The course of serum HER-2/neu levels as an independent prognostic factor for survival in metastatic breast cancer

The purpose of this study was to determine the impact of serum HER-2/neu level dynamics during the course of disease and treatment on the prognosis of patients with metastatic breast cancer. Two thousand and thirty-eight serum samples collected sequentially after disease relapse in 286 patients with metastatic breast cancer were measured by Bayer Immuno 1 trade mark assay retrospectively for serum HER-2/neu (cut-off level 15 ng/ml). One hundred and five patients (37%) presented with serum HER-2/neu continuously 相似文献   

Synchronisation by hydroxyurea does not affect the sensitivity of CEM-C7 lymphoblasts to glucocorticoids

The efficacy of high-dose intramuscular MPA therapy in controlling progressive measurable metastatic breast carcinoma was assessed in 32 women. In addition serial measurements of MPA blood levels were carried out in 20 of the patients and subjective effects of treatment were monitored in detail in 18 of the women. Overall 6 patients (19%) gained an objective response and a further 7 (22%) experienced disease stasis from 4-17 months whilst on treatment. Significant differences in serum MPA levels were seen between responders and non-responders, objective tumour shrinkage only being seen in those patients who rapidly attained, and sustained, blood levels in excess of 100 ng ml-1. Subjective assessment showed no evidence of a euphoriant effect of MPA therapy in the non-responders group.     

Combination therapy with medroxyprogesterone acetate and tegafur in tamoxifen- and adriamycin-resistant advanced breast cancers

Medroxyprogesterone acetate (MPA) plus Tegafur (TGF) therapy was performed to evaluate the efficacy in a treatment for Tamoxifen- and Adriamycin-resistant advanced breast cancers. The patients were medicated in different doses on 800 mg or 1,200 mg daily po for MPA and TGF. Sixteen patients were evaluable in this trial. According to criteria of the Japan Mammary Cancer Society, one was regarded as CR and five as PR. The response rate was 37.5%. There was no difference in response rates between premenopausal and postmenopausal patients or ER positive and negative patients. No difference was noted either in response rates and incidence of side effects between two different doses of MPA. This means that an 800 mg daily dose of MPA lower than the recommended 1,200 mg might be better in the treatment for Japanese patients with advanced breast cancers. Gastrointestinal disorders, bone marrow suppression and liver dysfunction which could be found in high-dose TGF therapy, were not frequently observed in this trial. Patients could expect good quality of life during the treatment because of fewer side effects. This combination therapy with MPA and TGF was regarded as a good modality for the treatment of Tamoxifen- and Adriamycin-resistant advanced breast cancers.     

Aminoglutethimide and medroxyprogesterone acetate in the treatment of patients with advanced breast cancer. A phase II study of the Association of Medical Oncology of the German Cancer Society (AIO)

One hundred twenty-eight women with advanced metastatic breast cancer were treated with a combination of aminoglutethimide (AG) (1000 mg orally, daily) and medroxyprogesterone acetate (MPA) (1500 mg orally, daily for six weeks and thereafter 500 mg orally, daily; omitting cortisone substitution). AG/MPA did not lead to side effects other than those described under AG or MPA monotherapy. Mental and personality changes seem to be more severe and frequent under combined therapy than under monotherapy. Impairment of mental functions, depressive syndromes, fatigue, ataxia, skin rash, and transient increase of gammaglutamyl transferase appeared and disappeared within the first 4 to 6 weeks of treatment. Objective remissions of at least 3 months duration from initiation of therapy were seen in 21 of 128 patients (21.9%) (3.9% complete remission [CR], 18% partial remission [PR]). A no change (NC) status occurred in an additional 25.8%. The remission duration (mean and range) was 19 (10.5-54) for CR, 16.5 (4.5-52+) for PR and 6 (3-27) months for NC patients. The highest response rate was registered for patients with only bone involvement (PR, 11; and NC, 11 of 26 patients). There was a distinct correlation of response to prior systemic treatment, receptor status of the primary tumor, disease-free interval, menopausal status, age and condition of the patient. PR was obtained in 4 of 20 patients with receptor-negative primary tumors. These results justify a prospective trial comparing AG/MPA with other forms of endocrine therapy in selected patient subgroups.     

