Evidence map›Paper›PMID 40897974›Full record

Trial reportNature medicine2025

Targeting dormant tumor cells to prevent recurrent breast cancer: a randomized phase 2 trial.

Angela DeMichele, Amy S Clark, Emily Shea, Lauren J Bayne, Christopher J Sterner, Killian Rohn, Samantha Dwyer, Tien-Chi Pan, Isoris Nivar, Yan Chen and 19 more

Abstract readClinical Trial, Phase IIRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in Nature medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
–field-weighted citation impact
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.

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

26 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Autophagy modulation in cancer.Nature reviews. Drug discovery · 2026
    Review
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Regulated cell death programs shaping cancer therapy.Cellular oncology (Dordrecht, Netherlands) · 2026
    Review
  11. Article
  12. Review
  13. Review
  14. Article
  15. Review
  16. Review
  17. Article
  18. Article
  19. Intervening on dormancy to prevent breast cancer recurrence.Nature reviews. Clinical oncology · 2026
    Article
  20. Review
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

29 authors.

Angela DeMicheleDivision of Hematology/Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA. angela.demichele@pennmedicine.upenn.edu.ORCID http://orcid.org/0000-0003-1297-4251
Amy S ClarkDivision of Hematology/Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-3685-6535
Emily Shea2-PREVENT Translational Center of Excellence, University of Pennsylvania, Philadelphia, PA, USA.
Lauren J BayneDivision of Hematology/Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Christopher J Sterner2-PREVENT Translational Center of Excellence, University of Pennsylvania, Philadelphia, PA, USA.
Killian RohnDivision of Hematology/Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Samantha DwyerDepartment of Cancer Biology, University of Pennsylvania, Philadelphia, PA, USA.
Tien-Chi Pan2-PREVENT Translational Center of Excellence, University of Pennsylvania, Philadelphia, PA, USA.
Isoris NivarDivision of Hematology/Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Yan Chen2-PREVENT Translational Center of Excellence, University of Pennsylvania, Philadelphia, PA, USA.
Paul WileytoDepartment of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, PA, USA.
Lindsay R BerryBerry Consultants, Austin, TX, USA.
Shannon DelucaDivision of Hematology/Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Jessica SavageAbramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.
Igor MakhlinDivision of Hematology/Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-7374-7330
Dhruv K Pant2-PREVENT Translational Center of Excellence, University of Pennsylvania, Philadelphia, PA, USA.
Heather Martin2-PREVENT Translational Center of Excellence, University of Pennsylvania, Philadelphia, PA, USA.
Adetutu Egunsola2-PREVENT Translational Center of Excellence, University of Pennsylvania, Philadelphia, PA, USA.
Nathan Mears2-PREVENT Translational Center of Excellence, University of Pennsylvania, Philadelphia, PA, USA.
Brooke L GoodspeedDivision of Hematology/Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Elizabeth M Chislock2-PREVENT Translational Center of Excellence, University of Pennsylvania, Philadelphia, PA, USA.
Jewell Graves2-PREVENT Translational Center of Excellence, University of Pennsylvania, Philadelphia, PA, USA.
Jianping Wang2-PREVENT Translational Center of Excellence, University of Pennsylvania, Philadelphia, PA, USA.
Natalie Shih2-PREVENT Translational Center of Excellence, University of Pennsylvania, Philadelphia, PA, USA.
George K Belka2-PREVENT Translational Center of Excellence, University of Pennsylvania, Philadelphia, PA, USA.
Don BerryBerry Consultants, Austin, TX, USA.
Anupma Nayak2-PREVENT Translational Center of Excellence, University of Pennsylvania, Philadelphia, PA, USA.
Michael Feldman2-PREVENT Translational Center of Excellence, University of Pennsylvania, Philadelphia, PA, USA.
Lewis A ChodoshAbramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. chodosh@pennmedicine.upenn.edu.ORCID http://orcid.org/0000-0003-1027-8674

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Breast cancer recurrence may arise from dormant disseminated tumor cells (DTCs) that persist in bone marrow and other sites. Clinically, DTCs are independently associated with breast cancer recurrence and death. Preclinical studies in mouse models identified autophagy and mammalian target of rapamycin (mTOR) signaling as critical mechanisms of tumor dormancy and escape. We subsequently tested the effects of transient versus chronic inhibition of autophagy with chloroquine or hydroxychloroquine (HCQ) and mTOR signaling with rapamycin (RAPA) or everolimus (EVE) on residual tumor cell (RTC) burden and recurrence-free survival (RFS). In mice harboring dormant RTCs, inhibition of mTOR alone or in combination with autophagy inhibition decreased RTC burden and improved RFS in a duration-dependent manner. RTC number was strongly and inversely correlated with RFS, suggesting that RTC reduction mediated an improvement in RFS. To translate findings clinically, we performed a randomized phase 2 trial (CLEVER) of HCQ, EVE or their combination in breast cancer survivors within 5 years of diagnosis who had detectable DTCs on bone marrow aspirate. Primary endpoints were feasibility and safety; secondary endpoints included DTC reduction/clearance and RFS. In total, 51 DTC

Indexed as

Breast NeoplasmsNeoplasm Recurrence, LocalAdultAgedAnimalsChloroquineDisease-Free SurvivalEverolimusFemaleHumansHydroxychloroquineMiceMiddle AgedNeoplasm, ResidualSignal TransductionSirolimusChloroquineEverolimusHydroxychloroquineMTOR protein, humanSirolimusTOR Serine-Threonine Kinases

Identifiers

PMID40897974

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.