scholarly journals Germline genetic variants associated with leukocyte-genes predict tumor recurrence in breast cancer patients

2018 ◽  
Author(s):  
Jean-Sébastien Milanese ◽  
Chabane Tibiche ◽  
Jinfeng Zou ◽  
Zhi Gang Meng ◽  
Andre Nantel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Clinical Outcomes ◽  
Genetic Variants ◽  
Cell Function ◽  
Breast Cancer Patients ◽  
Sequencing Data ◽  
Germline Variants ◽  
Gene Signatures ◽  
Cytokine Interactions

AbstractGermline genetic variants such as BRCA1/2 play an important role in tumorigenesis and clinical outcomes of cancer patients. However, only a small fraction (i.e., 5-10%) of inherited variants has been associated with clinical outcomes (e.g., BRCA1/2, APC, TP53, PTEN and so on). The challenge remains in using these inherited germline variants to predict clinical outcomes of cancer patient population. In an attempt to solve this issue, we applied our recently developed algorithm, eTumorMetastasis, which constructs predictive models, on exome sequencing data to ER+ breast (n=755) cancer patients. Gene signatures derived from the genes containing functionally germline genetic variants significantly distinguished recurred and non-recurred patients in two ER+ breast cancer independent cohorts (n=200 and 295, P=1.4×10−3). Furthermore, we found that recurred patients possessed a higher rate of germline genetic variants. In addition, the inherited germline variants from these gene signatures were predominately enriched in T cell function, antigen presentation and cytokine interactions, likely impairing the adaptive and innate immune response thus favoring a pro-tumorigenic environment. Hence, germline genomic information could be used for developing non-invasive genomic tests for predicting patients’ outcomes (or drug response) in breast cancer, other cancer types and even other complex diseases.

scholarly journals Germline variants associated with leukocyte genes predict tumor recurrence in breast cancer patients

2019 ◽  
Vol 3 (1) ◽  
Author(s):  
Jean-Sébastien Milanese ◽  
Chabane Tibiche ◽  
Jinfeng Zou ◽  
Zhigang Meng ◽  
Andre Nantel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Clinical Outcomes ◽  
Cell Function ◽  
Recurrence Score ◽  
Oncotype Dx ◽  
Breast Cancer Patients ◽  
Sequencing Data ◽  
Germline Variants ◽  
Gene Signatures

Abstract Germline variants such as BRCA1/2 play an important role in tumorigenesis and clinical outcomes of cancer patients. However, only a small fraction (i.e., 5–10%) of inherited variants has been associated with clinical outcomes (e.g., BRCA1/2, APC, TP53, PTEN and so on). The challenge remains in using these inherited germline variants to predict clinical outcomes of cancer patient population. In an attempt to solve this issue, we applied our recently developed algorithm, eTumorMetastasis, which constructs predictive models, on exome sequencing data to ER+ breast (n = 755) cancer patients. Gene signatures derived from the genes containing functionally germline variants significantly distinguished recurred and non-recurred patients in two ER+ breast cancer independent cohorts (n = 200 and 295, P = 1.4 × 10−3). Furthermore, we compared our results with the widely known Oncotype DX test (i.e., Oncotype DX breast cancer recurrence score) and outperformed prediction for both high- and low-risk groups. Finally, we found that recurred patients possessed a higher rate of germline variants. In addition, the inherited germline variants from these gene signatures were predominately enriched in T cell function, antigen presentation, and cytokine interactions, likely impairing the adaptive and innate immune response thus favoring a pro-tumorigenic environment. Hence, germline genomic information could be used for developing non-invasive genomic tests for predicting patients’ outcomes in breast cancer.

scholarly journals Prevalence of RECQL germline variants in Pakistani early-onset and familial breast cancer patients

