Breakthrough Advances at ESMO 2025 Redefine Breast Cancer Treatment with Targeted and ADC Therapies

The results presented at the European Society for Medical Oncology Congress (ESMO 2025) represent a new milestone in breast cancer research, with evidence that consolidates the role of antibody conjugates (ADCs) and targeted endocrine therapies in improving survival and reducing the risk of relapse in both early and metastatic disease.

Daiichi Sankyo | AstraZeneca’s Phase III Destiny-Breast05 trial demonstrated that trastuzumab deruxtecan reduced the risk of recurrence or death by 53% compared with T-DM1 in patients with early HER2-positive breast cancer with residual invasive disease after surgery. The three-year invasive disease-free survival rate was 92.4%, compared with 83.7% in the control group.

Trastuzumab deruxtecan reduced the risk of recurrence in early HER2+ breast cancer by 53%.
The results, presented at the ESMO Presidential Symposium, confirm that this ADC could set a new standard for post-neoadjuvant therapy for high-risk patients. “These data could transform clinical practice in the post-neoadjuvant setting ,” noted Dr. Charles Geyer , principal investigator of the study. The safety profile remained consistent with previous studies, with no new signals of toxicity.

The Destiny-Breast11 study showed that the same ADC, administered before surgery (neoadjuvant), achieved a complete pathological response of 67.3%, compared to 56.3% for standard treatment with anthracyclines followed by THP (trastuzumab, pertuzumab, and paclitaxel).

Datopotamab deruxtecan prolonged survival by five months in metastatic TNBC

According to lead investigator Dr. Nadia Harbeck (University of Munich), the results “suggest a new standard of neoadjuvant treatment for patients with high-risk HER2+ breast cancer .” The improvement was seen across all subgroups, including HR-positive and HR-negative patients, with a favorable safety profile and a lower rate of serious adverse events compared with conventional treatment.

The Vall d’Hebron Institute of Oncology (VHIO), with the participation of oncologist Dr. Santiago Escrivá de Romaní, highlighted the importance of achieving a pathological complete response (PCR) to reduce the risk of relapse in high-risk patients. “Achieving a PCR is a key objective to prevent relapse , ” explained the researcher, who emphasized that the trial results demonstrate the potential to replace anthracycline-based regimens with more targeted and less toxic therapies.

Sacituzumab govitecan delayed progression 38% more than chemotherapy

The Tropion-Breast02 trial confirmed that datopotamab deruxtecan (Dato-DXd) improved overall survival by five months versus chemotherapy in first-line treatment of metastatic triple-negative breast cancer , with a median of 23.7 months versus 18.7. It also reduced the risk of progression or death by 43%, with a median progression-free survival of 10.8 months versus 5.6.

The objective response rate was also higher (62.5% vs. 29.3%), and responses were maintained for more than a year on average. According to Dr. Rebecca Dent (Singapore), “This ADC significantly prolongs life and doubles progression-free time, even in patients with highly aggressive disease who are not candidates for immunotherapy.”

Ribociclib and abemaciclib consolidate their role in the management of HR+/HER2- breast cancer

In the same context, Gilead Sciences presented the results of Ascent-03, where sacituzumab govitecan (Trodelvy) achieved a 38% reduction in the risk of progression or death compared to chemotherapy in first-line metastatic triple-negative breast cancer. Progression-free survival was 9.7 months , compared to 6.9 months with chemotherapy.

Dr. Javier Cortés (IBCC, Spain) noted that “sacituzumab govitecan could become the first reference ADC for all patients with metastatic triple-negative breast cancer in first-line treatment.” The safety profile was manageable and consistent with previous trials.

In early HR+/HER2- disease , the Novartis Natalee study showed a 28.4% reduction in the risk of relapse at five years with ribociclib (Kisqali) in combination with endocrine therapy, compared with endocrine therapy alone. Invasive disease-free survival rates were 85.5% versus 81 %, confirming a sustained benefit after treatment completion.

Giredestrant offers an endocrine alternative without ovarian suppression

Researcher Dr. John Crown (Dublin) emphasized that “the benefit of ribociclib persists well beyond treatment, offering patients a greater chance of living cancer-free .” Spain had a prominent role in the trial, coordinated by the Geicam group, with 47 hospitals and more than 700 patients.

The monarchE study , presented by Lilly , confirmed that abemaciclib (Verzenios) combined with endocrine therapy reduced the risk of death by 15.8% in patients with high-risk, node-positive HR+/HER2- early breast cancer . Invasive disease-free survival also improved steadily over seven years of follow-up.

Dr. Stephen Johnston (The Royal Marsden) emphasized that “this is the first treatment in over two decades to demonstrate a clear overall survival benefit in this adjuvant setting.” The results consolidate abemaciclib as the gold standard.

The Empress study, from Medsir and Roche , showed that the selective estrogen receptor degrader giredestrant achieved a significant reduction in the proliferation marker Ki-67 in premenopausal women with ER+/HER2- breast cancer, without the need to suppress ovarian function. Researcher Dr. Antonio Llombart-Cussac noted that this approach “could significantly improve the quality of life of young patients by avoiding the side effects of ovarian suppression .” The study opens up new possibilities for managing this group of patients.

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(Featured image by Angiola Harry via Unsplash)

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