Posts Tagged ‘major’

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

Family conflicts, other non-physical worries before cancer surgery raise patients’ complication risk

The findings are published in the Journal of Gastrointestinal Surgery.

“We know that quality of life is a very complex thing, but we can now measure it and work with it almost like blood pressure,” says lead author Juliane Bingener, M.D., a gastroenterologic surgeon at Mayo Clinic in Rochester. “We can say, ‘This is good, this is in the normal range, but this one here, that is not good, and maybe we should do something.'”

Quality of life as measured in the study is about more than happiness and how well people feel physically, Dr. Bingener says. It also includes the financial, spiritual, emotional, mental and social aspects of their lives and whether their needs are being met.

Researchers studied 431 colon cancer surgery patients and found that before surgery, 13 percent had a quality of life deficit, defined as an overall quality of life score of less than 50 on a 100-point scale.

Nearly three times as many patients who entered surgery with a quality of life deficit experienced serious post-surgery complications as those with a normal or good quality of life score. Patients with a postoperative complication spent 3.5 days longer in the hospital on average than those who didn’t.

“The question I’m exploring is whether, if we understand before surgery that someone is in the red zone for quality of life, can we do something to help them cope with the new stress that’s going to come, so they’re better equipped to go through surgery?” Dr. Bingener says.

Preventing complications by intervening with behavioral therapy or other assistance would likely cost much less than an ICU stay for an infection after major surgery, Dr. Bingener notes.

Stress can weaken patients’ immune response, putting them at higher risk of infection. A patient’s outlook on life can also influence how active they are in working to recover.

“You have a surgery, you’re lying there in pain, now you wonder, ‘Why should I even get up and walk around? Why do I have to do these deep-breathing exercises? I don’t feel like it.’ You might get pneumonia much faster than somebody who says, ‘Oh, I have to get up. There’s something worth living for, my quality of life is good and I need to get back to that,'” Dr. Bingener says.

The study is part of ongoing work by Mayo to identify and address factors that can influence patients’ recovery from cancer surgery, to help improve their outcomes. Years ago, physicians were just concerned with whether patients survived cancer, because survival was so hard to achieve, Dr. Bingener says. Now, there is growing awareness of the mind’s influence on the body’s health.

“We’re understanding much better now that patients are not just a body with a disease: There’s a whole person with that, and everything plays together,” Dr. Bingener says. “Now that survival is possible, we want to achieve it in a way that preserves normal life for patients as much as possible. And we think that’s probably also the most economical way to go.”

source : http://www.sciencedaily.com/releases/2014/09/140902114416.htm

Understanding, improving body’s fight against pathogens

While they exist in small populations in humans, the large amounts of antibodies secreted by plasma cells make them key to the body’s immune system and its ability to defend itself against pathogens, such as bacteria and viruses. Proper maintenance of a pool of plasma cells is also critical for the establishment of lifelong immunity elicited by vaccination.

Dysregulation of plasma cell production and maintenance could lead to autoimmune diseases and multiple myeloma. Autoimmune diseases occur when the immune system does not distinguish between healthy tissue and antigens, which are found in pathogens. This results in expansion of plasma cells which produce excessive amounts of antibodies leading to destruction of one’s own healthy tissue. The discoveries by scientists in BTI’s Immunology Group have improved understanding of the mechanism by which plasma cells are developed from a major class of white blood cells called B cells.

For the first time, the molecule DOK3 was found to play an important role in formation of plasma cells. While calcium signalling typically controls a wide range of cellular processes that allow cells to adapt to changing environments, it was found to inhibit the expression of the membrane proteins essential for plasma cell formation. These membrane proteins include PDL1 and PDL2, and represent some of the key targets for the development of immunotherapy by pharmaceutical companies. DOK3 was able to promote the production of plasma cells by reducing the effects of calcium signalling on these membrane proteins. The absence of DOK3 would thus result in defective plasma cell formation.

In another study, BTI scientists discovered the importance of SHP1 signalling to the long term survival of plasma cells. While the molecule SHP1 has a proven role in prevention of autoimmune diseases, it was found that the absence of SHP1 would result in the failure of plasma cells to migrate from the spleen where they are generated to the bone marrow, a survival niche where they are able to survive for much longer periods. This could result in a reduction of the body’s immune response and thus, an increased susceptibility to infections and diseases. The scientists in this study also successfully rectified the defective immune response caused by an absence of SHP1 by applying antibody injections, which might advance the development of therapeutics. On the other hand, targeting SHP1 might be a strategy to treat multiple myeloma where the accumulation of cancerous plasma cells in the bone marrow survival niches is undesirable.

Findings hold potential for improved treatment

The discovery of these new targets for modulating the antibody response allows the development of novel therapeutic strategies for patients with autoimmune diseases and cancer.Understanding the mechanism that governs plasma cell differentiation is also critical for the optimal design of vaccines and adjuvants, which are added to vaccines to boost the body’s immune response.

Prof Lam Kong Peng, Executive Director of BTI, said, “These findings allow better understanding of plasma cells and their role in the immune system. The identification of these targets not only paves the way for development of therapeutics for those with autoimmune diseases and multiple myeloma, but also impacts the development of immunological agents for combating infections.”

source : http://www.sciencedaily.com/releases/2014/09/140902115036.htm