High response rates to neoadjuvant platinum-based therapy in ovarian cancer patients carrying germ-line BRCA mutation.
Preoperative therapy provides an advantage for clinical drug assessment, as it involves yet untreated patients and facilitates access to the post-treatment biological material. Testing for Slavic founder BRCA mutations was performed for 225 ovarian cancer (OC) patients, who were treated by platinum-based neoadjuvant therapy. 34 BRCA1 and 1 BRCA2 mutation carriers were identified. Complete clinical response was documented in 12/35 (34%) mutation carriers and 8/190 (4%) non-carriers (P = 0.000002). Histopathologic response was observed in 16/35 (46%) women with the germ-line mutation versus 42/169 (25%) patients with the wild-type genotype (P = 0.02). Somatic loss of heterozygosity (LOH) for the remaining wild-type BRCA1 allele was detected only in 7/24 (29%) post-neoadjuvant therapy residual tumor tissues as compared to 9/11 (82%) BRCA1-associated OC, which were not exposed to systemic treatment before the surgery (P = 0.009). Furthermore, comparison of pre- and post-treatment tumor material obtained from the same patients revealed restoration of BRCA1 heterozygosity in 2 out of 3 sample pairs presenting with LOH at diagnosis. The obtained data confirm high sensitivity of BRCA-driven OC to platinating agents and provide evidence for a rapid selection of tumor cell clones without LOH during the course of therapy.
Department of Gynecology, N.N. Petrov Institute of Oncology, St. Petersburg 197758, Russia.
Tatiana V
TV
Gorodnova
Department of Tumor Growth Biology, N.N. Petrov Institute of Oncology, St. Petersburg 197758, Russia; Department of Medical Genetics, St. Petersburg Pediatric Medical University, St. Petersburg 194100, Russia.
Anna P
AP
Sokolenko
Department of Medical Genetics, St. Petersburg Pediatric Medical University, St. Petersburg 194100, Russia; Department of Pathology, N.N. Petrov Institute of Oncology, St. Petersburg 197758, Russia.
Alexandr O
AO
Ivantsov
Department of Tumor Growth Biology, N.N. Petrov Institute of Oncology, St. Petersburg 197758, Russia; Department of Medical Genetics, St. Petersburg Pediatric Medical University, St. Petersburg 194100, Russia.
Aglaya G
AG
Iyevleva
Department of Tumor Growth Biology, N.N. Petrov Institute of Oncology, St. Petersburg 197758, Russia; Department of Medical Genetics, St. Petersburg Pediatric Medical University, St. Petersburg 194100, Russia.
Evgeny N
EN
Suspitsin
Department of Tumor Growth Biology, N.N. Petrov Institute of Oncology, St. Petersburg 197758, Russia.
Svetlana N
SN
Aleksakhina
Department of Tumor Growth Biology, N.N. Petrov Institute of Oncology, St. Petersburg 197758, Russia; Department of Medical Genetics, St. Petersburg Pediatric Medical University, St. Petersburg 194100, Russia.
Grigory A
GA
Yanus
Department of Tumor Growth Biology, N.N. Petrov Institute of Oncology, St. Petersburg 197758, Russia; Department of Medical Genetics, St. Petersburg Pediatric Medical University, St. Petersburg 194100, Russia.
Alexandr V
AV
Togo
Department of Gynecology, N.N. Petrov Institute of Oncology, St. Petersburg 197758, Russia.
Sergey Ya
SY
Maximov
Department of Tumor Growth Biology, N.N. Petrov Institute of Oncology, St. Petersburg 197758, Russia; Department of Medical Genetics, St. Petersburg Pediatric Medical University, St. Petersburg 194100, Russia; Department of Oncology, I.I. Mechnikov North-Western Medical University, St. Petersburg 191015, Russia; Department of Oncology, St. Petersburg State University, St. Petersburg 199034, Russia. Electronic address: evgeny@imyanitov.spb.ru.
Evgeny N
EN
Imyanitov
D000328:Adult; D000368:Aged; D005260:Female; D019398:Genes, BRCA1; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics*
BRCA1; Loss of heterozygosity (LOH); Neoadjuvant therapy; Ovarian cancer