Landscape of HER2+ Metastatic Breast Cancer: Patient Overview

Expert oncologist Kevin Kalinsky, MD, MS, reviews a patient case of HER2+ metastatic breast cancer and highlights key findings in this disease setting.


Kevin Kalinsky, MD, MS: Hi, and welcome to this OncLive® My Treatment Approach program titled “Improving Outcomes in Metastatic HER2-Positive Breast Cancer: Translating Evidence to Clinical Practice.” My name is Kevin Kalinsky, and I’m an associate professor of medicine at Winship Cancer Institute at Emory University in Atlanta, Georgia. I’m the director of the Glenn Family Breast Center and the director of breast medical oncology. Today I’m going to discuss recent advances in the treatment of metastatic HER2 [human epidermal growth factor receptor 2]–positive metastatic breast cancer and its impact on clinical practice. I’ll present a hypothetical patient case, and then we’ll discuss how I would treat this patient, illustrating how we incorporate recent data into our practice. Let’s get started.

The case is a 38-year-old woman who presents with a right-sided breast mass with ipsilateral enlarged axillary lymph nodes. Biopsy of the breast reveals ER [estrogen receptor]–negative, PR [progesterone receptor]–negative, HER2 3+, or hormone receptor–negative, HER2-positive breast tumor. It was invasive ductal, and then there was an FNA [fine-needle aspiration] done on the axillary lymph nodes that demonstrated malignant cells. She underwent staging scans, which unfortunately revealed suspicion for liver metastases. There was a biopsy of 1 of those liver lesions, which was consistent with what was seen in the primary breast tissue, which was hormone receptor negative and HER2 3+.

The patient was then started on THP [docetaxel, trastuzumab, pertuzumab] based on the CLEOPATRA regimen. She had a good response, with a reduction in those liver metastases. After 8 cycles of paclitaxel, she developed mild neuropathy, discontinued the ... and went on to HP [trastuzumab, pertuzumab] alone. That’s also how the CLEOPATRA study was designed, so patients could come off their chemotherapy. Unfortunately, 18 months after her diagnosis, she presented with headaches. A brain MRI revealed multiple small CNS [central nervous system] metastases, at least 8 to 10. Staging scans revealed continued control of her disease. The radiation oncologist felt she would need whole-brain radiation therapy and that she wouldn’t be a good candidate for SRS [stereotactic radiosurgery] given that she had multiple small brain lesions. Instead of starting with radiation, she started with capecitabine, tucatinib, and trastuzumab. Initially, she had elevations in her transaminase—AST [aspartate aminotransferase] and ALT [alanine aminotransferase] went up to 350, 400 IU/L, and these had been normal at baseline. At that point, her tucatinib was held. When her transaminase improved, tucatinib was started at a lower dose. She required Imodium to control her intermittent diarrhea, and then restaging revealed improvement those CNS metastases and improvement in the liver metastases. After 8 months of this regimen, she had progression of her liver metastases, but her CNS remained stable.

HER2+ breast cancer is seen in a quarter of breast tumors that we treat. Historically, HER2 positivity was associated with a worse prognosis. That prognosis changed given the presence of HER2 positivity, whether it’s by IHC [immunohistochemistry] or FISH [fluorescence in situ hybridization]. This associates with predictive utility, and these patients benefit from HER2-targeted therapy. The advent of HER2-targeted therapies changed the landscape of how these patients do. In terms of the stage when we see patients, most patients—similar to other subtypes of breast cancer—have early stage breast cancer, which is treatable; we’re going for cure. For patients with HER2+ early stage breast cancer, it’s common that we give neoadjuvant therapy. If patients don’t achieve a pathologic complete response, we have T-DM1 [trastuzumab emtansine] for patients with residual disease to improve outcomes in patients who have residual disease. Unfortunately, there’s a tropism for the CNS, for patients who have HER2+ breast cancer. Eventually, up to 50% of patients with metastases develop CNS metastases. The timeline can be a little different from what we see with triple-negative breast cancer, but it’s something that we’re very mindful of. When we think about the development of our new therapies, both in the metastatic and the early stage settings, we think about whether this agent has CNS activity, given that this subtype of breast cancer has an inclination to go to the CNS.

Transcript edited for clarity.

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