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)

The San Antonio Breast Cancer Symposium has become one of the leading forums for communication of important discoveries in breast cancer research. Over the past couple of years, seminal, practice-changing results have been presented at this meeting. The aromatase inhibitors represent the most effective endocrine interventions for postmenopausal women with hormone receptor-positive breast cancer. Their introduction into the adjuvant therapy of primary breast cancer was prompted by evidence from the ATAC trial. Progress in adjuvant chemotherapy included the introduction to taxanes, and more recently, the demonstration that the dose-dense administration of paclitaxel in association with doxorubicin and cyclophosphamide resulted in significant improvements in relapse-free and overall survival rates. Molecular targets have become accepted as rational targets, and targeted therapies are proceeding through clinical trials. The success of trastuzumab elicited much excitement, but a number of theoretical and practical hurdles must be overcome before other molecularly targeted agents are incorporated into standard therapy of primary and metastatic breast cancer.
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PMID:Breast cancer highlights: key findings from the San Antonio Breast Cancer Symposium: a U.S. perspective. 1526 1

Trastuzumab is an effective treatment for patients with metastatic breast cancer (MBC) that overexpresses HER-2. A high incidence of brain metastases (BM) has been noted in patients receiving trastuzumab. A retrospective chart review was conducted of 100 patients commencing trastuzumab for metastatic breast cancer from July 1999 to December 2002, at the Christie Hospital. Seven patients were excluded; five patients developed central nervous system metastases prior to starting trastuzumab, and inadequate data were available for two. Out of the remaining 93 patients, 23 (25%) have developed BM to date. In all, 46 patients have died, and of these 18 (39%) have been diagnosed with BM prior to death. Of the 23 patients developing BM, 18 (78%) were hormone receptor negative and 18 (78%) had visceral disease. Univariate analysis showed a significant association between the development of cerebral disease and both hormone receptor status and the presence of visceral disease. In conclusion, a high proportion of patients with MBC treated with trastuzumab develop symptomatic cerebral metastases. HER-2-positive breast cancer may have a predilection for the brain, or trastuzumab therapy may change the disease pattern by prolonging survival. New strategies to address this problem require investigation in this group of patients.
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PMID:Incidence of cerebral metastases in patients treated with trastuzumab for metastatic breast cancer. 1526 27

The selection of chemotherapeutic regimens is challenging for metastatic breast cancer (MBC) patients whose diseases have failed to respond to anthracyline and taxane. Capecitabine has advantages of oral administration and favorable toxicity profiles. This study was conducted to evaluate the efficacy of capecitabine and to identify the subgroup of patients who would potentially have benefit from capecitabine monotherapy in patients with anthracycline- and taxane-pretreated MBC. Female patients with MBC who had been previously treated with anthracycline and taxane received oral capecitabine 2500 mg/m(2) divided in two doses daily for 2 wk with 1-wk rest period. Between September, 1999, and December, 2002, a total of 38 patients were enrolled. Among the 36 evaluable patients, one patient achieved a complete response (CR), 9 patients had partial responses (PRs), and 13 patients had stable diseases (SDs). Response rate was 26% [95% confidence interval (CI), 12-40%] and the tumor control rate (TCR, CR+PR+SD) was 61% (95% CI, 45-77%). The median follow-up duration was 27.8 mo. The median duration of response was 8.9 mo, the median time to progression was 4.6 mo, and the median overall survival was 18.1 mo. The major toxicities were hand-foot syndrome, diarrhea, and emesis. There was no treatment-related death. The predictors of better overall survival were positivity of hormone receptor, disease-free survival longer than 1 yr, non-refractoriness to anthracycline, and fewer number (<or= 3) of involved organs. Capecitabine monotherapy is effective and well tolerated for MBC patients who had previously been treated with anthracycline and taxane. The TCR could predict overall survival as well as the objective response in this study, suggesting a possible role of TCR as a surrogate marker for survival in MBC patients on salvage chemotherapy. The patients who have relatively slow growing tumor and less tumor burden could have benefit from capecitabine monotherapy following anthracycline- and taxane-based chemotherapy.
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PMID:Capecitabine monotherapy in patients with anthracycline- and taxane-pretreated metastatic breast cancer. 1545 49

