Simple SummaryHER2+ and triple negative breast cancers are widely known for their aggressiveness, frequent resistance to treatment and poor prognosis. Neoadjuvant management has provided promising results for both subtypes, but there is still a subset of patients with no or low response. Consequently, a non-negligible number of patients is receiving a treatment regimen that might not be adequate. Identification of these patients is essential to avoid overtreatment and provide more effective treatment options.AbstractNeoadjuvant treatment (NAT) is one of the most widely used options for HER2+ and triple negative (TN) early breast cancer (BC). Since around half of the patients treated with NAT do not achieve a pathologically complete response (pCR), biomarkers to predict resistance are urgently needed. The correlation of clinicopathological factors with pCR was studied in 150 patients (HER2 = 81; TN = 69) and pre- and post-NAT differences in tumour biomarkers were compared. Low estrogen receptor (ER) expression, high tumour-infiltrating lymphocytes (TILs) and low cT-stage were associated with pCR in HER2+ tumours (p= 0.022;p= 0.032 andp= 0.005, respectively). Furthermore, ER expression was also associated with residual cancer burden (RCB;p= 0.046) in the HER2+ subtype. Similarly, pre-NAT, low progesterone receptor expression (PR; 1–10%) was associated with higher RCB (p< 0.001) in TN tumours. Only clinical and pathological T-stage (cpT-stage) had prognostic capacity in HER2+ tumours, whereas pre-NAT cpT-stage and post-NAT TILs had this capacity for the prognosis of TN tumours. We conclude that ER and PR expression may help predict response to NAT in HER2 and TN BC and should be taken into account in residual tumours. Also, changes observed in the phenotype after NAT suggest the need to reevaluate biomarkers in surviving residual tumour cells.