Serum markers and prognosis in locally advanced breast cancer

BACKGROUND: Locally advanced breast cancer (LABC) represents a heterogeneous subgroup of breast cancer with an often dismal outcome. Identifying prognostic factors has acquired great significance for the selection of optimal treatment in individual patients. METHODS: Between January 1993 and December 1997, 103 patients were treated in our institution with multimodality treatment consisting of neoadjuvant chemotherapy followed by surgery, adjuvant chemotherapy and radiotherapy; tamoxifen was added in hormone receptor-positive cases. In the search for prognostic factors well-established parameters (clinical, pathological and treatment-related) as well as new features with potential value (c-erbB-2, baseline serum levels of CA 15.3 and CEA) were included in the univariate and multivariate analysis. RESULTS: At a median follow-up of 92 months (range, 8-130), the estimated five-year cancer-specific overall survival (OS) and disease-free survival (DFS) were 71.34% and 57.7%, respectively. Among the 22 different variables studied, only 10 were significantly correlated with OS and DFS. In multivariate analysis five retained independent prognostic value for both OS and DFS: tumor grade, serum markers, features of inflammatory breast cancer (IBC), response to neoadjuvant chemotherapy and lymph node status. With cutoff values of 35 U/mL for CA 15.3 and 5 ng/mL for CEA, the probability of five-year OS (Cox hazard ratio 3.91, P = 0.0009) and DFS (Cox hazard ratio 2.40, P = 0.02) decreased from 78% to 52% and from 68% to 47%, respectively, when at least one of these markers was abnormal. CONCLUSIONS: Baseline serum levels of CEA and CA 15.3 emerged from this study as strong independent predictors of outcome in LABC, whose value adds to other established prognostic factors such as postoperative nodal status, IBC, histological grade and response to neoadjuvant chemotherapy.     

Long-term results of combined-modality therapy for inflammatory breast carcinoma

Sixty-eight patients with inflammatory breast carcinoma (IBC) received treatment in 2 prospective randomized trials of multimodality therapy for locally advanced breast cancer. The treatment plan consisted of 3 courses of neoadjuvant chemotherapy with CAF (cyclophosphamide/doxorubicin/5-fluorouracil [5-FU]) or CEF (cyclophosphamide/epirubicin/5-FU) followed by surgery and 6 adjuvant courses of CAF or CEF alternated with CMF (cyclophosphamide/methotrexate/5-FU). Radiation therapy was administered at the end of adjuvant treatment. All patients with estrogen receptor-positive tumors received tamoxifen 20 mg daily for 5 years. The response rate to induction chemotherapy was 73.6% (95% CI, 61.4%-83.5%): 4 of 68 patients (6%) exhibited a pathologic remission of primary breast tumor (persistent disease in the axilla), and 2 patients (3%) exhibited a pathologic complete response. Median follow-up was 10 years (range, 5 months to 14.7 years). Disease-free survival (DFS) rates at 5 and 10 years were 29% and 20%, respectively, and median DFS was 2.2 years (range, 3.8 months to 11.5 years). Overall survival (OS) rates at 5 and 10 years were 44% and 32%, respectively, and median OS was 4 years (range, 5 months to 14.7 years). Significant prognostic factors for DFS and OS were the number of axillary nodes and residual disease in the breast at surgery. This analysis confirmed that patients with IBC obtained significant long-term survival benefit from combined-modality therapy.     

Prognostic role of clinical, pathological and biological characteristics in patients with locally advanced breast cancer.

Forty-two patients with clinical stage IIIA or IIIB breast cancer were treated with neoadjuvant chemotherapy followed by mastectomy and radiotherapy. The median follow-up was 32 months (range 10-72 months) and the median time to progression was 17 months (range 10-30 months). A multivariate analysis showed that a longer disease-free survival (DFS) was related to more chemotherapy cycles given (P = 0.003), a better pathological response to chemotherapy (P = 0.04) and fewer positive axillary lymph nodes (P = 0.05). A better overall survival (OS) was related to more chemotherapy cycles given (P = 0.03) and better pathological response to chemotherapy (P = 0.04). In patients with residual tumour after neoadjuvant chemotherapy, high levels of staining for Ki-67 was correlated with a worse DFS (P = 0.008). Other biological characteristics, including oestrogen receptor status, microvessel density (CD31 staining), P-glycoprotein (P-gp) staining and nuclear accumulation of p53, were not independent prognostic factors for either DFS or OS. If both P-gp and p53 were expressed, DFS and OS were worse in the uni- and multivariate analysis. The preliminary results of this phase II study suggest that coexpression of P-gp/p53 and a high level of staining for Ki-67 after chemotherapy are associated with a worse prognosis, and that prolonged neoadjuvant chemotherapy and the attainment of a pathological complete remission are important factors in determining outcome for patients with this disease.     

