Novel treatment strategies in triple-negative breast cancer: specific role of poly(adenosine diphosphate-ribose) polymerase inhibition

Figures & data

Table 1 Timeline of PARP-inhibitor development

Event	Year	Reference
PARP-1 enzyme role in DNA repair	1963	^Citation32
First PARP inhibitor shown to inhibit DNA repair in vitro	1981	^Citation71
PARP inhibition produces synthetic lethality in BRCA-mutated cell lines	2005	^Citation20,Citation21
Phase I trial of PARP inhibitor in BRCA-mutated cancer	2009	^Citation46

Abbreviations: PARP, poly(adenosine triphosphate-ribose) polymerase; DNA, deoxyribonucleic acid.

Table 2 Clinical trials with single-agent PARP inhibitors in metastatic breast cancer (including TNBC)

PARP inhibitor	Trial	Breast cancer (n)	TNBC (n)	BRCA-mutation status	Clinical benefit (CR, PR, or SD)	Reference
Olaparib	Phase I	9	NA	3/9 mutation^+	2/3 BRCA^+ responses (PR and CR)	^Citation43
Olaparib	Phase II	54	29	54 mutation^+	11/29 PR, 11/29 SD	^Citation45
Olaparib	Phase II	62	NA	62 mutation^+	8/62 PR, 29/62 SD	^Citation46
Olaparib	Phase II	15	15	15 wild type	0/15	^Citation48
Niraparib	Phase I	12	NA	4 mutation^+	2/4 BRCA^+ PR, 2 BRCA wild type SD	^Citation54
Rucaparib	Phase II	17	NA	17 mutation^+	5% ORR, 28% SD (entire cohort; breast response not specified)	^Citation58
BMN 673	Phase I	8	NA	6 mutation^+	2/6 BRCA^+ with PR	^Citation57

Abbreviations: PARP, poly(adenosine triphosphate-ribose) polymerase; TNBC, triple-negative breast cancer; CR, complete response; PR, partial response; SD, stable disease; NA, not available; ORR, overall response rate (CR + PR).

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