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Breast cancer specialist reports advance in treatment of triple-negative breast cancer

“Impact of the Addition of Carboplatin and/or Bevacizumab to Neoadjuvant Once-Per-Week Paclitaxel Followed by Dose-Dense Doxorubicin and Cyclophosphamide on Pathologic Complete Response Rates in Stage II to III Triple-Negative Breast Cancer: CALGB 40603 (Alliance)” was accepted as a rapid publication and published online this month by the Journal of Clinical Oncology. It will come out in print in September.

Because of its rapid growth rate, many women with triple-negative breast cancer receive chemotherapy to try to shrink it before undergoing surgery. With the standard treatment, the cancer is eliminated from the breast and lymph nodes in the armpit before surgery in about one third of women. This is referred to as a pathologic complete response (pCR). In patients who achieve pCR, the cancer is much less likely to come back, spread to other parts of the body, and cause the patient’s death than if the cancer survives the chemotherapy.

Sikov and his collaborators studied the addition of other drugs — carboplatin and/or bevacizumab — to the standard treatment regimen to see if they could increase response rates. More than 440 women from cancer centers across the country enrolled in this randomized clinical trial.

“Adding either of these medications significantly increased the percentage of women who achieved a pCR with the preoperative treatment. We hope that this means fewer women will relapse and die of their cancer, though the study is not large enough to prove this conclusively. Of the two agents we studied, we are more encouraged by the results from the addition of carboplatin, since it was associated with fewer and less concerning additional side effects than bevacizumab,” Sikov explains.

“More studies are planned to confirm the role of carboplatin in women with triple-negative breast cancer, and also to see if we can better identify which of these patients are most likely to benefit from its use. Until we have those results, medical oncologists who treat women with triple-negative breast cancer will have to decide whether the potential benefits of adding carboplatin outweigh its risks for each individual patient.”

Triple-negative breast cancer accounts for 15 to 20 percent of invasive breast cancers diagnosed in the United States each year, and is more common in younger women, African-Americans, Hispanics, and BRCA1-mutation carriers. With no identified characteristic molecular abnormalities that can be targeted with medication, the current standard of treatment is chemotherapy.

“Overall prognosis for women with this type of breast cancer remains inferior to that of other breast cancer subtypes, with higher risk of early relapse,” Sikov says.

source : http://www.sciencedaily.com/releases/2014/09/140905153015.htm

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Breast radiation trial provides more convenience, better compliance, lowered cost and patient outcomes on par with current treatment

These interim results of the 5-year Phase II clinical trial using the experimental regimen are being presented at the Breast Cancer Symposium 2014 in San Francisco by Anthony E. Dragun, M.D., vice chair and associate professor of radiation oncology at the University of Louisville.

Dragun, a radiation oncologist with University of Louisville Physicians, launched the trial three years ago at UofL’s James Graham Brown Cancer Center, a part of KentuckyOne Health and the only site offering the experimental regimen in the United States. A second KentuckyOne Health site is being planned, he said, and is expected to begin enrolling patients this autumn.

Reviewing data from Europe — the United Kingdom in particular — Dragun found an alternative to the currently standard daily radiation treatments prescribed to patients after a lumpectomy. Physicians in the U.K. and other European countries were reporting excellent results with a regimen of radiation administered once-weekly.

“Instead of daily treatments for 25-30 days, five to six treatments administered once each week were being used,” he said. “I thought this regimen would give our patients here in Kentucky a great deal of access and choice, so we developed the trial and launched it in 2011.”

Approximately 150 female patients have been enrolled in the trial thus far, he said. Patients undergoing a lumpectomy following diagnosis of breast cancer are given a choice of the current standard of daily radiation treatments or the option to enroll in the trial and receive treatment one time per week.

The radiation dosing has been calibrated to compensate for the change in how the treatments are administered, but no adverse effects have been seen, Dragun said. “The outcomes with once-weekly treatments are absolutely in line with what we see in daily breast irradiation,” he said. “The standard of care is maintained.”

Giving women the choice of how their treatment is administered means more women complete their treatment, he said. “Finding time for daily treatments for 6 weeks or more just isn’t possible for many women,” Dragun said. “Scheduling once-weekly treatments is much easier to fit into the busy lives our patients lead.

“We also see many patients who depend on public transportation or live in rural areas that are 30 miles or more from our center, and they have told us that they would not have been able to complete a traditional course of daily radiation treatment. Their only alternative would be a mastectomy,” he said.

Because radiation treatment is reimbursed on a per-treatment basis, Dragun said the overall cost is lowered. “We have reduced the number of treatments to about one-fourth to one-third of what the current daily treatment regimen is,” he said. “Medicare reimburses radiation costs on a per-treatment basis, and most private insurers do likewise.

“This means we’ve been able to reduce the cost by 50 to 60 percent without jeopardizing the quality of care.”

Dragun plans to enroll another 50 patients at the Louisville site and 30 at the future trial site. After the completion of this trial, he intends to expand into a multi-center Phase III trial at facilities in other states.

“We believe the once-weekly regimen such as this will become a standard option in the next decade,” he said.

source : http://www.sciencedaily.com/releases/2014/09/140904121041.htm

Enzyme controlling metastasis of breast cancer identified

“The take-home message of the study is that we have found a way to target breast cancer metastasis through a pathway regulated by an enzyme,” said lead author Xuefeng Wu, PhD, a postdoctoral researcher at UC San Diego.

The enzyme, called UBC13, was found to be present in breast cancer cells at two to three times the levels of normal healthy cells. Although the enzyme’s role in regulating normal cell growth and healthy immune system function is well-documented, the study is among the first to show a link to the spread of breast cancer.

Specifically, Wu and colleagues with the UC San Diego Moores Cancer Center found that the enzyme regulates cancer cells’ ability to transmit signals that stimulate cell growth and survival by regulating the activity of a protein called p38 which when “knocked down” prevents metastasis. Of clinical note, the researchers said a compound that inhibits the activation of p38 is already being tested for treatment of rheumatoid arthritis.

In their experiments, scientists took human breast cancer cell lines and used a lentivirus to silence the expression of both the UBC13 and p38 proteins. These altered cancer cells were then injected into the mammary tissues of mice. Although the primary tumors grew in these mice, their cancers did not spread.

“Primary tumors are not normally lethal,” Wu said. “The real danger is cancer cells that have successfully left the primary site, escaped through the blood vessels and invaded new organs. It may be only a few cells that escape, but they are aggressive. Our study shows we may be able to block these cells and save lives.”

Researchers have also defined a metastasis gene signature that can be used to evaluate clinical responses to cancer therapies that target the metastasis pathway.

source : http://www.sciencedaily.com/releases/2014/09/140902205145.htm