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Query: UMLS:C0278488 (metastatic breast cancer)
 7,812 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treatment of metastatic breast cancer based on the estrogen receptor content (ER) of the primary tumor builds on the assumption that the ER status of the primary tumor and the metastases are largely equal. Studies addressing this question have used ligand-binding assays for ER determination and have consequently been subject to the limitations of this technique. Reported disparity rates have been 20%. In order to avoid some of these limitations, we used an immunohistochemical assay in paraffin-embedded tissue. Among a total of 92 examined regional lymph node metastases, ER status was equal with that of their 37 primaries in 84 cases (91%). Semiquantified ER content was significantly correlated in primary tumor and the metastases (r = 0.67, p less than 0.001). Among a total of 51 distant metastases, equal ER status was found in 44 (86%) cases and a quantitative relationship could not be established. Disparities can be due to methodological errors in the histochemical assay or tumor heterogeneity.
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PMID:Relationship between estrogen receptor status in the primary tumor and its regional and distant metastases. An immunohistochemical study in human breast cancer. 321 26

One hundred thirty-eight patients with recurrent or metastatic breast cancer were randomized to receive megestrol acetate 40 mg orally four times daily or tamoxifen 10 mg orally twice a day. Upon treatment failure patients were crossed over to the alternate treatment. Eligibility required that either the estrogen receptor (ER) or progesterone receptor (PR) be positive or that both values be unknown, and that the patients be at least 2 years post-spontaneous menopause or over 50 years of age. Pretreatment characteristics including performance status (PS), disease-free interval (DFI), receptor status, and prior treatment were similar for both groups. Only three patients had previous hormonal therapy while one third had prior chemotherapy. Objective response was determined using strict International Union Against Cancer (UICC) criteria. Seventeen of 61 patients achieved complete response (CR) or partial response (PR) on megestrol (28%) while 20 of 64 patients achieved CR or PR on tamoxifen (31%). Responses of skin and bone lesions were similar for both agents; however, more patients with visceral disease responded to tamoxifen. Response did not correlate with the level of ER or PR but was correlated with age. Both unadjusted and adjusted analysis of time to progression and adjusted analysis (for pretreatment variables) of survival showed significant differences favoring tamoxifen. Six of 44 patients (14%) crossed from megestrol to tamoxifen achieved CR or PR while only two of 38 patients (5%) crossed from tamoxifen to megestrol achieved response. Only one of the original patients randomized to megestrol remains on study, while 12 patients still remain on tamoxifen. These data indicate similar response rates for megestrol and tamoxifen; however, time to progression and overall survival significantly favor tamoxifen when used as first-line therapy in this trial.
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PMID:Megestrol acetate versus tamoxifen in advanced breast cancer: 5-year analysis--a phase III trial of the Piedmont Oncology Association. 329 10

Choices of treatment for patients with estrogen receptor (ER) positive metastatic breast cancer refractory to first-line endocrine therapies include progestins, antiadrenal drugs, and androgens. These treatments should be administered sequentially to achieve maximum palliation of the disease. For ER positive patients with disease that is refractory to endocrine therapies, chemotherapy of choice includes either CMF (cyclophosphamide, methotrexate, fluorouracil) or FAC (fluorouracil, doxorubicin, cyclophosphamide), which is CMF with doxorubicin substituted for methotrexate. Choices of therapy for those with disease refractory to CMF combinations include doxorubicin and vinca alkaloids or mitomycin C combinations. These combinations result in 45% to 55% response rates. For those who do not respond to FAC, the combinations active in refractory disease include vinca alkaloids and mitomycin C combinations. Other drugs with 15% to 25% antitumor activity include mitoxantrone, elliptinium acetate, CHIP (cis-dichloro-transdihydroxy-bis-isoprophylamine platinum), peptichemio, and fluorouracil infusion.
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PMID:Chemotherapeutic approaches to advanced breast cancer. 329 20

