Acquisition of metastatic tissue from patients with bone metastases from breast cancer

Abstract

Biopsies of metastatic tissue are increasingly being performed. Bone is the most frequent site of metastasis in breast cancer patients, but bone remains technically challenging to biopsy. Difficulties with both tissue acquisition and techniques for analysis of hormone receptor status are well described. Bone biopsies can be carried out by either by standard posterior iliac crest bone marrow trephine/aspiration or CT-guided biopsy of a radiologically evident bone metastasis. The differential yield of these techniques is unknown. Results from three prospective studies of similar methodology were pooled. Patients underwent both an outpatient posterior iliac crest bone marrow trephine/aspiration and a CT-guided biopsy of a radiologically evident bone metastasis. Samples were assessed for the presence of malignant cells and where possible also for estrogen (ER) and progesterone receptor (PgR) expression. 40 patients were enrolled. Bone marrow aspiration/trephine biopsy was completed in 39/40 (97.5%) and CT-guided biopsy was completed in 34/40 (85%) of patients. Sufficient tumor cells for hormone receptor analysis were available in 19/39 (48.8%) and 16/34 (47%) of and bone marrow aspiration/trephine and CT-guided biopsies, respectively. Significant discordance in ER and PgR between the primary and the bone metastasis was also seen. Nine patients had tissue available from both bone marrow and CT-guided bone biopsies. ER and PgR concordance between these sites was 100 and 78%, respectively. Performing studies on human bone metastases is technically challenging, with relatively low yields regardless of technique. Given resource issues and similar success rates when comparing both techniques, bone marrow examination may be utilized first and if inadequate tissue is obtained, CT-guided biopsies can then be used.

A meta-analysis of oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 discordance between primary breast cancer and metastases

“…Tumour heterogeneity may be attributable to tumour biological drift, selective pressure of therapy leading to clonal selection with the development of a novel tumour cell clone, or the presence of small sub-clones routinely undetected within the primary tumour. Along this line, as prospectively reported by Hilton and colleagues [45] tumour and metastatic deposits occurred, and a full concordance among metastases arising in multiple bone sites, suggesting the occurrence of a metastasising clone diverging in terms of ER immunoreactivity from the primary tumour. Whether and how ER, PgR and HER2 conversion modifies the treatment schedule and affects breast cancer patients survival has not been fully elucidated, and the available data are scarce and conflicting, as well as the optimal time to retest tumour biology.…”

Discordances in Estrogen Receptor Status, Progesterone Receptor Status, and HER2 Status Between Primary Breast Cancer and Metastasis

“…Moreover, we report here for the first time a statistically significant correlation between previous systemic treatments and modifications in receptors' expression. Several studies have addressed the issue of concordance/ discordance in receptors expression between primary tumor and metastases [9,[12][13][14][15][16][17][18][19][20][21][22][23][24]. Published studies have found discordance rates for ER status ranging from 10.2% to 56%, PR status ranging from 24.8% to 48.6%, and HER2 status ranging from 2.9% to 16%.…”

ER, HER2, and TOP2A expression in primary tumor, synchronous axillary nodes, and asynchronous metastases in breast cancer

“…A considerable proportion of patients with relapsed tumors had changes in ER, HER2 or TOP2A status. Biopsy confirmation is associated with a number of logistic as well as technical challenges, especially in the case of bone metastases [28]. However, it has become standard practise in our institution.…”