Tumors of female reproductive systemTumors of female reproductive systemОпухоли женской репродуктивной системы1994-40981999-8627Publishing House ABV Press46010.17650/1994-4098-2015-11-4-58-70MAMMOLOGY. BENIGN BREAST DISEASESМАММОЛОГИЯ. ДОБРОКАЧЕСТВЕННЫЕ ЗАБОЛЕВАНИЯ МОЛОЧНЫХ ЖЕЛЕЗFibrocystic disease and breast cancer risk (а review of literature)Фиброзно-кистозная болезнь и риск рака молочной железы (обзор литературы)BespalovV. G.БеспаловВ. Г.
Russian Federation
bespalov_niio@mail.ruTravinaM. L.ТравинаМ. Л.
Russian Federation
N.N. Petrov Research Institute of Oncology, Ministry of Health of RussiaФГБУ «Научно-исследовательский институт онкологии им. Н. Н. Петрова» Минздрава России68 Leningradskaya St., Pesochny, Saint-Petersburg, 197758, RussiaРоссия, 197758, Санкт-Петербург, пос. Песочный, ул. Ленинградская, 68Scientific Centre of Children Health, Ministry of Health of RussiaФГБУ «Научный центр здоровья детей» Минздрава России2 build. 1 Lomonosovsky Prospekt, Moscow, 119991, RussiaРоссия, 119991, Москва, Ломоносовский проспект, 2, стр. 12611201511458702511201525112015https://ojrs.abvpress.ru/ojrs/article/view/460

The article discusses the relationship between etiology and risk factors of fibrocystic disease (FCD) and breast cancer (BC), pathogenesis of FCD in connection with increasing risk of BC, assessment of BC risk in patients with FCD; pathogenetic treatment of FCD aimed for preventing BC; the use of the drug progestogel for the treatment of FCD and prevention of BC. FCD and BC have general etiology and the most risk factors are identical for the both pathologies. Multiple risk factors disturb hormonal balance in the organism of a woman, cause hyperestrogenism and epithelium hyperproliferation in the mammary tissue that results in the development of FCD and at presenceof congenital or acquired gene damage results in the development of BC. Decision value for the estimation of degree of a BC risk in patients with FCD has morphological research of mammary tissue got at a biopsy. The risk of developing BC for non-proliferative FCD does not rise or is minimal. Proliferative FCD without atypia or with atypia was associated with significantly increased BC risk in 2 or 4 times, correspondingly. The risk of developing BC for FCD with ductal or lobular carcinoma in situ is maximal and may be increased in 12 times. Progestogel is hormonal medicinal drug containing progesterone for local application. Results of undertaken studies and supervisions allow to conclude that progestogel is not only effective and safe drug for pathogenetic treatment of FCD and thus could be regarded as indirect factor to decrease BC risk.

В статье рассматриваются взаимосвязь этиологии и факторов риска фиброзно-кистозной болезни (ФКБ) и рака молочной железы (РМЖ), патогенез ФКБ в связи с повышением риска РМЖ, оценка риска РМЖ у больных ФКБ; патогенетическое лечение ФКБ, направленное на профилактику РМЖ; применение лекарственного препарата прожестожель для лечения ФКБ и профилактики РМЖ. ФКБ и РМЖ имеют общую этиологию, большинство факторов риска являются одинаковыми для них. Множественные факторы риска нарушают гормональный баланс в организме женщины, вызывают гиперэстрогению и гиперпролиферацию эпителия в ткани молочных желез, что приводит к развитию ФКБ, а при наличии врожденных или приобретенных повреждений генов – к развитию РМЖ. Решающим в оценке степени риска РМЖ у больных ФКБ является морфологическое исследование ткани молочных желез, полученной при биопсии. Риск РМЖ не повышается или является минимальным при непролиферативной форме ФКБ. При пролиферативной форме ФКБ без атипии риск РМЖ возрастает в 2 раза, с атипией – в 4 раза. Риск развития РМЖ при ФКБ с протоковой или дольковой карциномой in situ является максимальным и может увеличиваться в 12 раз. Прожестожель – гормональный лекарственный препарат, содержащий прогестерон, для местного применения. Результаты проведенных исследований и наблюдений позволяют заключить, что монотерапия препаратом прожестожель является эффективным и безопасным методом патогенетического лечения ФКБ, что может расцениваться как опосредованная профилактика риска РМЖ.

