Tumors of female reproductive systemTumors of female reproductive systemОпухоли женской репродуктивной системы1994-40981999-8627Publishing House ABV Press77810.17650/1994-4098-2020-16-4-54-65MAMMOLOGY. REVIEWSМАММОЛОГИЯ. ОБЗОРНЫЕ СТАТЬИHereditary breast cancer and ovarian cancer: clinical course and treatmentОсобенности клинического течения и лечения наследственных форм рака молочной железы и рака яичниковhttps://orcid.org/0000-0002-8825-5221SemiglazovV. V.СемиглазовВ. В.
Russian Federation

6–8 Lva Tolstogo St., Saint Petersburg 197022

68 Leningradskaya St.,  Pesochnyy Settlement, Saint Petersburg 197758

Владислав Владимирович Семиглазов 

197022 Санкт-Петербург, ул. Льва Толстого, 6–8

197758 Санкт-Петербург, пос. Песочный, ул. Ленинградская, 68

oncology.spbgmu@mail.ruProtasovaA. Е.ПротасоваА. Э.
Russian Federation

7–9 Universitetskaya Naberezhnaya, Saint-Petersburg 199034

199034 Санкт-Петербург,  Университетская набережная, 7–9

KalikeevG. K.КаликеевГ. К.
Russian Federation

6–8 Lva Tolstogo St., Saint Petersburg 197022

197022 Санкт-Петербург, ул. Льва Толстого, 6–8

I.P. Pavlov First Saint Petersburg State Medical University, Ministry of Health of RussiaФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова» Минздрава РоссииN.N. Petrov National Medical Research Center of Oncology, Ministry of Health of RussiaФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Петрова» Минздрава РоссииSaint-Petersburg State UniversityФБОУ ВО «Санкт-Петербургский государственный университет»13122020164546512032021120320212020https://ojrs.abvpress.ru/ojrs/article/view/778

This article analyzes current problems associated with surgical and systemic treatment for hereditary breast and ovarian cancers (including those associated with BRCA1/2 gene mutations). We discuss the issues related to clinical course of multiple primary tumors and their sensitivity to cytostatic and targeted therapy.

В статье освещены проблемы современного хирургического и системного лечения больных с наследственными (в том числе ассоциированными с мутациями генов BRCA1/2) формами рака молочной железы и яичника. Рассмотрены вопросы, касающиеся особенностей клинического течения первично-множественных опухолей, а также их чувствительности к цитостатической и таргетной терапии.

