A heterogeneous cancer, evolving management

By Ana Espino | Published on october 16, 2025 | 2 min read



Metastatic breast cancer (MBC) remains an incurable disease with highly heterogeneous clinical forms. Despite recent advances, standard treatments—hormone therapy, chemotherapy, and immunotherapy—have limitations in the face of secondary resistance, genetic variability of tumors, and the progressive exhaustion of therapeutic options. In this context, targeted therapy based on molecular alterations is emerging as a promising strategy, offering a more personalized, more effective, and better-tolerated approach to treatment.  

The main challenge in using targeted therapy lies in precisely characterizing the tumor’s genetic profile to identify actionable alterations. The development of next-generation sequencing (NGS) technologies now enables some therapeutic decisions to be guided, paving the way for biomarker-driven treatment strategies.

This study was initiated to provide an overview of currently available or developing targeted therapies based on the identification of specific molecular alterations in metastatic breast cancer.    

Targeting to treat better?  

In this review, key actionable genetic alterations in MBC and the corresponding targeted therapies were selected. Among the most frequently studied are PIK3CA and ESR1 mutations, BRCA1/2 alterations, and rearrangements involving HER2, AKT1, or NTRK. NGS enables the identification of these tumor profiles to guide treatment decisions. Treatment effectiveness is assessed based on tumor response, progression-free survival, and tolerability.  

Pictilisib and alpelisib represent progress in patients with PIK3CA mutations, especially when combined with CDK4/6 inhibitors, showing demonstrated benefits in tumor control. For BRCA1/2 mutations, PARP inhibitors such as olaparib and talazoparib are now part of treatment strategies.

Trastuzumab deruxtecan, an antibody-drug conjugate, has become an effective option even for patients with low HER2 expression, challenging previous therapeutic classifications.  

Furthermore, emerging targets such as AKT1, FGFR, and NTRK mutations, as well as MSI-high tumors or those with high tumor mutational burden (TMB-high), are opening the door to innovative approaches, particularly in immunotherapy. In this evolving landscape, NGS is becoming a central decision-making tool, although it remains underused in many regions of the world.    

Using genetics to guide clinical care  

Metastatic breast cancer remains a serious, progressive, and currently incurable disease. Its genetic complexity and variability in treatment response present a significant challenge for clinicians. The goal of this review was to identify relevant molecular alterations and their associated targeted therapies to better adapt care to individual tumor profiles.

Current data confirm that certain genetic mutations (such as PIK3CA or BRCA1/2) can effectively guide treatment, prolonging survival and delaying progression. However, limited access to sequencing, lack of standardized analysis, and the absence of available therapies for many alterations hinder the widespread adoption of this approach.  

Future efforts should focus on the widespread adoption of genomic profiling in clinical practice, the development of therapies for rare alterations, and the creation of protocols that incorporate real-time tumor biology for truly personalized medicine.

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About the author – Ana Espino
As a scientific writer, Ana is passionate about bridging the gap between research and real-world impact. With expertise in immunology, virology, oncology, and clinical studies, she makes complex science clear and accessible. Her mission: to accelerate knowledge sharing and empower evidence-based decisions through impactful communication.