The 2025 San Antonio Breast Cancer Symposium (SABCS 2025) featured some exciting presentations.
The early breast cancer highlights at SABCS 2025 included the landmark lidERA trial, which explored the efficacy of the oral selective estrogen receptor degrader (SERD) giredestrant in the adjuvant treatment of moderate- to high-risk early breast cancer regardless of ESR1 mutation status. This randomized trial compared giredestrant with standard endocrine therapy. The primary endpoint of invasive disease-free survival showed a hazard ratio of 0.70, indicating a 30% improvement (with 32-month median follow-up). The absolute invasive disease-free survival benefit was 2.8%. Although the follow-up was less than 3 years, these data are exciting because giredestrant is the first new endocrine agent introduced in over 20 years. Overall survival data are maturing.
Milana Dolezal, MD, MSci
While the main side effects were arthralgias and hot flashes, it is worth noting that approximately 40% of the participants were premenopausal and required ovarian function suppression with giredestrant. In addition, most patients received chemotherapy prior to enrollment. However, the standard of care arm had a higher treatment discontinuation rate compared to giredestrant, largely due to arthralgias. Additionally, 11.3% of patients experienced grade 1 to 2 bradycardia with giredestrant. Importantly, none of the patients on this trial received combinations with CDK4/6 inhibitors, which is an important standard of care in high-risk early breast cancer. Further data from the MonarchE trial presented at the 2025 European Society for Medical Oncology Congress (ESMO) showed a sustained overall survival benefit of 1.8%, with a significant reduction in mortality risk with the combination of adjuvant abemaciclib and endocrine therapy. There is ongoing interest in the adjuvant data from the lidERA substudy, which has enrolled patients receiving abemaciclib.
Several oral SERD adjuvant trials are ongoing, such as the sequencing EMBER 4 study, which has completed enrollment (n = 8,000) and randomly assigned patients with high-risk early breast cancer to imlunestrant or continued endocrine therapy after 2 to 5 years of treatment, potentially including CDK4/6 inhibitor therapy.
Ductal Carcinoma In Situ
The LORETTA trial focused on low-risk, low-grade, strongly estrogen-receptor positive ductal carcinoma in situ. In this prospective single-arm study, 340 patients were randomly assigned to receive tamoxifen (at 20 mg for 5 years), with the endpoint of a cumulative incidence of ipsilateral invasive breast cancer of under 7%. Unfortunately, the primary endpoint was not achieved (cumulative incidence was 9.8%). This result suggests that there remains a role for surgery and radiation in this patient group to remove an evolving index lesion. Furthermore, a lower dose of tamoxifen, at 5 or 10 mg every other day for 3 years, has demonstrated overall good tolerance.
The Italian TAM01 trial, which was previously presented at SABCS 2022, showed a 42% reduction in breast cancer recurrence (both invasive and ductal carcinoma in situ) over a 10-year follow-up, with a significant carryover effect lasting up to 7 years after end of treatment. TAM01 also showed a 74% reduction in the risk of contralateral breast cancer. This evidence points to the need for multidisciplinary care in managing ductal carcinoma in situ, particularly given that noncompliance rates with endocrine therapy can be as high as 40% across stages and even over 50% in Black women (THRIVE study) who suffer from more intense vasomotor symptoms. In October 2025, the FDA approved elinzanetant as the first dual neurokinin receptor antagonist for treatment of vasomotor symptoms including HR+ breast cancer studied in the OASIS 4 trial. Conjugated estrogens and bazedoxifene, an FDA-approved treatment for vasomotor symptoms, is also being studied presurgery in ductal carcinoma in situ in the PROMIS trial and was reviewed at ASCO 2025.
The ongoing “Lo Tam” trial (NCT06671912) is evaluating lower-dose tamoxifen by randomly assigning postmenopausal patients with low-risk lymph node–negative disease to either standard aromatase inhibitors or 20 mg tamoxifen for 5 years vs the lower dose. Enrollment completed quickly in early 2026.
Triple-Negative Early Breast Cancer
In the triple-negative early breast cancer space, the fertility impact of immune checkpoint inhibition with atezolizumab on premenopausal patients also receiving neoadjuvant chemotherapy was presented in the prospective NSABP B-59/GeparDouze trial. The subgroup included 173 patients overall (94 in the chemotherapy plus atezolizumab group vs 79 in the chemotherapy-only group), with a median age of 37 years; 37% of patients were under 35 years old at diagnosis. Only patients with premenopausal hormonal levels (estradiol and follicle-stimulating hormone) at baseline were included. Differences in ovarian function in checkpoint-treated patients were numerically higher but not statistically significant, although a numerical recovery of ovarian function was more pronounced in the chemotherapy-only arm. Thus, checkpoint inhibition may affect fertility, and further larger prospective studies are needed to elucidate the underlying reasons. This underscores the need for early upfront discussions with patients about fertility preservation prior to starting any neoadjuvant regimens.
Another significant focus was on carboplatin in the neoadjuvant treatment of triple-negative breast cancer, particularly prior to the advent of immunotherapy. A pooled analysis of the BrightNess, CALGB 40603, and GeparSixto studies found that adding carboplatin to the neoadjuvant regimen significantly improved pathologic complete response rates (55% vs 38.9%) and 5-year event-free survival rates (77% vs 69%). Notably, these benefits were observed not only in BRCA mutation carriers but also in patients with wild-type BRCA genes.
There is still an important role for carboplatin in early triple-negative breast cancer treatment along with immunotherapy. The CITRINE and RJBC-1501 trials, which were also presented at SABCS 2025, support the addition of carboplatin including in patients older than 50 years, but increases in hematologic toxicities are expected. Both trials conducted outside the United States incorporated adjuvant epirubicin as the anthracycline.