Trends of IL-6 and IL-8 levels in patients with recurrent breast cancer: preliminary report

BACKGROUND: We reported that IL-6 and IL-8 levels at the beginning of treatment are predictive indicators of response to therapy and prognosis of patients with recurrent breast cancer. The aim of this study was to investigate the trend of IL-6 and IL-8 levels in heavily pretreated patients with recurrent breast cancer. METHODS: Cytokine level trends in 12 patients heavily pretreated with anthracyclines were studied. Patients were divided into two groups according to the objective response. There were 5 partial response (PR)/no change (NC), and 7 progressive disease (PD) patients. Blood was taken every four weeks. IL-6 was measured by chemiluminescent enzyme immunoassay. IL-8 was measured by ELISA. RESULTS: The pretreatment level of IL-6 in the PR/NC group (11.0+/-2.1 pg/ml) was significantly lower than that (15.3+/-2.7 pg/ml) in the PD group. However, there was no difference in IL-8 level between the PR/NC group (12.5+/-5.5 pg/ml) and the PD group (11.5+/-1.1 pg/ml). IL-6 levels in the PR/NC group were maintained within normal levels or decreased to within normal levels after treatment, while levels of IL-6 in the PD group gradually increased until the time of patient death. A decrease in IL-8 level after treatment was observed in only one patient in the PR/NC group. Mild increase of IL-8 levels was observed in the PD group. CONCLUSION: Continuous elevation of IL-6 levels indicates poor prognosis in heavily pretreated patients with recurrent breast cancer. Combination therapy including agents that reduce IL-6 levels will be a new strategy for aggressively treating recurrent breast cancer.     

Correlation of serum tumor markers in advanced germ cell tumors with responses to chemotherapy and surgery

Remission rates induced by chemotherapy alone or by combined chemotherapy and surgery were analyzed in relation to specific serum tumor marker abnormalities immediately before treatment in 103 patients with Stage III or bulky Stage II nonseminomatous germ cell tumors. Complete remission occurred in 92% (12 of 13) of patients with normal levels of alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG), in 26% (6/23) with elevated AFP only, in 46% (13/28) with elevated HCG only, and in 39% (13/36) with abnormalities of both AFP and HCG. Patients with elevated AFP less frequently had a complete remission (CR) to chemotherapy (CR, 34% versus 61% with normal AFP), but benefitted from adjunct surgery (CR, up to 59%). Patients with very high (greater than 1000 ng/ml) serum AFP or HCG responded poorly to chemotherapy (CR, 17%) but especially large tumor burdens may have contributed to these unfavorable responses. Patients with both minimal and advanced metastatic disease had higher CR rates if they had serum tumor marker levels below rather than above 1000 ng/ml. Adjunct surgery eliminated the correlation between the "poor prognostic factors" associated with specific marker abnormality and an incomplete response to chemotherapy by rendering a significant number of such patients free of disease through resection of residual metastatic deposits.     

Caf versus caf plus medroxyprogesterone acetate for treatment of liver metastases of breast cancer

A controlled randomized trial was conducted to compare the effectiveness of a CAF therapy including cyclophosphamide (CPA), adriamycin (ADR) and 5-fluor-ouracil (5FU) with that of CAF plus medroxyprogesterone acetate (MPA) therapy including CPA, ADR and 5FU plus MPA for the treatment of liver metastases from breast cancer. A total of 34 patients with unresectable liver metastases from breast cancer were divided into two treatment groups (CAF and CAF + MPA) with stratification for estrogen receptor status. The response rate was 13% (2 PR in 16 patients) for CAF therapy and 22% (1 CR and 3 PR in 18 patients) for CAF plus MPA therapy. There was no significant difference in response rates, median survival periods and survival rates between the two treatment groups. However, CAF therapy had significantly more toxicity than did CAF plus MPA therapy. The findings of this study suggested that CAF plus MPA therapy is a well-tolerated and effective treatment for patients with liver metastases of breast cancer.     

