e23417 Background: With the advent of antibody–drug conjugates, HER2-low disease emerged as a clinically relevant subgroup. Yet the prognostic implications of HER2-low versus HER2-negative (IHC 0) disease are not fully defined, with scarce evidence in Latin America. Methods: We conducted a retrospective cohort study including adult patients with HER2-negative breast cancer treated at a tertiary cancer center in Colombia between 2018-2025. Tumors were classified as HER2-low (IHC 1+ or 2+ without amplification) or HER2-negative (IHC 0) according to pathology reports. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan–Meier method and comparedusing log-rank tests. Results: A total of 176 patients with HER2-negative breast cancer were included; 29 (16.5%) were HER2-low and 147 (83.5%) HER2-negative (IHC 0). Median age at diagnosis was similar between groups (59.9 vs 56.2 years; p = 0.3). Hormone receptor positivity was high in both cohorts (ER: 93.1% HER2-low vs 82.3% HER2-negative (IHC 0); p = 0.3). The distribution of molecular subtypes differed significantly between groups (p < 0.001). HER2-low tumors were more frequently classified as Luminal B HER2-negative (51.7%), whereas HER2-negative (IHC 0) were more heterogeneous (Luminal A 36.1%, Luminal B 34.7%, triple-negative 15.0%). HER2-low tumors less frequently presented with metastatic disease at diagnosis (0% vs 6.8%; p = 0.012), thus with a higher rate of curative-intent treatment. Treatment patterns were comparable between groups. After a median follow-up of approximately 52 months, there were no statistically significant differences in OS or PFS between HER2-low and HER2-negative (IHC 0) breast cancer. Median OS was 51.9 months for HER2-low and 53.2 months for HER2-negative (IHC 0) disease (p = 0.8), and median PFS was 49.8 and 49.6 months, respectively (p = 0.8). Conclusions: In this real-world cohort, differences in molecular subtype distribution and presentation at diagnosis were observed between HER2-low and HER2-negative (IHC 0) subgroups. However, no significant differences in OS or PFS were observed; survival results should be interpreted in the context of the smaller HER2-low subgroup. These findings underscore heterogeneity within HER2-negative breast cancer and the need for larger real-world studies on the prognostic and therapeutic relevance of HER2-low status, particularly in Latin America. Baseline clinicopathologic characteristics by HER2 status. Variable HER2-low (n=29) HER2-negative (IHC 0) (n=147) Age at diagnosis, median (IQR) 59.9 (48–67) 56.2 (44–68) Estrogen receptor positive, n (%) 27 (93.1%) 121 (82.3%) Ki-67 ≥30%, n (%) 10 (34.5%) 55 (40.1%) Invasive ductal carcinoma, n (%) 24 (82.8%) 108 (73.5%) Stage III–IV at diagnosis, n (%) 6 (20.7%) 32 (21.8%) Metastatic at diagnosis, n (%) 0 (0.0%) 10 (6.8%) Neoadjuvant therapy, n (%) 6 (20.7%) 34 (23.1%)
Uchima-Vera et al. (Thu,) studied this question.