Prophylactic surgery in carriers of BRCA1 or BRCA2 gene mutation

DOI

https://dx.doi.org/10.18565/aig.2020.1pril.56-62

Gorodnova T.V., Sokolenko A.P., Kotiv Kh.B., Yakovleva M.G., Lavrinovich O.E., Mikaya N.A., Ibragimov Z.N., Trifanov Yu.N., Bondarev N.E., Nekrasova E.A., Sidoruk A.A., Smirnova O.A., Guseinov K.D., Bakhidze E.V., Meshkova I.E., Bakaeva E.Kh., Shikhzadaeva M.G., Ul’rikh E.A., Urmancheeva A.F., Berlev I.V., Imyanitov E.N., Belyaev A.M.
1) N.N.Petrov Research Institute of Oncology, St.-Petersburg, Russia; 2) I.I. Mechnikov North-Western State Medical University, St.-Petersburg, Russia

Aim. To review strategies for prophylactic surgery in carriers of BRCA1 or BRCA2 gene mutations and their short and long-term outcomes regarding overall health and health-related quality of life.
Materials and methods. Between January 2007 and December 2018, 752 women with ovarian cancer were tested for the most common mutations of BRCA1 (5382insC, 4153delA, 185delAG, С61G, 2080delA, 3875del4, 3819del5) and BRCA2 (6174delT) genes using allele-specific PCR. Patients with suspected hereditary ovarian cancer (n = 327) or concurrent breast and ovarian cancer (n = 16) were identified. The entire coding sequences of BRCA1 and BRCA2 genes were analyzed in these patients using high-resolution analysis of melting PCR products followed by sequencing of fragments with abnormal denaturation curves.
Results. The study identified 97 patients with ovarian cancer who had common mutations of BRCA1 genes [5382insC in BRCA1 gene, 4153delA in BRCA1 gene, 185delAG in BRCA1 gene, and C61G in BRCA1 gene in 74 (76.3%), 13 (13.4%), 7 (7.2%), and 1 (1%) of patients, respectively], and BRCA1 gene C61G in 1 (1%), BRCA1 gene 2080delA in 2 (2.1%)) and two patients with the 617delLT mutation in the BRCA2 gene, as well as 19 patients with rare mutations: in the BRCA1 gene (n = 14) and the BRCA2 gene (n = 5). The following recurrent alleles of BRCA1 were identified among rare mutations: R1751X in 5 (35.7%), R1699W in 3 (21.4%), G1706E in 2 (14.3%), c.2643delA in 2 (14.3%), c.5215 + 1G> T in 2 (14.3%) (n = 2) and BRCA2: Y1762X in 2 (40%), and c. 6999dupA in 3 (60%). Among relatives who carried mutations, 2/72 (2.7%) were diagnosed with ovarian cancer and fallopian tube cancer. In healthy carriers of BRCA1 gene mutations, hysterectomy with adnexa removal and bilateral adnexectomy were performed in 5 (62.5%) and 3 (37.8%) patients, respectively. In all 8 cases of prophylactic surgery, no adenocarcinoma cells were detected in removed ovaries and fallopian tubes.
Conclusion. Thus, salpingectomy during various gynecological surgeries is safe and may offer protection against ovarian cancer without compromising endocrine function. Besides, a delayed salpingectomy strategy may also serve as an effective alternative preventive strategy for women with a genetic predisposition to ovarian cancer.

salpingectomy

ovarian cancer

prevention

gene mutations

oophorectomy

Full text (in Russian)

