Evidence map›Paper›PMID 42779790›Full record

ArticlebioRxiv : the preprint server for biology2026

TALAVE in Breast Cancer:

Filipa Lynce, Kenichi Shimada, Claudine Isaacs, Xue Geng, Edward T Richardson, Adam Nelson, Candace Mainor, Mei Wei, Julie M Collins, Paula R Pohlmann and 11 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

21 authors.

Filipa LynceDana-Farber Cancer Institute, Boston, MA, USA.
Kenichi ShimadaBrigham and Women's Hospital, Boston, MA, USA.ORCID 0000-0001-8540-9785
Claudine IsaacsGeorgetown University, Washington, DC, USA.
Xue GengGeorgetown University, Washington, DC, USA.
Edward T RichardsonBrigham and Women's Hospital, Boston, MA, USA.
Adam NelsonBrigham and Women's Hospital, Boston, MA, USA.
Candace MainorMedStar Georgetown University Hospital, Washington, DC, USA.
Mei WeiUniversity of Utah, Salt Lake City, UT, USA.
Julie M CollinsAstraZeneca, Gaithersburg, MD, USA.
Paula R PohlmannUniversity of Texas MD Anderson Cancer Center, Houston, TX.
Arielle L HeekeLevine Cancer Atrium Health, Charlotte, NC.
Kelly F ZhengBrigham and Women's Hospital, Boston, MA, USA.
Madeline G TownsendBrigham and Women's Hospital, Boston, MA, USA.
Nicole SwansonGeorgetown University, Washington, DC, USA.
Lauren M SloatBrigham and Women's Hospital, Boston, MA, USA.
Jane StauntonHarvard Medical School, Boston, MA, USA.
Stuart J SchnittBrigham and Women's Hospital, Boston, MA, USA.
Hongkun WangGeorgetown University, Washington, DC, USA.
Joan S BruggeHarvard Medical School, Boston, MA, USA.
Geoffrey I ShapiroDana-Farber Cancer Institute, Boston, MA, USA.ORCID 0000-0002-3331-4095
Jennifer L GuerrieroDana-Farber Cancer Institute, Boston, MA, USA.ORCID 0000-0002-2104-5457

Funding

VectorP30CA006516 · NCI · DANA-FARBER CANCER INSTITUTE · PI Irene M. Ghobrial · 1985 to 2026
$330.6M
Tissue Culture Shared ResourceP30CA051008 · NCI · GEORGETOWN UNIVERSITY · PI MARCUS S NOEL · 1990 to 2026
$71.5M
Tissue and Pathology CoreP50CA168504 · NCI · DANA-FARBER CANCER INST · PI LEIF W ELLISEN, NANCY U LIN · 2013 to 2026
$30.1M
Systems Pharmacology of Therapeutic and Adverse Responses to ImmuneCheckpoint and Small Molecule DrugsU54CA225088 · NCI · HARVARD MEDICAL SCHOOL · PI HAIGIS, MARCIA · 2018 to 2022
$10.8M
Immunometabolic pathways enabled by PARP inhibition in breast cancerR37CA269499 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI Jennifer L. Guerriero · 2022 to 2026
$2.3M
Macrophage-directed strategies for BRCA-associated breast cancerR01CA307291 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI Jennifer L. Guerriero, Filipa Lynce · 2026 to 2026
$772k
NCI NIH HHS P30 CA006516NCI NIH HHS P30 CA051008NCI NIH HHS P50 CA168504NCI NIH HHS R01 CA307291NCI NIH HHS R37 CA269499NCI NIH HHS U54 CA225088
6 · The paper itself

Abstract

PARP inhibitors (PARPi) drive efficacy in BRCA-mutant breast cancer (BC) via DNA damage-induced synthetic lethality and immune activation, supporting their combination with immune checkpoint blockade. In the TALAVE study, patients with advanced BRCA-mutant or wild-type (WT) HER2-negative BC received talazoparib followed by talazoparib plus avelumab. Only BRCA-mutant BC responded clinically. Serial multi-omic profiling revealed BRCA-dependent tumor-immune remodeling, including sustained γH2AX-pTBK1 signaling with increased CD8+ T cells, tumor cell depletion, and enrichment of CD163+ macrophages. In contrast, BRCA-WT tumors remained compact and immunosuppressed with reduced T cells after therapy. PD-1+ T cells localized to CD4+-rich neighborhoods and correlated with longer progression-free survival in BRCA-mutant tumors. However, PD-L1+ cells were rapidly depleted or confined to immune-excluded regions, spatially segregating them from PD-1+ T cells, impairing effective checkpoint blockade. These findings suggest limited benefit of PD-1/PD-L1 blockade in augmenting PARPi activity and highlight the need for alternative strategies to sustain PARPi-induced immunity.

Identifiers

PMID42779790
PMCPMC13596426

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.