Female Breast Cancer Status According to ER,PR and HER2 Expression: A Population Based Analysis

The aim of this study is to evaluate the prognostic values of some biological parameters in a population based series of female breast cancer patients. Through the Tuscan Cancer Registry all the invasive breast cancer cases diagnosed during the period 2004–2005 in the provinces of Florence and Prato, central Italy, were retrieved. Molecular subtypes were analyzed defined by immunohistochemical markers, by age, tumor size, lymph node status, histotype, grade of differentiation and proliferative marker. Out of 1487 patients 70.3% were luminal A subtype (ER/PR + HER2-), 15.6% luminal B (ER/PR + HER2+), 8.1% triple negative (ER/PR-HER2-), 6.0% HER2+ (ER/PR-HER2+); the 3 year survival rates were 93.3%, 89.5%, 86.3%, 82.7% respectively (p < 0.001). Analysis of survival by the Cox proportional hazards model showed an independent prognostic value of molecular classification. Our study revealed significant differences in clinicopathological characteristics among breast cancer molecular subtypes and confirmed their prognostic independent role.     

Phase II study of dose-dense doxorubicin and docetaxel as neoadjuvant chemotherapy with G-CSF support in patients with large or locally advanced breast cancer

Introduction  To evaluate the efficacy and safety profile of the concomitant dose-dense administration of doxorubicin and docetaxel as primary chemotherapy for patients with large or locally advanced breast cancer. Materials and methods  Forty-seven patients were included and received 50 mg/m² of doxorubicin and 75 mg/m² of docetaxel every two weeks for four cycles. Primary prophylaxis with granulocyte colony stimulating factor was administered. Results  Patients included had mainly stage III disease (66%). Efficacy and toxicity analyses were carried out on an intention-to-treat basis. After study treatment, the rate of clinical responses was 85% (95% CI: 75–95) with 6% judged as clinical complete responses. Surgery was performed on 94% patients for whom the breast was conserved in 27%. Only one patient obtained a pathological complete response (with no evidence of invasive or non-invasive tumour in the breast and the lymph nodes). In three additional patients, malignant cells were detected only in one lymph node. The single severe haematological toxicity was neutropenia, occurring in one patient (2%) and two cycles (1%), being grade 3 in one and grade 4 in the other. Severe non-haematological toxicities were grade 3, and the most common was asthenia (8% of patients), followed by cutaneous toxicity, arthromyalgia and stomatitis, which occurred in fewer than 4% of patients in each case. Conclusions  The concomitant dose-dense administration of doxorubicin and docetaxel as neoadjuvant chemotherapy with granulocyte colony stimulating factor support is a feasible and effective schedule with a safe toxicity profile for women with large or locally advanced breast cancer.     

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。     

High genomic grade index associated with poor prognosis for lymph node-negative and estrogen receptor-positive breast cancers and with good response to chemotherapy

BACKGROUND:

The aim of the present study was to investigate the prognostic value of the genomic grade index for lymph node‐negative and estrogen receptor (ER)‐positive breast cancers of Japanese women treated with adjuvant hormonal therapy alone, as well as the relation between genomic grade index and pathological complete response (CR) to neoadjuvant chemotherapy.

METHODS:

Genomic grade index was determined by DNA microarray (U133plus2.0; Affymetrix, Santa Clara, Calif) in tumor tissues obtained from lymph node‐negative and ER‐positive breast cancers (n = 105) treated with adjuvant hormonal therapy alone or in breast tumor biopsy specimens (n = 84, Mammotome) obtained before neoadjuvant chemotherapy (paclitaxel followed by 5‐fluorouracil/epirubicin/cyclophosphomide) to investigate the prognostic and predictive values of genomic grade index.

RESULTS:

Recurrence‐free survival of patients with high genomic grade index tumors was significantly (P < .001) lower than that of patients with low genomic grade index tumors (55% vs 88%, 10 years after surgery). Multivariate analysis demonstrated that genomic grade index was the most important and significant predictive factor for disease recurrence (P = .013) independently of other prognostic factors, including tumor size, histological grade, progesterone receptor, human epidermal growth receptor 2, and Ki67. High genomic grade index tumors showed a significantly (P = .022) higher pathological CR rate for neoadjuvant chemotherapy than low genomic grade index tumors (31.9% [15 of 47] vs 10.8% [4 of 37]).

