Pre-Treatment CD44 and CD47 Expression and Pathological Complete Response After Neoadjuvant Therapy in Breast Cancer: An Exploratory Single-Center Study

CD44, a stem cell-associated adhesion molecule, and CD47, an anti-phagocytic checkpoint, have been implicated in breast cancer chemoresistance, but their relationship to neoadjuvant response is poorly defined. We assessed both markers by immunohistochemistry in pre-treatment core biopsies from 43 women treated with neoadjuvant therapy at a single center. Total pathological complete response (pCR; ypT0/is ypN0), designated the primary endpoint during peer review, occurred in 12 patients (27.9%), and breast pCR (ypT0/is) in 14 (32.6%). Total pCR rates were 18.2% in CD44-positive and 38.1% in CD44-negative tumors (odds ratio, 0.36; 95% CI, 0.09–1.46; Fisher exact p = 0.185). CD44 positivity was concentrated in rarely responding hormone receptor-positive/HER2-negative tumors, and stratification by subtype moved the odds ratio toward the null (0.62; exact 95% CI, 0.07–5.25). For CD47, the odds ratio per one-point increase in immunoreactivity score was 0.80 (95% CI, 0.54–1.19; p = 0.264), but immunoreactivity was low (only two tumors reached the prespecified high-expression threshold) and possibly technically compromised, so these findings are inconclusive. No statistically detectable association was observed between either marker and total or breast pCR; treatment could not be adjusted for, and only very large effects were detectable. These exploratory data do not provide sufficient evidence to support CD44 or CD47 as response markers.