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In the JCOG1017 trial, untreated de novo Stage IV BC patients received 3\u00a0months of subtype-based systemic therapy before randomization for primary tumor resection. Among 569 treated patients, the overall non-progression disease (non-PD: no 10% or more increase in maximum diameter) rate was 77.2%, and the objective response rate (ORR) was 29.0%. By subtype, non-PD\/ORR rates were TN (78.2%\/36.4%), Luminal (75.4%\/13.4%), HER2 (92.9%\/81.0%), and Luminal-HER2 (66.7%\/40.3%). Multivariable analysis revealed higher non-PD rates in postmenopausal patients (odds ratio (OR) 1.673, p\u2009=\u20090.024) and those with PgR-positive tumors (OR 2.391, p\u2009=\u20090.0019). Endocrine therapy was more effective for patients with PgR-positive tumors (OR 3.258, p\u2009&lt;\u20090.0001) and less practical in those with visceral metastasis (OR 0.605, p\u2009=\u20090.0334). HPD (Trastuzumab, Pertuzumab, Docetaxel)\/HPTX (Trastuzumab, Paclitaxel) therapies (non-PD rate: 92.7%) were highly effective for visceral metastasis (OR\u2009=\u200915.818, p\u2009=\u20090.0030). Patients without progression at 3\u00a0months had significantly better overall survival (HR 0.508, 95% CI [0.398, 0.648]). These findings emphasize that initial therapy must align with subtype, and endocrine monotherapy is suboptimal for ER\u2009+\u2009HER2\u2009+\u2009BC. Effective strategies are needed for those with early progression.<\/jats:p>","DOI":"10.1007\/s12282-025-01821-4","type":"journal-article","created":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T06:34:27Z","timestamp":1769841267000},"page":"396-406","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and prognostic predictors of primary systemic therapy for de novo Stage IV breast cancer. Exploratory analysis of JCOG1017 PRIM-BC"],"prefix":"10.1007","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3202-5512","authenticated-orcid":false,"given":"Tadahiko","family":"Shien","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Ishitobi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keita","family":"Sasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyo","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiko","family":"Shimomura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Tsukioki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuaki","family":"Sagara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuri","family":"Kimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaori","family":"Terata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Ishiba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Yasojima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makiko","family":"Ono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoko","family":"Goda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoichi","family":"Naito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomomi","family":"Fujisawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumikata","family":"Hara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gakuto","family":"Ogawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruhiko","family":"Fukuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroji","family":"Iwata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Breast Cancer Study Group of Japan Clinical Oncology Group (JCOG), Japan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,31]]},"reference":[{"issue":"2","key":"1821_CR1","first-page":"353","volume":"32","author":"J Yamamura","year":"2018","unstructured":"Yamamura J, Kamigaki S, Fujita J, Osato H, Komoike Y. 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Jpn J Clin Oncol. 2023;53(10):893\u20138.","journal-title":"Jpn J Clin Oncol"}],"container-title":["Breast Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12282-025-01821-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12282-025-01821-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12282-025-01821-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T17:26:25Z","timestamp":1781630785000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12282-025-01821-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,31]]},"references-count":16,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["1821"],"URL":"https:\/\/doi.org\/10.1007\/s12282-025-01821-4","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-7776614\/v1","asserted-by":"object"}]},"ISSN":["1340-6868","1880-4233"],"issn-type":[{"value":"1340-6868","type":"print"},{"value":"1880-4233","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,31]]},"assertion":[{"value":"4 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 December 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 January 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Dr. Shien 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, Eizai, AstraZeneca, Taiho, Nihonkayaku, Gilead. Dr. Hara reported the personal fees from Pfizer, Ili Lilly, Daiichi Sankyo, Kyowa Kirin, Chugai, MSD. Dr. Ogawa reported the grants from Japan Agency for Medical Research and Development and Ministry of Health, Labour and Welfare, Japan. Dr. Fukuda 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. Dr. Iwata 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.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"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.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}}]}}