Abstract Introduction Invasive lobular breast cancer (ILC) accounts for 10-15% of all invasive breast carcinomas and has distinct clinical and biological characteristics compared with the more common invasive ductal carcinoma (IDC). They are generally ER-positive (ER+) with the exception of a small number of pleomorphic cases and there is some evidence that the 10-year survival rate of women with ILC is lower than that for ER+ IDC. Furthermore, studies have shown that ILC may be less sensitive to chemotherapy than IDC, with lower rates of complete pathological response after neoadjuvant chemotherapy, but it is not clear what effects this has on long term survival. The aim of this study was to investigate whether ER+ ILC patients who received chemotherapy (neoadjuvant or adjuvant) had similar outcomes to ER+ IDC patients who received chemotherapy. Methods Patients were diagnosed at Guy’s & St Thomas’ NHS Foundation Trust between 1971 and 2016 and were eligible for inclusion into the study if they were female, had been diagnosed with either IDC or ILC, if their tumours were ER+, and if they received chemotherapy. They were followed up from date of primary diagnosis until 30th June 2019 and were assumed to be alive in the absence of a reported death date. Patients with estrogen receptor negative (ER-) tumours were excluded, due to well-known chemosensitivity in these breast cancer subtypes. Data used was requested from the Guy’s & St Thomas’ Breast Cancer Database. Results Of 5526 patients diagnosed with ILC or IDC between 1971 and 2016, 3945 were ER+ with 3436 IDC and 509 ILC. ER+ IDC and ILC had similar survival for the first 10 years after diagnosis after which outcomes began to diverge with worse outcomes in ILC. The 10-year and 15-year survival of 59.3% and 47.5% respectively were seen in IDC, and 58.6% and 44.6% in ILC. 1327 ER+ patients who received chemotherapy were selected for analysis, of which 161 (12.1%) were ILC and 1166 (87.9%) were IDC. 159 (12.0%) of patients received neo-adjuvant chemotherapy, while 1168 (88.0%) received adjuvant chemotherapy. In chemotherapy patients, 10-year survival was 53.1% in ILC and 54.0% in IDC, and by 15 years this was 35.1% and 44.7% respectively. In ER+ chemotherapy patients, there was no evidence of a crude association between histological subtype and survival (HR: 1.19, 95% CI: 0.97, 1.47) using Cox regression. However, the multivariate Cox regression model estimated a significantly worse outcome in ILC compared to IDC (HR: 1.28, 95% CI: 1.02, 1.60), adjusted for chemotherapy (neo-adjuvant or adjuvant), stage (I-IV), grade, HER2 status, time period of diagnosis, and surgery type (mastectomy or excision). When stratified by chemotherapy, this association was only observed in patients that received adjuvant treatment. Conclusion This study suggests that ER+ ILC patients who received adjuvant chemotherapy may have a worse outcome than ER+ IDC when adjusted for stage and grade. This is a potentially important finding but needs to be studied in a larger population treated with modern chemotherapy regimens. Other studies have shown that the outcome for ILC is better in the first 5 years after diagnosis compared to ER+ IDC but worsens after 10 years, as it does in this study. Thus, having long follow up is essential in order to be able to detect any differences in survival between ILC and ER+ IDC. Nonetheless, this study has displayed a significant difference in survival between ER+ ILC and ER+ IDC receiving adjuvant chemotherapy, and thus recommendations for adjuvant chemotherapy may need to be considered separately for the two subtypes. Furthermore, it would be beneficial to develop a tool that could help in identifying cases of ILC that would most benefit from chemotherapy. Citation Format: Jasmine Timbres, Charlotte Moss, Anca Mera, Anna Haire, Cheryl Gillett, Mieke Van Hemelrijck, Elinor Sawyer. Survival outcomes after chemotherapy in invasive lobular carcinoma compared to estrogen receptor positive invasive ductal carcinoma [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS8-06.