doi: 10.56294/shp2024105

 

REVIEW

 

Impact of the PIK3CA mutation on breast cancer

 

Impacto de la mutación PIK3CA en el cáncer de mama

 

Bruno Franco Santoro1 *, Mónica Casalnuovo1 *

 

1Universidad Abierta Interamericana, Facultad de Medicina y Ciencias de la Salud, Carrera de Medicina. Buenos Aires, Argentina.

 

Cite as: Franco Santoro B, Casalnuovo M. Impact of the PIK3CA mutation on breast cancer. South Health and Policy. 2024; 3:105. https://doi.org/10.56294/shp2024105    

 

Submitted: 27-06-2023          Revised: 30-09-2023          Accepted: 14-01-2024          Published: 15-01-2024

 

Editor: Dr. Telmo Raúl Aveiro-Róbalo  

 

Corresponding Author: Bruno Franco Santoro *

 

ABSTRACT

 

Breast cancer was a health priority both globally and in Argentina, where it was the leading cause of death from tumours in women. Its molecular and genetic understanding has led to advances in diagnosis, prognosis and treatment. The luminal subtype, characterised by hormone receptors, and the PIK3CA gene mutation, involved in the PI3K/Akt/mTOR pathway, were highlighted as being associated with greater tumour aggressiveness and resistance to therapies. In Argentina, studies have shown a high prevalence of this mutation, prompting the use of targeted therapies such as Alpelisib. This personalised approach has improved the stratification and clinical management of the disease.

 

Keywords: PIK3CA; Breast Cancer; Targeted Therapy; Luminal Subtype; PI3K/Akt/Mtor Pathway.

 

RESUMEN

 

El cáncer de mama representó una prioridad sanitaria tanto a nivel mundial como en Argentina, donde fue la principal causa de muerte por tumores en mujeres. Su comprensión molecular y genética permitió avances en diagnóstico, pronóstico y tratamiento. Se destacó el subtipo luminal, caracterizado por receptores hormonales, y la mutación del gen PIK3CA, implicada en la vía PI3K/Akt/mTOR, la cual se asoció con mayor agresividad tumoral y resistencia a terapias. En Argentina, estudios evidenciaron una alta prevalencia de esta mutación, impulsando el uso de terapias dirigidas como Alpelisib. Este enfoque personalizado mejoró la estratificación y abordaje clínico de la enfermedad.

 

Palabras clave: PIK3CA; Cáncer de Mama; Terapia Dirigida; Subtipo Luminal; Vía PI3K/Akt/Mtor.

 

 

 

INTRODUCTION

Breast cancer is a priority challenge for global public health and, particularly, for the Argentine healthcare system, where it is the leading cause of death from tumors in women. Understanding its molecular and genetic mechanisms has led to significant advances in its diagnosis, treatment, and prognosis. Within this approach, the characterization of molecular subtypes, such as luminal breast cancer, and the identification of relevant mutations, such as the PIK3CA gene mutation, have revolutionized the clinical approach to this disease. This theoretical framework explores the relevance of this mutation in tumor progression, its impact on therapeutic response, and the role of targeted therapies as a key strategy in precision oncology.

 

DEVELOPMENT

Breast cancer is one of the leading causes of death in women worldwide, ranking first in Argentina in terms of deaths from tumors, with an increasing incidence in recent decades.(1,2) This disease originates from the abnormal and uncontrolled proliferation of epithelial cells in the mammary gland, which acquire a malignant phenotype with invasive and metastatic capacity. This transformation involves genetic and epigenetic alterations that affect key pathways in cell regulation.(1)

In clinical and pathological terms, the current classification of breast cancer is decisive for both prognosis and therapeutic choice. According to Alcaide Lucena et al.(3), the most common subtype is luminal, characterized by the expression of estrogen and/or progesterone hormone receptors and HER2 negativity. This classification is complemented by clinical staging based on anatomical and functional parameters,(4,5) allowing individualized treatment strategies to be defined.

One of the most relevant findings in the molecular biology of breast cancer has been the identification of specific mutations, such as that of the PIK3CA gene, which encodes a subunit of phosphatidylinositol 3-kinase (PI3K). This enzyme participates in the PI3K/Akt/mTOR pathway, which is involved in cellular processes such as proliferation, survival, autophagy, and angiogenesis.(6) Aberrant activation of this pathway has been associated with resistance to hormone therapies, accelerated tumor progression, and shorter survival.(7,8)

In the Argentine context, Mandó et al.(9) analyzed the prevalence of PIK3CA mutations in breast cancer patients, showing a significant association between the presence of the mutation and a more aggressive clinical-pathological profile. This finding raises a new paradigm in the therapeutic approach, considering that targeted treatments such as specific PI3K inhibitors, including Alpelisib (Piqray), have shown benefits in patients with this genetic alteration.(10)

On the other hand, disease progression is defined as the appearance of new lesions or a significant increase in existing ones, which allows the efficacy of the therapeutic lines applied to be assessed.(11) In this sense, the mutational status of PIK3CA could be considered a negative prognostic marker, as it is associated with faster progression and lower survival, as recent clinical studies have shown.(6,7,12,13)

