The “lows”: update on ER-low and HER2-low breast cancer DOI Open Access
Nicola Fusco,

G. Viale

The Breast, Journal Year: 2024, Volume and Issue: 78, P. 103831 - 103831

Published: Oct. 30, 2024

ER-low and HER2-low breast cancers have emerged as clinically significant subtypes that challenge traditional diagnostic categories treatment paradigms. These subtypes, representing a spectrum of disease, exhibit distinct biological behaviors, therapeutic responses, prognostic outcomes. cancer, defined by low HER2 protein expression (IHC score 1+ or 2+ without gene amplification), has achieved clinical significance, particularly following the DESTINY-Breast trials, which demonstrated efficacy trastuzumab deruxtecan (T-DXd) in population patients with advanced disease. Similarly, characterized estrogen receptor (in 1%-10 % invasive tumor cells), poses unique challenges due to its intermediate behavior uncertain response endocrine therapies. The identification these is further complicated inconsistencies testing methodologies, can lead misclassification impact decisions. As our understanding improves, need for standardized approaches individualized decisions becomes increasingly urgent. Ongoing research collaboration between pathologists oncologists are essential refining criteria improving outcomes theragnostic biomarkers. This review aims consolidate current knowledge on cancers, focusing associated their identification, implications treatment, future directions management. By examining recent studies interlaboratory assessments, this emphasizes critical accurate reproducible reporting, development tailored strategies "low" cancers.

Language: Английский

Case report: Near-complete response to neratinib-based treatment in HR-positive HER2-amplified metastatic breast cancer refractory to trastuzumab deruxtecan DOI Creative Commons
Ünal Metin Tokat, Ashkan Adibi, Esranur Aydın

et al.

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 14

Published: Jan. 21, 2025

Breast cancer (BC) is the leading cause of cancer-related mortality among women. The backbone first-line treatment in HR+/HER2+ BC dual anti-HER2 blockade combined with taxane chemotherapy. Although this regimen exhibits high rates response and disease control both HR+ HR− cohorts, some patients could have intrinsic or develop acquired resistance to trastuzumab and/or pertuzumab. Here, we achieved a near-complete HER2 -amplified overexpressing metastatic twice through molecular tumor board (MTB) discussions: initially, deruxtecan (T-DXd) when IHC was positive, and, then, neratinib plus fulvestrant paclitaxel negative. Our case presents GATA3 NOTCH2 mutations, MCL1 CKS1B amplifications, as well ERBB3/KRAS overexpression ER signaling potential new mechanisms T-DXd. Furthermore, demonstrated that triplet combination induce remarkable T-DXd–refractory setting, which be explored future clinical trials HER2-activated (by RNA protein overexpression, amplification, mutation) patients. also highlights importance MTBs dynamically reactively manage course on per-patient basis.

Language: Английский

Citations

1
The Biological Roles and Clinical Applications of the PI3K/AKT Pathway in Targeted Therapy Resistance in HER2-Positive Breast Cancer: A Comprehensive Review DOI Open Access

Hanyi Zhong,

Ziling Zhou,

Han Wang

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(24), P. 13376 - 13376

Published: Dec. 13, 2024

Epidermal growth factor receptor 2-positive breast cancer (HER2+ BC) is a highly invasive and malignant type of tumor. Due to its resistance HER2-targeted therapy, HER2+ BC has poor prognosis tendency for metastasis. Understanding the mechanisms underlying this developing effective treatments are major research challenges. The phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) pathway, which frequently altered in cancers, plays critical role cellular proliferation drug resistance. This signaling pathway activates various downstream pathways exhibits complex interactions with other networks. Given significance PI3K/AKT BC, several targeted drugs currently development. Multiple have entered clinical trials or gained market approval, bringing new hope therapy. However, therapies raise concerns related safety, regulation, ethics. Populations different races disease statuses exhibit varying responses treatments. Therefore, review, we summarize current knowledge on alteration biological roles as well applications perspectives, providing insights advancing BC.

