Awareness Fuels Progress: Upcoming Advances in Breast Cancer Treatment

October is Breast Cancer Awareness Month—a time to honor the millions of people impacted by breast cancer, reflect on the progress that has been made, and recommit to accelerating advances that will improve survival and quality of life. Awareness, however, must be matched with action. Fortunately, cancer research continues to deliver transformative treatment options, and the upcoming European Society of Medical Oncology (ESMO) 2025 Congress will showcase pivotal and practice-changing data.

Progress in Hormone Receptor (HR)–Positive, HER2 Non-Amplified Breast Cancer

Adjuvant CDK4/6 inhibition is a recent advance in the treatment of high- and moderate-risk HR–positive primary breast cancer, with both the MonarchE (NCT03155997) and NATALEE (NCT03701334) trials showing improvements in invasive disease-free survival (DFS) and distant relapse-free survival with abemaciclib (Verzenio) and ribociclib (Kisqali), respectively. Topline results from the primary overall survival (OS) analysis in MonarchE were recently announced and demonstrated improvement in OS with the use of abemaciclib.¹ These data will be presented at the upcoming ESMO 2025 meeting. Longer-term, 5-year outcomes from the NATALEE trial will also be presented for adjuvant ribociclib, including updated survival analyses. These eagerly anticipated survival data will likely reinforce the use of adjuvant CDK4/6 inhibition in primary breast cancer treatment.

In the metastatic setting, the development of novel anti-estrogen therapies such as oral selective estrogen receptor degraders (SERDs) has rapidly advanced, with several phase 3 trials now reporting initial results. On the heels of the phase 3 SERENA-6 trial (NCT04964934) presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, additional data regarding quality of life and biomarker-driven subgroup analyses are anticipated at ESMO 2025, which will help to contextualize the use of camizestrant for ESR1-emergent molecular progression. Several other oral SERDs have also recently advanced. In September, the FDA approved imlunestrant (Inluriyo) for the treatment of ESR1-mutated, HR–positive, HER2-negative metastatic breast cancer after progression on other hormone therapies, based on results from the EMBER3 trial (NCT04975308).² The FDA’s decision is awaited regarding the combination of imlunestrant plus abemaciclib, which was superior to imlunestrant monotherapy for ESR1 mutant and wild-type cancers. Also in September, positive topline results were announced from the phase 3 evERA trial (NCT05306340) demonstrating improvement in progression-free survival (PFS) with the oral SERD giridestrant plus everolimus (Afinitor) after progression on CDK4/6 inhibition plus endocrine therapy.³ Notably, improvements in both the ESR1 mutated population and the intent-to-treat population, including ESR1 wild type, were announced, and data will be presented at an upcoming scientific meeting. Several other updates in HR–positive breast cancer treatment are anticipated at ESMO 2025, including other oral SERD combinations, updated data for the PI3K inhibitor inavolisib (Itovebi) from the INAVO120 trial (NCT04191499), and new data from the VIKTORIA-1 trial (NCT05501886) testing the pan-PI3K/mTOR inhibitor gedatolisib in combination with fulvestrant (Faslodex) with or without palbociclib (Ibrance).

Progress in Triple-Negative Breast Cancer (TNBC)

At the ASCO 2025 Annual Meeting, primary results from the phase 3 ASCENT-04 trial (NCT05382286) were presented, which demonstrated improvement in PFS with sacituzumab govitecan (Trodelvy) plus pembrolizumab (Keytruda) as first-line therapy for metastatic, PD-L1–positive TNBC.⁴ For patients with metastatic TNBC that is PD-L1 negative or who are ineligible for immunotherapy, the phase 3 ASCENT-03 trial (NCT05382299) tested first-line sacituzumab govitecan vs standard chemotherapy, and results will be presented at the upcoming ESMO 2025 meeting. Positive topline results were announced, indicating that the trial met the primary endpoint with improvement in PFS.⁵ Data regarding another antibody-drug conjugate (ADC), datopotamab deruxtecan (Dato-DXd; Datroway), are also anticipated at ESMO 2025. Final results from the phase 1b/2 BEGONIA study (NCT03742102), testing Dato-DXd plus durvalumab (Imfinzi) as first-line therapy, will be reported. Data from the phase 3 TROPION-Breast02 trial (NCT05374512), which tested first-line Dato-DXd in PD-L1–negative TNBC, are also anticipated.

