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1.
The purpose of this study was to examine the association between the leucocyte nadir and prognosis in breast cancer patients receiving adjuvant chemotherapy consisting of cyclophosphamide, methotrexate and fluorouracil (CMF). Three hundred and sixty-eight patients with node-positive breast cancer without distant metastases were treated with six cycles of adjuvant CMF. Some patients (n = 60) also received tamoxifen. All patients underwent surgery and received radiotherapy to the axillary and supraclavicular lymph nodes and the chest wall. The effect of leucopenia caused by CMF on distant disease-free survival (DDFS) and overall survival (OS) was assessed. A low leucocyte nadir during the chemotherapy was associated with a long DDFS in univariate analysis when tested as a continuous variable (the relative risk (RR) 1.3, 95% confidence interval (CI) 1.04-1.06, P = 0.02). Similarly, when the leucocyte nadir count was divided into tertiles, the patients who had the highest nadir values during the six-cycle treatment had worst outcome (RR 1.6, 95% CI 1.07-2.5, P = 0.02). However, in a multivariate analysis only the number of affected lymph nodes, tumour size, progesterone receptor status, surgical procedure, age and adjuvant tamoxifen therapy retained prognostic significance, whereas the leucocyte nadir count did not. A low leucocyte nadir during the adjuvant CMF chemotherapy is associated with favourable DDFS and it may be a useful biological marker for chemotherapy efficacy. 相似文献
2.
T. Saarto C. Blomqvist P. Rissanen A. Auvinen I. Elomaa 《British journal of cancer》1997,75(2):301-305
Two hundred and eleven patients with node-positive stage II and III breast cancer were treated with eight cycles of adjuvant chemotherapy comprising cyclophosphamide, doxorubicin and oral ftorafur (CAFt), with and without tamoxifen. All patients had undergone radical surgery, and 148 patients were treated with post-operative radiotherapy in two randomized studies. The impact of haematological toxicity of CAFt on distant disease-free (DDFS) and overall survival (OS) was recorded. Dose intensity of all given cycles (DI), dose intensity of the two initial cycles (DI2) and total dose (TD) were calculated separately for all chemotherapy drugs and were correlated with DDFS and OS. Patients with a lower leucocyte nadir during the chemotherapy had significantly better DDFS and OS (P = 0.01 and 0.04 respectively). Dose intensity of the two first cycles also correlated significantly with DDFS (P = 0.05) in univariate but not in multivariate analysis, while the leucocyte nadir retained its prognostic value. These results indicate that the leucocyte nadir during the adjuvant chemotherapy is a biological marker of chemotherapy efficacy; this presents the possibility of establishing an optimal dose intensity for each patient. The initial dose intensity of adjuvant chemotherapy also seems to be important in assuring the optimal effect of adjuvant chemotherapy. 相似文献
3.
Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant chemotherapy for node-positive breast cancer: results from NSABP B-28. 总被引:16,自引:0,他引:16
Eleftherios P Mamounas John Bryant Barry Lembersky Louis Fehrenbacher Scot M Sedlacek Bernard Fisher D Lawrence Wickerham Greg Yothers Atilla Soran Norman Wolmark 《Journal of clinical oncology》2005,23(16):3686-3696
PURPOSE: The primary aim of National Surgical Adjuvant Breast and Bowel Project (NSABP) B-28 was to determine whether four cycles of adjuvant paclitaxel (PTX) after four cycles of adjuvant doxorubicin/cyclophosphamide (AC) will prolong disease-free survival (DFS) and overall survival (OS) compared with four cycles of AC alone in patients with resected operable breast cancer and histologically positive axillary nodes. PATIENTS AND METHODS: Between August 1995 and May 1998, 3,060 patients were randomly assigned (AC, 1,529; AC followed by PTX [AC --> PTX], 1,531). Patients > or = 50 years and those younger than 50 years with estrogen receptor (ER) or progesterone receptor (PR) -positive tumors also received tamoxifen for 5 years, starting with the first dose of AC. Postlumpectomy radiotherapy was mandated. Postmastectomy or regional radiotherapy was prohibited. Median follow-up is 64.6 months. RESULTS: The addition of PTX to AC significantly reduced the hazard for DFS event by 17% (relative risk [RR], 0.83; 95% CI, 0.72 to 0.95; P = .006). Five-year DFS was 76% +/- 2% for patients randomly assigned to AC --> PTX compared with 72% +/- 2% for those randomly assigned to AC. Improvement in OS was small and not statistically significant (RR, 0.93; 95% CI, 0.78 to 1.12; P = .46). Five-year OS was 85% +/- 2% for both groups. Subset analysis of the effect of paclitaxel according to hormone receptors or tamoxifen administration did not reveal statistically significant interaction (for DFS, P = .30 and P = .44, respectively). Toxicity with the AC --> PTX regimen was acceptable for the adjuvant setting. CONCLUSION: The addition of PTX to AC resulted in significant improvement in DFS but no significant improvement in OS with acceptable toxicity. No significant interaction between treatment effect and receptor status or tamoxifen administration was observed. 相似文献
4.