breast cancerovarian cancermultiple primary tumorsBRCA1BRCA2CHEK2PARP inhibitorsрак молочной железырак яичникапервично-множественные опухолиBRCA1BRCA2CHEK2PARP-ингибиторыMalignant tumors in Russia in 2018: incidence and mortality. Ed. by A. D. Kaprin, V.V. Starinskiy, G.V. Petrova. Moscow: P.A. Herzen Moscow Oncology Research Institute – a branch of the National Medical Research Radiological Center, Ministry of Health of Russia, 2019. 250 p. (In Russ.).Злокачественные новообразования в России в 2018 году: заболеваемость и смертность). Под ред. А.Д. Каприна, В.В. Старинского, Г.В. Петровой. М.: МНИОИ им. П.А. Герцена – филиал ФГБУ «НМИЦ радиологии» Минздрава России, 2019. 250 с.Valachis A., Nearchou A.D., Lind P. Surgical management of breast cancer in BRCA-mutation carriers: a systematic review and meta-analysis. Breast Cancer Res Treat 2014;144(3):443–55. DOI: 10.1007/s10549-014-2890-1.Valachis A., Nearchou A.D., Lind P. Surgical management of breast cancer in BRCA-mutation carriers: a systematic review and meta-analysis. Breast Cancer Res Treat 2014;144(3):443–55. DOI: 10.1007/s10549-014-2890-1.Bershteyn L.M. Role of extragonadal estrogens and hormonal carcinogenesis. Vestnik Rossiyskoy akademii meditsinskikh nauk = Bulletin of the Russian Academy of Medical Sciences 2007;(8):54. (In Russ.).Берштейн Л.М. Роль экстрагонадных эстрогенов и гормональный канцерогенез. Вестник Российской академии медицинских наук 2007;(8):54.Yager J.D., Davidson N.E. Estrogen carcinogenesis in breast cancer. N Engl J Med 2006;354:270–82. DOI: 10.1056/NEJMra050776.Yager J.D., Davidson N.E. Estrogen carcinogenesis in breast cancer. N Engl J Med 2006;354:270–82. DOI: 10.1056/NEJMra050776.Chang E.C., Frasor J., Komm B. et al. Impact of estrogen receptor β on gene networks regulated by estrogen receptor α in breast cancer cells. Endocrinology 2006;147:4831–42.Mungenast F., Thalhammer T. Estrogen biosynthesis and action in ovarian cancer. Front Endocrinol (Lausanne) 2014;5:192.Mungenast F., Thalhammer T. Estrogen biosynthesis and action in ovarian cancer. Front Endocrinol (Lausanne) 2014;5:192.Schuler-Toprak S., Moehle C., Skrzypczak M. et al. Effect of estrogen receptor beta agonists on proliferation and gene expression of ovarian cancer cells. BMC Cancer 2017;17:319.Schuler-Toprak S., Moehle C., Skrzypczak M. et al. Effect of estrogen receptor beta agonists on proliferation and gene expression of ovarian cancer cells. BMC Cancer 2017;17:319.Huzarski T., Byrski T., Gronwald J. et al. Ten-year survival in patients with BRCA1negative and BRCA1-positive breast cancer. J Clin Oncol 2013;31:3191–6.Foulkes W.D., Chappuis P.O., Wong N. et al. Primary node negative breast cancer in BRCA1 mutation carriers has a poor outcome. Ann Oncol 2000;11:307–13.Foulkes W.D., Chappuis P.O., Wong N. et al. Primary node negative breast cancer in BRCA1 mutation carriers has a poor outcome. Ann Oncol 2000;11:307–13.Moller P., Evans D.G., Reis M.M. et al. Surveillance for familial breast cancer: Differences in outcome according to BRCA mutation status. Int J Cancer 2007;121:1017–20.Moller P., Evans D.G., Reis M.M. et al. Surveillance for familial breast cancer: Differences in outcome according to BRCA mutation status. Int J Cancer 2007;121:1017–20.Lee E.H., Park S.K., Park B. et al. Effect of BRCA1/2 mutation on short-term and long-term breast cancer survival: a systematic review and metaanalysis. Breast Cancer Res Treat 2010;122:11–25.Lee E.H., Park S.K., Park B. et al. Effect of BRCA1/2 mutation on short-term and