While hormone receptor values are extremely valuable in breast cancer management, many variables leading to falsely negative receptor results should be considered before clinical decision making in the setting of metastatic disease. At the Papanicolaou Comprehensive Cancer Center in Miami, Florida 271 patients with metastatic breast cancer received tamoxifen over a 4-year period. Only 40 of the 204 patients (19.6%) with available estrogen receptor assay information had pretreatment receptor values classically considered receptor-poor. While four patients had inevaluable tamoxifen trials and 12 patients had "compassionate" use in end-stage situations, 24 patients received tamoxifen therapy in the face of receptor-poor values because of clinical or histopathological correlates suggesting the possibility of false negative assay results. Six of 36 evaluable patients (16.6%), including those treated on "compassionate grounds," responded to tamoxifen, while 6 of 24 more highly selected patients (25%) responded. Response durations in these six patients were 11, 12, 28, 28+, 49, and 51 months, respectively; two of these six also had significant, objective tamoxifen withdrawal responses of 9 and 14 months. Based on these results, it is urged that receptor values are studied and integrated with classical clinical and histopathologic variables before making a clinical decision so that patients with receptor-poor assay results are not prematurely labeled hormonally unresponsive.
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PMID:Response to tamoxifen in estrogen receptor-poor metastatic breast cancer. 330 11

One hundred thirty-three consecutive, previously untreated patients who had metastatic breast cancer were treated with a combination of 5-fluorouracil, doxorubicin (Adriamycin), and cyclophosphamide (FAC). They were randomly assigned to receive nonspecific immunotherapy with a heptavalent pseudomonas vaccine. Sixty-five patients were treated with pseudomonas vaccine, whereas 68 did not receive immunotherapy. In addition, all patients with estrogen receptor-positive tumors or tumors with an estrogen receptor status were also treated with tamoxifen. To allow clinical assessment of hormone sensitivity in vivo, tamoxifen was started 6 weeks before chemotherapy except in patients who had life-threatening disease. After the initial 6 weeks of tamoxifen, 3% of patients had achieved a complete remission, 9% a partial remission, while 16% achieved a minor response. The maximum response after tamoxifen and chemotherapy included complete remissions in 20% of patients and partial remissions in 61% of patients for an overall remission rate of 81%. The median response duration was 15 months, and the median survival time, 27 months. There were no differences in remission rate, remission duration, or survival time between the groups treated with or without pseudomonas vaccine. Eleven patients with limited metastatic disease received radiotherapy consolidation to initially involved sites. In these patients the median time from radiotherapy to progression of disease was 33 months, and the median survival time was 46 months. We conclude that nonspecific immunotherapy with pseudomonas vaccine failed to increase remission rate or survival time. Furthermore, the addition of tamoxifen to FAC chemotherapy did not improve the remission rate or duration compared to a recent, historical control group of patients treated with only FAC chemotherapy.
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PMID:Combined antiestrogen and cytotoxic therapy with pseudomonas vaccine immunotherapy for metastatic breast cancer. A prospective, randomized trial. 331 73