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Received 20.12.2019

Accepted 26.12.2019

Tatiana V. Gorodnova, Oncologist, PhD, Department of Gynecological Oncology in the N.N.Petrov Research Institute of Oncology. Tel.: (007)-(812)-596-84-21,
Fax: (007)-(812)596-89-47. E-mail: t.gorodnova@mail.ru SPIN-код: 7239-5933, AuthorID: 854658
Pesochny-2, St.-Petersburg, 197758, Russia.
Anna P. Sokolenko, MD, PhD, Department of Tumor Biology, N.N. Petrov Institute of Oncology (St.-Petersburg, Russia). E-mail: annasokolenko@mail.ru.
AuthorID: 153982.
Pesochny-2, St.-Petersburg, 197758, Russia.
Khristina B. Kotiv, Postgraduate, Department of Oncogynecology, N.N. Petrov Institute of Oncology (St.-Petersburg, Russia). E-mail: xristinabogdanovna@gmail.com.
SPIN-code: 3049-8250.
Pesochny-2, St.-Petersburg, 197758, Russia.
Maria G. Yakovleva Oncologist, PhD, Department of Gynecological Oncology in the N.N.Petrov Research Institute of Oncology; Tel.: (007)-(812)-596-84-21,
Fax: (007)-(812)-596-89-47. E-mail: mersend@mail.ru SPIN-код автора в РИНЦ: 2661-9106; ORCID: 0000-0003-1719-7498
Pesochny-2, St.-Petersburg, 197758, Russia.
Olga E. Lavrinovich, Oncologist, PhD, Head of department of Gynecological Oncology in the N.N.Petrov Research Institute of Oncology; Tel.: (007)-(812)-596-84-21,
Fax: (007)-(812)-596-89-47. E-mail: olgalav1973@mail.ru; AuthorID: 383329
Pesochny-2, St.-Petersburg, 197758, Russia.
Nikolay A. Mikaya, Oncologist, PhD, Department of Gynecological Oncology in the N.N.Petrov Research Institute of Oncology; Tel.: (007)-(812)-596-84-21,
Fax: (007)-(812)-596-89-47. E-mail: nmikaya@mail.ru; SPIN-код: 1566-1789, AuthorID: 919303; Scopus AuthorID: 56801905000
Pesochny-2, St.-Petersburg, 197758, Russia.
Zaur N. Ibragimov, Oncologist, PhD, Department of Gynecological Oncology in the N.N.Petrov Research Institute of Oncology; Tel.: (007)-(812)-596-84-21,
Fax: (007)-(812)-596-89-47. E-mail: oncl@rion.spb.ru; SPIN-код: 4788-1510; AuthorID: 277962.
Pesochny-2, St.-Petersburg, 197758, Russia.
Yuri N. Trifanov, Oncologist, PhD, Department of Gynecological Oncology in the N.N.Petrov Research Institute of Oncology; Pesochny-2, St.-Petersburg, 197758, Russia.
Tel.: (007)-(812)-596-84-21, Fax: (007)-(812)-596-89-47. E-mail: oncl@rion.spb.ru; AuthorID: 306796; Scopus AuthorID: 57031846900
Pesochny-2, St.-Petersburg, 197758, Russia.
Nikolay E. Bondarev, Oncologist, PhD, Department of Gynecological Oncology in the N.N.Petrov Research Institute of Oncology; Tel.: (007)-(812)-596-84-21,
Fax: (007)-(812)-596-89-47. E-mail: ssmirnova.oa@gmail.com; SPIN-код: 9309-7703, AuthorID: 1019011
Pesochny-2, St.-Petersburg, 197758, Russia.
Ekaterina A. Nekrasova, candidate of medical sciences, researcher at the Department of Oncogynecology of the Federal State Budgetary Institution “National Medical Research Center of Oncology named after N.N. Petrov” of the Ministry of Health of the Russian Federation. Tel .: +7 (812) 439-9555. Fax: (812) 596-8947.
E-mail: ekaterina_neks@mail.ru
Address: 197758 St. Petersburg, pos. Sand, st. Leningradskaya, 68
Anna A. Sidoruk, Resident at the Department of Gynecological Oncology in the N.N.Petrov Research Institute of Oncology; Tel.: (007)-(812)-596-84-21,
Fax: (007)-(812)-596-89-47. E-mail: sidoruk_ann@mail.ru.
Pesochny-2, St.-Petersburg, 197758, Russia.
Olga A. Smirnova, Oncologist, PhD, Department of Gynecological Oncology in the N.N.Petrov Research Institute of Oncology; Tel.: (007)-(812)-596-84-21,
Fax: (007)-(812)-596-89-47. E-mail: meshkova.62@bk.ru
Pesochny-2, St.-Petersburg, 197758, Russia.
Konstantin D. Guseynov, Oncologist, MD, PhD, Department of Gynecological Oncology in the N.N.Petrov Research Institute of Oncology; Tel.: (007)-(812)-596-84-21,
Fax: (007)-(812)-596-89-47.E-mail: oncl@rion.spb.ru; SPIN-код: 5191-8792, AuthorID: 203398; Scopus AuthorID 10739227400
Pesochny-2, St.-Petersburg, 197758, Russia.
