Outcomes of neoadjuvant endocrine therapy (NAET) versus neoadjuvant chemotherapy (NAC) in stage II-III invasive lobular carcinoma (ILC).

603 Background: ILC is a distinct subtype of breast cancer, accounting for up to 15% of cases, and is characterized by unique clinical and pathological features. ILC often yield poor responses to NAC. Case reports suggest that NAET yields favorable outcomes in ILC. However, no large-scale study has evaluated the impact of NAET in ILC patients. This is the first large study that aims to compare the outcomes of NAC versus NAET in stage II/III ILC. Methods: A retrospective analysis was performed on patients treated at MD Anderson Cancer Center with a diagnosis of anatomical stage II-III estrogen receptor-positive (ER+) HER2-ve ILC in our prospectively collected and curated electronic database. Data collected included demographics, receptor status (ER, PR, HER2), treatments received, clinical anatomic and pathologic stage, type of surgery, surgical pathology outcomes, and recurrence. Endpoints included pathologic complete response (pCR), modified Preoperative Endocrine Prognostic Index (mPEPI) score 0, endocrine therapy responsiveness (ETR; Ki67 ≤10%), rates of axillary downstaging (from node positive to negative), rate of lumpectomy, rate of axillary lymph node dissection (ALND), and 10-year distant recurrence-free survival (10y DRFS). For DFRS, NAC patients were compared to NAET patients who did not receive adjuvant chemotherapy (ACT). Univariate analysis identified variables associated with outcomes, and multivariate logistic regression was planned for significant factors (p < 0.05). Results: We analyzed 611 patients among who the median age was 55 (range 30–91), with 77% White, 8.5% Hispanic, and 8.1% Black. 65% were postmenopausal and all patients received adjuvant ET. 509 (80%) received NAC, and 102 (20%) received NAET. Among NAET patients, 83% received a non-steroidal AI, while 98% of NAC patients received anthracycline-containing regimens. pCR was achieved in 13 NAC patients (2.5%) and 2 NAET patients (1.9%). mPEPI score 0 was attained by 10 NAET patients (9.8%), and the ETR rate was 83%. Axillary downstaging occurred in 11% of NAC patients and 5% of NAET patients. Rates of lumpectomy (17.1% in NAC vs. 17.6% in NAET) and axillary lymph node dissection (ALND) (68.6% in NAC vs. 62.6% in NAET) were comparable between the groups. With a median follow-up of 85 months, 10y DRFS was 55% for NAC and 65% for NAET (HR 0.57, 95% CI 0.33–0.98, P = 0.02). Univariate analysis for DRFS revealed no significant associations with age, race, or initial stage (all p > 0.05), precluding multivariate analysis. Conclusions: This large-scale analysis highlights the limited efficacy of NAC in ILC, with minimal pCR rates. NAET yields promising results, including superior 10y DRFS. These findings underscore the potential of NAET as a viable neoadjuvant option for patients with stage II/III ER+ ILC.