Distribution of homologous recombination deficiency (HRD) and BRCA mutations (m) detected by HRD-One test among Brazilian patients (pts) with newly diagnosed advanced epithelial ovarian, fallopian tube, or peritoneal cancer.

Distribution of homologous recombination deficiency (HRD) and BRCA mutations (m) detected by HRD-One test among Brazilian patients (pts) with newly diagnosed advanced epithelial ovarian, fallopian tube, or peritoneal cancer. Scaranti, M., Lopes Yamamoto, G., Guarischi Sousa, R., J Paniza, A. C., Milanezi, F., & Scapulatempo-Neto, C. Journal of Clinical Oncology, 40(16_suppl):e17600–e17600, June, 2022. Publisher: Wolters Kluwer

Paper doi abstract bibtex

e17600 Background: In the Phase III PAOLA-1/ENGOT-ov25 (NCT02477644) and PRIMA/ENGOT-OV26/GOG-3012 (NCT02655016) trials, the addition of a poly(ADP-ribose) polymerase (PARP) inhibitor as maintenance therapy led to a significant progression-free survival benefit in pts with newly diagnosed advanced ovarian cancer, particularly in those who were HRD positive, both including pts with BRCA1m and/or BRCA2m and pts without a BRCAm. Both trials used Myriad's myChoice to determine HRD status. However, this test is economically inaccessible for a significant fraction of the Brazilian population. Methods: We explored the prevalence and distribution of HRD and tumor (t) BRCAmin Brazilian pts using the HRD-One test that detects not only sequence variants in genes involved in homologous recombination repair (HRR) but also the genomic scars due to HRD that might be present even when a pathogenic variant in one of the HRR genes is not detected. Firstly, 59 high-grade serous epithelial ovarian cancer (HGSOC) samples were tested and the accuracy of the HRD-One score was established both by correlation with Myriad's myChoice score and an internal validation considering that most of the samples that carry a pathogenic variant in BRCA1 or BRCA2 should have HRD. HRD-One score of 2.0 or greater predicted HRD and correlated to Myriad's myChoice score of 42. HRD-One achieved an overall categorical concordance of 94.74% with the previously available commercial HRD test. We then tested stage III and IV HGSOC and high-grade endometrioid ovarian cancer pts’ tumor samples with HRD-One test only. Results: Of the 468 pts, 224 (47,9%) had HRD positive tumors, 213 (45,5%) were HRD negative, and 31 (6,6%) had inconclusive results. Ninety-six pts had tBRCAm, 95 (98.9%) of them had a genomic instability score compatible with HRD, and 59 (61%) had BRCA1m. BRCA1c.5266dupC was the most prevalent pathogenic variant in this population followed by BRCA1c.470_471del, c.5074+2T \textgreater C, c.5251C \textgreater T, and c.3331_3334del. The most prevalent BRCA2m were c.8488-1G \textgreater A, c.5216dupA, c.5073dupA, c.1796_1800del, c.8351G \textgreater A, c.2808_2811del, and c.9382C \textgreater T. Median age at diagnosis was 63 in the study population, 57 in the BRCA1m, and 60 in the BRCA2m group. 47,6% of the HGSOC were HRD positive, whereas 25% of the high-grade endometrioid ovarian cancer were HRD positive. Conclusions: This is the first study to report HRD prevalence in a cohort of Brazilian pts using HRD-One test validated to detect HRD genomic scars and tBRCAm. HRD was detected in approximately 50% of HGSOC pts which is in line with previous studies in different populations. HRD-One might help us select pts to receive PARP inhibitors in the front-line therapy noticeably in a low-resource setting where Myriad's myChoice is not widely available.

@article{scaranti_distribution_2022,
	title = {Distribution of homologous recombination deficiency ({HRD}) and {BRCA} mutations (m) detected by {HRD}-{One} test among {Brazilian} patients (pts) with newly diagnosed advanced epithelial ovarian, fallopian tube, or peritoneal cancer.},
	volume = {40},
	issn = {0732-183X},
	url = {https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.16_suppl.e17600},
	doi = {10.1200/JCO.2022.40.16_suppl.e17600},
	abstract = {e17600

