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Journal of Cancer Research and Clinical Oncology

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Open Access 01-12-2019 | Fluorescence in Situ Hybridization | Original Article – Cancer Research

Variability of predictive markers (hormone receptors, Her2, Ki67) and intrinsic subtypes of breast cancer in four consecutive years 2015–2018

Authors: Lidija Stevanovic, Matthias Choschzick, Linda Moskovszky, Zsuzsanna Varga

Published in: Journal of Cancer Research and Clinical Oncology | Issue 12/2019

Abstract

Purpose

Accurate monitoring of predictive markers is of utmost importance as oncological treatment decisions almost entirely depend on these factors. In this study, we conducted a quality control assessment on hormone receptors, Her2 status, Ki67 Labelling Index (LI) and histological grading in breast cancer over 4 years (2015–2018).

Methods

Altogether 2214 consecutive breast cancer cases were included. Data on estrogen (ER) and progesterone receptors (PR), Her2 and Ki67, were available in all cases and were tested mostly on preoperative biopsies, in selected cases on postoperative surgical specimens. ER, PR, and Ki67 were assessed with immunohistochemistry (IHC), Her2 status with IHC and fluorescence in situ hybridization.

Results

ER/PR were positive in 74–79% cases, ER/PR/Her2 negative in 6.16–10.70% and Her2 positive in 11.49–13.88%/year. Ki67 had median values as 15–17.5% in ER/PR-positive cases, 55–60% in triple-negative cases and 30–32.50% in Her2-positive cases. Histological grading distribution for well (G1), moderately (G2) and poorly (G3) differentiated carcinomas was 15.8–19.1% for G1, 54.2–54.8% for G2 and 21.7–23.7% for G3 cases. Variation in yearly distributions was not significant in any of these markers.

Conclusions

Predictive markers displayed a yearly similar distribution in breast cancer cases independently of grading or of intrinsic subtypes. These results point to a qualitative high performance of predictive marker assessment in breast cancer, corresponding to expected on average positivity rate per marker and per year. It is recommended to monitor positivity rate of ER, PR, Ki67 and Her2 yearly or periodically to comply with quality assurance requirements.

Bilous M, Dowsett M, Hanna W, Isola J, Lebeau A, Moreno A et al (2003) Current perspectives on HER2 testing: a review of national testing guidelines. Mod Pathol 16(2):173–182PubMedCrossRef

Burstein HJ, Griggs JJ, Prestrud AA, Temin S (2010) American society of clinical oncology clinical practice guideline update on adjuvant endocrine therapy for women with hormone receptor-positive breast cancer. J Oncol Pract 6(5):243–246PubMedPubMedCentralCrossRef

Choritz H, Büsche G, Kreipe H, Monitor SGH (2011) Quality assessment of HER2 testing by monitoring of positivity rates. Virchows Arch 459(3):283–289PubMedPubMedCentralCrossRef

Chu KC, Anderson WF, Fritz A, Ries LA, Brawley OW (2001) Frequency distributions of breast cancer characteristics classified by estrogen receptor and progesterone receptor status for eight racial/ethnic groups. Cancer 92(1):37–45PubMedCrossRef

Cserni G, Vörös A, Liepniece-Karele I, Bianchi S, Vezzosi V, Grabau D et al (2014) Distribution pattern of the Ki67 Labelling Index in breast cancer and its implications for choosing cut-off values. Breast 23(3):259–263PubMedCrossRef

Curigliano G, Burstein HJ, Winer PE, Gnant M, Dubsky P, Loibl S et al (2017) De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen international expert consensus conference on the primary therapy of early breast cancer 2017. Ann Oncol 28(8):1700–1712PubMedPubMedCentralCrossRef

de Azambuja E, Cardoso F, de Castro G, Colozza M, Mano MS, Durbecq V et al (2007) Ki-67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12,155 patients. Br J Cancer 96(10):1504–1513PubMedPubMedCentralCrossRef

Dowsett M, Cooke T, Ellis I, Gullick WJ, Gusterson B, Mallon E et al (2000) Assessment of HER2 status in breast cancer: why, when and how? Eur J Cancer 36(2):170–176PubMedCrossRef

Duffy MJ, Harbeck N, Nap M, Molina R, Nicolini A, Senkus E et al (2017) Clinical use of biomarkers in breast cancer: updated guidelines from the European Group on Tumor Markers (EGTM). Eur J Cancer 75:284–298PubMedCrossRef

Ghaffari SR, Sabokbar T, Dastan J, Rafati M, Moossavi S (2011) Her2 amplification status in Iranian breast cancer patients: comparison of immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH). Asian Pac J Cancer Prev 12(4):1031–1034PubMed

Gruvberger S, Ringnér M, Chen Y, Panavally S, Saal LH, Borg A et al (2001) Estrogen receptor status in breast cancer is associated with remarkably distinct gene expression patterns. Cancer Res 61(16):5979–5984PubMed

Hammond ME, Hayes DF, Wolff AC, Mangu PB, Temin S (2010) American society of clinical oncology/college of american pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Oncol Pract 6(4):195–197PubMedPubMedCentralCrossRef

Harvey JM, Clark GM, Osborne CK, Allred DC (1999) Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer. J Clin Oncol 17(5):1474–1481PubMedCrossRef