The role of irradiation of the internal mammary lymph nodes in high-risk stage II to IIIA breast cancer patients after high-dose chemotherapy: a prospective sequential nonrandomized study.

PURPOSE: This phase II single-institution prospective, nonrandomized trial investigates high-dose adjuvant chemotherapy and locoregional radiotherapy in patients with breast cancer. We compared the outcome of patients in this study treated with radiotherapy fields including the internal mammary nodes (IMN) to a group of patients who did not receive IMN irradiation. PATIENTS AND METHODS: 100 patients with high-risk stage II-III breast cancer received doxorubicin-based adjuvant chemotherapy followed by high-dose chemotherapy, stem-cell support, and locoregional radiotherapy. The radiotherapy included electron-beam irradiation to the IMN. For 20 months during the study, no electron-beam facility was available and we were unable to deliver the IMN irradiation as planned to 33 patients. The remaining 67 patients (32 treated before and 35 treated after this period) received IMN irradiation. Patients with receptor-positive tumors received tamoxifen for 5 years. RESULTS: At a median follow-up of 77 months for all of the patients, disease-free survival (DFS) was significantly prolonged in patients receiving IMN radiation compared to those without IMN radiation (73% v 52%; P =.02). A trend was seen for overall survival (OS; 78% v 64%; P =.08). Cox regression multivariate analysis found IMN radiotherapy to be significant both for DFS and OS. Estrogen receptor positivity was also significant for DFS. There was no treatment related mortality. CONCLUSION: In patients with high-risk stage II to III breast cancer, the inclusion of the IMN in the radiotherapy field was associated with a statistically significant increase in DFS and a borderline increase in OS.     

Results of initial doxorubicin, 5-fluorouracil, and cyclophosphamide combination chemotherapy for inflammatory carcinoma of the breast

Forty-three patients with nonmetastatic inflammatory breast carcinoma have been treated by initial doxorubicin, 5-fluorouracil, and cyclophosphamide (FAC) combination chemotherapy. After three chemotherapy cycles, responding patients underwent surgery. Chemotherapy was then completed for nine cycles of FAC followed by locoregional radiation therapy. All patients received tamoxifen 40 mg/day for 1 year from the time of diagnosis. Thirty-eight patients (88%) had a clinical response to chemotherapy and underwent surgery. On histologic examination 17 patients had a residual tumor mass less than 1 cm diameter or a complete tumor disappearance; lymph nodes dissection was negative in 15 patients. With a median follow-up of 48 months, the predicted 5-year disease-free survival (DFS) is 48% (median DFS, 46 months). Analysis of prognosis factors shows that age, menopausal status, and histologic grade have no predictive value. The DFS and overall survival were significantly improved by the presence of hormonal receptors and a low number of positive lymph nodes (less than 4) at surgery. The most significant prognosis factor was the residual tumor mass after initial chemotherapy with an 80% predicted 5-year DFS for the responding patients versus 30% for the no responding patients (P less than 0.001).     

