Adjuvant hormone treatment and chemotherapy in postmenopausal women with operable breast cancer: a retrospective analysis.

Two hundred consecutive postmenopausal women with operable breast cancer and metastatic axillary nodes were treated during the period January - December 1981 with adjuvant chemotherapy (CMF) or hormonal treatment (tamoxifen). The distribution of receptor status (estrogen or progesterone), number of axillary metastatic nodes (less than = 3 or greater than 3), surgical treatment and size of the primary tumor were homogeneous in both groups. Receptor status and number of axillary lymph nodes were correlated with adjuvant treatment efficacy. Ten-year disease-free survival (DFS) was higher in the TAM-treated (72%) than in the CMF-treated group (52%) (p less than 0.01). In patients with less than = 3 axillary metastatic nodes, those treated with TAM had a higher DFS rate than those treated with CMF (75% vs 59%, p less than 0.01). There was no difference in DFS between CMF-and TAM-treated groups within the greater than 3 metastatic lymph node patients. In ER + primary tumors, DFS was higher in the subset treated with TAM (62%) than with CMF (51%) (p less than 0.05), whereas no difference in DFS was observed in ER- patients between the two treatment groups. Considering the TAM group, DFS was better (p less than 0.01) for ER+ cases than for ER- cases only at 5 years of observation. In the CMF group, DFS was not influenced by ER status. PgR content did not affect DFS in either adjuvant treatment group.     

ER阳性乳癌病人全身辅助治疗的研究

目的研究雌激素受体阳性(ER+)乳癌病人接受不同全身辅助治疗的预后,以期指导病人的治疗。方法387例ER+乳癌病人分成三组辅助内分泌治疗组(178例)绝经后(绝经前病人先切除卵巢)病人服用三苯氧胺(TAM)5年。辅助化疗组(154例)主要化疗方案有CMFVP;CMF;CF;FVC等。联合治疗组(55例)化疗+TAM,其中绝经前病人未切除卵巢。采用生命表的方法观察三组病人的5年无病生存率(DFS)和总生存率(OS)。结果在不同年龄、不同月经状态、不同局部肿瘤T期及不同转移淋巴结数目的病人中,都显示出辅助内分泌治疗的5年无病生存率和总生存率明显好于辅助化疗者,差异有显著意义。在转移淋巴结≥10个组内,虽然仍是内分泌治疗结果好于化疗组,但未显示统计学意义。联合治疗的病人,在各个亚组分析中,都不优于辅助内分泌治疗。结论ER及绝经状态应作为决定取舍辅助内分泌治疗的主要依据,对于ER阳性乳癌病人,术后内分泌治疗为最合适。     

Tamoxifen in high-risk premenopausal women with primary breast cancer receiving adjuvant chemotherapy. Report from the Danish Breast Cancer co-operative Group DBCG 82B Trial

Following modified radical mastectomy, pre- and perimenopausal (amenorrhoea for < 5 years) patients with stage II or III breast cancer received CMF (cyclophosphamide 600, methotrexate 40, 5-fluorouracil 600 mg/m2 intravenously (i.v.) every 4 weeks, 9 cycles). The effect on recurrence-free survival (RFS) and overall survival (OS) of the addition of adjuvant tamoxifen (TAM) to adjuvant chemotherapy was examined by randomisation either to no additional treatment (n = 314), or concurrently TAM 30 mg daily for 1 year (n = 320). 40% had positive, 12% negative and 48% unknown receptor status. One year after surgery 21% versus 35% (CMF + TAM versus CMF) were still menstruating (P < 0.01). With a median follow-up of 12.2 years there was no difference in RFS (10-year RFS 34% versus 35%, P = 0.81) or OS (45% versus 46%, P = 0.73). In a Cox proportional hazards model, tumour size, number of metastatic lymph nodes, frequency of metastatic nodes in relation to total number of nodes removed, degree of anaplasia, age, and menostasia within the first year after operation were significant independent prognostic factors for RFS, and the same factors except age for OS. No significant interactions with TAM were seen. Thus, in this group of pre- and perimenopausal high-risk early breast cancer patients with heterogeneous receptor status given CMF i.v., concurrent TAM for 1 year did not improve the outcome. These results do not exclude that receptor positive patients may benefit from adjuvant TAM for longer periods given sequentially to chemotherapy.     

