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1.
BACKGROUND: Primary chemotherapy (PC) is becoming an accepted practice to treat large tumors to avoid mastectomies and as a surrogate of outcome. METHODS: A series of 305 patients with tumors >3 cm with T2-3N0-1M0 classification were treated with a multimodal approach that consisted of 3 courses of primary cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) followed by appropriate local treatment and 3 more courses of CMF or 4 courses of doxorubicin. Response was assessed by mammography. RESULTS: The overall response rate was 48% (a 3% pathologic complete response rate). Conservative surgery was achieved in 79.64% of the patients with a low rate of local disease recurrences (5%). Toxicity was minimal. With a median follow-up of 104 months, the 8-year disease-free survival (DFS) rate was 57.63% and the 8-year overall survival (OS) was 67.65%. The DFS and OS rates for patients with a clinical response were significantly longer, i.e., 70% (P=0.0048) and 90% (P=0.0042), respectively. CONCLUSIONS: PC with CMF was feasible. A high rate of breast-conservative surgery was achieved. The current results stressed the value of PC to increase conservative surgery and as a predictor of outcome.  相似文献   

2.
One hundred fifty-six women with axillary node-negative breast cancer and primary tumors less than or equal to 5 cm in diameter (T1N0 or T2N0) were treated with a brief course of postoperative adjuvant chemotherapy consisting of doxorubicin and cyclophosphamide. Treatment was well tolerated and toxicity was minimal. With a median follow-up time of 58 months, there has been 1 relapse among 58 patients with T1 primary lesions and 15 relapses among 98 patients with T2 primary tumors. When compared with a matched historical control group receiving surgery alone, significant improvement was apparent in disease-free survival among the patients who received adjuvant chemotherapy. Prospective controlled trials are needed if we are to confirm this favorable experience with adjuvant chemotherapy in the treatment of women with node-negative breast cancer.  相似文献   

3.
To improve current adjuvant results in high-risk breast cancer, in February 1982 we activated a prospective randomized trial using both intravenous cyclophosphamide, methotrexate, and fluorouracil (CMF) and Adriamycin (doxorubicin; Farmitalia-Carlo Erba, Milan, Italy) involving patients with resectable mammary carcinoma and more than three positive axillary lymph nodes. The objective of the study was to assess the effectiveness of four courses of Adriamycin followed by eight courses of CMF versus two courses of CMF alternated with one course of Adriamycin for a total of 12 courses. All drug courses were recycled every 3 weeks. Rather than temporarily reducing doses in the event of myelosuppression on the planned day of treatment, drug administration was delayed for 1 to 2 weeks. At a median follow-up of 59 months, treatment outcome was significantly superior for patients who received Adriamycin followed by CMF (Adriamycin----CMF) than for those given alternating regimens (CMF/Adriamycin). The 5-year relapse-free survival was superior post-Adriamycin----CMF (61%) compared with post-CMF/Adriamycin administration (38%; P = .001). The corresponding figures for the 5-year total survival were 78% and 62%, respectively (P = .005). The benefit of Adriamycin----CMF was observed in all patient subsets. Treatment was fairly well tolerated, and we documented only one case of fatal congestive heart failure in a patient who received postoperative irradiation to the left breast in addition to Adriamycin. Present findings indicate that in women with extensive nodal involvement, Adriamycin----CMF yielded superior results compared with CMF/Adriamycin.  相似文献   

4.
PURPOSE: The optimal sequencing of adjuvant chemotherapy (CT) and radiation therapy (RT) in patients with early-stage breast cancer remains unclear. PATIENTS AND METHODS: We retrospectively compared 485 patients treated with conservative breast surgery and postoperative whole-breast RT and six courses of CMF (cyclophosphamide 600 mg/m(2), methotrexate 40 mg/m(2), and 5-fluorouracil 600 mg/m(2)) with 300 patients who received postoperative CMF only and with 509 patients treated with postoperative whole-breast RT only. The mean radiation dose delivered was 50 Gy (range, 46-52 Gy) with standard fractionation. The boost dose was 6-16 Gy according to resection margins and at the discretion of the radiation oncologist. Acute and late RT toxicity were scored using respectively the Radiation Therapy Oncology Group and the Late Effects in Normal Tissues Subjective, Objective, Management and Analytic scale. RESULTS: A slightly higher Grade 2 acute skin toxicity was recorded in the concurrent group (21.2% vs. 11.2% of the RT only group, p < 0.0001). RT was interrupted more frequently in the CMF/RT group respective to the RT group (8.5% vs. 4.1%; p = 0.006). There was no difference in late toxicity between the two groups. All patients in the concurrent group successfully received the planned dose of RT and CT. Local recurrence rate was 7.6% in CT/RT group and 9.8% in RT group; this difference was not statistically significant at univariate analysis (log-rank test p = 0.98). However, at multivariate analysis adjusted also for pathological tumor, pathological nodes, and age, the CT/RT group showed a statistically lower rate of local recurrence (p = 0.04). CONCLUSIONS: Whole-breast RT and concurrent CMF are a safe adjuvant treatment in terms of toxicity.  相似文献   