Chemoradiotherapy after curative surgery for locally advanced pancreatic cancer: A 20-year single center experience

IntroductionPancreatic adenocarcinoma (PAC) is a highly malignant tumor with relevant morbidity and mortality. The role of adjuvant chemoradiotherapy (CRT) for primarily resected tumors remains controversial. We aimed to assess the outcome of patients treated at our institution with postoperative CRT for PAC.MethodsWe present a retrospective case series of patients with pancreatic adenocarcinoma at a single center in Switzerland. These patients were treated by primary surgery followed by adjuvant CRT between 1995 and 2015. The results were compared with published data.ResultsMedian follow-up for the 60 patients was 33 months (range 19.9–193.9); median overall survival (OS) for patients undergoing a resection followed by combined CRT was 25.5 months. Overall, disease-free survival (DFS) was 15.2 months. A local recurrence occurred in 14 patients (23.3%) after a median time of 8.8 months, and in 43 patients (71.7%) distant metastasis was demonstrated with a median time to metastasis of 10.6 months.ConclusionThis retrospective study represents one of the sole reviews of outcome data after adjuvant CRT in resected PAC in Europe within the past years. OS was comparable to that of other institutional outcome data published previously but inferior when compared to most recent published results with an intense chemotherapy. However, not all patients are suitable to undergo such an intense chemotherapy with modified FOLFIRINOX after the extensive surgery for the PAC – these patients could benefit from adding adjuvant CRT to a less intensive chemotherapy with gemcitabine to enhance the benefit regarding locoregional recurrence-free survival.     

Prognosis of a series of 763 consecutive node-negative invasive breast cancer patients without adjuvant therapy: analysis of clinicopathological prognostic factor.

BACKGROUND AND OBJECTIVES: The objectives of this study were to confirm the favorable outcome of Japanese invasive breast cancer patients without lymph node metastasis, after treatment with surgery alone, and to evaluate clinicopathological prognostic factors in this population. METHODS: The subjects were 763 consecutive node-negative invasive breast cancer patients who underwent surgery without adjuvant therapies between 1988 and 1993 at our hospital. Disease-free survival (DFS) and overall survival (OS) rates were analyzed by clinicopathological factors. RESULTS: The median age of the patients at surgery was 52 years and the median follow-up period of patients was 74 months. At 5 years, the respective DFS and OS rates of all patients were 90.8% and 93.9%. Patients with a pathological tumor size of invasive component of more than 2 cm (319 patients) had a significantly lower DFS than those with tumors measuring 2 cm or less (361 patients) (P = 0.045). Patients with positive hormone receptor status (280 patients) (estrogen and/or progesterone receptor positive) tended to have a better OS than those negative for both hormone receptors (92 patients) (P = 0.078). Meanwhile, patients with tumors of histological grade 3 (328 patients) had a much poorer prognosis than those with tumors of histological grade 1 or 2 (413 patients) (P = 0.008 for OS and P = 0.042 for DFS). The respective 5-year DFS and OS rates of patients with histological grade 3 tumors larger than 2 cm in pathological tumor size of invasive component (195 patients) were 85.5% and 87.6%, indicating that these node-negative patients form a high risk group. CONCLUSIONS: Japanese invasive breast cancer patients without lymph node metastasis tended to show a survival advantage compared with their Caucasian counterparts. Histological grade was the most useful prognostic factor in this population.     

Neoadjuvant chemotherapy for operable breast carcinoma larger than 3 cm: A unicentre randomized trial with a 124-month median follow-up

Background: Neoadjuvant chemotherapy improves overall survival and renders possible breast-conserving treatment in locally advanced breast cancer. It was necessary for this method to be evaluated in operable breast tumors too large to be treated immediately by conserving surgery. Initial results of this randomized trial were published in Annals of Oncology (1991).Patients and methods: Women with T2 > 3 cm or T3 N0–1 M0 breast tumors were treated by either initial mastectomy followed by adjuvant chemotherapy, or neoadjuvant chemotherapy followed by adjusted locoregional treatment. Chemotherapy was the same in the two arms. The prognostic and predictive factors of response to chemotherapy were analyzed.Results: Conserving treatments were performed in 63% at the end of neoadjuvant chemotherapy and this rate had decreased to 45% at the median follow-up of 124 months. Survivals are identical in the two treatment groups. Initial clinical tumor size <40 mm, IHC-ER <10% and Mib1 >40% are predictive of tumor response to chemotherapy by uni- and multivariate analyses. For outcome prediction, c-erb-B2 >0% is the independent prognostic factor for overall and metastasis-free survivals.Conclusion: Breast-conserving therapy can be performed in more than half of all cases without alteration of survival, despite a non-negligible rate of local recurrences.     