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Muhammad Usman Rashid ◽  
Noor Muhammad ◽  
Faiz Ali Khan ◽  
Umara Shehzad ◽  
Humaira Naeemi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Early Onset ◽  
Familial Breast Cancer ◽  
High Performance ◽  
Breast Cancer Patients ◽  
Germline Variants ◽  
Variants Of Unknown Significance ◽  
Breast Cancer Predisposition ◽  
Novel Variants

Abstract Background The RecQ Like Helicase (RECQL) gene has previously been shown to predispose to breast cancer mainly in European populations, in particular to estrogen receptor (ER) and/or progesterone receptor (PR) positive tumor. Here, we investigated the contribution of pathogenic RECQL germline variants to hereditary breast cancer in early-onset and familial breast cancer patients from Pakistan. Methods Comprehensive RECQL variant analysis was performed in 302 BRCA1 and BRCA2 negative patients with ER and/or PR positive breast tumors using denaturing high-performance liquid chromatography followed by DNA sequencing. Novel variants were classified using Sherloc guidelines. Results One novel pathogenic protein-truncating variant (p.W75*) was identified in a 37-year-old familial breast cancer patient. The pathogenic variant frequencies were 0.3% (1/302) in early-onset and familial breast cancer patients and 0.8% (1/133) in familial patients. Further, three novel variants of unknown significance, p.I141F, p.S182S, and p.C475C, were identified in familial breast cancer patients at the age of 47, 68, and 47 respectively. All variants were absent in 250 controls. Conclusions Our data suggest that the RECQL gene plays a negligible role in breast cancer predisposition in Pakistan.

Real-world clinical outcomes and toxicity in metastatic breast cancer patients treated with palbociclib and endocrine therapy

2019 ◽  
Vol 176 (2) ◽  
pp. 429-434 ◽  
Author(s):  
Leticia Varella ◽  
Akaolisa Samuel Eziokwu ◽  
Xuefei Jia ◽  
Megan Kruse ◽  
Halle C. F. Moore ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Endocrine Therapy ◽  
Clinical Outcomes ◽  
Real World ◽  
Metastatic Breast ◽  
Breast Cancer Patients

Clinical Significance of Subtype Classification in Metastatic Lymph Nodes of Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy

2015 ◽  
Vol 30 (2) ◽  
pp. 174-183 ◽  
Author(s):  
Noriko Nemoto ◽  
Yukiko Shibahara ◽  
Hiroshi Tada ◽  
Keiko Uchida ◽  
Keely M. McNamara ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Lymph Nodes ◽  
Cancer Patients ◽  
Clinical Outcomes ◽  
Primary Tumor ◽  
Breast Cancer Patients ◽  
Ki 67 ◽  
Metastatic Lymph Nodes ◽  
Metastatic Lymph

Background Neoadjuvant chemotherapy has been increasingly utilized in the treatment of breast cancer patients. However, there are no established surrogate markers predicting the response to subsequent adjuvant therapy and clinical outcome of patients. In particular, whether primary or lymph nodes metastasis should be evaluated for these analyses has remained unknown. Therefore, in this study, we first evaluated the differences in biomarkers between primary and metastatic cancer tissues in the patients undergoing neoadjuvant chemotherapy. We then correlated the findings with the clinical outcomes of these patients. Methods We examined 49 patients receiving neoadjuvant chemotherapy and subsequent surgery with lymph node metastasis. Estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2) and Ki-67 were all immunohistochemically evaluated in core needle biopsy samples from primary and metastatic tumors following chemotherapy. Results No statistically significant differences in these markers were detected between the primary tumor and metastatic lymph nodes following therapy, but the Ki-67 labeling index was significantly higher in metastatic lymph nodes than in primary tumor (p = 0.017). The patients associated with luminal A type carcinoma in their lymph nodes following chemotherapy demonstrated significantly better clinical outcomes (disease-free survival: p = 0.0045, overall survival: p = 0.0006) than those who were not. Conclusion These data indicate that subtype classification following chemotherapy, in the metastatic lymph nodes rather than primary tumor could predict long-term outcomes of patients undergoing neoadjuvant chemotherapy.

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