Miami Breast Cancer Conference Provided Exciting Updates and Engaging Discussions

The Miami Breast Cancer Conference focused on ADCs such as Dato-DXd, sacituzumab govitecan-hziy, T-DXd, and patritumab deruxtecan.

The 42nd Annual Miami Breast Cancer Conference took place in March 2025 and, as in recent years, many exciting updates in breast cancer therapy were presented. The key topics at this year’s meeting included antibody-drug conjugates (ADCs), novel therapies targeting estrogen signaling, and patient-centered care.

The development of novel ADCs has identified key targets for the treatment of metastatic breast cancer, including TROP2, HER2, and HER3. The 2 key TROP2-directed ADCs discussed at the meeting were datopotamab deruxtecan-dlnx (Dato-DXd; Datroway) and sacituzumab govitecan-hziy (Trodelvy). TROP2 is an epithelial marker that is overexpressed in all breast cancer subtypes and is associated with more aggressive cancer characteristics. The differential expression of TROP2, with higher expression in breast cancers and lower expression in normal tissues, makes this antigen an ideal target.

In the phase 3 TROPION-Breast01 trial (NCT05104866), treatment with Dato-DXd improved progression-free survival (PFS) compared with standard chemotherapy in patients with metastatic hormone receptor–positive (HR+), HER2-negative breast cancer that progressed after hormone therapy and up to 2 lines of chemotherapy (HR, 0.63; 95% CI, 0.52-0.76; P <.0001).1 Although data for overall survival (OS) were immature, a trend favoring Dato-DXd was observed (HR, 0.84; 95% CI, 0.62-1.14). Notably, the adverse effect (AE) profile of Dato-DXd is somewhat unique compared with other ADCs and includes stomatitis, nausea, neutropenia, and ocular effects such as dry eye and keratitis.

The first TROP2-directed ADC approved for the treatment of metastatic breast cancer, sacituzumab govitecan, was also highlighted at the meeting.2 Data from the phase 3 TROPiCS-02 trial (NCT03901339) and the phase 3 ASCENT trial (NCT02574455) demonstrated superior PFS and OS with sacituzumab govitecan vs standard chemotherapy in HR+ and triple-negative metastatic breast cancer, respectively.3,4 Notable differences between Dato-DXd and sacituzumab govitecan include their AE profiles and scheduling (Dato-DXd is administered every 3 weeks while sacituzumab govitecan is administered on days 1 and 8 of a 21-day cycle). The approvals of both TROP-2-directed ADCs in HR+ breast cancer provide additional treatment options for our patients and highlight the importance of mutual decision-making when considering practical differences between both options.5

Other ADCs targeting HER2 and HER3, including fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) and patritumab deruxtecan (HER3-DXd), respectively, were also discussed at the meeting. Data regarding the optimal line of use for T-DXd were highlighted in panel discussions, noting that earlier use of T-DXd has proven superior to standard chemotherapy in both the HER2-amplified and HER2-low settings.

For HER2-amplified metastatic breast cancer, the fully accrued phase 3 DESTINY-Breast09 trial (NCT04784715) was highlighted, which tested first-line T-DXd vs the current standard of care treatment with taxane, trastuzumab (Herceptin), and pertuzumab (THP). While THP remains the current standard of care, results from the DESTINY-Breast09 trial are anticipated to be reported soon, and, if positive, could change the current standard. However, recently reported data from the phase 3 PATINA trial (NCT02947685) were also highlighted, which demonstrated significantly improved PFS when the CDK4/6 inhibitor palbociclib (Ibrance) was added to endocrine therapy plus trastuzumab and pertuzumab (HP) after response to taxane therapy with HP. These data may fuel the potential dilemma of choosing an induction/maintenance approach vs first line T-DXd with continuation until progression if the DESTINY-BREAST09 trial is positive. A patient-centered approach with mutual decision-making will likely be critical for navigating this potential dilemma.

Another ADC approach, targeting HER3, was an active area of discussion at the Miami Breast Cancer Conference. HER3 is commonly overexpressed in multiple cancers, including breast cancer, and phase 2 data have demonstrated promising clinical activity of HER3-DXd in metastatic breast cancer. While the ADC class has proven effective for treating breast cancer, ADCs with different cytotoxic payloads and antibody targets are needed to overcome concerns regarding decreasing efficacy when sequencing the currently approved ADCs.

