Abstract OT1-21-01: Preoperative radiotherapy and systemic therapy following surgery in ‘de novo’ metastatic breast cancer (Protocol MF22-01; Intervention Systemic Treatment METastasis-ISTMET)

Abstract Background Five to eight percent of breast cancer (BC) patients present with distant metastasis at diagnosis, known as ‘de Novo’ metastatic breast cancer (dnMBC). Recent data showed that approximately 40% of dnMBC patients undergo locoregional treatment (LRT). LRT treatment modalities for metastasis and primary tumor benefit a subset of patients with oligometastatic disease. Our study group has recently demonstrated two prospective studies regarding this topic with favorable outcomes. MF07-01 IMET study, one of the first clinical randomized trials, showed that the patients with the diagnosis of dnMBC undergoing LRT followed by systemic therapy had an additional 14% OS benefit by the end of the 10-year follow-up when compared with others who received only systemic therapy. A prospective multicenter registry study MF14-01 BOMET also presented LRT prolonged survival and decreased locoregional recurrence in a prospective registry study with a median follow-up of 3 years. Timing of primary breast surgery either at diagnosis or after systemic treatment provided a survival benefit similar to systemic therapy alone in bone-only dnMBC patients. Although, the optimal timing of concurrent endocrine therapy, radiotherapy, and/or sequential surgery remains unclear. Hypothesis We hypothesize that in the era of modern radiotherapy and endocrine therapy, concurrent radiation and endocrine therapy will be non-inferior to sequential treatment modalities in terms of locoregional and systemic disease control in dnMBC. ER/PR (+), Her2 neu (-) oligometastatic dnMBC patients are potentially curable with multimodality treatments. Objectives The primary objective is to perform a Phase I study to evaluate the feasibility of this curative intent treatment approach for patients with oligometastatic disease. Secondary objectives are to present the treatment response evaluating with CTC and/or ctDNA, and IHC and marker changes with multimodality treatments Methods Postmenopausal ER/PR (+) and Her2 neu (-), oligometastatic dnMBC patients will be enrolled in the study. Inclusion criteria: Primary breast tumor amenable for complete surgical resection, patients in good physical condition for receiving protocol-driven locoregional and systemic treatments and radiotherapy; Bone-only oligometastatic disease (5 or less metastasis); Primary tumor biopsy, metastatic site biopsy (ER/PR, Her2, Ki67). Exclusion criteria: Primary tumor not amenable for complete resection; primary tumor with extended infection, bleeding, or necrosis; patients with poor physical condition which prevents the patient from receiving protocol-driven locoregional and systemic treatment; synchronous primary cancer at the contralateral breast; clinically involved contralateral axillary nodes; patients not suitable for adequate follow-up, and failure to give informed consent. Study Design: • RT to the primary tumor (Hypo fractionated) + AI concurrent, Collect CTC and/or ctDNA • Add CDK4/6i to AI 2-4 weeks after RT + (6 months) • RT to bone metastasis (if still visible), Collect CTC and/or ctDNA + (12 months) • Primary Breast Surgery, Collect CTC and/orctDNA, ER/PR/Her 2 in the final specimen + • CDK4/6i +AI until progression and/or unmanageable toxicity Conclusion We hypothesize that in the era of modern radiotherapy and endocrine therapy, concurrent radiation and endocrine therapy will be non-inferior to sequential treatment modalities in terms of locoregional and systemic disease control in dnMBC. ER/PR (+), Her2 neu (-) oligometastatic dnMBC patients are potentially curable with multimodality treatments. Citation Format: Atilla Soran, Serdar Ozbas, Lutfi Dogan, Kamuran İbis, Mutlu Dogan, M Selam, Kazim Senol, Secil Ak Aksoy, Mine Ozsen, Sibel Cetintas, Turkkan Evrensel, Efe Sezgin. Preoperative radiotherapy and systemic therapy following surgery in ‘de novo’ metastatic breast cancer (Protocol MF22-01; Intervention Systemic Treatment METastasis-ISTMET) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-21-01.