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Randomized Controlled Trial
. 2025 Sep;133(5):625-632.
doi: 10.1038/s41416-025-03097-z. Epub 2025 Jul 4.

Primary tumour resection plus systemic therapy versus systemic therapy alone in metastatic breast cancer (JCOG1017, PRIM-BC): a randomised clinical trial

Tadahiko Shien  1 , Fumikata Hara  2 , Kenjiro Aogi  3 , Yasuhiro Yanagida  4 , Michiko Tsuneizumi  5 , Naohito Yamamoto  6 , Hiroshi Matsumoto  7 , Akihiko Suto  8 , Kenichi Watanabe  9 , Michiko Harao  10 , Chizuko Kanbayashi  11 , Mitsuya Itoh  12 , Takayuki Kadoya  13 , Keisei Anan  14 , Shigeto Maeda  15 , Keita Sasaki  8 , Gakuto Ogawa  8 , Shigehira Saji  16 , Haruhiko Fukuda  8 , Hiroji Iwata  17 ; JCOG Breast Cancer Study Group
Affiliations
Randomized Controlled Trial

Primary tumour resection plus systemic therapy versus systemic therapy alone in metastatic breast cancer (JCOG1017, PRIM-BC): a randomised clinical trial

Tadahiko Shien et al. Br J Cancer. 2025 Sep.

Abstract

Background: Several prospective studies have evaluated the benefit of primary tumour resection (PTR) in de novo Stage IV breast cancer (BC) patients, but it remains controversial. We aimed to investigate whether PTR improves the survival of de novo stage IV BC patients.

Methods: De novo stage IV BC patients were enrolled in the first registration and received systemic therapies according to clinical subtypes. Patients without progression after primary systemic therapy for 3 months were randomly assigned 1:1 to systemic therapy alone (arm A) or PTR plus systemic therapy (arm B). The primary endpoint was overall survival (OS), and the secondary endpoints included local relapse-free survival (LRFS).

Results: Five hundred seventy patients were enrolled between May 5, 2011, and May 31, 2018. Of these, 407 were randomised to arm A (N = 205) or arm B (N = 202). The median follow-up time of all randomised patients was 60 months. The difference in OS was not statistically significant (HR 0.86 90% CI 0.69-1.07, one-sided p = 0.13). Median OS was 69 months (arm A) and 75 months (arm B). In the subgroup analysis, PTR was associated with improved OS in pre-menopausal patients, or those with single-organ metastasis. LRFS in arm B was significantly longer than that in arm A (median LRFS 20 vs. 63 months: HR 0.42, 95% CI 0.33-0.53, p < 0.0001). There were no treatment-related deaths.

Conclusions: PTR did not prolong OS. However, it improved local control and might benefit a subset of patients, such as those with premenopausal status or with single-organ metastasis. It also improved local relapse-free survival (LRFS), which is a clinically meaningful outcome in trials of systemic therapy.

Clinical trial registration: UMIN Clinical Trials Registry (UMIN000005586); Japan Registry of Clinical Trials (jRCTs031180151).

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Conflict of interest statement

Competing interests: TS reported grants from the Ministry of Health, Labour and Welfare of Japan and from the Japan Agency for Medical Research and Development (AMED) during the conduct of the study, as well as personal fees from Pfizer, Chugai, Lilly, Daiichi Sankyo, MSD, Eisai, AstraZeneca, Taiho, Nihon Kayaku, Gilead. K Anan reported personal fees from EISAI, Daiichi Sankyo, Eli Lilly, Chugai Pharmaceutical, Pfizer, AstraZeneca, MSD, Kyowa Kirin. K Aogi reported the grant from Chugai Pharmaceutical and the personal fee from Eisai, Chugai Pharmaceutical, AstraZeneca, Eli Lilly Japan, Taiho Pharmaceutical, Daiichi Sankyo, Pfizer. FH reported the personal fees from Pfizer, Ili Lilly, Daiichi Sankyo, Kyowa Kirin, Chugai, MSD. TK reported the personal fees from Ili Lilly. GO reported the grants from Japan Agency for Medical Research and Development and Ministry of Health, Labour and Welfare, Japan. HF reported the grants from National Cancer Center and AstraZeneca, Ono Pharmaceutical Co., Ltd, Chugai Pharmaceutical Co., Ltd, Takeda Pharmaceutical Company Limited and the personal fees from Chugai Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., CMIC Co., Ltd. SS reported the grants from Taiho, Eisai, Chugai, Takeda, MSD, AstraZeneca, Daiichi Sankyo, Gilead, Eli Lilly, Sanofi and the personal fees from Chugai, Kyowa Kirin, MSD, Novartis, Eisai, Takeda, Daiichi Sankyo, Eli Lilly, AstraZeneca, Pfizer, Taiho, Ono, Nippon Kayaku, Gilead, Exact Sciences. HI reported the grants from Pfizer and Chugai, Daiichi Sankyo, AstraZeneca and personal fees from Daiichi Sankyo, Chugai, AstraZeneca, Lilly, MSD, Pfizer, Taiho, Kyowa Kirin. No other disclosures were reported. Ethics approval and consent to participate: All methods were performed by the relevant guidelines and regulations. This study was approved by the Ethics Committee of National Cancer Center Hospital East Certified Review Board, and the approval reference number is CRB3180009. Informed consent was obtained from all participants involved in the study.

Figures

Fig. 1
Fig. 1
CONSORT diagram.
Fig. 2
Fig. 2
Overall survival.
Fig. 3
Fig. 3
Forest plot of overall survival subgroup analyses (n = 407).
Fig. 4
Fig. 4
Local relapse-free survival (4-1), Progression-free survival (4-2) (n = 407).
See this image and copyright information in PMC

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