Efficacy and prognostic predictors of primary systemic therapy for de novo Stage IV breast cancer. Exploratory analysis of JCOG1017 PRIM-BC.

The optimal initial systemic therapy for de novo Stage IV breast cancer (BC) is critical, particularly to assess early drug efficacy. In the JCOG1017 trial, untreated de novo Stage IV BC patients received 3 months 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 = 0.024) and those with PgR-positive tumors (OR 2.391, p = 0.0019). Endocrine therapy was more effective for patients with PgR-positive tumors (OR 3.258, p < 0.0001) and less practical in those with visceral metastasis (OR 0.605, p = 0.0334). HPD (Trastuzumab, Pertuzumab, Docetaxel)/HPTX (Trastuzumab, Paclitaxel) therapies (non-PD rate: 92.7%) were highly effective for visceral metastasis (OR = 15.818, p = 0.0030). Patients without progression at 3 months 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 + HER2 + BC. Effective strategies are needed for those with early progression.