Multi-Gene Mutation Profiling by Targeted Next-Generation Sequencing in Premenopausal Breast Cancer

Zografos, Εleni; Andrikopoulou, Αngeliki; Papatheodoridi, Alkistis; Kaparelou, Maria; Bletsa, Garyfalia; Liontos, Michalis; Dimopoulos, Meletios Α.; Zagouri, Flora

doi:10.3390/genes13081362

Cited by 4 publications

(3 citation statements)

References 55 publications

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“…The remaining cases exhibited vari"ble 'utations in different combinations (NF1, PTEN, ATR, CHEK2, PMS2, and ATM), as previously reported, showing lower frequencies compared to a set of TP53 and PIK3CA mutations [39]. However, conversely, high-frequency variants were detected in the BLM gene, which was reported to rarely occur in Bca [34,40]. This observation emphasizes the complexity of oncogenic interactions among genes carrying mutations, highlighting that these interactions are not straightforward or linear processes.…”

Section: Discussionsupporting

confidence: 72%

Variation Analysis in Premenopausal and Postmenopausal Breast Cancer Cases

Erdogdu,

Orenay-Boyacioglu,

Boyacioglu

et al. 2024

JPM

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Menopausal status affects the prognoses and consequences of breast cancer. Therefore, this retrospective study aimed to reveal the molecular variation profile differences in breast cancer patients according to their menopausal status, with the hypothesis that the molecular variation profiles will be different at premenopausal and postmenopausal ages. Breast cancer patients (n = 254) who underwent molecular subtyping and QIAseq Human Breast Cancer NGS Panel screening between 2018 and 2022 were evaluated retrospectively. Their menopausal status was defined by age, and those aged 50 years and above were considered postmenopausal. Of the subjects, 58.66% (n = 149) were premenopausal and 41.34% (n = 105) were postmenopausal. The mean age at the time of diagnosis for all patients was 49.31 ± 11.19 years, with respective values of 42.11 ± 5.51 and 59.54 ± 9.01 years for the premenopausal and postmenopausal groups, respectively (p = 0.000). Among premenopausal patients, the percentages of patients in BCa subtypes (luminal A, luminal B-HER2(−), luminal B-HER2(+), HER2 positive, and triple-negative) were determined to be 34.90%, 8.05%, 26.17%, 10.74%, and 20.13%, respectively, while in the postmenopausal group, these values were 39.05%, 16.19%, 24.76%, 6.67%, and 13.33%, respectively (p > 0.05). Considering menopausal status, the distribution of hormone receptors in premenopausal patients was ER(+)/PgR(+) 63.76%, ER(−)/PgR(−) 23.49%, ER(+)/PgR(−) 10.74%, and ER(−)/PgR(+) 2.01%, respectively, while in postmenopausal women, this distribution was observed to be 74.29%, 23.81%, 1.90% and 0.00% in the same order (p = 0.008). The most frequently mutated gene was TP53 in 130 patients (51.18%), followed by PIK3CA in 85 patients (33.46%), BRCA2 and NF1 in 56 patients (22.05%), PTEN in 54 patients (21.26%), and ATR and CHEK2 in 53 patients (20.87%). TP53, PIK3CA, NF1, BRCA2, PTEN, and CHEK2 mutations were more frequently observed in premenopausal patients, while TP53, PIK3CA, BRCA2, BRCA1, and ATR mutations in postmenopausal patients. These findings contribute to a deeper understanding of the underlying causes of breast cancer with respect to menopausal status. This study is the first from Turkey that reflects the molecular subtyping and somatic mutation profiles of breast cancer patients according to menopausal status.

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Section: Discussionsupporting

confidence: 72%

Variation Analysis in Premenopausal and Postmenopausal Breast Cancer Cases

Erdogdu,

Orenay-Boyacioglu,

Boyacioglu

et al. 2024

JPM

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“…Compared with previous studies, [23][24][25] our findings indicate a substantial enhancement in the prognostic capability of specific gene mutations. Notably, the HRs for RFS and OS associated with these mutations were significantly higher than those previously reported.…”

Section: Any Mutation Months Mediancontrasting

confidence: 72%

Select gene mutations associated with survival outcomes in ER‐positive ERBB2‐negative early‐stage invasive breast cancer: A single‐institutional tissue bank study

Kok,

Huang,

Hsu

et al. 2024

Cancer Medicine

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IntroductionThe prognostic capability of targeted sequencing of primary tumors in patients with estrogen receptor‐positive, human epidermal growth factor receptor‐2‐negative early‐stage invasive breast cancer (EBC) in a real‐world setting is uncertain. Therefore, we aimed to determine the correlation between a 22‐gene mutational profile and long‐term survival outcomes in patients with ER+/ERBB2‐ EBC.Patients and MethodsA total of 73 women diagnosed with ER+/ERBB2‐ EBC between January 10, 2004, and June 2, 2008, were followed up until December 31, 2022. Univariate and multivariate Cox models were constructed to plot the relapse‐free survival (RFS) and overall survival (OS). The log‐rank test derived p‐value was obtained. For external validation, we performed a survival analysis of 1163 comparable patients retrieved from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset.ResultsAt follow‐up, 16 (21.9%) patients had relapsed, while 21 (nearly 29%) harbored mutant genes. Thirty‐three missense mutations were detected in 14 genes. The median ages were 51 and 46 years in patients with and without mutations, respectively. Patients with any mutation had a 1.85‐fold higher risk of relapse (hazard ratio [HR]: 1.85, 95% confidence interval [CI]: 0.60–5.69) compared to those without any mutation. Patients who harbored any of the six genes (MAP2K4, FGFR3, APC, KIT, RB1, and PTEN) had a nearly 6‐fold increase in the risk of relapse (HR: 5.82, 95% CI: 1.31–18.56; p = 0.0069). Multivariate Cox models revealed that the adjusted HR for RFS and OS were 6.67 (95% CI: 1.32–27.57) and 8.31 (p = 0.0443), respectively. METABRIC analysis also demonstrated a trend to significantly worse RFS (p = 0.0576) in the subcohort grouped by having a mutation in any of the six genes.ConclusionsOur single‐institution tissue bank study of Taiwanese women with ER+/ERBB2‐ EBC suggests that a novel combination of six gene mutations might have prognostic capability for survival outcomes.

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“… 9 Additionally, more cancer predisposition genes such as TP53, ATM, PALB2, CHEK2 , RAD51C, and RAD51D mutations have been discovered, and better understanding of these genes have led to more genes being integrated into routine multi-gene panel testing (MGPT). 10 , 11 Wider use of MGPT has shown that PGV are quite common and may be present in patients without family history of cancer. 12 , 13 …”

Section: Introductionmentioning

confidence: 99%