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.     

6周期AT新辅助化疗治疗乳腺癌临床疗效及其影响因素的分析

目的:探讨6周期AT方案(蒽环类联合紫杉类)新辅助化疗在乳腺癌治疗中的疗效及影响pCR 的因素.方法:回顾性分析159例顺利完成6周期AT方案患者的临床病理资料,对比治疗前后病理变化,评价其临床疗效及不良反应,并探究影响新辅助化疗达到pCR的因素.结果:159例完成6周期AT方案新辅助化疗的乳腺癌患者占同期进行新辅助化疗52.3%,总pCR为30.8%,降期率为76.1%.单因素及Logistic回归分析发现,肿瘤大小,组织学分级,ER、PR状态、HER-2表达、分子分型以及化疗的早期反应是影响pCR的重要因素,其中肿瘤≤3 cm、ER缺失、HER-2扩增、超声评价化疗早期反应阳性患者更容易达到pCR.结论:乳腺癌6周期AT方案新辅助化疗pCR率较高,超声评价的早期反应能够预测pCR,肿瘤大小以及肿瘤分子分型是影响pCR的重要因素,临床实践中需综合考虑影响因素,从而决定手术的最佳时机.     

Evaluation of ER,PgR, HER-2, Ki-67, cyclin D1, and nm23-H1 as predictors of pathological complete response to neoadjuvant chemotherapy for locally advanced breast cancer

The purpose of this study was to evaluate the importance of biological markers to predict pathologic complete response (pCR) to neoadjuvant docetaxel plus epirubicin combination chemotherapy in patients with locally advanced breast cancer (LABC). Two hundred and twenty consecutive patients with LABC who had received neoadjuvant chemotherapy (NCT) with docetaxel and epirubicin from March 2006 to March 2009 were included in this retrospective study. The pre- and post-neoadjuvant chemotherapy (NCT) treatment expression levels and changes of Ki-67 proliferation index, estrogen receptor (ER), progesterone receptor (PgR), epidermal growth factor receptor 2 (HER-2), cyclin D1, and nm23-H1 were detected by immunohistochemistry (IHC). The pCR rate was 9.1% (95% CI, 5.3–12.9%). In univariate analysis, poor tumor differentiation, OR after 2 cycles of NCT, both negative of ER/PgR, negative HER-2, positive cyclin D1, and positive nm23-H1 were found to be significantly predictive of a pCR. Histological grade and ER/PgR status were significant for pCR on multivariate analysis (P = 0.023 and 0.003, respectively). The expression levels of cyclin D1 (median, 8% vs. 9%; P = 0.016) after NCT treatment increased significantly, while the median Ki-67 proliferation index was dramatically decreased after NCT treatment from 35 to 15% (P = 0.036). However, after a Bonferroni adjustment, only the difference of Ki-67 proliferation index was still significant (P = 0.026). Histological grade and ER/PgR status are independent predictive factors of pCR to neoadjuvant docetaxel plus epirubicin combination chemotherapy in locally advanced breast cancer. Expression of HER-2, Ki-67, cyclin D1, and nm23-H1 were not predictive for pCR.

     

Correlation of breast cancer susceptibility loci with patient characteristics, metastasis-free survival, and mRNA expression of the nearest genes

Sequential doxorubicin/paclitaxel (AT) followed by CMF treatment was shown to be an active neoadjuvant chemotherapy regimen in the first European Cooperative Trial in Operable Breast Cancer (ECTO I trial). The aim of the current study (ECTO II) is to assess the complete pathological response (pCR) rate following three different anthracycline and taxane-containing neoadjuvant chemotherapy regimens, with or without capecitabine (X). Patients with operable, invasive breast cancer >2.0?cm in diameter, were randomized to AT??CMF, AT??CMX or AC??TX regimens in two parallel, randomized, open-label, phase II trials (within a single study) in patients with estrogen receptor negative (ER?) and estrogen receptor positive (ER+) diseases, respectively. Exemestane was delivered concomitantly with neoadjuvant chemotherapy in ER+ tumors. Achievement of pCR was more common in ER? than ER+ women (45.3 vs. 10.4%). Capecitabine was only associated with a higher frequency of pCR in ER+ patients receiving AT??CMX. Overall response rates (ORR) ranged from 88 to 97%, and this translated into high rates of breast-conserving surgery (67% of ER? patients and 72% of ER+ patients). All three regimens were well tolerated. Febrile neutropenia and gastrointestinal effects were the most common grade???3 adverse events. As expected, the ECTO II study showed higher pCR rates in patients with ER? disease. Substituting capecitabine for fluorouracil (± methotrexate) in anthracycline/taxane-containing regimens appeared to be beneficial only in ER+ tumors. Translational studies investigating interactions between therapeutic agents and tumor biology are warranted to refine patient selection and improve the results of neoadjuvant chemotherapy.     

