP Immunotherapy–related toxicity and its association with pathologic complete response in early-stage triple-negative breast cancer

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.