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Impact of Neoadjuvant Chemotherapy on Surgical Outcomes and Conversion to Node-Negativity in Invasive Lobular Breast Cancer: Analysis of Molecularly High-Risk Tumors by Histologic Subtype on the I-SPY2 Clinical Trial

Mukhtar RA, Dimitroff K, Yau C, Chien AJ, Connolly EP, Howard-McNatt M, Rao R, Ladores V et al.

Annals of surgical oncology, 2025

1,329 participants · 4 citations

Abstract

Background: Invasive lobular carcinoma (ILC) has lower response rates to neoadjuvant chemotherapy (NAC) than invasive ductal carcinoma. While ILC often has low-risk biology, there is a high-risk subset within this heterogeneous tumor type. We compared surgical treatment and response rates by histology in I-SPY2, a multicenter NAC trial.

Methods: We evaluated 1329 patients with stage II-III breast cancer and high-risk 70-gene assay. Patients with classic, pleomorphic, or mixed lobular/ductal histology were included in the lobular cohort. We evaluated rates of mastectomy, positive margins, axillary dissection, and conversion from clinical node-positive (cN+) to pathologic node-negative (ypN-) status after NAC.

Results: Overall, 124 patients (9.3%) had lobular histology, with 69% being hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-). There was no difference in mastectomy rate (57.2% for lobular vs. 55.8% for non-lobular). The ILC cohort had more positive margins after lumpectomy than the non-ILC cohort (21.2% vs. 7.9%; p = 0.023). Within cN0 cases, axillary dissection was significantly more common among the lobular cases (24.1% vs. 14.0%; p = 0.039). Conversion from cN+ to ypN0 did not differ statistically between lobular and non-lobular cases (40.9% vs. 51.2%; p = 0.11). The nodal conversion rate among cN+lobular tumors was 30.6% in HR+/HER2-, 72.7% in HER2+, and 66.7% in triple-negative cases.

Conclusions: These data demonstrate the…

How strong is the evidence?

Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 1,329 participants or records.

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