The Mutational Landscape of Early-Onset Breast Cancer: A Next-Generation Sequencing Analysis
BackgroundAround 5%–7% of breast cancer cases are diagnosed in women younger than 40, making it the leading cause of female cancer in the 25- to 39-year-old age group. Unfortunately, young age at diagnosis is linked to a more aggressive tumor biology and a worse clinical outcome. The identification...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.797505/full |
| _version_ | 1828125645636370432 |
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| author | Angeliki Andrikopoulou Spyridoula Chatzinikolaou Ilias Kyriopoulos Garyfalia Bletsa Maria Kaparelou Michalis Liontos Meletios-Athanasios Dimopoulos Flora Zagouri |
| author_facet | Angeliki Andrikopoulou Spyridoula Chatzinikolaou Ilias Kyriopoulos Garyfalia Bletsa Maria Kaparelou Michalis Liontos Meletios-Athanasios Dimopoulos Flora Zagouri |
| author_sort | Angeliki Andrikopoulou |
| collection | DOAJ |
| description | BackgroundAround 5%–7% of breast cancer cases are diagnosed in women younger than 40, making it the leading cause of female cancer in the 25- to 39-year-old age group. Unfortunately, young age at diagnosis is linked to a more aggressive tumor biology and a worse clinical outcome. The identification of the mutational landscape of breast cancer in this age group could optimize the management.MethodsWe performed NGS analysis in paraffin blocks and blood samples of 32 young patients with breast cancer [<40 years] and 90 older patients during the period 2019 through 2021. All patients were treated in a single institution at the Oncology Department of “Alexandra” Hospital, Medical School, University of Athens, Greece.ResultsBreast tumors were characterized more frequently by HER2 overexpression [25% vs 18.9%], higher ki67 levels [75% vs 61%] and lower differentiation [71.9% vs 60%] in the younger group. PIK3CA [6/20; 30%] and TP53 [6/20; 30%] were the most frequent pathogenic somatic mutations identified in young patients, while one case of BRCA2 somatic mutation [1/20; 5%] and one case of PTEN somatic mutation [1/20; 5%] were also identified. PIK3CA mutations [16/50; 32%] and TP53 mutations [20/50; 40%] were the most common somatic mutations identified in older patients, however other somatic mutations were also reported (ATM, AKT, CHEK2, NRAS, CDKN2A, PTEN, NF1, RB1, FGFR1, ERBB2). As for germline mutations, CHEK2 [3/25; 12%] was the most common pathogenic germline mutation in younger patients followed by BRCA1 [2/25; 8%]. Of note, CHEK2 germline mutations were identified less frequently in older patients [2/61; 3%] among others [BRCA1 (2/61; 3%), ATM (2/61; 3%), APC (1/61; 1,6%) and BRCA2 (1/61; 1,6%)].ConclusionWe here report the mutational profile identified via NGS in patients with early-onset breast cancer compared to their older counterparts. Although the sample size is small and no statistically significant differences were detected, we highlight the need of genetic testing to most patients in this subgroup. |
| first_indexed | 2024-04-11T15:23:39Z |
| format | Article |
| id | doaj.art-8d89da1b96f64f7ea8bd787a3b3fcf8d |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-11T15:23:39Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-8d89da1b96f64f7ea8bd787a3b3fcf8d2022-12-22T04:16:18ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-01-011110.3389/fonc.2021.797505797505The Mutational Landscape of Early-Onset Breast Cancer: A Next-Generation Sequencing AnalysisAngeliki Andrikopoulou0Spyridoula Chatzinikolaou1Ilias Kyriopoulos2Garyfalia Bletsa3Maria Kaparelou4Michalis Liontos5Meletios-Athanasios Dimopoulos6Flora Zagouri7Department of Clinical Therapeutics, Alexandra Hospital, Medical School, Athens, GreeceDepartment of Clinical Therapeutics, Alexandra Hospital, Medical School, Athens, GreeceDepartment