Hicks DG, Tubbs RR (2005) Assessment of the HER2 status in breast cancer by fluorescence in situ hybridization: a technical review with interpretive guidelines. Hum Pathol 36(3):250–261PubMedCrossRef

Makretsov N, Gilks CB, Alaghehbandan R, Garratt J, Quenneville L, Mercer J et al (2011) Development of an evidence-based approach to external quality assurance for breast cancer hormone receptor immunohistochemistry: comparison of reference values. Arch Pathol Lab Med 135(7):874–881PubMed

McGuire A, Brown JA, Malone C, McLaughlin R, Kerin MJ (2015) Effects of age on the detection and management of breast cancer. Cancers (Basel) 7(2):908–929CrossRef

Rakha EA, El-Sayed ME, Lee AH, Elston CW, Grainge MJ, Hodi Z et al (2008) Prognostic significance of Nottingham histologic grade in invasive breast carcinoma. J Clin Oncol 26(19):3153–3158PubMedCrossRef

Rakha EA, Gill MS, El-Sayed ME, Khan MM, Hodi Z, Blamey RW et al (2009) The biological and clinical characteristics of breast carcinoma with mixed ductal and lobular morphology. Breast Cancer Res Treat 114(2):243–250PubMedCrossRef

Rhodes A, Jasani B, Balaton AJ, Barnes DM, Miller KD (2000) Frequency of oestrogen and progesterone receptor positivity by immunohistochemical analysis in 7016 breast carcinomas: correlation with patient age, assay sensitivity, threshold value, and mammographic screening. J Clin Pathol 53(9):688–696PubMedPubMedCentralCrossRef

Romain S, Lainé Bidron C, Martin PM, Magdelenat H (1995) Steroid receptor distribution in 47,892 breast cancers. A collaborative study of 7 European laboratories The EORTC Receptor Study Group. Eur J Cancer 31A(3):411–417PubMedCrossRef

Rüschoff J, Lebeau A, Kreipe H, Sinn P, Gerharz CD, Koch W et al (2017) Assessing HER2 testing quality in breast cancer: variables that influence HER2 positivity rate from a large, multicenter, observational study in Germany. Mod Pathol 30(2):217–226PubMedCrossRef

Scholzen T, Gerdes J (2000) The Ki-67 protein: from the known and the unknown. J Cell Physiol 182(3):311–322PubMedCrossRef

Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235(4785):177–182PubMedCrossRef

Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M et al (2011) Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med 365(14):1273–1283PubMedPubMedCentralCrossRef

Sui W, Ou M, Chen J, Wan Y, Peng H, Qi M et al (2009) Comparison of immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) assessment for Her-2 status in breast cancer. World J Surg Oncol 7:83PubMedPubMedCentralCrossRef

Tashima R, Nishimura R, Osako T, Nishiyama Y, Okumura Y, Nakano M et al (2015) Evaluation of an optimal cut-off point for the Ki-67 Index as a prognostic factor in primary breast cancer: a retrospective study. PLoS One 10(7):e0119565PubMedPubMedCentralCrossRef

Varga Z, Noske A (2015) Impact of modified 2013 ASCO/CAP guidelines on HER2 testing in breast cancer. One year experience. PLoS One 10(10):e0140652PubMedPubMedCentralCrossRef

Varga Z, Noske A, Ramach C, Padberg B, Moch H (2013) Assessment of HER2 status in breast cancer: overall positivity rate and accuracy by fluorescence in situ hybridization and immunohistochemistry in a single institution over 12 years: a quality control study. BMC Cancer 13:615PubMedPubMedCentralCrossRef

Varga Z, Cassoly E, Li Q, Oehlschlegel C, Tapia C, Lehr HA et al (2015) Standardization for Ki-67 assessment in moderately differentiated breast cancer. A retrospective analysis of the SAKK 28/12 study. PLoS One 10(4):e0123435PubMedPubMedCentralCrossRef

Vogel UF (2010) Confirmation of a low HER2 positivity rate of breast carcinomas—limitations of immunohistochemistry and in situ hybridization. Diagn Pathol 5:50PubMedPubMedCentralCrossRef

Vohra P, Buelow B, Chen YY, Serrano M, Vohra MS, Berry A et al (2016) Estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression in breast cancer FNA cell blocks and paired histologic specimens: a large retrospective study. Cancer Cytopathol 124(11):828–835PubMedCrossRef

Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH et al (2013) Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol 31(31):3997–4013PubMedCrossRef

Wolff AC, Hammond MEH, Allison KH, Harvey BE, McShane LM, Dowsett M (2018) HER2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice guideline focused update summary. J Oncol Pract 14(7):437–441PubMedCrossRef

Title: Variability of predictive markers (hormone receptors, Her2, Ki67) and intrinsic subtypes of breast cancer in four consecutive years 2015–2018
Authors: Lidija Stevanovic
Matthias Choschzick
Linda Moskovszky
Zsuzsanna Varga
Publication date: 01-12-2019
Publisher: Springer Berlin Heidelberg
Keywords: Fluorescence in Situ Hybridization
Breast Cancer
Breast Cancer
Progesterone
Estrogens
Published in: Journal of Cancer Research and Clinical Oncology / Issue 12/2019
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-019-03057-0

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