fibrocystic diseasebreast cancerrisk factorsetiologypathogenesismammographic densityepithelium proliferationcellular atypiaprogestogelprevention of breast cancerфиброзно-кистозная болезньрак молочной железыфакторы рискаэтиологияпатогенезмаммографическая плотностьпролиферация эпителияклеточная атипияпрожестожельпрофилактика рака молочной железы1. Коган И.Ю., Мясникова М.О. Диагностика и лечение мастопатии. СПб., 2010. 32 с. [Kogan I.Yu., Myasnikova M.O. Diagnosis and treatment of mastopathy. Sаint- Petersburg, 2010. 32 p. (In Russ.)].Коган И.Ю., Мясникова М.О. Диагностика и лечение мастопатии. СПб., 2010. 32 с. [Kogan I.Yu., Myasnikova M.O. Diagnosis and treatment of mastopathy. Sаint- Petersburg, 2010. 32 p. (In Russ.)].2. Onstad M., Stuckey A. Benign breast disorders. Obstet Gynecol Clin North Am 2013;40(3):459–73.Onstad M., Stuckey A. Benign breast disorders. Obstet Gynecol Clin North Am 2013;40(3):459–73.3. Guray M., Sahin A.A. Benign breast diseases: classification, diagnosis, and management. Oncologist 2006;11(5):435–49.Guray M., Sahin A.A. Benign breast diseases: classification, diagnosis, and management. Oncologist 2006;11(5):435–49.4. Santen R.J., Mansel R. Benign breast disorders. N Engl J Med 2005;353(3):275–85.Santen R.J., Mansel R. Benign breast disorders. N Engl J Med 2005;353(3):275–85.5. Злокачественные новообразования в России в 2013 году (заболеваемость и смертность). Под ред. А.Д. Каприна, В.В. Старинского, Г.В. Петровой. М., 2015. 250 с. [Malignant neoplasms in Russia in 2013 (morbidity and mortality). Ed. by A.D. Kaprin, V.V. Starinsky, G.V. Petrova. Moscow, 2015. 250 p. (In Russ.)].Злокачественные новообразования в России в 2013 году (заболеваемость и смертность). Под ред. А.Д. Каприна, В.В. Старинского, Г.В. Петровой. М., 2015. 250 с. [Malignant neoplasms in Russia in 2013 (morbidity and mortality). Ed. by A.D. Kaprin, V.V. Starinsky, G.V. Petrova. Moscow, 2015. 250 p. (In Russ.)].6. Рожкова Н.И., Меских Е.В., Бурдина Л.М. и др. Лекарственная патогенетическая коррекция доброкачественных заболеваний молочной железы. Опухоли женской репродуктивной системы 2008;(2):48–54. [Rozhkova N.I., Meskikh E.V., Burdina L.M. et al. Medicinal pathogenetic correction of benign breast disease. Opukholi zhenskoy reproduktivnoy sistemy = Tumors of the Female Reproductive System 2008;(2):48–54. (In Russ.)].Рожкова Н.И., Меских Е.В., Бурдина Л.М. и др. Лекарственная патогенетическая коррекция доброкачественных заболеваний молочной железы. Опухоли женской репродуктивной системы 2008;(2):48–54. [Rozhkova N.I., Meskikh E.V., Burdina L.M. et al. Medicinal pathogenetic correction of benign breast disease. Opukholi zhenskoy reproduktivnoy sistemy = Tumors of the Female Reproductive System 2008;(2):48–54. (In Russ.)].7. Семиглазов В.Ф., Семиглазов В.В., Клецель А.Е. Неинвазивные и инвазивные опухоли молочной железы. СПб., 2006. C. 6–60. [Semiglazov V.F., Semiglazov V.V., Kletsel A.E. Noninvasive and invasive breast tumors. Saint-Petersburg, 2006. Pp. 6–60. (In Russ.)].Семиглазов В.Ф., Семиглазов В.В., Клецель А.Е. Неинвазивные и инвазивные опухоли молочной железы. СПб., 2006. C. 6–60. [Semiglazov V.F., Semiglazov V.V., Kletsel A.E. Noninvasive and invasive breast tumors. Saint-Petersburg, 2006. Pp. 6–60. (In Russ.)].8. Беспалов В.Г. Лечение мастопатии и первичная профилактика рака молочной железы. Лечащий врач 2007;(5):88–9. [Bespalov V.G. The treatment of mastopathy and primary prevention of breast cancer. Lechashchiy vrach = Attending Physician 2007;(5):88–9. (In Russ.)].Беспалов В.Г. Лечение мастопатии и первичная профилактика рака молочной железы. Лечащий врач 2007;(5):88–9. [Bespalov V.G. The treatment of mastopathy and primary prevention of breast cancer. Lechashchiy vrach = Attending Physician 2007;(5):88–9. (In Russ.)].9. Высоцкая И.B., Погодина Е.М., Гладилина И.А. и др. Клиническая маммология (практическое руководство). Под ред. М.И. Давыдова, В.П. Летягина. М., 2010. C. 54–6. [Vysotskaya I.V., Pogodina E.M., Gladilina I.A. et al. Clinical mammology (practical guide). Ed. by M.I. Davydov, V.P. Letyagin. Moscow, 2010. Pp. 54–6. (In Russ.)].Высоцкая И.B., Погодина Е.М., Гладилина И.