Phase I–II study of the farnesyl transferase inhibitor tipifarnib plus sequential weekly paclitaxel and doxorubicin–cyclophosphamide in HER2/neu-negative inflammatory carcinoma and non-inflammatory estrogen receptor-positive breast carcinoma

Tipifarnib (T) is a farnesyl transferase inhibitor (FTI) that enhances the antineoplastic effects of cytotoxic therapy in vitro, has activity in metastatic breast cancer, and enhances the pathologic complete response (pCR) rate to neoadjuvant doxorubicin–cyclophosphamide (AC) chemotherapy. We, therefore, performed a phase I–II trial of T plus neoadjuvant sequential weekly paclitaxel and 2-week AC chemotherapy in locally advanced breast cancer. Eligible patients with HER2-negative clinical stage IIB–IIIC breast cancer received 12 weekly doses of paclitaxel (80 mg/m²) followed by AC (60/600 mg/m² every 2 weeks and filgrastim), plus T (100 or 200 mg PO on days 1–3 of each P dose, and 200 mg PO on days 2–7 of each AC cycle). The trial was powered to detect an improvement in breast pCR rate from 15 to 35 % (α = 0.10, β = 0.10) in two strata, including ER and/or PR-positive, non-inflammatory (stratum A) and inflammatory carcinoma (stratum B). Of the 60 patients accrued, there were no dose-limiting toxicities among the first six patients treated at the first T dose level (100 mg BID; N = 3) or second T dose level (200 mg BID; N = 3) plus paclitaxel. Breast pCR occurred in 6/33 patients (18 %, 95 % confidence intervals (CI) 7–36 %) and 1/22 patients (4 %, 95 % CI 0–8 %) in stratum B. Combination of the FTI T with weekly paclitaxel–AC is unlikely to be associated with a breast pCR rate of 35 % or higher in patients with locally advanced HER2/neu-negative inflammatory or non-inflammatory ER- and/or PR-positive breast carcinoma.     

术前新辅助短程密集化疗疗效与乳腺癌受体亚型及组织学类型的关系

目的评价不同组织学类型和受体亚型的乳腺癌患者对新辅助短程密集化疗疗效反应的差异。方法 对2004年1月至2006年12月期间在西南医院乳腺疾病中心接受新辅助短程密集化疗的223例可手术乳腺癌患者资料进行回顾性分析。根据术前粗针穿刺结果,将患者的肿瘤分为雌激素受体（ER）阳性[人表皮生长因子受体（HER-2）阴性]、三阴性以及HER-2阳性。新辅助短程密集化疗为4个周期,化疗方案均为TE（多西紫杉醇75mg/m2d1＋表柔比星75mmg/m2d1）,14d为1个周期。采用χ2检验分析乳腺癌组织学分类和受体亚型与病理学完全缓解率和化疗有效率的关系。结果 总的化疗有效率和病理完全缓解（pCR）率分别为59%（132/223）和9%（21/223）。浸润性导管癌和浸润性小叶癌的化疗有效率分别为70%（122/175）和24%（8/33）（P〈0.01）,pCR率分别为11%（20/175）和3%（1/33）。ER阳性、三阴性和HER-2阳性乳腺癌患者的化疗有效率分别为46%（57/123）、84%（43/51）和65%（32/49）（χ2=22.49,P=0.00）,pCR率分别为2%（3/123）、23%（12/51）和12%（6/49）（χ2=19.39,P=0.00）。结论 浸润性小叶癌患者从新辅助化疗中获益较小,新辅助化疗后ER阳性乳腺癌的pCR率很低     