Ninety-seven eligible and evaluable women with metastatic breast cancer were placed on a prospective clinical protocol to evaluate the use of continuous cyclic therapy with dibromodulcitol, doxorubicin, vincristine, tamoxifen, and fluoxymesterone (DAVTH) v DAVTH alternating with cyclophosphamide, methotrexate, 5-fluorouracil, and prednisone (CMFP); and the use of pretreatment and serial carcinoembryonic antigen (CEA) levels in these patients. Continuous DAVTH and DAVTH/CMFP were equivalent therapies with respect to response rates, time to treatment failure (TTF), and survival. Pretreatment CEA levels were elevated (greater than 5 ng/mL) in 42/97 patients and less than 5 ng/mL in the remaining patients. Patients with elevated pretreatment CEA levels were more likely to be estrogen receptor (ER) positive (P = .006), to have prolonged disease-free intervals (P = .017), to have hepatic (P = .004) and/or osseous (P = .01) metastases, and to have multiple sites of metastatic disease (P = .004). Pretreatment CEA levels did not significantly predict for overall response rates, TTF, or survival; nonetheless, those patients with low pretreatment CEA levels had more complete responses (CRs) (16/55 v 4/42; P = .02). Serial CEA levels during therapy revealed a number of interesting patterns. During the first 4 months of treatment, serial CEA levels in responding patients either (1) progressively declined (15/29 women with elevated pretreatment CEA levels), or (2) initially rose significantly (mean, 243% of pretreatment value) and then declined (14/29 women with elevated pretreatment CEA levels). Peak CEA levels in the latter patients were seen 27 to 135 days following initiation of cytotoxic therapy. In some patients the initial increase in the CEA level was incorrectly interpreted as evidence of impending disease progression. CEA levels frequently increased around the time of clinical disease progression. However, rising CEA levels rarely provided a clinically meaningful lead time before the appearance of other clinical evidence of disease progression. These data suggest that routine pretreatment and monthly serial CEA levels in metastatic breast cancer patients have minimal use in clinical practice. Two further noteworthy findings were observed in this prospective study. First, patients with an unknown ER status had a prolonged median survival when compared with patients with ER positive or negative tumors; this appeared to be related to prolonged disease-free intervals in ER unknown patients. Second, two case of secondary acute leukemia were seen in patients treated with continuous DAVTH therapy.
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PMID:Prospective evaluation of carcinoembryonic antigen levels and alternating chemotherapeutic regimens in metastatic breast cancer. 351 Feb 82

In a randomized study 115 postmenopausal women with advanced breast cancer who were estrogen receptor-unknown or -positive were treated initially with tamoxifen or diethylstilbestrol (DES). Their pretreatment characteristics showed no significant difference. The frequency of response was identical with tamoxifen and DES, showing a complete response rate of 2% versus 2% and a partial response rate of 4% versus 8%, respectively; stable disease was present in 78% versus 73% of the patients, respectively. The median time to disease progression (5 vs 6 months) and median survival depending on initial hormone therapy (34 vs 35 months) were identical for tamoxifen and DES, respectively. Gastrointestinal toxicity was more frequent and more severe with DES than tamoxifen. Responses were seen with withdrawal of each agent and on crossover to the alternative agent. Our conclusions are that: DES and tamoxifen are equally effective in treating metastatic breast cancer in the postmenopausal patient who is estrogen receptor-positive or -unknown; withdrawal and crossover responses are seen with both agents; side effects are minimal but more frequent with DES; and on the basis of cost-effectiveness DES is the preferable agent.
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PMID:Randomized comparison of tamoxifen versus diethylstilbestrol in estrogen receptor-positive or -unknown metastatic breast cancer: a Southeastern Cancer Study Group trial. 353 Apr 47

Diethylstilbestrol (DES) can induce a recruitment into the proliferative pool of previously resting breast cancer cells in vivo. In order to verify if estrogenic recruitment could result in a larger tumor cell killing by chemotherapy, 117 patients with metastatic breast cancer were randomized to receive CEF (cyclophosphamide, 600 mg/m2; epidoxorubicin, 60 mg/m2; and 5-fluorouracil, 600 mg/m2 on day 1); DES-CEF (cyclophosphamide, 600 mg/m2 on day 1; DES, 1 mg orally on days 5, 6, and 7; and epidoxorubicin, 60 mg/m2, and 5-fluorouracil, 600 mg/m2, on day 8) every 21 days. No significant difference in objective response rates, survival, or progression-free survival was seen between the two regimens. Patients in the DES-CEF arm experienced a higher complete response (CR) rate (24.1% v 16.1%), which reached statistical significance in the case of soft-tissue metastasis (48% v 27.3%; P less than .05) and estrogen receptor-negative tumors (35.7% v 11.1%; P less than .025). Survival and progression-free survival of patients refractory to treatment were not worsened by estrogenic recruitment. In the subset of patients failing after adjuvant polychemotherapy, DES-CEF unexpectedly induced a significantly longer survival (greater than 802 days v 375 days; P = .029) and progression-free survival (239 days v 192 days; P = .041) than CEF. The DES-CEF regimen was more myelotoxic, and 43.3% of the DES-CEF cycles had to be delayed because of leukopenia in comparison with 11.8% of the CEF cycles (P less than .0001). In conclusion, chemotherapy with estrogenic recruitment was able to induce more CRs in certain subsets of patients and a significant prolongation in survival and progression-free survival of patients failing after adjuvant polychemotherapy. These results have been achieved despite a significantly lower dose intensity of chemotherapy.
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PMID:Conventional versus cytokinetic polychemotherapy with estrogenic recruitment in metastatic breast cancer: results of a randomized cooperative trial. 354 11

