Caution over haste: why novel endocrine therapy in early lines should wait in Estrogen receptor positive human epidermal growth factor receptor 2 negative breast cancer.

Lan Lei, Manali Bhave, Kevin Kalinsky, Shipra Gandhi

Abstract readReview

In one paragraph

Review in Breast cancer research : BCR, 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

4 authors.

Lan LeiDepartment of Hematology and Oncology, Winship Cancer Institute of Emory University, 1365 Clifton Rd N E Building C, Atlanta, GA, 30322, USA.

Manali BhaveDepartment of Hematology and Oncology, Winship Cancer Institute of Emory University, 1365 Clifton Rd N E Building C, Atlanta, GA, 30322, USA.

Kevin KalinskyDepartment of Hematology and Oncology, Winship Cancer Institute of Emory University, 1365 Clifton Rd N E Building C, Atlanta, GA, 30322, USA.

Shipra GandhiDepartment of Hematology and Oncology, Winship Cancer Institute of Emory University, 1365 Clifton Rd N E Building C, Atlanta, GA, 30322, USA. shipra.gandhi@emory.edu.

Funding

Stress-induced immunosuppression via downregulation of interferon in triple negative breast cancerK08CA279766 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI Shipra Gandhi · 2024 to 2026

$915k

Identifying the role of interferon and interferon-regulated chemokines in stress-induced immunosuppression in triple negative breast cancerR03TR004607 · NCATS · ROSWELL PARK CANCER INSTITUTE CORP · PI GANDHI, SHIPRA · 2023 to 2023

$174k

NCATS NIH HHS R03 TR004607NCI NIH HHS K08 CA279766

6 · The paper itself

Abstract

The rapid development of novel endocrine therapies (ETs), such as selective estrogen receptor degraders (SERDs), proteolysis targeting chimeras (PROTACs), selective estrogen receptor covalent antagonists (SERCAs), and complete estrogen receptor antagonists (CERANs) has generated enthusiasm for their use in earlier treatment lines in advanced estrogen receptor-positive (ER+) human epidermal receptor 2-negative (HER2-) breast cancer (BC). Multiple phase III trials have demonstrated progression-free survival (PFS) benefit for novel ETs, especially in patients harboring ESR1 mutations. However, their broader use may be limited by toxicity concerns, adherence challenges, need for combination therapy, and financial burden. In this manuscript, we provide a concise review of key clinical trial outcomes for novel ETs with a focus on SERDs and critically evaluate their use in earlier lines of therapy. We also examine the design of ongoing adjuvant and first-line trials and explore the clinical implications of circulating tumor DNA (ctDNA)-guided treatment strategies.

Indexed as

Antineoplastic Agents, HormonalBreast NeoplasmsErb-b2 Receptor Tyrosine KinasesReceptors, EstrogenCirculating Tumor DNAEstrogen Receptor alphaFemaleHumansProteolysis Targeting ChimeraAntineoplastic Agents, HormonalCirculating Tumor DNAERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesEstrogen Receptor alphaProteolysis Targeting ChimeraReceptors, EstrogenBreast cancerEstrogen receptor positiveNovel endocrine therapy

Identifiers

PMID41572375

DOI10.1186/s13058-025-02203-6

PMCPMC12918290

What OpenQuestion holds

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LicenceCC BY-NC-ND

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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.