7 Key Breast Cancer Updates From ASCO 2026

Key ASCO 2026 Presentations for Breast Cancer Oncologists

On the Oncology Brothers podcast, Hope Rugo, MD, FASCO, of City of Hope, met with Rahul Gosain, MD, MBA, of Wilmot Cancer Institute, and Rohit Gosain, MD, of Roswell Park Comprehensive Cancer Center, to discuss OPTIMA, lidERA, VIKTORIA-1, KEYNOTE-522, ASCENT-03, ASCENT-04, and TROPION-Breast02 data presented at the 2026 American Society of Clinical Oncology Annual Meeting (ASCO 2026).

OPTIMA

The phase 3 OPTIMA trial evaluated using the Prosigna gene expression test to guide chemotherapy decisions in patients with ER-positive, HER2-negative early breast cancer. The per-protocol analysis covered 2061 patients in the control arm and 2097 in the test-directed arm. 

Patients in the control arm received standard chemotherapy followed by endocrine therapy. In the test-directed arm, patients with a risk of recurrence (ROR) score over 60 received standard chemotherapy followed by endocrine therapy, while patients with a ROR score of 60 or lower received endocrine therapy alone. Overall, 68% of patients had a low ROR score.

After a median follow-up of 3.9 years (interquartile range, 2-5.9), 141 patients in the control arm and 139 in the test-directed arm had recurrence events, of which 66% were distant recurrences. The 5-year invasive breast cancer-free survival (IBCFS) rate was 91.5% (95% CI, 89.7-92.9) in the control arm and 93.7% (95% CI, 91.8-95.2) in the test-directed arm (HR, 0.99; 90% CI, 0.81-1.2; noninferiority P = .013). For low–ROR score patients, the 5-year IBCFS rates were 94.9% (95% CI, 92.9-96.4) in the control arm and 93.7% (95% CI, 91.8-95.2) in the test-directed arm (HR, 1.06; 90% CI, 0.78-1.46; P = .0051). There were no significant differences between subgroups based on menopausal and nodal status. 

lidERA

Previously, the phase 3 lidERA trial showed adjuvant giredestrant improved invasive disease-free survival (IDFS) versus standard endocrine therapy in patients with ER-positive, HER2-negative, stage I to III early breast cancer after surgery and adjuvant or perioperative chemotherapy. At ASCO 2026, authors presented updated data for premenopausal and postmenopausal subgroups. Out of 4170 patients, 40.7% were premenopausal and 59.3% were postmenopausal. At baseline, the premenopausal group had slightly higher risk of recurrence and higher use of (neo)adjuvant chemotherapy compared with postmenopausal patients. 

According to the presentation, giredestrant improved IDFS and distant recurrence-free interval (DRFI) versus standard endocrine therapy for both premenopausal and postmenopausal patients. The 3-year IDFS rates for giredestrant and endocrine therapy were 94% and 91.5% in premenopausal patients and 91.3% and 88.3% in postmenopausal patients, respectively. The respective 3-year DRFI rates were 95.5% and 92.6% in premenopausal patients and 93.6% and 91.6% in postmenopausal patients. Fewer patients discontinued due to adverse events with giredestrant compared with aromatase inhibitors (AIs) in either menopausal status subgroup.

VIKTORIA-1

The phase 3 VIKTORIA-1 trial evaluated gedatolisib plus fulvestrant with or without palbociclib against alpelisib plus fulvestrant in patients with hormone receptor–positive, HER2-negative, PIK3CA-mutated advanced breast cancer previously treated with a CDK4/6 inhibitor plus AI. Prior analysis showed the gedatolisib doublet and triplet significantly improved PFS versus fulvestrant in PIK3CA-unmutated patients. At ASCO 2026, researchers presented the primary analysis for the PIK3CA-mutated cohort.

The median follow-up for PFS was 11 months at the data cutoff. Overall, the median PFS was 11.1 months with the gedatolisib triplet versus 5.6 months with alpelisib plus fulvestrant (HR, 0.50; 95% CI, 0.37-0.68; P < .0001). Authors reported that safety was consistent with individual agents, with discontinuations due to treatment-related adverse events (TRAEs) in 2.6% of the gedatolisib triplet group, 3.8% of the gedatolisib doublet group, and 7.1% for alpelisib plus fulvestrant. Both gedatolisib combinations had lower rates of all-grade hyperglycemia and higher rates of all-grade stomatitis compared with alpelisib plus fulvestrant.

