Response and Long-Term Effect of Patients with Triple-Negative Breast Cancer Receiving Neo-Adjuvant Anthracycline-Based

OBJECTIVE The breast cancer lack of expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) is defined as the Triple-negative breast cancer (TNBC). Our purpose is to compare the response and long-term effect of the TNBC and non-TNBC patients receiving neo-adjuvant anthracycline-based chemotherapy, and to investigate the mechanisms of TNBC affecting the survivals. METHODS Data of long-term follow-up (median, 5.4 years) of 326 patients who received neo-adjuvant chemotherapy with anthracycline-based regimen, during a period from 2000 to 2003, were analyzed. Expressions of ER, PR, HER-2, P53, Ki-67 and E-cadherin were determined using immunohistochemical staining method. A multivariate Cox regression analysis was used to analyze independent prognostic factors affecting the relapse-free survival (RFS) and overall survival (OS) rates. Clinical effects of the neo-adjuvant anthracycline-based chemotherapeutic regimen and the RFS and OS rates were compared between the patients with TNBC and non-TNBC, and the correlations among the triple- negative phenotype (TNP), tumor grading and the expressions of P53, Ki-67 and E-cadherins were analyzed. RESULTS TNP, TNM staging, histological grades, clinical response of the neo-adjuvant chemotherapy and pathological complete remission (pCR) rate were the independent prognostic factors affecting the survival rates. Furthermore, 70 (21.5%) of the 326 patients suffered TNBC. Compared with the subjects in non- TNBC group, the patients with TNBC had a significantly higher pCR rate (P=0.046) and clinical response rate (P＝0.037), but also decreased 5-year RFS (P=0.001) and OS (P=0.004) rates. The RFS and OS rates were not improved in the TNBC patients who achieved a clinical remission after the neo-adjuvant chemotherapy. The triple-negative phenotype was positively correlated with the level of P53, Ki-67 expression (P＝0.007, P＝0.028), but negatively correlated with level of E-cadherin (P＝0.034).CONCLUSION Both clinical remission rate and pCR rate of the TNBC patients receiving neo-adjuvant anthracycline-based chemotherapy are high, however, the long-term effect is poor.The mechanism may relate to a strong potential of proliferation and invasive metastasis, as well as lack of an effective therapeutic target in the TNBC patients.     

Ki-67 can be used for further classification of triple negative breast cancer into two subtypes with different response and prognosis

Introduction

Triple negative breast cancer (TNBC) has a poorer survival, despite a higher response rate to neoadjuvant chemotherapy. The purpose of this study was to identify the predictive or prognostic value of Ki-67 among patients with TNBC treated with neoadjuvant chemotherapy, and the role of Ki-67 in further classification of TNBC.

Methods

A total of 105 TNBC patients who received neoadjuvant docetaxel/doxorubicin chemotherapy were included in the present study. Pathologic complete response (pCR) rate, relapse-free survival (RFS), and overall survival (OS) were compared according to the level of Ki-67.

Results

pCR was observed in 13.3% of patients. TNBC with high Ki-67 expression (≥10%) showed a higher pCR rate to neoadjuvant chemotherapy than TNBC with low Ki-67 expression. None of the low Ki-67 group achieved pCR (18.2% in the high Ki-67 group vs. 0.0% in the low Ki-67 group, P = 0.019). However, a high Ki-67 expression was significantly associated with poor RFS and OS in TNBC, despite a higher pCR rate (P = 0.005, P = 0.019, respectively). In multivariate analysis, high Ki-67 was an independent prognostic factor for RFS in TNBC (hazard ratio = 7.82, P = 0.002). The high Ki-67 group showed a similar pattern of recurrence with overall TNBC, whereas the low Ki-67 group demonstrated a relatively constant hazard rate for relapse.

Conclusions

TNBC with high Ki-67 was associated with a more aggressive clinical feature despite a higher pCR rate. High proliferation index Ki-67 can be used for further classification of TNBC into two subtypes with different responses and prognosis.     

SUVmax、Ki-67、p53、EGFR对三阴性乳腺癌新辅助化疗疗效的预测价值

目的 探讨18F-FDG PET/CT化疗前SUVmax、Ki-67、p53、EGFR对三阴性乳腺癌（TNBC）及非三阴性乳腺癌（非TNBC）对新辅助化疗完全病理缓解（pathologic complete response, pCR）率的预测价值。方法 初治TNBC患者27例,非TNBC患者184例,在新辅助化疗前行18F-FDG PET/CT显像并测量其SUVmax,取化疗前乳腺肿瘤组织进行Ki-67、p53、EGFR免疫组织化学分析并计算化疗后完全pCR率。结果 TNBC新辅助化疗前的SUVmax明显高于非TNBC的SUVmax（P=0.045）,TNBC新辅助化疗后pCR率明显高于非TNBC（P＜0.001）。在TNBC以及非TNBC中,达到pCR组的化疗前SUVmax与未达到pCR组之间差异无统计学意义（P＞0.05）。Ki-67、p53、EGFR阳性表达组的pCR率与阴性表达组之间差异无统计学意义（P＞0.05）。结论 TNBC对新辅助化疗的敏感度高于非TNBC,且TNBC化疗前SUVmax高于非TNBC,提示TNBC具有较高的能量代谢。化疗前SUVmax以及Ki-67、p53、EGFR不能预测TNBC及非TNBC新辅助化疗的pCR。     

