Case Study: Treating HER2-Positive MBC, Part I

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Moderator, Adam M. Brufsky, MD, PhD, presents a case study that examines a 59 year-old woman presenting with fatigue and dyspnea approximately 8 years following her initial treatment for breast cancer. At this first presentation, the patient was diagnosed with stage I, hormone receptor positive, and HER2-positive breast cancer. At this point, her treatment included adjuvant Adriamycin plus Cytoxan followed by paclitaxel with trastuzumab and finally the administration of anastrozole for five years.

At the 8-year follow-up, the fatigue and breathlessness led to a CT scan of the chest, abdomen, and pelvis, explains Brufsky. This examination identified pulmonary metastases, the largest of which was 2 cm. Additionally, multiple liver metastases were noted, with the largest measuring approximately 4 cm. However, liver function testing was normal. A liver biopsy confirmed estrogen receptor-positive disease that was also HER2-positive by FISH with a ratio of approximately 2.3, Brufsky notes.

Assessing disease burden and symptoms is the first step in the frontline setting for a patient with metastatic breast cancer that is both ER and HER2-positive, believes Sara Hurvitz, MD. In this case, the patient presents with an indolent tumor and may benefit from treatment with the combination of a hormonal and HER2-targeted agent. As a result, Hurvitz recommends the administration of a taxane with pertuzumab and trastuzumab in the frontline setting for 6 cycles or until a response reduces symptoms. After this point, treatment can be transitioned to HER2-targeted therapies alone with the potential to add an endocrine therapy.

The panel agrees with this treatment approach and transitions the discussion toward HER2 testing, specifically the ratio of HER2 to chromosome 17. The initial ratio of 2.3 is not very high but is adequate to label the disease as HER2-positive, believes Edith A. Perez, MD. Studies have indicated that the degree of HER2 amplification does not impact the efficacy of targeted therapies, such as trastuzumab. As a result, even a patient with a lower ratio for positivity should still receive HER2-targeted therapy.

Further complicating testing, heterogeneity is present in approximately 10% of patients with HER2-positive breast cancer. As a result, guidelines now recommend dual testing for patients with breast cancer to verify the findings, Perez states. Another approach for identifying HER2-positivity measures the number of HER2 gene copies. This approach may provide additional accuracy, when considered along with the ratio, believes Joyce A. O'Shaughnessy, MD.