Evidence map›Paper›PMID 30041599›Full record

ArticleBMC cancer2018

Mitotic count can predict tamoxifen benefit in postmenopausal breast cancer patients while Ki67 score cannot.

Karin Beelen, Mark Opdam, Tesa Severson, Rutger Koornstra, Andrew Vincent, Jelle Wesseling, Joyce Sanders, Jan Vermorken, Paul van Diest, Sabine Linn

Abstract read
In one paragraph

Article in BMC cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

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0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Prognostic and Predictive Value ofFrontiers in endocrinology · 2022
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Karin BeelenMolecular Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Mark OpdamMolecular Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Tesa SeversonMolecular Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Rutger KoornstraMolecular Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Andrew VincentDepartments of Biometrics, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Jelle WesselingPathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Joyce SandersPathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Jan VermorkenDepartment of Medical Oncology, University Hospital Antwerpen, Edegem, Belgium.
Paul van DiestDepartment of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
Sabine LinnMolecular Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. s.linn@nki.nl.ORCID http://orcid.org/0000-0001-5541-0347

Funding

Stichting A Sister's Hope 4400-41200TI-pharma T3-502
6 · The paper itself

Abstract

backgroundControversy exists for the use of Ki67 protein expression as a predictive marker to select patients who do or do not derive benefit from adjuvant endocrine therapy. Whether other proliferation markers, like Cyclin D1, and mitotic count can also be used to identify those estrogen receptor α (ERα) positive breast cancer patients that derive benefit from tamoxifen is not well established. We tested the predictive value of these markers for tamoxifen benefit in ERα positive postmenopausal breast cancer patients.

methodsWe collected primary tumor blocks from 563 ERα positive patients who had been randomized between tamoxifen (1 to 3 years) vs. no adjuvant therapy (IKA trial) with a median follow-up of 7.8 years. Mitotic count, Ki67 and Cyclin D1 protein expression were centrally assessed by immunohistochemistry on tissue microarrays. In addition, we tested the predictive value of CCND1 gene copy number variation using MLPA technology. Multivariate Cox proportional hazard models including interaction between marker and treatment were used to test the predictive value of these markers.

resultsPatients with high Ki67 (≥5%) as well as low (< 5%) expressing tumors equally benefitted from adjuvant tamoxifen (adjusted hazard ratio (HR) 0.5 for both groups)(p for interaction 0.97). We did not observe a significant interaction between either Cyclin D1 or Ki67 and tamoxifen, indicating that the relative benefit from tamoxifen was not dependent on the level of these markers. Patients with tumors with low mitotic count derived substantial benefit from tamoxifen (adjusted HR 0.24, p <  0.0001), while patients with tumors with high mitotic count derived no significant benefit (adjusted HR 0.64, p = 0.14) (p for interaction 0.03).

conclusionPostmenopausal breast cancer patients with high Ki67 counts do significantly benefit from adjuvant tamoxifen, while those with high mitotic count do not. Mitotic count is a better selection marker for reduced tamoxifen benefit than Ki67.

Indexed as

Breast NeoplasmsKi-67 AntigenMitosisAntineoplastic Agents, HormonalCell ProliferationCluster AnalysisCyclin D1FemaleHumansImmunohistochemistryKaplan-Meier EstimateMiddle AgedPostmenopauseRetrospective StudiesTamoxifenAntineoplastic Agents, HormonalCCND1 protein, humanCyclin D1Ki-67 AntigenTamoxifenBreast cancerCell proliferationKi67Mitotic countTamoxifen

Identifiers

PMID30041599
PMCPMC6057037

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.