Jan 03, 2014
By Faith Hayden, Senior Writer/Editor
When Kornelia Polyak, MD, PhD, of the Dana-Farber Cancer Institute, was a high school student, she was fascinated by microbiology and cancer biology specifically. It was this natural scientific curiosity that motivated her to enroll in medical school and pursue a career in oncology. Dr. Polyak wanted to be the researcher, the clinical investigator touching the lives of possibly hundreds of thousands of patients through the development of new and improved cancer treatments.
In 1999, Dr. Polyak applied for and received a Career Development Award from the Conquer Cancer Foundation for her project, “Isolation of Tumor Suppressor Genes Inactivated in DCIS of the Breast.” She was mentored by Bert Vogelstein, MD, whom she remains in contact with to this day.
The Foundation was founded by leaders of the American Society of Clinical Oncology to further advances in prevention, treatment, and cures of all types of cancer by funding breakthrough research and supporting the careers of young researchers. The Foundation’s Grants and Awards Program, which started as an ASCO program in 1984 before transitioning over to the Foundation 15 years ago, has supported more than 1,000 of the brightest minds in clinical and translational cancer research worldwide.
“The Career Development Award got me started,” she said. “When you’re starting out, it’s so good to feel you can accomplish something and get funding for your ideas. As a junior person, to know that someone appreciates your research and efforts—it’s a positive feeling.”
DCIS: A 'huge clinical problem'
Dr. Polyak was inspired to research DCIS in 1997 after reading Ductal Carcinoma in Situ of the Breast, by Melvin J. Silverstein, MD. “I read that book, and I realized that no one seemed to understand what DCIS was,” Dr. Polyak said. “I realized it was a huge clinical problem and a challenging scientific problem.”
DCIS accounts for approximately 25% of breast cancers diagnosed in the United States. Although the cancer is noninvasive, 20% to 30% of low-grade DCIS will progress to invasive breast cancer if left untreated. Exactly which patients will progress and why remain unclear, leaving patients who develop DCIS, and the oncologists who treat them, with much uncertainty. But Dr. Polyak and colleagues have spent the last 15 years performing research to further our understanding of the disease.
For the CDA project, “we wanted to identify genes that were important to the activation of DCIS,” Dr. Polyak said. “What are the gatekeeping mutations? What are the genes that are really important for breast cancers to start? To understand that, you have to study early lesions.”
Decoding DCIS through research
Through the CDA project, Dr. Polyak and colleagues discovered that HIN1, a novel breast tumor suppressor gene at the time, was the first gene function lost in a majority of breast cancers. The CDA provided Dr. Polyak with enough preliminary data to apply for a National Institutes of Health (NIH) RO1 grant, which was funded, allowing her to continue her research on DCIS.
Although Dr. Polyak began her DCIS research focusing on cancer cells as gatekeeping mutations, the complete picture is proving to be more complex. Her later work revealed that DCIS resembles an invasive breast cancer based on the gene expression profile, but the major difference between DCIS and invasive breast cancer is that DCIS grows only within the milk ducts, contained by an intact myoepithelial cell layer. This layer forms a protective barrier between the tumor and healthy tissue, both physically and through tumor-suppression functions.
In a study published in Cancer Cell in 2004, Dr. Polyak and colleagues showed that the microenvironment within the breast was already changing in patients with DCIS.1 This paper became one of the most cited papers in Cancer Cell in 2004 and altered the way the oncology community thought about the disease, she said.2
“Everybody was focusing on the cancer cells, but what we said is that cancer is not just the cancer cells, it’s the whole structure,” Dr. Polyak explained.
In 2008, Dr. Polyak and colleagues published a paper in Cancer Cell showing through a xenograft model that the myoepithelial cell layer and basement membrane are key diagnostic features within DCIS.3 The disappearance of the myoepithelial cell layer is what leads to DCIS progression, making it the so-called gatekeeper of the progression from DCIS to invasive cancer. Dr. Polyak’s research in this area is ongoing, but the hope is that understanding the pathways regulating the difference between DCIS and invasive breast cancer may open up new therapeutic venues. Furthermore, Dr. Polyak hopes that her research will provide clarity on how aggressively to treat patients with DCIS, which is an ongoing controversy in breast cancer care today.
In fact, some DCIS can be such an indolent (harmless) disease, there is some debate in the community on whether it should be called “cancer” at all.
“DCIS is certainly a cancer, and some women can progress very quickly,” explained Dr. Polyak. “In general, most women get surgery and radiation for DCIS treatment. The risk of recurrence is very low, but the question is, do we need this for everyone? Ideally, we would not treat people who don’t need excessive treatment. But the trend has been of treating people more and more, partly because we don’t understand who is progressing and who is not.”
Dr. Polyak admits there is more research to be done on DCIS to fully understand which patients will progress and how to best treat those patients. But significant strides have been made toward this goal as a direct result of her research since she received the CDA launching it all. Dr. Polyak calls the CDA “encouragement” for young researchers, especially nowadays when other funding, such as NIH grants, seem nearly impossible to receive.
In addition to her scientific achievements, Dr. Polyak has continued the line of mentoring that began with her relationship with Dr. Vogelstein in 1999. “I have my trainees in the lab, and I have people who left the lab who I’m still in contact with,” she said. “That’s one of the most rewarding things for me. An undergraduate who was in my lab 10 years ago became a breast oncologist. She just wrote to me saying that the experience of being in my lab made her want to pursue this career path. It’s really rewarding to see that I’ve been able to inherit this enthusiasm, and that what we’re doing is important. There’s a limit to what we can do in our lab and our lifetimes, and it’s important to continue to have an impact.”
- Cancer Cell. 2004;6:17-32.
- Cancer Cell Looking Back. http://www.cell.com/cancer-cell/10thanniversary. Accessed December 18, 2013.
- Cancer Cell. 2008;13:394-406.