Elena V. Bakhidze, Oncologist, PhD, Department of Gynecological Oncology in the N.N.Petrov Research Institute of Oncology; Tel.: (007)-(812)-596-84-21,
Fax: (007)-(812)-596-89-47. E-mail: oncl@rion.spb.ru SPIN-код: 5191-8792, AuthorID: 203398; Scopus AuthorID: 56632534700
Pesochny-2, St.-Petersburg, 197758, Russia.
Iryna E. Meshkova, Oncologist, PhD, Department of Gynecological Oncology in the N.N.Petrov Research Institute of Oncology; Tel.: (007)-(812)-596-84-21,
Fax: (007)-(812)-596-89-47. E-mail: oncl@rion.spb.ru; Scopus AuthorID:56801862100
Elvina Kh. Bakaeva, Resident at the Department of Gynecological Oncology in the N.N.Petrov Research Institute of Oncology; Tel.: (007)-(812)-596-84-21,
Fax: (007)-(812)-596-89-47. E-mail: oncl@rion.spb.ru
Pesochny-2, St.-Petersburg, 197758, Russia.
Marianna G. Shikhzadaeva, Resident at the Department of Gynecological Oncology in the N.N.Petrov Research Institute of Oncology; Tel.: (007)-(812)-596-84-21,
Fax: (007)-(812)-596-89-47. E-mail: oncl@rion.spb.ru
Pesochny-2, St.-Petersburg, 197758, Russia.
Elena A. Ulrikh, MD, professor, professor of the Department of Oncology, North-West State Medical University them. I.I. Mechnikov, a doctor of the highest category of oncogynecological department of the Federal State Budgetary Institution Scientific Research Center for Oncology N.N. Petrova ”Ministry of Health of the Russian Federation.Tel.: (007)-(812)-596-84-21. Fax: (007)-(812)-596-89-47. E-mail: elenaulrikh@yandex.ru; ORCID: 0000-0002-1593-6771
Pesochny-2, St.-Petersburg, 197758, Russia.
Adel F. Urmancheeva, M.D., Ph.D., Leading Researcher at the Department of Gynecological Oncology in the N.N.Petrov Research Institute of Oncology;
Tel.: (007)-(812)-596-84-21, Fax: (007)-(812)-596-89-47, Professor at the Department of Oncology of North-Western State Medical University
na I.I. Mechnikov, St.-Petersburg.
E-mail: adaurm@mail.ru; SPIN-код: 1110-1844; AuthorID: 668989; Scopus AuthorID: 55943009000
Pesochny-2, St.-Petersburg, 197758, Russia.
Igor V. Berlev, M.D., Ph.D, professor, Leading Researcher at the Department of Gynecological Oncology in the N.N.Petrov Research Institute of Oncology;
Tel.: (007)-(812)-596-84-21, Fax: (007)-(812)-596-89-47, Professor at the Department of Oncology of North-Western State Medical University
na I.I. Mechnikov, St.-Petersburg E-mail: iberlev@gmail.com; SPIN-код: 4169-6011; AuthorID: 668976; Scopus AuthorID: 6603322008
Pesochny-2, St.-Petersburg, 197758, Russia.
Evgeny N. Imyanitov, MD, DSc, Professor, Corresponding Member of the Russian Academy of Sciences, Head of the Department of Tumor Biology, N.N. Petrov Institute of Oncology (St.-Petersburg, Russia). E-mail: evgeny@imyanitov.spb.ru. SPIN-code: 1909-7323.
Pesochny-2, St.-Petersburg, 197758, Russia.
Alexey M. Belyaev, M.D., Ph.D., Professor, Нead of Department of Gynecological Oncology in the N.N.Petrov Research Institute of Oncology; Tel.: (007)-(812)-596-84-21, Fax: (007)-(812)-596-89-47, Нead of Department of Gynecology of North-Western State Medical University na I.I. Mechnikov, St.-Petersburg. E-mail: oncl@rion.spb.ru; Author ID: 274121; ORCID: 0000-0001-6937-2740; Scopus AuthorID: 54995192000
Pesochny-2, St.-Petersburg, 197758, Russia.

For citation: Gorodnova T.V., Sokolenko A.P., Kotiv Kh.B., Yakovleva M.G., Lavrinovich O.E., Mikaya N.A., Ibragimov Z.N., Trifanov Yu.N., Bondarev N.E., Nekrasova E.A., Sidoruk A.A., Smirnova O.A., Guseinov K.D., Bakhidze E.V., Meshkova I.E., Bakaeva E.Kh., Shikhzadaeva M.G., Ul’rikh E.A., Urmancheeva A.F., Berlev I.V., Imyanitov E.N., Belyaev A.M. Prophylactic surgery in carriers of BRCA1 or BRCA2 gene mutation.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2020; 1(Suppl): 56-62.(in Russian)
https://dx.doi.org/10.18565/aig.2020.1suppl.56-62

Prophylactic surgery in carriers of BRCA1 or BRCA2 gene mutation

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