Abstract PD9-05: The importance of the metastatic biopsy: Clinical and translational relevance in a real world series of patients with metastatic breast cancer

Abstract Background Metastatic breast cancer (MBC) is a heterogeneous disease, whose clinical course and prognosis may be unpredictable, creating significant uncertainty for patients and their families. Heterogeneity is breast cancer subtypes is now well recognized as a potential reason for treatment resistance. Sampling metastatic sites at the point of diagnosis or upon progression, when safe, is recommended to better guide therapy. Purpose This study evaluated patients currently undergoing treatment for MBC in the clinic to determine the clinical and translational significance of a metastatic sample. Methods Patients currently undergoing treatment for MBC at the Olivia Newton John Centre were identified. Data was collected on patient demographics, clinicopathological information, treatment and duration of response. Translational research tissue was collected, with consent, for DNA and RNA analysis. Results Between January 2017 and May 2018 111 patients were identified. The mean age of MBC diagnosis was 60 years (range 30-87), with a mean follow up time of 2.4 years (range 0.8-16). Fifteen patients died during the study period. Sixty-seven (60%) patients were initially treated for early breast cancer (EBC), with a median disease free interval (DFI) 4.7 years. Half (51%) these patients relapsed after five years. At MBC diagnosis, multiple sites of disease were identified including bone, visceral, brain, nodal and skin/chest wall disease. Bone only disease was common (25%), whereas brain disease was rare overall (9%). Metastatic tissue was collected in 67 (60%) patients, where up to four different sites were biopsied. The most commonly biopsied site was bone (n=21), followed by soft tissue (n=20), chest wall/skin disease (n=12), liver (n=9), lung (n=8) and brain (n=8). Serous disease was collected in 16 patients, including pleural, pericardial, ascitic and cerebrospinal fluid. Based on the EBC subtype (n=67), 70% had luminal disease, 19% had Her2 positive disease and 7% had TNBC. However, based on a metastatic biopsy (n=67), only 61% of patients had luminal disease, 21% had HER2 positive, and 18% had TNBC. Paired EBC and MBC samples were available in 48 patients, with significant change in breast cancer subtype demonstrated in 12 of these patients (25%). The most common change was a loss in ER staining, which included 6 patients from ER positive, HER2 negative to TNBC and three patients who became ER negative but remained HER2 positive. Molecular profiling was performed thus far on 8 samples at the single cell and bulk level. These results highlight a large level of inter- and intra-tumoral heterogeneity, and may result in a better understanding of the molecular pathways specifically deregulated in patients at the point of progression. Conclusion In this single institution series of patients with MBC, over half of the cohort underwent at least one metastatic biopsy. Strikingly, a quarter of patients demonstrated a change in their breast cancer subtype, which directly guided subsequent therapy. Metastatic tissue can provide vital information to inform treatment decisions, which may be guided by translational laboratories having access to fresh tissue at the point of metastatic diagnosis or disease progression. Citation Format: Yeo B, Molinaro T, Merino D, Berthelet J, Pouliot N, Fang C, Bell C, Anderson R. The importance of the metastatic biopsy: Clinical and translational relevance in a real world series of patients with metastatic breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD9-05.