激素受体和HER-2及Ki-67预NSL腺癌新辅助化疗疗效价值的分析

目的：探讨乳腺癌组织中雌激素受体（ER）、孕激素受体（PR）、人表皮生长因子受体2（HER-2）及Ki-67的表达状态对新辅助化疗反应的预测作用以及化疗前后其表达差异对疗效的影响。方法：免疫组织化学方法检测新辅助化疗前后118例乳腺癌组织的ER、PR、HER-2及Ki-67的表达情况,并分析其与新辅助化疗疗效的关系。结果：118例新辅助化疗乳腺癌病例中,ER-和PR-组pCR分别为26．1％和27．1％,明显高于ER＋组11．1％和PR＋组6．8％,P-0．003。HER-2和Ki-67的表达对新辅助化疗疗效无显著影响。新辅助化疗前ER、PR与Ki-67的表达呈明显负相关,P〈0．001;新辅助化疗后Ki-67的高表达病例数显著减少,P-0．001。结论：ER-／PR-的患者对新辅助化疗更为敏感,Ki-67在化疗后发生了显著下调,提示新辅助化疗能降低肿瘤的增殖活性。ER、PR及Ki-67可以作为新辅助化疗疗效的预测指标。     

新辅助化疗TE与CEF方案治疗乳腺癌的临床效果比较

目的比较新辅助化疗TE（紫杉类联合蒽环类）及CEF（环磷酰胺、表阿霉素、氟尿嘧啶）方案治疗乳腺癌的疗效，不良反应及其与组织病理学的关系；探讨新辅助化疗对ER、PR、HER-2、P53表达状况的影响。方法收集天津肿瘤医院2001年1月至2006年12月临床分期Ⅱ～Ⅲ期的行TE新辅助化疗患者167例，行CEF新辅助化疗患者256例。化疗皆以21d为1个周期。所有患者均完成3个周期以上的化疗后对两组患者临床效果的差异进行评价。结果乳腺癌原发肿瘤的总缓解率（RR），TE组为86％（144／167），CEF组为67％（172／256），两组间比较差异无统计学意义（P〈0．01）。临床完全缓解率（cCR），TE组为32％（54／167），CEF组为23％（59／256），两组间比较差异有统计学意义（P〈0．05）。病理完全缓解率（pCR），TE组为19％（32／167），CEF组为14％（36／256），两组间比较差异无统计学意义（P〉0．05）。两组各有2例患者出现疾病进展（PD）。主要不良反应为白细胞下降、胃肠道反应，TE组脱发较严重。两组化疗方案对ER、PR、HER-2、P53表达的差异均无统计学意义。结论新辅助化疗TE与CEF方案对乳腺癌均有较高的缓解率，且TE方案优于CEF方案。化疗的不良反应均在可耐受范围之内，而TE组患者的脱发等副反应要高于CEF组。两组新辅助化疗对ER、PR、HER-2、P53表达的影响无统计学意义。     

Association between HER2 status and response to neoadjuvant anthracycline followed by paclitaxel plus carboplatin chemotherapy without trastuzumab in breast cancer

Background

We recently showed HER2-positive breast cancers are less likely to respond to neoadjuvant anthracycline chemotherapy. Here, we investigated whether HER2-positive breast cancers responded to sequential neoadjuvant anthracycline followed by paclitaxel plus carboplatin regimen in the absence of trastuzumab.

Methods

Women (n=372) with operable primary breast cancer initially received two cycles of neoadjuvant anthracyclines, the clinical tumor response was assessed, then patients were received four cycles of paclitaxel plus carboplatin regimen. All the patients did not received trastuzumab treatment in the neoadjuvant setting. HER2 status was determined by immunohistochemistry and/or by fluorescence in situ hybridization in core-biopsy breast cancer tissue obtained before the neoadjuvant chemotherapy.

Results

Eighteen percent (67/372) of patients achieved a pathologic complete response (pCR) in their breast. HER2-positive tumors had a significant higher pCR rate than HER2-negative tumors (33.0% versus 13.5%, P<0.001) in this cohort of 372 patients, and positive HER2 status remained an independent favorable predictor of pCR in a multivariate analysis [odds ratio (OR), 2.26; 95% confidence interval (CI), 1.18 to 4.36, P=0.015]. Furthermore, patients who responded to initial anthracycline regimens were more likely to respond to paclitaxel plus carboplatin than patients who did not (pCR, 27.2% versus 14.6%, P=0.005). Patients with HER2-positive tumors exhibited a significant higher pCR rate than did patients with HER2-negative tumors in both anthracycline response group (40.5% versus 20.0%, P=0.025) and anthracycline non-response group (28.3% versus 11.3%, P=0.002).

Conclusions

Under the circumstance of no trastuzumab treatment, women with HER2-positive cancers derive a large benefit from paclitaxel-carboplatin-based neoadjuvant chemotherapy.     