Prognostic factors in node-positive operable breast cancer patients receiving adjuvant chemotherapy 总被引:1,自引:0,他引:1
E. Rakowsky B. Klein E. Kahan E. Derazne H. Lurie 《Breast cancer research and treatment》1992,21(2):121-131
Summary A retrospective analysis of prognostic factors in 214 consecutive node-positive (N+) operable breast cancer patients, receiving Melphalan+5-fluorouracil adjuvant chemotherapy between 1980 and 1984 was performed. Median follow-up was 95 months. Actuarial disease-free interval (DFI) and survival (S) were determined according to age, menopausal status, histology, size of primary tumor (T), multifocality, tumor location, hormonal receptor status, number of N+, size of N+, tumor spread in axillary fat, and interval between surgery and onset of adjuvant chemotherapy.On univariate analysis two factors were prognostic for DFI and S: number of N+and T size. A comparison between traditionally classified T1 and T2 patients revealed no signifciant difference, but when the cut-off point was shifted from 2 cm to 3 cm, T size represented a highly significant prognostic factor. In patients with T3 cm 5-year DFI was 54% and 5-year S was 76%, while in patients with T>3 cm the respective values were 23% (p<0.001) and 41% (p<0.001). These significant DFI and S differences persisted after adjustment for number of N+ by bivariate analysis.Multivariate analysis supported the importance of T>3 cm as a strong adverse predictor. Four adverse variables, T>3 cm, number of N+4, multifocality, and tumor spread in axillary fat were used to divide our patients into three subsets with significantly different DFI: Group I, with none of the above factors; Group II, with only one factor present; and Group III, with more than one factor present (5 years DFI 66%, 45%, and 21%, respectively; p<0.001). 相似文献
5.
Purpose of this study was to evaluate the efficacy of salvage chemotherapy given to women with breast cancer in relapse who had in the past received adjuvant treatment including adriamycin. Fourty-nine evaluable patients had an adjuvant chemotherapy with CMFAV in 6 or 12 cycles. On relapse these patients received either adriamycin 40 mg/m2, mitomycin 8 mg/m2 and vinblastine 6 mg/m2 (group A) or dibromodulcitol 500 mg, mitomycin 8 mg/m2 and vinblastine 6 mg/m2 (group B). In Group A, 22 patients with a mean age of 49.2 years relapsed 14 months on average after the end of adjuvant treatment. In 11 of them the main site of relapse was visceral. In group B, 27 patients with a mean age 49.5 years relapsed 6.5 months on average after the end of adjuvant treatment. In 15 of them the main site of relapse was visceral. According to the disease-free interval (DFI), in group A with DFI less than 12 months 3 patients (23%) responded partially whereas in patients with DFI longer than 12 months 4 patients (44.4%) had a partial response. In group B with DFI less than 12 months 4 patients (21%) responded partially, whereas 2 (25%) responded with DFI longer than 12 months. We conclude that salvage chemotherapy in this group of patients with an adriamycin-containing regimen is superior to a non-adriamycin regimen only if the DFI is longer than 12 months. 相似文献
6.