long-term breast cancer survival: a systematic review and metaanalysis. Breast Cancer Res Treat 2010;122:11–25.Cortesi L., Masini C., Cirilli C. et al. Favourable ten-year overall survival in a Caucasian population with high probability of hereditary breast cancer. BMC Cancer 2010;10:90.Cortesi L., Masini C., Cirilli C. et al. Favourable ten-year overall survival in a Caucasian population with high probability of hereditary breast cancer. BMC Cancer 2010;10:90.Tryggvadottir L., Olafsdottir E.J., Olafsdottir G.H. et al. Tumour diploidy and survival in breast cancer patients with BRCA2 mutations. Breast Cancer Res Treat 2013;140:375–84.Tryggvadottir L., Olafsdottir E.J., Olafsdottir G.H. et al. Tumour diploidy and survival in breast cancer patients with BRCA2 mutations. Breast Cancer Res Treat 2013;140:375–84.Zhong Q., Peng H.L., Zhao X. et al. Effects of BRCA1- and BRCA2-related mutations on ovarian and breast cancer survival: a meta-analysis. Clin Cancer Res 2015;21(1):211–20.Bolton K.L., Chenevix-Trench G., Goh C. et al. Association between BRCA1 and BRCA2 mutations and survival in women with invasive epithelial ovarian cancer. JAMA 2012;307:382–90.Bolton K.L., Chenevix-Trench G., Goh C. et al. Association between BRCA1 and BRCA2 mutations and survival in women with invasive epithelial ovarian cancer. JAMA 2012;307:382–90.Majdak E.J., Debniak J., Milczek T. et al. Prognostic impact of BRCA1 pathogenic and BRCA1/BRCA2 unclassified variant mutations in patients with ovarian carcinoma. Cancer 2005;104:1004–12.Cunningham J.M., Cicek M.S., Larson N.B. et al. Clinical characteristics of ovarian cancer classified by BRCA1, BRCA2, and RAD51C status. Sci Rep 2014;4:4026.Cunningham J.M., Cicek M.S., Larson N.B. et al. Clinical characteristics of ovarian cancer classified by BRCA1, BRCA2, and RAD51C status. Sci Rep 2014;4:4026.Bolton K.L., Chenevix-Trench G., Goh C. et al. Association between BRCA1 and BRCA2 mutations and survival in women with invasive epithelial ovarian cancer. JAMA 2012;307(4):382–90. DOI: 10.1001/jama.2012.20.Bolton K.L., Chenevix-Trench G., Goh C. et al. Association between BRCA1 and BRCA2 mutations and survival in women with invasive epithelial ovarian cancer. JAMA 2012;307(4):382–90. DOI: 10.1001/jama.2012.20.Hyman D.M., Zhou Q., Iasonos A. et al. Improved survival for BRCA2-associated serous ovarian cancer compared with both BRCA-negative and BRCA1-associated serous ovarian cancer. Cancer 2012;118:3703–9.Yang D., Khan S., Sun Y. et al. Association of BRCA1 and BRCA2 mutations with survival, chemotherapy sensitivity, and gene mutator phenotype in patients with ovarian cancer. JAMA 2011;306:1557–65.Yang D., Khan S., Sun Y. et al. Association of BRCA1 and BRCA2 mutations with survival, chemotherapy sensitivity, and gene mutator phenotype in patients with ovarian cancer. JAMA 2011;306:1557–65.Vencken P.M., Reitsma W., Kriege M. et al. Outcome of BRCA1-compares with BRCA2-associated ovarian cancer: a nationwide study in the Netherlands. Ann Oncol 2013;24:2036–42.Vencken P.M., Reitsma W., Kriege M. et al. Outcome of BRCA1-compares with BRCA2-associated ovarian cancer: a nationwide study in the Netherlands. Ann Oncol 2013;24:2036–42.Alsop K., Fereday S., Meldrum C. et al. BRCA mutation frequency and patterns of treatment response in BRCA mutationpositive women with ovarian: a report from the Australia ovarian cancer study group. J Clin Oncol Off J Am Soc Clin Oncol 2012;30:2654–63.Alsop K., Fereday S., Meldrum C. et al. BRCA mutation frequency and patterns of treatment