Kinetics of serum HER-2/neu changes in patients with HER-2-positive primary breast cancer after initiation of primary chemotherapy

BACKGROUND: The purpose of the study was to determine the utility of quantitation of the extracellular domain (ECD) of the HER-2/neu receptor in the serum for predicting response to treatment in patients with primary breast cancer receiving neoadjuvant therapy. METHODS: HER-2/neu ECD was measured in sera obtained from 39 patients with HER-2-amplified stage II-III primary breast cancer undergoing neoadjuvant chemotherapy. Patients were randomly assigned to either 4 cycles of paclitaxel followed by 4 cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC) (n = 10) or to the same chemotherapy with simultaneous weekly trastuzumab for 24 weeks (n = 29). Changes in HER-2 ECD were monitored with the Bayer HER-2/neu assay over 6 months and correlated with pathological response to treatment. RESULTS: Before initiation of chemotherapy, 28.2% of patients had elevated concentration of the HER-2 ECD (>15 ng/mL). The median baseline serum HER-2 ECD concentration was 13.6 ng/mL (mean +/- SD, 20.3 +/- 35.5 ng/mL). A decrease in the median HER-2 ECD levels from baseline to Week 3 and from baseline to Week 6 of chemotherapy was seen regardless of treatment regimen. No significant difference in baseline HER-2 ECD levels was observed between the groups who achieved pathological complete response (pCR) and the group with residual disease (P = .41). However, a 9% drop from Week 3 to Week 6 after initial chemotherapy was predictive of pCR (P = .04). CONCLUSION: A decrease in serum HER-2 ECD levels early during treatment was associated with pathological response in patients receiving primary chemotherapy, particularly trastuzumab-based regimens. Serum HER-2 ECD levels may serve to monitor neoadjuvant therapy in HER-2-positive primary breast cancer.     

ER,PgR, HER-2, Ki-67, topoisomerase IIα, and nm23-H1 proteins expression as predictors of pathological complete response to neoadjuvant chemotherapy for locally advanced breast cancer

The purpose of this study was to evaluate the importance of biological markers to predict pathologic complete response (pCR) to neoadjuvant chemotherapy (NCT) in patients with locally advanced breast cancer (LABC) One hundred and twelve consecutive patients with clinical stage III LABC who had received NCT with docetaxel and epirubicin from March 2006 to March 2009 were included in this retrospective study. The pre-NCT treatment expression levels of Ki-67 proliferation index, estrogen receptor (ER), progesterone receptor (PgR), epidermal growth factor receptor 2 (HER-2), Topoisomerase II alpha (Topo-II), and nm23-H1 were detected by immunohistochemistry (IHC). A total of 361 cycles were administered with the median number of three cycles per patient (range, 2–6). The pCR rate was 9.8% (95% CI, 4.3–15.3%). In univariate analysis, poor tumor differentiation, both negative of ER/PgR, negative Topo-II, and positive nm23-H1 were found to be significantly predictive of a pCR. ER/PgR status and nm23-H1 were significant for pCR on multivariate analysis (P = 0.006 and 0.025, respectively). ER/PgR status and nm23-H1 are independent predictive factors of pCR to neoadjuvant docetaxel plus epirubicin combination chemotherapy in patients with LABC.     

Tau expression correlated with breast cancer sensitivity to taxanes-based neoadjuvant chemotherapy

The purpose of this study was to investigate the correlation between tau expression in primary breast cancer and sensitivity to taxanes during neoadjuvant chemotherapy in patients with breast cancer. We used immunohistochemistry to examine tau expression in breast cancer biopsies from 113 primary breast cancer patients and evaluated the correlation between tau expression and taxane sensitivity. Twenty-eight (24.78 %, 28/113) patients were positive for tau expression. After taxanes-based neoadjuvant chemotherapy, 40 patients achieved pathological complete response (pCR) (35.4 %). Among the 40 patients with pCR, five (12.5 %) were positive for tau expression. In univariate analysis, estrogen receptor (ER), progesterone receptor, human epidermal growth factor receptor 2 (HER2), and tau were found to be significantly predictive of a pCR (P?=?0.001, 0.030, 0.002, and 0.025, respectively). Tau, ER, and HER2 status were significant for pCR on multivariate analysis (P?=?0.025, 0.005, and 0.043, respectively). Tau expression was positively related to ER (P?=?0.007) and progestin receptor (P?=?0.008). In conclusion, tau protein expression correlated with breast cancer sensitivity to taxanes-based neoadjuvant chemotherapy; patients negative for tau expression were more likely to achieve pCR.     