А. и др. Клиническая маммология (практическое руководство). Под ред. М.И. Давыдова, В.П. Летягина. М., 2010. C. 54–6. [Vysotskaya I.V., Pogodina E.M., Gladilina I.A. et al. Clinical mammology (practical guide). Ed. by M.I. Davydov, V.P. Letyagin. Moscow, 2010. Pp. 54–6. (In Russ.)].10. Любченко Л.Н. Генетическое тестирование при наследственном раке молочной железы. Практическая онкология 2014;15(3):107–17. [Lyubchenko L.N. Genetic testing for hereditary breast cancer. Prakticheskaya onkologiya = Practical Oncology 2014;15(3):107–17. (In Russ.)].Любченко Л.Н. Генетическое тестирование при наследственном раке молочной железы. Практическая онкология 2014;15(3):107–17. [Lyubchenko L.N. Genetic testing for hereditary breast cancer. Prakticheskaya onkologiya = Practical Oncology 2014;15(3):107–17. (In Russ.)].11. Семиглазов В.Ф., Семиглазов В.В. Рак молочной железы: биология, местное и системное лечение. М., 2014. 352 с. [Semiglazov V.F., Semiglazov V.V. Breast cancer: biology, local and systemic treatment. Moscow, 2014. 352 p. (In Russ.)].Семиглазов В.Ф., Семиглазов В.В. Рак молочной железы: биология, местное и системное лечение. М., 2014. 352 с. [Semiglazov V.F., Semiglazov V.V. Breast cancer: biology, local and systemic treatment. Moscow, 2014. 352 p. (In Russ.)].12. Colditz G.A., Bohlke K., Berkey C.S. Breast cancer risk accumulation starts early: prevention must also. Breast Cancer Res Treat 2014;145(3):567–79.Colditz G.A., Bohlke K., Berkey C.S. Breast cancer risk accumulation starts early: prevention must also. Breast Cancer Res Treat 2014;145(3):567–79.13. Meads C., Ahmed I., Riley R.D. A systematic review of breast cancer incidence risk prediction models with meta-analysis of their performance. Breast Cancer Res Treat 2012;132(2):365–77.Meads C., Ahmed I., Riley R.D. A systematic review of breast cancer incidence risk prediction models with meta-analysis of their performance. Breast Cancer Res Treat 2012;132(2):365–77.14. Pfeiffer R.M., Park Y., Kreimer A.R. et al. Risk prediction for breast, endometrial, and ovarian cancer in white women aged 50 y or older: derivation and validation from population-based cohort studies. PLoS Med 2013;10(7):e1001492.Pfeiffer R.M., Park Y., Kreimer A.R. et al. Risk prediction for breast, endometrial, and ovarian cancer in white women aged 50 y or older: derivation and validation from population-based cohort studies. PLoS Med 2013;10(7):e1001492.15. Горюшина О.Г. Мастопатия. Под ред. В.Ф. Семиглазова. СПб., 2000. 109 с. [Goryushina O.G. Mastopathy. Ed. by V.F. Semiglazov. Saint-Petersburg, 2000. 109 p. (In Russ.)].Горюшина О.Г. Мастопатия. Под ред. В.Ф. Семиглазова. СПб., 2000. 109 с. [Goryushina O.G. Mastopathy. Ed. by V.F. Semiglazov. Saint-Petersburg, 2000. 109 p. (In Russ.)].16. Мустафин Ч.К., Кузнецова С.В. Дисгормональные болезни молочной железы. Под ред. Е.Г. Пинхосевича. М., 2009. 126 с. [Mustafin Ch.K., Kuznetsova S.V. Dishormonal diseases of the breast. Ed. by E.G. Pinhosevich. Moscow, 2009. 126 p. (In Russ.)].Мустафин Ч.К., Кузнецова С.В. Дисгормональные болезни молочной железы. Под ред. Е.Г. Пинхосевича. М., 2009. 126 с. [Mustafin Ch.K., Kuznetsova S.V. Dishormonal diseases of the breast. Ed. by E.G. Pinhosevich. Moscow, 2009. 126 p. (In Russ.)].17. Пашов А.И., Коренев С.В. Доброкачественная дисплазия молочной железы в практике акушера-гинеколога. Калининград, 2015. 48 с. [Pashov A.I., Korenev S.V. Breast benign dysplasia in the practice of obstetrician-gynecologist. Kaliningrad, 2015. 48 p. (In Russ.)].Пашов А.И., Коренев С.В. Доброкачественная дисплазия молочной железы в практике акушера-гинеколога. Калининград, 2015. 48 с. [Pashov A.I., Korenev S.V. Breast benign dysplasia in the practice of obstetrician-gynecologist. Kaliningrad, 2015. 48 p. (In Russ.)].18. Чистяков С.С., Сельчук В.Ю., Гребенникова О.П. и др. Опухоли женской репродуктивной системы. Под ред. С.С. Чистякова. М., 2011. C. 53–83. [Chistyakov S.S., Selchuk V.Yu., Grebennikova O.P. et al. Tumors of the female reproductive system. Ed. by S.S. Chistyakov. Moscow, 2011. Pp. 53–83. (In Russ.)].Чистяков С.С., Сельчук В.Ю., Гребенникова О.П. и др. Опухоли женской репродуктивной системы. Под ред. С.