CONCLUSIONS:

Genomic grade index is a powerful prognostic factor for lymph node‐negative and ER‐positive tumors treated with adjuvant hormonal therapy alone, and high genomic grade index tumors are more likely to respond to chemotherapy. Genomic grade index also appears to be very useful for decision making regarding the need for adjuvant chemotherapy for lymph node‐negative and ER‐positive breast cancers. Cancer 2011. © 2010 American Cancer Society.     

Progesterone receptor is a significant factor associated with clinical outcomes and effect of adjuvant tamoxifen therapy in breast cancer patients

Estrogen receptor status in breast cancer is associated with response to hormonal therapy and clinical outcome. The additional value of progesterone receptor (PR) has remained controversial. We examine the value of PR for prognosis and response to tamoxifen on a population-based series of 4,046 invasive early stage breast cancer patients. Clinical information for age at diagnosis, stage, pathology, treatment and outcome was assembled for the study cohort; the median follow-up was 12.4 years. PR status was determined by immunohistochemistry using a rabbit monoclonal antibody on tissue microarrays built from breast tumor surgical excisions. Survival analyses, Kaplan–Meier functions and Cox proportional hazards regression models were applied to assess the associations between PR and breast cancer specific survival. Progesterone receptor was positive in 51% of all cases and 67% of estrogen receptor positive (ER+) cases. Survival analyses for both the whole cohort and ER+ cases given tamoxifen therapy showed that patients with PR+ tumors had 24% higher relative probability for breast cancer specific survival as compared to PR− patients, adjusted for ER, HER2, age at diagnosis, grade, tumor size, lymph node status and lymphovascular invasion covariates. Higher PR expression showed stronger association with patient survival. Log-likelihood ratio tests of multivariate Cox proportional hazards regression models demonstrated that PR was an independent statistically significant factor for breast cancer specific survival in both the whole cohort and among ER+ cases treated with tamoxifen. PR adds significant prognostic value in breast cancer beyond that obtained with estrogen receptor alone.     

乳腺癌新辅助化疗疗效的评价及影响因素分析

目的分析不同评价方法评估乳腺癌新辅助化疗疗效的价值,探讨化疗疗效的影响因素。方法对171例Ⅱ、Ⅲ期可手术乳腺癌患者分别行CEF、NE和TEC方案新辅助化疗。完成2个周期化疗者11例,3个周期者111例,≥4个周期者49例。采用触诊、超声和病理学方法评价疗效。化疗效果影响因素的判定采用单因素分析和多因素Logistic回归分析方法。结果触诊评价完全缓解（CR）32例（18．7％）,总有效率为88．3％。超声评价CR7例（4．1％）,总有效率为74．9％。病理组织学评价CR26例（15．2％）。触诊和超声评价与病理组织学评价的CR符合率分别为43．8％和42．9％。多因素分析结果表明,肿瘤大小是影响乳腺癌新辅助化疗病理CR的独立因素。结论化疗疗效的临床评价与病理组织学评价缺乏很好的一致性,触诊和超声评价CR易高估和低估。肿瘤大小是影响乳腺癌新辅助化疗病理CR的独立因素,肿块不易达到病理CR。     

Retrospective Analysis of Neoadjuvant Chemotherapy for Breast Cancer in Turkish Patients