In summary, the molecular approach to breast cancer has led to progress toward a more personalized approach, where the identification of biomarkers such as PIK3CA is crucial. This allows not only for better stratification of patients based on their prognosis but also for the targeting of therapies that can improve the quality of life and the clinical course of the disease.(1,6,9)

 

CONCLUSIONS

The incorporation of molecular knowledge into the study of breast cancer has led to a better understanding of its biological heterogeneity, highlighting the importance of biomarkers such as the PIK3CA gene mutation in determining prognosis and therapeutic choice. Its presence is associated with a more aggressive profile and lower survival, underscoring the need for its systematic detection in advanced stages of the disease. In this context, treatments aimed at inhibiting the PI3K/Akt/mTOR pathway are emerging as a promising therapeutic alternative, contributing to the development of a more personalized, effective, and equitable approach to breast cancer management in Argentina and worldwide.

 

BIBLIOGRAPHICAL REFERENCES

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2. Bosch X, Fillela X. Neoplasias. En: Farreras P, Rozman C, editores. Farreras-Rozman. Medicina interna. 19ª ed. Barcelona: Elsevier; 2020. p. 2000-2025.

 

3. Alcaide Lucena, Rodríguez González, de Reyes Lartategui, Gallart Aragón, Sánchez Barrón, García Rubio, Torné Poyatos. Clasificación actual del cáncer de mama. Implicación en el tratamiento y pronóstico de la enfermedad. Cir Andal [Internet]. 2021 [citado 2024 Jul 15];32(2). Disponible en: https://www.asacirujanos.com/documents/revista/pdf/2021/Cir_Andal_vol32_n2_09.pdf

 

4. Medline Plus. Estadificación del cáncer de mama [Internet]. 2022 [citado 2024 Jul 15]. Disponible en: https://medlineplus.gov/spanish/ency/patientinstructions/000911.htm

 

5. Mayo Clinic. Breast cancer staging [Internet]. Mayo Clinic; 2022 Feb 12 [citado 2024 Jul 15]. Disponible en: https://www.mayoclinic.org/es/diseases-conditions/breast-cancer/in-depth/breast-cancer-staging/art-20045087

 

6. Peng Y, Wang Y, Zhou C, Mei W, Zeng C. PI3K/Akt/mTOR Pathway and Its Role in Cancer Therapeutics: Are We Making Headway? Front Oncol [Internet]. 2022 [citado 2024 Jul 15]. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8987494/

 

7. Yamamoto S, Nakagawa K, Matsunaga N, Shibata H, Mori T, et al. Impact of genetic therapy on patient outcomes: a comprehensive review. J Clin Med [Internet]. 2022 [citado 2024 Jul 15];11(14). Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9633529/#CR1

 

8. Europa Press. Esta es la relación del gen PIK3CA y el cáncer de mama agresivo. Infosalus [Internet]. 2021 [citado 2024 Jul 15]. Disponible en: https://www.infosalus.com/mujer/noticia-relacion-gen-pik3ca-cancer-mama-agresivo-20211130070946.html

 

9. Mandó P, Vidal R, Alonso A, Brosio C, Recondo G, Crimi G, Von Stecher F, Dennighoff V, Perazzo F. Prevalencia de la mutación de PIK3CA en cáncer de mama en la Argentina y su asociación con variables clínico-patológicas. Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno (CEMIC), Buenos Aires; Hospital de Morón, Provincia de Buenos Aires; Sanatorio de la Trinidad, Buenos Aires, Argentina.

 

10. Breastcancer.org. Piqray (Alpelisib): Efectos secundarios, cómo funciona y más [Internet]. 2023 [citado 2024 Jul 15]. Disponible en: https://www.breastcancer.org/es/tratamiento/terapia-dirigida/piqray

 

11. Asociación Española de Cáncer de Mama Metastásico. Remisión, estabilidad y progresión. Situación de la enfermedad [Internet]. [citado 2024 Jul 15]. Disponible en: https://www.cancermamametastasico.es/situacion-de-la-enfermedad/

 

12. ¿Qué es el carcinoma in situ y que significa? Medicina Básica [Internet]. 2021 [citado 2024 Jul 15]. Disponible en: https://medicinabasica.com/que-es-el-carcinoma-in-situ-y-que-significa

 

13. Etapas del cáncer de mama. Medical News Today [Internet]. [citado 2024 Jul 15]. Disponible en: https://www.medicalnewstoday.com/articles/es/etapas-de-cancer-de-mama#pronostico

 

FUNDING

None.

 

CONFLICT OF INTEREST

The authors declare that there is no conflict of interest.

 

AUTHOR CONTRIBUTION

Conceptualization: Bruno Franco Santoro, Mónica Casalnuovo.

Writing – original draft: Bruno Franco Santoro, Mónica Casalnuovo.

Writing – review and editing: Bruno Franco Santoro, Mónica Casalnuovo.