Abstract Background - Involvement of internal mammary lymph nodes (IMLN) in early breast cancer (EBC) leads to an upstaging of the disease anatomically. Unrecognized involvement of IMLNs leading to under-staging and under-treatment has been a hypothesis of studies demonstrating worse outcomes for medial tumours. Since surgery for removal of IMLNs is associated with high morbidity and radical surgical excision does not improve survival, surgical excision of IMLNs is not part of routine EBC treatment. Recent NCCN guidelines recommend IMLN irradiation for high risk EBC patients to reduce mortality. Metastasis to IMLNs may have a different impact on prognosis and management according to whether detected at the time of primary diagnosis, or later. Aims - The primary aim was to document the incidence of IMLN involvement in an EBC cohort - who underwent autologous deep inferior epigastric perforator (DIEP) flap reconstruction with unplanned sampling of 1 or more IMLNs - to ascertain the incidence of IMLN involvement. Our secondary aim was to ascertain whether IMLN involvement had an impact on management and/or prognosis. Materials and methods -We analyzed retrospectively collected data from a prospectively maintained database of patients who underwent DIEP flap reconstruction at the Royal Marsden Hospital, from April 2006 to March 2018. We used Freeman - Halton extension for Fisher’s test to assess association of IMN involvement with overall survival. Results - Of the 1471 women who underwent free flap reconstruction (1729 flaps) during this time period, 300 with EBC had their IMLNs sampled at the time of DIEP surgery. Of these, 36 had metastasis to their IMLN (incidence of 12%). The median age was 47 years and mean follow up was 34.5 months. Based on timing from initial diagnosis, 17 women had immediate DIEP flap reconstruction, 9 had delayed reconstruction (mean time from primary surgery 25 months) and 10 had reconstruction after mastectomy for loco-regional recurrence (7 at time of mastectomy for recurrence, 3 delayed). We compared outcomes for these 3 groups. Of these 36 patients, 19 had no preoperative staging and were staged only after they were found to have involved IMLNs. Four (2 in the delayed and 2 in the reconstruction after local recurrence group) of these 19 were found to have more widespread metastatic disease. Apart from these 4, based on IMLN involvement, treatment was altered in 17 others (total 21/36, 58.3%) - 8/17 in the immediate group, 7/9 in the delayed group and 2/8 for DIEP after local recurrence. The commonest alteration in treatment was addition of IMLN chain RT in 7 followed by change in endocrine therapy in 5; three had both. One patient who underwent immediate reconstruction had a negative SLN and had systemic adjuvant chemotherapy based solely on the involved IMLN. At a median follow up of 14 months, 12 patients (all either delayed or after local recurrence) of 19 relapsed with metastatic disease and 8 of them died due to disease progression. The local recurrence group had the highest rate of cancer-related mortality (p value < 0.0001) Conclusion - IMLN involvement leads to upstaging of the disease resulting in more significant change in treatment in those undergoing delayed autologous reconstruction. Local recurrence carries the worst prognosis. Staging prior to delayed DIEP surgery purely for reconstruction should be based on risk (from primary diagnosis) and all patients planned for DIEP reconstruction after local recurrence should undergo appropriate pre-operative staging investigations. Multivariate survival analysis using Cox’ proportional hazards model for those with involved versus uninvolved IMLNs to ascertain their prognostic significance will also be reported. Citation Format: Pooja Padmanabhan, Tania Policastro, Natalie To, Jennifer E Rusby, Stuart E James, Paul A Harris, Peter A Barry. The relevance of internal mammary lymph nodes found during autologous breast reconstruction [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-44.