5.
Breast Cancer Research and Treatment - The axillary lymph node status is one of the most important prognostic factors in patients with early breast cancer. However, the impact of axillary lymph...  相似文献   

6.
BACKGROUND: Adjuvant combination chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil plus vincristine and prednisone (CMFVP) was compared with single-agent L-phenylalanine mustard (L-PAM) for the treatment of patients with axillary lymph node positive primary breast carcinoma over 20-years of follow-up. METHODS: Four hundred forty-one women with axillary lymph node positive breast carcinoma were randomized to receive either combination chemotherapy with cyclophosphamide (60 mg/m(2) orally every day for 1 year), fluorouracil (300 mg/m(2) intravenously [IV] weekly for 1 year), methotrexate (15 mg/m(2) IV weekly for 1 year), vincristine (0.625 mg/m(2) IV for 10 weeks), prednisone (30 mg/m(2) orally on Days 1-14, 20 mg/m(2) on Days 15-28, and 10 mg/m(2) on Days 29-42), or single-agent chemotherapy with L-PAM (5 mg/m(2) orally every day for 5 days every 6 weeks for 2 years) after undergoing surgery. Patients were stratified according to menopausal status and number of positive lymph nodes (1-3 positive lymph nodes or > 3 positive lymph nodes). Seventy-seven patients were ineligible. RESULTS: The maximum follow-up is 24 years, with a median follow-up of 21.5 years. Disease free survival and overall survival were superior with CMFVP (two-sided log-rank test; P = 0.0008 and P = 0.007, respectively). For all patients, the estimated 20-year survival rate of patients who received CMFVP was 40% compared with 27% for patients who received L-PAM. There was a substantial survival benefit for CMFVP compared with L-PAM in the subsets of premenopausal patients and patients with four or more positive lymph nodes. The estimated 20-year survival rate for premenopausal women who received CMFVP was 49% compared with 33% for premenopausal women who received L-PAM. Among women with > or = 4 positive lymph nodes, the estimated survival rate for patients who received CMFVP was 31% compared with 15% for patients who received L-PAM. Both regimens were tolerated well. Toxicity was more severe and frequent among patients who received CMFVP. CONCLUSIONS: The authors conclude that, after 20 years of follow-up, adjuvant chemotherapy with CMFVP remains superior to L-PAM for the treatment of patients with lymph node positive breast carcinoma.  相似文献   

7.
M Colozza  M Tonato  F Grignani  S Davis 《Cancer》1988,62(2):262-265
Forty-four evaluable patients with breast carcinoma previously treated with combination chemotherapy consisting of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) were treated with a combination chemotherapy regimen consisting of doxorubicin (A) (20 mg/m2 on days 1, 8, 15, and 22, repeated every 28 days) and mitomycin (MIT) (10 mg/m2 on day 1, repeated every 28 days). Five patients (11%) achieved a complete remission (CR) and 14 patients (32%) had a partial response (PR). The median duration of survival was 11.5 months and the median duration of response was 8 months for responders (CR and PR). Toxicity was moderate and consisted of neutropenia (74%), thrombocytopenia (25%), pneumonitis (11%), and cardiomyopathy (2%). The combination chemotherapy regimen A and MIT is an effective regimen for treating previously treated with CMF.  相似文献   

8.
This prospective clinical trial was designed to assess the impact of adjuvant chemotherapy in women with rapidly proliferating node-negative breast cancer. This group has been predicted to have a 5-year disease-free survival (DFS) of 70% without adjuvant chemotherapy. In this study, 449 women with rapidly proliferating breast cancer (91% measured by S-phase fraction and 9% by histochemistry) received adjuvant chemotherapy with doxorubicin/cyclophosphamide (AC) plus tamoxifen for estrogen receptor-positive or progesterone receptor-positive cancer. The 5-year DFS was 90% (+/- 2%) and the 5-year overall survival was 94% (+/- 1%). At a median follow-up of 62 months, the strategy of administering 6 cycles of AC to women with T2 N0 cancer and 3 cycles in those with smaller T1 N0 cancers appeared to eliminate tumor size as a potential prognostic factor. Adjuvant chemotherapy with AC appears effective in reducing recurrence rates for women with rapidly proliferating node-negative breast cancer.  相似文献   