Background: In the Phase III PAOLA-1/ENGOT-ov25 (NCT02477644) and PRIMA/ENGOT-OV26/GOG-3012 (NCT02655016) trials, the addition of a poly(ADP-ribose) polymerase (PARP) inhibitor as maintenance therapy led to a significant progression-free survival benefit in pts with newly diagnosed advanced ovarian cancer, particularly in those who were HRD positive, both including pts with BRCA1m and/or BRCA2m and pts without a BRCAm. Both trials used Myriad's myChoice to determine HRD status. However, this test is economically inaccessible for a significant fraction of the Brazilian population. Methods: We explored the prevalence and distribution of HRD and tumor (t) BRCAmin Brazilian pts using the HRD-One test that detects not only sequence variants in genes involved in homologous recombination repair (HRR) but also the genomic scars due to HRD that might be present even when a pathogenic variant in one of the HRR genes is not detected. Firstly, 59 high-grade serous epithelial ovarian cancer (HGSOC) samples were tested and the accuracy of the HRD-One score was established both by correlation with Myriad's myChoice score and an internal validation considering that most of the samples that carry a pathogenic variant in BRCA1 or BRCA2 should have HRD. HRD-One score of 2.0 or greater predicted HRD and correlated to Myriad's myChoice score of 42. HRD-One achieved an overall categorical concordance of 94.74\% with the previously available commercial HRD test. We then tested stage III and IV HGSOC and high-grade endometrioid ovarian cancer pts’ tumor samples with HRD-One test only. Results: Of the 468 pts, 224 (47,9\%) had HRD positive tumors, 213 (45,5\%) were HRD negative, and 31 (6,6\%) had inconclusive results. Ninety-six pts had tBRCAm, 95 (98.9\%) of them had a genomic instability score compatible with HRD, and 59 (61\%) had BRCA1m. BRCA1c.5266dupC was the most prevalent pathogenic variant in this population followed by BRCA1c.470\_471del, c.5074+2T {\textgreater} C, c.5251C {\textgreater} T, and c.3331\_3334del. The most prevalent BRCA2m were c.8488-1G {\textgreater} A, c.5216dupA, c.5073dupA, c.1796\_1800del, c.8351G {\textgreater} A, c.2808\_2811del, and c.9382C {\textgreater} T. Median age at diagnosis was 63 in the study population, 57 in the BRCA1m, and 60 in the BRCA2m group. 47,6\% of the HGSOC were HRD positive, whereas 25\% of the high-grade endometrioid ovarian cancer were HRD positive. Conclusions: This is the first study to report HRD prevalence in a cohort of Brazilian pts using HRD-One test validated to detect HRD genomic scars and tBRCAm. HRD was detected in approximately 50\% of HGSOC pts which is in line with previous studies in different populations. HRD-One might help us select pts to receive PARP inhibitors in the front-line therapy noticeably in a low-resource setting where Myriad's myChoice is not widely available.},
	number = {16\_suppl},
	urldate = {2022-09-28},
	journal = {Journal of Clinical Oncology},
	author = {Scaranti, Mariana and Lopes Yamamoto, Guilherme and Guarischi Sousa, Rodrigo and J Paniza, Ana Carolina and Milanezi, Fernanda and Scapulatempo-Neto, Cristovam},
	month = jun,
	year = {2022},
	note = {Publisher: Wolters Kluwer},
	pages = {e17600--e17600},
}

