Abstract P3-11-08: Treatment patterns and impact of adjuvant chemotherapy and targeted therapy on outcomes in HER2+ microinvasive breast cancer

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Abstract Microinvasive breast carcinoma (MiBC) is defined as invasive breast carcinoma ≤1 mm in size. MiBC is most commonly encountered in the setting of high-grade human epidermal growth factor receptor (HER2) positive ductal carcinoma in situ (DCIS) and may consist of one or more foci. Most MiBC is HER2+, and some studies suggest it may be associated with a worse prognosis than pure DCIS. Evidence-based guidelines on the role for adjuvant systemic therapy in HER2+ lymph node negative (LN-) MiBC are lacking, particularly for cases with multifocal microinvasion. Our objectives were to analyze treatment patterns and assess clinical benefit of adjuvant chemotherapy with or without HER2-targeted therapy (CT/H2TT) in this subgroup. We conducted a retrospective analysis of patients with HER2+ LN- MiBC treated at Memorial Sloan Kettering Cancer Center from 1/1/09-9/30/23. Patients with macroinvasive breast cancer in the preceding 20 years or concurrent to the index MiBC were excluded. Pathologic and clinical data were obtained by a review of pathology reports, slides, and medical records. Pathology slides were reviewed whenever available to confirm MiBC focality. The primary outcome was invasive disease-free survival (iDFS) defined as time from date of surgery to invasion, recurrence, or death. Alive patients without recurrence were censored at last known no evidence of disease (NED) date. The Kaplan-Meier method was used to estimate iDFS. The log-rank test was used to compare iDFS between different groups. We identified 213 patients with HER2+ LN- MiBC who met inclusion criteria. The number of MiBC foci ranged from 1 to 41. Most patients had <5 foci (141, 68%). Compared to patients with <5 foci of MiBC (n=141), patients with ≥5 foci (n=65) were more likely to undergo total mastectomy than breast conserving surgery (72% vs 55%, p=0.02), and receive adjuvant CT/H2TT (39% vs 6.4%, p<0.001), predominantly (94%) trastuzumab/paclitaxel. Age (56 vs 51 years, p=0.1), rates of ER/PR+ (27% vs 18%, p=0.12), adjuvant antiestrogen therapy (28% vs 22%, p=0.3), and adjuvant radiotherapy (44% vs 34%, p=0.2) did not differ significantly between the <5 foci and ≥5 foci cohorts. In the overall cohort, there were 12 invasive disease-free survival (iDFS) events: 2 distant recurrences, 7 local recurrences, 1 contralateral HER2-negative new breast primary, 1 non-BC related death, and 1 death from unknown cause. There was no significant difference in iDFS between patients with <5 vs ≥5 foci (p=0.7). The 5-year iDFS rates in patients with <5 and ≥5 foci were 94% and 95%, respectively. Among patients with ≥5 foci, there was no significant difference in iDFS between those who received adjuvant CT/H2TT (25, 39%) and those who did not (39, 61%) (p=0.4). iDFS did not differ between those with a single focus (n=58) and multiple foci (n=155) of MI (p=0.7). Our study found that there is no difference in iDFS between the patients with <5 and ≥5 foci or those with a single focus and multiple foci of MI. In the cohort with ≥5 foci, we did not detect a statistically significant iDFS advantage for adjuvant CT/H2TT compared to observation following local therapy. Although the small number of events limits statistical power, these findings suggest that patients with HER2+ LN- MiBC and ≥5 foci of MI are generally treated more aggressively than those with <5 foci without significant clinical benefit. Further investigation in a larger cohort is underway to determine optimal management of HER2+ LN- MiBC. Citation Format: Abha Kulkarni, Celine Yeh, Rachel Han, Charlie White, Yuan Chen, Edi Brogi, Andrew Seidman. Treatment patterns and impact of adjuvant chemotherapy and targeted therapy on outcomes in HER2+ microinvasive breast cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P3-11-08.

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