October’s Breast Cancer Awareness Month brings an opportunity to highlight the work of one of our physicians in the Department of Pathology and Molecular Medicine: Dr. Sonal Varma. Dr. Varma is a breast pathologist with a joint appointment at Queen’s University and Kingston Health Sciences Centre (KHSC). She completed five years of residency in anatomic pathology at Queen’s and then pursued a fellowship in breast pathology at Weill Cornell Medical College in New York. She splits her time between clinical diagnostics and breast cancer research.
Dr. Varma’s research is two-fold: first, she has been working for over ten years on a new drug development in triple negative breast cancer. She explains, “Early on, our group with Dr. Bruce Elliott and Dr. Peter Greer at Queen’s Health Sciences recognized 'ezrin' as a potential target in breast cancer signaling. We conducted several stages of experiments to identify the mechanisms by which ezrin is activated and over-expressed in breast cancer. Furthermore, our group has shown that ezrin plays a role in chemotherapy resistance in breast cancer. Our understanding of ezrin’s role in chemotherapy resistance is still evolving. Other groups have shown similar findings in pancreatic cancer and osteosarcoma recently. This led us to move forward to design ezrin inhibitors and study whether they can potentially work as synergistic drugs with standard chemotherapy by making the cancer cells more sensitive. Our work has now moved from early phase to accelerated phase of drug discovery. This essentially means that we gathered enough evidence by in vitro cell line work, animal studies and correlative studies from clinical trial material to say that inhibiting ezrin-CD44 interactions can lead to improved response to standard chemotherapy regimens. Through our network at OICR, we have screened a 24,000-compound library and identified 318 hits that we are running follow-up assays to further evaluate. We have also applied for a grant to screen another 120,000 compounds to identify molecules that may have the potential for inhibiting ezrin-CD44 in the event that none of the original screened compounds prove to be useful in-vivo.”
The second area of focus for Dr. Varma is the development and validation of i-knife for breast cancer surgeries. “Margin positivity in breast cancer is associated with high local recurrence and hence, requires re-operations to achieve negative margins. The rate of positive margins in breast cancer is in the order of 25 per cent. Our work with the i-knife project is to develop and now validate a tool for intra-operative margin assessment in real-time. i-knife is an electro-cautery toll coupled with mass spectrometry capability. At Queen's, we have added navigational and GPS capability to this tool as well and named it 'navi-knife' - i-knife that uses mass spectrometry to analyze the cautery generated smoke in real-time during a surgery.” Dr. Varma details. “Our study is validating the accuracy of this system in flagging cancerous areas on a margin during surgery, so that targeted shave excisions can be performed by the surgeon in that same sitting. Our team is comprised of many SEAMO physicians, Engineering and Computing faculty members and Department of Chemistry faculty along with several trainees from these Departments.” Dr. Varma says this work will also have substantial healthcare system benefits by reducing re-operation rates and OR times. “We are validating the use of i-knife by remote support. Our ultimate vision is that the spectra can be analyzed by a team located centrally at KHSC that can provide real-time guidance about margin status to community surgeons with no intraoperative pathology support. We are conducting a pilot study on this remote support system for breast surgeries that are performed at the Hotel Dieu hospital site.”
One misconception about breast cancer Dr. Varma wants to debunk is that it is an “age-related disease.” She explains, “The trend I am seeing in my diagnostic practice is more and more younger women are being afflicted with breast cancer. I’d like to urge women, and men, to be vigilant of any symptoms and get themselves screened.” CDC data actually shows 11 per cent of breast cancers happen in women under 45 years of age, and Dr. Varma wants people to be aware. “The idea of ‘I am 30 and can’t have breast cancer in the absence of family history’ is not holding true anymore. In fact, breast cancer is the most common cancer in women from 15 to 39 years old.” This is why people should be vigilant of any lumps, pain, skin changes, or nipple discharge and bring it to the attention of their family physician as soon as possible, Dr. Varma warns.
She says another pivotal shift in our thinking about this disease is to be aware of breast cancer risk in transgender people, both men and women. “A recent study found more than 46-fold higher incidences of breast cancer in trans-women than cis-gender men, with the caveat that the rates of breast cancer are low in cis-gender men. The rates were much lower compared to cis-gender women.”
Dr. Varma’s closing remark on breast cancer is, “Recent years have seen many advances in treatment options. We are able to detect breast cancer earlier than we did before screening measures came into place. The survival rate for early-stage breast cancer is very good. Therefore, being vigilant of any changes in your breasts and taking timely action can be very helpful,”. “Breast reconstruction techniques have come leaps and bounds ahead in the last few years. The psycho-social aspects of being affected by this disease can be brutal; but now with advances in reconstruction and newer surgical techniques, women can enjoy a much better quality of life.”
Finally, for Dr. Varma, the battle against breast cancer is a personal one. “My mother is a breast cancer survivor and I have been a part of her journey over the last 10 years. Seeing all the research and clinical advances in the management of breast cancer fills me with both hope and pride.”