Prognostic effect of amenorrhoea and elevated serum gonadotropin levels induced by adjuvant chemotherapy in premenopausal node-positive breast cancer patients

The purpose of the study was to determine the correlation between prognosis and chemotherapy induced amenorrhoea or elevated gonadotropin levels in node-positive breast cancer patients. Since we have previously found a better prognosis in patients with more profound leucopenia induced by adjuvant chemotherapy, we examined whether this effect was mediated through more efficient induction of amenorrhoea. The study population consisted of 126 premenopausal, primarily operable, node-positive breast cancer patients treated with cyclophosphamide, methotrexate and 5-fluorouracil (CMF) adjuvant chemotherapy at the Department of Oncology, Helsinki University Central Hospital between 1990 and 1993. 12 months after the beginning of adjuvant chemotherapy, the patients were divided into groups with respect to their menstrual function (regular menstruation, irregular menstruation or amenorrhoea). Information about menstruation status and serum concentration of follicle stimulating hormone (FSH) and oestradiol were recorded at 12 and 24 months from the beginning of adjuvant chemotherapy. Median follow-up time was 72 months. Women who experienced amenorrhoea or had irregular menstruation after chemotherapy had a significantly better 5-year disease-free survival (DFS) in univariate analysis than women who continued to menstruate (P = 0.02). Amenorrhoea and irregular menstruation were associated with a better DFS among patients with oestrogen receptor (ER) positive primary tumours (P = 0.007), whereas no such association was found in ER negative cases (P = 0.86). 5-year overall survival (OS) in univariate analysis was also better in patients who experienced amenorrhoea (81%) or who had irregular menstruation (90%) after chemotherapy as compared with patients with regular menstruation (68%; 81 versus 68%, P = 0.05). The serum FSH level did not correlate significantly with outcome irrespective of the cut-off point chosen. Nodal status, tumour size and menstruation status after chemotherapy were also significantly associated with DFS in a multivariate analysis. The menstruation status after chemotherapy lost its significance for OS in a multivariate analysis whilst the number of affected lymph nodes, tumour size and oestrogen/progesterone receptor status retained their impact. There was no association between the degree of leucopenia and induction of amenorrhoea by CMF. Chemotherapy-induced ovarian function suppression (amenorrhoea/irregular menstruation) after chemotherapy had a favourable effect on DFS in premenopausal breast cancer patients. The post-chemotherapy menstruation status is a clinically usable marker for sufficient endocrine effect of chemotherapy in ER/PR-positive patients in all premenopausal age groups. FSH level seemed to be a less reliable indicator of the castration effect of adjuvant chemotherapy in this study.     

Taxane-Based Regimens as Adjuvant Treatment for Breast Cancer: a Retrospective Study in Egyptian Cancer Patients

Background: To evaluate the impact of adding taxanes to anthracycline-based regimens in the adjuvant settingin localized young female breast cancer patients on the overall survival (OS) and the disease free survival (DFS).Materials and Methods: This retrospective study included all female breast cancer patients who were candidatesfor adjuvant chemotherapy presenting to Kasr Al Ainy centre of clinical oncology and Cairo oncology centre(Cairo Cure) in the period from January 2005 till December 2010. Results: Our study included 865 patients, 732of whom received anthracycline based regimens and 133 taxane based regimens. The mean age of patients was39 years. After a median follow up of 50 months the median DFS was 48.4 months. Survival analysis indicatedthat the tumor size (>5cm vs. <5cm) p=0.001), nodal involvement (Yes vs. No) p=0.0001) and pathology (invasivelobular vs. ductal) p=0.048) affected DFS. As regards hormonal status, ER, PR and HER 2neu positive patientshad longer DFS (p=0.001, 0.003, 0.106). On multivariate analysis DFS was affected by tumor size and lymph nodeinvolvement (p=0.014, 0.007). Subgroup analysis showed improvement in arms treated with taxanes in terms ofDFS with positive Her2neu, ER and PR, but this was not statistically significant. Conclusions: Adding adjuvanttaxanes to anthracyclines is beneficial for treatment of localized breast cancer among all subgroups, especiallyhigher risk groups .The type of adjuvant chemotherapy regimens and tumor characteristics have direct effectson DFS.     

