Abstract PD12-02: Eligibility for CDK4/6 inhibitor treatment in 861 patients with invasive lobular carcinoma of the breast: the importance of nodal staging for adjuvant therapy decisions

Abstract Background: The monarchE and NATALEE trials demonstrated significant improvement in invasive disease-free survival with the combination of adjuvant endocrine therapy and a cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6i). Namely, abemaciclib and ribociclib have been used in hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer. By inhibiting cell cycle progression, both abemaciclib and ribociclib can significantly improve invasive disease-free survival in selected patients. Standard indications for adjuvant CDK4/6i therapy include larger tumor size, nodal involvement, or high-risk features such as high grade, high proliferation, or high-risk genomic assay score. However, limited data exist on the indications for and use of CDK4/6i in invasive lobular carcinoma (ILC). ILC is the second most common subtype of breast cancer, comprising up to 15% of all breast malignancies. Nearly 90% of these tumors exhibit HR-positive and HER2-negative status, and they frequently present at a later stage with more indolent features such as lower grade, lower Ki-67, and less lymphovascular invasion than invasive ductal carcinoma. We hypothesized that given these features, a majority of patients with ILC only become eligible for CDK4/6i treatment because of their nodal status. If true, this has implications for the role of surgical staging of the axilla in patients with ILC. Methods: We retrospectively analyzed a prospectively maintained institutional ILC database to identify patients with stage I-III, HR-positive, HER2-negative ILC. Patients were considered eligible for adjuvant CDK4/6i treatment if they met any of the following criteria: nodal positivity, tumor size ≥ 5 cm, or tumor size 2-5 cm with either tumor grade 3, Ki-67 ≥ 20%, or high-risk genomic assay score (MammaPrint high risk or Oncotype Dx score ≥ 26). We determined the proportion of patients with ILC who were eligible for CDK4/6i therapy overall; among those, we evaluated which eligibility criteria were met and what proportion of patients would be considered ineligible in the absence of nodal staging data. Results: From 1,027 ILC cases, we included 861 patients with stage I-III, HR-positive, HER2-negative tumors. Overall, 390 (45.3%) met at least one eligibility criteria for treatment with a CDK4/6 inhibitor. Of those, the most common indication for CDK4/6 inhibitor treatment was nodal positivity, present in 255 (65.4%) patients; the mean number of positive nodes was 4.0 (range= 1-46). The next most common criteria was tumor size ≥ 5 cm (n= 201, 51.5%), followed by Ki67 >20% (n= 23, 5.9%), high-risk genomic assay (n= 11, 2.8%), or tumor grade 3 (n= 8, 2.1%). Of the 255 patients with nodal positivity, 121 (47.5%) met no other eligibility criteria for CDK4/6i treatment, whereas 107 (42.0%) also had a tumor size ≥ 5 cm and 27 (10.6%) also had other high-risk features. In total, 31.0% (121/390) of patients eligible for CDK4/6i therapy met criteria for treatment based on nodal status alone. Conclusion: In patients with early stage ILC, nodal positivity is the most common indication for treatment with CDK4/6 inhibitor, consistent with our hypothesis. These data suggest that implementation of surgical de-escalation strategies, namely the omission of sentinel lymph node surgery, should be applied with caution in patients with ILC. Nearly one third of ILC patients eligible for CDK4/6i therapy may no longer meet treatment criteria in the absence of confirmed nodal positivity, which is often difficult to detect based on imaging alone. Citation Format: N. S. Kim, A. Vertido, A. Quirarte, H. Batra-Sharma, E. Abeles, J. Moya, J. Chien, J. Mouabbi, R. Mukhtar. Eligibility for CDK4/6 inhibitor treatment in 861 patients with invasive lobular carcinoma of the breast: the importance of nodal staging for adjuvant therapy decisions [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PD12-02.