Intratumoral heterogeneity of HER-2 gene amplification and protein overexpression in breast cancer

We report a case of a patient with invasive breast carcinoma that demonstrated HER-2 gene amplification on core biopsy, who relapsed while on adjuvant trastuzumab therapy after her mastectomy and ultimately died 15 months after diagnosis. Surprisingly, analysis of multiple metastases harvested at rapid autopsy demonstrated no evidence of HER-2 gene amplification. Retrospective examination of the carcinoma in the patient's mastectomy specimen revealed only focal HER-2 amplification within the tumor, localized to the region of the prior core biopsy site. This case highlights several important issues in HER-2 testing of breast cancer, including core biopsy-excision specimen discordance, primary-metastasis discordance, and potential selection for unamplified portions of a heterogeneously amplified tumors by trastuzumab.