To optimize patient management in breast cancer a number of factors are considered, including hormone receptor and HER2 status. A feasible approach for women with less aggressive, estrogen receptor/HER2-positive metastatic breast cancer is to consider trastuzumab (Herceptin; F. Hoffmann-La Roche, Basel, Switzerland) combined with endocrine therapy. Randomized clinical trials are ongoing to assess the combination of trastuzumab with aromatase inhibitors. In patients with aggressive HER2-positive metastatic breast cancer, trastuzumab/chemotherapy combination regimens are warranted. When administered first line in combination with a taxane, trastuzumab improves all clinical outcome parameters, including survival, in such patients. Trastuzumab adds little to the toxicity profile of taxanes, and trastuzumab combination therapy is associated with improvements in quality of life when compared with chemotherapy alone. There is encouraging evidence of improved efficacy when trastuzumab is combined with other cytotoxic agents with proven single-agent activity in breast cancer, including capecitabine (Xeloda; F. Hoffmann-La Roche), gemcitabine, and vinorelbine. Trastuzumab is also being investigated as part of triplet drug regimens. Trastuzumab has good single-agent activity in first-line therapy. This is of relevance to women with HER2-positive disease who are not suitable for, or do not wish to receive, cytotoxic chemotherapy. The benefits noted with trastuzumab-containing regimens were documented in clinical trials where trastuzumab was given until disease progression. A further rationale exists to continue trastuzumab beyond progression. Data from retrospective reviews indicate that this strategy is feasible.
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PMID:Maximizing clinical benefit with trastuzumab. 1549 Mar 73

For metastatic breast cancer patients who have hormone receptor-positive tumors, hormonal therapy aiming at optimal palliation and prolongation of life is the initial treatment of choice. To enhance the effect of hormonal monotherapy, a combination therapy with Anastrozole 1 mg po and 5'-DFUR 800 mg po daily was given to 11 patients with metastatic breast cancer. At a median follow-up period of 15 months, the overall response rate was 45.5%. The median duration of response in responders was 25 months. The overall median survival for the entire series was 15 months after the start of treatment. No patients complained of adverse events of grade 2 and over. This combination therapy with good response and little side effects is useful for metastatic breast cancer patients.
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PMID:[Combination therapy with Anastrozole and 5'-DFUR as a treatment for metastatic breast cancer]. 1550 45

Third-generation aromatase inhibitors (AIs)--letrozole, anastrozole, and exemestane--are challenging tamoxifen as the standard endocrine therapy for postmenopausal women with hormone receptor-positive breast cancer. AIs suppress estrogen levels by inhibiting aromatase, the enzyme that catalyzes the final step of estrogen biosynthesis. Studies have shown that AIs are highly effective and safe in the treatment of advanced disease, and more recently, AIs have shown promise in the neoadjuvant, adjuvant, and extended adjuvant settings. However, all AIs are not equal. In direct comparisons with anastrozole, letrozole has demonstrated superior estrogen suppression and clinical response in patients with advanced metastatic breast cancer. In addition, letrozole is the only AI to demonstrate consistent superiority over tamoxifen in the neoadjuvant and first-line advanced breast cancer settings. This publication summarizes the available evidence for the efficacy of all 3 agents throughout the breast cancer continuum.
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PMID:Are all aromatase inhibitors the same? A review of the current evidence. 1558 78

The third-generation aromatase inhibitors suppress whole-body estrogen production in postmenopausal women with high specificity and potency. In women with hormone-sensitive breast cancer, three of these agents, letrozole, anastrozole, and exemestane, provide an important alternative endocrine therapy to the antiestrogen tamoxifen, which blocks estrogen activation of the estrogen receptor. For treatment of advanced or metastatic breast cancer that has progressed on first-line tamoxifen, all three agents are active. On that basis, they have each been compared with tamoxifen as first-line therapy of advanced breast cancer, in phase III trials. Letrozole was significantly superior to tamoxifen in the primary end point, median time to progression, as well as in response rate and clinical benefit rate, and treatment was well tolerated. Although there was no significant difference in median overall survival, an advantage seen with letrozole for the first 2 years may have been lost because of crossover to the alternate agent at disease progression. Anastrozole was evaluated in two separate trials designed for combined analysis. Overall, anastrozole was at least equivalent to tamoxifen in activity, but clearly superior only for median time to progression in the subgroup of patients with hormone receptor-positive disease. Treatment was generally as well tolerated as tamoxifen. In an early report, exemestane was significantly better than tamoxifen in response rate and median time to progression, with overall survival data not yet available. To date, letrozole appears to be the most effective aromatase inhibitor in the first-line advanced breast cancer setting.
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PMID:Aromatase inhibitors in advanced breast cancer. 1571 95