С. Чистякова. М., 2011. C. 53–83. [Chistyakov S.S., Selchuk V.Yu., Grebennikova O.P. et al. Tumors of the female reproductive system. Ed. by S.S. Chistyakov. Moscow, 2011. Pp. 53–83. (In Russ.)].19. Frazier A.L., Rosenberg S.M. Preadolescent and adolescent risk factors for benign breast disease. J Adolesc Health 2013;52(5 Suppl):S36–40.Frazier A.L., Rosenberg S.M. Preadolescent and adolescent risk factors for benign breast disease. J Adolesc Health 2013;52(5 Suppl):S36–40.20. Jorgensen T.J., Helzlsouer K.J., Clipp S.C. et al. DNA repair gene variants associated with benign breast disease in high cancer risk women. Cancer Epidemiol Biomarkers Prev 2009;18(1):346–50.Jorgensen T.J., Helzlsouer K.J., Clipp S.C. et al. DNA repair gene variants associated with benign breast disease in high cancer risk women. Cancer Epidemiol Biomarkers Prev 2009;18(1):346–50.21. Pearlman M.D., Griffin J.L. Benign breast disease. Obstet Gynecol 2010;116(3):747–58.Pearlman M.D., Griffin J.L. Benign breast disease. Obstet Gynecol 2010;116(3):747–58.22. Беспалов В.Г. Новое в лечении мастопатии. Лечащий врач 2007;(3):92–3. [Bespalov V.G. What is new in treatment of mastopathy. Lechashchiy vrach = Attending Physician 2007;(3):92–3. (In Russ.)].Беспалов В.Г. Новое в лечении мастопатии. Лечащий врач 2007;(3):92–3. [Bespalov V.G. What is new in treatment of mastopathy. Lechashchiy vrach = Attending Physician 2007;(3):92–3. (In Russ.)].23. Зотов А.С., Белик Е.О. Мастопатии и рак молочной железы. М., 2005. 112 с. [Zotov A.S., Belik E.O. Mastopathy and breast cancer. Moscow, 2005. 112 p. (In Russ.)].Зотов А.С., Белик Е.О. Мастопатии и рак молочной железы. М., 2005. 112 с. [Zotov A.S., Belik E.O. Mastopathy and breast cancer. Moscow, 2005. 112 p. (In Russ.)].24. Нейштадт Э.Л., Воробьева О.А. Патология молочной железы. СПб., 2003. Pp. 137–66. [Neishtadt E.L., Vorobyeva O.A. Pathology of the breast. Saint-Petersburg, 2003. Pp. 137–66. (In Russ.)].Нейштадт Э.Л., Воробьева О.А. Патология молочной железы. СПб., 2003. Pp. 137–66. [Neishtadt E.L., Vorobyeva O.A. Pathology of the breast. Saint-Petersburg, 2003. Pp. 137–66. (In Russ.)].25. Hartmann L.C., Sellers T.A., Frost M.H. et al. Benign breast disease and the risk of breast cancer. N Engl J Med 2005;353(3):229–37.Hartmann L.C., Sellers T.A., Frost M.H. et al. Benign breast disease and the risk of breast cancer. N Engl J Med 2005;353(3):229–37.26. Morrow M., Schnitt S.J., Norton L. Current management of lesions associated with an increased risk of breast cancer. Nat Rev Clin Oncol 2015;12(4):227–38.Morrow M., Schnitt S.J., Norton L. Current management of lesions associated with an increased risk of breast cancer. Nat Rev Clin Oncol 2015;12(4):227–38.27. Silvera S., Rohan T. Benign proliferative epithelial disorders of the breast: a review of the epidemiologic evidence. Breast Cancer Res Treat 2008;110(3):397–409.Silvera S., Rohan T. Benign proliferative epithelial disorders of the breast: a review of the epidemiologic evidence. Breast Cancer Res Treat 2008;110(3):397–409.28. Castells X., Domingo L., Corominas J.M. et al. Breast cancer risk after diagnosis by screening mammography of nonproliferative or proliferative benign breast disease: a study from a population-based screening program. Breast Cancer Res Treat 2015;149(1):237–44.Castells X., Domingo L., Corominas J.M. et al. Breast cancer risk after diagnosis by screening mammography of nonproliferative or proliferative benign breast disease: a study from a population-based screening program. Breast Cancer Res Treat 2015;149(1):237–44.29. Nassar A., Visscher D.W., Degnim A.C. et al. Complex fibroadenoma and breast cancer risk: a Mayo Clinic Benign Breast Disease Cohort Study. Breast Cancer Res Treat 2015;153(2):397–405.Nassar A., Visscher D.W., Degnim A.C. et al. Complex fibroadenoma and breast cancer risk: a Mayo Clinic Benign Breast Disease Cohort Study. Breast Cancer Res Treat 2015;153(2):397–405.30. Visscher D.W., Nassar A., Degnim A.C. et al. Sclerosing adenosis and risk of breast cancer. Breast Cancer Res Treat 2014;144(1):205–12.Visscher D.W., Nassar A., Degnim A.C. et al. Sclerosing adenosis and risk of breast cancer. Breast Cancer Res Treat 2014;144(1):205–12.31. Aroner