D Lamb C Atkinson D Joseph P OBrien S Ackland A Bonaventura P Dady C Hamilton N Spry J Stewart J Denham 《Journal of Medical Imaging and Radiation Oncology》1999,43(2):220-226
The purpose of the present paper was to evaluate treatment outcome after conservative breast surgery or mastectomy followed by simultaneous adjuvant radiotherapy and cyclophosphamide, methotrexate and fluorouracil (CMF) therapy. Two hundred and sixty eight (268) patients were treated at two Australian and two New Zealand centres between 1981 and July 1995. One hundred and sixty-nine patients underwent conservation surgery and 99 had mastectomies. Median follow-up was 53 months. Conventionally fractionated radiation was delivered simultaneously during the first two cycles of CMF, avoiding radiation on the Fridays that the intravenous components of CMF were delivered. In conservatively treated patients, 5-year actuarial rates of any recurrence, distant recurrence and overall survival were 34.5 ± 5.2%, 25.4 ± 4.5% and 75.5 ± 4.8%, respectively. Crude incidence of local relapse at 4 years was 6.3% and at regional/distant sites was 26.3%. Highest grades of granulocyte toxicity (< 0.5 × 109/L), moist desquamation, radiation pneumonitis and persistent breast oedema were recorded in 10.7, 8.5, 8.9 and 17.2%, respectively. In patients treated by mastectomy, 5-year actuarial rates of any recurrence, distant recurrence and overall survival were 59.7 ± 7.3%, 56.7 ± 7.4% and 50.1 ± 7%. The crude incidence of local relapse at 4 years was 5.6% and at regional/distant sites it was 45.7%. The issue of appropriate timing of adjuvant therapies has become particularly important with the increasing acknowledgement of the value of anthracycline-based regimens. For women in lower risk categories (e.g. 1–3 nodes positive or node negative), CMF may offer a potentially better therapy, particularly where breast-conserving surgical techniques have been used. In such cases CMF allows the simultaneous delivery of radiotherapy with the result of optimum local control, without compromise or regional or systemic relapse rates. Further randomized trials that directly address the optimal integration of the two modalities, such as the one carried out in Boston, are clearly necessary. 相似文献
7.
Bos AM de Graaf H de Vries EG Piersma H Willemse PH 《British journal of cancer》2000,82(12):1920-1924
Our aim was to study the feasibility of an intensified intravenous CMF (cyclophosphamide, methotrexate and 5-fluorouracil) schedule with the aim to escalate dose intensity (DI). Twenty-three premenopausal breast cancer patients received 6 cycles of adjuvant CMF intravenously on days 1 and 8 every 3 weeks and granulocyte colony-stimulating factor days 9-18. Endpoints were DI and toxicity. Twenty-one out of 23 patients (91%) received the projected total dose and reached > or =85% of the projected DI. Compared to 'classical' CMF, all patients reached > or = 111% DI. Nine patients received the planned schedule without delay. Thirteen patients (57%) were treated for infection and four patients (17%) were hospitalized for febrile neutropenia. Twelve patients received red blood cell transfusions (52%). Radiation therapy (n = 6) had no adverse impact on dose intensity or haematological toxicity. This dose-intensified CMF schedule was accompanied by enhanced haematological toxicity with clinical sequelae, namely fever, intravenous antibiotics and red blood cell transfusions, but allows a high dose intensity in a majority of patients. 相似文献
8.
Analysis of dose intensity for adjuvant chemotherapy trials in stage II breast cancer 总被引:4,自引:0,他引:4
We have analyzed the relationship between dose intensity of cyclophosphamide, methotrexate, and fluorouracil (CMF)-containing adjuvant chemotherapy of stage II breast cancer and 3-year relapse-free survival. Studies using only one or two drugs of CMF or melphalan instead of cyclophosphamide were included in the analysis by using simple techniques developed for this purpose. There was a clear-cut relationship between relapse-free survival and dose intensity in trials containing all four prognostic groups: less than 50 years, one to three and more than three positive nodes; and greater than or equal to 50 years, one to three and more than three positive nodes (P less than 10(-5)). Relapse-free survival also correlated with dose intensity for each of the four prognostic groups analyzed separately (P less than .005). Dose intensity was an independently significant correlate of relapse-free survival in multivariate analysis (P less than 10(-5)). This is a retrospective study, and the hypothesis that dose intensity contributes to outcome independently of other variables should be tested prospectively. Methods of increasing dose intensity also require testing in randomized trials before they can be applied to routine clinical practice. 相似文献
9.
