Role of phosphatidylinositol 3 kinase in metastasis and grading of luminal breast cancer subtypes
Keywords:
metastasis, breast cancer, phosphatidylinositol 3-kinase, HER2, luminal subtype, prognostic factorsAbstract
Background and aim: The luminal subtype (HR+/HER2-) represents 70% of breast cancer cases. This subtype frequently involves alterations of the phosphatidylinositol 3-kinase (PI3K) pathway that result in tumor development, disease progression, and endocrine therapy resistance. This study aimed to examine the association between PI3K expression in luminal subtype breast cancer cells and metastasis in breast cancer patients in Makassar, Indonesia.
Methods: A cross-sectional study was conducted to semi-quantitatively analyze PI3K expression in breast cancer patients. Staining intensities and percentages of carcinoma cell membranes stained relative to the total carcinoma cells were measured. Immunohistochemistry results were scored as follows: 0 (negative), 1 (weak), 2 (moderate), and 3 (strong) according to the percentage of the area. Chi-square tests were performed to assess the relationships between PI3K and breast cancer grading and metastasis.
Results: Breast cancer patients (74) who met the inclusion criteria for the study sample consisted of 30 (40.5%) patients with metastatic breast cancer and 44 (59.5%) with non-metastatic breast cancer. PI3K positivity was common in patients with high-grade malignant mammary carcinoma (75.9%; p-value 0.003 (≤0.05)) and those with metastasis (75.9%; p-value 0.015 (≤0.05)). Patients with PI3K-positive breast cancer had a 2.302 times greater probability of metastasis than those with negative PI3K values (95% CI 1.147–4.617).
Conclusions: As the overexpression of PI3K increases, the histopathological grading of breast cancer and the tendency for distant metastasis escalate.
References
Prihantono P, Rusli R, Christeven R, Faruk M. Cancer Incidence and Mortality in a Tertiary Hospital in Indonesia: An 18-Year Data Review. Ethiop J Health Sci. 2023;33(3). doi:10.4314/ejhs.v33i3.15
Smolarz B, Nowak AZ, Romanowicz H. Breast Cancer—Epidemiology, Classification, Pathogenesis and Treatment (Review of Literature). Cancers. 2022;14(10):2569. doi:10.3390/cancers14102569
Anderson EJ, Mollon LE, Dean JL, et al. A Systematic Review of the Prevalence and Diagnostic Workup of PIK3CA Mutations in HR+/HER2– Metastatic Breast Cancer. Int J Breast Cancer. 2020;2020:1-16. doi:10.1155/2020/3759179
Mosele F, Stefanovska B, Lusque A, et al. Outcome and molecular landscape of patients with PIK3CA-mutated metastatic breast cancer. Ann Oncol. 2020;31(3):377-386. doi:10.1016/j.annonc.2019.11.006
Lee MH, Cho JH, Kwon SY, Jung SJ, Lee JH. Clinicopathological Characteristics of PIK3CA Mutation and Amplification in Korean Patients with Breast Cancers. Int J Med Sci. 2020;17(8):1131-1135. doi:10.7150/ijms.44319
Martínez-Sáez O, Chic N, Pascual T, et al. Frequency and spectrum of PIK3CA somatic mutations in breast cancer. Breast Cancer Res. 2020;22(1):45. doi:10.1186/s13058-020-01284-9
Wang S, Liu M, Lian S, et al. Which Is the Most Appropriate PI3K Inhibitor for Breast Cancer Patients with or without PIK3CA Status Mutant? A Systematic Review and Network Meta-Analysis. Cai X, ed. BioMed Res Int. 2020;2020:1-12. doi:10.1155/2020/7451576
Siregar KB, Al Anas M. Unveiling bone metastasis: Exploring histological subtypes of breast cancer in Indonesia’s tertiary referral hospital. Cancer Treat Res Commun. 2023;37:100764. doi:10.1016/j.ctarc.2023.100764
Setyorini G, Sasmithae L, Fianza PI, Kurnia D. Hubungan subtipe molekuler kanker payudara dengan grading histopatologi di RSUD M Yunus Bengkulu. Intisari Sains Med. 2023;14(2):519-524. doi:10.15562/ism.v14i2.1738
Abidin Z. Peran Jalur Phosphatidyl-Inositol-3-kinase (PI3K) dalam Resistensi Kemoterapi pada Kanker. Qanun Med. 2018;2(01). doi:10.30651/qm.v2i01.545
Łukasiewicz S, Czeczelewski M, Forma A, Baj J, Sitarz R, Stanisławek A. Breast Cancer—Epidemiology, Risk Factors, Classification, Prognostic Markers, and Current Treatment Strategies—An Updated Review. Cancers. 2021;13(17):4287. doi:10.3390/cancers13174287
M. Pevzner A, A. Gaptulbarova K, M. Tsyganov M, et al. Investigation of somatic PIK3CA gene mutations in breast cancer patients. J Balk Union Oncol. 2021;26(3):747-752.
Şahin AB, Cubukcu E, Ocak B, et al. Low pan-immune-inflammation-value predicts better chemotherapy response and survival in breast cancer patients treated with neoadjuvant chemotherapy. Sci Rep. 2021;11(1):14662. doi:10.1038/s41598-021-94184-7
Lin F, Zhang LP, Xie SY, et al. Pan-Immune-Inflammation Value: A New Prognostic Index in Operative Breast Cancer. Front Oncol. 2022;12:830138. doi:10.3389/fonc.2022.830138
Lin J, Ding Q, Zhang G, Yin X. Study on PI3k gene expression in breast cancer samples and its association with clinical factors and patient survival. Cell Mol Biol. 2022;67(4):321-327. doi:10.14715/cmb/2021.67.4.36
Kołodziej P, Nicoś M, Krawczyk PA, et al. The Correlation of Mutations and Expressions of Genes within the PI3K/Akt/mTOR Pathway in Breast Cancer—A Preliminary Study. Int J Mol Sci. 2021;22(4):2061. doi:10.3390/ijms22042061
Mollon LE, Anderson EJ, Dean JL, et al. A Systematic Literature Review of the Prognostic and Predictive Value of PIK3CA Mutations in HR+/HER2− Metastatic Breast Cancer. Clin Breast Cancer. 2020;20(3):e232-e243. doi:10.1016/j.clbc.2019.08.011
Vernieri C, Corti F, Nichetti F, et al. Everolimus versus alpelisib in advanced hormone receptor-positive HER2-negative breast cancer: targeting different nodes of the PI3K/AKT/mTORC1 pathway with different clinical implications. Breast Cancer Res. 2020;22(1):33. doi:10.1186/s13058-020-01271-0
Li L, Liu D, Jin J, et al. PI3K expression predicts overall survival in lung adenocarcinoma. Int J Clin Exp Pathol. 2018;11(10):4889-4898.
Wang LL, Hao S, Zhang S, et al. PTEN/PI3K/AKT protein expression is related to clinicopathological features and prognosis in breast cancer with axillary lymph node metastases. Hum Pathol. 2017;61:49-57. doi:10.1016/j.humpath.2016.07.040
Fusco N, Malapelle U, Fassan M, et al. PIK3CA Mutations as a Molecular Target for Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer. Front Oncol. 2021;11:644737. doi:10.3389/fonc.2021.644737
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Copyright (c) 2025 Yusfitaria Alvina, Prihantono , John Pieter Jr. , Indra, Salman Ardi Syamsu, Nilam Smaradhania, Elridho Sampepajung, Berti Julian Nelwan, Abd. Rahman, Fahmi Razi Darkuthni, Muhammad Faruk
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