Cyclic and sequential therapy with tamoxifen and medroxyprogesterone acetate in metastatic breast cancer

A clinical trial of sequential tamoxifen and medroxyprogesterone acetate (MPA) was carried out in 36 women with metastatic breast cancer in order to evaluate the therapeutic efficacy of this regimen and to determine if tamoxifen would increase progesterone receptor (PR) levels and thereby increase response to MPA. Fourteen patients (39%) responded to this treatment, with the duration of remission ranging from 2 to 24 + months (the mean and median were 11 months). In 22 patients, PR levels were measured both before and after 7 days of tamoxifen administration. In PR-positive patients, PR changes induced by tamoxifen did not appear to increase the response rate. In PR-negative patients, PR became positive in 3 patients following tamoxifen treatment, with 2 of 3 responding to treatment, whereas in 11 others whose PR levels remained negative, only one response was observed. Our results suggest that potentiation by tamoxifen was not observed, since in our previous study, MPA alone was equally effective. Thus, tamoxifen and MPA should be given independently for palliation of metastatic breast cancer, and MPA should be administered following therapy with tamoxifen.     

血清VEGF、bFGF与乳腺癌生物学行为的关系

目的：探讨VEGF、bFGF与乳腺癌的生物学行为的关系,复发转移患者血清VEGF、bFGF的表达水平与化疗疗效的关系。方法：应用ABC—ELISA方法检测乳腺癌患者血清VEGF、bFGF的表达情况。结果：术前未作放化疗的乳腺癌患者术前血清VEGF、bFGF表达水平明显高于健康体检者、乳腺腺瘤患者（P〈0．05）,也明显高于同组患者术后血清VEGF、bFGF表达水平（P〈0．05）。术前未作放化疗的乳腺癌患者术前血清VEGF、bFGF的表达水平与原发肿瘤的大小、TNM分期、淋巴结转移有关。术前未作放化疗的乳腺癌患者术前血清VEGF与bFGF的表达水平呈正相关（r=0．210,P〈0．05）。乳腺癌复发转移组化疗前血清VEGF、bF—GF的表达水平比健康体检者及无病生存组明显增高（P〈0．05）。乳腺癌复发转移组化疗后CR＋PR组血清VEGF、bFGF表达水平比化疗前明显减低（P〈0．05）;化疗后NC＋PD组血清VEGF、bFGF表达水平比化疗前略高,但没有显著性差异（P〉0．05）。乳腺癌复发转移组化疗后CR＋PR组血清VEGF、bFGF表达水平比NC＋PD组明显降低（P〈0．05）。结论：乳腺癌患者血清VEGF、bFGF的表达水平与乳腺癌生物学行为有关,而且与化疗疗效有关,提示通过检测乳腺癌患者血清VEGF、bFGF的表达水平可能对乳腺癌的诊断、客观预测肿瘤的复发转移、选择合理有效的治疗方案有一定的参考价值。     

Serum VEGF levels in women with a benign breast tumor or breast cancer

Vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis and vascular permeability. Many types of malignant human tumors have been shown to produce VEGF. Recently, increased serum concentrations of VEGF (S-VEGF) have been reported in patients with various types of cancer, and high S-VEGF levels have also been associated with unfavorable prognosis. We have now measured S-VEGF in sera taken from 105 patients with a benign breast tumor or breast cancer. None of the women with a benign breast tumor had S-VEGF higher than 328 pg/ml (median, 57 pg/ml) whereas S-VEGF levels in metastatic breast cancer ranged from 7 to 1347 pg/ml (median, 186 pg/ml P=0.0018), and in locoregional breast cancer from 11 to 539 pg/ml (median, 104 pg/ml P=0.13). S-VEGF was higher in patients with locoregional ductal cancer (median, 107 pg/ml) than in those with locoregional lobular cancer (median, 44 pg/ml; P=0.029) or in patients with benign breast tumor (median, 57 pg/ml; P=0.033). Patients with metastatic cancer undergoing therapy had lower S-VEGF than those who had symptomatic treatment only (P=0.021). The results indicate that dissemination of breast cancer may be accompanied by an elevation of circulating VEGF and that primary ductal cancers are associated with higher S-VEGF levels than lobular cancers or benign breast lesions.     