E Caceres S Valdivia M Cotrina M Lingan L Leon M Gamboa L Olivares M Moran 《Journal of surgical oncology》1988,39(3):169-174
The results after 6 years of a prospective clinical trial of adjuvant chemotherapy with a regimen of two drugs--cyclophosphamide and 5-fluorouracil (CF)-- for 2 years in 97 women with stage II or III breast cancer are reported. Eligible patients were free from distant metastases. All patients began adjuvant therapy within 4 weeks of surgery; therapy consisted of radical, modified, or extended radical mastectomy. No postoperative radiotherapy was given. The results are compared with a historical control group from previous consecutive patients treated by surgery alone. Patients were stratified by age (younger than 50 or older than or equal to 50) and nodal status (one to three positive axillary nodes vs. four or more positive nodes). The estimated 6-year survival was 60% for CF patients vs. 31% for control patients (P = 0.001). The estimated 6-year disease-free survival was 53.6 and 30.3% for CF and control, respectively (P = 0.007). There was a trend toward longer disease-free survival (DFS) and survival (S) in patients treated with CF, but this was not significant in all the subgroups. Disease-free survival was statistically significant in the subgroup of women greater than or equal to 50 years old with one to three positive nodes (P = 0.038); survival in the patients less than or equal to 49 years old with four or more positive nodes (P = 0.0036); and in patients greater than or equal to 50 years old with one to three lymph nodes involvement (P = 0.038). 相似文献
10.
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12.
目的:了解淋巴结阳性绝经前乳腺癌患者新辅助化疗的疗效,探索乳腺癌新辅助化疗的敏感性预测指标对预后影响。方法:收集我院2006-06-01-2009-06-01治疗并符合条件的186例乳腺癌患者,96例淋巴结阳性绝经前乳腺癌患者接受TEC方案(新辅助化疗组)。分析患者反应率,进一步根据术后免疫组化及常规病理结果分层分析可以预测敏感性的临床指标。同期入组90例直接接受手术治疗的乳腺癌患者作为对照组。结果:新辅助化疗后40例(41.7%)临床完全缓解(cCR),42例(43.8%)临床部分缓解(cPR),总反应率(ORR)为85.5%。21例(21.9%)病理完全缓解(pCR)。雌激素受体(ER)阴性患者ORR高于ER阳性患者(94.1%vs80.7%,P=0.035);浸润性导管癌患者ORR高于浸润性小叶癌患者(87.8%vs55.5%,P=0.029)。新辅助化疗与直接手术组比较,3年无瘤生存率有提高(83.5%vs68.5%,P=0.039),3年总生存率差异无统计学意义(89.9%vs88.6%,P=0.473)。结论:淋巴结阳性绝经前乳腺癌采用TEC新辅助化疗可以取得较高的反应率,ER阴性和浸润性小叶癌是新辅助化疗敏感性预测指标。TEC方案有助于提高3年无瘤生存率,但对总生存率的延长尚不明确。 相似文献
13.