Background: Neoadjuvant systemic chemotherapy is the accepted approach for women with locally advancedbreast cancer. Anthracycline- and taxane-based regimens have been extensively studied in clinical trials andconsequently are widely used. In this study aimed to research the complete response (pCR) rates in differentregimens for neoadjuvant setting and determine associated clinical and biological factors. Methods: This studyincluded 63 patients diagnosed with breast carcinoma among 95 patients that had been treated with neoadjuvantchemotherapy between 2007 and 2010. TNM staging system was used for staging. The histologic response toneoadjuvant chemotherapy was characterized as a pCR when there was no evidence of residual invasive tumorin the breast or axillary lymph nodes. Biologic subclassification using estrogen receptor (ER), progesteronereceptor (PR), HER2 were performed. Luminal A was defined as ER+, PR+, HER2-; Luminal B tumor wasdefined as ER+, PR-, HER2-; ER+, PR-, HER2+; ER-, PR+, HER2-; ER+, PR+, HER2+; HER2 like tumorER-, PR+, HER2+; and triple negative tumor ER, PR, HER2 negative. Results: Patients median age was 54.14(min-max: 30-75). Thirty-two patients (50.8%) were premenapousal and 31 (49.2%) were postmenapousal.Staging was performed postoperatively based on the pathology report and appropriated imaging modalitiesThe TNM (tumor, lymph node, metastasis) system was used for clinical and pathological staging. Fifty-seven(90.5%) were invasive ductal carcinomas, 6 (9.5%) were other subtypes. Thirty nine (61.9%) were grade IIand 24 (38.1%) were grade III. Seven (11.1%) patients were stage II and 56 (88.9) patients were stage III. Thepatients were classified for ER, PR receptor and HER2 positivity. Seventeen patients had complete response tochemotherapy. Forty patients (63.5%) were treated with dose dense regimen (cyclophosphamide 600 mg/m2 anddoxorubicine 60 mg/m every two weeks than paclitaxel 175 mg/m2 every two weeks with filgrastim support) 40patients (48%) were treated anthracycline and taxane containing regimens. Thirteen patients (76%) from 17patients with pCR were treated with the dose dense regimen but without statistical significance (p=0.06). pCRwas higher in HER2(-), ER(-), grade III, premenopausal patients. Conclusion: pCR rate was higher in the groupthat treated with dose dense regimen, which should thus be the selected regimen in neoadjuvant setting. Someother factors can predict pCR in Turkish patients, like grade, menopausal status, triple negativity, percentageof ER positivity, and HER2 expression.     

Results of a phase II open-label,nonrandomized trial of oral satraplatin in patients with metastatic breast cancer

Cisplatin and carboplatin have antitumor activity in breast cancer. Satraplatin, an orally bioavailable platinum analog, offers a potential alternative to intravenous chemotherapy. We conducted a multicenter phase II study of this agent as first- or second-line treatment of metastatic breast cancer. Satraplatin 80 mg/m² was taken PO Days 1–5 q 21 days in cycles 1 and 2, and if tolerated, increased to 100 mg/m² for subsequent cycles. Restaging studies to assess response were performed after every 2 cycles. Between November 2005 and March 2006, 40 patients were enrolled. Baseline characteristics: 48% prior adjuvant chemotherapy, 60% prior chemotherapy for MBC; median age, 62 years (ranges 43–83), 58% ER+/PR+, 23% ER+/PR−, 18% ER−/PR−/HER2−, and 5% HER2+. In 31 patients with measurable disease, there were two partial responses (PR; 6%; 95% CI 0, 15.2); and four patients (13%) had SD ≥6 months for a clinical benefit rate of 19%. Among the subanalysis of seven triple-negative patients with measurable disease, there were 2 SD and 2 PD. Median survival was 15 months and median progression-free survival was 2.7 months. The most common grade 3–4 toxicities were neutropenia (28%) and thrombocytopenia (25%). AEs leading to treatment discontinuation were nausea (n = 3), thrombocytopenia (n = 3), fever (n = 2), and vomiting (n = 2). This phase II study demonstrates oral satraplatin has limited activity as a single agent for MBC. Satraplatin, at a lower dose used in this study, could be combined with other chemotherapy agents in future trials in breast cancer.     

The use of an LH-RH agonist (ICI 118630, Zoladex) in advanced premenopausal breast cancer

Fifty-three premenopausal patients presenting with advanced breast cancer have been treated with a potent new luteinising hormone-releasing hormone agonist Zoladex (ICI 118630) in a phase I clinical trial. On progression of disease 26 patients have undergone therapeutic oophorectomy. We present the clinical and endocrinological responses to treatment in 45 assessable patients. The response rate to Zoladex in this series was 31% and the ER status of the primary tumour was predictive of a response to the luteinising hormone-releasing hormone.     

