Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0278488 (metastatic breast cancer)
 7,812 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 38-year-old woman with cancer in the left breast underwent standard radical mastectomy. The estrogen receptor and progesterone receptor status of the primary tumor was unknown. Ten years after the surgery, a metastatic liver tumor was detected, and chemoendocrine therapy, consisting of cyclophosphamide, epirubicin, 5-fluorouracil (CEF) and medroxyprogesterone acetate (MPA) was initiated. The metastatic liver tumor showed a partial response after 11 cycles of such chemoendocrine therapy. Subsequently, MPA alone was given daily as maintenance therapy, and the disease has remained stable for 6 years. For women with metastatic breast cancer, complete remission is uncommon, and stable disease is a reasonable goal of successful therapy. In this respect, chemoendocrine therapy with CEF and MPA, followed by MPA alone as maintenance therapy, was successful in the patient reported here. Importantly, the patient's quality of life has remained favorable for several years after the partial response was achieved.
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PMID:Successful management of breast cancer with liver metastases with medroxyprogesterone acetate treatment. 1182 51

The extreme drug resistance (EDR) assay has not been widely studied in the setting of non-metastatic breast cancer. We evaluated the feasibility of performing the assay in 144 primary breast tumor specimens from two institutions by determining the rate of successful tumor culture for assays, number of drugs evaluated per assay, and time from tumor biopsy to receipt of results. We also sought to determine factors that are associated with assay success. An exploratory analysis was performed to detect possible associations between estrogen receptor (ER), progesterone receptor (PR) and HER2/NEU over-expression and extreme drug resistance demonstrated by the assay for specific chemotherapeutic agents. Of 144 tumor specimens submitted, tumor was successfully cultured for assay in 101(70%) of cases. A median of five drugs was evaluated per assay (range 2-9). Results were obtained in a median of 8 days (range 2-29). Young age, high tumor grade, PR negativity, and higher tumor submission weight were predictive for a successful assay. EDR was observed in 7-15% of tumors to doxorubicin, cyclophosphamide, 5-fluorouracil (5FU) and mitoxantrone, but EDR to paclitaxel was observed in 35%. Extreme drug resistance to 5-FU was associated with negative ER and PR status. There was a trend toward association between EDR to paclitaxel and HER2/NEU over-expression. The EDR assay may be successfully performed in the majority of tumors, and assay results are available in a timely fashion such that adjuvant treatment drug selection could be guided by results. These results may be helpful for designing possible future trials that evaluate the assay's role in adjuvant chemotherapy selection.
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PMID:Factors associated with success of the extreme drug resistance assay in primary breast cancer specimens. 1188 14

Preliminary results of a phase II study of gemcitabine plus trastuzumab in previously treated (up to 3 previous regimens) metastatic breast cancer patients are presented. Patients had histologically confirmed metastatic breast cancer, with 2+ or 3+ tumor HER2 expression. Treatment consisted of gemcitabine 1200 mg/m2 over 30 minutes intravenously on days 1 and 8 every 21 days, and trastuzumab 4 mg/kg over 90 minutes, followed by 2 mg/kg infused over 30 minutes weekly. Treatment was continued until disease progression or unacceptable toxicity occurred. Preliminary results are available on the first 38 patients enrolled. Median patient age was 53 years, 53% had estrogen receptor/progesterone receptor-positive disease, and HER2 staining was 2+ in 39% and 3+ in 61% of patients. There was a median of 3 previously administered (including adjuvant) chemotherapy regimens, and a median of 4.5 treatment cycles per patient has been administered so far. Twelve patients (32%) have had an objective partial response, with a median response duration of 8.6 months. Median time to disease progression is 6.7 months to date, with a median overall survival of 10.2 months. No unexpected toxicities or grade 4 nonhematologic toxicities have been observed; 2 patients developed grade 4 neutropenia and 1 patient had febrile neutropenia. Thus, gemcitabine/ trastuzumab resulted in an encouraging 32% response rate, given the heavily pretreated patient population. Tolerability was good overall, with no unexpected side effects observed.
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PMID:Phase II trial of gemcitabine plus trastuzumab in metastatic breast cancer patients previously treated with chemotherapy: preliminary results. 1205 40

