Estrogen Receptor and HER2 Status on Disseminated Tumor Cells and Primary Tumor in Patients with Early Breast Cancer

Abstract

BACKGROUND: We evaluated both estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) status on disseminated tumor cells (DTCs) in the bone marrow of 54 patients with early breast cancer and compared these with the corresponding primary tumor (PT). MATERIALS AND METHODS: Bone marrow aspirates were obtained at the time of first surgery, and ER and HER2 status on DTCs was assessed simultaneously by immunocytochemistry using a triple fluorescence staining method. RESULTS: The median number of DTCs was 13 (range 1-95). The concordance rate between ER status on DTC and PT was 74%. Patients with an ER-positive PT were significantly more likely to have at least one ER-positive DTC (34 out of 42) than patients with an ER-negative PT (6 out of 12; P = .031). Thirty-nine (93%) of the 42 patients with ER-positive PT had at least one ER-negative DTC. The concordance rate between HER2 status on DTC and PT was 52%. The probability of having at least one HER2-positive DTC was not related to the HER2 status of the PT (P = 0.56). Twenty-two (46%) of the 48 patients with a HER2-negative PT had at least one HER2-positive DTC. All the six patients with a HER2-positive PT had at least one HER2-negative DTC. CONCLUSION: Taken together, our study confirms that ER and/or HER2 status may differ between DTC and PT. This discordance could be important for patients lacking ER or HER2 expression on the PT but showing ER-positive or HER2-positive DTC because they might benefit from an endocrine and/or HER2-targeted therapy.

Circulating Tumour Cells, Circulating Tumour DNA and Circulating MicroRNA in Metastatic Breast Carcinoma – What is the Role of Liquid Biopsy in Breast Cancer?

“…Similar to the discordance of HR and HER2 expression of solid metastases, numerous studies have shown discrepant phenotypes between solid tumour tissue, i.e. primary tumour and/or metastases, and CTCs 14 , 15 , 16 , 17 . A recent study showed that discordance of HER2 expression between primary tumour and CTCs was associated with the histological subtype and HR status of the primary tumour as well as with the absolute number of detected CTCs in 7.5 ml of blood 18 .…”

“…In zahlreichen Untersuchungen konnten, analog zur Diskordanz der HR- bzw. HER2-Expression solider Metastasen, ähnliche Ergebnisse für die Diskrepanz des Phänotyps zwischen solidem Tumorgewebe, d. h. Primärtumor und/oder Metastasen, und CTCs demonstriert werden 14 , 15 , 16 , 17 . In einer weiteren aktuellen Untersuchung wurde gezeigt, dass die Diskordanz der HER2-Expression zwischen Primärtumor und CTCs mit dem histologischen Subtyp und dem HR-Status des Primärtumors sowie der absoluten Menge an detektierten CTCs in 7,5 ml Blut assoziiert ist 18 .…”

Disseminated tumour cells in bone marrow are the source of cancer relapse after therapy

“…Primary tumours and DTCs display a discordant ERα and HER2 status . This discordance may be important for determining which patients will benefit from endocrine and/or HER2 targeted therapy.…”

Enrichment and Molecular Analysis of Breast Cancer Disseminated Tumor Cells from Bone Marrow Using Microfiltration

“…DTCs found in the BM are shed from primary breast cancers and are thought to be intermediaries in the metastatic process[ 2 ]. DTCs are rare cells, found with a frequency of about 1 cancer cell per million nucleated BM cells[ 1 ], are molecularly heterogeneous, and are often molecularly distinct from their primary tumor of origin[ 3 – 5 ]. Not all patients with BM DTCs, detectable by conventional epithelial markers such as cytokeratin, will develop metastatic disease [ 6 ], indicating that DTCs themselves likely differ with regard to further metastatic potential.…”