Hormone responsive breast cancer is usually determined by the presence of estrogen receptors (ER) or progesterone receptors (PR) on primary invasive breast cancers. Adjuvant and metastatic hormone therapy are recommended based on primary ER and PR determination. Little information is available to determine if primary hormone receptors correlate with metastatic disease and if survival is influenced by metastatic receptor status. We retrospectively compared primary to metastatic tumor ER and PR content from 200 metastatic breast cancer patients. ER and PR analyses were available in both primary and metastatic disease in 200 and 173 patients, respectively. There was a correlation between both the ER and PR in the primary and metastatic lesion (p < 0.001). However, in 60 of 200 (30%) patients, discordance between primary and metastatic ER was noted. Tumors from 68 of 173 (39.3%) showed discordance for PR. In 39 (19.5%) patients, the ER primary status was positive and metastatic status was negative and in 21 (10.5%) patients, the primary status was negative and metastatic status was positive. Survival from the time of metastatic diagnosis was calculated. Those patients with ER positive primary and metastatic tumors (Positive/Positive) or only the metastatic lesion (Negative/Positive) had similar median survival (1131 and 1111 days, respectively). However, patients with tumors that changed from positive primary to negative metastasis (Positive/Negative) experienced significantly shorter median survival (669 days, p < 0.05). Likewise, median survival (580 days) was significantly shorter for patients with primary and metastasis ER negative (Negative/Negative, p < 0.001) compared to Positive/Positive (p < 0.001) or compared to Negative/Positive (p < 0.02). The changes in PR status were not associated with a change in survival. We found a significant discordance between hormone receptor content of primary versus metastatic breast cancer. The ER status of the metastatic lesion was a better predictor of survival. Therefore, optimal metastatic treatment cannot be determined solely on primary ER and PR analysis.
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PMID:Impact of metastatic estrogen receptor and progesterone receptor status on survival. 1577 May 28

There is currently no standard care for metastatic breast cancer; consequently, individual patient and tumor characteristics are among several factors considered in treatment decisions. Clinical studies continue to clarify the roles of endocrine therapy, chemotherapy, and biologic therapy, and results have been promising. For patients with hormone receptor-positive disease, several endocrine agents are currently available including selective estrogen receptor (ER) modulators (tamoxifen and toremifene), aromatase inhibitors (anastrozole, exemestane, and letrozole), as well as the selective ER down-regulator, fulvestrant. Effective first- and second-line, single-agent chemotherapeutic treatments include the taxanes, anthracyclines, vinorelbine, capecitabine, and gemcitabine. The benefits of sequential, single-agent versus combination chemotherapy are also being evaluated. Although combination chemotherapy generally results in a greater objective response, it is associated with similar survival and usually greater toxicity compared with sequential, single-agent chemotherapy. Research involving biologic therapy continues to provide encouraging results for patients with metastatic breast cancer. Chemotherapy plus trastuzumab has been shown to result in greater overall survival versus chemotherapy alone in human epidermal growth factor 2 (HER-2)-positive patients. Trastuzumab has been associated with cardiotoxicity when administered with conventional anthracyclines. Newer formulations of anthracyclines have been developed (e.g., liposomal anthracyclines) to decrease the incidence of cardiotoxicity, and these provide additional treatment options for patients with metastatic breast cancer. The potential effect of all of these endocrine, chemotherapeutic, and biologic treatments on quality of life is an important consideration. Additionally, integrating patient concerns into treatment decisions and collaborating with cross-disciplinary healthcare providers can help to manage the disease more effectively.
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PMID:Optimizing the treatment of metastatic breast cancer. 1577 May 36

Endocrine therapy of hormone receptor-positive breast tumors is widely used as palliative therapy for metastatic breast cancer and as adjuvant therapy for early stage breast cancer. Tamoxifen has been the definitive standard of hormonal therapies for the last 30 years because of its documented efficacy and reasonable safety profile. Based on encouraging results from trials utilizing the selective, third generation aromatase inhibitors (AIs) in metastatic breast cancer, a number of trials were designed to examine these agents as adjuvant therapies. Trials directly comparing AIs with tamoxifen have, to date, demonstrated superior disease-free-survival with AIs. Likewise, trials examining the use of AIs after tamoxifen have demonstrated better outcomes compared with tamoxifen alone. Additionally, letrozole has been demonstrated to result in superior disease-free-survival after 5 years of adjuvant tamoxifen, compared with no further therapy. In general, the AIs are tolerated at least as well as tamoxifen but decrease bone mineral density and increase osteoporosis due to their lack of estrogenic effects on bone. Based on the fact that AIs appear more effective at preventing contralateral breast cancers than tamoxifen, they are being examined as breast cancer preventives. Despite available data using the AIs as adjuvant therapies, many questions remain unanswered, and further trials will be needed to address these important issues.
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PMID:Aromatase inhibitors as adjuvant therapy for postmenopausal patients with early stage breast cancer. 1589 Jun 38


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