HER2-Positive Early Breast Cancer
The role of carboplatin has been challenged in HER2-positive early breast cancer, with the deescalation neoCARHP study (ASCO 2025) showing THP (taxane, trastuzumab, and pertuzumab) to be noninferior to TCHP (taxane, carboplatin, trastuzumab, and pertuzumab) in pathologic complete response rates, and we are awaiting the primary endpoint of recurrence-free survival from Compass HER2 (EA1181).
Tumor-infiltrating lymphocytes (TILs) and pathologic complete response in stage 2 or 3 HER2-positive early breast cancer with THP (and no carboplatin) were presented at SABCS 2025 from Compass HER2. The trial enrolled 2,175 patients, and the median percentage of TILs was 10%. Using a TIL cutoff at 10%, the difference in pathologic complete response rates was more pronounced in patients with ER-positive/triple-positive disease with 10% or greater TILs (40%) compared to those with less than 10% TILs (27%).
Metastatic Breast Cancer
In the metastatic breast cancer arena, the EMBER 3 study provided updated efficacy results, including a numerical trend in overall survival at 50% maturity in the hormone receptor–positive (HR+) HER2-negative metastic breast cancer space after progression on a prior CDK4/6 inhibitor (mostly palbociclib) using the oral SERD imlunestrant. Among patients with ESR1 mutant disease, the imlunestrant monotherapy arm reported a median overall survival of 34.5 months compared to 23.1 months for the standard endocrine therapy arm, but this finding is not statistically significant.
Imlunestrant monotherapy received FDA approval on September 25, 2025, for metastatic breast cancer with ESR1mutation based on a median progression-free survival endpoint (with close to four times more progression-free patients), and updated subgroup analyses revealed important and consistent outcomes for patients who had previously received various durations of CDK4/6 inhibitors (similar to the EMERALD trial with oral SERD elacestrant), along with ESR1 and PI3K co-mutation group data. In addition, the combination arm of imlunestrant plus abemaciclib showed improved progression-free survival compared with imlunestrant alone regardless of ESR1 mutation status, and it is now denoted as category 2A in the recent NCCN footnotes. There is a rapidly expanding landscape of oral SERD backbone combinations in clinical development, but only monotherapy with imlunestrant or elacestrant are FDA approved and currently restricted to patients with ESR1 mutation.
The ongoing ELEVATE trial is examining elacestrant with abemaciclib or everolimus. At ESMO 2025, the eVERA trial highlighted results from combining giredestrant with everolimus, which showed a 62% improvement in progression-free survival to 10 months after prior CDK4/6 inhibition for patients with ESR1 mutation. At SABCS 2025, the eVERA subgroup analysis included patients who had received a prior CDK4/6 inhibitor for 12 to 24 months or > 24 months, further refining the definition of “endocrine- or hormone-sensitive” disease in the hormone receptor–positive metastatic breast cancer space. Toxicity was as expected, and using dexamethasone mouthwash (per the SWISH study) will be important with everolimus for stomatitis prevention. Unfortunately, the ASCENT-07 trial, which used the first-line antibody drug conjugate sacituzumab govitecan in HR+/HER– MBC, did not meet its primary endpoint for progression-free survival.
The field of HER2-positive metastatic breast cancer continues to evolve, as evidenced by the HER2 Climb 5 trial, which investigated the addition of tucatinib to maintenance therapy trastuzumab plus pertuzumab (HP) after induction with the first-line Cleopatra trial taxane chemotherapy (T) HP. This trial demonstrated improved investigator-assessed progression-free survival from 16.3 to 24.9 months with tucatinib (hazard ratio = 0.64). In the context of the first-line Cleopatra arm, the THP median progression-free survival was 18.5 months, whereas the control THP arm of the Destiny Breast 09 (DB09) antibody drug conjugate T-Dxd study reported a progression-free survival of 26.9 months.
The PATINA maintenance trial in patients with triple-positive first-line metastatic breast cancer had a control progression-free survival of 29.1 to 44 months, where patients continued endocrine therapy along with HP maintenance without or with palbociclib, respectively. The progression-free survival from the placebo plus HP control arm in HER2 Climb 5 is curious. Notably, approximately 52% of participants had triple-positive metastatic breast cancer, and approximately 70% presented with de novo HER2-positive metastatic disease, possibly reflecting a different enrolled population. The progression-free survival benefit from tucatinib appeared more pronounced among patients with HR-negative HER2-positive disease, with a 12.3-month improvement in progression-free survival. Moreover, patients with baseline brain metastasis also benefited from tucatinib, although overall survival data are not yet mature. This raises important clinical considerations regarding the potential addition of tucatinib in the HR-negative population compared to using palbociclib in HR-positive/triple-positive first-line maintenance settings.
Since the approval of first-line antibody drug conjugate T-Dxd (DB-09) on December 15, 2025, the role of patient selection, T-Dxd duration/“induction,” biomarkers, and maintenance strategies in HER2+ metastatic breast cancer has continued to be an active area of debate.
Impressions of SABCS 2025 highlights are solely the opinion of Dr. Milana Dolezal.
DISCLOSURE: Dr. Dolezal reported consultancy roles with Gilead, Bayer, CytoDyn, Pfizer, and AstraZeneca.
Dr. Dolezal is a hematologist-oncologist with Stanford Medicine Cancer Center in Emeryville, California, and a Clinical Associate Professor, Division of Oncology, Stanford School of Medicine.
