ASCO Annual Meeting 2025 Meeting Highlights: Breast Cancer

May 30–June 2, 2025

The American Society of Clinical Oncology (ASCO) held its 2025 Annual Meeting on May 30–June 2, 2025, in Chicago, Illinois. The conference gave researchers, physicians, and members of industry the opportunity to share and learn about the latest research in oncology, including breast cancer. The event included speaker presentations on various clinical topics in breast cancer, as well as posters reporting the latest data on breast cancer pathophysiology, epidemiology, and treatment options. Summaries of key abstracts from the meeting are included here.

Patient-reported outcomes (PROs) in patients with ER+, HER2– advanced breast cancer (ABC) treated with imlunestrant, investigator’s choice standard endocrine therapy, or imlunestrant+abemaciclib: results from the Phase III EMBER-3 trial.
Imlunestrant, an oral selective estrogen receptor degrader (SERD), was found to significantly improve progression-free survival (PFS) versus standard of care (SOC) endocrine therapy (ET) in patients with estrogen receptor–positive (ER+), human epidermal growth factor receptor 2–negative (HER2–) advanced breast cancer with ESR1 mutations who experienced disease progression on or after aromatase inhibitor-based therapy in the Phase III EMBER-3 trial; additionally, imlunestrant plus abemaciclib improved PFS in all patients, regardless of ESR1 mutation status, compared to imlunestrant alone. This study reported exploratory patient-reported outcome (PRO) analyses from the EMBER-3 trial. Patients completed the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) at baseline and every eight weeks until treatment discontinuation. The PRO-Common Terminology Criteria for Adverse Events (CTCAE) for injection-site reactions was administered to fulvestrant-treated patients each week for two weeks following injection, and the PRO-CTCAE for diarrhea frequency was administered weekly. Among patients with ESR1-mutated advanced breast cancer, those who received imlunestrant experienced improved EORTC QLQ-C30 global health status (GHS)/quality of life (QoL) and physical function scores, whereas scores declined in patients who received SOC; mean change differences between imlunestrant monotherapy and SOC groups were 9.9 for GHS/QoL and 6.2 for physical function. Both imlunestrant monotherapy and SOC were associated with minor decline in GHS/QoL scores in the overall population, with a mean change difference of 0.5. Physical function scores were maintained with imlunestrant monotherapy and declined slightly with SOC in the overall population (mean change difference: 2.5). Injection-site reaction was reported by 72 percent of fulvestrant-treated patients at any time during treatment, with a mean of 31 percent during the first week of the initial six cycles. Among all patients, declines in GHS/QoL and physical function scores were comparable with imlunestrant monotherapy and imlunestrant plus abemaciclib. The rate of “frequent” or “almost constant” diarrhea frequency was increased with imlunestrant plus abemaciclib treatment (22%) compared to imlunestrant monotherapy (3%) or SOC (2%).

Access abstract here: https://meetings.asco.org/abstracts-presentations/246102

21-gene expression assay in postpartum vs. nonpostpartum breast cancer and correlation with outcomes in young women with breast cancer.
In this retrospective chart review, researchers compared genomic profiles and patient outcomes in postpartum versus nonpostpartum breast cancer. Patients aged 45 years or younger with ER+, HER2– breast cancer were eligible for inclusion. Cases of postpartum breast cancer were diagnosed at five years or less postpartum; cases diagnosed during pregnancy were excluded. Genomic profiles were measured via 21-gene expression assay. Among 43 patients, 24 had nonpostpartum breast cancer and 19 had postpartum breast cancer. Stage I disease was reported in 54.2 percent of patients with nonpostpartum breast cancer versus 31.6 percent with postpartum breast cancer (p=0.128). A greater percentage of patients with postpartum disease versus nonpostpartum disease had lymph node involvement (73.7% vs. 45.8%, p=0.066). The rate of systemic chemotherapy receipt was 68.4 percent in the postpartum breast cancer cohort and 45.8 percent in the nonpostpartum breast cancer cohort (p=0.128). Genomic profiling data was available in 16 patients with nonpostpartum disease and eight patients with postpartum disease. Average 21-gene expression assay recurrence score was comparable between postpartum and nonpostpartum disease (19.3 and 18.9, respectively; p=0.919). Recurrence score of 16 or higher was more frequently reported in the postpartum disease cohort compared to the nonpostpartum disease cohort (75% vs. 50%, p=0.242). At median 66.1-month follow-up, the rate of distant recurrence was higher among patients with postpartum breast cancer (21.1%) versus those with nonpostpartum breast cancer (8.33%). Five-year distant recurrence–free survival (DRFS) and overall survival (OS) rates did not significantly differ between groups (p=0.26 and 0.55, respectively).

