Abstract Background: Neoadjuvant endocrine therapy (NET) is increasingly used in the management of early-stage estrogen receptor-positive (ER+), HER2-negative (HER2-) breast cancer to downstage tumors and evaluate treatment response. The Preoperative Endocrine Prognostic Index (PEPI) score is a validated tool for estimating recurrence risk and informing adjuvant chemotherapy decisions following NET. Prior trials, including IMPACT and Z1031, have shown that patients with a low PEPI score (PEPI=0) have a significantly lower risk of recurrence compared to those with a higher score (PEPI 0). The modified PEPI (mPEPI) score, which omits the ER Allred score, was also developed for patients treated with selective estrogen receptor degraders (SERDs) and is currently being evaluated in the ALTERNATE trial. However, neither the PEPI nor mPEPI score has been studied specifically in patients with invasive lobular carcinoma (ILC), a histologic subtype accounting for 10–15% of all breast cancers and known for its unique clinical features. We evaluated the ability of the mPEPI score to predict recurrence-free survival (RFS) in patients with ILC. Methods: We retrospectively analyzed a prospectively maintained institutional ILC database to identify patients with stage I-III ER+, HER2- ILC treated with NET. An mPEPI score for each patient was calculated as 0-3, with 1 point given for each of the following factors: pathologic tumor size 5 cm, positive pathologic nodal status, and post-treatment Ki-67 2.7%. RFS was analyzed using the Kaplan-Meier method and log-rank tests, with patients grouped by mPEPI score (0 versus 1+; 0–1 versus 2–3) and stratified by menopausal status. Statistical analyses were conducted using R software. Survival analyses were right-censored at 100 months. Results: We identified 124 patients with ER+, HER2- ILC who received NET and had available post-treatment Ki-67 data. Of these, 81 (65.3%) patients were postmenopausal and 43 (34.7%) premenopausal. Eleven (8.9%) patients had a prior history of ipsilateral breast cancer, and 15 (12.1%) had prior exposure to endocrine therapy. At surgery, the mean tumor size was 4.5 cm (range: 0.11-13.7 cm), and most patients were node-negative (n=78, 62.9%). Tumor grade was predominantly grade 1 (29.0%) or grade 2 (67.7%). Most patients received an aromatase inhibitor (n=88, 71.0%), including five (4.0%) with a CDK4/6 inhibitor and six (4.8%) with ovarian suppression. Thirteen (10.5%) patients received a SERD-based regimen, while 22 (17.7%) received tamoxifen alone. mPEPI scores were distributed as follows: score 0 in 19 (15.3%) patients, score 1 in 51 (41.1%), score 2 in 39 (31.5%), and score 3 in 15 (12.1%). Fourteen recurrence events occurred during follow-up (median 41.0 months). When comparing patients with mPEPI 0–1 versus 2–3, RFS at 100 months was significantly higher in the 0–1 group (82.2% versus 73.6%, p=0.04). No significant differences were observed when comparing mPEPI 0 versus 1+, or when stratified by menopausal status regardless of grouping. Conclusions: In this retrospective cohort of ILC patients treated with NET, the mPEPI score demonstrated a significant association with RFS when grouped as 0–1 versus 2–3. These findings suggest that the mPEPI score may help stratify recurrence risk in patients with ILC. Larger studies are warranted to validate the prognostic utility of the mPEPI score in ILC. Citation Format: A. Vertido, A. Quirarte, J. A. Mouabbi, J. Chien, R. A. Mukhtar. Validation of the Modified Preoperative Endocrine Prognostic Index (mPEPI) in a single institution cohort of patients with invasive lobular carcinoma 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 PS3-08-01.
Vertido et al. (Tue,) studied this question.