Basser Center for BRCA

Basser Investigator Publications

Investigators at the Basser Center for BRCA publish in a wide range of peer-reviewed journals focused on all aspects of cancer and genetics such as Journal of Clinical Oncology, Cancer, Breast Cancer Research and Treatment, PLOS Genetics, Nature Genetics, Nature Structural and Molecular Biology, Cancer Discovery, Journal of Medical Genetics, and many more.

Research Roundup

Penn Study Shows Risk of Breast and Ovarian Cancer May Differ By Type of BRCA1, BRCA2 Mutation

In a study involving more than 31,000 women with cancer-causing mutations in the BRCA1 or BRCA2 genes, researchers at the Basser Center for BRCA, the Abramson Cancer Center, and the Perelman School of Medicine at the University of Pennsylvania demonstrated that risks of breast or ovarian cancer are different depending on where the mutation is within the gene. Authors say the results – which show that some mutations in some areas confer higher risks of breast cancer relative to other mutations, while mutations other areas show relatively higher risks of ovarian cancer – may lead to more effective cancer risk assessment, care and prevention strategies. The results are published in the April 7 issue of the Journal of the American Medical Association.

 

The present study identified “Breast Cancer Cluster Regions” and “Ovarian Cancer Cluster Regions,” which are groups of mutations in the BRCA genes, that tend to be associated with different relative risks for developing cancer.  In this study, relative risk describes the likelihood that one mutation leads to cancer in comparison to the likelihood of another mutation leading to cancer.  This is different from absolute risk (or, actual risk), which describes the probability of a carrier developing a certain cancer in general. An example of absolute risk is the 60-80% lifetime risk of breast cancer in women who carry a BRCA1 mutation. At this time, it is not possible to compute an individual's personal risk and these data do not change that range of absolute risk for breast and ovarian cancer.

 

This study is the most detailed study defining the differences in risk associated with different BRCA1 and BRCA2 mutations. However, although these results are intriguing the difference between the absolute numbers are relatively small. In addition, it is critically important that these finding be confirmed prior to using these results in the clinic. It has not been determined what level of absolute risk change between mutation types will influence medical decision making and standards of care, such as timing of preventive surgery, for carriers of BRCA1 and BRCA2 mutations. Read the press release here.

Olaparib Shows Success in Tumor Response Rate for Patients with BRCA-Related Cancers

Olaparib, an experimental twice-daily oral cancer drug, produces an overall tumor response rate of 26 percent in several advanced cancers associated with BRCA1 and BRCA2 mutations, according to new research co-led by the Abramson Cancer Center, including Susan Domchek, MD, Executive Director of the Basser Center for BRCA and senior author. Results of the phase II study were recently published in the Journal of Clinical Oncology. The international research team studied nearly 300 patients with inherited BRCA1 and BRCA2 mutations who had advanced cancers that were still growing despite standard treatments. Patients were enrolled and treated at 13 centers around the world. In addition to the overall shrinkage or disappearance rate in tumors following treatment with olaparib, researchers also found no further growth in cancer for at least eight weeks in 42 percent of patients. Read more about the results of this study here. The drug was recently approved by the FDA to treat advanced stage ovarian cancer in women with BRCA mutations. Read the FDA press release here.

Basser-Funded Team Finds Ovarian Cancer Oncogene in "Junk DNA"

Basser-funded investigator Lin Zhang, MD, Research Associate Professor in the Department of Obstetrics and Gynecology at the Perelman School of Medicine at the University of Pennsylvania, mined “junk DNA,” or what lies outside of protein-coding genes, and recently identified a non-protein coding  RNA whose expression is linked to ovarian cancer. This discovery provides a potential biomarker of BRCA-related cancer and the potential for new anti-cancer therapeutics. The study was published in Cancer Cell. Read more about this discovery and publication here.

Penn Researchers Explain How Ends of Chromosomes are Maintained for Cancer Cell Immortality

Maintaining the ends of chromosomes, called telomeres, is a requisite feature of cells that are able to continuously divide and also a hallmark of human cancer. “Telomeres are much like the plastic cap on the ends of shoelaces -- they keep the ends of DNA from fraying,” says Roger Greenberg, MD, PhD, Associate Professor of Cancer Biology in the Perelman School of Medicine at the University of Pennsylvania and Director of Basic Science for the Basser Center for BRCA. In a study published in Cell, he and his colleagues describe a mechanism for how cancer cells take over one of the processes for telomere maintenance to gain an infinite lifespan. Read more about this discovery and publication here

Basser-Funded Team Describes Cell Communications That Contribute to Treatment Resistance in Breast Cancer Patients

In a study published in the journal Cell, Andy J. Minn, MD, Assistant Professor of Radiation Oncology at the Perelman School of Medicine and the Abramson Family Cancer Research Institute, and colleagues report findings from a preclinical study investigating the communication between stromal cells (those in the microenvironment of the tumor) and cancer cells in an effort to better understand treatment resistance in breast cancer patients. The researchers revealed a “crosstalk” between both sets of cells using paracrine signaling (communication by nearby cells) and juxtacrine signaling (communication by adjacent cells)—which increased the number of therapy-resistance cancer cells. Identifying such pathways not only provides insight into important biological mechanisms but also potential biomarkers for prognosis, prediction, and therapy. Read more here.

 

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