紫杉类新辅助治疗人表皮生长因子受体2阳性乳腺癌的近期疗效分析

目的探讨HER-2阳性乳腺癌对含紫杉类新辅助化疗的敏感性。方法回顾分析159例HER-2阳性的进展期乳腺癌新辅助化疗疗效,采用X2检验比较蒽环类为主化疗方案（蒽环组）和紫杉类为主化疗方案（紫杉组）病理完全缓解率和化疗有效率的差异。结果葸环组和紫杉组的病理完全缓解率分别为7．4％和25．6％,紫杉组明显高于葸环组（X2=9．658,P=0．002）;化疗有效率分别为85．2％和80．8％,两组间差异无统计学意义（x2=0．550,P=0．458）。结论HER-2阳性的进展期乳腺癌患者选择含紫杉类药物联合化疗方案可取得更好的病理完全缓解率。     

Response to neoadjuvant chemotherapy in ductal compared to lobular carcinoma of the breast: a meta-analysis of published trials including 1,764 lobular breast cancer

Infiltrating lobular carcinoma (ILC) of the breast is associated with greater oestrogen receptor expression and poorer response to neoadjuvant chemotherapy, when compared to infiltrating ductal carcinoma (IDC). In order to compare the pathological complete response rate (pCR) and breast conserving surgery (BCS) in patients with ILC versus IDC treated with neoadjuvant chemotherapy, we performed a systematic review and meta-analysis of all published studies. A search of PubMed, EMBASE, the Web of Science, SCOPUS and the Cochrane Central Register of Controlled Trials was performed to identify studies that investigated pCR, clinical response and BCS in patients with ILC that were treated with neoadjuvant chemotherapy. Random-effect models were adopted to estimate the summary odds ratio (OR), and the publication bias was evaluated using a funnel plot and Egger’s regression asymmetry test. Seventeen studies were included (one randomized controlled trial, three prospective series and 13 retrospective trials), for a total of 12,645 IDCs and 1,764 ILCs to be compared. Ductal carcinoma of the breast was associated with a better pCR (from 5.9 to 16.7 %; OR = 3.1, 95 % CI 2.48–3.87, P < 0.00001) and rate of BCS (from 35.4 to 54.8 %; OR = 2.1, 95 % CI 1.8–2.45, P < 0.00001) compared to ILC. The overall pCR rates and BCS decreased in the ILCs compared with IDC when treated with neoadjuvant chemotherapy.     

Incident comorbidities and all-cause mortality among 5-year survivors of Stage I and II breast cancer diagnosed at age 65 or older: a prospective-matched cohort study

Addition of carboplatin to neoadjuvant chemotherapy in HER2-negative breast cancer may improve pathological complete response (pCR) rates. We evaluated the efficacy and safety of carboplatin and weekly paclitaxel (wPTX) followed by cyclophosphamide, epirubicin, and 5-fluorouracil (CEF) as neoadjuvant chemotherapy for HER2-negative breast cancer. Patients with stage II/IIIA HER2-negative breast cancer were randomly assigned to preoperatively receive CP-CEF (four 3-week cycles of carboplatin [area under the curve 5 mg/mL/min, day 1] and wPTX [80 mg/m², day 1, 8, 15] followed by four 3-week cycles of CEF [500/100/500 mg/m²] or P-CEF (four cycles of wPTX followed by four cycles of CEF). The primary objective was pCR rate. Of 181 eligible patients, 89 were randomly assigned to the CP-CEF and 92 to the P-CEF. Two patients in each arm refused to receive neoadjuvant chemotherapy. Overall 88 patients in the CP-CEF and 91 patients in the P-CEF were assessable for efficacy and safety. The pCR rate in the CP-CEF was significantly higher than that in the P-CEF (31.8 vs. 17.6 %, one-sided P = 0.01). Among patients with triple-negative breast cancer, the pCR rate in the CP-CEF was significantly higher than that in the P-CEF [61.2 (23/37) vs. 26.3 % (10/38), P = 0.003]. Grade 3–4 neutropenia was observed in the CP-CEF more frequently than in the P-CEF (65.9 vs. 38.5 %). Adding carboplatin to neoadjuvant wPTX followed by CEF for HER2-negative breast cancer improved the pCR rate and exacerbated hematotoxicity.     

