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

FDA approves new game changing drug to fight melanoma

The drug, Keytruda (pembrolizumab), was tested on more than 600 patients who had melanoma that had spread throughout their bodies. Because so many of the patients in the early testing showed significant long-lasting responses, the study was continued and the FDA granted the drug “breakthrough therapy” status, allowing it to be fast-tracked for approval.

The largest Phase 1 study in the history of oncology, the research was conducted at UCLA and 11 other sites in the U.S., Europe and Australia.

Keytruda, formerly known as MK-3475, is an antibody that targets a protein called PD-1 that is expressed by immune cells. The protein puts the immune system’s brakes on, keeping its T cells from recognizing and attacking cancer cells, said Dr. Antoni Ribas, the study’s principal investigator and a professor of medicine in the division of hematology-oncology at the David Geffen School of Medicine at UCLA.

For many years, when using immunotherapy to fight cancer, doctors’ strategy has been to bolster the immune system so it could kill the cancer cells. But the approach had limited success because PD-1 prevented the immune system from becoming active enough to attack the cancer.

Keytruda, in effect, cuts the brake lines, freeing up the immune system to attack the cancer.

“This drug is a game changer, a very significant advance in the treatment of melanoma,” said Ribas, who also is a researcher at UCLA’s Jonsson Comprehensive Cancer Center. “For patients who have not responded to prior therapies, this drug now provides a very real chance to shrink their tumors and the hope of a lasting response to treatment.”

Judith Gasson, senior associate dean for research at the David Geffen School of Medicine at UCLA and director of the Jonsson Cancer Center, said researchers have long hoped to develop an effective and lasting immunotherapy to fight cancer.

“We have long believed that harnessing the power of our own immune systems would dramatically alter cancer treatment,” she said. “Based upon work conducted over the past two decades, we are beginning to see the clinical benefits of this research in some of the most challenging cancers.”

Generally, about 1 in 10 patients responded to previous immunotherapy drugs. Some of those who responded, however, exhibited long-lived benefits, which sustained scientists’ interest in the method as an effective mechanism to fight cancer.

The response and duration rates for Keytruda were much greater than for previous drugs, Ribas said. In the new study, 72 percent of patients responded to the drug, meaning that their tumors shrank to some degree. Overall, 34 percent of patients showed an objective response, meaning that their tumors shrank by more than 30 percent, and did not re-grow.

Ribas said Keytruda has the potential to be used to treat other cancers that the immune system can recognize, including cancers of the lung, bladder, head and neck.

Survivors’ stories Kathy Thomas, 59, of Torrance, California, was diagnosed in September 2011 with melanoma that had spread to her liver and was invading her left breast. She underwent several therapies that did not work, and she was weakening fast.

“I lost weight. I threw up nearly every day,” Thomas said. “My hair was thinning. I just had no strength at all. I was so sick I had to use a wheelchair.”

Thomas met with Ribas in 2012 but was skeptical about enrolling in a trial to test an experimental therapy. She soon overcame her hesitation.

“I decided I wanted to survive,” she said. “I wasn’t going to let this disease beat me.”

Since enrolling in the study, Thomas’ tumors have shrunk. She regained her strength and her appetite. She’s out of her wheelchair and walking normally again. She said she has experienced no side effects from the therapy, and she travels monthly to San Francisco to visit her grandson.

“I just enjoy life now, really enjoy it,” she said.

Watch Kathy Thomas discuss her therapeutic experience: http://youtu.be/BOgw7mgQEdc

Tom Stutz, 74, of Sherman Oaks, California, was diagnosed in June 2011 with melanoma that had spread to his lung, liver and other parts of his body. He didn’t see how he could survive, but he decided to enroll in the clinical trial of Keytruda anyway.

“I wasn’t eating. I was on oxygen. I couldn’t walk,” he said. “When I went into the hospital at the end of May [2012], I didn’t think I was coming out.”

Gradually, though, Stutz started feeling better. Today, he’s no longer on oxygen and walks several miles every day.

“It’s the little things that make me happy now,” Stutz said. “I’m very appreciative that I get to get up in the morning, go into my backyard and see my garden. I’m able to be with my children and grandchildren, go on vacations with them. I was close to the end of the road, as far as you can get to the edge of the cliff, and I was pulled back by this treatment.”

Watch Tom Stutz discuss his therapeutic experience: http://youtu.be/-HV2W5XrOZY

Melanoma incidence rates have been increasing for at least 30 years. An estimated 76,100 new cases of melanoma will be diagnosed in the U.S. in 2014, and nearly 10,000 Americans will die from the disease this year. While melanoma accounts for less than 2 percent of all skin cancer cases, it is responsible for the vast majority of skin cancer deaths, according to the American Cancer Society.

source : http://www.sciencedaily.com/releases/2014/09/140904183602.htm

Soy supplementation adversely effects expression of breast cancer-related genes

The impact of soy consumption on breast cancer prevention and treatment is not clear although many women believe soy supplementation is beneficial based primarily on results from epidemiological studies. Moshe Shike, M.D., from the Department of Medicine at Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College in New York, NY, and colleagues conducted a randomized placebo-controlled study of the effects of soy supplementation on gene expression and markers of breast cancer risk among women diagnosed with invasive breast cancer. The study, run between 2003 and 2007 at Memorial Sloan-Kettering, enrolled a total of 140 patients who were randomized to either soy supplementation (soy protein) or placebo (milk protein), which lasted from the initial surgical consultation to the day before surgery (range=7-30 days). Tumor tissues from the diagnostic biopsy (pre-treatment) and at the time of resection (post-treatment) were then analyzed. They observed changes in several genes that promote cell cycle progression and cell proliferation among women in the soy group.

The authors conclude, “These data raise concern that soy may exert a stimulating effect on breast cancer in a subset of women.”

In an accompanying editorial, V. Craig Jordan, O.B.E., D.Sc., Ph.D., FMedSci, from the Department of Oncology at the Georgetown University Lombardi Comprehensive Cancer Center, Washington, DC, discusses how timing of soy supplementation is critical and reviews the evidence in the literature on phytoestrogens, which are contained in soy, and their known action in breast cancer. He writes, the study by Shike et al. “…illustrates the dangers of phytoestrogen consumption too soon, around menopause, but the biology of estrogen in estrogen-deprived conditions suggests that phytoestrogen could have benefit a decade after menopause.” He cautions that appropriate doses of soy and timing of consumption are critical considerations.

source : http://www.sciencedaily.com/releases/2014/09/140904183725.htm