25 Years of
Transformational BRCA
Breakthroughs
2019
Progress Report
The BRCA1 and BRCA2 genes were discovered 25 years ago. Since then, our understanding of hereditary cancers has profoundly changed. The Basser Center was founded in 2012 to accelerate this understanding and propel progress in treatment opportunities and scientific discovery. Basser’s mission is to see a world free of the devastating effects of BRCA-related cancers.
Basser Center Takes Aim at BRCA
SUSAN M. DOMCHEK, MD
Basser Professor in Oncology
Basser Center Executive Director
At Basser, 25 million people affected means 25 million opportunities for a cure.
The discovery of BRCA1 and BRCA2 sparked incredible innovation in cancer research. The Basser Center at Penn Medicine’s Abramson Cancer Center turned that initial spark into a flame of promise — a focus on ensuring that future generations have better options. Basser is committed to collaborative science and compassionate clinical care. We know that approximately 25 million people are affected worldwide, but only 10% are aware of their mutation status. By raising awareness, Basser is saving lives. While our innovative research starts at Penn, it extends to best-in-class institutions around the world. This collective spirit has led to unparalleled collaboration and will push us to faster progress.
Our goal is to engage as many esteemed partners as possible in this mission. This collaborative approach is revolutionizing the field, expanding genetic testing, and spreading life-saving information to high-risk populations.
How Your Dollars Have Made a Difference
How Your Dollars Have Made a Difference
SWIPE 
BRCA by the Numbers
1 in 300
people in the general population are estimated to have a BRCA mutation
1 in 40
people in the Ashkenazi Jewish population have a BRCA mutation
1 in 7
women with ovarian cancer have a BRCA mutation
Increased Risk of Cancer
7%
Men and women with a BRCA2 mutation have up to a 7% lifetime risk of pancreatic cancer
25%
Men with a BRCA2 mutation have up to a 25% lifetime risk of aggressive prostate cancer
50%
Women with a BRCA1 mutation have up to a 50% lifetime risk of ovarian cancer
75%
Women with a BRCA1 or BRCA2 mutation have up to a 75% lifetime risk of breast cancer
Past
Where We Started
Past
The journey to understanding BRCA1 and BRCA2 began with a spark. In 2019, we recognized the 25th anniversary of the first time researchers identified the complete sequence of BRCA1 and quantified the corresponding lifetime risks of breast and ovarian cancers.
BRCA1 is cloned.
The most common BRCA1 mutation is traced back to families of Ashkenazi Jewish descent. Subsequently, two additional mutations — one in BRCA1 and one in BRCA2 — are identified as common Founder mutations in individuals of Ashkenazi Jewish descent. Mutations in BRCA1 and BRCA2 are seen in every race and ethnicity.
BRCA2 is cloned.
BRCA2 mutations are linked to male breast cancer.
BRCA2 mutations are linked to prostate cancer.
Research solidifies the role of BRCA1 in homologous recombination.
Bilateral preventive mastectomy is demonstrated to substantially reduce the incidence of breast cancer among women with mutations in BRCA1 or BRCA2.
The role of 53bp1 in regulating BRCA1 is discovered. (Penn Medicine's Roger Greenberg, MD, PhD, is currently pursuing research in this critical area.)
PARP inhibitors are shown to kill cells that do not have BRCA1 or BRCA2 protein present.
A paradigm-changing discovery by Basser Center’s Ronny Drapkin, MD, and colleagues revealed that the majority of high-grade serous ovarian cancers arise in the fallopian tubes.
Research led by Basser Center Executive Director Susan M. Domchek, MD, showed strong evidence that removal of the ovaries improved overall survival in BRCA1 and BRCA2 mutation carriers.
Mindy and Jon Gray established the Basser Center for BRCA.
Basser Global Prize is established and endowed by Shari and Len Potter.
FDA approved first PARP-inhibitor olaparib for BRCA-related ovarian cancer based on research led by the Basser Center. (PARP-inhibitors are a therapy that can stop cancerous cells from repairing themselves.)
Evidence shows that PARP inhibitors may be helpful in BRCA1/2-related pancreatic and prostate cancer.
Basser Center research supported the FDA approval of rucaparib for BRCA-related ovarian cancer.
FDA approved niraparib for all ovarian cancers.
Basser Center studies led to the FDA approval of olaparib and talazoparib for BRCA-related breast cancer.
Basser Center investigator Kim Reiss Binder, MD, showed that PARP Inhibitors are an effective and less toxic maintenance therapy for patients with BRCA-related pancreatic cancer.
Olaparib is approved in first line maintenance for BRCA1/2-related ovarian cancer.
Present
New in 2019
Present
The Basser Center continues to extend the reach of its top researchers and clinicians by constantly innovating and collaborating to bring the best care possible to patients around the world.
In 2019 alone, Basser has:
20
Funded Research
Projects
6
External
Grants Awarded
$12M
Raised From Over
1,000 Donors
Our Key Research Breakthroughs
PARP Inhibitor Trial for BRCA 1/2 and PALB2-Related Pancreatic Cancer
Pancreatic cancer is the third-leading cause of cancer deaths in the United States, and one of the most difficult cancers to treat. And while BRCA mutations are most closely associated with breast and ovarian cancers, they also lead to an increased risk for pancreatic cancer. The discovery of these relationships is already improving outcomes for affected patients. The Basser Center’s Kim Reiss Binder, MD, an Assistant Professor of Hematology-Oncology, is studying the use of PARP inhibitors for pancreatic cancer patients with a BRCA mutation.
In 2019, Dr. Reiss Binder presented preliminary results from a clinical trial that showed that switching patients with incurable pancreatic cancer to the PARP inhibitor rucaparib as maintenance therapy instead of continuing intensive chemotherapy either shrunk tumors or stopped them from growing altogether. She is now preparing to launch a national trial to use this therapy in a frontline treatment setting, in the hope that it will offer cures to more patients. These discoveries represent on opportunity to change the face of BRCA-related pancreatic cancer, and give affected patients a chance at a better and longer life.
To be able to offer a targeted therapy with much less toxicity, even if only for a subset of our patients, was an extraordinary breakthrough for our patients with metastatic pancreatic cancer. Now we will apply this same therapy to patients with curable disease, in the hope that we can save more lives.
KIM REISS BINDER, MD
Assistant Professor of Medicine
Research Insight
The PARP Inhibitor study investigates whether patients can safely discontinue intravenous chemotherapy and, instead, keep their cancer in check with a pill.
Combination Approaches to Treat BRCA-Related Breast Cancer
Basser Center Executive Director Susan M. Domchek, MD, led a multicenter study evaluating the combination of the drugs olaparib and durvalumab in patients with germline (inherited) BRCA-related breast and ovarian cancer with advanced disease. The study results found that this combination shows promise. This research will be published in The Lancet Oncology 2020.
“Patients with responses showed durable benefit,” Dr. Domchek says of the breast cancer cohort, “and progression-free survival and overall survival compared well with standard-of-care therapy for these populations.” While additional analysis is needed to determine which types of patients would benefit most from these combination therapies, it offers the hope of new viable and less toxic treatment options for patients.
An additional study of individuals with advanced BRCA1/2 cancer of many types treated with avelumab (an immune therapy) and talazoparib (a PARP inhibitor) has just closed to accrual and final results are being eagerly awaited.
The hope is that by combining these two therapies we are able to prolong a patient’s response, helping them fight their disease longer.