International Journal of Inflammation, Cancer and Integrative Therapy
Open Access

Breast cancer; Biomarkers, Estrogen receptor (ER), HER2, Triple-negative breast cancer (TNBC)

Introduction

Breast cancer is the most frequently diagnosed cancer and a leading cause of cancer-related death among women globally. Its heterogeneity is reflected in the various subtypes, each with distinct biological characteristics and clinical behaviors. The classification of breast cancer into subtypes is primarily based on the expression of hormone receptors such as the estrogen receptor (ER) and the progesterone receptor (PR), as well as the human epidermal growth factor receptor 2 (HER2). Understanding these subtypes and their associated biomarkers has revolutionized breast cancer management, allowing for more personalized treatment approaches. This article provides a comprehensive review of the different breast cancer subtypes, the biomarkers associated with each subtype, and the clinical applications of these biomarkers in the context of diagnosis, prognosis, and targeted therapy [1].

Discussion

Major breast cancer subtypes and their biomarkers

Hormone receptor-positive breast cancer: This subtype includes tumors that express ER and/or PR. Hormone receptor-positive breast cancers are the most common, accounting for about 70% of all breast cancer cases. Biomarkers such as ER and PR are crucial for determining the likelihood of response to hormone therapies like tamoxifen and aromatase inhibitors. The Ki-67 protein is another important biomarker used to assess the proliferation rate of cancer cells, helping to further stratify patients and guide treatment decisions [2].

Her2-positive breast cancer: Characterized by the overexpression of the HER2 protein, this subtype accounts for approximately 15-20% of breast cancers. HER2-positive tumors tend to be more aggressive but are responsive to targeted therapies such as trastuzumab (Herceptin) and pertuzumab (Perjeta). The HER2 biomarker is essential for identifying patients who would benefit from these therapies. Additionally, the measurement of HER2 mRNA levels and HER2 gene amplification through techniques such as immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) plays a crucial role in diagnosis and treatment planning [3].

Triple-negative breast cancer (TNBC): This subtype lacks the expression of ER, PR, and HER2, making up about 10-15% of breast cancer cases. TNBC is more common in younger women and those with BRCA1 mutations. Due to the absence of targeted receptors, treatment options are limited to chemotherapy. Biomarkers such as androgen receptor (AR), epidermal growth factor receptor (EGFR), and basal-like markers (e.g., cytokeratin 5/6) are under investigation for their potential roles in targeted therapy and prognosis.

The clinical utility of biomarkers extends beyond subtype classification. They are essential for early detection, risk stratification, and monitoring treatment response. Techniques such as immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and next-generation sequencing (NGS) are employed to evaluate biomarker expression and genetic alterations in tumor tissues. These advancements in molecular diagnostics have paved the way for precision medicine, where treatment is tailored to the individual patient's tumor profile [4].

Despite significant progress, challenges remain in the clinical application of biomarkers, including tumor heterogeneity, resistance to targeted therapies, and the need for novel biomarkers to address unmet clinical needs. Continuous research and technological innovations are essential to overcome these challenges and further enhance personalized breast cancer care.

This comprehensive review aims to provide an in-depth understanding of the major breast cancer subtypes, their associated biomarkers, and the clinical implications of these biomarkers. By examining the current state of knowledge and highlighting future directions, we hope to contribute to the ongoing efforts to improve breast cancer diagnosis, prognosis, and treatment [5].

Clinical implications of breast cancer biomarkers

Diagnosis: Biomarkers play a vital role in the initial diagnosis of breast cancer subtypes. IHC and FISH are commonly used techniques to assess the expression of ER, PR, and HER2 in tumor tissues. These biomarkers help pathologists accurately classify the cancer subtype, which is essential for guiding treatment decisions.

Prognosis: The presence and levels of specific biomarkers can provide prognostic information. For example, high levels of ER and PR are generally associated with a better prognosis and a higher likelihood of response to hormone therapy. Conversely, high HER2 expression is linked to more aggressive disease but also to a favorable response to HER2-targeted therapies. The Ki-67 proliferation index is used to gauge tumor aggressiveness and predict outcomes.

Targeted therapy: The identification of biomarkers has enabled the development of targeted therapies that specifically address the molecular characteristics of different breast cancer subtypes. For instance, ER-positive tumors benefit from hormone therapies, HER2-positive cancers are treated with HER2 inhibitors, and ongoing research aims to identify effective targeted treatments for TNBC based on emerging biomarkers [6].

Challenges and Future Directions

Heterogeneity and Resistance: Intratumor heterogeneity and the development of resistance to targeted therapies pose significant challenges [7]. Continuous monitoring of biomarker expression and the genetic landscape of tumors is necessary to adapt treatment strategies and overcome resistance mechanisms.

Emerging Biomarkers: Research is ongoing to discover new biomarkers that can better predict treatment response and improve patient outcomes. Multi-omics approaches, including genomics, proteomics, and metabolomics, are being explored to identify novel biomarkers and therapeutic targets.

Personalized Medicine: Advances in technology, such as next-generation sequencing (NGS) and liquid biopsies, are enhancing the ability to personalize treatment [8]. These tools allow for the real-time monitoring of disease progression and the identification of minimal residual disease, leading to more tailored and effective treatment plans.

The identification and characterization of breast cancer subtypes and their associated biomarkers have significantly improved the diagnosis, prognosis, and treatment of breast cancer [9]. While challenges such as heterogeneity and resistance remain, ongoing research and technological advancements hold promise for further enhancing personalized medicine in breast cancer care. By continuing to refine our understanding of these biomarkers and integrating them into clinical practice, we can achieve better outcomes and more effective treatments for patients with breast cancer.

Acknowledgement

None

Conflict of Interest

None

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