National Cancer Center Hospital East, Chiba, Japan
Nobuaki Matsubara , Hirofumi Mukai , Yoichi Naito , Ako Hosono , Kuniaki Itoh , Satoshi Fujii , Kimiyasu Yoneyama , Noriaki Wada
Background: A pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) is well established predictive marker for long-term prognosis in patients (pts) with HER2 or triple negative (TN) breast cancer. However, predictive marker has not been established in pts with non-pCR after NAC yet. Reduction of Ki-67 value after NAC has been reported to be associated with a favorable prognosis. However, the association between the reduction rate of Ki-67 and prognosis has not been investigated in detail. This study investigates whether reduction rate of the Ki-67 could indicate a survival advantage in pts with non-pCR. Methods: A total of 450 pts who had received neoadjuvant anthracycline with or without taxane chemotherapy and surgery were analyzed retrospectively. Ki-67, hormone receptor and HER2 status were examined by immunohistochemistry (IHC) in pre-NAC biopsy samples and post-NAC surgical specimens. Pts with non-pCR were subdivided into threesubgroups according to Ki-67 change after NAC: High-reduction (absolute value of Ki-67 was reduced by > 80% compared with that prior to NAC), low-reduction (absolute value of Ki-67 was reduced by from 0% to 80% compared with that prior to NAC), and increase groups (absolute value of Ki-67 was increased compared with that prior to NAC). The relapse-free survival (RFS) rates were compared among subgroups. Results: pCR was observed in 19.5% of pts. In pts with non-pCR, a reduction in Ki-67 was observed in 64% (232/362 pts) and the median reduction rate was 60%. A total of 15% of pts were in the high-reduction, 63% in the low-reduction and 22% in theincrease group. The median follow-up was 64.5 months. The 5-year RFS rates among three groups were significantly different (p<0.0001). Similar positive results were observed in the HER2(p=0.033), TN (p=0.034) and luminal subtype (p=0.001). Pts in the high-reduction group showed comparable RFS to pts with pCR (hazard ratio 1.12 p=0.792). Conclusions: In pts with non-pCR, the reduction rate of Ki-67 after NAC significantly predicted RFS regardless of their tumor subtypes. Pts who are non-pCR but achieve a high reduction of the Ki-67 can be expected to have a favorable prognosis similar to that of pts with pCR.
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