Abstract P2-03-02: Clinical utility of bone scan index (BSI) for breast cancer patients with bone metastasis -Multi-institutional prospective cohort study-
Authors: Kondo Naoto , Naito Yoichi , Yokota Isao Yokota , Nakamura Rikiya , Kikawa Yuichiro , Maeda Hideki , Akabane Hiromitsu Akabane , Sagara Yasuaki Sagara , Aihara Tomohiko , Takahashi Mina , Ohtani Yoko , Ohtani Shoichiro , Mukai Hirofumi 
Published: March 2020

Abstract
Background: The bone is the most frequent site of metastasis from breast cancer. However, evaluation for the response to systemic therapy in bone lesion is troublesome. The bone scan index (BSI) is a quantitative tool for improving the interpretability and clinical relevance of bone scans. The utility of the BSI is well studied in prostate cancer. In both hormone-sensitive and castration-resistant prostate cancer, the pre-treatment BSI is significantly correlated with overall survival. Moreover, patients with a lower BSI after endocrine therapy or chemotherapy exhibited better survival than those without a lower BSI. owever its utility for metastatic breast cancer is unknown. The purpose of this study was to investigate whether pretreatment BSI and treatment-related changes in BSI are related with prognosis and adverse events of breast cancer patients with bone metastasis. Patients and Methods: To evaluate the utility of BSI in patients with breast cancer and bone metastasis, we conducted a multi-institutional prospective cohort study. Key inclusion criteria are histologically or cytologically diagnosed breast cancer with bone metastasis, and less than 3 lines of systemic treatments. Primary endpoint is progression free survival (PFS), and the secondary endpoints are overall survaival (OS) and skeletal related events (SREs). Bone scintigraphy was performed at enrollment, 12 and 24 weeks after enrollment. BSI was calculated by determining the percentage of each bone that is involved by the tracer in relationship to the total skeletal mass, as determined from reference man, which is using the BONEVAVI® automated method (FUJIFILM RI Pharma Co., Ltd., Tokyo, Japan). All patients received standard medical treatment according to guidelines and bone modifying agent. A landmarking Cox model was used to predict PFS and OS by baseline and on-treatment BSI changes. Because on-treatment BSI changes could be observed 12 or 24 weeks, the origin of PFS/OS was set to 12 or 24 weeks and analysis set was defined those who are at risk at 12 or 24 weeks, respectively.Results:Between June 2015 and November 2017, a total of 153 patients from 19 centers were enrolled. The median age of was 63 years old [interquartile range,(IQR): 54-70]. All the patients had bone disease, 17 % (n=26) patients had lung and 5 % (n=7) had liver metastasis. The proportion of each intrinsic subtype was follows; luminal type; 84 % (n=125), luminal HER2 type; 6 % (n=9), HER2 type; 4 % (n=6), TN type; 6 % (n=9) and unknown; n=4. 71% (n=109) of the patients received endocrine therapy, 18% (n=27) received chemotherapy and 11% (n=17) received Anti-HER2 therapy. During the follow-up period (median: 22.5 month, IQR:16.8-29.5), 124 events of disease progression and 51 events of death were observed. The baseline BSI was merely associated with PFS [hazard ratio (HR): 1.01, 95% CI: 0.93 to 1.09] and OS (HR: 1.07, 95%CI: 0.95 to 1.21). The change in BSI from baseline to 12 weeks were significantly correlated with PFS (HR, 1.25, 95% CI: 1.13 to 1.40) and OS (HR: 1.26, 95% CI: 1.08 to 1.47). Similarly, the change in BSI from baseline to 24 weeks on treatment prognosticated for PFS (HR: 1.32, 95% CI: 1.06 to 1.65) and OS (HR: 1.47, 95% CI: 1.11 to 1.95). Conclusion: This study is the first to report the clinical significance of evaluating BSI for metastatic breast cancer patients with bone metastasis. Changes in BSI from baseline to 12 weeks and 24 weeks predicts PFS and OS, which could help patients and physicians to guide treatment decision making.
Citation Format: Naoto Kondo, Yoichi Naito, Isao Yokota Yokota, Rikiya Nakamura, Yuichiro Kikawa, Hideki Maeda, Hiromitsu Akabane Akabane, Yasuaki Sagara Sagara, Tomohiko Aihara, Mina Takahashi, Yoko Ohtani, Shoichiro Ohtani, Hirofumi Mukai. Clinical utility of bone scan index (BSI) for breast cancer patients with bone metastasis -Multi-institutional prospective cohort study- [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 P2-03-02.