Rouëssé J de la Lande B Bertheault-Cvitkovic F Serin D Graïc Y Combe M Leduc B Lucas V Demange L Nguyen TD Castèra D Krzisch C Villet R Mouret-Fourme E Garbay JR Noguès C;Centre René Huguenin Breast Cancer Group 《International journal of radiation oncology, biology, physics》2006,64(4):1072-1080
PURPOSE: To compare concomitant and sequential adjuvant chemoradiotherapy regimens in node-positive, operable breast cancer patients. METHODS AND MATERIALS: This was a randomized, French, multicenter, phase III trial enrolling 638 eligible women with prior breast surgery and positive axillary dissection. Patients in Arm A received 500 mg/m2 5-fluorouracil, 12 mg/m2 mitoxantrone, and 500 mg/m2 cyclophosphamide, with concomitant radiotherapy (50 Gy +/- 10-20-Gy boost). Patients in Arm B received 500 mg/m2 5-fluorouracil, 60 mg/m2 epirubicin, and 500 mg/m2 cyclophosphamide, with subsequent radiotherapy. Chemotherapy was administered on Day 1 every 21 days for 4 cycles. RESULTS: Median treatment durations were 64 and 126 days (Arms A and B, respectively), with no significant difference in overall or disease-free survival. Five-year locoregional relapse-free survival favored patients with conservative surgery (two thirds of the population), with less local and/or regional recurrence in Arm A than in Arm B (3% vs. 9%; p = 0.01). Multivariate analysis in this subgroup showed a 2.8-fold increased risk of locoregional recurrence with sequential chemoradiotherapy, independent of other prognostic factors (p = 0.027). Febrile neutropenia and Grade 3-4 leukopenia were significantly more frequent in Arm A. Subclinical left ventricular ejection fraction events at 1 year were more frequent with concomitant radiotherapy (p = 0.02). CONCLUSIONS: Concomitant radiotherapy with adjuvant fluorouracil, mitoxantrone, and cyclophosphamide has significantly better locoregional control in node-positive breast cancer after conservative surgery and 50% shorter treatment, albeit with slightly more acute toxicity. With mitoxantrone no longer available for adjuvant breast cancer treatment, alternative concomitant chemoradiotherapy studies are needed. 相似文献
14.
目的:研究TC方案(多西紫杉醇75mg/m2,d1+环磷酰胺600mg/m2,d1)在乳腺癌术后辅助化疗中的近期不良反应。方法:84例乳腺癌患者,行乳腺癌改良根治术,St Gallen复发风险分级为中危,术后给予TC方案辅助化疗,每3周1周期,共4周期,观察近期不良反应。结果:TC方案的主要不良反应为粒细胞减少,其次为恶心呕吐。无心脏毒性、过敏反应发生。<65岁与≥65岁的患者相比,粒缺性发热的发生率、减量化疗率的差异均具有统计学意义。结论:<65岁的患者可以耐受标准剂量的TC方案辅助化疗,而≥65岁的患者则需预防性应用G-CSF或化疗减量。 相似文献
15.
Endocrine effects of adjuvant chemotherapy and long-term tamoxifen administration on node-positive patients with breast cancer 总被引:2,自引:0,他引:2
Ovarian and pituitary hormones were determined in pre- and postmenopausal breast cancer patients before and at intervals during adjuvant chemotherapy or chemotherapy plus tamoxifen (TAM). Chemotherapy did not affect gonadotrophin levels in postmenopausal patients; however, inclusion of TAM in the regimen produced a partial (approximately 50%) reduction in circulating levels of luteinizing hormone (LH) and follicle-stimulating hormone. Gonadotrophin levels remained reduced as long as TAM therapy continued, at which time they rose to postmenopausal values. Chemotherapy (6-12 months) caused ovarian failure in premenopausal patients with decreases in estrogen (estrone plus estradiol) and rises in gonadotrophin levels to postmenopausal levels. Inclusion of TAM in the regimen caused an initial 3-fold rise in peak circulating estrogen levels before ovarian failure (6-9 months of therapy). Some younger patients (approximately 40 years of age) who had a short course (4 months) of chemotherapy plus TAM followed by continuous TAM therapy alone resumed ovulatory menstrual cycles. Estrogen, progesterone, and follicle-stimulating hormone levels were increased compared with control subjects. Those patients who experienced ovarian failure with adjuvant chemotherapy plus TAM only had a partial rise in gonadotrophins compared with patients receiving chemotherapy alone. TAM maintained the levels of gonadotrophins for as long as therapy was administered, at which time they rose to postmenopausal levels. Although TAM exhibited estrogen-like effects on gonadotrophins there was no estrogen-like increase in circulating prolactin levels in either pre- or postmenopausal patients. One patient experienced an estrogen receptor-positive recurrence during long-term tamoxifen therapy. Serum levels of tamoxifen and metabolites declined in the year prior to the recurrence and this was associated with a rise in gonadotrophins. This indicated noncompliance by the patient. Compliance can be monitored either directly with serum levels of TAM or by serial gonadotrophin determinations. We suggest that the optimal antitumor activity of TAM will be achieved in a low estrogen environment with continuous high levels of the drug in the serum. We recommend that patients undergoing long-term TAM therapy be monitored for complete ovarian failure and drug compliance. 相似文献
16.
