Ki-67 Change in Anthracyline-containing Neoadjuvant Chemotherapy Response in Breast Cancer

Objective Anthracycline-containing regimens are irreplaceable in neoadjuvant chemotherapy(NAC)for breast cancer(BC)at present.However,30% of early breast cancer(EBC)patients are resistant to anthracycline-containing chemotherapy,leading to poor prognosis and higher mortality.Ki-67 is associated with the prognosis and response to therapy,and it changes after NAC.Methods A total of 105 BC patients who received anthracycline-containing NAC were enrolled.Then,the optimal model of Ki-67 was selected,and its predictive efficacy was analyzed.Immunohistochemistry(IHC)was used to determine the estrogen receptor(ER),progesterone receptor(PR),and human epidermal growth factor receptor 2(HER-2)status and Ki-67 level.Fluorescent in situ hybridization(FISH)was used to verify the HER-2 when the IHC score was 2+.Results The post-NAC Ki67 level after treatment with anthracycline drugs was lower than pre-NAC Ki-67(19.6%±23.3%vs.45.6%±23.1%,P<0.001).Furthermore,patients with the Ki-67 decrease had a border line higher pathological complete response(pCR)rate(17.2%vs.0.0%,P=0.068),and a higher overall response rate(ORR)(73.6%vs.27.8%,P<0.001),when compared to patients without the Ki-67 decrease.The ΔKi-67 and ΔKi-67%were valuable markers for the prediction of both the pCR rate and ORR.The area under the curve(AUC)for ΔKi-67 on pCR and ORR was 0.809(0.698-0.921)and 0.755(0.655-0.855),respectively,while the AUC for ΔKi-67% on pCR and ORR was 0.857(0.742-0.972)and 0.720(0.618-0.822),respectively.Multivariate logistic regression model 1 revealed thatΔKi-67 was an independent predictor for both pCR[odds ratio(OR)=61.030,95% confidence interval(CI)=4.709-790.965;P=0.002]and ORR(OR=10.001,95%CI:3.044-32.858;P<0.001).Multivariate logistic regression model 2 revealed thatΔKi-67%was also an independent predictor for both pCR(OR=408.922,95%CI=8.908-18771.224;P=0.002)and ORR(OR=5.419,95%CI=1.842-15.943;P=0.002).Conclusions The present study results suggest thatΔKi67 andΔKi67%are candidate predictors for anthracycline-containing NAC response,and that they may provide various information for further systematic therapy after surgery in clinical practice.

Relationship between expression of ER, PR, Her-2, Ki-67 and neoadjuvant chemotherapy effect in breast cancer

Objective: The purpose of the study was to investigate the relationship between the expression of estrogen receptor(ER), progestogen receptor(PR), human epidermal growth factor receptor(Her-2), Ki-67 and the effect of neoadjuvant chemotherapy in breast cancer. Methods: The expression of ER, PR, Her-2 and Ki-67 in 45 breast cancers which received neoadjuvant chemotherapy was detected by immunohistochemistry. Results: The effective rates in ER negative and PR negative groups were higher than those in ER positive and PR positive groups(83.3% vs 59. 4%, 82.4% vs 60.6%). There was no significant difference of the effective rate between Her-2 overexpressed group and Her-2 non-overexpressed group(81.8% vs 64.1%), and the same thing happened between Ki-67 negative group and Ki-67 positive group(67.7% vs 63.2%). Conclusion: In the patients with breast cancer, ER, PR negative ones were more sensitive to neoadjuvant chemotherapy. These patients may get more benefits from chemotherapy. ER, PR could be feasible markers for predicting the effective rate of neoadjuvant chemotherapy.

新辅助化疗对乳腺癌患者ER、PR、C-erbB-2、Ki-67表达的影响

背景与目的:新辅助化疗在提高保乳及可手术率,评价化疗敏感性,消除全身微转移灶等方面有其突出的优越性,在局部晚期乳腺癌的治疗中已被越来越广泛的应用。肿瘤组织中ER、PR、C-erbB-2、Ki-67的表达状态对于治疗方式的选择及治疗效果的预测有重要的意义。本研究探讨新辅助化疗对乳腺癌组织中ER、PR、C-erbB-2、Ki-67表达的影响有助于乳腺癌治疗的选择及预后。方法:通过免疫组化Envision法分别检测40例Ⅱ/Ⅲ期的乳腺癌病例在化疗前后乳腺癌组织中ER、PR、C-erbB-2、Ki-67的表达。术前采用空心针穿刺活检予以病理确诊并行ER、PR、C-erbB-2、Ki-67的测定。化疗方法统一采用CEF方案[氟尿嘧啶(5-FU),500mg/m2,表柔比星(Epi-ADM)75mg/m2,环磷酰胺(CTX)500mg/m2],经过2个疗程的化疗,再行乳腺癌改良根治术,比较化疗前后以上各指标表达的变化。新辅助化疗的临床疗效通过体检和乳腺B超测量肿瘤的最大直径,按WHO判定的统一标准来评价。结果:40例Ⅱ/Ⅲ期乳腺癌患者经2个周期的新辅助化疗后,29例(72.5%)获得了PR,无完全缓解病例,无进展病例。化疗前后ER、PR和C-erbB-2的表达均无显著变化(P>0.05);40例患者中ER发生变化为3例,PR为5例,C-erbB-2为5例;化疗后27例Ki-67由高表达变为低表达(P<0.01)。结论:新辅助化疗(NAC)可能部分通过抑制Ki-67的表达来抑制乳腺癌的增值,但对ER、PR、C-erbB-2的表达化疗前后无显著差异。

Effect of neoadjuvant chemotherapy on expressions of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and Ki-67 in breast cancer

Background This study was designed in an attempt to determine the influence of neoadjuvant chemotherapy on estrogen receptor （ER）, progesterone receptor （PR）, human epidermal growth factor receptor 2 （Her-2）, and Ki-67 expressions in patients with breast cancer. Methods Pre- and post-neoadjuvant chemotherapy, paired-tumor specimens from 103 patients with breast cancer administrated with anthracycline or anthracycline combined taxane regimen were collected. Immunohistochemical staining for ER, PR, Her-2, and Ki-67 was performed by the DAKO EnVision method. Results Among the 103 cases, five patients （4.9%） had a complete response （CR）, 82 （79.6%） partial response （PR）, 15 （14.6%） stable disease （SD）, and one （0.9%） progressive disease （PD）, yielding an overall response rate （CR ＋ PR） of 84.5%. Nine patients achieved pathological CR. There was a significant decrease in the average index of Ki-67 post- neoadjuvant chemotherapy, compared with that before chemotherapy （24.1% vs. 39.7%, P 〈0.001）. After neoadjuvant chemotherapy, the changes of Ki-67 in different subtypes of breast cancer were different （P 〈0.001）, and these changes correlated with response to neoadjuvant chemotherapy （P 〈0.001）. No significant changes in immunohistochemical expression were observed for ER, PR and Her-2. Conclusions Neoadjuvant chemotherapy apparently reduced Ki-67 index in primary breast carcinomas, but profiles for ER, PR and Her-2 were not significantly different before and after neoadjuvant chemotherapy. The change of Ki- 67 correlated with molecular subtypes and response to neoadjuvant chemotherapy, suggesting that Ki-67 index was a surrogate marker to predict the treatment response of neoadjuvant chemotherapy.