9.
Summary After total mastectomy and partial axillary dissection, 805 premenopausal women with stage II breast cancer were randomized to receive postoperative radiotherapy (RT) alone, RT + cyclophosphamide (C) for 12 monthly cycles, or RT + cyclophosphamide/methotrexate/5-fluorouracil (CMF) for 12 monthly cycles. At 3 years actuarial relapse-free survival for RT + C and RT + CMF was significantly better than for RT alone (p = 0.0009 and 0.0001, respectively). There was no significant difference in relapse-free survival between RT + C and RT + CMF.C resulted in more pronounced haematologic toxicity and a higher frequency of amenorrhoea and of alopecia than CMF, while CMF resulted in more pronounced nausea and stomatitis than C.In the preliminary results, C alone may be as effective as CMF in prolonging relapse-free survival in premenopausal women with stage II breast cancer.  相似文献   

10.
11.
Seventy-eight advanced breast cancer patients with hormone-resistant disease or visceral metastases were randomized to receive either of two low dose regimens consisting of cyclophosphamide (C), methotrexate (M), 5-fluorouracil (F), and Adriamycin (A) as their initial chemotherapy. One group was treated with CAMF, and the other with CMF until progression, followed by A (CMF leads to A). C was given at 50 mg/m2, po, days 1-14; M at 20 mg/m2, F at 300 mg/m2, and A at 20 mg/m2, iv, days 1 and 8 of each 28-day cycle. The response rates for CAMF vs. CMF did not differ significantly (complete and partial responses-62% vs. 49%; stabilizations-23% vs. 31%). Responses by site of metasis, median times to progression and median survivals were similar for both groups. Poor and good risk partial responders had similar survivals. Twelve percent of CMF patients treated with Adriamycin at the time of progression had partial responses with an associated improved survival. Since CMF is as effective as CAMF, but has less toxicity, low dose therapy with CMF is more acceptable than CAMF as an initial chemotherapy regimen for metastatic breast cancer. Adriamycin may be reserved for subsequent regression induction.  相似文献   

12.
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).  相似文献   

13.
Hartman AR  Fleming GF  Dillon JJ 《Clinical breast cancer》2001,2(2):138-43; discussion 144
Conflicting results have been published regarding the efficacy of adjuvant cyclophosphamide/methotrexate/5-fluorouracil (CMF)-type chemotherapy in postmenopausal, estrogen receptor (ER)-positive women. The Oxford overview suggests real but limited benefit of any chemotherapy in this group of patients but avoids analyzing smaller subsets. We wished to better quantitate the benefit of adding CMF to tamoxifen in postmenopausal ER-positive women with tumor involvement of axillary lymph nodes. Six randomized studies comparing CMF plus tamoxifen to tomoxifen alone in postmenopausal, ER-positive, node-positive women have been published since 1992. They include 2368 patients. We performed a meta-analysis of 6 endpoints: survival, disease-free survival, locoregional recurrence, distant recurrence, contralateral breast recurrence, and thromboembolic complications. There was a statistically significant increase in disease-free survival from the addition of CMF-type chemotherapy to tamoxifen in this population; the absolute risk of relapse was reduced by 5.5% at 5 years. Effects of locoregional recurrence were greater than those on overall recurrence. No significant survival benefit was observed.  相似文献   

