Predictive factors of response to neoadjuvant chemotherapy (NAT) in triple negative breast (TNBC) cancer patients: A restrospective multicenter observational study.

Background: This is a multicenter observational study with the aim to evaluate predictive factors of response to NAT in TNBC pts. Methods: 196 TNBC pts treated with NAT were enrolled from 7 Italian cancer centres and retrospectively evaluated for % of pCR, ki67 pre and postNAT and treatment duration. Pts receiving NAT regimens were divided in 2 groups: longer (TAC and anthra-taxane sequences) and shorter (< 6 cycles) therapy duration and in 3 groups as a function of Ki67 levels (low (LL) ≤15 %, intermediate(IL) 15.1–35% and high(HL) >35%).OS and PFS were calculated by the Kaplan-Meier product-limit method. Log-rank and Tarone-Ware tests were used to assess differences between groups. A multivariate logistic regression model was developed using stepwise regression (forward selection) to compare the predictive power of different factors. Results: Pts' median age was 47 yrs (25-77), cT1-T2 62%and cT3-cT4 38%, 79% of pts had clinical axillary disease, 41% of pts received longer NAT and 59% shorter. PreNAT ki67 levels were: LL 20%, IL 12% and HL 68%. PostNAT Ki-67: LL 22%, IL 6%, and HL 42%, and 52 pts (26.5%) achieved pCR (95%CI 20-33). In the group of pts that received longer NAT, pCR was significantly more frequent compared to the group that received shorter NAT (38% vs 19% p = 0.005). Moreover pCR was more frequent in pts HL of Ki-67 (34%) compared to those with LL/IL (20%)(p = 0.05). In multivariate analysis HL of preNAT Ki-67 (OR 1.2 CI 95%1-1.3, p = 0.02) and longer duration of NAT response (OR 2.1 CI95% 1-4.3, p = 0.04) were significant predictive factors for. Conversely, cT and cN didn’t appear predictive. At a median follow-up of 42 months (2-190) overall PFS at 3yrs was 65% and 5yrs OS 76%. Pts with pCR had higher DFS and OS than pts with NopCR. DFS and OS gradually worsened with increasing postNAT Ki-67 level. Conclusions: Our analysis suggests that in TNBC treated with pre-NAT high ki67 levels and “adeguate” chemotherapy regimen are predictive factors of response and that post-NAT high ki67 levels and nopCR are negative predictors of survival. Data collection is ongoing and update results will be presented.
DFS 3yrs (%) OS 5yrs (%)
Ki67 HL >35% 56.3 62.2
pCR 92.9 92.9
No pCR 56.4 70.7