Semi-quantitative evaluation of estrogen receptor expression is a strong predictive factor of pathological complete response after anthracycline-based neo-adjuvant chemotherapy in hormonal-sensitive breast cancer

Absence of hormonal receptors (HR) expression is a predictive factor of high pathologic complete response (pCR) rate after neo-adjuvant chemotherapy. However, HR-positive tumors are less chemosensitive. In the present study, we evaluated the predictive value of estrogen (ER) and progesterone (PgR) semi-quantitative expression in patients with HR-positive tumors treated uniformly with antracycline-based neoadjuvant chemotherapy without hormonal treatment. Value of HR expression as a predictive factor was then evaluated in a multivariate analysis with tumor grade, Ki67 index and HER2 expression. From January 2000 and December 2006, 177 patients with HR-positive breast ductal invasive carcinoma ≥2 cm in its largest diameter were treated with six cycles of an anthracycline-based neo-adjuvant chemotherapy. Tumor grade, ER, PgR, HER2 status and Ki67 index were determined on microbiopsy performed before chemotherapy. A semi-quantitative evaluation of ER and PgR expression by IHC was performed using the Barnes’score. pCR rate was significantly different (P < 0.001) according to the ER expression score. pCR rate was 28% for low score, 9% for medium score and 3% for high score. On the contrary, pCR rate was not significantly different (P = 0.49) according to the PgR expression score. In the multivariate analysis, ER expression score (P = 0.0002) and Ki67 index (P = 0.02) were the only predictive factors of response for HR-positive tumors. pCR after anthracycline-based chemotherapy is significantly correlated with the ER expression score.     

Prognostic implications of residual disease tumor-infiltrating lymphocytes and residual cancer burden in triple-negative breast cancer patients after neoadjuvant chemotherapy

BackgroundFor primary triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy (NAC), higher pretreatment tumor-infiltrating lymphocytes (TILs) correlates with increased pathologic complete response (pCR) rates, and improved survival. We evaluated the added prognostic value of residual disease (RD) TILs to residual cancer burden (RCB) in predicting survival post-NAC.Patients and methodsWe combined four TNBC NAC patient cohorts who did not achieve pCR. RD TILs were investigated for associations with recurrence-free survival (RFS), and overall survival (OS) using Cox models with stromal TILs as a continuous variable (per 10% increment). The likelihood ratio test was used to evaluate added prognostic value of RD TILs.ResultsA total of 375 RD TNBC samples were evaluable for TILs and RCB. The median age was 50 years, with 62% receiving anthracycline/taxane chemotherapy. The RCB class after NAC was 11%, 50%, and 39% for I, II, and III, respectively. The median RD TIL level was 20% (IQR 10–40). There was a positive correlation between RD TIL levels and CD8+ T-cell density (ρ = 0.41). TIL levels were significantly lower with increasing post-NAC tumor (P = 0.005), nodal stage (P = 0.032), but did not differ by RCB class (P = 0.84). Higher RD TILs were significantly associated with improved RFS (HR: 0.86; 95% CI 0.79–0.92; P < 0.001), and improved OS (HR: 0.87; 95% CI 0.80–0.94; P < 0.001), and remained significant predictors in multivariate analysis (RFS P = 0.032; OS P = 0.038 for OS). RD TILs added significant prognostic value to multivariate models including RCB class (P < 0.001 for RFS; P = 0.021 for OS). The positive prognostic effect of RD TILs significantly differed by RCB class for RFS (P_Int=0.003) and OS (P_Int=0.008) with a greater magnitude of positive effect observed for RCB class II than class III.ConclusionsTIL levels in TNBC RD are significantly associated with improved RFS and OS and add further prognostic information to RCB class, particularly in RCB class II.     

