High response rates to neoadjuvant platinum-based therapy in ovarian cancer patients carrying germ-line BRCA mutation

作者：Gorodnova Tatiana V; Sokolenko Anna P; Ivantsov Alexandr O; Iyevleva Aglaya G; Suspitsin Evgeny N; Aleksakhina Svetlana N; Yanus Grigory A; Togo Alexandr V; Maximov Sergey Ya; Imyanitov Evgeny N^*

来源：Cancer Letters, 2015, 369(2): 363-367.

DOI：10.1016/j.canlet.2015.08.028

• BRCA1
• Ovarian cancer
• Neoadjuvant therapy
• Loss of heterozygosity (LOH)

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%) BRCAl-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.

• 出版日期2015-12-28