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Breast cancer
PIK3CA Mutation is Associated with Poor Response to HER2-Targeted Therapy in Breast Cancer Patients
Ju Won Kim, Ah Reum Lim, Ji Young You, Jung Hyun Lee, Sung Eun Song, Nam Kwon Lee, Seung Pil Jung, Kyu Ran Cho, Cheol Yong Kim, Kyong Hwa Park
Cancer Res Treat. 2023;55(2):531-541.   Published online September 7, 2022
DOI: https://doi.org/10.4143/crt.2022.221
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Mutations in the PIK3CA gene occur frequently in breast cancer patients. Activating PIK3CA mutations confer resistance to human epidermal growth factor receptor 2 (HER2)-targeted treatments. In this study, we investigated whether PIK3CA mutations were correlated with treatment response or duration in patients with HER2-positive (HER2+) breast cancer.
Materials and Methods
We retrospectively reviewed the clinical information of patients with HER2+ breast cancer who received HER2-targeted therapy for early-stage or metastatic cancers. The pathologic complete response (pCR), progression-free survival (PFS), and overall survival were compared between patients with wild-type PIK3CA (PIK3CAw) and those with mutated PIK3CA (PIK3CAm). Next-generation sequencing was combined with examination of PFS associated with anti-HER2 monoclonal antibody (mAb) treatment.
Results
Data from 90 patients with HER2+ breast cancer were analyzed. Overall, 34 (37.8%) patients had pathogenic PIK3CA mutations. The pCR rate of the PIK3CAm group was lower than that of the PIK3CAw group among patients who received neoadjuvant chemotherapy for early-stage cancer. In the metastatic setting, the PIK3CAm group showed a significantly shorter mean PFS (mPFS) with first-line anti-HER2 mAb. The mPFS of second-line T-DM1 was lower in the PIK3CAm group than that in the PIK3CAw group. Sequencing revealed differences in the mutational landscape between PIK3CAm and PIK3CAw tumors.
Conclusion
Patients with HER2+ breast cancer with activating PIK3CA mutations had lower pCR rates and shorter PFS with palliative HER2-targeted therapy than those with wild-type PIK3CA. Precise targeted-therapy is needed to improve survival of patients with HER2+/PIK3CAm breast cancer.

Citations

Citations to this article as recorded by  
  • Safety and efficacy of pyrotinib for HER‑2‑positive breast cancer in the neoadjuvant setting: A systematic review and meta‑analysis
    Qian Ma, Bai Wei, Bi-Cheng Wang, Ganxin Wang, Xuan Zhou, Yan Wang
    Oncology Letters.2024;[Epub]     CrossRef
  • A novel PIK3CA hot-spot mutation in breast cancer patients detected by HRM-COLD-PCR analysis
    Saoussen Debouki-Joudi, Wala Ben Kridis, Fatma Trifa, Wajdi Ayadi, Abdelmajid Khabir, Tahia Sellami-Boudawara, Jamel Daoud, Afef Khanfir, Raja Mokdad-Gargouri
    Breast Disease.2024; 43(1): 213.     CrossRef
  • Liquid Biopsy in the Clinical Management of Cancers
    Ho-Yin Ho, Kei-See (Kasey) Chung, Chau-Ming Kan, Sze-Chuen (Cesar) Wong
    International Journal of Molecular Sciences.2024; 25(16): 8594.     CrossRef
  • Modeling the management of patients with human epidermal growth factor receptor 2-positive breast cancer with liquid biopsy: the future of precision medicine
    Eleonora Nicolò, Caterina Gianni, Giuseppe Curigliano, Carolina Reduzzi, Massimo Cristofanilli
    Current Opinion in Oncology.2024; 36(6): 503.     CrossRef
  • Current progress in chimeric antigen receptor-modified T cells for the treatment of metastatic breast cancer
    Li Yin, Gui-lai Chen, Zhuo Xiang, Yu-lin Liu, Xing-yu Li, Jing-wang Bi, Qiang Wang
    Biomedicine & Pharmacotherapy.2023; 162: 114648.     CrossRef
  • Genomic analysis of plasma circulating tumor DNA in patients with heavily pretreated HER2 + metastatic breast cancer
    Kyoungmin Lee, Jongwon Lee, Jungmin Choi, Sung Hoon Sim, Jeong Eun Kim, Min Hwan Kim, Yeon Hee Park, Jee Hyun Kim, Su-Jin Koh, Kyong Hwa Park, Myoung Joo Kang, Mi Sun Ahn, Kyoung Eun Lee, Hee-Jun Kim, Hee Kyung Ahn, Han Jo Kim, Keon Uk Park, In Hae Park
    Scientific Reports.2023;[Epub]     CrossRef
  • Association of PIK3CA mutation with outcomes in HER2-positive breast cancer treated with anti-HER2 therapy: A meta-analysis and bioinformatic analysis of TCGA‑BRCA data
    Haizhu Chen, Xingbin Hu, Daquan Wang, Ying Wang, Yunfang Yu, Herui Yao
    Translational Oncology.2023; 37: 101738.     CrossRef
  • Appraisal of Systemic Treatment Strategies in Early HER2-Positive Breast Cancer—A Literature Review
    Danilo Giffoni de Mello Morais Mata, Rania Chehade, Malek B. Hannouf, Jacques Raphael, Phillip Blanchette, Abdullah Al-Humiqani, Monali Ray
    Cancers.2023; 15(17): 4336.     CrossRef
  • The clinical significance of HER2 expression in DCIS
    Ioanna Akrida, Francesk Mulita
    Medical Oncology.2022;[Epub]     CrossRef
  • 7,230 View
  • 287 Download
  • 8 Web of Science
  • 9 Crossref
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Genomic Signatures from Clinical Tumor Sequencing in Patients with Breast Cancer Having Germline BRCA1/2 Mutation
Ju Won Kim, Hyo Eun Kang, Jimi Choi, Seung Gyu Yun, Seung Pil Jung, Soo Yeon Bae, Ji Young You, Yoon-Ji Choi, Yeul Hong Kim, Kyong Hwa Park
Cancer Res Treat. 2023;55(1):155-166.   Published online June 8, 2022
DOI: https://doi.org/10.4143/crt.2021.1567
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
BRCA1 and BRCA2 are among the most important genes involved in DNA repair via homologous recombination (HR). Germline BRCA1/2 (gBRCA1/2)-related cancers have specific characteristics and treatment options but conducting gBRCA1/2 testing and interpreting the genetic imprint are sometimes complicated. Here, we describe the concordance of gBRCA1/2 derived from a panel of clinical tumor tissues using next-generation sequencing (NGS) and genetic aspects of tumors harboring gBRCA1/2 pathogenic variants.
Materials and Methods
Targeted sequencing was performed using available tumor tissue from patients who underwent gBRCA1/2 testing. Comparative genomic analysis was performed according to gBRCA1/2 pathogenicity.
Results
A total of 321 patients who underwent gBRCA1/2 testing were screened, and 26 patients with gBRCA1/2 pathogenic (gBRCA1/2p) variants, eight patients with gBRCA1/2 variants of uncertain significance (VUS; gBRCA1/2v), and 43 patients with gBRCA1/2 wild-type (gBRCA1/2w) were included in analysis. Mutations in TP53 (49.4%) and PIK3CA (23.4%) were frequently detected in all samples. The number of single-nucleotide variants (SNVs) per tumor tissue was higher in the gBRCA1/2w group than that in the gBRCA1/2p group (14.81 vs. 18.86, p=0.278). Tumor mutation burden (TMB) was significantly higher in the gBRCA1/2w group than in the gBRCA1/2p group (10.21 vs. 13.47, p=0.017). Except for BRCA1/2, other HR-related genes were frequently mutated in patients with gBRCA1/2w.
Conclusion
We demonstrated high sensitivity of gBRCA1/2 in tumors analyzed by NGS using a panel of tumor tissues. TMB value and aberration of non-BRCA1/2 HR-related genes differed significantly according to gBRCA1/2 pathogenicity in patients with breast cancer.

