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 EspinoPhD in Immunology, specialized in Virology