Access abstract here: https://meetings.asco.org/abstracts-presentations/244634

Bilateral mastectomy and breast cancer mortality for invasive lobular carcinoma: a SEER-based study.
Researchers analyzed 20-year data from the Surveillance, Epidemiology, and End Results (SEER) database to determine the impact of bilateral mastectomy on breast cancer mortality risk in patients with unilateral invasive lobular carcinoma (ILC). Among 58,861 patients, 59 percent underwent lumpectomy, 32 percent underwent unilateral mastectomy, and 9.1 percent underwent bilateral mastectomy. Mean age was 57 years in patients who underwent bilateral mastectomy, 62 years in those who underwent unilateral mastectomy, and 64 years in those who underwent lumpectomy (p<0.0001). The lumpectomy group had a significantly smaller mean tumor size compared to unilateral and bilateral mastectomy groups (1.9cm vs. 3.6cm for both, p<0.0001). The rate of 20-year cumulative invasive contralateral breast cancer risk was lowest in the bilateral mastectomy group (0.3%), followed by the lumpectomy (7.3%) and unilateral mastectomy groups (7.5%). The 20-year cumulative breast cancer mortality rate was 13.4, 24.3, and 30.2 percent in the lumpectomy, bilateral mastectomy, and unilateral mastectomy groups, respectively. In adjusted analyses, bilateral mastectomy was associated with significantly lower breast cancer mortality compared to lumpectomy (adjusted hazard ratio [aHR]: 0.90; p=0.04), whereas breast cancer mortality did not significantly differ between lumpectomy and unilateral mastectomy groups (aHR: 1.01).

Access abstract here: https://meetings.asco.org/abstracts-presentations/244550

ESR1 mutations and associated alterations in patients with estrogen receptor (ER+), HER2-positive (HER2+) breast cancers at diagnosis of metastatic disease (mBC).
In this study, researchers assessed the characteristics of ESR1-mutated ER+, HER2+ metastatic breast cancer. In a cohort of 421 patients, ESR1 mutations were present in 18 (4.3%); demographic characteristics did not significantly differ between ESR1-wildtype and ESR1-mutated patients. Most ESR1 mutations (94%) occurred at the 536–538 hotspot. Thirty-nine and 22 percent of ESR1-mutated tumors were enriched for GATA3 and KMT2C alterations, respectively, compared to 13 and eight percent of ESR1-wildtype tumors, respectively (p=0.007 and 0.05, respectively). Compared to patients with ESR1-wildtype disease, those with ESR1-mutated disease more frequently harbored MYC (22% vs. 8%, p=0.05) and RNF139 amplifications (22% vs. 7%, p=0.03). ERBB2 amplifications were reported in 76 percent of ESR1-wildtype tumors compared to 44 percent of ESR1-mutated tumors (p=0.005). CDK12 amplifications were significantly more prevalent in ESR1-wildtype versus ESR1-mutated tumors (51% vs. 11%, p<0.001). TP53 alterations were more common in ESR1-wildtype tumors compared to ESR1-mutated tumors (52% vs. 33%), though this difference was not significant (p=0.12). 