response in BRCA mutationpositive women with ovarian: a report from the Australia ovarian cancer study group. J Clin Oncol Off J Am Soc Clin Oncol 2012;30:2654–63.Tan D.S., Rothermundt C., Thomas K. et al. “BRCAness” syndrome in ovarian cancer: a case-control study describing the clinical features and outcome of patients with epithelial ovarian cancer associated with BRCA1 and BRCA2 mutations. J Clin Oncol Off J Am Soc Clin Oncol 2008;26:5530–6.McLaughlin J.R., Rosen B., Moody J. et al. Long-term ovarian cancer survival associated with mutation in BRCA1 or BRCA2. J Natl Cancer Inst 2013;105:141–8.Candido-dos-Reis F.J., Song H., Goode E.L. et al. Germline mutation in BRCA1 or BRCA2 and ten-year survival for women diagnosed with epithelial ovarian cancer. Clin Cancer Res 2015;21:652–7. 26. Kurta M.L., Edwards R.P., Moysich K.B. et al. Prognosis and conditional disease-free survival among patients with ovarian cancer. J Clin Oncol Off J Am Soc Clin Oncol 2014;32:4102–12.Candido-dos-Reis F.J., Song H., Goode E.L. et al. Germline mutation in BRCA1 or BRCA2 and ten-year survival for women diagnosed with epithelial ovarian cancer. Clin Cancer Res 2015;21:652–7. 26. Kurta M.L., Edwards R.P., Moysich K.B. et al. Prognosis and conditional disease-free survival among patients with ovarian cancer. J Clin Oncol Off J Am Soc Clin Oncol 2014;32:4102–12.Vencken P.M., Kriege M., Hooning M. et al. The risk of primary and contralateral breast cancer after ovarian cancer in BRCA1/BRCA2 mutation carriers: implications for counseling. Cancer 2013;119:955–62.Vencken P.M., Kriege M., Hooning M. et al. The risk of primary and contralateral breast cancer after ovarian cancer in BRCA1/BRCA2 mutation carriers: implications for counseling. Cancer 2013;119:955–62.Domchek S.M., Jhaveri K., Patil S. et al. Risk of metachronous breast cancer after BRCA mutation-associated ovarian cancer. Cancer 2013;119:1344–8.Gangi A., Cass I., Paik D. et al. Breast cancer following ovarian cancer in BRCA mutation carriers. JAMA Surg 2014;149:1306–13.Zhang W., Zhang W., Lin Z. et al. Survival outcomes of patients with primary breast cancer following primary ovarian cancer. Med Sci Monit 2019;25:3869–79.Gangi A., Cass I., Paik D. et al. Breast cancer following ovarian cancer in BRCA mutation carriers. JAMA Surg 2014;149(12):1306–13.Zaaijer L.H., van Doorn H.C., Mourits M.J. et al. Outcome of ovarian cancer after breast cancer in BRCA1 and BRCA2 mutation carriers. Br J Cancer 2016;115(10):1174–8.Zaaijer L.H., van Doorn H.C., Mourits M.J. et al. Outcome of ovarian cancer after breast cancer in BRCA1 and BRCA2 mutation carriers. Br J Cancer 2016;115(10):1174–8.Domchek S.M., Friebel T.M., Singer C.F. et al. Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. JAMA 2010;304:967–75.Domchek S.M., Friebel T.M., Singer C.F. et al. Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. JAMA 2010;304:967–75.Rebbeck T.R., Kauff N.D., Domchek S.M. Meta-analysis of risk reduction estimates associated with risk-reducing salpingooophorectomy in BRCA1 or BRCA2 mutation carriers. J Natl Cancer Inst 2009;8(8):CD012464. DOI: 10.1002/14651858.CD012464.pub2.Rebbeck T.R., Kauff N.D., Domchek S.M. Meta-analysis of risk reduction estimates associated with risk-reducing salpingooophorectomy in BRCA1 or BRCA2 mutation carriers. J Natl Cancer Inst 2009;8(8):CD012464. DOI: 10.1002/14651858.CD012464.pub2.Heemskerk-Gerritsen B.A.M., Seynaeve C., Van Asperen C.J. et al. Breast cancer risk after salpingo-oophorectomy in healthy BRCA1/2 mutation