We retrospectively analyzed the effect of maintenance endocrine therapy (MET) after high-dose chemotherapy with hematopoietic progenitor cell transplant (HDCT) on the progression-free survival (PFS) of patients with hormone-dependent metastatic breast cancer (MBC). One hundred and nine consecutive patients with estrogen receptor (ER) and/or progesterone receptor (PgR)-positive MBC, who were progression free for at least 4 months after HDCT with cyclophosphamide, carmustine and thiotepa (CBT), were analyzed. Of these, 55 were non-randomly submitted to MET. After a median follow-up of 34.4 months (17.1-91.0), univariate analysis showed that MET was significantly associated with improved median PFS (31.1 vs 19.2 months, P = 0.022). Complete response to HDCT, pattern of metastatic spread, extent of the disease, single vs multiple metastatic sites, prior endocrine therapy for metastatic disease and prior exposure to any hormonal therapy (adjuvant and/or for the advanced disease) were also associated with PFS at univariate analysis. A multivariate Cox proportional hazard model was fitted to the data in order to correct the effect of MET for the other significant covariates. After correcting for these covariates, MET was still significant, predicting improved PFS (hazard ratio (HR) 0.580, 95% CI; 0.362-0.931). Administration of MET after optimal cytoreduction might result in increased efficacy of HDCT in hormone-dependent metastatic breast cancer.
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PMID:Factors affecting progression-free survival in hormone-dependent metastatic breast cancer patients receiving high-dose chemotherapy and hematopoietic progenitor cell transplantation: role of maintenance endocrine therapy. 1205 36

Endocrine therapy is first-line therapy for patients with estrogen receptor-positive or progesterone receptor-positive metastatic breast cancer. Commonly used endocrine therapies are tamoxifen, megestrol acetate, and aromatase inhibitors. Although tamoxifen and megestrol acetate have a favorable therapeutic profile, there are risks associated with these agents. With tamoxifen, the partial agonist property can lead to thromboembolic events. An important adverse event of megestrol acetate is weight gain and fluid retention in some patients. The aromatase inhibitors are currently used as second-line therapy after tamoxifen failure. A recent study showed that anastrozole, an aromatase inhibitor, is as effective or even superior to tamoxifen when used as a first-line therapy. However, not all patients will respond to currently available therapies. A new class of drug, the estrogen receptor downregulators, has been developed. Fulvestrant, the first agent in this new class, not only induces the degradation of the estrogen receptor but also is an estrogen antagonist; further, its lack of agonist activity provides a better safety profile. Two phase III trials have proven that fulvestrant is at least as effective as anastrozole in postmenopausal women with advanced breast cancer. Fulvestrant is an effective and safe endocrine therapy for postmenopausal women who have failed prior endocrine therapy.
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PMID:Existing and emerging endocrine therapies for breast cancer. 1208 May 38

Two groups of patients were chosen from among 4,025 subjects examined in a breast screening program, one consisting of patients with stage I and the other of patients with stage IV breast cancer, characterized by neoplastic recurrence. In this comparison p53, HER and grading are of no direct help. We investigated receptor status at the time of the first operation and after complete surgical excision of the recurrence. The following variables were determined: oestrogen and progesterone receptor measures (ER, PR) in f.mol/ml, the 4 receptor phenotypes, the oestrogen-progesterone ratio and histological tumour grading in relation to oestrogen receptor positivity or negativity. Surgery consisted in quadrantectomy or total mastectomy, with axillary dissection or complete surgical excision of the recurrence. Adjuvant therapy was administered. The results show a different receptor percentage in recurrence compared to early breast cancer, which though not significant, indicates a reduced presence of ER+ PR+, ER- PR-, and an increase in the ER+PR- phenotype. Recurrence occurs more frequently when the lesion at the first operation is more advanced and if radiotherapy has not been included in the treatment. Histological grading shows a greater number of undifferentiated cells and a reduction in ER+ in recurrence, thus indicating a reduced target for the most widely used hormone treatments. The oestrogen-progesterone ratio is significantly increased (P < 0.01) in recurrence compared to stage I cancers. The cause of recurrence is a neoplastic embolism, often documented histologically. Recurrence does not necessarily mean a poor prognosis, because there is a survival rate after two years of 77% of the cases treated. These results obtained with widely used methods show the aggressiveness of some breast tumours, which can evolve and have a very poor prognosis even with the most complete therapy.
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PMID:The oestrogen-progesterone receptor ratio: an indicator of breast cancer evolution. 1223 50