目的:研究TC方案(多西紫杉醇75mg/m2,d1+环磷酰胺600mg/m2,d1)在乳腺癌术后辅助化疗中的近期不良反应。方法:84例乳腺癌患者,行乳腺癌改良根治术,St Gallen复发风险分级为中危,术后给予TC方案辅助化疗,每3周1周期,共4周期,观察近期不良反应。结果:TC方案的主要不良反应为粒细胞减少,其次为恶心呕吐。无心脏毒性、过敏反应发生。〈65岁与≥65岁的患者相比,粒缺性发热的发生率、减量化疗率的差异均具有统计学意义。结论:〈65岁的患者可以耐受标准剂量的TC方案辅助化疗,而≥65岁的患者则需预防性应用G-CSF或化疗减量。 相似文献
17.
Kümmel S Krocker J Kohls A Breitbach GP Morack G Budner M Blohmer JU Elling D 《British journal of cancer》2006,94(9):1237-1244
We evaluated the survival benefit, safety, feasibility, and tolerability of dose-dense (DD) adjuvant chemotherapy with epirubicin and paclitaxel for women with node-positive primary breast cancer. Randomised patients (n=216) received DD or conventional-schedule (CS) chemotherapy. Dose-dense regimen patients (n=108) received epirubicin 90 mg m-2 plus paclitaxel 175 mg m-2 in four 14-day cycles, then cyclophosphamide 600 mg m-2, methotrexate 40 mg m-2, and fluorouracil 600 mg m-2 (CMF 600/40/600) in three 14-day cycles, plus filgrastim 5 microg kg day-1 as growth support in every cycle. Conventional-schedule regimen patients (n=108) received epirubicin 90 mg m-2 plus cyclophosphamide 600 mg m-2 in four 21-day cycles, then CMF 600/40/600 in three 21-day cycles, plus filgrastim if required. After a median follow-up of 38.4 months, 71 patients (33%) relapsed or died: DD, 33 patients (15 deaths); CS, 38 patients (22 deaths). Dose dense showed a trend for improved disease-free survival (DFS) and overall survival (OS). Four-year rates of DFS and OS were 64 and 85% for DD, and 58 and 75% for CS. All seven cycles were administered to 208 patients (96%). Rates of cycle delay, discontinuation, dose reduction, and adverse events were similar in both groups. Dose-dense sequential chemotherapy with epirubicin/paclitaxel then CMF, supported by filgrastim, is safe and improves survival for patients with node-positive breast cancer. 相似文献
18.
C Bernard-Marty M Mano M Paesmans C Accettura R Munoz-Bermeo T Richard K Kleiber F Cardoso J P Lobelle D Larsimont M J Piccart A Di Leo 《Annals of oncology》2003,14(5):693-698
BACKGROUND: Alkylating agents and topoisomerase-II inhibitors have been associated with the occurrence of secondary leukemias and myelodysplastic syndromes in breast cancer patients treated with adjuvant chemotherapy. Conversely, data on the occurrence of second solid malignancies in this setting are scarce. PATIENTS AND METHODS: This study retrospectively evaluates the occurrence of second hematological and solid malignancies in the context of a prospective multicenter phase III trial comparing epirubicin-cyclophosphamide at intermediate doses (EC), or at full doses (HEC), with classical cyclophosphamide, methotrexate and 5-fluorouracil (CMF) in 777 patients with early breast cancer. RESULTS: At a median follow-up of 73 months, the following 8-year actuarial rates of second solid primaries were observed: CMF 5.5% [95% confidence interval (CI) 1.5% to 9.5%], EC 4.1% (95% CI 0.1% to 8.1%), and HEC 7.2% (95% CI 3.2% to 11.2%) (P = 0.79 by log rank test). Three secondary acute myeloid leukemias (AML) were reported, all in the HEC arm (incidence = 1.2%, 95% CI 0.0% to 2.5%), which by a three arm comparison allows us to conclude that HEC is statistically different (borderline significance) from CMF and EC (P = 0.05). CONCLUSIONS: HEC, as delivered in this trial, cannot be recommended in clinical practice because of the lack of superiority over classic CMF and because of the increased risk of AML observed in this arm. Prolongation of conventional anthracycline-based treatment beyond the current standard of four to six cycles is not recommended in clinical practice. 相似文献
19.
