Title
Author
DOI
Article Type
Special Issue
Volume
Issue
The effects of PIK3CA and TP53 on prognosis in patients with Triple-negative breast cancer (TNBC): a single institution’s long-term follow-up (6 years)
1Faculty of Life Science and Technology, Kunming University of Science and Technoloy, 650500 Kunming, Yunnan, China
2Department of Oncology, The Affiliated Hospital of Kunming University of Science and Technology, 650500 Kunming, Yunnan, China
3Laboratory of Molecular Genetics of Aging & Tumor, Medical School, Kunming University of Science and Technology, 650500 Kunming, Yunnan, China
DOI: 10.31083/j.ejgo4206191 Vol.42,Issue 6,December 2021 pp.1320-1325
Submitted: 28 April 2021 Accepted: 09 September 2021
Published: 15 December 2021
*Corresponding Author(s): Miaomiao Sheng E-mail: shengmm@kust.edu.cn
*Corresponding Author(s): Ying Luo E-mail: luoying@gmc.edu.cn
Objectives: This study investigated the prognostic value of PIK3CA and TP53 during a 6-year follow-up of breast cancer patients. We also analyzed the impact of other factors on progression-free survival (PFS) and patients’ overall survival (OS). Methods: The expression of estrogen receptor (ER), progesterone receptor (PR), and Ki67 in cancer tissues was detected by immunohistochemistry. For each patient, Epidermal Growth Factor Receptor 2 (HER2 was evaluated using fluorescence in situ hybridization (FISH). Sanger sequencing was used to detect hotspot mutations in PIK3CA and TP53 genes. Results: Lymph node metastasis is the most important factor affecting the patient’s prognosis (74.3% vs. 81.6%, p = 0.04). The mutation rates of PIK3CA and TP53 in Triple-negative breast cancer (TNBC) patients were significantly higher than those of other breast cancer types (29.4% vs. 3.6%, p = 0.002). In TNBC, the PFS of patients with PIK3CA and TP53 mutations is poorer than non-carriers (0% vs. 75%, p = 0.003). The OS of breast cancer patients in Yunnan Province is lower than that of regions with rapid economic development in China (78.08% vs. 90.5%). Conclusions: Our results indicate that PIK3CA and TP53 mutations are poor prognostic factors for patients with TNBC. PIK3CA and TP53 mutations could be used as a predictor for prognosis in TNBC patients.
PIK3CA; TP53; Breast cancer; Survival
Yuan Zhao, Wenru Tang,Limei Sun,Dun Xiong,Miaomiao Sheng,Ying Luo. The effects of PIK3CA and TP53 on prognosis in patients with Triple-negative breast cancer (TNBC): a single institution’s long-term follow-up (6 years). European Journal of Gynaecological Oncology. 2021. 42(6);1320-1325.
[1] Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians. 2018; 68: 394–424.
[2] Lawrence MS, Stojanov P, Mermel CH, Robinson JT, Garraway LA, Golub TR, et al. Discovery and saturation analysis of cancer genes across 21 tumour types. Nature. 2014; 505: 495–501.
[3] Yaeger R, Chatila WK, Lipsyc MD, Hechtman JF, Cercek A, Sanchez-Vega F, et al. Clinical Sequencing Defines the Genomic Landscape of Metastatic Colorectal Cancer. Cancer Cell. 2018; 33: 125–136.e3.
[4] Cancer Genome Atlas Network. Comprehensive molecular por- traits of human breast tumours. Nature. 2012; 490: 61–70.
[5] Volinia S, Hiles I, Ormondroyd E, Nizetic D, Antonacci R, Rocchi M, et al. Molecular cloning, cDNA sequence, and chromosomal lo- calization of the human phosphatidylinositol 3-kinase p110 alpha (PIK3CA) gene. Genomics. 1994; 24: 472–477.
[6] Magri J, Gasparetto A, Conti L, Calautti E, Cossu C, Ruiu R, et al. Tumor-Associated Antigen xCT and Mutant-p53 as Molecular Targets for New Combinatorial Antitumor Strategies. Cells. 2021; 10: 108.
