Impact of clinical response to neoadjuvant endocrine therapy on patient outcomes: a follow-up study of JFMC34-0601 multicentre prospective neoadjuvant endocrine trial

Takayuki Ueno; Shigehira Saji; Norikazu Masuda; Katsumasa Kuroi; Nobuaki Sato; Hiroyuki Takei; Yutaka Yamamoto; Shinji Ohno; Hiroko Yamashita; Kazufumi Hisamatsu; Kenjiro Aogi; Hiroji Iwata; Takeharu Yamanaka; Hironobu Sasano; Masakazu Toi

doi:10.1136/esmoopen-2017-000314

Impact of clinical response to neoadjuvant endocrine therapy on patient outcomes: a follow-up study of JFMC34-0601 multicentre prospective neoadjuvant endocrine trial

ESMO Open. 2018 Feb 14;3(2):e000314. doi: 10.1136/esmoopen-2017-000314. eCollection 2018.

Authors

Takayuki Ueno¹, Shigehira Saji², Norikazu Masuda³, Katsumasa Kuroi⁴, Nobuaki Sato⁵, Hiroyuki Takei⁶, Yutaka Yamamoto⁷, Shinji Ohno⁸, Hiroko Yamashita⁹, Kazufumi Hisamatsu¹⁰, Kenjiro Aogi¹¹, Hiroji Iwata¹², Takeharu Yamanaka¹³, Hironobu Sasano¹⁴, Masakazu Toi¹⁵

Affiliations

¹ Department of Breast Surgery, Breast Oncology Center, The Cancer Institute Hospital, The Japanese Foundation for Cancer Research, Tokyo, Japan.
² Department of Medical Oncology, Fukushima Medical University, Fukushima, Japan.
³ Department of Surgery, Breast Oncology, National Hospital Organization Osaka National Hospital, Osaka, Japan.
⁴ Department of Surgery, Tokyo Metropolitan Health and Medical Treatment Cooperation Ebara Hospital, Tokyo, Japan.
⁵ Department of Breast Oncology, Niigata Cancer Center, Niigata, Japan.
⁶ Department of Breast Surgery, Nippon Medical School, Tokyo, Japan.
⁷ Department of Breast and Endocrine Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
⁸ Breast Oncology Center, The Cancer Institute Hospital, The Japanese Foundation for Cancer Research, Tokyo, Japan.
⁹ Department of Breast Surgery, Hokkaido University Hospital, Sapporo, Japan.
¹⁰ Oikawa Hospital, Fukuoka, Japan.
¹¹ National Hospital Organization Shikoku Cancer Center, Ehime, Japan.
¹² The department of Breast Oncology, Aichi Cancer Center Hospital, Nagoya, Japan, Nagoya, Japan.
¹³ Department of Biostatistics, Yokohama City University, Yokohama, Japan.
¹⁴ Department of Pathology, Tohoku University School of Medicine, Sendai, Japan.
¹⁵ Department of Surgery (Breast Surgery), Kyoto University, Kyoto, Japan.

Abstract

Background: Neoadjuvant endocrine therapy (NET) has been demonstrated to improve breast-conserving rate and is a widely accepted treatment option for postmenopausal patients with hormone receptor-positive breast cancer. There are few reports on the association of NET response and long-term outcomes.

Objectives: To investigate the prognostic value of clinical response to NET.

Methods: Long-term outcomes of NET were examined in 107 patients who participated in the multicentre prospective neoadjuvant exemestane study, JFMC34-0601. Patients were treated with 25 mg/day exemestane for 16 weeks followed by an 8-week extension depending on the treatment response.

Results: Clinical response included partial response (PR) in 58 patients, stable disease in 41 patients and progressive disease (PD) in 8 patients. Clinical response was significantly associated with disease-free survival (DFS), distant disease-free survival (DDFS) and overall survival (OS) (P<0.0001 for all). Especially, patients with PD showed markedly poor outcomes with median DFS=17.8 months (HR (vs PR): 7.7 (95% CI 1.6 to 33)) and median OS=37.7 months (HR (vs PR): 26.3 (95% CI 2.4 to 655)). Preoperative endocrine prognostic index (PEPI) were associated with DFS and marginally with OS (P=0.022 and 0.066, respectively). PEPI=0 indicated an excellent prognosis with 95% 5-year DFS (95% CI 73 to 99). In the multivariate analysis including T stage, nodal status and Ki67, clinical response was an independent prognostic factor for DFS, DDFS and OS (P=0.032, 0.0007 and 0.020, respectively), whereas PEPI was marginally associated with DFS and OS (P=0.079 and 0.068, respectively).

Conclusions: Clinical response to NET showed an independent prognostic value. Patients with PD had markedly poor prognosis, indicating a need of additional therapy. PEPI=0 indicated an excellent prognosis. The integration of clinical response and PEPI would improve decision-making with regard to treatment options for endocrine-responsive breast cancer when these results are validated in a larger clinical trial.

Trial registration number: UMIN C000000345.

Keywords: breast cancer; clinical response; neoadjuvant endocrine therapy; pepi.