The Changing Treatment Paradigm of HER2+ Metastatic Breast Cancer - Episode 2

Patient Case: Biomarker Testing in Breast Cancer

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Centered on a patient presentation of breast cancer, panelists consider optimal biomarker testing strategies to inform their treatment approach.

Vijayakrishna Gadi, MD, PhD: Let’s go ahead and move through. We have a few cases that are going to spark some conversation. I’ll start with the first 1. A 62-year-old woman who from the current mammogram identifies a new mass, 1.5 cm, in her right breast. She has 2 adult children. Menopause at age 47. No known or particular family history for cancers. Our imaging reveals a 1.9-cm regular mass in the right breast with suspicious adenopathy. MRI bone scans seem to be negative. PET [positron emission tomography]–CT shows the axillary nodes and some pulmonary nodules, unfortunately. The breast mass, lymph node, pulmonary nodules are all biopsied and sent to pathology. Her PS [performance status] is 0. At this point, let’s focus on some of the diagnostics. Michelle, you can tell me some of the additional tests beyond those imaging diagnostics you might order in this patient.

Michelle Melisko, MD: The twist to this case, as happens not infrequently, is the presence of a possible metastasis based on PET–CT scan. That’s another topic of discussion: the use of imaging studies in higher-risk disease, who gets it, who doesn’t, and how that impacts the treatment of these patients. In this case, she did have the PET scan. It shows these nodules. The case doesn’t present how big they are, but we’d want to try to determine whether these were possible to be biopsied. Once that’s determined, then for the breast mass itself, we’d send it for the standard receptor studies: ER [estrogen receptor], PR [progesterone receptor], and HER2 [human epidermal growth factor receptor 2]. With HER2, we’d want to test with both IHC [immunohistochemistry] and FISH [fluorescence in situ hybridization], given that we’re not talking about HER2-positive in the conventional way of 3-plus IHC and FISH-positive, but we’d also want to know the IHC if it was 1-plus or 2-plus to define the HER2-low population. And then of course the receptor studies, ER/PR, to know down the road the role of endocrine therapy.

The biopsy of the lung is critical because if it’s positive, then that puts the patient into a particular bucket of disease. If her disease is triple-negative and she has metastatic disease, then we need to know the PD-L1 status. However, if the biopsy of the lung is negative and we have a locally advanced high-risk triple-negative breast cancer, then we can treat with immunotherapy-chemotherapy combination without knowing the PD-L1 status. If the patient ends up having a biopsy-proved metastatic disease in the lung, there’s a question about the role of next-generation sequencing to look at actionable mutations. That’s a whole other conversation, a bag of worms about the value of performing NGS [next-generation sequencing] as first-line therapy, to guide first-line therapy. I know many centers do it on every patient.

Given the circumstances, if we know the patient is HER2+, we’d treat them with metastatic disease under 1 very defined pathway. If they’re HER2-negative, triple-negative, it would be another pathway. I’m not sure the role of next-generation sequencing in selecting the first line of therapy for HER2+ and triple-negative. It has more value in ER+, where the course isn’t as defined. I’m curious to hear what my colleagues think in terms of biomarker selection and what needs to be done with the tissue.

Vijayakrishna Gadi, MD, PhD: I would think there’s 1 exception to the last point you made about doing genetic testing on the tumor itself for somatic mutations: if we had clinical trials.

Michelle Melisko, MD: Exactly.

Nancy Lin, MD: Yes, and I often set it even in the first-line setting, even if it’s not going to affect my first-line regimen, because there’s a turnaround time associated with the test. We see a lot of patients as consultations. It takes awhile to get outside tissue in for us to send it out for testing. At the time of progression, you don’t want to wait 6 or 8 weeks to get the tissue, get it sent out, get a turnaround time, get the result. We have sent it off when we first see patients, more for practical reasons—it’s not necessarily going to affect first-line therapy. Certainly, in ER+ patients, we routinely sendoff NGS because we want to know the PIK3CA status of the tumor. Obviously, there are some interesting data about TMB [tumor mutational burden], so could we offer some subset of patients with ER+ disease immunotherapy? I agree with Michelle that for HER2+ disease, with the exception of looking for potential clinical trials, we’re not translating the results into clinical practice from NGS.

Vijayakrishna Gadi, MD, PhD: True.

Charles Geyer, MD, FACP: Keeping in mind a community audience, for community practitioners, the next-generation sequencing isn’t at all a standard. It isn’t that you’re undermanaging your patient if you don’t do that with the newly diagnosed cases. There clearly are situations where you need to be thinking about it sooner than later that are appropriate subsets and clinical situations. But it’s different in the academic centers, working in a very different environment from a community doctor for sure.

Transcript edited for clarity.