Progress Driven by ADCs

Once again, ADCs will be in the spotlight at the ESMO 2025 Congress. In addition to the benefits in TNBC described above, several presentations will report data from studies testing the HER2-directed ADC, fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu), in multiple different contexts. Additional analyses in key subgroups will be presented from the DESTINY-Breast09 trial (NCT04784715), which previously reported significant improvement in PFS with first-line T-DXd for HER2-amplified metastatic breast cancer.⁶ Primary results from the DESTINY-Breast11 trial (NCT05113251) will also be presented. Positive topline results were announced, demonstrating that neoadjuvant T-DXd followed by paclitaxel, trastuzumab (Herceptin), and pertuzumab (Perjeta) improved pathologic complete response rates compared with standard anthracycline-based regimens for high-risk, locally advanced HER2-positive early-stage breast cancer.⁷ Another advancement in the treatment of high-risk, early-stage HER2-positive breast cancer will be presented at ESMO 2025 from the DESTINY-Breast05 trial (NCT04622319), which tested T-DXd vs ado-trastuzumab emtansine (T-DM1) for patients with residual disease following neoadjuvant therapy. Positive topline results showing improvement in invasive DFS with T-DXd were recently announced.⁸

Progress in Breast Cancer Treatment Translates to More Survivors

The ESMO 2025 Congress will also showcase several studies testing strategies to improve quality of life in patients living with and surviving breast cancer. The exciting progress in breast cancer therapeutics underscores the need to continue advancing strategies to support the long-term health of survivors and those living with breast cancer, particularly for young onset cancers. In a special session at the ESMO 2025 meeting, key survivorship topics will be presented, including lifestyle interventions, surveillance and screening, and implementation of digital tools to improve patient-reported outcomes.

As we recognize Breast Cancer Awareness Month, these data remind us that awareness must fuel investment in research and equitable access to innovations. The progress on display at ESMO 2025 is not just scientific progress—it is human progress, representing the combined efforts of patients, clinicians, and scientists determined to outpace breast cancer.

References

1. Lilly's Verzenio® (abemaciclib) increases overall survival in HR+, HER2-, high-risk early breast cancer with two years of therapy. News release. Eli Lilly and Company. Accessed August 27, 2025. Accessed September 29, 2025. https://tinyurl.com/4p5w2krp
2. U.S. FDA approves Inluriyo (imlunestrant) for adults with ER+, HER2-, ESR1-mutated advanced or metastatic breast cancer. News release. Eli Lilly and Company. September 25, 2025. Accessed September 29, 2025. https://tinyurl.com/2fexwcem
3. Positive phase III results show Roche’s giredestrant significantly improved progression-free survival in ER-positive advanced breast cancer. News release. Roche. September 22, 2025. Accessed September 29, 2025. https://tinyurl.com/2jrawxtt
4. 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(suppl 17):LBA109. doi:10.1200/JCO.2025.43.17_suppl.LBA109
5. ASCENT-03: Trodelvy® demonstrates highly statistically significant & clinically meaningful improvement in progression free survival in patients with first-line metastatic triple-negative breast cancer who are not candidates for checkpoint inhibitors. News release. Gilead Sciences. May 23, 2025. Accessed September 29, 2025. https://tinyurl.com/4ryhk4ts
6. ENHERTU (fam-trastuzumab deruxtecan-nxki) plus pertuzumab demonstrated highly statistically significant and clinically meaningful improvement in progression-free survival vs. THP as 1st-line therapy for patients with HER2-positive metastatic breast cancer. News release. AstraZeneca. April 21, 2025. Accessed September 29, 2025. https://tinyurl.com/ycxdtrvw
7. ENHERTU® (fam-trastuzumab deruxtecan-nxki) followed by THP before surgery showed statistically significant and clinically meaningful improvement in pathologic complete response in patients with high-risk HER2-positive early-stage breast cancer in DESTINY-Breast11 Phase III trial. News release. AstraZeneca. May 7, 2025. Accessed September 29, 2025. https://tinyurl.com/4bm25a6f
8. ENHERTU® (fam-trastuzumab deruxtecan-nxki) demonstrated highly statistically significant and clinically meaningful improvement in invasive disease-free survival vs. T-DM1 in DESTINY-Breast05 Phase III trial in patients with high-risk early breast cancer following neoadjuvant therapy. News release. AstraZeneca. September 29, 2025. Accessed September 29, 2025. https://tinyurl.com/4v3ax79f