Survival outcomes in patients with BRCA mutated, variant of unknown significance, and wild type ovarian cancer treated with PARP inhibitors
© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ..
OBJECTIVE: Correlation between BRCA1/2 (BRCA) pathogenic variants and the response to poly (ADP-ribose) polymerase inhibitors (PARPi) has been recognized in patients with ovarian cancer. Moreover, data on the clinical implications of variants of unknown significance are lacking. The aim of this study was to evaluate differences in survival outcomes in patients with BRCA variants of unknown significance, mutated, and wild type relapsed ovarian cancer treated with PARPi.
METHODS: Patients with ovarian cancer whose somatic BRCA testing was available and who were receiving PARPi as maintenance treatment at the first recurrence between January 2014 and January 2021 were included in the present study and analyzed. Patients were divided into three groups according to BRCA mutational status (variant of unknown significance, mutated, and wild type). Progression-free survival was assessed in each study group.
RESULTS: Of 67 patients identified, 20 (29.9%), 24 (35.8%), and 23 (34.3%) had BRCA variant of unknown significance, mutated, and wild type, respectively. Patients received PARPi as maintenance treatment at the time of the first relapse after a complete response or partial response to platinum-based chemotherapy without differences in the previous platinum-free interval among the analyzed groups. The median progression-free survival of patients with BRCA mutation was significantly longer than for those with BRCA wild type or variant of unknown significance (not reached vs 4 months vs 7 months, respectively; p<0.001). Additionally, no significant difference was found between patients with BRCA wild type and BRCA variant of unknown significance (p=0.50).
CONCLUSION: Our study suggests that carriers of BRCA variant of unknown significance have survival outcomes comparable to patients with BRCA wild type and shorter progression-free survival than women harboring BRCA pathogenic variants.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:33 |
|---|---|
| Enthalten in: |
International journal of gynecological cancer : official journal of the International Gynecological Cancer Society - 33(2023), 6 vom: 05. Juni, Seite 922-928 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Musacchio, Lucia [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
BRCA1 Protein |
|---|
| Anmerkungen: |
Date Completed 07.06.2023 Date Revised 07.06.2023 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1136/ijgc-2022-003903 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM352687843 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM352687843 | ||
| 003 | DE-627 | ||
| 005 | 20231226054310.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1136/ijgc-2022-003903 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1175.xml |
| 035 | |a (DE-627)NLM352687843 | ||
| 035 | |a (NLM)36759000 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Musacchio, Lucia |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Survival outcomes in patients with BRCA mutated, variant of unknown significance, and wild type ovarian cancer treated with PARP inhibitors |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 07.06.2023 | ||
| 500 | |a Date Revised 07.06.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ. | ||
| 520 | |a OBJECTIVE: Correlation between BRCA1/2 (BRCA) pathogenic variants and the response to poly (ADP-ribose) polymerase inhibitors (PARPi) has been recognized in patients with ovarian cancer. Moreover, data on the clinical implications of variants of unknown significance are lacking. The aim of this study was to evaluate differences in survival outcomes in patients with BRCA variants of unknown significance, mutated, and wild type relapsed ovarian cancer treated with PARPi | ||
| 520 | |a METHODS: Patients with ovarian cancer whose somatic BRCA testing was available and who were receiving PARPi as maintenance treatment at the first recurrence between January 2014 and January 2021 were included in the present study and analyzed. Patients were divided into three groups according to BRCA mutational status (variant of unknown significance, mutated, and wild type). Progression-free survival was assessed in each study group | ||
| 520 | |a RESULTS: Of 67 patients identified, 20 (29.9%), 24 (35.8%), and 23 (34.3%) had BRCA variant of unknown significance, mutated, and wild type, respectively. Patients received PARPi as maintenance treatment at the time of the first relapse after a complete response or partial response to platinum-based chemotherapy without differences in the previous platinum-free interval among the analyzed groups. The median progression-free survival of patients with BRCA mutation was significantly longer than for those with BRCA wild type or variant of unknown significance (not reached vs 4 months vs 7 months, respectively; p<0.001). Additionally, no significant difference was found between patients with BRCA wild type and BRCA variant of unknown significance (p=0.50) | ||
| 520 | |a CONCLUSION: Our study suggests that carriers of BRCA variant of unknown significance have survival outcomes comparable to patients with BRCA wild type and shorter progression-free survival than women harboring BRCA pathogenic variants | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a BRCA1 protein | |
| 650 | 4 | |a BRCA2 protein | |
| 650 | 4 | |a ovarian cancer | |
| 650 | 7 | |a Poly(ADP-ribose) Polymerase Inhibitors |2 NLM | |
| 650 | 7 | |a BRCA1 protein, human |2 NLM | |
| 650 | 7 | |a BRCA1 Protein |2 NLM | |
| 650 | 7 | |a BRCA2 protein, human |2 NLM | |
| 650 | 7 | |a BRCA2 Protein |2 NLM | |
| 700 | 1 | |a Boccia, Serena |e verfasserin |4 aut | |
| 700 | 1 | |a Marchetti, Claudia |e verfasserin |4 aut | |
| 700 | 1 | |a Minucci, Angelo |e verfasserin |4 aut | |
| 700 | 1 | |a Camarda, Floriana |e verfasserin |4 aut | |
| 700 | 1 | |a Cassani, Chiara |e verfasserin |4 aut | |
| 700 | 1 | |a Ventriglia, Jole |e verfasserin |4 aut | |
| 700 | 1 | |a Salutari, Vanda |e verfasserin |4 aut | |
| 700 | 1 | |a Ghizzoni, Viola |e verfasserin |4 aut | |
| 700 | 1 | |a Giudice, Elena |e verfasserin |4 aut | |
| 700 | 1 | |a Perri, Maria Teresa |e verfasserin |4 aut | |
| 700 | 1 | |a Carbone, Maria Vittoria |e verfasserin |4 aut | |
| 700 | 1 | |a Ricci, Caterina |e verfasserin |4 aut | |
| 700 | 1 | |a Pignata, Sandro |e verfasserin |4 aut | |
| 700 | 1 | |a Fagotti, Anna |e verfasserin |4 aut | |
| 700 | 1 | |a Scambia, Giovanni |e verfasserin |4 aut | |
| 700 | 1 | |a Lorusso, Domenica |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t International journal of gynecological cancer : official journal of the International Gynecological Cancer Society |d 1992 |g 33(2023), 6 vom: 05. Juni, Seite 922-928 |w (DE-627)NLM090676645 |x 1525-1438 |7 nnns |
| 773 | 1 | 8 | |g volume:33 |g year:2023 |g number:6 |g day:05 |g month:06 |g pages:922-928 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1136/ijgc-2022-003903 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 33 |j 2023 |e 6 |b 05 |c 06 |h 922-928 | ||