S.A., Collins L.C., Connolly J.L. et al. Radial scars and subsequent breast cancer risk: results from the Nurses’ Health Studies. Breast Cancer Res Treat 2013;139(1):277–85.Aroner S.A., Collins L.C., Connolly J.L. et al. Radial scars and subsequent breast cancer risk: results from the Nurses’ Health Studies. Breast Cancer Res Treat 2013;139(1):277–85.32. Cote M.L., Ruterbusch J.J., Alosh B. et al. Benign breast disease and the risk of subsequent breast cancer in African American women. Cancer Prev Res (Phila) 2012;5(12):1375–80.Cote M.L., Ruterbusch J.J., Alosh B. et al. Benign breast disease and the risk of subsequent breast cancer in African American women. Cancer Prev Res (Phila) 2012;5(12):1375–80.33. Goldacre M.J., Abisgold J.D., Yeates D.G., Vessey M.P. Benign breast disease and subsequent breast cancer: English record linkage studies. J Public Health (Oxf) 2010;32(4):565–71.Goldacre M.J., Abisgold J.D., Yeates D.G., Vessey M.P. Benign breast disease and subsequent breast cancer: English record linkage studies. J Public Health (Oxf) 2010;32(4):565–71.34. Kabat G.C., Jones J.G. Olson N. et al. A multi-center prospective cohort study of benign breast disease and risk of subsequent breast cancer. Cancer Causes Control 2010;21(6):821–8.Kabat G.C., Jones J.G. Olson N. et al. A multi-center prospective cohort study of benign breast disease and risk of subsequent breast cancer. Cancer Causes Control 2010;21(6):821–8.35. Worsham M.J., Raju U., Lu M. et al. Risk factors for breast cancer from benign breast disease in a diverse population. Breast Cancer Res Treat 2009;118(1):1–7.Worsham M.J., Raju U., Lu M. et al. Risk factors for breast cancer from benign breast disease in a diverse population. Breast Cancer Res Treat 2009;118(1):1–7.36. Ashbeck E.L., Rosenberg R.D., Stauber P.M., Key C.R. Benign breast biopsy diagnosis and subsequent risk of breast cancer. Cancer Epidemiol Biomarkers Prev 2007;16(3): 467–72.Ashbeck E.L., Rosenberg R.D., Stauber P.M., Key C.R. Benign breast biopsy diagnosis and subsequent risk of breast cancer. Cancer Epidemiol Biomarkers Prev 2007;16(3): 467–72.37. Degnim A.C., Visscher D.W., Berman H.K. et al. Stratification of breast cancer risk in women with atypia: a Mayo cohort study. J Clin Oncol 2007;25(19):2671–7.Degnim A.C., Visscher D.W., Berman H.K. et al. Stratification of breast cancer risk in women with atypia: a Mayo cohort study. J Clin Oncol 2007;25(19):2671–7.38. Worsham M.J., Abrams J., Raju U. Breast cancer incidence in a cohort of women with benign breast disease from a multiethnic, primary health care population. Breast J 2007;13(2):115–21.Worsham M.J., Abrams J., Raju U. Breast cancer incidence in a cohort of women with benign breast disease from a multiethnic, primary health care population. Breast J 2007;13(2):115–21.39. Collins L.C., Baer H.J., Tamimi R.M. et al. The influence of family history on breast cancer risk in women with biopsy-confirmed benign breast disease: results from the Nurses’ Health Study. Cancer 2006;107(6):1240–7.Collins L.C., Baer H.J., Tamimi R.M. et al. The influence of family history on breast cancer risk in women with biopsy-confirmed benign breast disease: results from the Nurses’ Health Study. Cancer 2006;107(6):1240–7.40. Lewis J.T., Hartmann L.C., Vierkant R.A. et al. An analysis of breast cancer risk in women with single, multiple, and atypical papilloma. Am J Surg Pathol 2006;30(6):665–72.Lewis J.T., Hartmann L.C., Vierkant R.A. et al. An analysis of breast cancer risk in women with single, multiple, and atypical papilloma. Am J Surg Pathol 2006;30(6):665–72.41. Plu-Bureau G., Le M.G., Sitruk-Ware R., Thalabard J.C. Cyclical mastalgia and breast cancer risk: results of a French cohort study. Cancer Epidemiol Biomarkers Prev 2006;15(6):1229–31.Plu-Bureau G., Le M.G., Sitruk-Ware R., Thalabard J.C. Cyclical mastalgia and breast cancer risk: results of a French cohort study. Cancer Epidemiol Biomarkers Prev 2006;15(6):1229–31.42. Sanders M.E., Page D.L., Simpson J.F. et al. Interdependence of radial scar and proliferative disease with respect to invasive breast carcinoma risk in patients with benign breast biopsies. Cancer 2006;106(7):1453–61.Sanders