Universität zu Köln

Grote, Isabel ORCID: 0000-0002-6731-187X, Bartels, Stephan ORCID: 0000-0002-8903-2345, Christgen, Henriette, Radner, Martin, Gronewold, Malte, Kandt, Leonie, Raap, Mieke ORCID: 0000-0001-8338-6209, Lehmann, Ulrich ORCID: 0000-0003-2350-6584, Gluz, Oleg, Graeser, Monika, Kuemmel, Sherko, Nitz, Ulrike, Harbeck, Nadia, Kreipe, Hans and Christgen, Matthias (2022). ERBB2 mutation is associated with sustained tumor cell proliferation after short-term preoperative endocrine therapy in early lobular breast cancer. Mod. Pathol., 35 (12). S. 1804 - 1812. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1530-0285

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Abstract

Invasive lobular breast cancer (ILC) is a special breast cancer (BC) subtype and is mostly hormone receptor (HR)-positive and ERBB2 non-amplified. Endocrine therapy restrains tumor proliferation and is the mainstay of lobular BC treatment. Mutation of ERBB2 has been associated with recurrent ILC. However, it is unknown whether ERBB2 mutation impacts on the otherwise exquisite responsiveness of early ILC to endocrine therapy. We have recently profiled n = 622 HR-positive early BCs from the ADAPT trial for mutations in candidate genes involved in endocrine resistance, including ERBB2. All patients were treated with short-term preoperative endocrine therapy (pET, tamoxifen or aromatase inhibitors) before tumor resection. Tumor proliferation after endocrine therapy (post-pET Ki67 index) was determined prospectively by standardized central pathology assessment supported by computer-assisted image analysis. Sustained or suppressed proliferation were defined as post-pET Ki67 =10% or <10%. Here, we report a subgroup analysis pertaining to ILCs in this cohort. ILCs accounted for 179/622 (28.8%) cases. ILCs were enriched in mutations in CDH1 (124/179, 69.3%, P < 0.0001) and ERBB2 (14/179, 7.8%, P < 0.0001), but showed fewer mutations in TP53 (7/179, 3.9%, P = 0.0048) and GATA3 (11/179, 6.1%, P < 0.0001). Considering all BCs irrespective of subtypes, ERBB2 mutation was not associated with proliferation. In ILCs, however, ERBB2 mutations were 3.5-fold more common in cases with sustained post-pET proliferation compared to cases with suppressed post-pET proliferation (10/75, 13.3% versus 4/104, 3.8%, P = 0.0248). Moreover, ERBB2 mutation was associated with high Oncotype DX recurrence scores (P = 0.0087). In summary, our findings support that ERBB2 mutation influences endocrine responsiveness in early lobular BC.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Grote, Isabel UNSPECIFIED orcid.org/0000-0002-6731-187X UNSPECIFIED Bartels, Stephan UNSPECIFIED orcid.org/0000-0002-8903-2345 UNSPECIFIED Christgen, Henriette UNSPECIFIED UNSPECIFIED UNSPECIFIED Radner, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Gronewold, Malte UNSPECIFIED UNSPECIFIED UNSPECIFIED Kandt, Leonie UNSPECIFIED UNSPECIFIED UNSPECIFIED Raap, Mieke UNSPECIFIED orcid.org/0000-0001-8338-6209 UNSPECIFIED Lehmann, Ulrich UNSPECIFIED orcid.org/0000-0003-2350-6584 UNSPECIFIED Gluz, Oleg UNSPECIFIED UNSPECIFIED UNSPECIFIED Graeser, Monika UNSPECIFIED UNSPECIFIED UNSPECIFIED Kuemmel, Sherko UNSPECIFIED UNSPECIFIED UNSPECIFIED Nitz, Ulrike UNSPECIFIED UNSPECIFIED UNSPECIFIED Harbeck, Nadia UNSPECIFIED UNSPECIFIED UNSPECIFIED Kreipe, Hans UNSPECIFIED UNSPECIFIED UNSPECIFIED Christgen, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-689030
DOI:	10.1038/s41379-022-01130-7
Journal or Publication Title:	Mod. Pathol.
Volume:	35
Number:	12
Page Range:	S. 1804 - 1812
Date:	2022
Publisher:	ELSEVIER SCIENCE INC
Place of Publication:	NEW YORK
ISSN:	1530-0285
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PROGNOSTIC VALUE; KI67; MULTICENTER; TAMOXIFEN Multiple languages Pathology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/68903