Chemotherapy (CT) and hormonotherapy (HT) as neoadjuvant treatment in luminal breast cancer patients: results from the GEICAM/2006-03, a multicenter,randomized, phase-II study

BackgroundLuminal breast cancer is a highly endocrine responsive disease. However, the therapeutic benefit of chemotherapy (CT) in this population is not fully characterized. This study investigates the value of CT and hormone therapy (HT) in luminal breast cancer patients in the neoadjuvant setting.Patients and MethodsPatients with operable breast cancer and immunophenotypically defined luminal disease (ER+/PR+/HER2-/cytokeratin 8/18+) were recruited. Patients were randomized to CT (epirubicin 90 mg/m² plus cyclophosphamide 600 mg/m² × 4 cycles followed by docetaxel 100 mg/m² × 4 cycles [EC-T]) or HT (exemestane 25 mg daily × 24 weeks [combined with goserelin in premenopausal patients]). The primary end point was the clinical response measured by magnetic resonance imaging.ResultsNinety-five patients were randomized (47 CT, 48 HT). The clinical response rate was 66% for CT and 48% for HT (P = 0.075). We performed an unplanned analysis based on Ki67 levels (cut-off of 10%). Similar clinical response was seen between arms in patients with low Ki67 (CT: 63%, HT: 58%; P = 0.74); patients with high Ki67 had a better response with CT (67 versus 42%; P = 0.075). Grade 3/4 toxicity was more frequent with CT.ConclusionsLuminal immunophenotype is not enough to identify patients who do not benefit from neoadjuvant CT. Luminal patients with low proliferation index could potentially avoid CT.     

Triple negative breast cancer in Korea-distinct biology with different impact of prognostic factors on survival

We analyzed breast cancer subtypes using Korean Breast Cancer Society Registration Program data to compare clinical features and prognosis for triple-negative breast cancer (TNBC). A cohort of 26,767 breast cancer patients were divided in four groups: luminal A (ER+ and/or PR+, HER2−), luminal B (ER+ and/or PR+ HER2+), HER2+ (ER−, PR−, HER2+), and triple-negative (ER−, PR−, HER2−). Clinicopathologic factors were evaluated. The luminal A (14,437 patients, 53.9%) subtype was the largest in our study. Compared with luminal A subtype, TNBC correlated with younger age, more aggressive characteristics and poor overall survival and breast cancer-specific survival. The hazard rate showed a peak at 24 months for the TNBC subtype, but after 60 months, risk was similar to that of the luminal A subtype. Higher T, N stage and histologic grade, and lymphatic and vascular invasion showed poor prognosis in TNBC patients, but on multivariate analysis only histologic grade and ki-67 status were related. Young age was related to poor prognosis in the luminal A subtype, however, age was not related to prognosis in the TNBC subtype. Of the 5,586 TNBC patients, 282 patients (7.11%) expired within 3 years of diagnosis. T and N stage and grade were significantly associated with prognosis on multivariate analysis. TNBC subtype is characterized by younger age with poorer outcome. However, younger age is not related to prognosis, and mortality risk decreases to that of the luminal A subtype, which is known to have the best prognosis after a few years.     

The value of COX-2 expression in the prognostic parameters of invasive ductal carcinoma of the breast

Cyclooxygenase is an enzyme that changes the immune response to malign cells and catalyzes prostaglandins that may have an impact on cell proliferation. The purpose of this study was to examine the relation between established clinicopathological parameters in breast carcinomas and COX-2 protein expression. COX-2, estrogen receptor (ER), progesterone receptor (PR) and c-erB-2 primary antibodies were assessed in the slides prepared from the paraffin blocks of 62 invasive ductal carcinoma cases. The relation between ER, PR, and c-erbB-2 positivity, histological grade, nuclear grade, lymphovascular invasion, tumor diameter, lymph node positivity, metastasis, and age were evaluated. The results were analyzed statistically. Cytoplasmic COX-2 expression was seen in 75.8% of all breast carcinomas. In both univariate and multivariate logistic regression analysis, there was a positive correlation between COX-2 expression and negative ER status, respectively (P = 0.0173) (P = 0.016). There was any statistically significant relation between PR positivity, c-erbB-2 positivity, histological grade, nuclear grade, lymphovascular invasion, tumor diameter, lymph node positivity, metastasis, and age (P ≥ 0.05). Given that there was found a statistically significant relation between COX-2 expression and negative ER status, which is considered a poor prognostic parameter, suggests that COX-2 expression can have a place among the other prognostic parameters of breast carcinoma.     