carriers: revisiting the evidence for risk reduction. J Natl Cancer Inst 2015;107(5):djv033. DOI: 10.1093/jnci/djv033.Heemskerk-Gerritsen B.A.M., Seynaeve C., Van Asperen C.J. et al. Breast cancer risk after salpingo-oophorectomy in healthy BRCA1/2 mutation carriers: revisiting the evidence for risk reduction. J Natl Cancer Inst 2015;107(5):djv033. DOI: 10.1093/jnci/djv033.Heemskerk-Gerritsen B.A.M., Rookus M.A., Aalfs C.M. et al. Improved overall survival after contralateral risk-reducing mastectomy in BRCA1/2 mutation carriers with a history of unilateral breast cancer: a prospective analysis. Int J Cancer 2015;136(3):668–77. DOI: 10.1002/ijc.29032.Heemskerk-Gerritsen B.A.M., Rookus M.A., Aalfs C.M. et al. Improved overall survival after contralateral risk-reducing mastectomy in BRCA1/2 mutation carriers with a history of unilateral breast cancer: a prospective analysis. Int J Cancer 2015;136(3):668–77. DOI: 10.1002/ijc.29032.Soenderstrup I.M.H., Laenkholm A.V., Jensen M.B. et al. Clinical and molecular characterization of BRCA-associated breast cancer: Results from the DBCG. Acta Oncol 2018;57:95–101.Schmidt M.K., van den Broek A.J., Tollenaar R.A. et al. Breast cancer survival of BRCA1/BRCA2 mutation carriers in a hospital-based cohort of young women. J Natl Cancer Inst 2017;109:djw329. DOI: 10.1093/jnci/djw329.Schmidt M.K., van den Broek A.J., Tollenaar R.A. et al. Breast cancer survival of BRCA1/BRCA2 mutation carriers in a hospital-based cohort of young women. J Natl Cancer Inst 2017;109:djw329. DOI: 10.1093/jnci/djw329.Van Sprundel T.C., Schmidt M.K., Rookus M.A. et al. Risk reduction of contralateral breast cancer and survival after contralateral prophylactic mastectomy in BRCA1 or BRCA2 mutation carriers. Br J Cancer 2005;93:287–92.Van Sprundel T.C., Schmidt M.K., Rookus M.A. et al. Risk reduction of contralateral breast cancer and survival after contralateral prophylactic mastectomy in BRCA1 or BRCA2 mutation carriers. Br J Cancer 2005;93:287–92.Tung N.M., Boughey J.C., Pierce L.J. et al. Management of Hereditary Breast Cancer: American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Guideline. J Clin Oncol 2020;38(18):2080–106.Walsh T., King MC. Ten genes for inherited breast cancer. Cancer Cell 2007;11:103–5.Walsh T., King MC. Ten genes for inherited breast cancer. Cancer Cell 2007;11:103–5.National Research Genome Institute (NIH). Learning about the BRCAX study. Available at: http://www.genome. gov/10000532.Eisen A., Lubinski J., Klijn J. et al. Breast cancer risk following bilateral oophorectomy in BRCA1 and BRCA2 pathogenic variant carriers: international case-control study. J Clin Oncol 2005;23:7491–6.Eisen A., Lubinski J., Klijn J. et al. Breast cancer risk following bilateral oophorectomy in BRCA1 and BRCA2 pathogenic variant carriers: international case-control study. J Clin Oncol 2005;23:7491–6.Robson M.E., Chappuis P.O., Satagopan J. et al. A combined analysis of outcome following breast cancer: differences in survival based on BRCA1/BRCA2 mutation status and administration of adjuvant treatment. Breast Cancer Res 2004.Robson M.E., Chappuis P.O., Satagopan J. et al. A combined analysis of outcome following breast cancer: differences in survival based on BRCA1/BRCA2 mutation status and administration of adjuvant treatment. Breast Cancer Res 2004.Kirova Y.M., Stoppa-Lyonnet D., Savignoni A. et al. Risk of breast cancer recurrence and contralateral breast cancer in relation to BRCA1 and BRCA2 mutation status following breast-conserving surgery and