Neoadjuvant chemotherapy for triple-negative breast cancer: a meta-analysis with 7168 cases简

Objective:The pathological complete response (pCR) rates of neoadjuvant chemotherapy (NAC) in triple-nega-tive breast cancer (TNBC) was reported higher than that in non-TNBC but ranged from 12%to 48%. pCR was reported to be a predictor of long overal survival and exact pCR rate of NAC in TNBC would give us some hints on how to improve outcomes of TNBC patients. The meta-analysis was conducted to estimate the pCR rate of NAC for TNBC through contrasting the pCR rates of TNBC and non-TNBC tumors in NAC. Methods:Studies were selected from the PubMed database and Cochrane Col aboration Library. pCR rates were col ected in groups of TNBC and non-TNBC tumors. Review Manager 4.2 was used to perform forest plots and funnel plots. Results:The analysis included 22 studies with 7168 patients, the aggregate pCR rate was 29.5%in TNBC group, which was 17.7%higher than non-TNBC. The summary relative risk (RR) for pCR rate of TNBC group with that of non-TNBC group was 2.55. No obvious statistical heterogeneity and publication bias was detected. Conclu-sion:This meta-analysis demonstrated that NAC showed a higher pCR rate in TNBC than non-TNBC.     

Pathologic complete response to neoadjuvant chemotherapy with trastuzumab predicts for improved survival in women with HER2-overexpressing breast cancer

BackgroundWe sought to determine the prognostic value of pathologic response to neoadjuvant chemotherapy with concurrent trastuzumab.Patients and methodsTwo hundred and twenty-nine women with HER2/neu (HER2)-overexpressing breast cancer were treated with neoadjuvant chemotherapy plus trastuzumab between 2001 and 2008. Patients were grouped based on pathologic complete response (pCR, n = 114) or less than pCR (<pCR, n = 115); as well as by pathologic stage. Locoregional recurrence-free (LRFS), distant metastasis-free (DMFS), recurrence-free (RFS), and overall survival (OS) rates were compared.ResultsThe median follow-up was 63 (range 53–77) months. There was no difference in clinical stage between patients with pCR or <pCR. Compared with patients achieving <pCR, those with the pCR had higher 5-year rates of LRFS (100% versus 95%, P = 0.011), DMFS (96% versus 80%, P < 0.001), RFS (96% versus 79%, P < 0.001), and OS (95% versus 84%, P = 0.006). Improvements in RFS and OS were seen with decreasing post-treatment stage. Failure to achieve a pCR was the strongest independent predictor of recurrence (hazard ratio [HR] = 4.09, 95% confidence interval [CI]: 1.67–10.04, P = 0.002) and death (HR = 4.15, 95% CI: 1.39–12.38, P = 0.011).ConclusionspCR and lower pathologic stage after neoadjuvant chemotherapy with trastuzumab are the strongest predictors of recurrence and survival and are surrogates of the long-term outcome in patients with HER2-overexpressing disease.     

Survival analysis of carboplatin added to an anthracycline/taxane-based neoadjuvant chemotherapy and HRD score as predictor of response—final results from GeparSixto

BackgroundIn the neoadjuvant GeparSixto study, adding carboplatin to taxane- and anthracycline-based chemotherapy improved pathological complete response (pCR) rates in patients with triple-negative breast cancer (TNBC). Here, we present survival data and the potential prognostic and predictive role of homologous recombination deficiency (HRD).Patients and methodsPatients were randomized to paclitaxel plus nonpegylated liposomal doxorubicin (Myocet®) (PM) or PM plus carboplatin (PMCb). The secondary study end points disease-free survival (DFS) and overall survival (OS) were analyzed. Median follow-up was 47.3 months. HRD was among the exploratory analyses in GeparSixto and was successfully measured in formalin-fixed, paraffin-embedded tumor samples of 193/315 (61.3%) participants with TNBC. Homologous recombination (HR) deficiency was defined as HRD score ≥42 and/or presence of tumor BRCA mutations (tmBRCA).ResultsA significantly better DFS (hazard ratio 0.56, 95% CI 0.34–0.93; P = 0.022) was observed in patients with TNBC when treated with PMCb. The improvement of OS with PMCb was not statistically significant. Additional carboplatin did not improve DFS or OS in patients with HER2-positive tumors. HR deficiency was detected in 136 (70.5%) of 193 triple-negative tumors, of which 82 (60.3%) showed high HRD score without tmBRCA. HR deficiency independently predicted pCR (ypT0 ypN0) [odds ratio (OR) 2.60, 95% CI 1.26–5.37, P = 0.008]. Adding carboplatin to PM significantly increased the pCR rate from 33.9% to 63.5% in HR deficient tumors (P = 0.001), but only marginally in HR nondeficient tumors (from 20.0% to 29.6%, P = 0.540; test for interaction P = 0.327). pCR rates with carboplatin were also higher (63.2%) than without carboplatin (31.7%; OR 3.69, 1.46–9.37, P = 0.005) in patients with high HRD score but no tmBRCA. DFS rates were improved with addition of carboplatin, both in HR nondeficient (hazard ratio 0.44, 0.17–1.17, P = 0.086) and HR deficient tumors (hazard ratio 0.49, 0.23–1.04, P = 0.059).ConclusionsThe addition of carboplatin to neoadjuvant PM improved DFS significantly in TNBC. Long-term survival analyses support the neoadjuvant use of carboplatin in TNBC. HR deficiency in TNBC and HRD score in non-tmBRCA TNBC are predictors of response. HRD does not predict for carboplatin benefit.     

