Cancer Biomarkers - Volume 12, issue 6

Authors: Niikura, Naoki | Ueno, Naoto T.

Article Type: Editorial

DOI: 10.3233/CBM-130321

Citation: Cancer Biomarkers, vol. 12, no. 6, pp. 205-206, 2013

Authors: Gong, Yun

Article Type: Research Article

Abstract: Information on hormone receptor and human epidermal growth factor receptor 2 (HER2) is important for making optimal therapeutic decisions for breast cancer patients. Discordance in these biomarkers between primary breast carcinomas and corresponding metastases is well documented and may lead to changes in management option. The underlying mechanisms of biomarker discordance are complicated and multifactorial. Whereas biologic evolution, intratumoral heterogeneity, and subclonal selection may account for discordance, variations in sampling, processing, staining procedure and interpretation are the important contributory yet controllable factors. This article reviews the effects of different factors on the biomarker discordance, the clinical significance and the importance …of standardizing methodology and interpretation criteria. Show more

Keywords: Estrogen receptor, ER, progesterone receptor, PR, HER2, discordance, concordance

DOI: 10.3233/CBM-130316

Citation: Cancer Biomarkers, vol. 12, no. 6, pp. 207-218, 2013

Authors: Lower, Elyse E. | Khan, Shagufta

Article Type: Research Article

Abstract: Although the analysis of hormone receptors and HER-2/neu has usually been performed on primary tumors only, a growing body of evidence suggests that substantial discordance exists between primary and metastatic disease for estrogen receptors (30–40%) and HER-2/neu (10–30%). This discordance may reflect alterations in pathologic assessment techniques, changes between primary and metastatic breast cancer, differences within a heterogenous tumor, or the effect of treatment. The etiology of discordance is poorly understood and frequently may reflect tumor heterogeneity along with lack of standardized preanalytic and analytic variables. Standardization of diagnostic variables can improve diagnostic reproducibility. Because of the emergence of targeted …hormonal and HER-2/neu therapies, tumor biomarkers assume a pivotal role in treatment decisions. The loss of sensitivity to hormones or HER-2/neu may suggest tumor resistance; whereas, the acquisition of hormone receptors and HER-2/neu provides potential new treatment targets which can improve overall patient outcomes. Show more

Keywords: Breast cancer, estrogen receptors, hormone receptors, HER-2/neu, discordance

DOI: 10.3233/CBM-130317

Citation: Cancer Biomarkers, vol. 12, no. 6, pp. 219-230, 2013

Authors: Moussa, Osama | Purdie, Colin | Vinnicombe, Sarah | Thompson, Alastair M.

Article Type: Research Article

Abstract: Prospective studies of biomarker status in primary and recurrent or metastatic breast cancer have confirmed the findings of historical retrospective studies which demonstrate that for biomarkers which influence routine clinical practice, Estrogen Receptor (ER), Progesterone Receptor (PR) and Human Epidermal growth factor Receptor type 2 (HER2), biopsy of recurrent or metastatic disease is essential not only to confirm the presence of malignancy but to guide targeted medical therapy. Historically, discordance rates for the expression of receptors between primary and metastatic tumors, though variable, may have led to suboptimal treatment for a significant proportion of patients. While changes in …PR are most common, changes in ER (positive to negative or less frequently negative to positive) and the less common changes in HER2 (usually gain of HER2 amplification) influence subsequent therapy for 1 in 6 patients and may thus impact upon survival. Recognition of the potential for heterogeneity within the primary, between metastatic sites and over time requires further prospective study in breast cancer where the comparability of metastases from multiple sites and the need to biopsy successive recurrences have been less well documented. Recent prospective studies confirm the retrospective evidence that optimal patient care requires appropriate biopsy and pathological assessment of recurrent or metastatic breast cancer. Show more

Keywords: Breast cancer, recurrence, metastasis, biomarker, discordance

DOI: 10.3233/CBM-130314

Citation: Cancer Biomarkers, vol. 12, no. 6, pp. 231-239, 2013

Authors: Dawood, Shaheenah | Gonzalez-Angulo, Ana M.

Article Type: Research Article

Abstract: With the increasing use of neoadjuvant chemotherapy it is increasingly being observed that differences in the status of molecular markers may exist between core biopsy specimens and the residual disease in the breast post chemotherapy. Several hypotheses have been postulated to explain the biomarker discordance observed following neoadjuvant chemotherapy including intratumor heterogeneity, technical variance in the assays used to assess biomarkers and a genetic switch in the biology of the disease. Here we review published data looking at discordance of biomarkers following neoadjuvant chemotherapy and the prognostic and therapeutic implications of the observed discordance. We will review some of the …biological explanations to account for the observed discordance and will look at its impact on the role of the pathologist as well as propose essential components required in a pathology report issued for patients receiving neoadjuvant chemotherapy that would help the medical oncologist in treatment planning. Show more

Keywords: Breast cancer, neoadjuvant, biomarker discordance

DOI: 10.3233/CBM-130315

Citation: Cancer Biomarkers, vol. 12, no. 6, pp. 241-250, 2013

Authors: Niikura, Naoki | Ueno, Naoto T.

Article Type: Research Article

Abstract: The HER2 status of breast cancers is routinely assessed using the testing algorithm standardized by the American Society of Clinical Oncology and the College of American Pathologists, which includes immunohistochemical analysis of HER2 protein expression and fluorescence in situ hybridization (FISH) analysis of HER2 gene copy number. Studies have suggested that HER2 status may differ between primary and metastatic tumors. Furthermore, studies have suggested that trastuzumab may convert HER2 status from positive in a primary tumor to negative in a metastatic site. Assessment of HER2 status is affected by aspects of the pathologic analysis, including the method of tumor sampling, …the method of specimen fixation, whether immunohistochemical or FISH analysis is used. In this review, we discuss the clinical significance of HER2 discordance in breast cancer. Moreover, the importance of tumor sample handling in assessing HER2-positivity. Show more

Keywords: Breast neoplasms, HER-2/neu, biomarker

DOI: 10.3233/CBM-130313

Citation: Cancer Biomarkers, vol. 12, no. 6, pp. 251-255, 2013

Article Type: Other

DOI: 10.3233/CBM-2013-12607

Citation: Cancer Biomarkers, vol. 12, no. 6, pp. 257-259, 2013