of Clinical Therapeutics, Alexandra Hospital, Medical School, Athens, GreeceHellenic Anticancer Institute, Athens, GreeceDepartment of Clinical Therapeutics, Alexandra Hospital, Medical School, Athens, GreeceDepartment of Clinical Therapeutics, Alexandra Hospital, Medical School, Athens, GreeceDepartment of Clinical Therapeutics, Alexandra Hospital, Medical School, Athens, GreeceDepartment of Clinical Therapeutics, Alexandra Hospital, Medical School, Athens, GreeceBackgroundAround 5%–7% of breast cancer cases are diagnosed in women younger than 40, making it the leading cause of female cancer in the 25- to 39-year-old age group. Unfortunately, young age at diagnosis is linked to a more aggressive tumor biology and a worse clinical outcome. The identification of the mutational landscape of breast cancer in this age group could optimize the management.MethodsWe performed NGS analysis in paraffin blocks and blood samples of 32 young patients with breast cancer [<40 years] and 90 older patients during the period 2019 through 2021. All patients were treated in a single institution at the Oncology Department of “Alexandra” Hospital, Medical School, University of Athens, Greece.ResultsBreast tumors were characterized more frequently by HER2 overexpression [25% vs 18.9%], higher ki67 levels [75% vs 61%] and lower differentiation [71.9% vs 60%] in the younger group. PIK3CA [6/20; 30%] and TP53 [6/20; 30%] were the most frequent pathogenic somatic mutations identified in young patients, while one case of BRCA2 somatic mutation [1/20; 5%] and one case of PTEN somatic mutation [1/20; 5%] were also identified. PIK3CA mutations [16/50; 32%] and TP53 mutations [20/50; 40%] were the most common somatic mutations identified in older patients, however other somatic mutations were also reported (ATM, AKT, CHEK2, NRAS, CDKN2A, PTEN, NF1, RB1, FGFR1, ERBB2). As for germline mutations, CHEK2 [3/25; 12%] was the most common pathogenic germline mutation in younger patients followed by BRCA1 [2/25; 8%]. Of note, CHEK2 germline mutations were identified less frequently in older patients [2/61; 3%] among others [BRCA1 (2/61; 3%), ATM (2/61; 3%), APC (1/61; 1,6%) and BRCA2 (1/61; 1,6%)].ConclusionWe here report the mutational profile identified via NGS in patients with early-onset breast cancer compared to their older counterparts. Although the sample size is small and no statistically significant differences were detected, we highlight the need of genetic testing to most patients in this subgroup.https://www.frontiersin.org/articles/10.3389/fonc.2021.797505/fullNGSbreast cancerearly-onsetgenetic testingyoung women |
| spellingShingle | Angeliki Andrikopoulou Spyridoula Chatzinikolaou Ilias Kyriopoulos Garyfalia Bletsa Maria Kaparelou Michalis Liontos Meletios-Athanasios Dimopoulos Flora Zagouri The Mutational Landscape of Early-Onset Breast Cancer: A Next-Generation Sequencing Analysis Frontiers in Oncology NGS breast cancer early-onset genetic testing young women |
| title | The Mutational Landscape of Early-Onset Breast Cancer: A Next-Generation Sequencing Analysis |
| title_full | The Mutational Landscape of Early-Onset Breast Cancer: A Next-Generation Sequencing Analysis |
| title_fullStr | The Mutational Landscape of Early-Onset Breast Cancer: A Next-Generation Sequencing Analysis |
| title_full_unstemmed | The Mutational Landscape of Early-Onset Breast Cancer: A Next-Generation Sequencing Analysis |
| title_short | The Mutational Landscape of Early-Onset Breast Cancer: A Next-Generation Sequencing Analysis |
| title_sort | mutational landscape of early onset breast cancer a next generation sequencing analysis |
| topic | NGS breast cancer early-onset genetic testing young women |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.797505/full |
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