Identifying homologous recombination deficiency in breast cancer: genomic instability score distributions differ among breast cancer subtypes.
Breast cancer
DNA damage
Genomic instability
Homologous recombination deficiency
Tumor biomarker
Journal
Breast cancer research and treatment
ISSN: 1573-7217
Titre abrégé: Breast Cancer Res Treat
Pays: Netherlands
ID NLM: 8111104
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
received:
01
06
2023
accepted:
07
07
2023
medline:
18
9
2023
pubmed:
17
8
2023
entrez:
17
8
2023
Statut:
ppublish
Résumé
A 3-biomarker homologous recombination deficiency (HRD) score is a key component of a currently FDA-approved companion diagnostic assay to identify HRD in patients with ovarian cancer using a threshold score of ≥ 42, though recent studies have explored the utility of a lower threshold (GIS ≥ 33). The present study evaluated whether the ovarian cancer thresholds may also be appropriate for major breast cancer subtypes by comparing the genomic instability score (GIS) distributions of BRCA1/2-deficient estrogen receptor-positive breast cancer (ER + BC) and triple-negative breast cancer (TNBC) to the GIS distribution of BRCA1/2-deficient ovarian cancer. Ovarian cancer and breast cancer (ER + BC and TNBC) tumors from ten study cohorts were sequenced to identify pathogenic BRCA1/2 mutations, and GIS was calculated using a previously described algorithm. Pathologic complete response (pCR) to platinum therapy was evaluated in a subset of TNBC samples. For TNBC, a threshold was set and threshold validity was assessed relative to clinical outcomes. A total of 560 ovarian cancer, 805 ER + BC, and 443 TNBC tumors were included. Compared to ovarian cancer, the GIS distribution of BRCA1/2-deficient samples was shifted lower for ER + BC (p = 0.015), but not TNBC (p = 0.35). In the subset of TNBC samples, univariable logistic regression models revealed that GIS status using thresholds of ≥ 42 and ≥ 33 were significant predictors of response to platinum therapy. This study demonstrated that the GIS thresholds used for ovarian cancer may also be appropriate for TNBC, but not ER + BC. GIS thresholds in TNBC were validated using clinical response data to platinum therapy.
Identifiants
pubmed: 37589839
doi: 10.1007/s10549-023-07046-3
pii: 10.1007/s10549-023-07046-3
pmc: PMC10504389
doi:
Substances chimiques
BRCA1 protein, human
0
BRCA1 Protein
0
Platinum
49DFR088MY
BRCA2 protein, human
0
BRCA2 Protein
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
191-201Subventions
Organisme : Myriad Genetics
ID : Myriad Genetics
Informations de copyright
© 2023. The Author(s).
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