Survival analyses from the ZEBRA study. goserelin (Zoladex) versus CMF in premenopausal women with node-positive breast cancer

The Zoladex Early Breast Cancer Research Association (ZEBRA) trial compared the efficacy and tolerability of goserelin (Zoladex) with cyclophosphamide, methotrexate and 5-fluorouracil (CMF) chemotherapy in pre-/perimenopausal women with node-positive early breast cancer. The results of disease-free survival (DFS) analyses have already been published. Here we present an update including data on overall survival (OS) from the ZEBRA trial at a median follow-up of 7.3 years. In patients with oestrogen receptor (ER)-positive tumours, non-inferiority of goserelin versus CMF for OS was shown; goserelin was again shown to be equivalent to CMF for DFS. This updated analysis has demonstrated that the two treatments are also equivalent for distant disease-free survival (DDFS). In patients with ER-negative disease, goserelin was inferior to CMF for DFS, DDFS and OS. This follow-up analysis confirms the previously reported outcomes from the ZEBRA trial and demonstrates that goserelin offers an effective alternative to CMF chemotherapy for adjuvant therapy of premenopausal patients with ER-positive, node-positive early breast cancer.     

Adjuvant treatment for early breast cancer: the Ludwig breast cancer studies

The Ludwig Breast Cancer Study Group conducted four concomitant trials involving adjuvant chemotherapy and endocrine therapy. In Ludwig I, adjuvant combination chemotherapy was used with or without prednisone to treat premenopausal and perimenopausal women with metastases in 1-3 axillary lymph nodes. The impact of adding low-dose, continuous prednisone (7.5 mg/day) to an adjuvant, chemotherapy regimen of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) was investigated in a randomized trial of 491 premenopausal and perimenopausal patients with operable breast cancer and metastases in 1-3 axillary lymph nodes. As a consequence of lower hematologic toxicity, a significantly higher dose of CMF could be administered with added prednisone (P less than 0.0001). However, at the 4-year median follow-up, no significant improvement was observed in disease-free survival (DFS) (73% vs. 77%; P = 0.35) or overall survival (OS) (both 86%; P = 0.73). Induced amenorrhea was associated with a longer DFS for younger patients, those who received lower CMF doses, and those with tumors that were estrogen receptor (ER) positive. In Ludwig III, adjuvant therapy was administered to younger postmenopausal women in a study of chemotherapy plus endocrine therapy versus endocrine therapy alone versus mastectomy alone. In this randomized trial of 463 postmenopausal women 65 years of age or younger with axillary node metastases, treatment with the combination of CMF plus low-dose prednisone and tamoxifen (CMFp + T), was compared to endocrine therapy alone (p + T) or to no further treatment after total mastectomy and axillary clearance. At a median follow-up of 4 years, the DFS was 61% for the CMFp + T group, compared with 48% for the p + T group (P = 0.01) and 31% for the observation group (P less than 0.0001). The 4-year OS rates were not statistically different (76%, 67%, and 68%, respectively; P = 0.30). Treatment with CMFp + T reduced local, regional, and distant metastases and was equally effective in improving DFS in patients with ER-positive or ER-negative tumors. In Ludwig II, chemotherapy was given with or without oophorectomy in premenopausal and perimenopausal patients with metastases in 4 or more axillary nodes.(ABSTRACT TRUNCATED AT 400 WORDS)     

A comparison of the outcomes of non-randomised chemotherapy regimens in node positive breast cancer

Adjuvant chemotherapy increases disease-free survival (DFS) and overall survival (OS) following surgery for breast cancer. However, debates concerning the type of adjuvant chemotherapy continue. The effect of adjuvant chemotherapy on loco-regional recurrence-free survival (LFS) was also reported. The present study was undertaken to compare the results of adjuvant FAC (5-fluorouracil, Doxorubicin, Cyclophosphamide) and CMF (Cyclophosphamide, Methotrexate, 5-fluorouracil) chemotherapy on DFS, OS and LFS for node positive breast carcinoma treated with mastectomy in a non-randomised setting. Data from 688 consecutive lymph node positive breast cancer patients who underwent radical or modified radical mastectomy and received adjuvant FAC (600/60/600 mgr/m2 for 6 cycles every three weeks) or CMF (600/40/600 mgr/m2 for 6 cycles on days land 8 every four weeks) chemotherapy were reviewed. The effect of FAC on DFS, OS and LFS as compared with CMF was analysed. Survival curves were generated by the Kaplan-Meier method, and a multivariate analysis was performed by the Cox proportional hazard model. Adjuvant FAC was found to improve DFS, OS and LFS. 5-year DFS, OS and LFS were longer for patients treated with FAC as compared to CMF (67% versus 53%, p < 0.001; 77% versus 66%, p < 0.001, and 97% versus 91%). Adjusted hazard ratio (HR) for potential risk factors and tamoxifen treatment showed that FAC treated patients much benefitted in terms of survival as compared to CMF treated patients (HR 0.53, CI 0.40-0.69 for DFS; HR 0.48, CI 0.35-0.65 for OS, and HR 0.33, CI 0.16-0.65 for LFS). In conclusion, adjuvant FAC improves DFS, OS and LFS as compared to CMF in node positive breast carcinoma patients treated with mastectomy.     