[7] Silwal-Pandit L, Vollan HKM, Chin S, Rueda OM, McKinney S, Osako T, et al. TP53 Mutation Spectrum in Breast Cancer is Subtype Specific and has Distinct Prognostic Relevance. Clinical Cancer Research. 2014; 20: 3569–3580.
[8] Nik-Zainal S, Davies H, Staaf J, Ramakrishna M, Glodzik D, Zou X, et al. Landscape of somatic mutations in 560 breast cancer whole-genome sequences. Nature. 2016; 534: 47–54.
[9] Kadosh E, Snir-Alkalay I, Venkatachalam A, May S, Lasry A, Elyada E, et al. The gut microbiome switches mutant p53 from tumour-suppressive to oncogenic. Nature. 2020; 586: 133–138.
[10] Ji P, Gong Y, Jin ML, Hu X, Di GH, Shao ZM. The Burden and Trends of Breast Cancer From 1990 to 2017 at the Global, Regional, and National Levels: Results From the Global Burden of Disease Study 2017. Frontiers in Oncology. 2020; 10: 650.
[11] Australian Institute of Health and Welfare. Cancer survival and prevalence in Australia: period estimates from 1982 to 2010. Asia-Pacific Journal of Clinical Oncology. 2013; 9: 29–39.
[12] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA: A Cancer Journal for Clinicians. 2019; 69: 7–34.
[13] Sharma R. Breast cancer incidence, mortality and mortality-to-incidence ratio (MIR) are associated with human development, 1990–2016: evidence from Global Burden of Disease Study 2016. Breast Cancer. 2019; 26: 428–445.
[14] Guo F, Kuo Y, Shih YCT, Giordano SH, Berenson AB. Trends in breast cancer mortality by stage at diagnosis among young women in the United States. Cancer. 2018; 124: 3500–3509.
[15] Zielonke N, Gini A, Jansen EEL, Anttila A, Segnan N, Ponti A, et al. Evidence for reducing cancer-specific mortality due to screening for breast cancer in Europe: a systematic review. European Journal of Cancer. 2020; 127: 191–206.
[16] Xu L, Duan X, Zhou B, Liu Y, Ye J, Liu Z, et al. Validation of the CPS+eg and Neo-Bioscore staging systems after preoperative systemic therapy for breast cancer in a single center in China. Breast. 2018; 40: 29–37.
[17] Joko‐Fru WY, Miranda‐Filho A, Soerjomataram I, Egue M, Akele‐Akpo M, N’da G, et al. Breast cancer survival in sub‐Saharan Africa by age, stage at diagnosis and human development index: a population‐based registry study. International Journal of Cancer. 2020; 146: 1208–1218.
[18] Hernandez-Aya LF, Chavez-Macgregor M, Lei X, Meric- Bernstam F, Buchholz TA, Hsu L, et al. Nodal status and clinical outcomes in a large cohort of patients with triple-negative breast cancer. Journal of Clinical Oncology. 2011; 29: 2628–2634.
[19] LoRusso PM. Inhibition of the PI3K/AKT/mTOR Pathway in Solid Tumors. Journal of Clinical Oncology. 2016; 34: 3803–3815.
[20] Fujimoto Y, Morita TY, Ohashi A, Haeno H, Hakozaki Y, Fujii M, et al. Combination treatment with a PI3K/Akt/mTOR pathway inhibitor overcomes resistance to anti-her2 therapy in PIK3CA- mutant her2-positive breast cancer cells. Scientific Reports. 2020; 10: 21762.
[21] Stemke-Hale K, Gonzalez-Angulo AM, Lluch A, Neve RM, Kuo W, Davies M, et al. An integrative genomic and proteomic analysis of PIK3CA, PTEN, and AKT mutations in breast cancer. Cancer Research. 2008; 68: 6084–6091.
[22] Wang L, Zhang Q, Zhang J, Sun S, Guo H, Jia Z, et al. PI3K pathway activation results in low efficacy of both trastuzumab and lapatinib. BMC Cancer. 2011; 11: 248.
