The San Antonio Breast Cancer Symposium 2025 showcased pivotal breast cancer trials across the field. From the first adjuvant oral SERD to show a meaningful disease-free survival benefit, to new maintenance approaches in HER2-positive metastatic breast cancer and evolving roles for antibody drug conjugates and next-generation endocrine agents, the key studies shown below highlight a shift toward more personalized treatment. Together, they offer clinicians new ways to balance efficacy, toxicity and long-term disease control across multiple breast cancer subtypes. Below, Dr Suchita Pakkala (Emory Winship Cancer Institute, Atlanta, GA, USA) breaks down her highlights and key take-aways from from SABCS 2025.
The phase III lidERA trial explored giredestrant (an oral selective estrogen receptor degrader [SERD]) versus standard-of-care adjuvant endocrine therapy in stage I–III hormone-positive HER2-negative breast cancer with higher-risk features (node positive, pT4, OR >1 cm with grade 3 or Ki-67 >20% or high genomic score). Ovarian suppression was required for premenopausal patients receiving giredestrant or aromatase inhibitors. Prior endocrine therapy and CDK inhibitors were allowed for up to 12 weeks, but CDK inhibitors were not allowed to continue on study.
Overall, 70% of patients were high risk (pT4, pN2, pN3 OR pN1 with grade 3, Ki-67 >20%, tumours >5 cm, or high genomic risk). Forty percent were premenopausal, 84% received an aromatase inhibitor, only ~13% were stage I, and ~80% had received prior chemotherapy.
There was a 2.8% improvement in invasive disease-free survival at 3 years with giredestrant, with a hazard ratio of 0.70 (0.57–0.87, p=0.0014), higher compared to tamoxifen (HR 0.53, 0.35–0.80). Giredestrant distant relapse-free survival improved by 2.1% (HR 0.69, 0.54–0.89). There were minimal events in the medium-risk group.
Grade 3/4 adverse events (AEs) were similar in both arms. Arthralgias were the most common treatment-related AE, followed by hot flashes, but those on giredestrant were less likely to discontinue treatment, including those who experienced arthralgias. While bradycardia did occur, it was asymptomatic and did not require intervention in 95% of patients, with no grade >3 AEs.
Other ongoing oral SERD adjuvant trials include camizestrant initially and after two years of endocrine therapy. Those after two years of endocrine therapy include elacestrant and imulunestrant. The lidERA study presents a potentially new adjuvant endocrine option for higher-risk HR+ HER2-negative breast cancer patients.
HER2+ metastatic breast cancer patients without evidence of progression after 4–6 cycles of THP (median of 6) were started on HP maintenance ± endocrine therapy if HR+, and were randomized to the addition of tucatinib versus placebo. Asymptomatic brain metastases were allowed and included ~12% of the population.
Overall, ~69% had de novo metastatic disease, ~52% were triple positive, of whom ~45% received endocrine therapy; ~70% had prior trastuzumab and ~17% had prior pertuzumab, with the majority (~63%) having had a partial response and ~23% having had stable disease to induction therapy.
Progression-free survival (PFS) was improved by 8.6 months with the addition of tucatinib (24.9 vs. 16.3 months, HR 0.64 [0.514–0.799]). While patients benefited irrespective of hormone receptor (HR) status, the magnitude of the benefit was larger for HR-negative patients, at a 12.3-month benefit versus 6.9 months in HR-positive patients. Central nervous system PFS in 81 patients was an exploratory analysis but showed a 4.2% trend towards benefit with tucatinib.
Side effects more common with tucatinib were diarrhea, nausea, and increased ALT/AST. While more patients discontinued treatment on the tucatinib arm (13.8% vs. 4.6%), this was mainly due to hepatic-related AEs.
Recent studies have provided multiple first-line options for metastatic HER2-positive breast cancer. The DESTINY-Breast09 study showed a 13.8-month improvement in PFS with trastuzumab deruxtecan (TDXd) + pertuzumab (P) over docetaxel, trastuzumab, and pertuzumab (THP); however, patients on TDXd+P continued therapy until progression or toxicity. For triple-positive patients who completed THP for 6–8 cycles, the addition of palbociclib to endocrine + HP therapy improved PFS by 15.2 months.
Therefore, the choice of therapy is likely to be influenced by patient factors. TDXd-P would be favored in a more fit, younger patient with brain metastases, early relapse, more visceral disease or multiple sites of disease, or those with a known PIK3CA mutation (who did worse with THP), where the goal is maximal response (higher CR rates with TDXd-P), as they may be less likely to receive second-line therapy. However, for patients in whom ongoing treatment toxicity is a concern, a maintenance strategy is more reasonable, especially in triple-positive patients with more limited disease.