Fifty-two patients with hormonally unresponsive or estrogen receptor negative metastatic breast cancer who had not received prior chemotherapy received mitoxantrone 10 mg/m2, cyclophosphamide 500 mg/m2, and 5-fluorouracil 1000 mg/m2 (MCF) by short intravenous infusion every 21 days. Disease that was resistant or stable to this regimen was treated with doxorubicin 25 mg/m2/day for two days and vinblastine 1.4 mg/m2/day for four days (DV). Both drugs were given by continuous infusion. Thirty-one partial remissions and four complete remissions occurred after treatment with MCF. Only thirty-four evaluable patients crossed to the DV phase with partial remission (11 patients), stable (five patients), or resistant (18 patients) disease. Eleven patients' responses were upgraded. The median overall time to progression (TTP), defined as the sum of the TTP on MCF and TTP on DV, was 12 months. The median survival of all patients was 19 months. Granulocytopenia was the dose limiting toxicity for MCF, but cumulative thrombocytopenia was noted. Nausea and vomiting occurred in most patients but was mild. Severe alopecia occurred in half the patients. One patient developed congestive heart failure after receiving a cumulative dose of 206 mg/m2 of mitoxantrone. The incidence of infectious complications was 35% on each regimen; 50% of these were mild. MCF is an effective combination that was well tolerated. Objective responses, durations of response, and survival were similar, but not superior, to standard doxorubicin-based combinations. Toxicity was somewhat less.
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PMID:Mitoxantrone, cyclophosphamide, and fluorouracil in metastatic breast cancer unresponsive to hormonal therapy. 356 61

One hundred thirty-one premenopausal women with metastatic breast cancer who had received no prior systemic treatment for metastases were entered on study. Patients without prior chemotherapy with estrogen receptor (ER)-positive and ER-unknown disease were randomized to receive cyclophosphamide, Adriamycin (Adria Laboratories, Columbus, OH), and 5-fluorouracil (CAF) or surgical oophorectomy followed directly by CAF (O + CAF). ER-negative patients without prior chemotherapy were directly assigned to treatment with CAF. Among randomized patients 83% have responded, and 37% have achieved a complete remission. Among ER-negative patients the complete response rate was 38%, and the complete plus partial response rate was 70%. Characteristics significantly associated with a longer time to treatment failure were age 45 or over, one or two organ sites, and performance status O. The median survival time of ER-positive patients treated with CAF is 29 months, and with O + CAF it has not yet been reached, whereas for ER-unknown patients the equivalent survival times are 41 months and 43 months respectively. For ER-negative patients treated with CAF the median survival time is 17 months. Characteristics associated with significantly longer survival among randomized patients were age 35 or over (P = .009) and only one or two organ sites involved (P = .02). Neither treatment (P = .33) nor ER status (P = .70) was significant.
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PMID:Treatment of metastatic breast cancer in premenopausal women using CAF with or without oophorectomy: an Eastern Cooperative Oncology Group Study. 358 44


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