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.
To view a list of all recent publications from Basser affiliated researchers, visit PubMed.org
Looking Beyond BRCA1/2 Among Breast Cancer Patients (August 2018)
Research from Kara N. Maxwell, MD, PhD, an assistant professor of Hematology-Oncology, finds rates of inherited mutations in genes other than BRCA1/2 are twice as high in breast cancer patients who have had a second primary cancer – including, in some cases, different types of breast cancer – as compared to patients who have only had a single breast cancer. Read more at Oncology Times.
Ovarian Cancer Drug Shows Promise in Pancreatic Cancer Patients with BRCA Mutation (May 2018)
A targeted therapy that has shown its power in fighting ovarian cancer in women, including those with BRCA1 and BRCA2 mutations, may also help patients with aggressive pancreatic cancer who harbor these mutations and have few or no other treatment options. An international team of researchers led by the Perelman School of Medicine and the Basser Center reported their findings this week in JCO Precision Oncology. Read more at Penn Medicine.
PARP-1 May be Key to Effectiveness of PARP Inhibitors, and Now Researchers Can Image It (April 2018)
Penn Medicine researchers – including Basser's Director of Basic Science, Roger Greenberg, PhD, MD – have used CRISPR/Cas9 gene editing technology to isolate a key genetic feature that could cause resistance to PARP inhibitors in patients with ovarian cancer – and they’ve also proven they have a way to see that feature using PET imaging. The team found PARP inhibitors – a type of targeted therapy that kills cancer cells with mutations in their DNA repair genes while sparing healthy tissue that does not have the mutations – specifically require the presence of PARP-1 in order to take effect. They also show that a radioactive tracer developed at Penn makes PARP-1 visible during PET scans and may provide a method of measuring PARP-1 in ovarian cancer that complements biopsy. The findings of this multidisciplinary team – which included radiologists, pathologists, and oncologists from the University of Pennsylvania’s Perelman School of Medicine – were published in the Journal of Clinical Investigation this month. Read more at Penn Medicine.
Penn Study Finds Relationship between PTEN Loss, Potential for Immune Response in BRCA 1/2-Deficient Ovarian Cancer (April 2018)
The protein known as phosphatase and tensin homolog (PTEN) is frequently mutated or affected by cancer as tumors develop. Now a new study from the Basser Center shows PTEN may serve as a marker for whether a patient with BRCA 1-2 deficient ovarian cancer is likely to respond to checkpoint inhibitor therapy. Researchers found the tumors that had PTEN loss were less likely to generate an immune response than tumors that maintain PTEN levels.
Breast Cancer Caused by Genetic Mutation Gets First Approved Treatment Through FDA Approval of Olaparib (January 2018)
The U.S. Food and Drug Administration recently approved olaparib as the first treatment for advanced breast cancer caused by mutations in BRCA genes, in an important step in the fight against inherited cancers. This is an extension of the approval of olaparib from 2014, when it was approved to treat BRCA-related ovarian cancer. Basser Executive Director Susan Domchek co-led the OlympiAD trials that led to FDA approval of olaparib for the treatment of breast cancer. “Fifty percent of the BRCA patients in this trial were triple negative,” she said. “So all of a sudden, we have a new option for a subset of triple negative patients.” Trials are now underway to see if Lynparza (olaparib) can prevent recurrence if it is given to patients after initial surgery and chemotheraphy, and to see its results in combination with other targeted therapies. Read more at Philly.com.
Penn Effort to Expand Trials of Olaparib Leads to New Treatment Options for Patients with Advanced BRCA-Related Breast Cancer (June 2017)
Six years ago an international team of physician scientists known as BRCA-TAC led a charge to advance clinical testing of the PARP inhibitor olaparib in cancer patients with known inherited mutations in BRCA1 and BRCA2. This June, during the plenary session of the American Society of Clinical Oncology Annual Meeting, that push came full circle with the presentation of results of the phase III OlympiAD trial demonstrating for the first time that olaparib is superior to chemotherapy in patients with BRCA-related advanced breast cancer.
Hope and Hype Around Cancer Immunotherapy (June 2017)
Immunotherapy treatments are on the rise, thanks to recent studies carried out by international researchers. These treatments harnesses the body's own immune system to target and attack a disease, and includes vaccines, antibodies, drugs, and more. The Abramson Cancer Center's Dr. Robert Vonderheide, in collaboration with the Basser Center, is leading vaccine-based trials for the prevention of cancers associated with BRCA1 and BRCA2 gene mutations.
Study Sheds Light on Racial Disparities of Cancer-Causing Genetic Mutations (December 2016)
Most studies reporting the prevalence of breast- and ovarian-cancer causing genes have been conducted with Caucasian women, leaving questions about the role that these same genes play in African-American patients with inherited cancers. A team led by researchers at the Basser Center for BRCA in the Abramson Cancer Center has taken a step towards a better understanding of this complex subject. Among the results, when compared to previous research focusing on Caucasian women, the study revealed differing patterns of cancer-causing mutations in African-American women.
First Glimpse of End-of Chromosome Repair in Real Time (October 2016)
In a new study published this week in Nature, senior author Greenberg and colleagues have developed a first-of-its- kind system to observe repair to broken DNA in newly synthesized telomeres, an effort that has implications for designing new cancer drugs.
Teen Girls with a Family History of Breast Cancer Do Not Experience Increased Depression or Anxiety (September 2016)
More and more girls are expected to have to confront breast cancer fears as modern genomics technology makes it easier to detect strong risk factors such as inherited BRCA1/2 mutations. But a new study shows that adolescent girls in families with a history of breast cancer or a high-risk BRCA1/2 mutation do not experience negative psychological effects, on average, and even seem to have higher self-esteem than their peers. Read more at Philly.com.
Some at-risk patients opted out of comprehensive cancer gene screening when presented with the opportunity to be tested for the presence of genes linked to various cancers, according to a recent study led by researchers at the Perelman School of Medicine and the Basser Center for BRCA in Penn's Abramson Cancer Center. The results of the study by lead author Angela R. Bradbury, MD, an assistant professor of Hematology/Oncology in Penn's Abramson Cancer Center, were published in Genetics in Medicine. Read more here.
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, 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.
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.
Basser-Funded Team Finds Ovarian Cancer Oncogene in "Junk DNA" (September 2014)
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.
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.