Molecular Subtypes and Mechanisms of Breast Cancer: Precision Medicine Approaches for Targeted Therapies

Abstract

Breast cancer remains one of the most prevalent diseases worldwide, primarily affecting women. Its heterogeneous nature poses a significant challenge in the development of effective and targeted treatments. Molecular characterization has enabled breast cancer to be classified into four main subtypes: luminal A, luminal B, HER2-positive, and triple-negative breast cancer, based on hormone receptor expression and HER2 status. A deeper understanding of these molecular markers and their associated signaling pathways, such as MAPK and PI3K/AKT, is essential for improving prognosis and optimizing treatment strategies. Currently, several therapeutic agents are utilized in neoadjuvant and adjuvant therapies, often in combination with surgical interventions. However, emerging evidence highlights the growing challenge of drug resistance, which significantly limits the efficacy of existing treatments. Addressing this issue may require innovative approaches, including combination therapies and precision medicine strategies, tailored to the molecular profile of each patient. Therefore, a comprehensive understanding of the pathophysiologic mechanisms driving breast cancer progression and resistance is crucial for the development of advanced targeted therapies with greater precision and efficacy. This review aims to explore recent advancements in molecular research related to breast cancer subtypes and provide a critical analysis of current therapeutic approaches within the framework of precision medicine.

Keywords: HER2; breast cancer; combination therapies; hormone receptor; precision medicine.

Figure 1

Estimated breast cancer numbers of incidence and mortality in European countries per 100,000 population in 2022 (developed from 1–3).

Figure 2

Mechanism of action of tamoxifen on ER-positive breast cancer. Tamoxifen binds to estrogen receptors (ER), preventing estrogen (E2) from binding. This inhibits the activation of estrogen-responsive elements (ERE) and the subsequent recruitment of coactivators, stopping gene transcription. Tamoxifen can also bind to estrogen receptors to inhibit the activation of PI3K/AKT/mTOR signaling cascade to decrease the transcription of genes involved in tumor progression. Together, they hamper cancer proliferation and progression. [BioRender, 2025].

Figure 3

Mechanism of action of trastuzumab and pertuzumab on HER2-positive breast cancer. Trastuzumab binds to the extracellular domain of HER2 receptor to prevent it from being activated, decreasing the expression of the MAPK signaling cascade that results in a reduction of transcription factors’ transcription important for tumor proliferation. Pertuzumab binds to HER3, preventing HER2-HER3 heterodimerization, which inhibits the phosphorylation of PI3K subunits, decreasing the activation of the PI3K/AKT signaling pathway, which in turn does not activate the transcription of transcription factors important for cell proliferation. [Biorender, 2025].

Figure 4

Anthracycline intercalates with DNA base pairs, causing the strand to break and leading to cell apoptosis. Paclitaxel-based chemotherapy increases the microtubule stabilization, causing the loss of their dynamic instability, important for chromosome alignment and segregation, which leads to M phase arrest and cell death. Atezolizumab inhibits PD-L1 from binding to PD-1 by binding itself to PD-L1, which promotes the T cell to recognize tumor cells again and leads to tumor cell death. [Biorender, 2025].