Differential response of triple‐negative breast cancer to a docetaxel and carboplatin‐based neoadjuvant treatment

BACKGROUND:

In this study, the authors evaluated whether a pathologic complete response (pCR) or a clinical complete response (cCR) to neoadjuvant treatment in patients with locally advanced breast cancer differed among the 3 subtypes of breast cancer: triple‐negative breast cancer (TNBC), human epidermal growth factor receptor 2 (HER2)‐positive breast cancer, and hormone receptor‐positive/HER2‐negative breast cancer. Whether a cCR or a pCR was correlated with fewer recurrences and better survival also was investigated.

METHODS:

Patients with stage II/III breast cancer received 4 cycles of neoadjuvant docetaxel and carboplatin (TC) every 3 weeks. Patients with HER2‐positive tumors were randomized to receive either additional weekly trastuzumab preoperatively or TC alone. Postoperatively, all patients received 4 cycles of TC, and all HER2‐positive patients received a total of 52 weeks of trastuzumab. The recurrence‐free survival (RFS) and overall survival (OS) rates at 2 years were reported.

RESULTS:

Seventy‐four patients were enrolled, including 11 patients with TNBC, 30 patients with HER2‐positive tumors, and 33 patients with hormone receptor‐positive/HER2‐negative tumor. The cCR rates were 45.4%, 50% and 40.6% in TNBC, HER2‐positive, and hormone receptor‐positive/HER2‐negative groups, respectively. The pCR rate for the entire group was 26.8%, and patients with TNBC had the best response (54.6%) followed by patients with HER2‐positive tumors (24.1%) and patients with hormone receptor‐positive/HER2‐negative tumors (19.4%; P = .0126). The pCR rate for patients with HER2‐positive tumors improved from 7% to 40% if trastuzumab was added (P = .08). Infiltrating ductal cancer, TNBC, negative estrogen receptor and/or progesterone receptor status, tumor classification predicted a pCR (P ≤ .05). Multivariate analysis using a logistic regression test indicated that tumor type was an independent predictor. The RFS rate for patients who did versus patients who did not achieve a pCR was 93.8% versus 78.4% at 2 years, respectively, and 83.3% versus 58% at 3 years, respectively (P = .1227); whereas, for patients who did versus patients who did not achieve a cCR, the RFS rate was 80.9% versus 83.9%, respectively, at 2 years and 65% versus 64.3%, respectively, at 3 years (P = .999).

CONCLUSIONS:

The current results indicated that the TC combination is promising for the treatment of TNBC. The addition of trastuzumab to TC improved the pCR rate significantly in patients with HER2‐positive breast cancer. Cancer 2010. © 2010 American Cancer Society.     

三阴性乳腺癌患者的临床特征及新辅助化疗疗效与预后的相关性

 目的　探讨三阴性乳腺癌（TNBC）的临床病理特点及远期生存率。并分析其新辅助化疗的疗效与生存率的相关性。方法　研究对象为535例乳腺癌患者,其中TNBC患者75例,非TNBC患者460例,对其临床和病理资料以及 5年的无病生存（DFS）率及总生存（OS）率进行回顾性分析,并与同期的非TNBC患者进行对比。535例中88例患者接受术前新辅助化疗,TNBC患者26例,非TNBC患者62例,分析其化疗疗效与远期生存的相关性。结果　TNBC患者与非TNBC患者相比,中位年龄轻（35岁比44岁）,绝经前患者居多（88.0 % 比67.2 %,P＝0.009）;浸润性导管癌多见（92. 0 % 比80.4 %,P＝0.020）,组织学分级Ⅱ级者居多（56.0 %比17.2 %,P＝0.000）;淋巴结转移阳性者较少（33.3 %比53.9 %,P＝0.001）;TNBC组5年DFS（66.67 %）、OS（80.0 %）明显低于非TNBC组（74.78 %、90.0 %）。接受新辅助化疗的TNBC患者与非TNBC患者相比,化疗的总有效（OR）率（88.46 %比82.26 %）、临床完全缓解（cCR）率（65.38 %比37.10 %）、部分缓解（PR）率（23.08 %比45.16 %）差异均有统计学意义（P＜0.05）。新辅助化疗的TNBC患者与非TNBC患者相比,5年的OS率（73.08 %比80.65 %）差异具有统计学意义（P＝0.049）;5年的DFS率（65.38 %比72.58 %）差异具有统计学意义（P＝0.253）。分层分析发现：获得cCR的TNBC与非TNBC患者的5年DFS及OS差异无统计学意义（P＞0.05）。未获得cCR TNBC患者的5年DFS及OS均显著低于非TNBC患者（P＜0.05）,临床OR对两组的5年DFS及OS无影响（P＞0.05）。结论　TNBC多见于年轻的绝经前妇女,主要病理类型为浸润性导管癌,核分级高,淋巴结转移少见,但相对非TNBC患者有较低的DFS率和OS率,TNBC患者对新辅助化疗更敏感,更易获得cCR,获得cCR的TNBC患者预后好,未获得cCR的TNBC患者远期生存率明显低于非TNBC患者     

