Breast Cancer Is Not Just One Disease: Exploring Lobular Breast Cancer Research With Jason Mouabbi, MD

Oncology Data Advisor: Welcome to Oncology Data Advisor, I'm Keira Smith. Today I'm here with Dr. Jason Mouabbi, who is an Assistant Professor in the Department of Breast Medical Oncology at the University of Texas MD Anderson Cancer Center.

In light of Breast Cancer Awareness Month, it's important to recognize that breast cancer is not just one disease, but that there are many subtypes. Would you like to explain a little bit about all the subtypes?

Jason Mouabbi, MD: This Breast Cancer Awareness Month, it's very important to talk about how breast cancer does not come in one flavor. Breast cancer actually has multiple subtypes. Those different subtypes have different prognoses and are treated differently, and it's very important to highlight that breast cancer does not come as one entity.

Generally, there are three categories that we discuss with patients, which depend on the receptors of the breast cancer. Sometimes we call the cancer hormone receptor–positive, sometimes we call it human epidermal growth factor receptor 2 (HER2)–positive, and sometimes it's called triple-negative if it doesn't express the hormone receptor or the HER2 receptor.

But we can go to another layer of differentiation, and that's based on histology. The bulk of breast cancers, 80% of breast cancers, are what we call invasive ductal carcinoma. Those are the ductal cells that are becoming cancerous. The ductal cells are structural cells that form the ducts and the nipple to take the milk from the breast outside the body. This is the most common histology that we see in breast cancer.

However, up to 15% of breast cancers are called invasive lobular carcinoma. Those are coming from the lobules. The lobules are the cells that produce the milk in the body. They are different than the ductal cells. Then there is a third group that's smaller, about up to 5%. Sometimes you see a mixture between lobular and ductal, and sometimes there is another entity we call inflammatory breast cancer. These are also important. Ductal carcinoma has its own advocacy group that sheds the light on that.

Me, I am a lobular expert. I like to speak about lobular breast cancer because it's a very important subtype that is not being talked about enough and that has not been studied enough. Lobular breast cancer accounts for 15% of all breast cancers, so it's already equivalent to that of triple-negative and HER2-positive disease. About 15% of breast cancers are triple-negative, and around 15% of breast cancers are HER2-positive. Those are studied on their own, yet lobular has historically always been grouped with ductal and studied as one entity.

There lies the main problem, because whenever you enroll a patient without stratifying by histology, well, guess what? Most of the patients in studies will have the ductal subtype, and the conclusions we get from those studies are going to be driven by the ductal patient. Even if the lobular patients don't benefit from a certain therapy or from a certain recommendation, they're going to be obscured a lot between all the ductal patients.

Right now, because of nonprofit organizations like the Lobular Breast Cancer Alliance (LBCA), we are finally shedding more light on the important subtype of lobular breast cancer. This year, the American Cancer Society anticipates 40,000 new lobular breast cancer cases in the US, which makes it the sixth most common female cancer. It's already double the incidence of ovarian cancer and cervical cancer. It's very important to study it, and it's very important to get more answers to our patients.

Why is lobular cancer different than ductal? Lobular cancer has a hallmark, which is loss of the very important anchoring protein called E-cadherin. You can think about E-cadherin as a small protein that goes on the surface of the cell and interacts with E-cadherin from other cells, so it's kind of like they're holding hands. The cell is anchoring itself to the environment. Lobular loses that. By this loss, lobular cancer tends to have a peculiar growth pattern. If you think about ductal cells, because they have this anchoring protein, cancer grows like an onion. You have one ring followed by another, followed by another, so there's a mass. When you feel the ductal cancer in the breast, you can actually feel a mass.

However, with lobular, because this anchoring protein is lost, it grows distantly. It grows in a single-file pattern. By this peculiar growth, lobular cancer does not always present as a mass. That's why we always tell patients that sometimes this cancer does not present as a mass. Lobular cancer grows through lines or streaks of cells and not through that discrete mass. It doesn't distort the architecture of the breast. That's why it can be easily missed, and that's why conventional screening imaging like mammograms and ultrasounds often miss lobular, for that reason. It's because those cells are very small and they're growing in streaks. It's important to find better imaging, it's important to better understand lobular breast cancer, and it's important to raise awareness.

Also, because of that feature, most lobular cases are diagnosed at a very advanced stage. If you look at the stages of lobular cancer, most of them are diagnosed at stage II, whereas ductal, with the screening tools we have nowadays, are often diagnosed at stage I. We want to be able to screen patients earlier with better detection tools and identify lobular cancer at stage I, when it can really impact the overall survival of those patients.

Now, talking a little about the detection and a little about lobular treatment, we have enough studies nowadays showing that lobular cancer does respond well to endocrine therapy. In lobular cancer, 95% of cases are driven by hormones. They express the female hormone receptors and that's how they feed. I always tell my patients that having cancer is like having a car. Cancer by itself cannot go without something feeding it—something has to feed it to grow, something has to be the fuel. The fuel is those hormones. You can lower those hormones by taking an endocrine therapy, what we call in layman's terms "the anti-hormone pills". Those work well for lobular; however, some patients, like in ductal, still need something else. The only something else we have nowadays is chemotherapy.

But for lobular, we still do not know which patients can benefit from chemotherapy. We know that there is a subset that will benefit, but we just don't know who will benefit. The reason is because throughout the years, there's been a lot of testing done to be able to identify which patients can benefit from chemo and which cannot. I will name one of those tests that is commonly used in the US­—we call it the Oncotype DX^®. This is a tool distinguishes between patients are high-risk versus intermediate-risk and low-risk.

For the high-risk patients, this does predict benefits of chemotherapy. But this test was not made for lobular patients, again, for the same reason as before—that they allowed all histologies to join, and the bulk of the histology was ductal. This test was really validated mostly for ductal because we have now a myriad of studies that look back in time and found that for lobular patients, this test failed to predict a benefit of chemotherapy. Yet it is still being used for lobular patients. We need a new tool to better strategize the risk of lobular breast cancer—which patients are high-risk for the cancer coming back and which patients are low-risk—and then use the appropriate therapy for those patients.