Xue Wang 1 , Nanlin Hu 2 , Lina Cui 3 , Yiran Si 2 , Jian Yue 1 , Fangchao Zheng 2 , Yikun Kang 2 , Peng Yuan 1 . Show Affiliations »
Abstract
BACKGROUND: Metastatic triple-negative breast cancer (mTNBC) has a poor prognosis and few effective targeted therapy options. Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, has been granted accelerated approval by FDA for patients with deleterious BRCA-mutated human epidermal growth factor receptor 2 (HER2)-negative advanced/metastatic breast cancer. However, there is little data demonstrating that patients with particular forms of germline and/or somatic BRCA1/2, such as large fragment variation, can benefit from PARP inhibitors. CASE PRESENTATION: In 2011, a 40-year-old woman was diagnosed with TNBC having pT2N0M0 in the right breast, and a new irregular lesser tubercle in the left breast appeared after approximately 3 years, which was also diagnosed as TNBC. In 2017, computed tomography (CT) showed TNBC metastases to the lung and brain. A next-generation sequencing (NGS) was performed with a lung metastasis sample, and results showed a homologous recombination deficiency (HRD) score of 67, a germline large deletion of exon 2 in BRCA1, a novel somatic BRCA2-STARD13 rearrangement and copy number loss of RAD51. Since September 2017, the patient was treated with olaparib. Till the report date of this case, the patient underwent regular follow-up without disease recurrence. CONCLUSION: To our knowledge, this is the first case describing a patient with lung- and brainmetastatic TNBC with combined germline and somatic large rearrangement and a high HRD score who achieved a long-term benefit from olaparib monotherapy. The use of NGS is promising in the treatment of TNBC in clinical practice. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
BACKGROUND: Metastatic triple-negative breast cancer (mTNBC) has a poor prognosis and few effective targeted therapy options. Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, has been granted accelerated approval by FDA for patients with deleterious BRCA-mutated human epidermal growth factor receptor 2 (HER2)-negative advanced/metastatic breast cancer. However, there is little data demonstrating that patients with particular forms of germline and/or somatic BRCA1/2, such as large fragment variation, can benefit from PARP inhibitors. CASE PRESENTATION: In 2011, a 40-year-old woman was diagnosed with TNBC having pT2N0M0 in the right breast, and a new irregular lesser tubercle in the left breast appeared after approximately 3 years, which was also diagnosed as TNBC. In 2017, computed tomography (CT) showed TNBC metastases to the lung and brain. A next-generation sequencing (NGS) was performed with a lung metastasis sample, and results showed a homologous recombination deficiency (HRD) score of 67, a germline large deletion of exon 2 in BRCA1, a novel somatic BRCA2-STARD13 rearrangement and copy number loss of RAD51. Since September 2017, the patient was treated with olaparib. Till the report date of this case, the patient underwent regular follow-up without disease recurrence. CONCLUSION: To our knowledge, this is the first case describing a patient with lung- and brainmetastatic TNBC with combined germline and somatic large rearrangement and a high HRD score who achieved a long-term benefit from olaparib monotherapy. The use of NGS is promising in the treatment of TNBC in clinical practice. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
Entities: Chemical
Keywords:
BRCA1/2 rearrangement; HRD positive; PARP inhibitor; longterm disease-free survival; metastatic triple-negative breast cancer; olaparib
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Year: 2022
PMID: 35156571 DOI: 10.2174/1568009622666220214092207
Source DB: PubMed Journal: Curr Cancer Drug Targets ISSN: 1568-0096 Impact factor: 2.907