M.E., Page D.L., Simpson J.F. et al. Interdependence of radial scar and proliferative disease with respect to invasive breast carcinoma risk in patients with benign breast biopsies. Cancer 2006;106(7):1453–61.43. Wang J., Costantino J.P., Tan-Chiu E. et al. Lower-category benign breast disease and he risk of invasive breast cancer. J Natl Cancer Inst 2004;96(8):616–20.Wang J., Costantino J.P., Tan-Chiu E. et al. Lower-category benign breast disease and he risk of invasive breast cancer. J Natl Cancer Inst 2004;96(8):616–20.44. Shaaban A.M., Sloane J.P., West C.R. et al. Histopathologic types of benign breast esions and the risk of breast cancer: case-control study. Am J Surg Pathol 2002;26(4):421–30Shaaban A.M., Sloane J.P., West C.R. et al. Histopathologic types of benign breast esions and the risk of breast cancer: case-control study. Am J Surg Pathol 2002;26(4):421–3045. Byrne C., Connolly J.L., Colditz G.A., Schnitt S.J. Biopsy confirmed benign breast disease, postmenopausal use of exogenous female hormones, and breast carcinoma risk. Cancer 2000;89(10):2046–52.Byrne C., Connolly J.L., Colditz G.A., Schnitt S.J. Biopsy confirmed benign breast disease, postmenopausal use of exogenous female hormones, and breast carcinoma risk. Cancer 2000;89(10):2046–52.46. Dupont W.D., Page D.L., Parl F.F. et al. Long-term risk of breast cancer in women with fibroadenoma. N Engl J Med 1994;331(1): 10–5.Dupont W.D., Page D.L., Parl F.F. et al. Long-term risk of breast cancer in women with fibroadenoma. N Engl J Med 1994;331(1): 10–5.47. Krieger N., Hiatt R.A. Risk of breast cancer after benign breast diseases. Variation by histologic type, degree of atypia, age at biopsy, and length of follow-up. Am J Epidemiol 1992;135(6):619–31.Krieger N., Hiatt R.A. Risk of breast cancer after benign breast diseases. Variation by histologic type, degree of atypia, age at biopsy, and length of follow-up. Am J Epidemiol 1992;135(6):619–31.48. Hornberger J., Chen S.C., Li Q. et al. Proliferative epithelial disease identified in nipple aspirate fluid and risk of developing breast cancer: a systematic review. Curr Med Res Opin 2015;31(2):253–62.Hornberger J., Chen S.C., Li Q. et al. Proliferative epithelial disease identified in nipple aspirate fluid and risk of developing breast cancer: a systematic review. Curr Med Res Opin 2015;31(2):253–62.49. Kabat G.C., Jones J.G., Olson N. et al. Risk factors for breast cancer in women biopsied for benign breast disease: a nested case-control study. Cancer Epidemiol 2010;34(1):34–9.Kabat G.C., Jones J.G., Olson N. et al. Risk factors for breast cancer in women biopsied for benign breast disease: a nested case-control study. Cancer Epidemiol 2010;34(1):34–9.50. Васильев Д.А., Зайцев А.Н., Берштейн Л.М. Маммографическая плотность молочных желез и определяющие ее факторы в свете повышенного онкологического риска. Опухоли женской репродуктивной системы 2011;(3):15–22. [Vasilyev D.A., Zaitsev A.N., Berstein L.M. Mammographic density and factors determining it from the point of view of high oncological risks. Opukholi zhenskoy reproduktivnoy sistemy = Tumors of the Female Reproductive System 2011;(3):15–22. (In Russ.)].Васильев Д.А., Зайцев А.Н., Берштейн Л.М. Маммографическая плотность молочных желез и определяющие ее факторы в свете повышенного онкологического риска. Опухоли женской репродуктивной системы 2011;(3):15–22. [Vasilyev D.A., Zaitsev A.N., Berstein L.M. Mammographic density and factors determining it from the point of view of high oncological risks. Opukholi zhenskoy reproduktivnoy sistemy = Tumors of the Female Reproductive System 2011;(3):15–22. (In Russ.)].51. Pettersson A., Graff R.E., Ursin G. et al. Mammographic density phenotypes and risk of dreast cancer: a meta-analysis. J Natl Cancer Inst 2014;106(5). pii: dju078.Pettersson A., Graff R.E., Ursin G. et al. Mammographic density phenotypes and risk of dreast cancer: a meta-analysis. J Natl Cancer Inst 2014;106(5). pii: dju078.52. Tice J.A., Miglioretti D.L., Li C.S. et al. Breast density and benign breast disease: risk assessment to identify women at high risk of breast cancer. J Clin Oncol 2015;33(28):3137–43.Tice J.A., Miglioretti