Combined-modality treatment for isolated recurrences of breast carcinoma: update on 30 years of experience at the University of Texas M.D. Anderson Cancer Center and assessment of prognostic factors

BACKGROUND: In three prospective, single-arm studies, the authors previously showed an improved outcome for anthracycline-na?ve patients with isolated sites of recurrent breast carcinoma (BC) who were treated with doxorubicin-based chemotherapy after local therapy (surgery and/or radiotherapy). In the current report, the initial results are presented from a Phase II trial of docetaxel (100 mg/m(2) every 21 days for 6 cycles) given after local therapy for recurrent BC (Stage IV BC with no evidence of clinically measurable disease) in patients who received prior adjuvant anthracycline-based chemotherapy, and the authors provide an update of the 3 previous studies. An analysis of prognostic factors for these patients also is presented. METHODS: Eligibility criteria for all studies included histologic proof of recurrent BC that had been resected and/or irradiated with curative intent. Survival was calculated using the Kaplan-Meier method. Univariate survival analyses were performed to test for associations between patient characteristics and outcome (log-rank test). Cox proportional hazards models were used to determine the multivariable correlations between patient characteristics and outcome. RESULTS: The median follow-up for the docetaxel-based trial (n = 26 patients) was 45 months. Early outcomes for this study are promising. The median disease-free survival (DFS) was 44 months, and the 3-year DFS and overall survival (OS) rates were 58% and 87%, respectively. In the 3 doxorubicin-based studies, the median follow-up was 121.5 months for all living patients, and the estimated 20-year DFS and OS rates were both 26%. On multivariable analysis of patients from all 4 studies, the only significant prognostic factor for DFS and OS (P = 0.0006) was the number of involved axillary lymph nodes at initial diagnosis. CONCLUSIONS: A proportion of patients with isolated BC recurrences achieved prolonged DFS with combined-modality treatment. Patients who receive anthracycline-based chemotherapy at primary diagnosis may benefit from local treatment followed by docetaxel-based chemotherapy for isolated recurrences. The only significant independent prognostic factor was the number of involved axillary lymph nodes at initial diagnosis.     

Outcomes of high-dose chemotherapy and autologous stem-cell transplantation in stage IIIB inflammatory breast cancer.

PURPOSE: To evaluate the disease-free survival (DFS) and overall survival (OS), prognostic factors, and treatment-related mortality of women with stage IIIB inflammatory breast cancer (IBC) treated with combined modality therapy (CMT) and high-dose chemotherapy (HDCT) with autologous stem-cell transplantation. PATIENTS AND METHODS: Between 1989 and 1997, 47 consecutive patients with stage IIIB IBC were treated with CMT and HDCT and were the subject of this retrospective analysis. Chemotherapy was administered to all patients before and/or after definitive surgery. Neoadjuvant and adjuvant chemotherapy was administered to 33 and 34 patients, respectively, and 20 patients received both. All patients received HDCT with autologous stem-cell transplantation, and 41 patients received locoregional radiation therapy. Tamoxifen was prescribed to patients with estrogen receptor (ER)-positive cancer. RESULTS: The mean duration of follow-up from diagnosis was 30 months (range, 6 to 91 months) and from HDCT was 22 months (range, 0.5 to 82 months). At 30 months, the Kaplan-Meier estimates of DFS and OS from diagnosis were 57.7% and 59.1%, respectively. At 4 years, the Kaplan-Meier estimates of DFS and OS from diagnosis were 51.3% and 51.7%, respectively. In a multivariate analysis, the only factors associated with better survival were favorable response to neoadjuvant chemotherapy (P =.04) and receipt of tamoxifen (P =.06); however, the benefit of tamoxifen was only demonstrated in patients with ER-positive breast cancer. At last follow-up, 28 patients (59. 6%) were alive and disease-free. Seventeen patients (36.2%) developed recurrent breast cancer. Seventeen patients died: 15 from disease recurrence and two (4.2%) from treatment-related mortality due to HDCT. CONCLUSION: In this analysis, the early results of treatment with CMT and HDCT compare favorably with other series of patients with stage IIIB IBC treated with CMT alone. These outcomes must be confirmed with longer follow-up and controlled studies.     