The role of 18F-FDG-PET in the local/regional evaluation of women with breast cancer

Purpose. In women with breast cancer, knowledge of the local/regional extent of the tumor is essential for staging, treatment planning, monitoring response to therapy, and follow-up. Positron emission tomography (PET) is an important imaging test which can detect tumor at multiple sites in women with breast cancer. We compared the ability of PET to provide a comprehensive view of the local/regional extent of tumor in women with stage I, II and stage III, IV breast cancer. Materials and methods. Forty-six women with breast cancer underwent PET using ¹⁸F-FDG. ¹⁸FDG uptake in the breast primary tumor, associated skin, axillary and internal mammary lymph nodes, and the contralateral breast was determined qualitatively, and correlated with histologic, clinical and radiographic findings. Results. Twenty-four patients were premenopausal and 22 were postmenopausal, with the following distribution according to clinical stage: stage I – 2 patients, stage II – 16, stage III – 16, stage IV – 12 patients. Among stage I, II patients, the sensitivity for detection of the primary tumor was 83.3%, and for detection of axillary lymph node metastases was 42.9%. ¹⁸FDG-PET was negative for the breast skin, contralateral breast, and internal mammary lymph nodes in all stage I, II patients, in agreement with clinical and radiographic findings. Among 28 stage III, IV patients, the sensitivity of ¹⁸FDG-PET for detection of the primary tumor was 90.5%, and for detection of axillary lymph node metastases 83.3%. Fourteen patients had clinically advanced changes in the skin, and the sensitivity of PET for detection of skin changes was 76.9%. ¹⁸FDG-PET was positive in the internal mammary lymph nodes in 25.0%, and negative in the contralateral breast in all patients with stage III, IV breast cancer. ¹⁸FDG-PET was studied in 10 patients following neoadjuvant chemotherapy, and showed a strong correlation with clinical response, and with clinical and pathological findings post-treatment at multiple local/regional sites. Conclusion. ¹⁸FDG-PET can provide a comprehensive image of local/regional tumor in women with breast cancer. ¹⁸FDG-PET may play a greater role in women with stage III, IV breast cancer because of increased sensitivity and the increased involvement of multiple local/regional sites with tumor.     

A Phase II Study Evaluating the Safety and Efficacy of Sunitinib Malate in Combination With Weekly Paclitaxel Followed by Doxorubicin and Daily Oral Cyclophosphamide Plus G-CSF as Neoadjuvant Chemotherapy for Locally Advanced or Inflammatory Breast Cancer

IntroductionNeoadjuvant chemotherapy is standard treatment for locally advanced breast cancer (LABC) or inflammatory breast cancer (IBC). We hypothesized that adding sunitinib, a tyrosine kinase inhibitor with antitumor and antiangiogenic activity, to an anthracycline and taxane regimen would improve pathologic complete response (pCR) rates to a prespecified endpoint of 45% in patients with HER2-negative LABC or IBC.MethodsWe conducted a multicenter, phase II trial of neoadjuvant sunitinib with paclitaxel (S+T) followed by doxorubicin and cyclophosphamide plus G-CSF for patients with HER2-negative LABC or IBC. Patients received sunitinib 25 mg PO daily with paclitaxel 80 mg/m² IV weekly ×12 followed by doxorubicin 24 mg/m² IV weekly + cyclophosphamide 60 mg/m² PO daily with G-CSF support. Response was evaluated using pCR in the breast and the CPS + EG score (clinical-pathologic scoring + estrogen receptor [ER] and grade).ResultsSeventy patients enrolled, and 66 were evaluable for efficacy. Eighteen patients (27%) had pCR in the breast (10 had ER⁺ disease and 8 had triple-negative disease). When defining response as pCR and/or CPS + EG score ≤2, 31 (47%) were responders. In pateints with ER positive disease, 23 (64%) were responders. The most common toxicities were cytopenias and fatigue.ConclusionsNeoadjuvant S+T followed by AC+G-CSF was safe and tolerable in LABC and IBC. The study did not meet the prespecified endpoint for pCR; however, 47% were responders using pCR and/or CPS + EG score ≤2. ER positive patients had the highest response rate (64%). The addition of sunitinib to neoadjuvant chemotherapy may provide promising incremental benefit for patients with ER positive LABC.     

