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A new study published May 31 in the Journal of Clinical Oncology reports that beta-blocker use is associated with improved relapse-free survival in all patients with breast cancer, including those with triple-negative breast cancer (TNBC), a particularly aggressive form of the disease.

Previous epidemiological research has shown that breast cancer is potentially more likely to recur in the context of chronic stress and that beta-blockers -- a class of drugs that help in diminishing the effects of the stress pathway by blocking adrenergic stimulation -- may improve breast cancer relapse. These drugs are often used for cardioprotection after heart attacks and to control cardiac arrhythmias and hypertension.

This collaborative study led by Amal Melhem-Bertrandt, M.D., an assistant professor in the Department of Breast Medical Oncology at MD Anderson, found that the use of beta-blockers in patients with breast cancer was associated with an approximately 50% reduction in breast cancer relapse after three years when compared to patients who were not on beta-blockers. The associated improvement in three-year overall survival in the beta-blocker group, although not significant, was approximately 35%..

Zometa.jpgMuch-anticipated and highly-disappointing results were presented today at the 33rd Annual CTRC-AACR San Antonio Breast Cancer Symposium. In an international trial of 3,360 women, the bone-building drug Zometa failed to prevent breast cancer recurrence and found no disease-free survival benefit among the majority of women with stage II/III disease.
 
Zometa did offer benefit to one subset of women: in those who were five years or more post-menopausal, there was a 29% improvement in overall survival.
 
Bisphosphonates' role in the treatment of breast cancer has been an active area of research focus, as previous clinical trials had shown that the class of drugs may have anti-cancer activity.
 
Sharon Giordano, M.D., associate professor in MD Anderson's Department of Breast Medical Oncology, was a commentator on today's press program where the findings were presented. In this video she shares her perspective.

In two small clinical trials, the experimental agent Olaparib has shown early promise in the treatment of inherited breast and ovarian cancers. The findings, recently published in Lancet, represent the first therapy to target the deleterious hereditary mutations BRCA1 and BRCA2.
 
Olaparib, is a PARP inhibitor, a class of drugs of growing interest in cancer research. The drug, an oral agent, specifically targets cancers caused by faulty BRCA1 or BRCA2 genes. Both parp enzymes and proteins produced by the BRCA genes are involved in the repair of DNA.
 
Approximately 5% to 10% of all cancers are inherited. About 10% of women with ovarian cancer and 5% of women with breast cancer have a BRCA1 or BRCA2 mutation. Those with the genetic predisposition have a far higher chance of developing cancer in their lifetime, and at an earlier age.
 
"Women with a BRCA mutation and their family members who may also be at risk have a unique set of medical needs. Currently, we are able to offer cancer risk management to healthy women with BRCA mutations -- ranging from screening to preventative surgeries -- so that they can make personal decisions, in terms of their individualized cancer risk," says Banu Arun, M.D., associate professor in the Department of Breast Medical Oncology at MD Anderson. "Yet, we now know that BRCA cancers might behave differently than those without the mutation. Given this understanding, our ultimate goal is to be able to provide personalized treatment strategies to women with a BRCA-related cancer."
   
MD Anderson enrolled patients in both of the international multi-center studies. The trials were similar in design -- both compared dosage levels of Olaparib in women previously treated for their disease. The results were impressive: the objective response rates in women taking the higher dose in the ovarian and breast cancer studies was 41% and 33%, respectively. The drug was well tolerated with women experiencing few side effects.

"These findings, while early, may represent a paradigm shift in how we approach breast and ovarian cancer patients with BRCA mutations," says Karen Lu, M.D, professor in the Department of Gynecologic Oncology. "In addition to offering counseling and screening that are of benefit to the sisters, daughters and other female members of the patient's family, one day we may be able offer women with BRCA positive breast and/or ovarian cancers a therapy specifically targeted at their mutation."
 
Follow-up clinical trials in both diseases are ongoing. In the lab, Arun is investigating the role of parp inhibition in hormone positive disease and in combination with other chemotherapy agents.


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By Jennifer Litton, M.D.

In today's oral abstract session for local and adjuvant treatment of breast cancer at ASCO, several studies were reported, and two are highlighted below.

Dr. Giuliano reported the results from ACOSOG study Z0011. This study evaluated the need for further axillary lymph node dissection in women who had up to three sentinel lymph nodes removed during surgery, had a positive lymph node, but did not go on to have further lymph node surgery. The researchers reported no significant differences in local disease recurrence or in overall survival.

This may be the beginning of a major shift in how we address and treat lymph nodes during surgery for women who have biologically low-risk tumors and are treated with whole-breast radiation that also encompass the lymph node area.

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Additionally, Dr. Albain reported on potential causes of racial survival disparities in the SWOG 8814 study. Historically, African-American women have been reported to have worse breast cancer outcomes and overall survival after a diagnosis of breast cancer. This analysis tried to evaluate if there was a biological difference in the tumors by race when evaluated in a controlled clinical trial setting.

The researchers looked at postmenopausal women with ER-positive tumors. Nine percent of the women involved in the above trial were African-American. All trial participants had the same treatment and scheduled follow-ups. Additionally, the researchers used the Oncotype DX test to estimate risk of recurrence by using recurrence scores (RS). There was no significant difference in the distribution of recurrence scores, although there was a trend to higher recurrence scores in African-American women. 


Chemotherapy worked equally well in African-American women compared with the rest of the women who participated in the study. The outcomes did, however, show differences in recurrence and survival when controlled for all other factors. The researchers noted a difference with higher ki-67 - a marker of proliferation, or how fast a tumor divides - in the tumors of African-American breast cancer patients. Therefore, further evaluations of these differences in a controlled clinical trial setting need to be done.


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