Rôle de l’irradiation ganglionnaire chez les patientes indemnes d’envahissement ganglionnaire après chimiothérapie néoadjuvante pour un cancer du sein : expérience du centre René-Huguenin

PurposeNeoadjuvant chemotherapy generally induces significant changes in the pathological extent of disease. This potential down-staging challenges the standard indications of adjuvant radiation therapy. We assessed the utility of lymph node irradiation in breast cancer patients with pathological N0 status (pN0) after neoadjuvant chemotherapy and breast-conserving surgery.Patients and materialsAmong 1054 breast cancer patients treated with neoadjuvant chemotherapy in our institution between 1990 and 2004, 248 patients with clinical N0 or N1-N2 lymph node status at diagnosis had pN0 status after neoadjuvant chemotherapy and breast-conserving surgery. Cox regression analysis was used to identify factors influencing locoregional recurrence-free survival, disease-free survival and overall survival.ResultsAll 248 patients received breast irradiation, and 158 patients (63.7%) also received lymph node irradiation. With a median follow-up of 88 months, the 5-year locoregional recurrence-free survival and overall survival rates were respectively 89.4% and 88.7% with lymph node irradiation and 86.2% and 92% without lymph node irradiation (no significant difference). Survival was poorer among patients who did not have a pathological complete primary tumor response (pCR) (hazards ratio [HR] = 3.05; 95% CI, 1.17 to 7.99) and in patients with N1-N2 clinical status at diagnosis ([HR] = 2.24; 95% CI, 1.15 to 4.36). Lymph node irradiation did not significantly affect survival.ConclusionsRelative to combined breast and local lymph node irradiation, isolated breast irradiation does not appear to be associated with a higher risk of locoregional relapse or death among breast cancer patients with pN0 status after neoadjuvant chemotherapy. These results need to be confirmed in a prospective study.     

Neoadjuvant chemotherapy with infusional 5-fluorouracil, adriamycin and cyclophosphamide (iFAC) in locally advanced breast cancer: an early response predicts good prognosis.

BACKGROUND: The aim of this study was to evaluate the efficacy and safety of neoadjuvant chemotherapy with infusional 5-fluorouracil (5-FU), adriamycin and cyclophosphamide (iFAC) in locally advanced breast cancer (LABC). PATIENTS AND METHODS: Eighty-two LABC patients were treated with neoadjuvant iFAC chemotherapy including infusional 5-FU (1000 mg/m2, continuous intravenous infusion, days 1-3), adriamycin (40 mg/m2, intravenous bolus, day 1) and cyclophosphamide (600 mg/m2, intravenous bolus, day 1) every 3 weeks until maximum tumor response. Patients subsequently received surgery, adjuvant chemotherapy, radiotherapy and hormonal therapy as appropriate. RESULTS: Downstaging occurred in 71 of the 82 patients (86.6%). Seventy-two patients (67 patients with downstaging and five patients without downstaging) were resectable (resectability rate, 87.8%). The clinical response rate was 84.2%, with a complete response (CR) rate of 17.1% and a pathological CR rate of 7.8%. During 891 cycles of chemotherapy, the most common grade 3/4 hematological toxicity was leukopenia (36.0%). There were no treatment-related deaths. The median follow-up period was 51 months, with a median overall survival (OS) of 66 months, and a 5 year OS rate of 50.9% for all patients. The 5 year OS and disease-free survival (DFS) rates of the 64 patients who underwent surgery were 55.8% and 44.7%, respectively. CONCLUSIONS: Neoadjuvant chemotherapy with iFAC had a comparable response rate and DFS to the conventional bolus FAC regimen, with an acceptable toxicity in LABC using the AJCC 2002 staging system. An early response to neoadjuvant iFAC was a favorable prognostic factor.     