D.L., Li C.S. et al. Breast density and benign breast disease: risk assessment to identify women at high risk of breast cancer. J Clin Oncol 2015;33(28):3137–43.53. Friedenreich C., Bryant H., Alexander F. et al. Risk factors for benign proliferative breast disease. Int J Epidemiol 2000;29(4):637–44.Friedenreich C., Bryant H., Alexander F. et al. Risk factors for benign proliferative breast disease. Int J Epidemiol 2000;29(4):637–44.54. Boyd N.F., Jensen H.M., Cooke G. et al. Mammographic densities and the prevalence and incidence of histological types of benignbreast disease. Reference Pathologists of the Canadian National Breast Screening Study. Eur J Cancer Prev 2000;9(1):15–24.Boyd N.F., Jensen H.M., Cooke G. et al. Mammographic densities and the prevalence and incidence of histological types of benignbreast disease. Reference Pathologists of the Canadian National Breast Screening Study. Eur J Cancer Prev 2000;9(1):15–24.55. Dyrstad S.W., Yan Y., Fowler A.M., Colditz G.A. Breast cancer risk associated with benign breast disease: systematic review and meta-analysis. Breast Cancer Res Treat 2015;149(3):569–75.Dyrstad S.W., Yan Y., Fowler A.M., Colditz G.A. Breast cancer risk associated with benign breast disease: systematic review and meta-analysis. Breast Cancer Res Treat 2015;149(3):569–75.56. Socolov D., Anghelache I., Ilea C. et al. Benign breast disease and the risk of breast cancer in the next 15 years. Rev Med Chir Soc Med Nat Iasi 2015;119(1):135–40.Socolov D., Anghelache I., Ilea C. et al. Benign breast disease and the risk of breast cancer in the next 15 years. Rev Med Chir Soc Med Nat Iasi 2015;119(1):135–40.57. Высоцкая И.В., Летягин В.П., Ким Е.А., Левкина Н.В. Практические рекомендации по лекарственной коррекции диффузной дисгормональной дисплазии молочных желез. Опухоли женской репродуктивной системы 2014;(2):45–52. [Vysotskaya I.V., Letyagin V.P., Kim E.A., Levkina N.V. Practical guidelines for drug correction of diffuse dyshormonal dysplasia of the breast. Opukholi zhenskoy reproduktivnoy sistemy = Tumors of the Female Reproductive System 2014;(2):45–52. (In Russ.)].Высоцкая И.В., Летягин В.П., Ким Е.А., Левкина Н.В. Практические рекомендации по лекарственной коррекции диффузной дисгормональной дисплазии молочных желез. Опухоли женской репродуктивной системы 2014;(2):45–52. [Vysotskaya I.V., Letyagin V.P., Kim E.A., Levkina N.V. Practical guidelines for drug correction of diffuse dyshormonal dysplasia of the breast. Opukholi zhenskoy reproduktivnoy sistemy = Tumors of the Female Reproductive System 2014;(2):45–52. (In Russ.)].58. Высоцкая И.В., Летягин В.П., Левкина Н.В. Гормональная терапия диффузной мастопатии. Опухоли женской репродуктивной системы 2014;(3):53–7. [Vysotskaya I.V., Letyagin V.P., Levkina N.V. Hormone therapy for diffuse mastopathy. Opukholi zhenskoy reproduktivnoy sistemy = Tumors of the Female Reproductive System 2014;(3):53–7. (In Russ.)].Высоцкая И.В., Летягин В.П., Левкина Н.В. Гормональная терапия диффузной мастопатии. Опухоли женской репродуктивной системы 2014;(3):53–7. [Vysotskaya I.V., Letyagin V.P., Levkina N.V. Hormone therapy for diffuse mastopathy. Opukholi zhenskoy reproduktivnoy sistemy = Tumors of the Female Reproductive System 2014;(3):53–7. (In Russ.)].59. Меских Е.В., Рожкова Н.И. Применение прожестожеля при диффузных формах мастопатии. Опухоли женской репродуктивной системы 2012;(1):57–60. [Meskikh E.V., Rozhkova N.I. Use of progestogel in diffuse forms of mastopathy. Opukholi zhenskoy reproduktivnoy sistemy = Tumors of the Female Reproductive System 2012;(1):57–60. (In Russ.)].Меских Е.В., Рожкова Н.И. Применение прожестожеля при диффузных формах мастопатии. Опухоли женской репродуктивной системы 2012;(1):57–60. [Meskikh E.V., Rozhkova N.I. Use of progestogel in diffuse forms of mastopathy. Opukholi zhenskoy reproduktivnoy sistemy = Tumors of the Female Reproductive System 2012;(1):57–60. (In Russ.)].60. Коган И.Ю., Мясникова М.О., Мусина Е.В. Прогестерон в лечении мастопатии. Под ред. Э.К. Айламазяна. СПб., 2012. 68 с. [Kogan I.Yu., Myasnikova M.O., Musina E.V. Progesterone in the treatment of mastopathy. Ed. by E.K. Aylamazyan. Saint-Petersburg, 2012. 