Expression of sialyl-Tn predicts the effect of adjuvant chemotherapy in node-positive breast cancer.
D. W. Miles L. C. Happerfield P. Smith R. Gillibrand L. G. Bobrow W. M. Gregory R. D. Rubens 《British journal of cancer》1994,70(6):1272-1275
Sialyl-Tn (STn) is a carcinoma-associated carbohydrate determinant expressed on cancer-associated mucins and has the structure NANA alpha(2-6)alpha GalNAc. Expression of STn in colon and ovarian cancer is associated with a poor prognosis independent of tumour grade, stage or histological type. We have examined 237 cases of primary breast cancer for expression of this antigen using the antibody HB-STn (Dako). The frequency of STn expression was 31% in the whole group, 36% in the node-negative and 28% in the node-positive group. Survival was lower, but not significantly so, in the STn-positive group (P = 0.07), but this effect was highly significant for patients with node-positive disease (P < 0.002), the curves for node-negative disease being coincident (P = 0.31). In node-positive disease the effect was limited to those receiving adjuvant chemotherapy (P = 0.001). In a multivariate (Cox) analysis on the whole group STn staining, combined with adjuvant chemotherapy, showed a highly significant correlation with survival. In STn-negative cases, adjuvant chemotherapy improved survival (relative risk 2.3, 95% confidence intervals 1.4-3.9), whereas adjuvant chemotherapy did not influence survival in patients which expressed STn (relative risk 1.1, 95% confidence intervals 0.6-2.2). Thus, by either direct or indirect mechanisms, STn positivity appears to be a marker of resistance to adjuvant chemotherapy. 相似文献
20.
Bent Ejlertsen Maj-Britt Jensen Johanna Elversang Birgitte B. Rasmussen Michael Andersson Jørn Andersen Dorte L. Nielsen Søren Cold Henning T. Mouridsen 《European journal of cancer (Oxford, England : 1990)》2013,49(14):2986-2994
PurposeWe report the long-term results of a randomised trial comparing tamoxifen with tamoxifen plus cyclophosphamide, methotrexate and fluorouracil (CMF) in postmenopausal high-risk breast cancer patients. In addition, we analyse the prognostic and predictive value of centrally assessed subtypes.MethodsPostmenopausal patients with breast cancer and positive nodes, deep invasion or size exceeding 5 cm were randomly assigned to 1 year of tamoxifen, or cyclophosphamide 600 mg/m2, methotrexate 40 mg/m2 and fluorouracil 600 mg/m2 intravenously on day 1 every 4 weeks for nine cycles plus tamoxifen (CMFT). Tissue microarrays were constructed retrospectively and oestrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), and proliferation-related Ki-67 antigen (Ki67) status were assessed.ResultsFrom October 1982 through March 1990 we randomised 1445 patients and 969 (67%) were eligible for the biomarker analysis. At 10-years 936 women had suffered a disease-free survival (DFS) event (tamoxifen, 495 events in 686 patients; CMFT, 441 events in 642 patients). The addition of CMF to tamoxifen significantly improved DFS (adjusted hazard ratio 0.82; 95% confidence interval (CI) 0.71–0.93; P = 0.003) but not overall survival (adjusted hazard ratio 0.95; 95% CI 0.85–1.08; P = 0.44). DFS was superior in Luminal A tumours (ER or PgR positive, HER2 negative and Ki67 ?14%) when compared to Luminal B or non-luminal (ER and PgR negative) tumours. There was no statistical evidence of heterogeneity by subtype in the benefit from CMF (Pinteraction = 0.45).ConclusionCMF added to 1 year of tamoxifen reduces the risk of a DFS event. The benefit from CMF was not significantly different in Luminal A and B subtypes. 相似文献