14.
OBJECTIVE: We conducted a retrospective analysis of prognosis factors for survival in breast cancer patients with 1-3 axillary lymph node metastases and tried to identify a subset of patients with good prognosis suitable for cyclophosphamide, methotrexate and 5-fluorouracil (CMF) adjuvant chemotherapy. METHODS: A cohort of 446 breast cancer patients received definite surgery and adjuvant chemotherapy with CMF at Chang Gung Memorial Hospital from 1990 to 1998. They were enrolled in the study. The median follow-up time was 69 months. Prognostic factors including age, tumor size, number of involved nodes, steroid receptor status, tumor ploidy, synthetic-phase fraction, histologic grade and administration of tamoxifen were analysed for disease-free survival (DFS) and overall survival (OS) by Cox regression model. RESULTS: The estimated 5 year OS and DFS for all patients were 85.4 and 71.5%, respectively. Multivariate analysis revealed that tumor size, age and estrogen receptor (ER) status were independent prognostic factors for OS, and tumor size, age, ER status and number of involved nodes were independent prognostic factors for DFS. The 5 year OS rates of the low-risk group (age >40, tumor < or =3 cm and positive ER) and average-risk group (either age < or =40, tumor >3 cm or negative ER) were 98.8 and 82.4%, respectively (P = 0.0001). The 5 year DFS of the low-risk and high-risk group were 88.2 and 67.7%, respectively (P = 0.0001). CONCLUSION: Among breast cancer patients with 1-3 positive lymph nodes excellent survival rate was found in those who had favorable prognostic factors, including age >40, tumor size < or =3 cm and positive ER. Adjuvant chemotherapy with CMF regimen is optimal for these low-risk patients.  相似文献   

15.
Schrenk P  Rieger R  Shamiyeh A  Wayand W 《Cancer》2000,88(3):608-614
BACKGROUND: Axillary lymph node dissection for staging the axilla in breast carcinoma patients is associated with considerable morbidity, such as edema of the arm, pain, sensory disturbances, impairment of arm mobility, and shoulder stiffness. Sentinel lymph node biopsy electively removes the first lymph node, which gets the drainage from the tumor and should therefore be associated with nearly zero morbidity. METHODS: Postoperative morbidity (increase in arm circumference, subjective lymphedema, pain, numbness, effect on arm strength and mobility, and stiffness) of the operated arm was prospectively compared in 35 breast carcinoma patients after axillary lymph node dissection (ALND) of Level I and II and 35 patients following sentinel lymph node (SN) biopsy. RESULTS: Patient characteristics were comparable between the two groups. Postoperative follow-up was 15.4 months (range, 4-28 months) in the SN group and 17.0 months (range, 4-28 months) in the ALND group. Following axillary dissection, patients showed a significant increase in upper and forearm circumference of the operated arm compared with the SN patients, as well as a significantly higher rate of subjective lymphedema, pain, numbness, and motion restriction. No difference between the two groups was found regarding arm stiffness or arm strength, nor did the type of surgery affect daily living. CONCLUSIONS: SN biopsy is associated with negligible morbidity compared with complete axillary lymph node dissection.  相似文献   

16.
F Richards  T L Pajak  M R Cooper  C L Spurr 《Cancer》1975,36(5):1589-1592
Thirty-eight patients with metastatic colorecal carcinoma were treated with 5-fluorouracil (5-FU), and 38 patients were treated with the combination of 5-FU, cyclophosphamide, and methotrexate. In terms of percent response, response duration, and survival there was no apparent difference between the two regimens. Combination chemotherapy was found to be effective in 6 of 16 patients refractory to treatment with 5-FU alone, but was associated with more morbidity.  相似文献   

17.
BACKGROUND: The objective of this study was to determine whether HER-2 overexpression is associated with improved response to neoadjuvant chemotherapy with 5-fluorouracil, doxorubicin, cyclophosphamide (FAC) in patients with breast carcinoma. METHODS: Ninety-seven patients with Stage I-III breast carcinoma were included. HER-2 expression was determined by routine clinical laboratory assessment, and tumors with 3 + immunohistochemistry staining intensity or gene amplification by fluorescent in situ hybridization were considered HER-2 positive. Response was assessed by physical examination, imaging assessment, and pathologic assessment at the time of surgery. RESULTS: The median patient age was 45 years. At baseline, 68% of patients had lymph node positive disease, 87% had >/= T2 tumors, and 28% of patients had HER-2 positive tumors. Eighty-four percent of patients received four courses of FAC, 8% of patients received 3 courses of FAC, and the remaining 8% of patients received 5-6 courses of FAC. The clinical response rate (complete response [CR] and partial response [PR]) was 78%, the imaging response rate (CR and PR) was 64%, and 15% of patients had a good pathologic response, defined as a CR or minimal residual disease (tumor measuring < 1 cm in greatest dimension and negative lymph nodes). Concordance between the three methods of response assessment (clinical, pathologic, and imaging) was modest and was best between clinical assessment and imaging assessment (64% concordance). HER-2 status did not correlate with pathologic or clinical response (assessed by physical examination or imaging), although a nonsignificant trend was noted toward better response in patients with breast tumors that overexpressed HER-2. CONCLUSIONS: The authors found no significant correlation between HER-2 expression and clinical or pathologic response to neoadjuvant chemotherapy in patients with breast carcinoma.  相似文献   