Combined-modality treatment of inflammatory breast carcinoma: twenty years of experience at M. D. Anderson Cancer Center

Purpose: To review the 20 years of experience at M. D. Anderson Cancer Center with a combined-modality approach against inflammatory breast carcinoma. Patients and methods: A total of 178 patients with inflammatory breast carcinoma were treated in the past 20 years at M. D. Anderson Cancer Center by a combined-modality approach under four different protocols. Each protocol included induction chemotherapy, then local therapy (radiotherapy or mastectomy), then adjuvant chemotherapy, and, if mastectomy was performed, adjuvant radiotherapy. Chemotherapy consisted of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) with or without vincristine and prednisone (VP). In protocol D, patients received an alternate adjuvant chemotherapy regimen, methotrexate and vinblastine (MV), if they did not have a complete response (CR) to induction chemotherapy. Results: The median follow-up of live patients in group A was 215 months, in group B 186 months, in group C 116 months, and in group D 45 months. An estimated 28% of patients were currently free of disease beyond 15 years. At the time of analysis, 50 patients were alive without any evidence of disease. A further 12 patients died of intercurrent illness, and 15 patients were followed beyond 10 years without recurrence of disease. Among initial recurrence, 20% of patients had local failure, 39% systemic failure, and 9% CNS recurrence. Initial response to induction chemotherapy was an important prognostic factor. Disease-free survival (DFS) at 15 years was 44% in patients who had a CR to induction chemotherapy, 31% in those who had a partial response (PR), and 7% in those who had less than a PR. There was no improvement in overall survival (OS) or DFS among patients who underwent alternate chemotherapy (MV) compared with those who did not. Using surgery and radiotherapy as opposed to radiotherapy alone as local therapy did not have an impact on the DFS or OS rate. Conclusion: These long-term follow-up data show that with a combined-modality approach a significant fraction of patients (28%) remained free of disease beyond 15 years. In contrast, single-modality treatments yielded a DFS of less than 5%. Thus, using combined-modality treatment (chemotherapy, then mastectomy, then chemotherapy and radiotherapy) is recommended as a standard of care for inflammatory breast carcinoma. Received: 16 April 1996 / Accepted: 16 November 1996     

Role of Postoperative Radiotherapy After Curative Resection and Adjuvant Chemotherapy for Patients With Pathological Stage N2 Non–Small-Cell Lung Cancer: A Propensity Score Matching Analysis

BackgroundThe objective of this study was to evaluate the role of postoperative radiotherapy (PORT) in the setting of adjuvant chemotherapy for pathological stage N2 (pN2) non–small-cell lung cancer (NSCLC).Materials and MethodsA retrospective review of 219 consecutive pN2 NSCLC patients who underwent curative surgery followed by adjuvant chemotherapy was performed. Forty-one patients additionally received PORT. Propensity scores for PORT receipt were individually calculated and used for matching to compare the outcome between patients who did (+) and did not (-) receive PORT. One hundred eleven patients in the PORT (-) group and 38 patients in PORT (+) group were matched. Clinical and pathologic characteristics were well-balanced.ResultsThe median follow-up duration was 48 months. In the matched patients, PORT resulted in a significantly lower crude locoregional relapse (43.2% vs. 23.7%; P = .032). Also, PORT was associated with improved locoregional control (LRC) rate (5-year LRC 63.7% vs. 48.6%; P = .036), but not distant metastasis-free survival, disease-free survival (DFS), and overall survival. An exploratory subgroup analysis suggested a potential DFS benefit of PORT in patients with multiple station mediastinal lymph node metastases (5-year DFS, 43.2% vs. 16.6%; P = .037) and squamous cell carcinoma histology (5-year DFS, 70.1% vs. 23.3%; P = .011).ConclusionsEven in the setting of adjuvant chemotherapy, PORT significantly increased LRC for patients with curatively resected pN2 NSCLC. Some subgroups appear to benefit from PORT in terms of DFS and LRC. Individualized strategies based on risk factors might be considered.     

Prognostic significance of a complete pathological response after induction chemotherapy in operable breast cancer

Only a few papers have been published concerning the incidence and outcome of patients with a pathological complete response after cytotoxic treatment in breast cancer. The purpose of this retrospective study was to assess the outcome of patients found to have a pathological complete response in both the breast and axillary lymph nodes after neoadjuvant chemotherapy for operable breast cancer. Our goal was also to determine whether the residual pathological size of the tumour in breast could be correlated with pathological node status. Between 1982 and 2000, 451 consecutive patients were registered into five prospective phase II trials. After six cycles, 396 patients underwent surgery with axillary dissection for 277 patients (69.9%). Pathological response was evaluated according to the Chevallier's classification. At a median follow-up of 8 years, survival was analysed as a function of pathological response. A pathological complete response rate was obtained in 60 patients (15.2%) after induction chemotherapy. Breast tumour persistence was significantly related to positive axillary nodes (P=5.10(-6)). At 15 years, overall survival and disease-free survival rates were significantly higher in the group who had a pathological complete response than in the group who had less than a pathological complete response (P=0.047 and P=0.024, respectively). In the absence of pathological complete response and furthermore when there is a notable remaining pathological disease, axillary dissection is still important to determine a major prognostic factor and subsequently, a second non cross resistant adjuvant regimen or high dose chemotherapy could lead to a survival benefit.     

