Evidence map›Paper›PMID 41316049›Full record

ArticleBMC cancer2025

Clinical characteristics and prognostic impact of HER2-ultralow breast cancer and tumor-infiltrating lymphocytes (TILs).

Koji Takada, Shinichiro Kashiwagi, Mariko Nishikawa, Asuka Kochi, Chika Watanabe, Haruhito Kinoshita, Kana Ogisawa, Masatsune Shibutani, Tamami Morisaki

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PubMed Full text at PMC Publisher
In one paragraph

Article in BMC cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed, 1 pooled it
–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

2 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. 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

9 authors.

Koji TakadaDepartment of Breast Surgical Oncology, Graduate School of Medicine, Osaka Metropolitan University, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.
Shinichiro KashiwagiDepartment of Breast Surgical Oncology, Graduate School of Medicine, Osaka Metropolitan University, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan. spqv9ke9@view.ocn.ne.jp.
Mariko NishikawaDepartment of Breast Surgical Oncology, Graduate School of Medicine, Osaka Metropolitan University, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.
Asuka KochiDepartment of Breast Surgical Oncology, Graduate School of Medicine, Osaka Metropolitan University, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.
Chika WatanabeDepartment of Breast Surgical Oncology, Graduate School of Medicine, Osaka Metropolitan University, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.
Haruhito KinoshitaDepartment of Breast Surgical Oncology, Graduate School of Medicine, Osaka Metropolitan University, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.
Kana OgisawaDepartment of Breast Surgical Oncology, Graduate School of Medicine, Osaka Metropolitan University, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.
Masatsune ShibutaniDepartment of Gastrointestinal Surgery, Graduate School of Medicine, Osaka Metropolitan University, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.
Tamami MorisakiDepartment of Breast Surgical Oncology, Graduate School of Medicine, Osaka Metropolitan University, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.

Funding

Japan Society for the Promotion of Science 20K08938
6 · The paper itself

Abstract

purposeHER2 expression is crucial in breast cancer classification and treatment. Traditionally, tumors were categorized as HER2-positive or HER2-negative, but HER2-low (IHC 1 + or 2 + without ISH amplification) has emerged as a new classification. Among HER2-negative cases, HER2-ultralow (≤ 10% faint HER2 staining) and HER2-null (completely HER2-negative) have been proposed. While differences between HER2-low and HER2-zero tumors are studied, little is known about the clinical and prognostic characteristics of HER2-ultralow breast cancer. This study aimed to clarify the clinical characteristics, immune microenvironment, treatment response, and prognosis of HER2-ultralow tumors, with HER2-null and HER2-low tumors analyzed as comparators.

methodsA retrospective analysis of 244 HER2-negative breast cancer patients treated with neoadjuvant chemotherapy (NAC) at Osaka Metropolitan University Hospital (2007-2018) classified tumors into HER2-low (41.0%), HER2-ultralow (36.1%), and HER2-null (23.0%). Clinicopathological features, tumor-infiltrating lymphocyte (TIL) counts, pathological complete response (pCR), and prognostic outcomes (disease-free survival [DFS] and overall survival [OS]) were evaluated.

resultsHER2-ultralow tumors showed significantly higher estrogen receptor (ER) positivity compared with HER2-null tumors (51.8% vs. 19.6%, p < 0.001), and also tended to have higher progesterone receptor positivity (p = 0.048). In contrast, HER2-null tumors were associated with younger age (median 50.0 vs. 56.0 years, p = 0.004) and higher TIL density (50.0% vs. 36.8%, p = 0.016). The overall pCR rate was 27.9%. DFS showed no significant differences among the three groups (p = 0.087), but OS was significantly worse in HER2-null compared with Not HER2-null tumors (p = 0.026, HR = 0.454). HER2-ultralow cases demonstrated an intermediate prognosis between HER2-low and HER2-null (OS comparison with HER2-null,>p= 0.101).

conclusionHER2-ultralow tumors represent a distinct subgroup characterized by higher hormone receptor positivity, whereas HER2-null tumors were associated with younger age, higher TIL density, and poorer survival. These findings emphasize the clinical significance of refining HER2-negative subclassification to distinguish HER2-ultralow, while acknowledging limitations of sample size and retrospective design.

Indexed as

Breast NeoplasmsErb-b2 Receptor Tyrosine KinasesLymphocytes, Tumor-InfiltratingAdultAgedBiomarkers, TumorFemaleHumansMiddle AgedNeoadjuvant TherapyPrognosisRetrospective StudiesTumor MicroenvironmentBiomarkers, TumorERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesBreast cancerHER2-lowHER2-ultaralowNeoadjuvant chemotherapyTumor-infiltrating lymphocytes

Identifiers

PMID41316049
PMCPMC12751392

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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.