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
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
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