Relationship between initial tumor burden and the probability of pathological complete response within molecular subtypes of early breast cancer treated with neoadjuvant chemotherapy

BackgroundThe relationship between initial tumor burden and the probability of pathological complete response (pCR) in each molecular subtype (MS) of early breast cancer (eBC) patients treated with neoadjuvant chemotherapy (NAC) is poorly described.MethodsIn this analysis, we pooled all cases of eBC treated with NAC in a French cancer center (GF Leclerc center) and in the prospective multicenter PRIMUNEO clinical trial (NCT01513408). The different molecular subtypes (MS) of eBC (LumA, LumB, HER2-amplified, and triple negative (TN)) were determined by immunohistochemistry analysis of the initial tumor biopsies before NAC.ResultsOverall, N=1315 eBC patients were included. The probability of pCR decreased with increasing breast tumor size (cT) (p=0.0241) and cAJCC stage (p=0.0160). There was a significant correlation between initial tumor size and the burden of pathological residual disease after NAC (p=0.0006), but that varied according to MS: while there was a moderate but significant correlation for LumA (p=0.0184), LumB (p=0.0302), and TN (p=0.0247), it was not observed for HER2-amplified eBC. No stage I LumA/LumB eBC reached pCR. Among stage I TN and HER2-amplified eBC, 45.5% and 42% did not achieve pCR, respectively. By multivariate analyses, variables independently associated with pCR achievement in the whole cohort were MS (p<0.001), lower cAJCC stage (p=0.034) and higher tumor grade (p=0.003), but again, this differed depending on the MS considered. Lower cAJCC was independently associated with the probability of pCR only in TN (p=0.021), while factors associated with pCR achievement were higher SBR grade (p<0.001) and young age (p=0.015) for LumA/LumB, higher SBR grade (p=0.04) and ER negative status (p<0.001) for HER2-amplified eBC.ConclusionsInitial tumor burden before NAC is not independently associated with the probability of pCR, except for TN eBC. Important pCR rates observed for HER2-amplified eBC, regardless of the initial tumor burden, may result from HER2-targeted therapy efficacy. Importantly, a certain part of stage I TN and HER2-amplified eBC did not reach pCR, which would make them candidates for adjuvant therapeutic escalation.Legal entity responsible for the studyCentre Georges-François Leclerc.FundingHas not received any funding.DisclosureAll authors have declared no conflicts of interest.