The incorporation of novel endocrine therapies into the breast cancer treatment paradigm was also discussed at the conference. The phase 3 EMERALD trial (NCT03778931) led to the first approval of an oral selective estrogen receptor degrader (SERD), elacestrant (Orserdu), for HR+, HER2-negative metastatic breast cancer with an ESR1 mutation.6,7 Several other SERDs are also under development, as well as therapies with differing mechanisms of action, including selective estrogen receptor modulators, proteolysis targeting chimeras (PROTACs), selective estrogen receptor covalent antagonists, and complete estrogen receptor antagonists. In preclinical models, vepdegestrant, a novel PROTAC, leads to greater estrogen receptor (ER) degradation compared with fulvestrant, which degrades approximately 40% to 50% of ER proteins. This potent degradation of ER led to greater inhibition of tumor growth by vepdegestrant compared with fulvestrant in breast xenograft models. In humans, the phase 1/2 VERITAC trial (NCT04072952) demonstrated a well-tolerated safety profile for vepdegestrant, and results from the phase 3 VERITAC-2trial (NCT05654623) are anticipated soon.8

Patient-centered care was another central theme at this year’s meeting. Several sessions included panels of clinicians and patient advocates discussing quality of life and compassionate care. These sessions provided an important reminder that despite the excitement around many new therapeutics, improving toxicity remains an urgent need. With the growing number of treatment options, transparency regarding AEs and mutual decision-making are even more critical. Whole-person care, including lifestyle and mental health care, is an essential component of cancer treatment plans and leads to improved outcomes. For community practices or networks with limited resources, providing lifestyle and whole-person care may be challenging. To address this challenge, novel approaches were presented at the meeting, such as the Dawn Oncology telehealth lifestyle and survivorship clinic that can be integrated into existing clinical practices.9 

The Miami Breast Cancer Conference provides an inclusive forum to address how best to integrate emerging and recently approved therapeutics into clinical practice. With the rapidly evolving landscape of breast cancer therapy, continued discussion to contextualize new data is critical for arming oncology clinicians to provide the best care for our patients.

References

1. Bardia A, Jhaveri K, Im SA, et al. Datopotamab deruxtecan versus chemotherapy in previously treated inoperable/metastatic hormone receptor–positive human epidermal growth factor receptor 2–negative breast cancer: primary results from TROPION-Breast01. J Clin Oncol. 2024;43(3). doi:10.1200/JCO.24.00920
2. FDA approves sacituzumab govitecan-hziy for HR-positive breast cancer. News release. FDA. February 3, 2023. Accessed April 2, 2025. https://tinyurl.com/5ak4c67z
3. Rugo HS, Bardia A, Marmé F, et al. Overall survival with sacituzumab govitecan in hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer (TROPiCS-02): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2023;402(10411):1423-1433. doi:10.1016/S0140-6736(23)01245-X
4. Bardia A, Rugo HS, Tolaney SM, et al. Final results from the randomized phase iii ascent clinical trial in metastatic triple-negative breast cancer and association of outcomes by human epidermal growth factor receptor 2 and trophoblast cell surface antigen 2 expression. J Clin Oncol. 2024;42(15). doi:10.1200/JCO.23.01409
5. FDA approves datopotamab deruxtecan-dlnk for unresectable or metastatic, HR-positive, HER2-negative breast cancer. News release. FDA. January 17, 2025. Accessed April 2, 2025. https://tinyurl.com/msea4r9t
6. FDA approves elacestrant for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer. News release. FDA. January 27, 2023. Accessed April 2, 2025. https://tinyurl.com/5ftxkrs3
7. Bidard FC, Kaklamani VG, Neven P, et al. Elacestrant (oral selective estrogen receptor degrader) versus standard endocrine therapy for estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: results from the randomized phase III EMERALD trial. J Clin Oncol. 2022;40(28):3246-3256. doi:10.1200/JCO.22.00338. Published correction appears in J Clin Oncol. 2023;41(23):3962. doi:10.1200/JCO.23.01239.
8. Hurvitz SA, Schott A, Ma CX, et al. VERITAC update: Phase II study of ARV-471, a PROteolysis TArgeting Chimera (PROTAC) estrogen receptor (ER) degrader in ER+/human epidermal growth factor receptor 2 (HER2)- advanced breast cancer. ESMO Open. 2023;8(1):4. doi:10.1016/j.esmoop.2023.101394
9. Dawn Oncology. Accessed April 2, 2025. https://tinyurl.com/3kcpwrv4