Case 1: Guidelines for HER2 Testing in Breast Cancer

Hope Rugo, MD, FASCO: Evita, we're so fortunate to have you with us on the Virtual Tumor Board® today. In regard to the guidelines for HER2 testing in breast cancer, I’m interested in hearing what your approach is for molecular testing. Do you first use IHC [immunohistochemistry], or FISH [fluorescence in situ hybridization]? Do you test everybody with FISH, or only those who are IHC 2+? How does that work at your institution? Then, I'll have a follow-on question after that.

Evita Sadimin, MD: Sure, glad to be here. In our institution, we have implemented the 2018 [American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP)] guidelines. We are currently doing IHC first, and we perform FISH testing on those with 2+ on IHC. We do a dual-probe test, and we report the results as a certain group number. Group 1 is the straightforward positive patients, and group 5 represents the straightforward negative patients. With the other 3 groups—group 2, group 3, and group 4—we usually have discussions with the clinicians.

In particular, for the monosomy cases that used to be considered positive and now are considered negative, we do still get calls about those cases because patients had a history of HER2 positivity—so we really have to look into them more closely depending on what the actual numbers were previously.

Hope Rugo, MD, FASCO: Evita, can you explain what monosomy means?

Evita Sadimin, MD: In normal chromosomes, you will have 2 chromosomes. In a monosomy case, you will only have 1. When you have the HER2 assessment of the genes, it appears as if you have more copies of the HER2 if you just consider the ratio. The ratio will seem elevated, not because of increased copy number of the HER2, but because there are not as many chromosome 17.

Hope Rugo, MD, FASCO: So you use the standard new testing. What happens for these patients who were in the indeterminant area? I still see a lot of people who are really confused about patients who, for example, have a copy number of 3 but have a ratio of 2.02.

Evita Sadimin, MD: Unfortunately, these cut-off points are somewhat arbitrary. Therefore, we like to always maintain an ongoing discussion with everyone involved in the care of the patient, and we try to make the best judgment. Unfortunately, it’s not always clear-cut.

Hope Rugo, MD, FASCO: I understand that. One of the issues that we face is HER2 heterogeneity. Have you seen that? How do manage that?

Evita Sadimin, MD: Usually, with heterogeneity we try to see if there are any parts of the tumor that would be expressive of the HER2, and we will go by that. If the majority of the tumor is not HER2-positive, but there’s at least 10%, we usually go by 10%. If it’s positive, then we would consider that as a positive test.

Hope Rugo, MD, FASCO: Do you generally say that if any test is positive, it’s HER2-positive? For example, 3+ with no amplification or amplification without the HER2 IHC being positive?

Evita Sadimin, MD: That's an interesting question. Yes, there are some cases where the HER2 IHC is positive. It depends on the situation. For example, with HER2-positive cases on IHC that are lobular carcinoma, we tend to also do the FISH test to see whether the results of the IHC correlate with the results of the FISH test. In other institutions, if it’s a very low-grade tumor, mucinous tumor—usually not HER2-positive—then we would also do both IHC and FISH. And again, I'll put the results together, depending on the patient’s situation, to make the best judgment.

Transcript edited for clarity.