Medroxyprogesterone acetate and cancer cachexia: Interleukin-6 involvement

Cancer cachexia is a significant problem facing both patients and physicians. Many interventions have been tried in an attempt to remedy undernutrition in cancer patients. However, there is no convincing evidence that enteral/parenteral nutrition or the use of anabolic steroids is of any benefit in patients with cachexia. A recent prospective study revealed that oral medroxyprogesterone acetate (MPA) treatment reduces serum levels of interleukin (IL)-6, an important mediator of cancer cachexia, in patients with metastatic breast carcinoma regardless of response to the therapy. A decrease in serum IL-6 levels was well associated with subjective improvement in patients with metastatic breast carcinoma. Furthermore, clinically attainable concentrations of MPA can inhibit the growth of some human pancreatic carcinoma cells by inducing apoptosis in association with the phosphorylation of bcl-2. These results suggest that this agent may contribute to improved quality of life in patients with various cancers.     

Concentrations of galectin-3 in the sera of normal controls and cancer patients.

Galectin-3, a member of the beta-galactoside-binding animal lectins, has been implicated in tumor invasion and metastasis. Using an immunoligand assay, we assessed the circulating levels of galectin-3 in sera from cancer patients as well as from healthy controls. Low serum levels of galectin-3 were detected in healthy individuals (median, 62 ng/ml; range, 20-313 ng/ml; 95th percentile, 184.3 ng/ml). Compared with healthy individuals, galectin-3 serum levels in patients with breast, gastrointestinal, lung, or ovarian cancer, melanoma, and non-Hodgkin's lymphoma were significantly elevated (P = 0.014). Moreover, galectin-3 concentrations in sera from patients with metastatic disease were higher than in sera from patients with localized tumors. Maximum serum concentrations of galectin-3 (median, 320 ng/ml; range, 20-950 ng/ml) were found in patients with metastatic gastrointestinal carcinoma. These results suggest that circulating galectin-3 may play a role in tumor progression. The possibility of using this assay in early-stage cancer to predict metastasis should be studied.     

Soluble Fas and Fas ligand provide new information on metastasis and response to chemotherapy in SCLC patients

BACKGROUND: The Fas/Fas ligand (FasL) system is a major regulator of apoptosis. Chemotherapeutic drugs have been shown to induce Fas expression on the surface of lung cancer cells, and cancer cell apoptosis. However, this mechanism is not considered to be associated with Fas expressed on lung cancer cells. Soluble Fas and FasL concentrations are reportedly elevated in the peripheral blood of patients with lung cancer, but the roles of circulating soluble Fas and FasL in that disease have not been clarified. MATERIALS AND METHODS: We measured the circulating soluble Fas and FasL levels in 21 patients with small cell lung cancer (SCLC), and 12 healthy matched controls, in order to examine whether such ligands could provide any important information and/or reveal any new clinical features of SCLC. RESULTS: In the CR patients, the neuronal specific enolase (NSE), soluble Fas and soluble FasL concentrations were 21.26+/-3.65 ng/ml, 3.58+/-0.19 ng/ml and 0.50+/-0.15 ng/ml, while in the partial response (PR)/no change (NC)/progressive disease (PD) group of patients they were 33.96+/-7.86 ng/ml, 5.29+/-0.29 ng/ml and 0.59+/-0.07 ng/ml, respectively. The NSE, soluble Fas and soluble FasL concentrations were all elevated in the PR/NC/PD patients, however, significant differences were only seen in Fas concentration between CR and PR/NC/PD patients and CR patients and the controls (p<0.001). CONCLUSIONS: Serum soluble Fas and FasL play important roles in the proliferation and metastasis of SCLC, as well as in the cytotoxic reaction and apoptosis induced by anticancer drugs in SCLC. Further study of the mechanisms and participation of circulating soluble Fas and FasL is necessary to develop treatment strategies for SCLC.     

Remarkable response with pembrolizumab plus albumin-bound paclitaxel in 2 cases of HER2-positive metastatic breast cancer who have failed to multi-anti-HER2 targeted therapy

In clinical practice, one subgroup patients of breast cancer might have developed resistance to multi-anti-HER2 targeted drugs(trastuzumab, lapatinib and/or T-DM1) and can not benefit from the anti-HER2 targeted therapy continuously. We attempt to change the next therapic way for these patients. Two patients with metastatic breast cancer who have failed to multi-anti-HER2 targeted therapy were treated with pembrolizumab (2 mg/Kg, day1) plus albumin-bound paclitaxel (125 mg/m², day1,8) every 3 weeks. CT evaluation and HER2 ECD test were performed every 2 cycles. Both of the two patients achieved remarkable response with Partial Remission (PR), meanwhile serum HER2 ECD levels (the upper normal limit is 15 ng/ml) showed a remarkable decreases(compared to the base line decreases 75% and 60% respectively). The results indicate that regimen of pembrolizumab combination with albumin-bound paclitaxel might produce response in patients with HER2-positive metastatic breast cancer who have failed to multi-anti-HER2 targeted therapy.     

