Universität zu Köln

Wirtz, Ralph M., Sihto, Harri, Isola, Jorma, Heikkila, Paivi, Kellokumpu-Lehtinen, Pirkko-Liisa, Auvinen, Paivi, Turpeenniemi-Hujanen, Taina, Jyrkkio, Sirkku, Lakis, Sotiris, Schlombs, Kornelia, Laible, Mark, Weber, Stefan, Eidt, Sebastian, Sahin, Ugur and Joensuu, Heikki ORCID: 0000-0003-0281-2507 (2016). Biological subtyping of early breast cancer: a study comparing RT-qPCR with immunohistochemistry. Breast Cancer Res. Treat., 157 (3). S. 437 - 447. NEW YORK: SPRINGER. ISSN 1573-7217

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Abstract

The biological subtype of breast cancer influences the selection of systemic therapy. Distinction between luminal A and B cancers depends on consistent assessment of Ki-67, but substantial intra-observer and inter-observer variability exists when immunohistochemistry (IHC) is used. We compared RT-qPCR with IHC in the assessment of Ki-67 and other standard factors used in breast cancer subtyping. RNA was extracted from archival breast tumour tissue of 769 women randomly assigned to the FinHer trial. Cancer ESR1, PGR, ERBB2 and MKI67 mRNA content was quantitated with an RT-qPCR assay. Local pathologists assessed ER, PgR and Ki-67 expression using IHC. HER2 amplification was identified with chromogenic in situ hybridization (CISH) centrally. The results were correlated with distant disease-free survival (DDFS) and overall survival (OS). qPCR-based and IHC-based assessments of ER and PgR showed good concordance. Both low tumour MKI67 mRNA (RT-qPCR) and Ki-67 protein (IHC) levels were prognostic for favourable DDFS [hazard ratio (HR) 0.42, 95 % CI 0.25-0.71, P = 0.001; and HR 0.56, 0.37-0.84, P = 0.005, respectively] and OS. In multivariable analyses, cancer MKI67 mRNA content had independent influence on DDFS (adjusted HR 0.51, 95 % CI 0.29-0.89, P = 0.019) while Ki-67 protein expression had not any influence (P = 0.266) whereas both assessments influenced independently OS. Luminal B patients treated with docetaxel-FEC had more favourable DDFS and OS than those treated with vinorelbine-FEC when the subtype was defined by RT-qPCR (for DDFS, HR 0.52, 95 % CI 0.29-0.94, P = 0.031), but not when defined using IHC. Breast cancer subtypes approximated with RT-qPCR and IHC show good concordance, but cancer MKI67 mRNA content correlated slightly better with DDFS than Ki-67 expression. The findings based on MKI67 mRNA content suggest that patients with luminal B cancer benefit more from docetaxel-FEC than from vinorelbine-FEC.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Wirtz, Ralph M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sihto, Harri UNSPECIFIED UNSPECIFIED UNSPECIFIED Isola, Jorma UNSPECIFIED UNSPECIFIED UNSPECIFIED Heikkila, Paivi UNSPECIFIED UNSPECIFIED UNSPECIFIED Kellokumpu-Lehtinen, Pirkko-Liisa UNSPECIFIED UNSPECIFIED UNSPECIFIED Auvinen, Paivi UNSPECIFIED UNSPECIFIED UNSPECIFIED Turpeenniemi-Hujanen, Taina UNSPECIFIED UNSPECIFIED UNSPECIFIED Jyrkkio, Sirkku UNSPECIFIED UNSPECIFIED UNSPECIFIED Lakis, Sotiris UNSPECIFIED UNSPECIFIED UNSPECIFIED Schlombs, Kornelia UNSPECIFIED UNSPECIFIED UNSPECIFIED Laible, Mark UNSPECIFIED UNSPECIFIED UNSPECIFIED Weber, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Eidt, Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Sahin, Ugur UNSPECIFIED UNSPECIFIED UNSPECIFIED Joensuu, Heikki UNSPECIFIED orcid.org/0000-0003-0281-2507 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-274318
DOI:	10.1007/s10549-016-3835-7
Journal or Publication Title:	Breast Cancer Res. Treat.
Volume:	157
Number:	3
Page Range:	S. 437 - 447
Date:	2016
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1573-7217
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PATHOLOGISTS GUIDELINE RECOMMENDATIONS; AMERICAN-SOCIETY; DOCETAXEL; KI67; CHEMOTHERAPY; ESTROGEN; BENEFIT Multiple languages Oncology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/27431