Distinct implications of different BRCA mutations: efficacy of cytotoxic chemotherapy, PARP inhibition and clinical outcome in ovarian cancer

Figures & data

Figure 1 Structure of BRCA1 and BRCA2 genes, showing regions encoding identified protein domains, BCCRs and OCCRs.

Abbreviations: BCCR, breast cancer cluster region; OCCR, ovarian cancer cluster region; NLS, nuclear localization sequence; SCD, serine cluster domain; BRCT, BRCA1 C-terminal domain; OB, oligonucleotide binding.

Table 1 Characteristics of BRCA1-associated, BRCA2-associated, and BRCA wild-type OC

	BRCAI -associated OC	BRCA2-associated OC	BRCA wild-type OC	References
Clinicopathological features
Age at diagnosis	Younger versus WT	Similar to WT	Older versus BRCAI-mutant	^Citation47^–^Citation52, ^Citation54
Histology	Predominantly HGS OC		All OC histotypes	^Citation8, ^Citation47, ^Citation66
Visceral metastasis	Highly likely	Likely	Unlikely	^Citation69, ^Citation70
Chemosensitivity
Platinum	Highly sensitive Exon 11 and RING domain mutants may be more resistant	Highly sensitive May be more sensitive versus BRCAI-mutant	Sensitive Less sensitive versus BRCA-mutant	^Citation8, ^Citation49, ^Citation53, ^Citation71, ^Citation72, ^Citation74, ^Citation75
PLD	More sensitive versus WT		Less sensitive versus BRCA-mutant	^Citation96, ^Citation97
Taxanes	May be more resistant versus WT	Undetermined	May be more sensitive versus BRCAI-mutant	^Citation82, ^Citation84^–^Citation87, ^Citation92, ^Citation93
PARP inhibitors	Sensitive Exon 11 and RiNG domain mutants may be more resistant	Sensitive	Resistant versus BRCA-mutant	^Citation72, ^Citation74, ^Citation75, ^Citation121^–^Citation130
Clinical outcome
PFS	Superior May be inferior to BRCA2-mutant	Superior May be superior to BRCAI-mutant	Inferior versus BRCA-mutant	^Citation53, ^Citation71, ^Citation144-^Citation149
Short-term OS	Superior versus WT Inferior versus BRCA2-mutant	Superior versus WT Superior versus BRCAI-mutant	Inferior versus BRCA-mutant	^Citation53, ^Citation66, ^Citation143, ^Citation147, ^Citation149, ^Citation155, ^Citation156
Long-term OS	Inferior versus BRCA2-mutant	Superior versus WT Superior versus BRCAI-mutant	Inferior versus BRCA2-mutant	^Citation8, ^Citation47, ^Citation66, ^Citation143, ^Citation147, ^Citation149, ^Citation155, ^Citation156

Abbreviations: BRCA, BRCA1 or BRCA2; OC, ovarian carcinoma; WT, wild-type; HGS, high grade serous; PLD, pegylated liposomal doxorubicin; PFS, progression-free survival; OS, overall survival; PARP, poly-(ADP-ribose) polymerase.

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