HER2-positive Apocrine Carcinoma of the Breast: A population-based Analysis of Treatment and Outcome

Abstract Aims Apocrine carcinoma of the breast (APO) expresses HER2 in 30-50% of cases. This study explored the clinicopathological features and outcome of HER2+ APO (HER2+/APO) and matched HER2-positive invasive carcinomas of no special type (HER2+/NST). Methods We used the SEER database to explore the HER2+/APO and HER2+/NST cohorts. Univariate and multivariate analyses were used to assess the breast cancer-specific (BCSS) and overall survival (OS). Based on ER and PR [=HR] and HER2 status, we divided the cohorts to match the intrinsic molecular subtypes for comparisons [Apocrine Luminal B (HER2+/HR+/APO) vs. NST Luminal B (HER2+/HR+/NST) and Apocrine HER2-Enriched (HER2+/HR-/APO) vs. NST HER2-Enriched (HER2+/HR-/NST)]. Results We retrieved 259 cases of HER2+/APO with an active follow-up among the 446,806 breast malignancies (frequency ~0.06%). Most HER2+/APO were HR negative (65%). HER2+/APO carcinomas were more prevalent in the 80+ age group (24.7% vs. 15.7%, p<0.001). HER2+/HR-/APO had a significantly lower histological grade than the HER2+/HR-/NST (p<0.001). Breast cancer-related deaths were more prevalent in HER2+/NST (7.8% vs. 3.9%, p=0.019). This was particularly evident between HR- subgroups (10.4% in HER2+/HR-/NST vs. 4.2% in HER2+/HR-/APO, p=0.008) and was reaffirmed in BCSS in univariate analysis (p=0.03). Other than race and ER/PR status, HER2+/APO subgroups did not differ in clinicopathological parameters. Conclusions Our study confirms the rarity of the APO and reveals that ER/PR status in HER2+ APO does not affect these patients' prognosis. HER2+/APO tumors tend to have a less aggressive phenotype and a more favorable outcome despite a markedly lower ER/PR positivity.