During 1986-1987, 192 women aged 26-86 with invasive breast cancer were treated with radiotherapy, hormonotherapy, and chemotherapy and then underwent modified radical mastectomy or wide local excision at Luis Castelazo Ayala Hospital of Obstetrics and Gynecology of the Mexican Social Security Institute in Mexico City. At diagnosis, metastatic bone surveys and bone scans showed that no one had distant metastasis. The physicians used incisional biopsy to determine the type of breast carcinoma (infiltrating ductal carcinoma [IDC] and infiltrating lobular carcinoma [ILC]). The researchers aimed to identify prognostic factors in primary breast cancer. 156 patients (81.3%) and 36 patients (18.7%) had IDC and ILC, respectively. Among women with IDC, axillary nodes were involved in 23.5% of premenopausal women and in 23% of postmenopausal women. 83.8% of all patients with IDC and 52.3% of IDC patients aged at least 50 had clinical stage III disease. Among women with ILC, axillary nodes were involved in 19.4% of premenopausal women and in 19.4% of postmenopausal women. 70% of all patients with ILC and 84.6% of ILC patients aged at least 50 had clinical stage III disease. All the patients had advanced breast cancer (i.e., clinical stage II and III). Some tumors were only estrogen receptor types, while others were only progesterone receptor types. Some tumors were even both receptor types, while another category had neither steroid hormone receptor. Survival rates for metastatic and non-metastatic breast cancer was greater among postmenopausal women than premenopausal women (32.7% vs. 14.8% and 21.8% vs. 12.8% for ICD and 19.4% vs. 8.4% and 30.5% vs. 13.9% for ILC, respectively). These findings suggest that axillary node status, status of estrogen and progesterone receptors, and menstrual status were important prognostic factors of breast cancer.
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PMID:Infiltrating ductal / lobular carcinoma: an evaluation of prognostic factors in primary breast cancer. 1232 22

A patient with dysphagia and a history of breast cancer 11 yr ago was admitted to the hospital. A tumor presumably originating from the esophagus was detected. It could not be surgically removed and biopsy revealed adenocarcinoma. The patient received radiotherapy and chemotherapy consisting of etoposide, adriamycin, and cisplatin. An unexpectedly good response was achieved and the possibility of metastatic breast cancer was reinvestigated. Biopsy specimens showed positive estrogen and progesterone receptor staining. Tamoxifen treatment was started. The patient is well after 5 yr following relapse. Solitary esophageal metastasis of breast cancer is a rare event, especially after a remission period lasting more than a decade. Dysphagia in breast cancer patients should raise the suspicion of metastatic disease as well as esophageal cancer and benign strictures.
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PMID:Solitary esophageal metastasis of breast cancer after 11 years: a case report. 1248 28

