Abstract P5-12-07: Influence of aromatase inhibitor-related adverse events on the prognosis in postmenopausal Japanese patients with breast cancer: A prospective multicenter cohort study on patient-reported outcomes
Authors: Egawa Chiyomi , Takao Shintaro , Yamagami Kazuhiro , Miyashita Masaru , Baba Masashi , Ichii Shigetoshi , Konishi Muneharu , Kikawa Yuichiro , Minohata Junya , Okuno Toshitaka , Miyauchi Keisuke , Wakita Kazuyuki , Suwa Hirofumi , Hashimoto Takashi , Nishino Masayuki , Matsumoto Takashi , Hidaka Toshiharu , Konishi Yutaka , Sakoda Yoko , Miya Akihiro , Kishimoto Masahiro , Nishikawa Hidefumi , Kono Seishi , Kokufu Ikuo , Sakita Isao , Kitatsuji Koushiro , Oh Koushi , Miyoshi Yasuo 
Published: March 2020

Background Five-year adjuvant treatment with aromatase inhibitors is a standard treatment for postmenopausal women with estrogen receptor-positive breast cancer. However, aromatase inhibitor-related adverse events, including joint and vasomotor symptoms, have a strong impact on patient quality of life and sometimes cause the discontinuation of treatment. The aim of this prospective cohort study based on patient-reported outcomes (PROs) was to examine the influence of adverse events on prognosis in Japanese postmenopausal patients with breast cancer treated with adjuvant anastrozole. Patients and Methods A total of 391 postmenopausal Japanese women with estrogen receptor-positive breast cancer who were treated with adjuvant anastrozole were enrolled from 28 centers in this prospective cohort study (SAVS-JP, UMIN000002455). PRO assessments of adverse events, which included joint and vasomotor symptoms, were obtained at baseline and 3, 6, 9, and 12 months. Symptoms were assessed and assigned to one of four categories: none (G0), mild (G1), moderate (G2), and severe (G3). The questionnaires covered joint symptoms (arthralgia, decrease in range of joint motion, and joint stiffness), vasomotor symptoms (hot flashes, night sweats, and cold sweats), and adherence to anastrozole. The median follow-up was 82 months, and we analyzed the prognosis in patients, focusing on the occurrence of joint and vasomotor symptoms induced by treatment. Results Of the 391 patients, 204 (52.2%) completed 5-year treatment, 75 (19.2%) discontinued (adverse events (n=35), recurrence (n=19), secondary malignancies (n=4), death from non-breast cancer (n=4), and other reasons (n=13)), 48 (12.3%) are receiving treatment, and 64 (16.4%) were unknown. Patients who experienced G2+3 joint symptoms had significantly better disease-free survival (DFS) compared with patients with G0+1 joint symptoms (5-year DFS, 96.1% vs. 83.3%, p=0.002). Similarly, the DFS in patients with G2+3 vasomotor symptoms was significantly better than that in those with G0+1 vasomotor symptoms (5-year DFS, 93.5% vs. 86.3%, p=0.049). Joint symptoms were marginally associated with overall survival (OS) (p=0.062), but no significant association was found with vasomotor symptoms. The DFS was superior in patients with G2+3 joint and vasomotor symptoms (5-year DFS, 100%), inferior in those with G0+1 joint and vasomotor symptoms (5-year DFS, 82.6%), and intermediate in others (5-year DFS, 93.3%; p=0.0024). By multivariable analysis including tumor size and grade, G2+3 joint symptoms were a significant and independent predictive factor for DFS (hazard ratio, 0.298, 95% confidence interval 0.122-0.621, p=0.0007). Conclusion Although adverse events might make patients uncomfortable and reduce their quality of life, it is suggested that worse or new vasomotor symptoms and severe joint symptoms, especially if they are grade 2 or 3, seem to associate with better prognosis.

Citation Format: Chiyomi Egawa, Shintaro Takao, Kazuhiro Yamagami, Masaru Miyashita, Masashi Baba, Shigetoshi Ichii, Muneharu Konishi, Yuichiro Kikawa, Junya Minohata, Toshitaka Okuno, Keisuke Miyauchi, Kazuyuki Wakita, Hirofumi Suwa, Takashi Hashimoto, Masayuki Nishino, Takashi Matsumoto, Toshiharu Hidaka, Yutaka Konishi, Yoko Sakoda, Akihiro Miya, Masahiro Kishimoto, Hidefumi Nishikawa, Seishi Kono, Ikuo Kokufu, Isao Sakita, Koushiro Kitatsuji, Koushi Oh, Yasuo Miyoshi. Influence of aromatase inhibitor-related adverse events on the prognosis in postmenopausal Japanese patients with breast cancer: A prospective multicenter cohort study on patient-reported outcomes [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 P5-12-07.