Locoregional Recurrence and Survival Outcomes in Breast Cancer Treated With Modern Neoadjuvant Chemotherapy: A Contemporary Population-based Analysis

BackgroundData guiding radiotherapy (RT) decisions after neoadjuvant chemotherapy (NAC) is largely retrospective, based on older treatment approaches without molecular subtype information. This study evaluated outcomes in breast cancer patients treated with modern NAC by molecular subtype and locoregional treatment.Materials and MethodsThere were 949 patients diagnosed between 2005 and 2016 treated with NAC followed by surgery ± locoregional radiotherapy (LRRT). Outcomes were 7-year locoregional relapse-free survival (LRRFS), breast cancer-specific survival (BCSS), and overall survival (OS).ResultsMedian follow-up was 6.5 years, 92% had cT2-4 and 72% cN1-3 disease. Subtypes were: 21% Luminal A, 18% Luminal B, 35% Her2+, and 21% triple-negative breast cancer (TNBC). Combined taxane and anthracycline-based NAC was used in 91.7% of cases. All patients with Her2+ disease received anti-Her2 therapy. After NAC, the majority (84.9%) underwent mastectomy, and received LRRT (86.1%). Only 11% had mastectomy without RT. Pathologic complete response (pCR) rates were 2.5% for Luminal A, 14.4% Luminal B, 27% TNBC, and 35.1% Her2+. Overall, adjuvant LRRT was associated with improved outcomes but was most significant for improved LRRFS in TNBC (92.5% vs. 68.5%, P < .001; Her2+ 95.4% vs. 93.6%, P = .81; Luminal A 97.4% vs. 100%, P = .49; Luminal B 89.7% vs. 100%, P = .17). On multivariable analysis, factors associated with reduced LRRFS were grade 3 histology (HR 4.96, P = .009) and no pCR (HR 7.0, P = .0008). Predictors of lower BCSS and OS were age >50, grade 3, cT3-4, lack of pCR, LRRT omission, and TNBC and Her2+ subtypes.ConclusionIn this analysis of patients treated with modern NAC, pCR rates varied by molecular subtype. Patients who did not receive LRRT, particularly those with TNBC, had lower survival compared to those treated with LRRT. These findings support the need for prospective studies to evaluate the safety of de-escalating RT after NAC.     

三阴性乳腺癌新辅助化疗后组织中Ki-67表达变化及其与疗效和预后的相关性

目的:探讨三阴性乳腺癌（triple negative breast cancer,TNBC）新辅助化疗（neoadjuvant chemotherapy,NAC）后组织中Ki-67表达变化及其与疗效和预后的相关性。方法:选取我院2013年01月至2018年01月经病理确诊为TNBC的患者70例,根据免疫组化法检测NAC后组织中Ki-67表达的变化,并根据Ki-67的表达变化将患者分为三组,分别为:低表达转为高表达组、表达无变化组和高表达转为低表达组,对比三组患者NAC的疗效,并应用Kaplan-Meier法绘制三组患者的生存曲线进行生存分析。结果:NAC后49例患者达到临床缓解,27例患者达到病理完全缓解（pathological complete response,pCR）。NAC后高表达转为低表达组可获得较好的临床缓解率及pCR率,三组患者的比较结果显示差异具有明显统计学意义（P＜均0.05）。无病生存率（disease free survival,DFS）在低表达转为高表达组、表达无变化组及高表达转为低表达组中的差异具有明显统计学意义（P=0.001）;三组患者的OS比较结果显示差异无明显统计学意义（P=0.085）。结论:TNBC患者NAC后组织中Ki-67的表达可发生改变,Ki-67表达降低的患者可能具有较好的疗效及预后。     

Effect of adding gefitinib to neoadjuvant chemotherapy in estrogen receptor negative early breast cancer in a randomized phase II trial

Gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, has shown both anti-proliferative and anti-tumoral activity in breast cancer. This study was designed to determine the effect of adding gefitinib to neoadjuvant epirubicin and cyclophosphamide (EC) on tumor response rates. Women with unilateral, primary operable, estrogen receptor negative invasive breast cancer ≥ 2 cm were eligible for inclusion. Randomized patients were to receive four cycles of neoadjuvant EC plus 12 weeks of either gefitinib (250 mg daily) or placebo. Primary endpoint was pathologic complete response (pCR), and secondary endpoints were complete response (CR) and overall objective response (OR). 181 patients were randomized. A pCR was observed in 17% (12/71) of patients treated with gefitinib and in 12% (9/73) of patients treated with placebo (4.57% difference, 95% CI −7.19 to 6.33; P = 0.44). CR was observed in 10% of patients in both the gefitinib (7/71) and the placebo group (7/73) (0.27% difference, 95% CI −9.6 to 10.2; P = 0.96). There was no significant difference in OR (5.96%; 95% CI −9.9 to 21.9; P = 0.45) between the two groups. Post hoc subgroup analysis showed a significant difference in pCR between triple negative breast cancer (TNBC) and non-TNBC tumors (P = 0.03). More patients in the gefitinib arm had hematological toxicity (P = 0.15) and discontinued treatment (9/94 vs. 2/86) because of adverse events (AE). Tumor response rates were similar in the two groups. A significantly higher pCR rate was observed post hoc in TNBC versus non-TNBC independent of treatment. More patients in the gefitinib group discontinued treatment because of AE.     

Adjuvant chemotherapy and radiotherapy in triple-negative breast carcinoma: A prospective randomized controlled multi-center trial

Background and purpose: Triple-negative breast cancer (TNBC) presents a high risk breast cancer that lacks the benefit from hormone treatment, chemotherapy is the main strategy even though it exists in poor prognosis. Use of adjuvant radiation therapy, which significantly decreases breast cancer mortality, has not been well described among poor TNBC women. The aim of this study was to evaluate whether the combination of chemotherapy and radiotherapy could significantly increase survival outcomes in TNBC women after mastectomy. Patients and methods: A prospective randomized controlled multi-center study was performed between February 2001 and February 2006 and comprised 681 women with triple-negative stage I–II breast cancer received mastectomy, of them, 315 cases received systemic chemotherapy alone, 366 patients received radiation after the course of chemotherapy. Recurrence-free survival (RFS) and overall survival (OS) were estimated. Simultaneously local and systemic toxicity were observed. Results: After a median follow-up of 86.5 months, five-year RFS rates were 88.3% and 74.6% for adjuvant chemotherapy plus radiation and adjuvant chemotherapy alone, respectively, with significant difference between the two groups (HR 0.77 [95% CI 0.72, 0.98]; P = 0.02). Five-year OS significantly improved in adjuvant chemotherapy plus radiation group compared with chemotherapy alone (90.4% and 78.7%) (HR 0.79 [95% CI 0.74, 0.97]; P = 0.03). No severe toxicity was reported. Conclusions: Patients received standard adjuvant chemotherapy plus radiation therapy was more effective than chemotherapy alone in women with triple-negative early-stage breast cancer after mastectomy.     

Pathologic complete response in breast cancer patients receiving anthracycline‐ and taxane‐based neoadjuvant chemotherapy

BACKGROUND:

The current study was conducted to evaluate the influence of race/ethnicity and tumor subtype in pathologic complete response (pCR) following treatment with neoadjuvant chemotherapy.

METHODS:

A total of 2074 patients diagnosed with breast cancer between 1994 and 2008 who were treated with neoadjuvant anthracycline‐ and taxane‐based chemotherapy were included. pCR was defined as no residual invasive cancer in the breast and axilla. The Kaplan‐Meier product‐limit was used to calculate survival outcomes. Cox proportional hazards models were fitted to determine the relationship of patient and tumor variables with outcome.

RESULTS:

The median patient age was 50 years; 14.6% of patients were black, were 15.2% Hispanic, 64.3% were white, and 5.9% were of other race. There were no differences in pCR rates among race/ethnicity (12.3% in black, 14.2% in Hispanics, 12.3% in whites, and 11.5% in others, P = .788). Lack of pCR, breast cancer subtype, grade 3 tumors, and lymphovascular invasion were associated with worse recurrence‐free survival (RFS) and overall survival (OS) (P ≤ .0001). Differences in RFS by race/ethnicity were noted in the patients with hormone receptor‐positive disease (P = .007). On multivariate analysis, Hispanics had improved RFS (hazard ratio [HR], 0.69; 95% confidence interval [95% CI], 0.49‐0.97) and OS (HR, 0.63; 95% CI, 0.41‐0.97); blacks had a trend toward worse outcomes (RFS: HR, 1.28 [95% CI, 0.97‐1.68] and OS: HR, 1.32 [95% CI, 0.97‐1.81]) when compared with whites.

CONCLUSIONS:

In this cohort of patients, race/ethnicity was not found to be significantly associated with pCR rates. On a multivariate analysis, improved outcomes were observed in Hispanics and a trend toward worse outcomes in black patients, when compared with white patients. Further research was needed to explore the potential differences in biology and outcomes. Cancer 2010. © 2010 American Cancer Society.     

Efficacy of neoadjuvant therapy with trastuzumab concurrent with anthracycline- and nonanthracycline-based regimens for HER2-positive breast cancer

BACKGROUND:

The aim of this study was to evaluate the pathologic complete response (pCR) rates and relapse‐free survival (RFS) and overall survival (OS) of patients receiving neoadjuvant systemic therapy (NST) with trastuzumab in combination with an anthracycline‐ or nonanthracycline‐based regimen.

