image: The t-shirt logo above was designed for the researchers by Ginny Espina. view more
Credit: Ginny Espina
FAIRFAX, Va.—Can a drug that has been used to treat malaria for years possibly be used to treat breast cancer before it becomes invasive? That's what researchers at George Mason University's Center for Applied Proteomics and Molecular Medicine (CAPMM) and Inova Breast Care Institute (IBCI) are trying to prove.
In January, the IBCI and CAPMM launched the PINC Trial, short for Preventing Invasive Breast Neoplasia with Chloroquine. This three-year clinical trial will test the effectiveness of the anti-malarial drug chloroquine in treating 90 women with ductal carcinoma in situ (DCIS), a type of breast cancer in which the cancer cells start in the milk ducts but have not yet become invasive and spread in the breast. Once the cancer cells start to spread in the breast and throughout the body, the condition is considered invasive and can often be fatal.
With an estimated 254,650 patients diagnosed in 2009 alone, breast cancer is the most common form of cancer in women according to statistics by the American Cancer Society. Approximately one quarter of those patients will have DCIS. Many more women are being diagnosed with DCIS, non-invasive breast cancer, with the routine use of screening mammography.
According to Kirsten Edmiston, MD, the trial's principal investigator and medical director of cancer services at Inova Health System, the trial is designed to prevent breast cancer cells from becoming deadly by killing pre-invasive cancer cells using a novel therapy with chloroquine, which has been used to treat malaria in the past.
"We have identified a particular cellular process called autophagy that is very involved in the survival of DCIS. In pre-clinical work, our team found that if we block autophagy in DCIS cells with chloroquine, that it kills the cells so that they're not able to become invasive," says Edmiston. "What this trial is proposing is to treat DCIS patients with chloroquine, an autophagy blocker before they receive standard of care surgery to treat their DCIS disease. We believe that the treatment will kill the DCIS cells before they become invasive and shrink the size of the DCIS. We may be able to prevent someone from needing a mastectomy and offer them breast conserving surgery."
Once patients have consented and enrolled, the size of their breast tumor will be measured through a non-invasive imaging technique called magnetic resonance imaging (MRI). Tissue samples will be taken from patients by Inova's doctors and transported to CAPMM for analysis. The PINC trial will combine chloroquine with Tamoxifen depending on the patient's tumor profile. After treatment, the MRI will be repeated to see if the tumor has shrunk and the patient will then proceed with surgery and follow up therapy.
What made the researchers think to use a malaria drug to treat breast cancer? According to Ginny Espina, a CAPMM research assistant professor, it works by starving the cancerous cells.
"Pre-cancerous cells have adapted to survive inside the milk duct without a blood supply and with very few nutrients. They overcome starvation through a process called autophagy. It's a way for a cell to make its own food and store it in a 'cookie jar.' In the breast ducts, the DCIS cells use these 'cookies' to survive and potentially spread. Simply put, chloroquine goes into the cell's 'cookie jars' and prevents the cells from using that food so that they eventually die from starvation," says Espina.
Of note, researchers are also using chloroquine in patients with unique types of brain tumors.
The treatment of DCIS is controversial because most DCIS lesions remain dormant and do not become invasive. Physicians do not want to over treat DCIS and cause unnecessary side effects if the DCIS does not become aggressive. However, chloroquine is a relatively safe treatment that does not have the severe side effects of typical chemotherapy.
"I think the most exciting thing is that we are able to offer women a new clinical trial using a well tolerated therapy in a new way to help prevent the development of invasive breast cancer and hopefully, ultimately, it will keep them from needing any additional treatment or surgery," says Edmiston. "We look forward to a future where all breast cancer can be prevented or destroyed."
The clinical study is being funded by George Mason University and Inova Health System. This study is based on scientific findings made under a Department of Defense funded breast cancer grant to George Mason University (Lance Liotta MD, PhD) in partnership with Inova.
Editors Note: Patients who are interested in participating should contact Stacey Banks, Inova's clinical research coordinator at 703-776-3565. In addition, an image of the t-shirt logo that was designed by one of the researcher's daughters is available to the media upon request.
About Inova Health System
Inova Health System is a not-for-profit healthcare system based in Northern Virginia that consists of hospitals and other health services, including emergency- and urgent-care centers, home care, nursing homes, mental health and blood donor services, and wellness classes. Governed by a voluntary board of community members, Inova's mission is to improve the health of the diverse community it serves through excellence in patient care, education and research. Inova provides a healthy environment for its patients, families, visitors, staff and physicians by prohibiting tobacco use on its campuses.
About George Mason University
Named the #1 national university to watch in the 2009 rankings of U.S. News & World Report, George Mason University is an innovative, entrepreneurial institution with global distinction in a range of academic fields. Located in Northern Virginia near Washington, D.C., Mason provides students access to diverse cultural experiences and the most sought-after internships and employers in the country. Mason offers strong undergraduate and graduate degree programs in engineering and information technology, organizational psychology, health care and visual and performing arts. With Mason professors conducting groundbreaking research in areas such as climate change, public policy and the biosciences, George Mason University is a leading example of the modern, public university.