Outcomes of fulvestrant therapy among japanese women with advanced breast cancer: a retrospective multicenter cohort study (JBCRG-C06; Safari).
OBJECTIVE
This retrospective study evaluated the effect of clinical background and treatment line on time to treatment failure (TTF) in advanced/metastatic breast cancer (AMBC) patients receiving F500 in Japan (UMIN 000015168).


METHODS
Patients who commenced F500 treatment were registered at 16 sites in Japan. Correlations between baseline clinicopathological factors, treatment line, and TTF were investigated by Kaplan-Meier analysis. TTF data were analyzed using univariate analysis and multivariate analysis with a Cox proportional hazards model.


RESULTS
Data for 1072 patients were available; 1031 patients (96.2%) were evaluable for efficacy. F500 was administered as first-line treatment in 2.0%, second-line in 22.7%, third-line in 26.7%, and ≥fourth-line in 48.6% patients. Median TTF was 5.4 months. Multivariate analysis found that earlier F500 use (first and second vs. third vs. ≥fourth line; hazard ratio (HR) = 0.80, 95% confidence interval (CI) 0.74-0.86; P < 0.001), longer period from AMBC diagnosis to F500 use (≥3 vs. <3 years; HR 0.60, 95% CI 0.51-0.70; P < 0.001), and no prior palliative chemotherapy administered for unresectable or metastatic breast cancer (no vs. yes; HR 0.69, 95% CI 0.60-0.80; P < 0.001) were associated with significantly longer TTF. Among 691 patients, where information on histologic/nuclear grade was available, a low grade was also associated with a longer TTF, but this finding was not maintained among patients with recurrent breast cancer (N = 558). Among women with recurrent breast cancer, a longer DFI between a patient's initial breast cancer diagnosis and their recurrence was associated with a longer TTF on F500 therapy.


CONCLUSIONS
Our study showed that treatment period of F500 was longer when used in earlier-line treatment. For patients on F500, TTF was also longer for patients who had not received prior palliative chemotherapy and for those who had a longer period from their AMBC diagnosis to F500 use.
Department of Breast Surgery, Matsuyama Red Cross Hospital, 1 Bunkyo-cho, Matsuyama, Ehime, 790-8524, Japan. hkawaguchi@matsuyama.jrc.or.jp.
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http://orcid.org/0000-0002-0811-9335
H
Kawaguchi
Department of Surgery, Breast Oncology, NHO Osaka National Hospital, Osaka, 540-0006, Japan.
N
N
Masuda
Department of Breast and Endocrine Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, 537-0025, Japan.
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T
Nakayama
Department of Breast Oncology, Shikoku Cancer Center, Matsuyama, 791-0280, Japan.
K
K
Aogi
Department of Surgery, Kitakyushu Municipal Medical Center, Kitakyushu, 802-0077, Japan.
K
K
Anan
Breast Medical Oncology Department, The Cancer Institute Hospital Of JFCR, Tokyo, 135-8550, Japan.
Y
Y
Ito
Department of Breast Surgery, Hiroshima City Hiroshima Citizens Hospital, Hiroshima, 730-8518, Japan.
S
S
Ohtani
Department of Breast Oncology, Niigata Cancer Center Hospital, Niigata, 951-8566, Japan.
N
N
Sato
Department of Medical Oncology, Fukushima Medical University, Fukushima, 960-1295, Japan.
S
S
Saji
Department of Breast Oncology, Kyushu Cancer Center, Fukuoka, 811-1395, Japan.
E
E
Tokunaga
Department of Surgery, Division of Breast Surgical Oncology, Showa University School of Medicine, Tokyo, 142-8666, Japan.
S
S
Nakamura
Department of Breast Surgery, Hirosaki Municipal Hospital, Hirosaki, 036-8187, Japan.
Y
Y
Hasegawa
Department of Breast Oncology, Aichi Cancer Center Hospital, Nagoya, 464-8681, Japan.
M
M
Hattori
Department of Breast Oncology, Gunma Prefectural Cancer Center, Ohta, 373-8550, Japan.
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T
Fujisawa
Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, 606-8507, Japan.
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S
Morita
Department of Breast Surgery, JCHO Kurume General Hospital, Kurume, 830-0013, Japan.
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M
Yamaguchi
Department of Breast Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, 113-8677, Japan.
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T
Yamashita
Department of Breast and Endocrine Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, 135-8550, Japan.
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Y
Yamamoto
Breast Oncology Center, The Cancer Institute Hospital Of JFCR, Tokyo, 135-8550, Japan.
S
S
Ohno
Department of Breast Surgery, Graduate School of Medicine, Kyoto University, Kyoto, 606-8507, Japan.
M
M
Toi
D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D004958:Estradiol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D007564:Japan; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D017211:Treatment Failure; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; D000077267:Fulvestrant; D004958:Estradiol
Advanced; Breast cancer; Endocrine therapy; Fulvestrant; Metastatic; Treatment line