Endocrine therapy remains an important approach to the treatment of metastatic breast cancer because of its effectiveness and excellent tolerability. In the last 10 years, a number of new endocrine therapies have been introduced. These include the luteinizing hormone-releasing hormone agonists, which produce menopausal changes in premenopausal women; the aromatase inhibitors, which prevent production of estrogen in postmenopausal women; and the estrogen receptor down-regulator fulvestrant (Faslodex), which is effective in postmenopausal women whose tumors have progressed following response to other selective estrogen receptor modulators. The endocrine cascade for the treatment of premenopausal women with metastatic disease now involves the concurrent or sequential combination of a luteinizing hormone-releasing hormone analogue and tamoxifen, whereas the cascade for the treatment of postmenopausal women can begin with tamoxifen followed by an aromatase inhibitor or with an aromatase inhibitor followed by tamoxifen. The optimal cascade following the use of an aromatase inhibitor and tamoxifen in postmenopausal women remains unclear, but fulvestrant and megestrol acetate or the use of an aromatase inactivator (exemestane) following an aromatase inhibitor are all available options with some activity. Over the next few years, clinical trials will clarify the optimal sequence of endocrine therapy for postmenopausal women. The use of estrogen and progesterone receptor status to select for endocrine therapy is undeniably crucial. HER2/neu overexpression may also predict response to endocrine therapy, but this remains controversial.
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PMID:Endocrine therapy of advanced disease: analysis and implications of the existing data. 1253 1

The goal of endocrine therapy in breast cancer is to block the action of estrogen on the tumor cells either by inhibiting estrogen from binding to the specific estrogen receptor or by inhibiting its synthesis. Tamoxifen, a selective estrogen receptor modulator, is the standard endocrine treatment for hormone receptor-positive breast cancer, both in the adjuvant and metastatic settings. Tamoxifen inhibits the binding of estrogen to the receptor, resulting in inhibition of hormone action. However, as tamoxifen is also weakly estrogenic, it may not be optimally effective and increases the risk of endometrial cancer and stroke. Furthermore, patients may be refractory or may become resistant to tamoxifen treatment. Since aromatase inhibitors (AI) block the synthesis of estrogen and have no intrinsic estrogenic activity, they have the potential to be more effective than tamoxifen. Their different mechanism of action and chemical structures may also circumvent tamoxifen resistance. Consequently, AIs are currently being evaluated as an alternative to tamoxifen treatment. A preclinical model has recently been developed to compare the efficacy of AIs and antiestrogens in different treatment schemes and to assist in the design of clinical trials. Current studies with the MCF-7Ca xenograft model are exploring the effects of combination and sequential therapy on tumor growth. The efficacy of AIs in the treatment of hormone receptor-positive breast cancer was first demonstrated in five multicenter second-line trials enrolling several hundreds of postmenopausal patients with metastatic breast cancer who had failed tamoxifen treatment. More recently, anastrozole demonstrated efficacy at least equivalent to that of tamoxifen in first-line randomized, phase III clinical trials in postmenopausal women with hormone receptor-positive or unknown metastatic breast cancer, whereas letrozole demonstrated superiority. The steroidal AI exemestane is currently under evaluation. Letrozole is the only AI to have been studied in a randomized, phase III trial in the neoadjuvant setting. In this trial, more patients underwent breast-conserving surgery with letrozole than with tamoxifen. Smaller phase II studies also suggest that both anastrozole and exemestane are active in the neoadjuvant setting. Because neoadjuvant trials permit temporal sampling of breast tissue, substudies in the phase III trial with letrozole have examined the impact of such biomarkers as estrogen receptor, progesterone receptor and epidermal growth factor receptor family members, HER-1 and HER-2, on patient response. AIs are currently under evaluation in the adjuvant setting, and preliminary results of the Arimidex, Tamoxifen Alone or in Combination (ATAC) trial have been reported. AIs have proven as safe as tamoxifen in trials in patients with metastatic breast cancer. Ongoing clinical trials in the adjuvant setting include companion studies of end-organ effects, particularly bone metabolism and lipid metabolism evaluations. Quality-of-life assessments are also parts of major clinical trials. A head-to-head quality-of-life assessment of anastrozole compared with letrozole demonstrated patient preference for letrozole. These assessments also clearly indicated the eagerness of patients to participate actively in treatment decisions
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PMID:Challenges in the endocrine management of breast cancer. 1465 38


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