男性乳腺癌的临床病理特征和预后分析

目的 分析男性乳腺癌(MBC)患者的临床病理特征,并探讨影响其预后的因素.方法 对23例MBC患者的病历资料进行回顾性分析.采用Kaplan-Meier法计算患者的生存率,并对影响患者预后的危险因素进行分析.结果 23例MBC患者的发病年龄为37~82岁,中位年龄61.6岁;肿瘤平均直径为3.8 cm.全组患者的3年、5年、10年总生存率分别为84.0%、61.6%、54.8%;3年、5年、10年无病生存率分别为63.1%、51.6%、51.6%.单因素分析结果显示,TNM分期、原发肿瘤大小、腋窝淋巴结是否转移对MBC患者的5年总生存率和无病生存率均有影响(P﹤0.05);激素受体状态对MBC患者的5年生存率有影响(P﹤0.05),对MBC患者的5年无病生存率无影响(P﹥0.05).结论 TNM分期、原发肿瘤大小、腋窝淋巴结是否转移是影响MBC患者5年总生存率和无病生存率的预后因素;激素受体状态是影响MBC患者5年生存率的预后因素.早期诊断及综合治疗是延长MBC患者生存期的关键.     

Randomized, controlled trial of cyclophosphamide, methotrexate, and fluorouracil versus cyclophosphamide, doxorubicin, and fluorouracil with and without tamoxifen for high-risk, node-negative breast cancer: treatment results of Intergroup Protocol INT-0102.

PURPOSE: We evaluated the efficacy of cyclophosphamide, methotrexate, and fluorouracil (CMF) versus cyclophosphamide, doxorubicin, and fluorouracil (CAF) in node-negative breast cancer patients with and without tamoxifen (TAM), overall and by hormone receptor (HR) status. PATIENTS AND METHODS: Node-negative patients identified by tumor size (> 2 cm), negative HR, or high S-phase fraction (n = 2,690) were randomly assigned to CMF, CAF, CMF + TAM (CMFT), or CAF + TAM (CAFT). Cox regression evaluated overall survival (OS) and disease-free survival (DFS) for CAF versus CMF and TAM versus no TAM separately. Two-sided CIs and one-sided P values for planned comparisons were calculated. RESULTS: Ten-year estimates indicated that CAF was not significantly better than CMF (P = .13) for the primary outcome of DFS (77% v 75%; HR = 1.09; 95% CI, 0.94 to 1.27). CAF had slightly better OS than CMF (85% v 82%, HR = 1.19 for CMF v CAF; 95% CI, 0.99 to 1.43); values were statistically significant in the planned one-sided test (P = .03). Toxicity was greater with CAF and did not increase with TAM. Overall, TAM had no benefit (DFS, P = .16; OS, P = .37), but the TAM effect differed by HR groups. For HR-positive patients, TAM was beneficial (DFS, HR = 1.32 for no TAM v TAM; 95% CI, 1.09 to 1.61; P = .003; OS, HR = 1.26; 95% CI, 0.99 to 1.61; P = .03), but not for HR-negative patients (DFS, HR = 0.81 for no TAM v TAM; 95% CI, 0.64 to 1.03; OS, HR = 0.79; 95% CI, 0.60 to 1.05). CONCLUSION: CAF did not improve DFS compared with CMF; there was a slight effect on OS. Given greater toxicity, we cannot conclude CAF to be superior to CMF. TAM is effective in HR-positive disease, but not in HR-negative disease.     