radiotherapy. Eur J Cancer 2005;41:2304–11.Brekelmans C.T., Tilanus-Linthorst M.M., Seynaeve C. et al. Tumour characteristics, survival and prognostic factors of hereditary breast cancer from BRCA2-, BRCA1- and non-BRCA1/2 families as compared to sporadic breast cancer cases. Eur J Cancer 2007;43:867–76.Brekelmans C.T., Tilanus-Linthorst M.M., Seynaeve C. et al. Tumour characteristics, survival and prognostic factors of hereditary breast cancer from BRCA2-, BRCA1- and non-BRCA1/2 families as compared to sporadic breast cancer cases. Eur J Cancer 2007;43:867–76.Pierce L.J., Levin A.M., Rebbeck T.R. et al. Ten-year multi-institutional results of breast-conserving surgery and radiotherapy in BRCA1/2-associated stage I/II breast cancer. J Clin Oncol 2006; 24(16):2437–43. DOI: 10.1200/JCO.2005.02.7888.Pierce L.J., Levin A.M., Rebbeck T.R. et al. Ten-year multi-institutional results of breast-conserving surgery and radiotherapy in BRCA1/2-associated stage I/II breast cancer. J Clin Oncol 2006; 24(16):2437–43. DOI: 10.1200/JCO.2005.02.7888.Pierce L.J., Phillips K.A., Griffith K.A. et al. Local therapy in BRCA1 and BRCA2 mutation carriers with operable breast cancer: comparison of breast conservation and mastectomy. Breast Cancer Res Treat 2010;121(2):389–98. DOI: 10.1007/s10549-010-0894-z.Pierce L.J., Phillips K.A., Griffith K.A. et al. Local therapy in BRCA1 and BRCA2 mutation carriers with operable breast cancer: comparison of breast conservation and mastectomy. Breast Cancer Res Treat 2010;121(2):389–98. DOI: 10.1007/s10549-010-0894-z.Nilsson M.P., Hartman L., Kristoffersson U. et al. High risk of in-breast tumor recurrence after BRCA1/2-associated breast cancer. Breast Cancer Res Treat 2014;147:571–8.Haffty B.G., Harrold E., Khan A.J. et al. Outcome of conservatively managed early onset breast cancer by BRCA1/2 status. Lancet 2002;359(9316):1471–7. DOI: 10.1016/S0140-6736(02)08434-9.Haffty B.G., Harrold E., Khan A.J. et al. Outcome of conservatively managed early onset breast cancer by BRCA1/2 status. Lancet 2002;359(9316):1471–7. DOI: 10.1016/S0140-6736(02)08434-9.Van den Broek A.J., Schmidt M.K., van ’t Veer LJ. et al. Prognostic impact of breast-conserving therapy versus mastectomy of BRCA1/2 mutation carriers compared with noncarriers in a consecutive series of young breast cancer patients. Ann Surg 2019;270:364–72.Van den Broek A.J., Schmidt M.K., van ’t Veer LJ. et al. Prognostic impact of breast-conserving therapy versus mastectomy of BRCA1/2 mutation carriers compared with noncarriers in a consecutive series of young breast cancer patients. Ann Surg 2019;270:364–72.«Золотой стандарт» диагностики и лечения рака молочной железы 2021. Российское общество онкомаммологов. Версия 2.0. [Gold standard for the diagnosis and treatment of breast cancer 2021. Russian Association of Oncological Mammology. Version 2.0. (In Russ.)].«Золотой стандарт» диагностики и лечения рака молочной железы 2021. Российское общество онкомаммологов. Версия 2.0.Boyd J., Sonoda Y., Federici M.G. et al. Clinicopathologic features of BRCA-linked and sporadic ovarian cancer. JAMA 2000;283(17):2260–5.Du Bois A., Vergote I., Ferron G. et al. Randomized controlled phase III study evaluating the impact of secondary cytoreductive surgery in recurrent ovarian cancer: AGO DESKTOP III/ENGOT ov20. J Clin Oncol 2017;35(Suppl): abstract 5501.Van Driel W.J., Koole S.N., Sikorska K. et al. Hyperthermic intraperitoneal chemotherapy in ovarian cancer. N Engl J Med 2018;378(3):230–40.Van Driel W.J., Koole S.N., Sikorska