Biological considerations in locally advanced breast cancer treated with anthracycline-based neoadjuvant chemotherapy: thymidine labelling index is an independent indicator of clinical outcome

The present retrospective study aims to determine the clinical value of thymidine labelling index (TLI) together with other established clinical and biological factors in 116 locally advanced breast cancer (LABC) patients treated with anthracycline-based neoadjuvant chemotherapy, surgery, adjuvant chemotherapy and radiotherapy. TLI was determined in 71 LABC patients with a median of 2.62% (0–23.64%) and a mean of 4.71%±5.54. As a result of neoadjuvant chemotherapy, 85 patients (73%) responded to chemotherapy (CT), whereas 31 patients were unresponsive (27%). No relationship has been found between the pretreatment biological variables including TLI, estrogen receptor (ER), progesteron receptor (PgR) status and clinical parameters such as the chemotherapy response rates and axillary lymph node involvement following chemotherapy. Median follow-up was 35 months (18–97 months) and the 3-year overall survival (OS) and disease free survival (DFS) rates were 71.6% and 52.2%, respectively. In univariate analysis, patients with inflammatory breast cancer, high TLI-index (2.62%), lymph node (LN) positivity or >3 positive lymph nodes following neoadjuvant chemotherapy and without any response to neoadjuvant chemotherapy were found to have worse DFS and OS-rates and high local and systemic recurrence rates. In multivariate analysis, TLI was estimated as the most powerful independent factor affecting the OS in LABC patients among the other established clinical and biological parameters (p=0.02). These results suggest that TLI is an important independent indicator of clinical outcome in patients with LABC and these patients with high TLI levels require more effective treatment modalities.     

Prospective randomized study of cyclophosphamide, epirubicin, and 5-fluorouracil versus cyclophosphamide, adriamycin, and 5-fluorouracil in advanced or recurrent breast cancer

Background  Treatment with cyclophosphamide, adriamycin, and 5-fluorouracil (CAF), a widely used, potent regimen is sometimes restricted by the myelotoxicity and myocardiotoxicity of adriamycin (ADR). In a prospective randomized controlled study of patients with advanced or recurrent breast cancer, the efficacy and toxicity of a CEF regimen, in which epirubicin (EPI) was substituted for ADR, was compared with CAF. Methods  138 female patients under 75 years of age who had unresectable or recurrent breast cancer during the period from October, 1989 to September, 1991, were randomized to one of two treatment regimens. The first regimen consisted of cyclophosphamide 100 mg p.o. d1-14, adriamycin 30 mg/m^p2 i.v. d1, 8 and 5-fluorouracil 500 mg/m^p2 i.v. d1, 8 (CAF). In the second regimen, EPI 30 mg/m^p2 i.v. d1, 8 was substituted for ADR (CEF). Both regimens were delivered q4 weeks. Results  Of 138 patients, 105 (CEF 56, CAF 49) were evaluable for response and survival, and all were evaluable for toxicity (CEF 68, CAF 70). The median course of lots CEF and CAF was 3 cycles. Response rates (complete response plus partial response) with CEF and CAF were 35.7% (20/56) and 36.7% (1 8/49), respectively. Adverse effects were similar in the two groups, but severe leukopenia (CEF 36.8%, CAF 64.3%) and hepatic toxicity (CEF 1.5%, CAF 12.9%) were encountered more frequently with CAF than with CEF. The duration of 50% survival was 135.9 weeks for CEF and 172.1 weeks for CAF (not significant). Conclusion  At an equal dose of EPI and ADR response rates and survival of the CEF group were similar to those of the CAF group, but adverse effects were fewer in the CEF group.     

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     

Neoadjuvant tamoxifen for operable breast cancer: a need for phase III studies?

We conducted a case-control study to analyze the effect of neoadjuvant tamoxifen on steroid receptors and histologic grade and to evaluate the feasibility of phase III studies in operable breast cancer. Between 1987 and 1990, 107 patients without clinical metastases who had had no chemotherapy preoperatively, were treated preoperatively with 20 mg/day of tamoxifen for 3 weeks. Of them, 92 were matched with controls for age at diagnosis, year of diagnosis, presence or absence of lymph node involvement, and preoperative radiotherapy. The percentage of ER1 tumors (P = .03) and the mean and median ER levels (P<.001 for both) were lower in the tamoxifen group than in the control group. In six patients analyzed longitudinally, the mean ER decreased from 52 to 19 fmol/mg protein. The difference in relapse-free survival between the two groups was not significant (mean follow-up 87 months). This study suggests a decrease in ER content in patients treated with neoadjuvant tamoxifen. This change may thus be taken into account when ER determination is performed after tamoxifen therapy is started. Further randomized trials should determine whether patients with operable breast cancer benefit from neoadjuvant tamoxifen treatment.