At the European Society for Medical Oncology (ESMO) 2025 congress, the landscape of early and advanced breast cancer management was powerfully reshaped, with new data spanning hormone-receptor positive (HR+), human epidermal growth factor receptor 2-positive (HER2+) and triple-negative (TNBC) subtypes. Several late-breaking and proffered papers presented practice-changing signals. Dr Ana Tecic Vuger (University Hospital for Tumors, Zagreb, Croatia) breaks down the most practice-changing trials – and what they mean for patient care.

Early breast cancer

HR+/HER2−

The monarchE update (LBA13) delivered much awaited statistically significant overall-survival advantage: the addition of two years of abemaciclib to endocrine therapy yielded a 15.8% reduction in risk of death (HR 0.84; 95% CI 0.72–0.98), in comparison to endocrine therapy alone, on top of sustained invasive-DFS and distant-DFS gains. This reassures the CDK4/6 inhibiton as a strategy to reduce both recurrence and death in carefully selected, node-positive/high-risk patients and will further focus discussion on patient selection, toxicity management and access.

HER2+

DESTINY‑Breast05 (LBA1) and DESTINY‑Breast11 (291O) mark a paradigm shift in curative-intent treatment. DESTINY-Breast05 compared the ADC trastuzumab deruxtecan (T-DXd) versus T-DM1 in patients with residual disease after neoadjuvant therapy and reported a ~53% reduction in risk of invasive disease recurrence or death (HR ~0.47) and 3-year IDFS of ~92.4% vs ~83.7%. DESTINY-Breast11 evaluated neoadjuvant T-DXd (±THP) vs standard anthracycline-taxane → THP and found a significant increase in pCR (67.3% vs 56.3%) with improved early event-free survival signal. These data suggest that potent ADCs are migrating into the early-disease setting – not just for salvage but potentially for curative therapy in high-risk HER2+ patients.

TNBC

GeparNuevo (292MO) (neoadjuvant durvalumab + chemotherapy in early triple-negative breast cancer) provided longer-term results reinforcing that checkpoint inhibitor additions need careful patient-selection: modest pCR increases do not always mirror long-term survival signals. Extended analysis gives nuance about which patients may derive durable benefit from checkpoint inhibition when used perioperatively. This reinforces the need to refine biomarkers beyond PD-L1 and to individualize neoadjuvant strategies.

Metastatic breast cancer

HR+HER2-

In HR+/HER2− metastatic disease previously exposed to CDK4/6 inhibitors, the evERA trial (LBA16) reported a strong progression-free-survival advantage for oral SERD giredestrant plus everolimus over standard endocrine therapy plus everolimus, particularly in ESR1-mutant tumours. This is the first successful Phase III SERD combination in this setting, and offers a promising new treatment option in endocrine-resistant advanced breast cancer, in a difficult post-CDK setting.

Triple-negative breast cancer

ASCENT‑03 (LBA20) and TROPION‑Breast02 (LBA21) (first-line metastatic TNBC not eligible for checkpoint inhibitors) brought practice-changing ADC data. ASCENT-03 (sacituzumab govitecan vs chemotherapy) met its primary PFS endpoint: median PFS 9.7 vs 6.9 months (HR 0.62). TROPION-Breast02 (datopotamab deruxtecan vs investigator’s choice chemo) achieved median PFS ~10.8 vs 5.6 months (HR 0.57) and showed an overall survival benefit (23.7 vs 18.7 months; HR 0.79). These results herald ADCs becoming first-line standards in TNBC subsets, shifting paradigms away from chemotherapy alone, changing the therapeutic landscape for a large subset of metastatic TNBC.

Fertility and survivorship

The POSITIVE trial’s (LBA12) 5-year follow-up reassures that temporary interruption of adjuvant endocrine therapy to attempt pregnancy appears safe in well-selected young women: no statistically significant increase in recurrence risk was seen and pregnancy outcomes were favourable. This advances survivorship care by enabling more confident fertility-preserving discussions without automatic compromise of oncologic safety.

Clinical implications

Taken together, ESMO 2025 reaffirmed the value of risk-adapted intensification (monarchE), introduced ADCs into earlier disease settings (DESTINY trials), advanced survivorship (POSITIVE), introduced novel endocrine-resistant options (evERA), and redefined first-line therapy in metastatic TNBC (ASCENT-03, TROPION-Breast02). For clinical practice, the message would be to refine selection (risk, biology, subtype), update pathways (earlier ADCs, SERD combinations) and engage in shared decision-making (fertility, toxicity, sequencing). The challenge ahead will be equitable access, toxicity management (especially ILD with T-DXd), and integration of these innovations into multidisciplinary care.

Disclosure: Ana Tecic Vuger has nothing to disclose in relation to this interview.

This content has been developed independently by Touch Medical Media for touchONCOLOGY. It is not affiliated with the European Society for Medical Oncology (ESMO). Views expressed are the speaker’s own and do not necessarily reflect the views of Touch Medical Media.

Cite: ESMO25 breast cancer round-up: What’s new and what matters? touchONCOLOGY. November 11th, 2025

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