曲妥珠单抗治疗141例人表皮生长因子受体2阳性乳腺癌的回顾性分析

目的 总结曲妥珠单抗在人表皮生长因子受体2(Her-2)阳性乳腺癌患者新辅助、辅助和复发转移治疗中的临床应用经验,评价其与化疗联用的疗效.方法 对2004年1月至2008年12月门诊应用曲妥珠单抗治疗的141乳腺癌患者进行回顾性分析.随访时间为3～319个月.分析患者的无病生存时间(DFS),比较患者辅助、复发转移一线及二线使用曲妥珠单抗治疗的总生存时间(OS)、治疗失败时间(TTF)和临床有效率的差异.结果 与曲妥珠单抗治疗联用的新辅助化疗中,紫杉醇联合卡铂方案占66.7%;辅助治疗中,蒽环类和蒽环类序贯紫杉类方案占53.9%.复发转移的患者治疗后中位DFS为17个月.复发转移的患者经一线曲妥珠单抗联合化疗治疗后,临床总有效 率为84.5%,中位TTF为24个月;二线治疗有效率为44.4%,中位TTF为5个月.两者比较,差异有统计学意义(P=0.002).结论 紫杉醇和卡铂化疗联合曲妥珠单抗,值得在新辅助治疗中推广,紫杉类和蒽环类联合或序贯靶向治疗仍是辅助治疗的标准方案.转移性乳腺癌一线应用曲妥珠单抗联合化疗比二线治疗的临床有效率更高,在继续应用曲妥珠单抗的基础上改用化疗方案,可提高治疗有效率,减少治疗失败的概率.     

Randomized clinical trial of adjuvant fluorouracil, epirubicin, and cyclophosphamide chemotherapy for patients with fast-proliferating, node-negative breast cancer.

PURPOSE: The prospective applicability of new biologic tumor information to personalize adjuvant treatment of women with operable breast cancer remains to be demonstrated. The aim of the present study was to investigate whether patients with fast-proliferating, node-negative breast cancer could benefit from adjuvant chemotherapy with fluorouracil, epirubicin, and cyclophosphamide (FEC). PATIENTS AND METHODS: Beginning in November 1989, we analyzed the proliferative activity of primary tumors in a consecutive series of women with node-negative breast cancer to identify subgroups of patients with a worse prognosis and who were therefore suitable candidates for adjuvant systemic therapy. Proliferative activity was determined by means of the [3H]-thymidine incorporation assay using an autoradiographic technique. Women with fast-proliferating breast cancer ([3H]-thymidine labeling index, > 2.3%) were randomized to receive either six cycles of adjuvant FEC or no adjuvant therapy until disease progression. RESULTS: One-hundred twenty-five and 123 patients treated with radical surgery for pT1 to T2, N0, M0 breast cancer were randomized to the FEC and control arms, respectively. After a median follow-up of 70 months, 27 events (21.6%) were observed in the FEC arm and 39 (32.2%) in the control arm, with a significantly lower number of locoregional relapses in the FEC group. Five-year disease-free survival (DFS) was 81% in the FEC group and 69% in the control group (P <.02 by log-rank test). Cox multivariate analysis described the impact of adjuvant therapy with FEC on DFS as independent of the patients' main clinical-pathologic characteristics. CONCLUSION: FEC adjuvant polychemotherapy seems able to significantly improve the clinical outcome of patients with fast-proliferating, node-negative breast cancer.     

