Evidence map›Paper›PMID 33292612›Full record

ArticleCancer & metabolism2020

The effect of statin treatment on intratumoral cholesterol levels and LDL receptor expression: a window-of-opportunity breast cancer trial.

Maria Feldt, Julien Menard, Ann H Rosendahl, Barbara Lettiero, Pär-Ola Bendahl, Mattias Belting, Signe Borgquist

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in Cancer & metabolism, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00816244 (A Phase II Study of Neo-Adjuvant Statin Therapy in Postmenopausal Primary Breast Cancer), which is not on this map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 1 pooled it
0.7field-weighted citation impact, top 35% of its field
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

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00816244 phase2completednot on this map

A Phase II Study of Neo-Adjuvant Statin Therapy in Postmenopausal Primary Breast Cancer: A Window-of-Opportunity Study

TypeinterventionalSponsorLund University HospitalRan2009 to 2012Enrolled50ConditionsBreast Cancer, PostmenopausalArmsAtorvastatin
3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Effects of Obesity and Calorie Restriction on Cancer Development.International journal of molecular sciences · 2023
    Review
  10. Review
  11. Article
  12. Exploration of targeted anti-tumor therapy · 2022
    Article
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

7 authors at 2 institutions in 2 countries.

Maria FeldtDepartment of Clinical Sciences Lund, Division of Oncology and Pathology, Lund University, Lund, Sweden. maria.feldt@med.lu.se.ORCID http://orcid.org/0000-0003-3793-1506
Julien MenardDepartment of Clinical Sciences Lund, Division of Oncology and Pathology, Lund University, Lund, Sweden.
Ann H RosendahlDepartment of Clinical Sciences Lund, Division of Oncology and Pathology, Lund University, Lund, Sweden.
Barbara LettieroDepartment of Clinical Sciences Lund, Division of Oncology and Pathology, Lund University, Lund, Sweden.
Pär-Ola BendahlDepartment of Clinical Sciences Lund, Division of Oncology and Pathology, Lund University, Lund, Sweden.
Mattias BeltingDepartment of Clinical Sciences Lund, Division of Oncology and Pathology, Lund University, Lund, Sweden.
Signe BorgquistDepartment of Clinical Sciences Lund, Division of Oncology and Pathology, Lund University, Lund, Sweden.
Lund University · SEUppsala University · SE

Funding

Bröstcancerförbundet -
6 · The paper itself

Abstract

backgroundDeregulated lipid metabolism is common in cancer cells and the mevalonate pathway, which synthesizes cholesterol, is central in lipid metabolism. This study aimed to assess statin-induced changes of the intratumoral levels of cholesterol and the expression of the low-density lipoprotein receptor (LDLR) to enhance our understanding of the role of the mevalonate pathway in cancer cholesterol metabolism.

methodsThis study is based on a phase II clinical trial designed as a window-of-opportunity trial including 50 breast cancer patients treated with 80 mg of atorvastatin/day for 2 weeks, between the time of diagnosis and breast surgery. Lipids were extracted from frozen tumor tissue sampled pre- and post-atorvastatin treatment. Intratumoral cholesterol levels were measured using a fluorometric quantitation assay. LDLR expression was evaluated by immunohistochemistry on formalin-fixed paraffin-embedded tumor tissue. Paired blood samples pre- and post-atorvastatin were analyzed for circulating low-density lipoprotein (LDL), high-density lipoprotein (HDL), apolipoprotein A1, and apolipoprotein B. In vitro experiments on MCF-7 breast cancer cells treated with atorvastatin were performed for comparison on the cellular level.

resultsIn the trial, 42 patients completed all study parts. From the paired tumor tissue samples, assessment of the cholesterol levels was achievable for 14 tumors, and for the LDLR expression in 24 tumors. Following atorvastatin treatment, the expression of LDLR was significantly increased (P = 0.004), while the intratumoral levels of total cholesterol remained stable. A positive association between intratumoral cholesterol levels and tumor proliferation measured by Ki-67 expression was found. In agreement with the clinical findings, results from in vitro experiments showed no significant changes of the intracellular cholesterol levels after atorvastatin treatment while increased expression of the LDLR was found, although not reaching statistical significance.

conclusionsThis study shows an upregulation of LDLR and preserved intratumoral cholesterol levels in breast cancer patients treated with statins. Together with previous findings on the anti-proliferative effect of statins in breast cancer, the present data suggest a potential role for LDLR in the statin-induced regulation of breast cancer cell proliferation.

trial registrationThe study has been registered at ClinicalTrials.gov (i.e., ID number: NCT00816244 , NIH), December 30, 2008.

Indexed as

Breast cancerCholesterolLDL receptorStatin

Identifiers

PMID33292612
PMCPMC7682108
OpenAlexW3108158719

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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.