KEYNOTE-522

The phase 3 KEYNOTE-522 trial showed the addition of perioperative pembrolizumab to chemotherapy improved pathologic complete response (pCR), event-free survival (EFS), and overall survival (OS) for patients with high-risk early-stage TNBC. The final 7-year data update was presented at ASCO 2026. 

The study randomized 784 patients to pembrolizumab and 390 to placebo. At the data cutoff, the median follow-up was 93.8 months (range, 84.7-102.8). The 7-year EFS rate was 78.3% (95% CI, 75.3-81.1) in the pembrolizumab group compared with 69.8% (95% CI, 65-74.2) in the placebo group (HR, 0.68; 95% CI, 0.54-0.86). The EFS and OS benefits with pembrolizumab were “generally consistent” for most prespecified subgroups, including PD-L1 expression, nodal status, and disease stage. The rates of grade 3 or higher TRAEs were 77.1% with pembrolizumab and 73.3% with placebo, and the rates of any-grade immune-related AEs were 35% and 13.1%, respectively. 

ASCENT-03 and ASCENT-04

The ASCENT trial series investigated sacituzumab govitecan across different stages and treatment settings of TNBC. Previously, ASCENT-03 showed sacituzumab govitecan improved PFS versus chemotherapy for previously untreated metastatic TNBC, and ASCENT-04 showed sacituzumab govitecan plus pembrolizumab improved survival PFS versus chemotherapy plus pembrolizumab for previously untreated, PD-L1–positive metastatic TNBC. Although OS data remain immature, the authors presented data on subsequent treatments and PFS after subsequent treatment (PFS2) for both trials.

In ASCENT-03, the median follow-up for OS was 13.2 months, and 27% of patients in the sacituzumab govitecan group remained on treatment compared with 14% in the chemotherapy group. Following discontinuation of sacituzumab govitecan, the most common subsequent therapies were platinum-based chemotherapy (40%), taxanes (29%), and gemcitabine (19%). Following discontinuation of chemotherapy, the most common subsequent therapies were sacituzumab govitecan (82%), capecitabine (16%), platinum-based chemotherapy (9%), and trastuzumab deruxtecan (9%). The median PFS2 was 18.2 months (95% CI, 15.9–not reached [NR]) with sacituzumab govitecan and 14 months (95% CI, 12.5-17.4) with chemotherapy (HR, 0.70; 95% CI, 0.55-0.90).

In ASCENT-04, the median follow-up for OS was 14 months, and 43% of patients in the sacituzumab govitecan plus pembrolizumab group remained on treatment compared with 23% in the chemotherapy plus pembrolizumab group. Following discontinuation of sacituzumab govitecan plus pembrolizumab, the most common subsequent therapies were taxanes (42%), platinum-based chemotherapy (33%), and capecitabine (9%). Following discontinuation of chemotherapy plus pembrolizumab, the most common subsequent therapies were sacituzumab govitecan (91%), taxanes (9%), and capecitabine (9%). The median PFS2 was not reached (95% CI, NR-NR) with sacituzumab govitecan and 21 months (95% CI, 16-NR) with chemotherapy (HR, 0.67; 95% CI, 0.48-0.95).

TROPION-Breast02

The primary analysis of the TROPION-Breast02 trial showed Dato-DXd significantly improved OS and PFS compared with standard chemotherapy in immunotherapy-ineligible patients with locally recurrent inoperable or metastatic TNBC. At ASCO 2026, authors presented additional efficacy end points including PFS2, time to first subsequent therapy or death (TFST), and time to second subsequent therapy or death (TSST) from the trial.

After a median study follow-up of 27.5 months, 14.1% of patients remained on Dato-DXd and 2.6% remained on chemotherapy. The median PFS2 was 15.6 months with Dato-DXd compared with 11.8 months with chemotherapy (HR, 0.61; 95% CI, 0.5-0.74). The median TFST rates were 10.9 months with Dato-DXd and 5.6 months with chemotherapy (HR, 0.49; 95% CI, 0.41-0.59), and respective median TSST rates were 16.7 months and 12.6 months (HR, 0.67; 95% CI, 0.55-0.81).