Language: Английский

Citations

5
Anticancer Potential of Prebiotics: Targeting Estrogen Receptors and PI3K/AKT/mTOR in Breast Cancer DOI Creative Commons
Hussein Sabit,

Sama Abouelnour,

Bassel M. Hassen

et al.

Biomedicines, Journal Year: 2025, Volume and Issue: 13(4), P. 990 - 990

Published: April 18, 2025

Estrogen receptors (ERs) play a critical role in breast cancer (BC) development and progression, with ERα being oncogenic ERβ exhibiting tumor-suppressive properties. The interaction between ER signaling other molecular pathways, such as PI3K/AKT/mTOR, influences tumor growth endocrine resistance. Emerging research highlights the of prebiotics modulating gut microbiota, which may influence estrogen metabolism, immune function, therapeutic responses BC. This review explores impact on receptor modulation, microbiota composition, regulation, metabolic pathways cancer. potential adjunctive therapies to enhance treatment efficacy mitigate chemotherapy-related side effects is discussed. A comprehensive analysis recent preclinical clinical studies was conducted, examining reprogramming short-chain fatty acids (SCFAs) derived from prebiotic fermentation epigenetic regulation resistance also evaluated. Prebiotics were found modulate microbiota-estrogen axis, reduce inflammation, responses. SCFAs demonstrated selective downregulation reprogramming, suppressing growth. Synbiotic interventions effects, improving quality life patients. offer promising avenue for prevention therapy by pathways. Future trials are needed validate their treatments management.

Language: Английский

Citations

0
The role of circRNAs and miRNAs in drug resistance and targeted therapy responses in breast cancer DOI Open Access

Meilan Zhang,

Zhaokuan Zheng,

Shouliang Wang

et al.

Cancer Drug Resistance, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 19, 2024

MicroRNAs (miRNAs) are small non-coding RNAs comprising 19-24 nucleotides that indirectly control gene expression. In contrast to other (ncRNAs), circular (circRNAs) defined by their covalently closed loops, forming covalent bonds between the 3’ and 5’ ends. circRNAs regulate expression interacting with miRNAs at transcriptional or post-transcriptional levels. Accordingly, many biological events related cancer, including cell proliferation, metabolism, cycle, apoptosis. Both involved in pathogenesis of diseases, such as breast cancer. This review focuses on latest discoveries dysregulated highlighting potential biomarkers for clinical diagnosis, prognosis, chemotherapy response.

Language: Английский

Citations

3
The “lows”: update on ER-low and HER2-low breast cancer DOI Open Access
Nicola Fusco,

G. Viale

The Breast, Journal Year: 2024, Volume and Issue: 78, P. 103831 - 103831

Published: Oct. 30, 2024

ER-low and HER2-low breast cancers have emerged as clinically significant subtypes that challenge traditional diagnostic categories treatment paradigms. These subtypes, representing a spectrum of disease, exhibit distinct biological behaviors, therapeutic responses, prognostic outcomes. cancer, defined by low HER2 protein expression (IHC score 1+ or 2+ without gene amplification), has achieved clinical significance, particularly following the DESTINY-Breast trials, which demonstrated efficacy trastuzumab deruxtecan (T-DXd) in population patients with advanced disease. Similarly, characterized estrogen receptor (in 1%-10 % invasive tumor cells), poses unique challenges due to its intermediate behavior uncertain response endocrine therapies. The identification these is further complicated inconsistencies testing methodologies, can lead misclassification impact decisions. As our understanding improves, need for standardized approaches individualized decisions becomes increasingly urgent. Ongoing research collaboration between pathologists oncologists are essential refining criteria improving outcomes theragnostic biomarkers. This review aims consolidate current knowledge on cancers, focusing associated their identification, implications treatment, future directions management. By examining recent studies interlaboratory assessments, this emphasizes critical accurate reproducible reporting, development tailored strategies "low" cancers.

Language: Английский

Citations

2