Influence of aminoglutethimide on plasma levels of medroxyprogesterone acetate

To confirm that concomitant administration of aminoglutethimide (AG) reduces plasma levels of medroxyprogesterone acetate (MPA), MPA levels were assayed in six patients with advanced breast cancer receiving the two agents. Patients had disease resistant to AG and were studied during conversion to therapy with MPA. Hydrocortisone was discontinued at the commencement of study and MPA introduced and given at a constant dose of 800 mg daily while AG was reduced in dose from 250 mg b.d. to 125 mg b.d. and then discontinued. MPA levels were measured after two weeks at each dose of AG and after two weeks on MPA alone. Mean MPA levels showed a progressive and significant (P less than 0.01) rise as the AG dose was reduced--180 ng ml-1, 250 ng ml-1 and 740 ng ml-1 respectively. MPA levels were always in excess of the accepted therapeutic level of 100 ng ml-1 and plasma cortisol levels fell in parallel with the rise in MPA levels.     

Low-dose oral methotrexate and cyclophosphamide in metastatic breast cancer: antitumor activity and correlation with vascular endothelial growth factor levels.

BACKGROUND: Anticancer chemotherapy is thought to be effective by means of direct cytotoxicity on tumor cells. Alternative mechanisms of efficacy have been ascribed to several common anticancer agents, including cyclophosphamide (CTX), methotrexate (MTX), anthracyclines and taxanes, postulating an antiangiogenic activity. PATIENTS AND METHODS: We evaluated the clinical efficacy and impact on serum vascular endothelial growth factor (VEGF) levels of low-dose oral MTX and CTX in patients with metastatic breast cancer. MTX was administered 2.5 mg bd on days 1 and 2 each week and CTX 50 mg/day administered continuously. RESULTS: Sixty-four patients were enrolled, 63 were evaluable: Eastern Cooperative Oncology Group (ECOG) performance status 0-1, > or =2 sites of metastatic disease (n = 50 patients), progressive disease at study entry (n = 51), 1 regimen for metastatic disease (n = 32) and > or =2 regimens (n = 20). Among the 63 evaluable patients, there were two complete remissions (CR), 10 partial remissions (PR) for an overall response rate of 19.0% (95% CI 10.2% to 30.9%) and an overall clinical benefit (CR+ PR+ stable disease >24 weeks) of 31.7% (95% CI 20.6% to 44.7%). Grade > or =2 leucopenia was registered in only 13 patients. The median serum VEGF level for the subgroup of patients on treatment for at least 2 months decreased with treatment from 315 pg/ml (95% CI 245 to 435) at baseline to 248 pg/ml (95% CI 205 to 311) at 2 months (P <0.001). Both responders and non-responders showed similar reductions in serum VEGF (P = 0.78). After 6 months patients still on treatment had a median VEGF level of 195 pg/ml (95% CI 96 to 355), which was significantly lower than the median baseline values (P = 0.001). CONCLUSIONS: Continuously low-dose CTX and MTX is minimally toxic and effective in heavily pretreated breast cancer patients. A drop in VEGF was associated with the treatment and so alternative hypotheses, other than that of direct toxicity on tumor cells, must be favored when trying to explain the anticancer effect.     

Oral high-dose medroxyprogesterone acetate (MPA) treatment: cortisol/MPA serum profiles in relation to breast cancer regression

Medroxyprogesterone acetate (MPA), a potent synthetic progestin, has been widely used in the hormonal treatment of advanced breast cancer, but presently with varying dose schedules. The availability of a sensitive RIA-method for determination of serum MPA has stimulated the research on MPA serum levels in patients after repeated MPA administration. The aim of this study was to assay blood level profiles of MPA as well as of cortisol during repeated high-dose orally administered MPA. 34 patients with metastatic breast cancer were enrolled in this study. 12 patients died already within the first 4 weeks of MPA treatment due to multiple metastases. The dosage regimen based on the daily oral administration of 1,000 mg MPA suspension. During MPA treatment, a decrease of cortisol serum levels was observed in nearly all patients. Within the observation time of 8 months out of 22 evaluable cases 18.2% responded to the therapy (complete and partial response). No change was observed in 36.4% and progression in 45.5% of the patients. Within the remission (complete and partial) group, a good correlation between constant MPA serum levels above 150 ng/ml and remission was observed. But in the groups with no change and progression no such correlation could be observed.     