Randomised trial: One cycle of anthracycline-containing adjuvant chemotherapy compared with six cycles of CMF treatment in node-positive,hormone receptor-negative breast cancer patients

AIM: A randomised, controlled clinical trial was initiated in 1984 to test whether 1 cycle of anthracycline-containing adjuvant chemotherapy improves the outcome of breast cancer patients presenting with stage II disease and negative oestrogen and progesterone receptors (ER, PgR), as compared with 6 cycles of dose-reduced CMF. PATIENTS AND METHODS: Within 7 years 263 women with stage II breast cancer were randomised either to receive 1 cycle of doxorubicin, vinblastine, cyclophosphamide, methotrexate and 5- fluorouracil (AV-CMF) or to receive 6 cycles of cyclophosphamide, methotrexate and 5-fluorouracil (CMF). Patients were stratified for tumour stage, nodal stage, menopausal status, type of surgery and participating centre. RESULTS: After a median follow-up of 100 months, neither disease-free (DFS) nor overall survival (OS) differed significantly between the two groups. CONCLUSIONS: Compared to 6 cycles of a non-standard low-dose CMF regimen 1 cycle of anthracycline- containing adjuvant chemotherapy failed to improve the outcome in women with stage II receptor-negative breast cancer in terms of DFS and OS.     

Low proliferative rate of invasive node-negative breast cancer predicts for a favorable outcome: a prospective evaluation of 669 patients

This study was designed to compare outcome in terms of disease-free survival (DFS) in women with histologically negative axillary lymph nodes and documented low proliferative rate cancer to other well-defined prognostic factors including type of adjuvant treatment. Between 1988 and 1998, we studied 669 patients with invasive node-negative breast cancer up to 5 cm in size and low proliferative rate measured by flow cytometry to determine S-phase fraction (SPF) or by histochemistry (Ki67/MIB1). At a median follow-up of 53 months, 5-year DFS for the entire group was 94% and did not differ significantly by type of systemic adjuvant treatment: none (133 patients, 95% DFS), tamoxifen (441 patients, 94% DFS), or chemotherapy with doxorubicin and cyclophosphamide (95 patients, 92% DFS). In a multivariate prognostic factor analysis, only tumor size was significant; 5-year DFS was 96% for T1N0 cancer versus 89% for T2N0 cancer (P = 0.01). We have prospectively confirmed that a low rate of proliferation as measured by SPF or MIB1 determination confers an excellent prognosis in invasive node-negative breast cancer up to 5 cm in size, regardless of adjuvant treatment.     

Profile of prognostic factors in 1022 Indian women with early-stage breast cancer treated with breast-conserving therapy

PURPOSE: The outcome of breast cancer treatment can vary in different geographic and ethnic groups. A multivariate analysis was performed for various prognostic factors in 1022 Indian women with pathologic Stage I-II breast cancer treated between 1980 and 2000 with standard breast-conserving therapy with or without systemic adjuvant therapy. METHODS AND MATERIALS: At a mean follow-up of 53 months, the outcomes studied were local failure, locoregional failure, and distant failure, overall survival (OS), and disease-free survival (DFS). RESULTS: The median pathologic tumor size was 3 cm (range, 1-5 cm), and axillary lymph node metastasis was present in 39% of women. The actuarial 5- and 10-year OS and DFS rate was 87% and 77% and 76% and 68%, respectively. Lymphovascular emboli or invasion (LVI) was the strongest independent adverse factor for all failure and survival (local failure, hazard ratio 2.85; 95% confidence interval, 1.68-4.83; OS; hazard ratio, 2.01, 95% confidence interval, 1.35-2.99). Lymph node metastasis was also an independent adverse factor for local failure, locoregional failure, distant failure, DFS, and OS (hazard ratio, 1.55, 95% confidence interval, 1.04-2.30). Age < or =40 years increased the incidence of local recurrence, and patients with inner quadrant tumors had inferior DFS. The incidence of LVI was significantly greater in women with lymph node metastases than in node-negative women (p < 0.001) and in women with Grade 3 tumors than in those with Grade 1 or 2 tumors (p = 0.001). CONCLUSION: In Indian women, LVI was the strongest independent prognostic factor for OS, DFS, and local recurrence, irrespective of nodal status and systemic adjuvant treatment. Although LVI may not be a contraindication for BCT, as has been proposed by certain groups, it is necessary to define its role in prospective studies in determining local and systemic treatment.