Abstract
Eighty per cent of patients who develop metastatic breast cancer will experience a skeletal metastasis. National guidelines recommend biopsy and repeat estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) testing for all metastatic breast cancers to guide further treatment planning. Biomarker analysis in bone biopsy samples is challenging due to the necessity of decalcification of the bone sample in order to allow tissue sectioning. The decalcification solutions may result in the degradation of proteins and thus affect the results of immunohistochemical (IHC) testing for ER, PR, and HER2. The decalcification solutions may also degrade nucleic acids, and result in poor or no hybridization signals when attempting in situ hybridization (ISH) testing for HER2. Here, we report a patient with metastatic breast cancer to the bone who underwent image guided core needle biopsy. Her past medical history was significant for ER+, PR+, and HER2+ breast cancer. The biopsy yielded cores of bone, which were decalcified, and a blood clot that was separated from the bone and fixed in formalin without decalcification. Both specimens showed metastatic carcinoma consistent with a breast primary when viewing hematoxylin and eosin (H&E) stained sections. Immunohistochemical analysis, which was performed only on the clot sections, showed ER+, PR − , and HER2 equivocal (2+) tumor cells. Immunohistochemical analysis was not performed on the bony tissue, because our assays are not validated for use on decalcified tissue. Human epidermal growth factor receptor-2 fluorescence in situ hybridization (FISH) analysis was attempted on the bone biopsy and yielded no signals (analytic failure). This is typical of HER2 FISH analysis in decalcified specimens, due to the impaired deoxyribonucleic acid (DNA) quality. However, HER2 FISH analysis on the clot sections showed that the HER2 gene was amplified. Given the clinical importance of repeat HER2 testing in patients with recurrent breast cancer, techniques that avoid decalcification are needed. Separating the blood clot from the bony tissue, and processing it without decalcification may yield viable tumor whose DNA has not been degraded, and it then can be used for the analysis of ER, PR, and HER2.
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