METHODS:

In this retrospective nonrandomized study, the authors reviewed records of 300 patients with HER2‐positive breast cancer treated with either sequential paclitaxel and trastuzumab and FEC75 in combination with trastuzumab (PH‐FECH) or docetaxel, carboplatin, and trastuzumab (TCH). The Kaplan‐Meier product‐limit method was used to estimate RFS and OS rates. Logistic regression models and Cox proportional hazards models were fit to determine the associations between NST, pCR, and survival.

RESULTS:

There was no significant difference in the decline in cardiac ejection fraction; however, patients who received PH‐FECH had fewer cardiac comorbidities at baseline (P = .002). pCR rates were 60.6% and 43.3% for patients who received PH‐FECH (n = 235) and TCH (n = 65), respectively (P = .016). Patients who received PH‐FECH were 1.45 times more likely to have a pCR (odds ratio [OR], 1.45; 95% confidence interval [CI], 1.06‐1.98; P = .02). Three‐year RFS rates were 93% and 71% (P < .001), and 3‐year OS rates were 96% and 86% (P = .008) for patients who received PH‐FECH and TCH, respectively. Patients who received PH‐FECH had a lower risk of recurrence (hazard ratio [HR], 0.27; 95% CI, 0.12‐0.60; P = .001) and death (HR, 0.37; 95% CI, 0.12‐1.13; P = .08) than those treated with TCH.

CONCLUSIONS:

The type of NST in HER2‐positive breast cancer is predictive of pCR rate independent of disease and patient characteristics. Although TCH is active, PH‐FECH shows a higher pCR rate and RFS advantage. Cancer 2012. © 2011 American Cancer Society.     

Predictive and prognostic significance of cytoplasmic expression of ELAV-like protein HuR in invasive breast cancer treated with neoadjuvant chemotherapy

Cytoplasmic HuR is associated with reduced survival in invasive breast cancer. We designed this study to determine the predictive and prognostic value of HuR expression in women with breast cancer who underwent neoadjuvant chemotherapy followed by surgical resection. We immunohistochemically analyzed cytoplasmic HuR expression in tumor biopsy cores obtained from 139 patients with invasive breast cancers who received paclitaxel and anthracycline-based neoadjuvant chemotherapy. We evaluated the relationship of HuR expression level with pathologic complete response (pCR), local recurrence-free survival (LRFS), distant recurrence-free survival (DRFS), recurrence-free survival (RFS), and overall survival (OS). Cytoplasmic HuR expression was present in 60 cases (43.2 %). The expression of cytoplasmic HuR was significantly associated with high nuclear grade (P < 0.0001) and ER (P = 0.001) and PR (P = 0.005) status. Multivariate regression analysis further revealed that high nuclear grade (P = 0.023), negative ER status (P = 0.043), and human epidermal growth factor receptor 2 (HER2) overexpression (P < 0.0001), but not cytoplasmic HuR expression, were significant independent predictors of pCR. Interestingly, multivariate Cox analysis revealed that cytoplasmic HuR expression was a strong independent predictor of reduced LRFS (P = 0.014), DRFS (P = 0.001), RFS (P < 0.0001), and OS (P = 0.019) irrespective of pCR. Furthermore, the patient group with tumors showing both expression of cytoplasmic HuR and non-pCR had a worse prognosis in LRFS (P = 0.048), DRFS (P < 0.0001), RFS (P < 0.0001), and OS (P = 0.001) than did other patient groups; patients with tumors showing negative cytoplasmic expression of HuR and pCR had the best prognosis in all RFS and OS. Cytoplasmic expression of HuR is an independent prognostic marker in breast cancer patients undergoing chemotherapy. Combination analyses of HuR expression and pCR, compared with pCR alone, can better predict clinical outcome in patients with primary breast cancer.     

新辅助化疗方案治疗三阴性乳腺癌的效果及生存观察

目的 观察多西他赛＋吡柔比星＋环磷酰胺（TAC方案）治疗三阴性乳腺癌患者的疗效和生存情况.方法 乳腺癌患者51例,三阴组：26例三阴性乳腺癌,Ⅱ期16期,Ⅲ期10例,非三阴组：25例非三阴性乳腺癌,Ⅱ期14期,Ⅲ期11例,两组患者均接受多西他赛联合吡柔比星化疗,多西他赛75 mg/m2,静脉滴注,第1天;吡柔比星40 mg/m2,静脉滴注,第1天;环磷酰胺500 mg/m2,第1天,21d重复.51例患者中位治疗周期数为4个周期.分析乳腺癌患者的疗效和生存情况.结果 三阴组术前临床完全缓解（cCR）9例（34.62％）,临床部分缓解（cPR） 14例（53.85％）,总有效率88.46％.术后病理完全缓解（pCR）7例（26.92％）,非三阴组：术前cCR 6例（24.00％）,cPR 8例（32.00％）,总有效率56.00％,术后pCR 4例（16.00％）,两组3年的总生存率分别为73.08％、88.00％,显示三阴性乳腺癌有较差的预后,达pCR的三阴性乳腺癌患者5年生存率（88.89％）高于未达到pCR的三阴性乳腺癌患者（47.06％）.结论 TAC方案对局部晚期三阴性乳腺癌有较高缓解率和降期效果,可提高三阴性乳腺癌的疗效,安全性较好.     