3-year results of docetaxel-based sequential and combination regimens in the adjuvant therapy of node-positive breast cancer: a pilot study

BACKGROUND: Docetaxel has proven efficacy in metastatic breast cancer. In this pilot study, we explored the efficacy/feasibility of docetaxel-based sequential and combination regimens as adjuvant therapy of node-positive breast cancer. PATIENTS AND METHODS: From March 1996 till March 1998, four consecutive groups of patients with stages II and III breast cancer, aged < or = 70 years, received one of the following regimens: a) sequential Doxorubicin (A) --> Docetaxel (T) --> CMF (Cyclophosphamide+Methotrexate+5-Fluorouracil): A 75 mg/m q 3 wks x 3, followed by T100 mg/m2 q 3 wks x 3, followed by i.v. CMF Days 1+8 q 4 wks x 3; b) sequential accelerated A --> T --> CMF: A and T administered at the same doses q 2 wks with Lenograstin support; c) combination therapy: A 50 mg/m2 + T 75 mg/m2 q 3 wks x 4, followed by CMF x 4; d) sequential T --> A --> CMF: T and A, administered as in group a), with the reverse sequence. When indicated, radiotherapy was administered during or after CMF, and Tamoxifen after CMF. RESULTS: Ninety-three patients were treated. The median age was 48 years (29-66) and the median number of positive axillary nodes was 6 (1-25). Tumors were operable in 94% and locally advanced in 6% of cases. Pathological tumor size was >2 cm in 72% of cases. There were 21 relapses, (18 systemic, 3 locoregional) and 11 patients (12%) have died from disease progression. At median follow-up of 39 months (6-57), overall survival (OS) was 87% (95% CI, 79-94%) and disease-free survival (DFS) was 76% (95% CI, 67%-85%). CONCLUSION: The efficacy of these docetaxel-based regimens, in terms of OS and DFS, appears to be at least as good as standard anthracycline-based adjuvant chemotherapy (CT), in similar high-risk patient populations.     

Prognostic factors in node positive primary breast cancer patients treated with adjuvant CMF.

The influence of various patient and disease-related parameters on survival (S) and disease-free survival (DFS) in 217 node positive primary breast cancer patients treated with surgery followed by adjuvant i.v. cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) was evaluated by univariate and multivariate analyses. Five year actuarial S and DFS were 73.3% and 54.8%, respectively. Univariate analysis revealed that patient age, number of involved axillary nodes and ER status had a significant impact on both S and DFS. PgR positive tumors had improved DFS but no S difference was observed. Menopausal status predicted S but not DFS. Primary tumor size and CMF-induced amenorrhea did not predict disease outcome. Multivariate analysis demonstrated that only degree of nodal involvement and PgR status had independent significant impact on prognosis. Both S and DFS are significantly influenced by the number of involved nodes, whereas improved DFS but not S was evident in patients with PgR positive tumors.     

Comparison of CVF (Cyclophosphamide+Vinorelbine+5-Fluorouracil) and CMF (Cyclophosphamide+Methotrexate+5-Fluorouracil) Adjuvant Chemotherapy in Early Breast Cancer

Purpose

Our study aimed to evaluate the feasibility of adjuvant cyclophosphamide/vinorelbine/5-fluorourail (CVF) chemotherapy as an alternative to cyclophosphamide/methotrexate/5-fluorouracil (CMF) chemotherapy for treating early breast cancer.

Methods

One hundred and forty-nine patients were randomly assigned to CMF or CVF adjuvant chemotherapy for treating their early stage breast cancer between September 2000 and December 2007. The disease-free survival (DFS), the overall survival (OS), and the toxicity profiles of both groups were compared.

Results

Sixty-seven patients underwent CMF chemotherapy whereas 82 patients underwent CVF chemotherapy. The DFS and OS were 88 months (95% confidence interval [CI], 76-101 months) and 94 months (95% CI, 83-104 months), respectively for the CMF group, and 97 months (95% CI, 93-101 months), and 101 months (95% CI, 98-104 months), respectively for the CVF group. However, those survival gains of the CVF group were not statistically significant (p-value=0.069 for the DFS and 0.99 for the OS). The CVF group showed a favorable toxicity profile in terms of the grade 3/4 hematologic toxicities as compared to that of the CMF group.

Conclusion

Clinical outcome of CVF chemotherapy was comparable to CMF with a favorable toxicity profiles. However, it is difficult to conclude the feasibility of CVF regimen because of small number of studied patients.     

