Multidisciplinary Care for a Patient With Metastatic HER2+ Breast Cancer

Mark D. Pegram, MD: For metastatic HER2 [human epidermal growth factor receptor 2]–positive breast cancer relapse, that’s most frequently going to be detected by the medical oncologist who’s following that patient longitudinally from the time of diagnosis through their neoadjuvant or postneoadjuvant therapy. The medical oncologist is most likely going to pick up signs, symptoms, laboratory abnormalities, and imaging findings that suggest metastasis. At that point, it’s necessary to get a biopsy to confirm distant metastasis because you don’t want to mistake an inflammatory condition that might be benign, or even some other malignancy that has metastasized from a different organ.

Someone can have a history of breast cancer but then have a new metastatic colon cancer. So it’s necessary to get a biopsy of the first suspected metastasis to confirm that it’s breast cancer and then to repeat the biomarker work on the metastasis. This is because biomarkers can be inconsistent between the primary tumor and the metastatic tumor. These biomarkers are used to inform what treatment is best in metastatic HER2+ breast cancer. It’s important to get the biopsy, to confirm that it’s not only breast cancer but that it remains HER2+ and whether it expresses steroid receptors. All those are still important.

Finally, we rely on the radiologist also at that juncture, in addition to the pathologist, to catalog the extent of metastatic spread. We’re often using multiple imaging techniques like CT scans, bone scans, sometimes CT/PET [positron emission tomography], which is whole body. We rely on echocardiography in HER2+ disease to make sure the baseline cardiac ejection fraction is suitable to entertain the possibility of HER2-targeted therapy. If patients have signs or symptoms of neurological dysfunction that could suggest central nervous system metastasis, then we’ll get an MRI imaging of the brain. Often, that involves consultation with the neuro-oncologist if there are breast cancer brain metastasis at that point. The neuro-oncology team consists of neurosurgeons, as well as radiotherapists, who might be doing, for example, stereotactic radiation or sometimes even whole-brain radiation for HER2+ breast cancer brain metastasis. Of course, now we have therapeutic drugs that work in the brain as well, so the medical oncologist would supervise that type of treatment.

It’s often an integration of all those approaches for the modern treatment of HER2+ brain metastasis. The HER2+ metastatic landscape is very complex. There are a number of treatment options, and you need to know the biomarker perspective, as well as just the staging information—does it involve visceral disease, non-visceral CNS [central nervous system], and so forth—to come up with the best possible treatment plan for a metastatic patient.

Joyce A. O’Shaughnessy, MD: If a woman presents with metastatic disease, she may have de novo metastatic disease because with first-line therapy for HER2+ metastatic breast cancer, more than 50% of those patients will fall into the category of de novometastatic disease, so she’ll have a primary breast cancer. She’ll often have regional nodal disease involved. Then you get your imaging studies—a PET/CT scan or CT scans, a bone scan—and she’s found to have what appears to be metastatic disease. You’ve gotten a biopsy of the primary breast cancer to ascertain what subtype it is, but then you have to biopsy a metastatic lesion to be sure that it’s metastatic disease. Second, you have to confirm it’s breast cancer; it could be a different primary cancer. Then you have to understand the subtype. HER2 testing still remains tricky.

About 20% of the time, when patients are enrolled on clinical trials for metastatic HER2+ breast cancer, the HER2 results from a variety of community hospitals don’t match up with the central pathology review of the HER2. It’s generally in favor of overcalling: about 15%, 20% of the time it’s called HER2+, but it’s not. It’s more of a borderline equivocal or HER2 low. But it’s not HER2+. It’s very important to get the diagnosis right. Over the years I’ve figured out which ones I’m not 100% certain of. Even if it may say positive, I’m not 100% certain looking at it. I just err on the side of sending it though a central reference laboratory because if I treat the patient with the HER2-directed therapy and they’re not HER2+, they’re not going to have an optimal outcome basically. So diagnosis is very critical.

Staging is very critical, whether a brain MRI is controversial, but I usually will get it at diagnosis. Basically, we have to see what’s going on with the patient at that time or her level of pain or other discomfort. We have to evaluate the problems she’s having that we may need to address. She may present with brain metastasis. She may have issues with an antecedent cardiac history. You have to involve a cardiologist and get an echocardiogram before you can start HER2-directed therapy. That’s another part of the multidisciplinary team.

Onco-cardiology is very important. We need to get all that squared away. Then the medical oncologist and the patient sit down and talk about the systemic treatment options because we want to get started with that. We may, however, get around to being able to do locoregional therapy for the patient. Many patients with HER2+ disease who are de novo metastatic are going to do well for many years. We tend to be proactive about management of their primary breast cancer and regional lymph nodes. We’ll get the patients sooner than later to the breast surgeon and to the radiation oncologist, so they can see the patient from the beginning. This is so they can start to talk to her about potential surgical and radiation approaches.

Once the patient starts anti-HER2 directed therapy in the metastatic state, we obviously get echocardiograms every 3 months. Any type of diminution in cardiac functions, we get our cardiology colleagues involved. But oftentimes early on, patients do really well, and then we won’t have to do the imaging that often because we know patients are doing well and they have a serum tumor marker, for example, that’s going down. You don’t have to get that many scans. But sometimes you’re not sure how they’re responding, and you need to reengage your breast surgeons to ascertain what they think about the locoregional disease, and you have to rescan to see if somebody is benefiting. Sometimes you have to rebiopsy to understand what you’re dealing with, to get enough tissue for NGS [next-generation sequencing], etc. Those are the beginnings of the metastatic journey.

Transcript Edited for Clarity