At Work: Experimental Pathologist Jorge Reis-Filho

Pictured: Luciano Martelotto, Catherine Cowell & Jorge Reis-Filho

Postdoctoral research fellows Luciano Martelotto and Catherine Cowell with experimental pathologist Jorge Reis-Filho

The focus of Jorge Reis-Filho’s research is to develop a classification system for all breast cancers that is reflective not only of features seen under the microscope but also of a tumor’s molecular characteristics and response to therapies. Here, he talks with us about how he and his colleagues work to determine the genetic alterations that drive the malignant behavior of certain breast cancer cells. The ultimate aim of his research is to find new ways to match patients with the therapies that will be of most benefit to them.

Breast cancer is not a single disease, but a collection of different diseases that originate in the breast. Pathologists have described many types of breast cancer based on careful analysis of tumor samples under the microscope.

There are at least 20 types of breast cancer with distinctive features in their morphology (structure and form) that allow them to be identified by microscopy. These tumors collectively are known as special types of breast cancer. Each of them is relatively rare, but together they account for about 25 percent of all breast cancers.

The most common type of breast cancer, called invasive ductal carcinoma of no special type, makes up the other 75 percent of breast cancers. As the name implies, the category comprises all breast cancers that cannot be classified as of one of the special types. This group of tumors is diverse, with varying morphologic characteristics, clinical behaviors, molecular features, and responses to therapies. Although special types of breast cancer have been known for a long time, patients with the rare types are currently treated in the same way as patients with ductal cancers.

Recent large-scale studies investigating the genetic basis of breast cancer have focused on the common type of the disease, and have confirmed that these tumors are diverse in their repertoire of gene mutations. Little is known, however, about the genetic characteristics of rare types of breast cancer.

The main goal of my lab is to develop a classification system for all breast cancers that is reflective not only of features seen under the microscope, but also of their molecular characteristics and response to therapies. To achieve this goal, we are studying the special types of breast cancer that are not categorized as ductal carcinoma.

In recent years, we and others have found that tumors from each of these rare types are less diverse than ductal carcinomas at the molecular level, and that some of these special types of breast cancer are underpinned by very specific genetic changes.

By using the molecular tools that we have access to here at Memorial Sloan Kettering Cancer Center, we can now determine, at an unprecedented level, the genetic alterations that drive the malignant behavior of the cells of each special type of breast cancer. Once we know which mutations cause these cells to be malignant or are required for cancer cell survival, we can start figuring out how to develop therapies tailored for patients with these rare types of breast cancer. Furthermore, when we find the molecular drivers for these cancers, we will be able to go back and look for the same drivers in ductal carcinoma and then further classify subsets of these common tumors into groups that have molecular features and behave like the rare types.

Our laboratory is also developing approaches to assess the molecular alterations in breast cancer cells by analyzing blood samples from breast cancer patients. We know that cells and genetic material from breast cancers can be found in the blood. We are currently applying cutting-edge genetic tools to compare cancerous materials obtained from blood samples with those from the tumors themselves. Our aim is to determine how the information obtained from these “liquid biopsies” can be employed to guide treatment decision making for breast cancer patients.

I have only been at Memorial Sloan Kettering a short time, but I already appreciate what a fantastic institution this is. The critical mass of basic, translational, and clinical scientists is unparalleled, and the clinicians are world-class. There is no other place that brings together people of this caliber who are working on issues that affect cancer patients. I have already had the chance to set up collaborations with other scientists and clinicians at Memorial Sloan Kettering, and am looking forward to developing my research program with the aim of matching breast cancer patients with the therapy that will be most beneficial for them.

This profile was featured in Memorial Sloan Kettering’s 2012 Annual Report.