[23] Karakas B, Bachman KE, Park BH. Mutation of the PIK3CA onco-gene in human cancers. British Journal of Cancer. 2006; 94: 455– 459.
[24] Fruman DA, Chiu H, Hopkins BD, Bagrodia S, Cantley LC, Abra- ham RT. The PI3K Pathway in Human Disease. Cell. 2017; 170: 605–635.
[25] Liu L, Yan J, Cao Y, Yan Y, Shen X, Yu B, et al. Prolifera- tion, migration and invasion of triple negative breast cancer cells are suppressed by berbamine via the PI3K/Akt/MDM2/p53 and PI3K/Akt/mTOR signaling pathways. Oncology Letters. 2021; 21: 70.
[26] Lian J, Xu E, Xi Y, Wang H, Bu P, Wang J, et al. Clinical-Pathologic Analysis of Breast Cancer with PIK3CA Mutations in Chinese Women. Technology in Cancer Research & Treatment. 2020; 19: 153303382095083.
[27] Ellis H, Ma CX. PI3K Inhibitors in Breast Cancer Therapy. Current Oncology Reports. 2019; 21: 110.
[28] McCarthy AM, Kumar NP, He W, Regan S, Welch M, Moy B, et al. Different associations of tumor PIK3CA mutations and clinical outcomes according to aspirin use among women with metastatic hormone receptor positive breast cancer. BMC Cancer. 2020; 20: 347.
[29] Duffy MJ, Synnott NC, Crown J. Mutant p53 in breast cancer: potential as a therapeutic target and biomarker. Breast Cancer Research and Treatment. 2018; 170: 213–219.
[30] Wu J, Li X, Song W, Fang Y, Yu L, Liu S, et al. The roles and applications of autoantibodies in progression, diagnosis, treatment and prognosis of human malignant tumours. Autoimmunity Reviews. 2017; 16: 1270–1281.
[31] Kulić A, Sirotković-Skerlev M, Jelisavac-Ćosić S, Herceg D, Kovač Z, Vrbanec D. Anti-p53 antibodies in serum: relationship to tu- mor biology and prognosis of breast cancer patients. Medical Oncology. 2010; 27: 887–893.
[32] Hotchkiss RS, Strasser A, McDunn JE, Swanson PE. Cell Death. New England Journal of Medicine. 2009; 361: 1570–1583.
[33] Singh B. P53 regulates cell survival by inhibiting PIK3CA in squamous cell carcinomas. Genes & Development. 2002; 16: 984–993.
[34] Astanehe A, Arenillas D, Wasserman WW, Leung PCK, Dunn SE, Davies BR, et al. Expression of Concern: Mechanisms underlying p53 regulation of PIK3CA transcription in ovarian surface epithelium and in ovarian cancer. Journal of Cell Science. 2020; 133: jcs253260.
Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,500 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.
Biological Abstracts Easily discover critical journal coverage of the life sciences with Biological Abstracts, produced by the Web of Science Group, with topics ranging from botany to microbiology to pharmacology. Including BIOSIS indexing and MeSH terms, specialized indexing in Biological Abstracts helps you to discover more accurate, context-sensitive results.
Google Scholar Google Scholar is a freely accessible web search engine that indexes the full text or metadata of scholarly literature across an array of publishing formats and disciplines.
JournalSeek Genamics JournalSeek is the largest completely categorized database of freely available journal information available on the internet. The database presently contains 39226 titles. Journal information includes the description (aims and scope), journal abbreviation, journal homepage link, subject category and ISSN.
Current Contents - Clinical Medicine Current Contents - Clinical Medicine provides easy access to complete tables of contents, abstracts, bibliographic information and all other significant items in recently published issues from over 1,000 leading journals in clinical medicine.
BIOSIS Previews BIOSIS Previews is an English-language, bibliographic database service, with abstracts and citation indexing. It is part of Clarivate Analytics Web of Science suite. BIOSIS Previews indexes data from 1926 to the present.
Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.
Top