The ALLTO study was designed for early-stage HER2+ breast cancer patients who received various chemotherapy options and also compared trastuzumab, lapatinib, or combinations of both. This was an exploratory analysis of HR+/HER2+ patients who received either adjuvant aromatase inhibitor (AI) ± ovarian suppression if premenopausal versus tamoxifen.
Patients who received lapatinib alone, switched endocrine therapy, or did not receive prior chemotherapy were excluded from the subset analysis. There was an improvement in 10-year disease-free survival for patients receiving adjuvant AI ± OS compared with SERM (aHR 0.65, 95% CI 0.52–0.82), which was more notable in premenopausal patients (aHR 0.45, 0.24–0.86) versus postmenopausal patients (aHR 0.65, 0.50–0.85).
This study suggests that adjuvant AI ± ovarian suppression should be favored over SERMs for patients with T2 or node-positive triple-positive cancers.
Patients with measurable metastatic HR+/HER2– breast cancer who had progressed on at least two prior endocrine therapies ± targeted therapies, had progression within 6 months of starting first-line endocrine therapy ± CDK4/6 inhibitors, or had recurrence within 24 months of starting endocrine therapy plus a CDK4/6 inhibitor and were not candidates for additional endocrine therapy were randomized 2:1 to sacituzumab versus capecitabine, paclitaxel, or nab-paclitaxel (57% of patients received taxanes).
Fifty-eight percent of patients were HER2-low, 26–31% had primary endocrine resistance, ~88% had visceral disease, ~21% had de novo disease, the median number of prior lines of therapy was 2, and ~91% had received prior endocrine therapy with CDK4/6 inhibitors.
There was no PFS benefit with sacituzumab over chemotherapy, with a median PFS of 8.3 months in both arms and a hazard ratio of 0.85 (0.69–1.05). Survival data are immature. Dose interruptions (75% vs. 46%) were higher with sacituzumab, with higher rates of neutropenia, and only 20% received primary prophylaxis with G-CSF. Sixty-one percent of patients received subsequent antibody–drug conjugates (ADCs) in the chemotherapy arm compared with 32% in the sacituzumab arm.
While sacituzumab is approved for HR+/HER2– metastatic breast cancer after prior endocrine therapy and chemotherapy, PFS was not improved in the first-line chemotherapy setting for HR+/HER2– endocrine-refractory disease. In contrast, in triple-negative metastatic breast cancer, sacituzumab has shown a PFS benefit over chemotherapy in the first-line setting.
In evERA, the addition of giredestrant to everolimus improved PFS after CDK4/6 inhibitors, especially in the ESR1-mutated population (9.99 vs. 5.45 months, HR 0.38 vs. HR 0.56 ITT) in patients who had received <2 prior lines of endocrine therapy (50% prior fulvestrant).
EMBER3 updates showed that imlunestrant + abemaciclib improved PFS to 10.9 months regardless of ESR1 mutation status, versus 5.5 months with imlunestrant alone (HR 0.59, 0.47–0.74) and 3.8 months with standard-of-care therapy after recurrence or progression on an AI ± CDK4/6 inhibitor (65% of patients). There was an 11.4-month increase in overall survival with imlunestrant versus standard-of-care therapy, although this was not statistically significant.
Other highlights included AI recurrence prediction models that could be used instead of genomic assays such as Oncotype; the FEATURE trial, in which PET response for bone-only or bone-predominant metastatic breast cancer improved overall survival; and the WISDOM study, which demonstrated that a risk-based model for breast cancer screening can reduce the number of mammograms while detecting similar rates of stage IIB or higher cancers.
While the LORETTA study was negative for active monitoring with tamoxifen-treated low-risk DCIS, it was informative in showing that the 5-year cumulative incidence of ipsilateral breast cancer was 9.8% for patients considering foregoing surgery.
Disclosure: Suchita Pakkala discloses minor stake holdings in BMS and Merck.
This content has been developed independently by Touch Medical Media for touchONCOLOGY. It is not affiliated with the San Antonio Breast Cancer Symposium (SABCS). Views expressed are the speaker’s own and do not necessarily reflect the views of Touch Medical Media.
Cite: SABCS 2025: Breast cancer highlights & key take-aways. touchONCOLOGY. January 14th, 2026
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