Citations

Citations to this article as recorded by  
  • Clinico-Pathological Factors Determining Recurrence of Phyllodes Tumors of the Breast: The 25-Year Experience at a Tertiary Cancer Centre
    Baijaeek Sain, Arnab Gupta, Aruni Ghose, Sudip Halder, Vishal Mukherjee, Samir Bhattacharya, Radha Raman Mondal, Aditya Narayan Sen, Bijan Saha, Shravasti Roy, Stergios Boussios
    Journal of Personalized Medicine.2023; 13(5): 866.     CrossRef
  • 6,174 View
  • 203 Download
  • 1 Web of Science
  • 1 Crossref
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Case Report
Primary Follicular Lymphoma in a Male Breast: A Case Report
Seung Pil Jung, Kang Min Han, Seok Jin Kim, Seok Jin Nam, Jeoung Won Bae, Jeong Eon Lee
Cancer Res Treat. 2014;46(1):104-107.   Published online January 15, 2014
DOI: https://doi.org/10.4143/crt.2014.46.1.104
AbstractAbstract PDFPubReaderePub
Primary breast lymphoma (PBL) is a rare disease, particularly in males. Diffuse large B cell lymphoma is the most common PBL, while follicular lymphoma is less common. Furthermore, primary follicular lymphoma of a male breast is rarely reported. We report a male patient with primary follicular lymphoma of the breast and hepatocellular carcinoma (HCC). A 46-year-old man was diagnosed with liver cirrhosis secondary to chronic hepatitis B infection. Ten years later, he underwent segmentectomy of the liver due to HCC. Another 5 months later, he presented with a painless mass in the right chest wall. The mass was diagnosed as follicular lymphoma of the breast. The stage was IEA and he did not receive adjuvant therapy. Although only a few cases have been reported, lymphoma should be considered as a possible cause of breast mass, even in male patients.

Citations

Citations to this article as recorded by  
  • Clinicopathologic and mutational profiles of primary breast diffuse large B cell lymphoma in a male patient: case report and literature review
    Fengbo Huang, Yachao Ruan, Xiaojuan He, Hui Lian, Jinhua Yang
    World Journal of Surgical Oncology.2023;[Epub]     CrossRef
  • Primary breast lymphoma in males: Incidence, demographics, prognostic factors, survival, and comparisons with females
    Jie Zhang, Binbin Ma, Hong Ji, Rong Guo
    Frontiers in Surgery.2022;[Epub]     CrossRef
  • Hematologic Malignancies of the Breast: A Contemporary Series Investigating Incidence, Presentation, Accuracy of Diagnosis on Core Needle Biopsy, and Hormone Receptor Expression
    Marie-Christine Guilbert, Jason L Hornick, Sona A Chikarmane, Susan C Lester
    Breast Cancer: Basic and Clinical Research.2019;[Epub]     CrossRef
  • 15,492 View
  • 66 Download
  • 5 Web of Science
  • 3 Crossref
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