K. et al. Hyperthermic intraperitoneal chemotherapy in ovarian cancer. N Engl J Med 2018;378(3):230–40.Chiva L.M., Gonzalez-Martin A. A critical appraisal of hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of advanced and recurrent ovarian cancer. Gynecol Oncol 2015;136(1):130–5. DOI: 10.1016/j.ygyno.2014.11.072.Chiva L.M., Gonzalez-Martin A. A critical appraisal of hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of advanced and recurrent ovarian cancer. Gynecol Oncol 2015;136(1):130–5. DOI: 10.1016/j.ygyno.2014.11.072.Arun B., Bayraktar S., Liu D.D. et al. Response to neoadjuvant systemic therapy for breast cancer in BRCA mutation carriers and noncarriers: A single-institution experience. J Clin Oncol 2011;29:3739–46.Arun B., Bayraktar S., Liu D.D. et al. Response to neoadjuvant systemic therapy for breast cancer in BRCA mutation carriers and noncarriers: A single-institution experience. J Clin Oncol 2011;29:3739–46.Silver D.P., Richardson A.L., Eklund A.C. et al. Efficacy of neoadjuvant cisplatin in triple-negative breast cancer. J Clin Oncol 2010;28:1145–53.Silver D.P., Richardson A.L., Eklund A.C. et al. Efficacy of neoadjuvant cisplatin in triple-negative breast cancer. J Clin Oncol 2010;28:1145–53.Byrski T., Huzarski T., Dent R. et al. Pathologic complete response to neoadjuvant cisplatin in BRCA1-positive breast cancer patients. Breast Cancer Res Treat 2014;147:401–5.Byrski T., Huzarski T., Dent R. et al. Pathologic complete response to neoadjuvant cisplatin in BRCA1-positive breast cancer patients. Breast Cancer Res Treat 2014;147:401–5.Hahnen E., Lederer B., Hauke J. et al. Germline mutation status, pathological complete response, and disease-free survival in triple-negative breast cancer: Secondary analysis of the GeparSixto randomized clinical trial. JAMA Oncol 2017;3:1378–85.Hahnen E., Lederer B., Hauke J. et al. Germline mutation status, pathological complete response, and disease-free survival in triple-negative breast cancer: Secondary analysis of the GeparSixto randomized clinical trial. JAMA Oncol 2017;3:1378–85.Loibl S., O’Shaughnessy J., Untch M. et al. Addition of the PARP inhibitor veliparib plus carboplatin or carboplatin alone to standard neoadjuvant chemotherapy in triple-negative breast cancer (BrighTNess): a randomised, phase 3 trial. Lancet Oncol 2018;19(4):497–509.Loibl S., O’Shaughnessy J., Untch M. et al. Addition of the PARP inhibitor veliparib plus carboplatin or carboplatin alone to standard neoadjuvant chemotherapy in triple-negative breast cancer (BrighTNess): a randomised, phase 3 trial. Lancet Oncol 2018;19(4):497–509.Tung N., Arun B., Hacker M.R. et al. Randomized phase II study of neoadjuvant cisplatin versus doxorubicincyclophosphamide in germline BRCA carriers with HER2-negative breast cancer (the INFORM trial). J Clin Oncol 2020;38(14):1539–48.Tung N., Arun B., Hacker M.R. et al. Randomized phase II study of neoadjuvant cisplatin versus doxorubicincyclophosphamide in germline BRCA carriers with HER2-negative breast cancer (the INFORM trial). J Clin Oncol 2020;38(14):1539–48.Robson M., Im S.A., Senkus E. et al. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med 2017;377(6):523–33. DOI: 10.1056/NEJMoa1706450. Erratum in: N Engl J Med 2017;377(17):1700.Robson M., Im S.A., Senkus E. et al. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med 2017;377(6):523–33. DOI: 10.1056/NEJMoa1706450. Erratum in: N Engl J Med 2017;377(17):1700.Litton JK., Rugo HS., Ettl J. et al. Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. N Engl J Med. 2018 Aug 23;379(8):753-763Litton J.K., Scoggins M.E., Hess K.R. et al. Neoadjuvant talazoparib for patients with operable breast cancer with a germline BRCA pathogenic variant. J Clin Oncol 2020;38(5):388–94.Dieras V., Han H.S., Kaufman B. et al. Veliparib with carboplatin and paclitaxel in BRCA-mutated advanced breast cancer (BROCADE3): a randomised, doubleblind, placebo-controlled, phase 3 trial. Lancet Oncol 2020;21(10):1269–82.Dieras V., Han H.S., Kaufman B. et al. Veliparib with carboplatin and paclitaxel in BRCA-mutated advanced breast cancer (BROCADE3): a randomised, doubleblind, placebo-controlled, phase 3 trial. Lancet Oncol 2020;21(10):1269–82.Gruber J.J., Afghahi A., Hatton A. et al. Talazoparib beyond BRCA: A phase II trial of talazoparib monotherapy in BRCA1 and BRCA2 wild-type patients with advanced HER2-negative breast cancer or other solid tumors with a mutation in homologous recombination (HR) pathway genes. J Clinl Oncol 2019;37:3006.Gruber J.J., Afghahi A., Hatton A. et al. Talazoparib beyond BRCA: A phase II trial of talazoparib monotherapy in BRCA1 and BRCA2 wild-type patients with advanced HER2-negative breast cancer or other solid tumors with a mutation in homologous recombination (HR) pathway genes. J Clinl Oncol 2019;37:3006.Moore K., Colombo N., Scambia G. et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med 2018;379(26):2495–505.Ledermann J., Harter P., Gourley C. et al. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med 2012;366(15):1382–92.Pujade-Lauraine E., Ledermann J.A., Selle F. et al. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol 2017;18(9):1274–84.Mirza M.R., Monk B.J., Herrstedt J. et al. Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. N Engl J Med 2016;375(22): 2154–64.Mirza M.R., Monk B.J., Herrstedt J. et al. Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. N Engl J Med 2016;375(22): 2154–64.Del Campo J.M., Matulonis U.A., Malander S. et al. Niraparib maintenance therapy in patients with recurrent ovarian cancer after a partial response to the last platinum-based chemotherapy in the ENGOT-OV16/NOVA trial. J Clin Oncol 2019;37(32):2968–73.Del Campo J.M., Matulonis U.A., Malander S. et al. Niraparib maintenance therapy in patients with recurrent ovarian cancer after a partial response to the last platinum-based chemotherapy in the ENGOT-OV16/NOVA trial. J Clin Oncol 2019;37(32):2968–73.Coleman R.L., Oza A.M., Lorusso D. et al. ARIEL3 investigators. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebocontrolled, phase 3 trial. Lancet 2017;390(10106):1949–61.Coleman R.L., Oza A.M., Lorusso D. et al. ARIEL3 investigators. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebocontrolled, phase 3 trial. Lancet 2017;390(10106):1949–61.Vos J.R., Fakkert I.E., de Hullu J.A. et al. OPA Working Group. Universal tumor DNA BRCA1/2 testing of ovarian cancer: Prescreening PARPi treatment and genetic predisposition. J Natl Cancer Inst 2020;112(2):161–9.Vos J.R., Fakkert I.E., de Hullu J.A. et al. OPA Working Group. Universal tumor DNA BRCA1/2 testing of ovarian cancer: Prescreening PARPi treatment and genetic predisposition. J Natl Cancer Inst 2020;112(2):161–9.Hodgson D.R., Dougherty B.A., Lai Z. et al. Candidate biomarkers of PARP inhibitor sensitivity in ovarian cancer beyond the BRCA genes. Br J Cancer 2018;119:1401–9.Hodgson D.R., Dougherty B.A., Lai Z. et al. Candidate biomarkers of PARP inhibitor sensitivity in ovarian cancer beyond the BRCA genes. Br J Cancer 2018;119:1401–9.