The Top Breast Cancer News of 2025

The landscape of breast cancer treatment in 2025 has been defined by significant regulatory approvals and breakthrough clinical data, particularly involving antibody-drug conjugates (ADCs) and immunotherapies. Major milestones include the FDA's January approval of datopotamab deruxtecan (Dato-DXd; Datroway) for hormone receptor-positive (HR+), HER2-negative (–) disease, alongside the first significant first-line efficacy improvements in over a decade seen in the DESTINY-Breast09 trial.

Furthermore, advancements in treating aggressive triple-negative breast cancer (TNBC) have sparked excitement, driven by successful ADC-immunotherapy combinations and new fast-track designations for novel targets like B7-H4.Here, we highlight these transformative developments shaping patient care this year.

FDA Approves Dato-DXd in HR+/HER2– Breast Cancer

In January, the FDA approved Dato-DXd, a TROP2-directed ADC, for treating unresectable or metastatic HR+, HER2– breast cancer in patients who have received prior systemic therapy.

This approval was based on the phase 3 TROPION-Breast01 trial, which demonstrated that Dato-DXd significantly improved progression-free survival (PFS) compared with chemotherapy (median PFS of 6.9 months vs 4.9 months). Dato-DXd also showed a higher overall response rate (ORR; 36% vs 23%) and a longer duration of response. Common adverse effects included stomatitis, nausea, fatigue, and decreased leukocytes.

DESTINY-Breast09: T-DXd Plus Pertuzumab Leads in HER2+ Breast Cancer

The phase 3 DESTINY-Breast09 trial demonstrated a highly significant and clinically meaningful improvement in PFS when trastuzumab deruxtecan (T-DXd; Enhertu) was combined with pertuzumab (Perjeta) compared with the current standard-of-care regimen of taxane, trastuzumab, and pertuzumab.

This ADC combination is the first treatment in over a decade to show superior efficacy as a first-line therapy for patients with HER2-positive metastatic breast cancer across a broad patient population. While overall survival (OS) data were not yet mature, the combination arm showed an early positive trend. The safety profile of the T-DXd plus pertuzumab combination was consistent with the known safety of each drug administered separately.

FDA Fast Tracks Emiltatug Ledadotin in Advanced/Metastatic Breast Cancer

The FDA granted fast track designation to emiltatug ledadotin (Emi-Le), a B7-H4-targeting ADC for patients with advanced or metastatic breast cancer. This designation is for those with HER2-low or HER2– disease, including TNBC, who have previously been treated with a topoisomerase-1 inhibitor ADC. HR+patients must have received or be ineligible for endocrine therapy. The designation aims to expedite development for this difficult-to-treat, pretreated population. Initial phase 1 data showed Emi-Le was generally well tolerated with a differentiated safety profile and demonstrated a 23% confirmed ORR in B7-H4 high tumors.

Sacituzumab Govitecan Plus Pembrolizumab Improves PFS in PD-L1+ TNBC

The phase 3 ASCENT-04/KEYNOTE-D19 trial showed that the combination of sacituzumab govitecan (Trodelvy), a TROP2-directed ADC and the immunotherapy agent pembrolizumab (Keytruda) significantly improved PFS. This improvement was observed when used as a first-line treatment for patients with unresectable, locally advanced, or metastatic TNBC whose tumors expressed PD-L1 (combined positive score [CPS] ≥ 10).

The combination was compared with pembrolizumab plus chemotherapy and met its primary end point. This is the first time an ADC combined with an immuno-oncology agent has demonstrated superior efficacy in the early treatment of metastatic breast cancer. The safety profile of the combination was consistent with the known profiles of each drug, with no new safety signals reported.

Immunotherapies Spark Excitement in Triple-Negative Breast Cancer Treatment

2025 has shown that the field of immunotherapies has advanced the treatment of TNBC, a subtype known for being aggressive and difficult to treat. Key advances center on utilizing immune checkpoint inhibitors like pembrolizumab, often combined with other agents, to personalize treatment.

The KEYNOTE-355 trial showed that adding pembrolizumab to chemotherapy significantly improved OS in patients with advanced TNBC expressing high levels of PD-L1 (CPS ≥ 10).The phase 2 SPARK study demonstrated a high ORR and a favorable median PFS with the triplet combination of tislelizumab (Tevimbra), sitravatinib, and nab-paclitaxel. Other approaches include combining chemotherapy/ICIs with a PARP inhibitor and novel regimens using bispecific antibodies that simultaneously target multiple pathways, showing significant antitumor activity regardless of PD-L1 expression.