Rare Special Breast Cancer Histologies in the ALTTO Trial: Central Histology Review and Outcomes

Rare special histological subtypes (rST) account for ~10% of early-stage breast cancer (eBC) but their prognostic value remains poorly defined, particularly in HER2-positive disease. This sub-analysis of patients with HER2-positive eBC treated with adjuvant trastuzumab-based therapy in the ALTTO trial (NCT00490139) aims to compare baseline characteristics and clinical outcomes between patients with rST (n=239) and those with invasive carcinoma of no special type (NST, n=5,981). Among the cases with central histopathological review (n=5,302), 82% of locally diagnosed rST cases were reclassified as NST. When adjusted for baseline differences between different rST and NST, the histological subtype was not associated with survival outcomes. Non-significant trends of better outcomes were observed for mucinous subgroup (n=35) (10-year OS: 96.6% vs 88.2%, aHR 0.41, 95%CI 0.06–2.93). Although rST did not have independent prognostic value in HER2-positive eBC setting, the high diagnostic discordance raises concerns about existing evidence supporting differential management according to rST.