(Press-News.org) Most triple-negative breast cancer patients who were treated with chemotherapy to shrink the tumor prior to surgery still had multiple genetic mutations in their tumor cells, according to a study by Vanderbilt-Ingram Cancer Center (VICC) investigators.
Finding multiple mutations instead of just one primary mutation that can be targeted for therapy sheds more light on the challenges of treating triple-negative breast cancer.
The study, led by Justin Balko, Pharm.D., Ph.D., and research faculty in the laboratory of Carlos Arteaga, M.D., director of the Breast Cancer Program at VICC, was presented at the 2012 CTRC-AACR San Antonio Breast Cancer Symposium, held Dec. 4-8.
Approximately 15 percent of breast cancer patients in the U.S. have triple-negative cancer – a form of the disease that disproportionately affects young African-American women. Triple-negative breast cancer has traditionally been more difficult to treat than other forms of the disease.
"The standard of care for many patients with triple-negative breast cancer is to administer chemotherapy before surgery to shrink the tumor," Balko said. "Unfortunately, about 70 percent of patients still have some residual disease at the time of surgery, despite treatment."
Balko and colleagues profiled residual tumor tissue from 114 patients with triple-negative breast cancer who had received chemotherapy prior to surgery. Triple-negative breast cancer cells do not have estrogen receptors, progesterone receptors, or large amounts of the HER2/neu protein.
The investigators were able to evaluate DNA from 81 tumors and used deep sequencing to examine 182 oncogenes and tumor suppressors that are known to be altered in human cancers. Instead of finding similar genes affected among the patients, they found a diverse set of genes were altered.
"We already knew that triple-negative breast cancer is driven by a diverse group of genetic alterations," Balko said. "So, in one way, we fell further down this rabbit hole, but we also found some things that could be promising therapeutically, such as frequent MYC, MCL1 and JAK2 amplifications as well as mutations in the PI3K pathway."
The additional genetic alterations found in the study may provide targets for new therapies.
Balko said the next step is to confirm the findings in a larger patient group, and if the findings are replicated, broad molecular approaches will be needed to help develop personalized therapies for triple-negative breast cancer. It also will be necessary to explore the therapeutic sensitivity of breast cancers harboring these lesions in the laboratory to know how to treat patients who have these alterations.
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This research was a collaboration of the Breast Cancer Research Program at Vanderbilt, the Instituto Nacional de Enfermedades Neoplásicas (Lima, Perú) and Foundation Medicine (Cambridge, Mass.). It was funded by the Susan G. Komen for the Cure Foundation, the National Cancer Institute – a division of the National Institutes of Health (Vanderbilt Breast SPORE Grant P50 CA98131) and the Lee Jeans/Entertainment Industry Foundation Translational Breast Cancer Research Program.
The Cancer Therapy & Research Center (CTRC) at The University of Texas Health Science Center at San Antonio, the American Association for Cancer Research (AACR) and Baylor College of Medicine are joint sponsors of the San Antonio Breast Cancer Symposium. END
(Boston) – According to a new study from the Slone Epidemiology Center (SEC) at Boston University, African-American women who reported suffering abuse before age 11 had a greater likelihood of adult-onset asthma compared to women whose childhood and adolescence were free of abuse.
The study, which is published online in the Journal of Allergy and Clinical Immunology, was led by Patricia Coogan, DSc, senior epidemiologist at SEC and associate professor of epidemiology at the Boston University School of Public Health.
This study followed 28,456 African-American women, ...
New Rochelle, NY, December 6, 2012—Enzymes play a crucial role as biocatalysts, increasing the speed and efficiency and decreasing the energy consumption of biochemical reactions in many industrial processes. The advantages of using compressed propane to enhance the biocatalytic activity of an industrial enzyme are described in an article published in Industrial Biotechnology, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers (http://www.liebertpub.com). The article is available free on the Industrial Biotechnology website (http://www.liebertpub.com/ind). ...
PHILADELPHIA — Periodontitis, a form of chronic gum disease that affects nearly half of the U.S. adult population, results when the bacterial community in the mouth becomes unbalanced, leading to inflammation and eventually bone loss. In its most severe form, which affects 8.5 percent of U.S. adults, periodontitis can impact systemic health.
By blocking a molecular receptor that bacteria normally target to cause the disease, scientists from the University of Pennsylvania have now demonstrated an ability in a mouse model to both prevent periodontitis from developing and ...
Highlights
The incidence of the most severe form of acute kidney injury has increased 10% per year on average over the past decade.
Deaths associated with the condition have doubled during that time.
Washington, DC (December 6, 2012) — Acute kidney injury (AKI), an abrupt or rapid decline in kidney function, is a serious and increasingly prevalent condition that can occur after major infections, major surgery, or exposure to certain medications. The incidence rates of the most serious form of AKI—which requires dialysis—increased rapidly in all patient subgroups ...
The catastrophic drought last year in the Horn of Africa affected millions of people but also caused the extremely late arrival into northern Europe of several migratory songbird species, a study from University of Copenhagen published today in Science shows. Details of the migration route was revealed by data collected from small back-packs fitted on birds showing that the delay resulted from an extended stay in the Horn of Africa.
The extensive 2011 drought in the Horn of Africa had significant consequences for European songbirds such as thrush nightingale and red-backed ...
HOUSTON – (Dec. 7, 2012) – For much of her professional life, Dr. Susan Rosenberg (www.bcm.edu/genetics/?pmid=11034) has studied the puzzling response of bacteria to stress and the mutations that result. In the current issue of the journal Science (www.sciencemag.org), she puts together the pieces of that puzzle, describing most of the members of an elaborate gene network that functions in causing mutations during repair of double-stranded breaks in the DNA of stressed cells.
"We now know the 93 genes more than half of which are funneling into three nodes that go down ...
Scientists from New Zealand, Austria and the UK have created the world's smallest reaction chamber, with a mixing volume that can be measured in femtolitres (million billionths of a litre).
Using this minuscule reaction chamber, lead researcher Peter Derrick, professor of chemical physics and physical chemistry and head of the Institute of Fundamental Sciences at Massey University in New Zealand, plans to study the kind of speedy, nanoscale biochemical reactions that take place inside individual cells. This work appears in the latest issue of the European Journal of Mass ...
Antidepressants are the most widely used treatment for people with moderate to severe depression. However, up to two thirds of people with depression don't respond fully to this type of treatment. New findings, published in The Lancet, have shown cognitive behavioural therapy (CBT)*, provided in addition to usual care, can reduce symptoms of depression and help improve patients' quality of life.
This is the first large-scale trial to test the effectiveness of CBT — a type of talking psychotherapy — given in addition to usual care that includes antidepressants. The National ...
The family of disorders known as ataxia can impair speech, balance and coordination, and have varying levels of severity. Scientists from the Universities of Oxford and Edinburgh have identified a new member of this group of conditions which is connected to 'Lincoln ataxia', so called because it was first found in the relatives of US President Abraham Lincoln. The results are published in the journal PLOS Genetics.
Lincoln ataxia affects the cerebellum, a crucial part of the brain controlling movement and balance. It is caused by an alteration in the gene for 'beta-III ...
Women with higher circulating carotenoid levels are at a reduced risk of breast cancer according to a study published December 6 in the Journal of the National Cancer Institute
Carotenoids, which are micronutrients found in fruits and vegetables, have been found to have anticarcinogenic properties. Previous experimental studies have shown that carotenoids inhibit the tumor progression and reduce proliferation of estrogen receptor–positive (ER+) and estrogen receptor–negative (ER-) breast cancers. Despite the inverse association between carotenoids and breast cancer ...