Thirty-year follow-up of chemo/hormonal therapy in node-positive breast cancer

Results of a thirty-year follow-up of a clinical trial of chemo-hormonal therapy are reported. Eligible patients had recently diagnosed operable breast cancer, positive lymph nodes, no previous history of cancer, age less than 76 years, and no evidence of metastatic disease. A total of 311 patients were stratified by estrogen receptor (ER) status and number of axillary nodes involved with tumor. After stratification, patients were randomly assigned to one of three treatment regimens: cyclophosphamide, methotrexate and 5-fluorouracil (CMF) for 1 year; CMF chemotherapy combined with anti-estrogen therapy (tamoxifen) for 1 year; or CMF plus tamoxifen with BCG during the second year. The endpoint of the trial was a first recurrence. Factors measured at diagnosis and used in the analyses were age, body mass index, ER status, menopausal status, number of positive nodes, tumor diameter, Charlson comorbidity index, socioeconomic status, and race. Causes of death and incidence of other cancer primaries were obtained from death certificates and medical records. Patients treated with tamoxifen had a marginally longer disease-free survival (hazard ratio (HR) = 0.83, 95% CI ≡ [0.66, 1.04]) and statistically significant longer overall survival (HR = 0.77, 95% CI ≡ [0.63, 0.96]) that decreased with time. Incidence of other primary cancers and causes of death were similar for the two treatment groups. The addition of 1 year of tamoxifen to CMF therapy provides an early disease-free and overall survival advantage; however long-term effects are negligible. Similarly, the survival advantage of patients diagnosed with ER+ tumors persists for the first two decades after diagnosis. Supported by Public Service contracts CA-78517 National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA     

What are the prognostic factors in operable breast cancer without histologic axillary lymph node invasiveness. Results of an uni- and multifactorial analysis

Between October 1977 and December 1983, 379 consecutive patients have been treated for unilateral, non metastatic breast cancer, either with conservative (n = 205) or radical surgery (n = 174), with axillary dissection in all the cases. None of them had histologically proved lymph node involvement. Adjuvant radiotherapy was given in 268 cases. Estrogen receptor (ER) and progesterone receptor (PR) levels were measured on each tumor. Levels greater than 5 fmoles/mg cytosolic protein were considered as positive for both ER and PR. At 5 years, overall survival (OS) and disease-free survival (DFS) are respectively 88% and 79%. Unifactorial analysis using KAPLAN and MEIER estimates and Logrank test revealed that OS was significantly related to age, tumor size, histopathological grading, ER and PR. DFS was significantly related to the same factors. Menopausal status, number of intra mammary tumor foci, previous familial history of breast cancer were not significant. Multifactorial analysis revealed that DFS was significantly related to age (bad prognosis [bp]: less than or equal to 37 years old), tumor size, histopathological grading (bp: SBR = 3) and that OS was significantly related to tumor size and PR (bp: PR less than or equal to 5 fmoles/mg protein). A prognostic score was obtained which sampled our patients into 3 significantly different (P less than 0.0001) groups with high, intermediate and low risk of relapse. These results suggest that tumor size, histopathological grading and PR have their own prognostic weight in histologically node negative breast cancer. Grouping these factors together allows to define a high risk relapse group that could benefit from adjuvant treatment.     

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.     

Metaplastic breast cancer: Prognosis and response to systemic therapy

Background: Metaplastic breast cancer is a rare disease with little information available to guide therapy. The goals of this study were to describe the patient characteristics, systemic therapies and clinical outcomes of all patients with primary metaplastic breast cancer treated at Mayo Clinic between 1976 and 1997.Patients and methods: Patients were identified through the medical index of Mayo Clinic. Clinical information was abstracted from the medical record of each patient. A literature search using MEDLINE and CANCERLIT for the years 1966–1997 was performed to identify all previously reported case series in the English language containing 10 or more patients.Results: Twenty-seven patients were identified with a median age at diagnosis of 59 years (range 39–90 years). The median tumor size was 3.4 cm (range 0.5–7.0 cm). One patient had metastatic disease at presentation. Twenty-three patients had information available on nodal status, estrogen receptor (ER) and progesterone receptor (PR) status. Twenty patients (87%) were node-negative and three patients (13%) were both ER and PR positive. Disease-free survival (DFS) and overall survival (OS) were assessed for those who presented with local-regional disease. The three-year DFS was 40% (95% CI: 23%–73%) and the three-year OS was 71% (95% CI: 51%–97%). In univariate analysis, those patients 60 years of age or older at diagnosis were found to have an increased DFS (P = 0.011). Among those with prior estrogen use, both DFS (P = 0.022) and OS (P = 0.003) were decreased. Thirteen patients (50%) developed metastases with a median DFS time of 2.4 years. Ten different chemotherapy regimens were utilized for metastatic disease and one partial response was observed. There were no responses to tamoxifen in four patients with metastatic disease. Median survival after the development of metastases was eight months.Conclusions: Despite presenting more commonly as node-negative disease, DFS and OS in metaplastic breast cancer is decreased compared to typical adenocarcinomas. Systemic therapy also appears to be less effective. Patients with metaplastic breast cancer, particularly those with metastatic disease could be appropriate candidates for innovative therapeutic regimens.     

