Evidence map›Paper›PMID 42550611›Full record

Trial reportThe Journal of clinical investigation2026

Molecular evaluation of residual disease following neoadjuvant chemotherapy in triple-negative breast cancer CALGB 40603 (Alliance).

Patrick D Rädler, Brooke M Felsheim, Aranzazu Fernandez-Martinez, Adam D Pfefferle, Michele C Hayward, Baljit Singh, William Sikov, Lisa A Carey, Charles M Perou

Registry-linked trialAbstract readClinical Trial, Phase IIRandomized Controlled Trial
In one paragraph

Trial report in The Journal of clinical investigation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00861705 (Randomized Phase II 2 x 2 Factorial Trial of the Addition of Carboplatin +/- Bevacizumab to Neoadjuvant Weekly Paclitaxel Followed by Dose-Dense AC in Hormone Receptor-Poor/HER2-Negative Resectable Breast Cancer), which is not on this 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.

NCT00861705 phase2completednot on this map

Randomized Phase II 2 x 2 Factorial Trial of the Addition of Carboplatin +/- Bevacizumab to Neoadjuvant Weekly Paclitaxel Followed by Dose-Dense AC in Hormone Receptor-Poor/HER2-Negative Resectable Breast Cancer

TypeinterventionalSponsorNational Cancer Institute (NCI)Ran2009 to 2025Enrolled454ConditionsMale Breast Carcinoma, Stage IIA Breast Cancer AJCC v6 and v7, Stage IIB Breast Cancer AJCC v6 and v7, Stage IIIA Breast Cancer AJCC v7ArmsBevacizumab, Carboplatin, Cyclophosphamide, Doxorubicin Hydrochloride, Laboratory Biomarker Analysis
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

9 authors.

Patrick D RädlerLineberger Comprehensive Cancer Center (LCCC) and.
Brooke M FelsheimLineberger Comprehensive Cancer Center (LCCC) and.
Aranzazu Fernandez-MartinezDrug Development Department (DITEP), INSERM UMR981, IHU-National PRecISion Medicine Center in Oncology, Gustave Roussy Cancer Campus, Villejuif, France.
Adam D PfefferleLineberger Comprehensive Cancer Center (LCCC) and.
Michele C HaywardLineberger Comprehensive Cancer Center (LCCC) and.
Baljit SinghWhite Plains Hospital, White Plains, New York, USA.
William SikovProgram in Women's Oncology, Women and Infants Hospital of Rhode Island, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA.
Lisa A CareyLineberger Comprehensive Cancer Center (LCCC) and.
Charles M PerouLineberger Comprehensive Cancer Center (LCCC) and.

Funding

Member Site CoreU10CA180821 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI Evanthia Galanis, Olwen Hahn · 2014 to 2026
$177.3M
Statistics CoreU10CA180882 · NCI · MAYO CLINIC ROCHESTER · PI Sumithra Jay Mandrekar · 2014 to 2026
$115.0M
Tissue Procurement & PathologyP50CA058223 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BENJAMIN CARLISLE CALHOUN · 1992 to 2026
$59.3M
THE ALLIANCE NCTN BIOREPOSITORY AND BIOSPECIMEN RESOURCEU24CA196171 · NCI · WASHINGTON UNIVERSITY · PI Mine Cicek, Wendy Frankel · 2015 to 2026
$35.0M
UNITS: The UNC / UT National Clinical Trials Network Group Integrated Translational Science Production and Consultation CenterUG1CA233333 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI HAYES, DAVID N, MERKER, JASON DEREK · 2019 to 2025
$4.8M
Optimizing prognostic and predictive algorithms using residual disease (RD) genomic biomarkers in HER2+ and TNBCR01CA229409 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI LISA A CAREY, CHARLES M PEROU · 2019 to 2026
$4.0M
UNC Lead Academic Participating SiteUG1CA233373 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI CAREY, LISA A, DEES, ELIZABETH CLAIRE · 2019 to 2025
$3.5M
NCI NIH HHS P50 CA058223NCI NIH HHS R01 CA229409NCI NIH HHS U10 CA180821NCI NIH HHS U10 CA180882NCI NIH HHS U24 CA196171NCI NIH HHS UG1 CA233333NCI NIH HHS UG1 CA233373
6 · The paper itself

Abstract

BACKGROUNDDespite therapeutic advances in early-stage triple-negative breast cancer (TNBC), residual disease (RD) following neoadjuvant therapy remains a key predictor of a worse prognosis and obstacle to improving patient outcomes.METHODSTo better characterize RD and identify survival-associated features, we performed comprehensive transcriptomic profiling of 340 pretreatment stage II/III TNBCs and 70 matched posttreatment RD samples from the randomized CALGB 40603 (Alliance) phase II clinical trial. To explore preclinical treatment strategies for RD, patient-derived xenograft (PDX) mouse models mimicking RD were treated with antibody-drug conjugates (ADCs).RESULTSOur study shows prognostic genomic features measured pretreatment may differ from prognostic features measured posttreatment from RD specimens. Patients with a genomic PAM50 subtype of basal-like in RD specimens had a poor survival outcome, and their matching pretreatment tumors were characterized by elevated chromosomal amplifications of oncogenic drivers and significantly reduced B and T cell expression features. Paired analyses of basal-like RD and matched pretreatment tumors revealed further lymphocyte depletion in RD, along with lower expression of MHC class I and interferon signaling, indicating an immune-cold RD microenvironment. Treatment of a basal-like and conventional chemotherapy-resistant PDX model, resembling basal-like RD, with sacituzumab govitecan or trastuzumab deruxtecan produced a marked antitumor response.CONCLUSIONRD biology differs from pretreatment tumors, with basal-like subtype RD following neoadjuvant chemotherapy being immune cold and associated with poor survival. Preclinical modeling suggests this high-risk group may benefit from adjuvant ADC therapy.TRIAL REGISTRATIONClinicalTrials.gov NCT00861705.FUNDINGNIH NCI U10CA180821 (Alliance for Clinical Trials in Oncology), NCI U24CA176171 (Alliance for Clinical Trials in Oncology), NCI UG1CA233373 (Alliance for Clinical Trials in Oncology), NCI Breast SPORE program P50-CA058223; Susan G. Komen SAC-160074; Breast Cancer Research Foundation BCRF-23-127; NIH NCI R01-CA229409; UNC LCCC Triple Negative Breast Cancer Center.

Indexed as

ImmunoconjugatesNeoadjuvant TherapyTriple Negative Breast NeoplasmsAnimalsFemaleHumansMiceMiddle AgedNeoplasm, ResidualXenograft Model Antitumor AssaysImmunoconjugatesBiomarkersBreast cancerClinical ResearchOncologyTranscriptomics

Identifiers

PMID42550611
PMCPMC13574147

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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.