As part of our coverage of the 2018 Miami Breast Cancer Conference, held March 8–11 in Miami Beach, Florida, we spoke with Patrick Borgen, MD, about management of ductal carcinoma in situ (DCIS). Dr. Borgen, a surgical oncologist who specializes in breast cancer at the Maimonides Medical Center in Brooklyn, New York, discussed this topic at the meeting in a talk entitled, “DCIS: Rational Approach to Management in the Era of Genomic Profiling”.
—Interviewed by Anna Azvolinsky
Cancer Network: First, can you talk briefly about how DCIS is defined and diagnosed and whether any of this has evolved over the last 5 to 10 years?
Dr. Borgen: Sure, thank you very much. DCIS makes up about 25% of everything we call “breast cancer” in this field. DCIS is defined as a growth that occurs in milk ducts in the breast. There are two microscopic organs in the breast that can give rise to breast cancer: the milk-producing gland, or the lobule, and the duct that carries that milk to the nipple. DCIS is a condition that grows within the confines of the milk duct but it is trapped within the duct. The implication is that DCIS cannot travel or metastasize.
Cancer Network: In the context of genomic profiling, is it standard for patients diagnosed with DCIS to undergo genetic testing and how does that genomic information then influence management?
Dr. Borgen: I think the key thing to understand about DCIS is that our fundamental assumptions about this condition for the past 30 years have been flawed. Our profession assumed that these milk ducts containing the DCIS would inevitably break open and allow these cells to become invasive ductal breast cancer. The assumption was after diagnosis, if DCIS was untreated, it would virtually always become a potentially life-threatening breast cancer. However, we now know that it is likely that more than half of the cases of DCIS were destined to remain confined within the milk ducts and therefore not become a threat to our patients. That means that in many cases, we may be overtreating DCIS. The genomic profiling that you mentioned allows us to identify low-risk DCIS that is destined to remain trapped in the milk ducts from a high-risk DCIS, when there is a high chance of the milk ducts breaking open and the cancer becoming invasive.
Cancer Network: What are the genes or markers you analyze when you perform the genomic profiling to identify either low- or high-risk DCIS patients?
Dr. Borgen: We use the term “genomic profiling” but in fact, the more accurate term is “gene expression profiling”. What we are looking for are normal, wild-type genes that are producing variable amounts of transcripts. What we are measuring is the amount of messenger RNA that is being produced from these key genes we are analyzing. In the case of DCIS, the commercially available platform is a 12-gene expression profile. So gene 1, 2, and 3 are measured and produce what looks like a bar code that is unique for that patient’s specific DCIS. Using a mathematical model, the patient’s gene expression profile is then compared to both a standardized high- and low-risk DCIS result. So the 12-gene panel provides us with a 10-year risk of recurrence depending on whether the only treatment is a lumpectomy and no mastectomy or chemotherapy or radiation. This test tells us whether the patient’s DCIS is low-, intermediate-, or high-risk.
Cancer Network: If patients are classified as intermediate risk, is it clear which of those patients should be treated as a high-risk patient and receive more aggressive intervention and which actually fall on the low side of the risk spectrum? And how are high-risk patients treated compared to those with low risk?
Dr. Borgen: I think that is a great question. The test is designed to provide us with a risk of recurrence without radiation therapy. Radiation, as we know, is capable of reducing risk by 40% to 50%, so we really don’t use hard and fast cut-offs to say that this patient should receive radiation and then the next patient should not. Rather, we look at the risk of recurrence and calculate the reduction that radiation could afford. For example, for a patient with a 10-year risk of 5%, radiation would cut that to 2.5%. That is a very low benefit and most patients in this case would not elect to receive radiation. However, the same patient with a 50% risk that is cut in half to 25% risk, that is a more clear-cut decision. For many other patients, falling in the middle becomes a value judgment where you must look at the risk with and without radiation. The patient and her health care team make a decision together about the potential benefit of the radiation. It’s really more about understanding the disease that the patient has and what the risks and benefits of interventions like radiation could be.
Cancer Network: Is this gene expression panel test now considered standard of care for DCIS or is this still mostly used at academic centers?
Dr. Borgen: It is available nationwide and it is certainly used as an acceptable standard of care; however, it has not been universally adopted although its adoption is certainly accelerating. Part of what we need to do is move away from a one-size-fits-all to any breast cancer, and for DCIS, it would be incorrect to assume that every single patient with DCIS needs to receive radiation therapy. I think that more centers are embracing the reality that we need to predict risk of invasive breast cancer and identify the low-risk patients who may not benefit at all from radiation versus those who are high risk who will benefit. What we saw in Miami this year compared to previous years’ meetings is that the use of the 12-gene panel for DCIS has increased dramatically over the past 2 years. In one of the sessions in which the audience was polled on their practices, it looked like about 30% to 40% of the U.S. attendees at the meeting were using the test on a relatively routine basis.
Cancer Network: And lastly, the Food and Drug Administration recently authorized use of the first at-home test for consumers to check their germ-line breast cancer risk, which looks for germ-line mutations in the BRCA1 and BRCA2 genes. Do you think that the availability of this test will impact the screening for breast cancer and perhaps the management of DCIS or breast cancer in general?
Dr. Borgen: I really do. Just to draw a distinction here, what we have been discussing are about acquired abnormalities in genes that can lead to DCIS and breast cancer. The 23andMe analysis is testing for germ-line mutations, which are gene abnormalities that someone is born with and that can greatly increase the risk of developing breast cancer. We dramatically underuse genetic testing in this country and for most women, they don't know that they are carrying a germ-line mutation until they are diagnosed with breast cancer. That is a failure of the system. By identifying more women at increased risk, we can do a better job of screening and find breast cancers when they are at the DCIS stage before they become invasive. There are medical ways to block estrogen and reduce risk, and also risk-reducing surgeries that are options for some women with germ-line mutations. The key is to identify those families that carry these mutations, and that is what the 23andMe genetic test approval is all about.