68 p. (In Russ.)].Коган И.Ю., Мясникова М.О., Мусина Е.В. Прогестерон в лечении мастопатии. Под ред. Э.К. Айламазяна. СПб., 2012. 68 с. [Kogan I.Yu., Myasnikova M.O., Musina E.V. Progesterone in the treatment of mastopathy. Ed. by E.K. Aylamazyan. Saint-Petersburg, 2012. 68 p. (In Russ.)].61. De Boever J., Verheugen C., Van Maele G., Vandekerckhove D. Steroid concentrations in erum, glandular breast tissue, and breast cyst fluid of control and progesterone-treated patients. Endocrinology of Cystic Breast Disease. Ed. by A. Angeli. New York: Raven Press, 1983. Рр. 93–9.De Boever J., Verheugen C., Van Maele G., Vandekerckhove D. Steroid concentrations in erum, glandular breast tissue, and breast cyst fluid of control and progesterone-treated patients. Endocrinology of Cystic Breast Disease. Ed. by A. Angeli. New York: Raven Press, 1983. Рр. 93–9.62. Du J.Y., Sanchez P., Kim L. et al. Percutaneous progesterone delivery via cream or gel application in postmenopausal women: a randomized cross-over study of progesterone levels in serum, whole blood, saliva, and capillary blood. Menopause 2013;20(11):1169–75.Du J.Y., Sanchez P., Kim L. et al. Percutaneous progesterone delivery via cream or gel application in postmenopausal women: a randomized cross-over study of progesterone levels in serum, whole blood, saliva, and capillary blood. Menopause 2013;20(11):1169–75.63. Zava D.T., Groves M.N., Stanczyk F.Z. Percutaneous absorption of progesterone. Maturitas 2014;77(2):91–2.Zava D.T., Groves M.N., Stanczyk F.Z. Percutaneous absorption of progesterone. Maturitas 2014;77(2):91–2.64. Sitruk-Ware R., Sterkers N., Mauvais-Jarvis P. Benign breast disease I: hormonal investigation. Obstet Gynecol 1979;53(4):457–60.Sitruk-Ware R., Sterkers N., Mauvais-Jarvis P. Benign breast disease I: hormonal investigation. Obstet Gynecol 1979;53(4):457–60.65. Коган И.Ю., Мусина Е.В. Местное применение микронизированного прогестерона у больных репродуктивного возраста с мастопатией. Акушерство и гинекология 2012;(2):102–6. [Kogan I.Yu., Musina E.V. Topical application of micronized progesterone in patients of reproductive age with mastopathy. Akusherstvo i ginekologiya = Obstetrics and Gynecology 2012;(2):102–6. (In Russ.)].Коган И.Ю., Мусина Е.В. Местное применение микронизированного прогестерона у больных репродуктивного возраста с мастопатией. Акушерство и гинекология 2012;(2):102–6. [Kogan I.Yu., Musina E.V. Topical application of micronized progesterone in patients of reproductive age with mastopathy. Akusherstvo i ginekologiya = Obstetrics and Gynecology 2012;(2):102–6. (In Russ.)].66. Obr A.E., Edwards D.P. The biology of progesterone receptor in the normal mammary gland and in breast cancer. Mol Cell Endocrinol 2012;357(1):4–17.Obr A.E., Edwards D.P. The biology of progesterone receptor in the normal mammary gland and in breast cancer. Mol Cell Endocrinol 2012;357(1):4–17.67. Pasqualini J.R. Differential effects of progestins on breast tissue enzymes. Maturitas 2003;46(Suppl l):S45–54.Pasqualini J.R. Differential effects of progestins on breast tissue enzymes. Maturitas 2003;46(Suppl l):S45–54.68. Barrat J., de Lignieres B. , Marpeau L. et al. Effet in vivo de l’administration locale de progesterone sur l’activité mitotique des galactophores humains. J Gynecol Obstet Biol Reprod (Paris) 1990;19(3):269–74.Barrat J., de Lignieres B. , Marpeau L. et al. Effet in vivo de l’administration locale de progesterone sur l’activité mitotique des galactophores humains. J Gynecol Obstet Biol Reprod (Paris) 1990;19(3):269–74.69. Tanos T., Brisken C. What signals operate in the mammary niche? Breast Dis 2008;29(1):69–82.Tanos T., Brisken C. What signals operate in the mammary niche? Breast Dis 2008;29(1):69–82.70. Plu-Bureau G., Le M.G., Thalabard J.C. et al. Percutaneous progesterone use and risk of breast cancer: Results from a French cohort study of premenopausal women with benign breast disease. Cancer Det Prev 1999;23(4): 290–6.Plu-Bureau G., Le M.G., Thalabard J.C. et al. Percutaneous progesterone use and risk of breast cancer: Results from a French cohort study of premenopausal women with benign breast disease. Cancer Det Prev 1999;23(4): 290–6.