Patient and tumor characteristics associated with breast cancer recurrence after complete pathological response to neoadjuvant chemotherapy

Breast cancer patients whose tumors achieve a pathological complete response (pCR) with neoadjuvant chemotherapy have a prognosis which is better than that predicted for the stage of their disease. However, within this subgroup of patients, recurrences have been observed. We sought to examine factors associated with recurrence in a population of breast cancer patients who achieved a pCR with neoadjuvant chemotherapy. A retrospective chart review was conducted of all patients with unilateral breast cancer treated with neoadjuvant chemotherapy from January 1, 2000 to December 31, 2010 at one comprehensive cancer center. A pCR was defined as no residual invasive cancer in the breast in the surgical specimen following neoadjuvant therapy. Recurrence was defined as visceral or bony reappearance of cancer after completion of all therapy. Of 818 patients who completed neoadjuvant chemotherapy, 144 (17.6 %) had pCR; six with bilateral breast cancer were excluded from further analysis. The mean time to follow-up was 47.2 months. Among the 138 patients with unilateral breast cancer, there were 14 recurrences (10.1 %). Using a binary multiple logistic regression model, examining types of chemotherapy and surgery, race, lymph node assessment, and lymph node status, breast cancer side, triple-negative status, and radiation receipt, only African-American patients (OR: 5.827, 95 % CI: 1.280–26.525; p = 0.023) were more likely to develop distant recurrence. The mean time to recurrence was 31.9 months. In our study, race was the only independent predictor of recurrence after achieving pCR with neoadjuvant chemotherapy. The reasons for this observation require further study.     

CK5/6, EGFR,Ki-67, cyclin D1, and nm23-H1 protein expressions as predictors of pathological complete response to neoadjuvant chemotherapy in triple-negative breast cancer patients

The purpose of this study was to evaluate the importance of biological markers to predict pathologic complete response (pCR) to neoadjuvant chemotherapy (NCT) in patients with locally advanced triple-negative breast cancers (TNBCs). Forty-one patients (18.6%) among 220 breast cancer patients were identified as TNBCs from March 2006 to 2009 were included in this prospective study. The pre-NCT treatment expression levels of Ki-67 proliferation index, estrogen receptor (ER), progesterone receptor (PgR), epidermal growth factor receptor 2 (HER-2), CK5/6, epidermal growth factor receptor (EGFR), cyclin D1, and nm23-H1 were detected by immunohistochemistry (IHC). A total of 180 cycles were administered with the median number of four cycles per patient (range, 4–6). The pCR rate was 34.1% (95% CI, 19.6–48.6%). In univariate analysis, early T stage, clinical response after 2 cycles, negative basal-like, negative EGFR, high Ki-67 proliferation index, and positive nm23-H1 were found to be significantly predictive of a pCR (P = 0.010, 0.040, 0.007, 0.001, 0.019, and 0.010, respectively). Basal-like status and nm23-H1 status were significant for pCR on multivariate analysis (P = 0.004 and 0.031, respectively). Basal-like status and nm23-H1 are independent predictive factors of pCR to neoadjuvant docetaxel plus epirubicin combination chemotherapy in patients with TNBCs.     

Reassessing risk models for atypical hyperplasia: age may not matter

Purpose

Estrogen receptor (ER) negative (?) breast cancer (BC) patients have better tumor response rates than ER-positive (+) patients after neoadjuvant chemotherapy (NCT). We conducted a retrospective review using the institutional database “Biomatrix” to assess the value of quantitative ER status in predicting tumor response at surgery and to identify potential predictors of survival outcomes.

Methods

Univariate followed by multivariable regression analyses were conducted to assess the association between quantitative ER and tumor response assessed as tumor size reduction and pathologic complete response (pCR). Predictors of recurrence-free survival (RFS) were identified using a cox proportional hazards model (CPH). A log-rank test was used to compare RFS between groups if a significant predictor was identified.

Results

304 patients were included with a median follow-up of 43.3 months (Q1–Q3 28.7–61.1) and a mean age of 49.7 years (SD 10.9). Quantitative ER was inversely associated with tumor size reduction and pCR (OR 0.99, 95% CI 0.99–1.00, p = 0.027 and 0.98 95% CI 0.97–0.99, p < 0.0001, respectively). A cut-off of 60 and 80% predicted best the association with tumor size reduction and pCR, respectively. pCR was shown to be an independent predictor of RFS (HR 0.17, 95% CI 0.07–0.43, p = 0.0002) in all patients. At 5 years, 93% of patients with pCR and 72% of patients with residual tumor were recurrence-free, respectively (p = 0.0012).

