Sometimes hormone-receptor-positive breast cancer comes back or grows during treatment with hormonal therapy. Abnormal genes give breast cancer cells the ability to grow, divide, and spread uncontrollably. The abnormal genes that make cells cancerous also make them more likely to have still more abnormal genetic changes. This partly explains why breast cancer treatments stop working and why everyone doesn't get the same benefits from a treatment. In this study, the cancer cells changed so they weren't affected by hormones, so that reducing the amount of hormones or blocking their effects with hormonal therapy wouldn't work anymore.
The small study reviewed here suggests that the targeted therapy medicine Nexavar (chemical name: sorafenib) may be able to make hormone-receptor-positive breast cancers that have stopped responding to hormonal therapy start responding again.
Nexavar was given to 27 women diagnosed with hormone-receptor-positive breast cancer that came back or grew during treatment with Arimidex (chemical name: anastrazole), an aromatase inhibitor that is one type of hormonal therapy. After Nexavar treatment, about 25% of the cancers seemed to respond again to Arimidex. The findings were reported during the 2008 American Society of Clinical Oncology (ASCO) Breast Cancer Symposium.
Nexavar is a targeted therapy approved to treat liver cancer. Nexavar is not approved to treat breast cancer.
Nexavar is a kinase inhibitor; kinases are certain proteins inside a cell that can stimulate the cells to grow uncontrollably. Nexavar works by interfering with kinases inside the cancer cell, which limits the amount of energy the cells have to grow and multiply. Other research suggests that changes in kinase proteins may be why hormone-receptor-positive breast cancers stop responding to hormonal therapy. Nexavar may reduce the effect of the altered kinases and make the cancer respond again to hormonal therapy.
While this study is promising, it is very small. More research is needed to figure out how targeted therapies like Nexavar might be used with other breast cancer treatments to offer more benefits.
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WASHINGTON, Sept. 8 (MedPage Today) -- Breast cancer that has become hormone insensitive may revert to sensitive status with targeted therapy, investigators reported here.
A quarter of breast cancer patients whose disease had recurred or progressed during treatment with an aromatase inhibitor had partial responses or prolonged stable disease when treated with sorafenib (Nexavar) and anastrozole (Arimidex), Deepa Subramaniam, M.D., of Georgetown University, said at the 2008 Breast Cancer Symposium.
"Given what we know about the ineffectiveness of sorafenib alone in metastatic breast cancer, we believe the benefit that we're seeing may be attributable to the restoration of sensitivity to aromatase inhibitors," commented senior investigator Claudine Isaacs, M.D., also of Georgetown.
"To manage breast cancer long term, it's apparent that we may need to continually switch drugs to keep up with how a cancer evolves and evades each approach."
Over time, most cases of hormone receptor-positive metastatic breast cancer develop resistance to endocrine therapy. Proposed mechanisms of resistance include activation of the ras-raf-MAPK pathway, said Dr. Subramaniam.
Because sorafenib targets and inhibits multiple kinases in the pathway, a rationale existed for evaluating the agent as a means of overcoming resistance to aromatase inhibitors, he said.
Dr. Subramaniam reported findings from an ongoing study that had accrued 27 patients. Study participants were postmenopausal women with receptor-positive metastatic breast cancer that had become unresponsive to aromatase inhibitors.
The patients had received no more than two prior chemotherapy regimens for metastatic disease.
All patients received sorafenib 400 mg twice daily plus a standard dose of anastrozole.
Of the 27 patients two had partial responses that lasted more than six months and five had stable disease for more than 24 weeks. Ten patients had progressed, and six were not evaluable for response.
The patients who had partial responses and prolonged stable disease translated into an overall clinical benefit of 26.08%.
Preliminary analysis of factors associated with clinical benefit suggests that a decline in circulating endothelial cells during the first week of treatment predicts response to therapy, the researchers said.
Dr. Subramaniam said agents that target other pathways, such as insulin-like growth factor receptor, might offer other approaches to overcome resistance to endocrine therapy.
The strategy of adding a targeted agent to another type also has applicability to other cancers, she added, noting that studies have demonstrated unusually high response rates in patients with lung cancers that have become resistant to erlotinib (Tarceva).
Dr. Subramaniam reported no disclosures. Dr. Isaacs is a member of Pfizer's speaker bureau.
Primary source: 2008 Breast Cancer Symposium Source reference: Subramaniam DS, et al "Sorafenib in hormone-receptor positive (ER/PR+) metastatic breast cancer (MBC) resistant to aromatase inhibitors (AIs)" ASCO Breast 2008; Abstract 162.
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