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C.","Milanezi, F.","Scapulatempo-Neto, C."],"bibdata":{"bibtype":"article","type":"article","title":"Distribution of homologous recombination deficiency (HRD) and BRCA mutations (m) detected by HRD-One test among Brazilian patients (pts) with newly diagnosed advanced epithelial ovarian, fallopian tube, or peritoneal cancer.","volume":"40","issn":"0732-183X","url":"https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.16_suppl.e17600","doi":"10.1200/JCO.2022.40.16_suppl.e17600","abstract":"e17600 Background: In the Phase III PAOLA-1/ENGOT-ov25 (NCT02477644) and PRIMA/ENGOT-OV26/GOG-3012 (NCT02655016) trials, the addition of a poly(ADP-ribose) polymerase (PARP) inhibitor as maintenance therapy led to a significant progression-free survival benefit in pts with newly diagnosed advanced ovarian cancer, particularly in those who were HRD positive, both including pts with BRCA1m and/or BRCA2m and pts without a BRCAm. Both trials used Myriad's myChoice to determine HRD status. However, this test is economically inaccessible for a significant fraction of the Brazilian population. Methods: We explored the prevalence and distribution of HRD and tumor (t) BRCAmin Brazilian pts using the HRD-One test that detects not only sequence variants in genes involved in homologous recombination repair (HRR) but also the genomic scars due to HRD that might be present even when a pathogenic variant in one of the HRR genes is not detected. Firstly, 59 high-grade serous epithelial ovarian cancer (HGSOC) samples were tested and the accuracy of the HRD-One score was established both by correlation with Myriad's myChoice score and an internal validation considering that most of the samples that carry a pathogenic variant in BRCA1 or BRCA2 should have HRD. HRD-One score of 2.0 or greater predicted HRD and correlated to Myriad's myChoice score of 42. HRD-One achieved an overall categorical concordance of 94.74% with the previously available commercial HRD test. We then tested stage III and IV HGSOC and high-grade endometrioid ovarian cancer pts’ tumor samples with HRD-One test only. Results: Of the 468 pts, 224 (47,9%) had HRD positive tumors, 213 (45,5%) were HRD negative, and 31 (6,6%) had inconclusive results. Ninety-six pts had tBRCAm, 95 (98.9%) of them had a genomic instability score compatible with HRD, and 59 (61%) had BRCA1m. BRCA1c.5266dupC was the most prevalent pathogenic variant in this population followed by BRCA1c.470_471del, c.5074+2T \\textgreater C, c.5251C \\textgreater T, and c.3331_3334del. The most prevalent BRCA2m were c.8488-1G \\textgreater A, c.5216dupA, c.5073dupA, c.1796_1800del, c.8351G \\textgreater A, c.2808_2811del, and c.9382C \\textgreater T. Median age at diagnosis was 63 in the study population, 57 in the BRCA1m, and 60 in the BRCA2m group. 47,6% of the HGSOC were HRD positive, whereas 25% of the high-grade endometrioid ovarian cancer were HRD positive. Conclusions: This is the first study to report HRD prevalence in a cohort of Brazilian pts using HRD-One test validated to detect HRD genomic scars and tBRCAm. HRD was detected in approximately 50% of HGSOC pts which is in line with previous studies in different populations. HRD-One might help us select pts to receive PARP inhibitors in the front-line therapy noticeably in a low-resource setting where Myriad's myChoice is not widely available.","number":"16_suppl","urldate":"2022-09-28","journal":"Journal of Clinical Oncology","author":[{"propositions":[],"lastnames":["Scaranti"],"firstnames":["Mariana"],"suffixes":[]},{"propositions":[],"lastnames":["Lopes","Yamamoto"],"firstnames":["Guilherme"],"suffixes":[]},{"propositions":[],"lastnames":["Guarischi","Sousa"],"firstnames":["Rodrigo"],"suffixes":[]},{"propositions":[],"lastnames":["J","Paniza"],"firstnames":["Ana","Carolina"],"suffixes":[]},{"propositions":[],"lastnames":["Milanezi"],"firstnames":["Fernanda"],"suffixes":[]},{"propositions":[],"lastnames":["Scapulatempo-Neto"],"firstnames":["Cristovam"],"suffixes":[]}],"month":"June","year":"2022","note":"Publisher: Wolters Kluwer","pages":"e17600–e17600","bibtex":"@article{scaranti_distribution_2022,\n\ttitle = {Distribution of homologous recombination deficiency ({HRD}) and {BRCA} mutations (m) detected by {HRD}-{One} test among {Brazilian} patients (pts) with newly diagnosed advanced epithelial ovarian, fallopian tube, or peritoneal cancer.},\n\tvolume = {40},\n\tissn = {0732-183X},\n\turl = {https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.16_suppl.e17600},\n\tdoi = {10.1200/JCO.2022.40.16_suppl.e17600},\n\tabstract = {e17600\n\nBackground: In the Phase III PAOLA-1/ENGOT-ov25 (NCT02477644) and PRIMA/ENGOT-OV26/GOG-3012 (NCT02655016) trials, the addition of a poly(ADP-ribose) polymerase (PARP) inhibitor as maintenance therapy led to a significant progression-free survival benefit in pts with newly diagnosed advanced ovarian cancer, particularly in those who were HRD positive, both including pts with BRCA1m and/or BRCA2m and pts without a BRCAm. Both trials used Myriad's myChoice to determine HRD status. However, this test is economically inaccessible for a significant fraction of the Brazilian population. Methods: We explored the prevalence and distribution of HRD and tumor (t) BRCAmin Brazilian pts using the HRD-One test that detects not only sequence variants in genes involved in homologous recombination repair (HRR) but also the genomic scars due to HRD that might be present even when a pathogenic variant in one of the HRR genes is not detected. Firstly, 59 high-grade serous epithelial ovarian cancer (HGSOC) samples were tested and the accuracy of the HRD-One score was established both by correlation with Myriad's myChoice score and an internal validation considering that most of the samples that carry a pathogenic variant in BRCA1 or BRCA2 should have HRD. HRD-One score of 2.0 or greater predicted HRD and correlated to Myriad's myChoice score of 42. HRD-One achieved an overall categorical concordance of 94.74\\% with the previously available commercial HRD test. We then tested stage III and IV HGSOC and high-grade endometrioid ovarian cancer pts’ tumor samples with HRD-One test only. Results: Of the 468 pts, 224 (47,9\\%) had HRD positive tumors, 213 (45,5\\%) were HRD negative, and 31 (6,6\\%) had inconclusive results. Ninety-six pts had tBRCAm, 95 (98.9\\%) of them had a genomic instability score compatible with HRD, and 59 (61\\%) had BRCA1m. BRCA1c.5266dupC was the most prevalent pathogenic variant in this population followed by BRCA1c.470\\_471del, c.5074+2T {\\textgreater} C, c.5251C {\\textgreater} T, and c.3331\\_3334del. The most prevalent BRCA2m were c.8488-1G {\\textgreater} A, c.5216dupA, c.5073dupA, c.1796\\_1800del, c.8351G {\\textgreater} A, c.2808\\_2811del, and c.9382C {\\textgreater} T. Median age at diagnosis was 63 in the study population, 57 in the BRCA1m, and 60 in the BRCA2m group. 47,6\\% of the HGSOC were HRD positive, whereas 25\\% of the high-grade endometrioid ovarian cancer were HRD positive. Conclusions: This is the first study to report HRD prevalence in a cohort of Brazilian pts using HRD-One test validated to detect HRD genomic scars and tBRCAm. HRD was detected in approximately 50\\% of HGSOC pts which is in line with previous studies in different populations. 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