Conclusions

Quantitative ER status is inversely associated with tumor response in BC patients treated with NCT. A cut-off of 60 and 80% predicts best the association with tumor size reduction and pCR, respectively. Therefore, patients with an ER status higher than the cut-off might benefit from a neoadjuvant endocrine therapy approach. Patients with pCR had better survival outcomes independently of their tumor phenotype. Further prospective studies are needed to validate the clinical utility of quantitative ER as a predictive marker of tumor response.

     

DNA损伤修复基因胚系突变乳腺癌新辅助化疗疗效分析

  目的   分析携带DNA损伤修复（DNA damage repair,DDR）相关基因突变的乳腺癌患者对基础蒽环类新辅助化疗方案（anthracycline,A）、蒽环联合紫杉类新辅助化疗方案（anthracycline-taxane,A-T）、蒽环联合紫杉和铂类新辅助化疗方案（anthracycline-taxane/carboplatin,A-TP）的疗效反应。  方法  2003年10月至2015年5月,105例携带DDR基因胚系突变（非BRCA）的原发性乳腺癌患者在北京大学肿瘤医院分别接受A（n=69）、A-T（n=19）、A-TP（n=17）3种新辅助化疗方案。通过χ2检验或Fisher精确检验比较3组患者的病理完全缓解（pathological complete remission,pCR）率;采用Kaplan-Meier生存分析和Cox回归模型分析患者的乳腺癌特异生存（breast cancer-specific survival,BCSS）及无复发生存（recurrence-free survival,RFS）。  结果  93.3%（98/105）的患者接受了4～8个周期的新辅助化疗。接受A、A-T、A-TP新辅助方案的3组患者的pCR率分别为11.6%、21.1%和35.3%。A-TP组pCR率显著高于A组（P=0.028）,A-TP组pCR率也高于A-T组,但未达到统计学差异。经过65.6个月的中位随访, A-TP组的BCSS（HR=0.50,95%CI:0.09～2.73,P=0.41）和RFS（HR=0.51,95%CI:0.15～1.74,P=0.27）略优于A-T组,但无统计学差异。  结论   DDR基因胚系突变患者应用A-TP新辅助化疗方案可显著提高pCR率,加入铂类药物或可提高患者的药物反应性及预后 。       

Disease-free and overall survival after pathologic complete disease remission of cytologically proven inflammatory breast carcinoma axillary lymph node metastases after primary systemic chemotherapy

BACKGROUND: Breast carcinoma axillary lymph node (ALN) pathologic complete response (pCR) after primary chemotherapy is associated with significantly higher recurrence-free survival (RFS) and overall survival (OS) rates. The purpose of the current study was to determine long-term outcome in patients achieving a pCR of cytologically proven inflammatory breast carcinoma ALN metastases after primary chemotherapy. METHODS: Patients with cytologically documented ALN metastases from inflammatory breast carcinoma were treated in three prospective primary chemotherapy trials. After surgery, patients were subdivided into those patients with and those patients without residual ALN carcinoma. Survival was calculated using the Kaplan-Meier method. RESULTS: Of 175 patients treated, 61 had cytologically confirmed ALN metastases. Fourteen patients (23%) achieved a pCR of the ALNs after primary chemotherapy. The 5-year OS and RFS rates were found to be improved in those patients achieving a pCR of the ALNs (82.5% [95% confidence interval (95% CI), 62.8-100%] and 78.6% [95%CI, 59.8-100%], respectively, vs. 37.1% [95%CI, 25.4-54.2%] and 25.4% [95%CI, 15.5-41.5%], respectively) (P = 0.01 [for OS] and P = 0.001 [for RFS]). Combination anthracycline and taxane-based primary chemotherapy resulted in significantly more patients achieving an ALN pCR (45% vs. 16%; P = 0.01). CONCLUSIONS: pCR of ALN metastases is associated with an excellent prognosis in patients with inflammatory breast carcinoma. The rates of ALN pCR are nearly 50% in patients with inflammatory breast carcinoma who are treated with anthracyclines and weekly paclitaxel before surgery. However, those patients with residual ALN disease at the time of surgery greatly require the introduction of novel therapeutic strategies.