Updates in Breast Cancer From ASCO 2025

Zunairah Shah, MD Roswell Park Comprehensive Cancer Center

August 26, 2025

Microscopic view of cancer cells with surrounding blood cells and immune response, illustrating recent oncological updates and advancements in cancer research.
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The 2025 American Society of Clinical Oncology (ASCO) Annual Meeting highlighted a wave of promising developments in breast cancer research, spanning novel systemic therapies, precision medicine, symptom management, and prevention strategies. Collectively, these advances bring renewed optimism for improving outcomes across disease stages and subtypes.

Metastatic Breast Cancer: New Treatment Frontiers

A marquee presentation came from the DESTINY-Breast09 trial, which highlighted a potentially practice-changing advance in HER2-positive metastatic disease. The combination of trastuzumab deruxtecan (T-DXd) plus pertuzumab as first-line therapy extended progression-free survival (PFS) by 13.8 months compared with the long-standing THP regimen (trastuzumab/pertuzumab/taxane), with a hazard ratio (HR) of 0.56 (95% CI, 0.44–0.71; P < .00001). These results suggest a likely paradigm shift in the frontline management of this population.1 

In triple-negative breast cancer (TNBC), the ASCENT-04/KEYNOTE-D19 trial demonstrated that replacing chemotherapy with sacituzumab govitecan (SG) in combination with pembrolizumab reduced the risk of progression or death by 35% (HR 0.65; 95% CI, 0.51–0.84; P = .0009). Median duration of response was 16.5 months for SG plus pembrolizumab versus 9.2 months for chemotherapy plus pembrolizumab, with improved tolerability. This regimen may emerge as a new first-line standard for PD-L1–positive TNBC.2

Targeting Resistance

Adaptive resistance remains a central challenge in hormone receptor(HR)–positive breast cancer. The SERENA-6 study provided proof of concept that biomarker-driven adaptation can alter the disease course: switching to the oral selective estrogen receptor degrader  camizestrant upon  circulating tumor DNA detection of ESR1 mutations, before radiographic progression, significantly improved PFS (16 vs 9.2 months; HR 0.44; 95% CI, 0.31–0.60; P <.0001).3 

Similarly, the INAVO120 trial showed that adding the PI3Kα inhibitor inavolisib to palbociclib and fulvestrant in PIK3CA-mutant, HR-positive metastatic breast cancer extended median overall survival to 34 months versus 27 months with placebo (HR for death 0.67; 95% CI, 0.48–0.94; P = .02). In addition, chemotherapy was postponed by nearly 2 years. On the strength of these results, inavolisib has now been approved by both the FDA and European Medicines Agency.4

Early Disease and Symptom Management

In early-stage breast cancer, the BWEL trial reinforced the importance of lifestyle interventions. A structured program of diet and exercise in overweight or obese women with early disease reduced recurrence risk, underscoring that non-pharmacologic strategies can meaningfully affect long-term outcomes.5 

In addition, this year’s advances were not limited to tumor-directed therapy. The OASIS 4 trial showed that elinzanetant, a non-hormonal therapy, significantly reduced moderate to severe vasomotor symptoms in women receiving endocrine therapy, with good tolerability. This offers a meaningful supportive care option for a common and burdensome side effect.6

Putting It All Together

The ASCO  breast cancer program showcased broad advances across HER2-positive, TNBC, and HR-positive disease, anchored in precision, biomarker-guided strategies that anticipate resistance, reduce toxicity, and extend survival. At the same time, innovations in supportive care and survivorship remind us that holistic, patient-centered approaches remain essential to comprehensive cancer care.

References 

  1. Tolaney SM, Jiang Z, Zhang O, et al. Trastuzumab deruxtecan (T-DXd) + pertuzumab (P) vs taxane + trastuzumab + pertuzumab (THP) for first-line (1L) treatment of patients (pts) with human epidermal growth factor receptor 2–positive (HER2+) advanced/metastatic breast cancer (a/mBC): Interim results from DESTINY-Breast09. J Clin Oncol. 2025; 43(17_suppl). doi:10.1200/JCO.2025.43.17_suppl.LBA100
  2. Tolaney SM, de Azambuja E, Kalinsky K, et al. Sacituzumab govitecan (SG) + pembrolizumab (pembro) vs chemotherapy (chemo) + pembro in previously untreated PD-L1–positive advanced triple-negative breast cancer (TNBC): Primary results from the randomized phase 3 ASCENT-04/KEYNOTE-D19 study. J Clin Oncol. 2025;43(17_suppl). doi:10.1200/JCO.2025.43.17_suppl.LBA109
  3. Bidard F-C, Mayer EL, Park YH, et al. First-line camizestrant for emerging ESR1-mutated advanced breast cancer. N Engl J Med. 2025;393(6):569-580. doi:10.1056/NEJMoa2502929
  4. Jhaveri KL, Im S-A, Saura C, et al. Overall survival with inavolisib in PIK3CA-mutated advanced breast cancer. N Engl J Med. 2025;393(2):151-161. doi:10.1056/NEJMoa2501796
  5. Sposetti C, Ballman KV, Mackie McCall L, et al. Association of lifestyle factors and pathological characteristics in patients with early breast cancer and overweight/obesity: Results from the Breast Cancer Weight Loss (BWEL) trial. J Clin Oncol. 2025;43(16_suppl):561. doi:10.1200/JCO.2025.43.16_suppl.561
  6. Cardoso F, Parke S, Brennan DJ, et al. Elinzanetant for vasomotor symptoms from endocrine therapy for breast cancer. N Engl J Med. 2025;393(8):753-763. doi:10.1056/NEJMoa2415566