Impact in delay of starting chemotherapy and surgery on pCR/survival in breast cancer (BC)-pooled analysis of individual patient data from six prospectively randomized neoadjuvant trials

Background:

Time interval from diagnostic biopsy to neoadjuvant chemotherapy (NACT) start (TBC) and from last chemotherapy application to surgery (TCS) are influenced by many factors. It is unclear whether a delay of systemic therapy or surgery impacts patients outcome.

Methods:

9127 patients with early BC from 6 German trials receiving anthracycline-taxane-based NACT were included. pCR (ypT0/is ypN0), disease free survival (DFS) and overall survival (OS) were compared according to TBC and TCS length (cut-off ≤4 vs. > 4 weeks), overall and in subgroups (BC subtypes and pCR for survival endpoints), adjusted by study.

Results:

Median age was 49yrs, 25.6% had cT3 – 4, 48.6% N+, 44.1% G3, 46.0% luminal, 26.4% TNBC, 27.6% HER2+ tumors. Median-follow-up-time was 65 months, medianTBC 23 days (67.5%≤4w vs. 32.5%> 4w), medianTCS 28 days (53.7%≤4w vs. 46.3%> 4w). TBC did not influence pCR. At multivariable logistic regression analysis TBC length did not independently predict pCR. TBC did not influence DFS or OS. TCS< 4w was associated with a trend towards a better DFS in all patients (HR = 1.11 95%CI(0.99 – 1.24), p = 0.08) and in patients not achieving pCR (HR = 1.12, 95%CI(0.99 – 1.26), p = 0.08). OS was not impacted by TCS length. At multivariable Cox regression analysis neither TBC nor TCS did independently influence DFS or OS.

Conclusion:

A delay in starting NACT does not impact pCR, DFS, OS. Results are independent of the subgroup. However, early surgery after NACT in patients without pCR seems to influence outcome. Our analysis is explorative, but indicates, that time interval of starting NACT might be uncritical. Further research is ongoing.