Clinical breast cancer
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Clinical breast cancer · Apr 2012
Phase II trial of exemestane in combination with fulvestrant in postmenopausal women with advanced, hormone-responsive breast cancer.
Exemestane, the irreversible steroidal aromatase inhibitor, and fulvestrant, the pure estrogen antagonist, are active as single drugs in postmenopausal women with advanced hormone-responsive breast cancer. We designed a phase II study with the purpose of determining whether combining these 2 drugs with different and potentially complementary mechanisms of action will improve the clinical benefit. ⋯ The combination of exemestane and fulvestrant did not improve clinical benefit. The observed lack of improved efficacy was not related to altered drug exposure.
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Clinical breast cancer · Feb 2012
Randomized Controlled Trial Multicenter StudyImmediate Administration of Zoledronic Acid Reduces Aromatase Inhibitor-Associated Bone Loss in Postmenopausal Women With Early Breast Cancer: 12-month analysis of the E-ZO-FAST trial.
Letrozole is a proven and effective adjuvant therapy in postmenopausal women with hormone receptor-positive (HR(+)) early breast cancer (EBC). As with other aromatase inhibitors (AIs), long-term letrozole administration is associated with decreased bone mineral density (BMD) and increased fracture risk. This study compared potential bone-protecting effects of immediate vs. delayed administration of zoledronic acid (ZOL) in patients with EBC receiving adjuvant letrozole. ⋯ Immediate ZOL administration effectively prevented BMD loss and increased BMD in postmenopausal women with HR(+) EBC receiving adjuvant letrozole, regardless of BMD status at baseline.
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Clinical breast cancer · Feb 2012
Randomized Controlled TrialRandomized phase II study of primary systemic chemotherapy and trastuzumab for operable HER2 positive breast cancer.
In primary systemic therapy in patients with human epidermal growth factor receptor 2 positive (HER2(+)) breast cancer, improvements in pathologic complete response (pCR) rate have been achieved by administering trastuzumab. ⋯ There was no significant difference in pCR rate between FEC-PH and FEC-DH. Both regimens achieved higher pCR rates in HR(-) than HR(+) breast cancer, and there was a trend toward higher pCR in HR(-) tumors with FEC-PH compared with FEC-DH. Further investigation is warranted to explore the relationship between efficacy and HR status.
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Clinical breast cancer · Feb 2012
ReviewTrastuzumab treatment in multiple lines: current data and future directions.
Trastuzumab improves response rate, time to progression, and overall survival when combined with first-line chemotherapy in patients with human epidermal growth factor receptor 2-positive (HER2-positive) metastatic breast cancer (MBC). However, the benefits of continuing trastuzumab beyond disease progression have not been clearly established. The literature was reviewed to obtain data on trastuzumab use beyond disease progression. ⋯ Moreover, recent data from two prospective randomized phase III trials have shown that adding trastuzumab to the treatment regimen in patients with MBC who have progressed on trastuzumab-based therapy significantly prolongs progression-free survival. Emerging evidence from randomized controlled trials supports the potential clinical utility of continuing trastuzumab-based therapy beyond progression and supports the National Comprehensive Cancer Network recommendation to consider this treatment approach. Future treatment of HER2-positive MBC may involve trastuzumab being used in successive regimens in combination with other targeted therapies.
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Clinical breast cancer · Feb 2012
ReviewBlockade of the HER family of receptors in the treatment of HER2-positive metastatic breast cancer.
Breast cancer is the most common type of cancer among women and the second leading cause of cancer death in the United States. Metastatic breast cancer is considered incurable, and treatment is aimed at palliating symptoms, achieving remission, and prolonging survival. Treatment options for metastatic disease vary based on tumor surface markers and clinical factors in an individual patient and include cytotoxic chemotherapy, hormonal therapy, biological therapy, or some combination of these. ⋯ Resistance to therapy is a challenge that limits the duration of benefit achieved with these agents. Therefore, combinations of HER family-targeted agents with other therapies such as cytotoxic agents, hormonal therapy, or inhibitors of other cellular pathways, are being developed to exploit synergy and overcome resistance mechanisms. Here we review the HER family-targeted agents currently approved or in development for HER2-positive metastatic breast cancer with a focus on strategies to overcome tumor resistance.