18.
BACKGROUND: The current study was conducted to assess the toxicity of concurrent adjuvant cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) chemotherapy and radiotherapy (RT) for early breast carcinoma. METHODS: In the current study, the authors reviewed the records of 680 consecutive breast carcinoma patients who received adjuvant CMF at the Princess Margaret Hospital between 1980-1990. Surgery was comprised of mastectomy in 64% of patients, breast conservation in 35% of patients, and was unknown in 1% of patients. Two hundred two patients received concurrent CMF/RT that was defined as an overlap in CMF and RT administration of at least 21 days. Forty-seven patients received sequential CMF/RT (defined as no overlap or an overlap of < 7 days in CMF and RT administration). Other patients received CMF alone. Adverse effects of RT were graded retrospectively using the Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of Cancer (EORTC) system. Reasons for interruption or failure to complete RT were recorded. The magnitude of chemotherapy dose reductions and delays also were noted. RESULTS: The median age of the patients was 44 years (range, 26-68 years) and 88% of the patients had lymph node-positive disease. RT was interrupted or discontinued due to side effects in 4% of patients (95% confidence interval [95% CI], 1.7-7.7%) and 0% (95% CI, 0-7.6%), respectively, of the concurrent and sequential groups (P = 0.36). The incidence of Grade 3 or Grade 4 RT toxicity was 1.5% (95% CI, 0.3-4.3%) and 2.1% (95% CI, 0.1-11.3%), respectively, for the concurrent and sequential groups (P = 0.57). The median relative dose intensity of chemotherapy for patients receiving concurrent CMF/RT, sequential CMF/RT, and CMF alone was 0.87, 0.84, and 0.85, respectively (P = 0.22). CONCLUSIONS: The results of the current study demonstrate that the concurrent administration of CMF and RT is associated with a low risk of serious toxicity and is an acceptable adjuvant regimen for patients with breast carcinoma.  相似文献   

19.
A multicenter phase III randomized study comparing the efficacies of two adjuvant polychemotherapeutic regimens in 145 patients with stage II node-positive breast cancer: the standard chemotherapy combination, CMF (cyclophosphamide, methotrexate, 5-fluorouracil), and an experimental protocol, CNF (cyclophosphamide, mitoxantrone [Novantrone], 5-fluorouracil) in which mitoxantrone replaced methotrexate. The finding of a significant advantage ( p= 0.04) in the disease-free survival for those receiving mitoxantrone (mean survival 4.4 years for CNF versus 2.7 years for CMF) led the authors to break the data down in subpopulations to determine exactly which groups of women responded more favorably to CNF than CMF. An advantage in disease-free survival was found, most notable in four subgroups: Sephardic women, women less than 45 years of age, premenopausal women, and women with 4 to 10 positive axillary lymph nodes. Although the small numbers of women in each of these subgroups rule out drawing definitive conclusions, the trend merits further study to confirm these observations.  相似文献   

20.

Background

It is still controversial whether axillary lymph node (ALN) dissection (ALND) can be omitted after negative sentinel lymph node (SLN) biopsy (SLNB) in breast cancer (BC) patients with clinically positive ALNs at presentation treated with neoadjuvant chemotherapy (NAC). The study aim was to analyze whether SLNB could be useful in these patients.

Methods

In a retrospective study, eligible patients were women with invasive BC with clinically positive ALNs at presentation, treated with NAC then a total or partial mastectomy, with an intraoperative histological examination of SLNs and non-SLNs suspicious for metastasis followed by ALND. Non-SLNs suspicious for metastasis were defined as hard or large nodes located in the same level of the axilla where clinically positive ALNs had been initially identified. The results of SLNB and clinicopathological characteristics were analyzed for correlation with pathological ALN status.

Results

In a consecutive series of 105 women with 107 BC cases, 81 (75.7 %) had at least 1 SLN, and the remaining 26 (24.3 %) had at least 1 non-SLN suspicious for metastasis. The intraoperative (or final) histological examination of these nodes revealed that the false-negative (FN) rate and accuracy were 8.2 (or 6.3) % and 95.1 (or 96.3) %, respectively. Estrogen receptor status at presentation, pathological tumor response, lymphovascular invasion after NAC, and NAC regimen were correlated with pathological ALN status.

Conclusion

The histological examination of SLNs and that of non-SLNs suspicious for metastasis are useful for predicting pathological ALN status in BC patients with clinically positive ALNs at presentation who are treated with NAC.  相似文献   

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