Access abstract here: https://meetings.asco.org/abstracts-presentations/250124

Comprehensive characterization of interleukin-enhanced factor 2 (ILF2) in triple-negative breast cancer (TNBC). Compared to HR+, HER2+; HR–, HER2+; and HR+, HER2– breast cancer samples, triple-negative breast cancer (TNBC) samples had significantly greater ILF2 expression. Among primary and metastatic TNBC cases, a significantly greater proportion of patients with high ILF2 expression were below the age of 50 years compared to those with low expression. TP53 mutations were significantly more frequent with high versus low ILF2 expression in primary (94.5% vs. 79.6%) and metastatic (92.4% vs. 74.4%) TNBC. Patients with low ILF2 had greater rates of PIK3CA (primary TNBC: 23.4%; metastatic TNBC: 27.4%) and CDH1 (primary TNBC: 6.1%; metastatic TNBC: 12.2%) compared to those with high ILF2 (primary TNBC: 5.1 and 0.8%, respectively; metastatic TNBC: 8.8% and 2.8%, respectively). Natural killer cell infiltration was increased whereas infiltration of regulatory T cells and M2 macrophages was decreased with high ILF2 expression. Additionally, the high ILF2 expression group exhibited higher expression of immune checkpoint genes, drug efflux genes, and stem cell genes. OS was significantly decreased in patients with high ILF2 expression compared to those with low expression in the primary TNBC group (p=0.03), but not the metastatic TNBC group (p=0.2). 

Access abstract here: https://meetings.asco.org/abstracts-presentations/253484

Quantifying the clinical impact of tissue reflex testing for liquid biopsy ESR1 mutation–negative cases with low ctDNA tumor fraction (TF) in HR+, HER2– breast cancer.
In this study, researchers analyzed the rate of ESR1 mutation positivity on tissue biopsy in patients with HR+, HER2– breast cancer who received an indeterminate negative result (circulating tumor deoxyribonucleic acid [ctDNA] tumor fraction [TF] <1%) on liquid biopsy. Among a cohort of 522 patients who underwent liquid and tissue biopsy, 229 (43.9%) had ctDNA TF of less than one percent. Overall, there was a 6.3-percent false negative rate and 67.1-percent positive percent agreement for ESR1 mutation. Stratifying by TF status revealed that the false negative rate was lower and positive percent agreement was higher in liquid biopsies with TF of one percent or higher (0.9% and 96.0%, respectively) compared to biopsies with a TF of less than one percent (12.0% and 25.7%, respectively). Among 101 patients included in a clinicogenomic database, 56 (55.4%) had ctDNA TF of less than one percent. Overall false negative rate and positive percent agreement for ESR1 mutation were 9.5 and 61.9 percent, respectively. TF-stratified findings were similar to those of the cohort; in biopsies with TF of one percent or higher, the false negative rate was zero percent and positive percent agreement was 100 percent, whereas biopsies with a TF of less than one percent had a false negative rate of 15.1 percent and positive percent agreement of 20.0 percent. These findings suggest that patients with ER+, HER2– breast cancer who receive an indeterminate negative result for ESR1 mutation status on liquid biopsy might benefit from reflex tissue biopsy to identify potential cases of ESR1 mutation positivity missed on the initial biopsy.

Access abstract here: https://meetings.asco.org/abstracts-presentations/248585

Breast cancer recurrence and mortality among survivors of childhood cancer: a report from the Childhood Cancer Survivor Study (CCSS).
Researchers assessed outcomes among childhood cancer female survivors (aged ≥18 years) with subsequent breast cancer. A total of 431 childhood cancer survivors had subsequent breast cancer, diagnosed at a median age of 40 years; 68 of these patients developed recurrent breast cancer. Ten-year breast cancer recurrence risk was similar between survivors and matched controls with first primary breast cancer (14% vs. 12%; p=0.52). Survivors most often presented with Stage I/II breast cancer (69%). Eighty percent of survivors had progesterone receptor–positive (PR+) disease, and 71 percent had ER+ disease. Eighty-four percent of survivors received first breast cancer treatment in accordance with national guidelines, and 47 percent underwent bilateral mastectomy. Among survivors with recurrent breast cancer, 48 died after recurrence, largely related to breast cancer (83%). Survivors had a 10-year overall mortality probability of 89 percent (95% confidence interval [CI]: 61–97%) compared to 42 percent for controls (95% CI: 18–58%), which was a significant difference (p=0.0025). Adjusted risk of death was 2.6-fold (95% CI: 1.05–6.49) higher in survivors versus controls.

Access abstract here: https://meetings.asco.org/abstracts-presentations/253402

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