Percent positive axillary lymph node metastasis predicts survival in patients with non-metastatic breast cancer

PURPOSE: We retrospectively evaluated the impact of percent positive axillary nodal involvement on the therapeutic outcomes in patients with non-metastatic breast cancer receiving postmastectomy radiotherapy and chemotherapy. MATERIALS AND METHODS: Between January 1994 and December 2002, the medical records of 939 eligible non metastatic breast carcinoma patients were analyzed. Chest wall radiotherapy was indicated in case of positive surgical margin, tumor size equal or more than 4 cm, skin-fascia invasion. Lymphatic irradiation was applied for more than three metastatic axillary lymph nodes, incomplete axillary dissection (<10 lymph nodes), extracapsular extension or perinodal fat tissue invasion. A total dose of 50 Gy was given to chest wall and lymph node regions with 2 Gy daily fractions. Statistical analyses were performed by Kaplan-Meier method, Log-rank test and Cox's regression analysis. RESULTS: The median follow-up for all patients alive was 62 months. The 5-year overall survival (OS) and disease-free survival (DFS) for entire cohort were 81%, and 65%, respectively. Univariate analysis for OS revealed significance for tumour size (< or =5 cm vs. >5 cm, p<0.001), metastatic nodal involvement (0 vs. 1-3 vs. >4 LN, p<0.001), percent positive nodal involvement ([metastatic nodes/total nodes removed] x 100; 0 vs. < or =25% vs. 26-50% vs. >50%, p<0.001), surgical margin status (negative vs. positive, p=0.05), and hormonal treatment (present vs. absent, p=0.03). DFS had similarly significance for age (< or =40 years vs. >40 years, p=0.006), tumour size (0.02), metastatic nodal involvement (p<0.001), percent positive nodal involvement (p<0.001), and perinodal invasion (present vs. absent, p=0.01). Multivariate analysis revealed significance for tumour size, percent positive nodal involvement, hormonal treatment, and surgical margin status for OS. Age and percent positive nodal involvement were found to be significant for DFS. CONCLUSION: Percent positive nodal involvement was found to be a significant prognostic factor for survival in all end-points.     

Prognostic impact of multidrug resistance gene expression on the management of breast cancer in the context of adjuvant therapy based on a series of 171 patients

Study of the prognostic impact of multidrug resistance gene expression in the management of breast cancer in the context of adjuvant therapy. This study involved 171 patients treated by surgery, adjuvant chemotherapy+/-radiotherapy+/-hormonal therapy (mean follow-up: 55 months). We studied the expression of multidrug resistance gene 1 (MDR1), multidrug resistance-associated protein (MRP1), and glutathione-S-transferase P1 (GSTP1) using a standardised, semiquantitative rt-PCR method performed on frozen samples of breast cancer tissue. Patients were classified as presenting low or high levels of expression of these three genes. rt-PCR values were correlated with T stage, N stage, Scarff-Bloom-Richardson (SBR) grade, age and hormonal status. The impact of gene expression levels on 5-year disease-free survival (DFS) and overall survival (OS) was studied by univariate and multivariate Cox analysis. No statistically significant correlation was demonstrated between MDR1, MRP1 and GSTP1 expressions. On univariate analysis, DFS was significantly decreased in a context of low GSTP1 expression (P = 0.0005) and high SBR grade (P = 0.003), size > or = 5 cm (P = 0.038), high T stage (P = 0.013), presence of intravascular embolus (P = 0.034), and >3 N+ (P = 0.05). On multivariate analysis, GSTP1 expression and the presence of ER remained independent prognostic factors for DFS. GSTP1 expression did not affect OS. The levels of MDR1 and MRP1 expression had no significant influence on DFS or OS. GSTP1 expression can be considered to be an independent prognostic factor for DFS in patients receiving adjuvant chemotherapy for breast cancer.