Phase 2 trial of primary systemic therapy with doxorubicin and docetaxel followed by surgery,radiotherapy, and adjuvant chemotherapy with cyclophosphamide,methotrexate, and 5‐fluorouracil based on clinical and pathologic response in patients with stage IIB to III breast cancer

BACKGROUND:

This study was performed to evaluate the outcomes of patients with locally advanced breast cancer (LABC) who were treated with a multidisciplinary approach including primary systemic chemotherapy and noncross‐resistant adjuvant chemotherapy.

METHODS:

Patients with LABC received 4 or 6 cycles of doxorubicin and docetaxel (DT) as primary systemic chemotherapy (PST) every 21 days. Patients with adequate response underwent surgery followed by adjuvant chemotherapy according to pathologic response: complete (pCR), 2 more cycles of DT; partial (pPR), 2 more cycles of DT followed by 6 cycles of cyclophosphamide, methotrexate, and 5‐fluorouracil (5‐FU) (CMF); and minor (pMR), 6 cycles of CMF. Patients then received radiation and tamoxifen (hormone receptor‐positive patients only).

RESULTS:

Eighty‐eight patients were evaluable. Seventy‐four patients had an adequate response to DT and were considered operable, and 72 underwent surgery. Ten patients (13.9%) achieved a pCR, 22 (30.5%) achieved a pPR, and 40 achieved a pMR (55.5%). Fourteen patients were considered nonoperable after DT and underwent salvage CMF therapy. Five of these patients underwent surgery and 1 had achieved a pCR. The estimated 5‐year recurrence‐free survival (RFS) rates for patients with pCR, pPR, and pMR were 80%, 77%, and 59%, respectively, and the estimated 5‐year overall survival (OS) rates were 90%, 91%, and 74%, respectively. The 5‐year OS rates were 82% for initially operable and 21% for initially inoperable patients (P ≤ .001)

CONCLUSIONS:

Multidisciplinary therapy that includes PST with DT and adjuvant therapy with CMF administered according to the clinical and pathologic response is associated with high long‐term RFS and OS rates in patients with LABC. Clinical or pathologic PR or CR to DT predicts improved RFS and OS. Cancer 2010. Published 2010 by the American Cancer Society.     

Complete pathological response after chemotherapy or immune checkpoint inhibitors in deficient MMR metastatic colorectal cancer: Results of a retrospective multicenter study

About 5% of the patients with metastatic colorectal cancers (mCRC) present microsatellite instability (MSI)/deficient mismatch repair system (dMMR). While metastasectomy is known to improve overall and progression-free survival in mCRC, specific results in selected patients with dMMR/MSI mCRC are lacking. Our study aimed to describe metastasectomy results, characterize histological response and evaluate pathological complete response (pCR) rate in patients with dMMR/MSI mCRC. We retrospectively reviewed data from all consecutive patients with dMMR/MSI mCRC who underwent surgical metastasectomy between January 2010 and June 2021 in 17 French centers. Primary outcome was to assess the pCR rate defined by tumor regression grade (TRG) 0. Secondary endpoints included relapse-free survival (RFS) and overall survival (OS), and explored TRG as predictive factor for RFS and OS. Among the 88 patients operated, 109 metastasectomies were performed in 81 patients after neoadjuvant treatment [chemotherapy ± targeted therapy (CTT): 69, 85.2%; immunotherapy (ICI): 12, 14.8%], and pCR was achieved in 13 (16.1%) patients. Among the latter, pCR rate were 10.2% in the patients having received CTT (N = 7) and 50.0% in the patients treated with ICI (N = 6). Radiological response did not predict TRG. With a median follow-up of 57.9 (IQR 34.2-81.6) months, median RFS was 20.2 (15.4-not reached) months, median OS was not reached. Major pathological responses (TRG0 + TRG1) were significantly associated with longer RFS (HR 0.12, 95% CI 0.03-0.55; P = .006). The pCR rate of 16.1% achieved with neoadjuvant treatment in patients with dMMR/MSI mCRC is consistent with previously reported rates in pMMR/MSS mCRC. Immunotherapy showed better pCR rate than chemotherapy ± targeted therapy. Further prospective trials are needed to validate immunotherapy as neoadjuvant treatment in resectable/potentially resectable dMMR/MSI mCRC and identify predictive factors for pCR.