A controlled study with medroxyprogesterone acetate (MPA) alone or in combination with cyclophosphamide (CPA) in the treatment of advanced or recurrent breast cancer unresponsive to other therapies. Osaka Study Group for the Treatment of Breast Cancer]

Forty-eight patients with advanced or recurrent breast cancer unresponsive to other therapies were treated orally with medroxyprogesterone acetate (MPA) 1,200 mg/day alone (Group A: 28 patients) or in combination with cyclophosphamide (CPA) 100 mg/day (Group B: 20 patients). Either complete response (CR) or partial response (PR) was obtained in eight (28.6%) patients of Group A and PR in five (25.0%) of Group B. The median duration of the response was 5.3 months in Group A and 4.4 months in Group B. Despite the expected better result of the combined chemo-endocrine therapy for Group B, there were no statistical difference in usefulness between the two regimens. No severe adverse reactions were observed in this study. We conclude that MPA alone is useful for treatment of patients with advanced or recurrent breast cancer unresponsive to other therapies.     

A phase II study of high-dose cyclophosphamide, thiotepa, and carboplatin with autologous marrow support in women with measurable advanced breast cancer responding to standard-dose therapy.

PURPOSE: The study was designed to determine the duration of complete response (CR) for patients with unresectable or metastatic breast cancer treated with high-dose cyclophosphamide, thiotepa, and carboplatin (CTCb) while responding to conventional-dose therapy. METHODS: Eligibility criteria included histologically documented metastatic or unresectable breast cancer, at least a partial response (PR) to conventional-dose therapy, no prior pelvic radiotherapy, cumulative doxorubicin of less than 500 mg/m3, and physiologic age between 18 and 55 years. Patients with inadequate renal, hepatic, pulmonary, and/or cardiac function or tumor involvement of marrow or CNS were excluded. Cyclophosphamide 6,000 mg/m2, thiotepa 500 mg/m2, and carboplatin 800 mg/m2 were given by continuous infusion over 4 days. After recovery, sites of prior bulk disease were to be radiated or resected if feasible. RESULTS: Of 29 registered patients, one died of toxicity (3%; hemorrhage). CRs and PRs continued a median of 16 and 5 months after transplant, respectively (26 and 9 months from initiation of chemotherapy for metastatic disease). Of 10 patients transplanted in CR, four have not progressed at 17 to 31 months after transplantation (25 to 43 months after beginning standard-dose therapy). One of four patients with uptake on bone scan as their only sites of residual disease before transplant and one of three who converted from PR to CR with transplant have not progressed at 27 and 29 months, respectively, after transplant. CONCLUSIONS: CTCb is an intensification regimen with a low mortality that delivers a significantly increased dose of agents with known activity at conventional doses in breast cancer. Although the duration of PR is short as expected, CRs appear to be durable.     

兰他隆治疗绝经后晚期乳腺癌临床观察

目的：观察兰他隆（Lentaron）治疗绝经后复发转移乳腺癌的疗效和副作用。方法：34例绝经后复发转移乳腺癌患者给予兰他隆250mg肌肉注射,每2周1次,至少1个月。结果：34例可评价疗效和毒副作用的患者中,部分缓解（PR）5例,占14．7％,稳定（SD）20例,占58．8％,其中病情稳定≥6个月者12例,占35．3％,临床获益患者（PR＋SD≥6个月）17例,占50．0％,病情进展9例,占26．5％,骨、软组织和内脏转移有效率依次为30．8％（4／13）,13．6％（3／22）和5．3（1／19）,治疗中无严重不良反应。结论：兰他隆治疗绝经后复发转移乳腺癌有一定疗效,药物不良反应轻,患者容易耐受。