Роль овариальной супрессии в адъювантной терапии рака молочной железы

Адъювантная эндокринная терапия является неотъемлемым компонентом лечения резектабельного люминального рака молочной железы. Стандартом в течение многих лет было назначение монотерапии тамоксифеном или ингибиторов ароматазы, однако недавние исследования показали, что добавление овариальной супрессии статистически значимо увеличивает показатели выживаемости у пациенток с высоким риском рецидива и с факторами неблагоприятного прогноза. В данном обзоре литературы мы проанализировали последние данные, касающиеся роли овариальной супрессии в адъювантной терапии гормон-положительного рака молочной железы. Подавление функции яичников является наиболее эффективным у молодых пациенток (до 35 лет) в пременопаузе при наличии факторов неблагоприятного прогноза (показания к [нео-]адъювантной ХТ, G3 и др.) Авторами было отмечено, что использование ингибиторов ароматазы вместо тамоксифена у данной подгруппы значимо снижало риск рецидива рака молочной железы. Овариальная супрессия, в особенности в комбинации с ингибиторами ароматазы, сопровождалась увеличением частоты нежелательных побочных явлений, в частности остеопороза и переломов костей, которая может быть снижена путем назначения адекватной сопроводительной терапии ОМА. Оптимальная продолжительность подавления функции яичников также не определена, однако, учитывая результаты крупных клинических исследований, проведение двухлетнего курса представляется оптимальным. В проведенных протоколах не было отмечено значимого влияния временной овариальной супрессии на вероятность последующей беременности.

1. Cathcart-Rake E.J. et al. Breast Cancer in Adolescent and Young Adult Women Under the Age of 40 Years. JCO Oncol Pract. 2021. Vol. 17, No. 6. P. 305–313.

2. Adami H.-O. et al. The Relation between Survival and Age at Diagnosis in Breast Cancer. New England Journal of Medicine. Massachusetts Medical Society, 1986. Vol. 315, No. 9. P. 559–563.

3. DeSantis C.E. et al. Breast cancer statistics, 2019. CA: A Cancer Journal for Clinicians. 2019. Vol. 69, No. 6. P. 438–451.

4. Pagani O. et al. Absolute Improvements in Freedom from Distant Recurrence to Tailor Adjuvant Endocrine Therapies for Premenopausal Women: Results from TEXT and SOFT. J Clin Oncol. 2020. Vol. 38, No. 12. P. 1293–1303.

5. Ribnikar D. et al. Breast cancer under age 40: A different approach. Curr Treat Options Oncol. 2015. Vol. 16, No. 4. P. 16.

6. Siegel R.L. et al. Cancer statistics, 2022. CA Cancer J Clin. 2022. Vol. 72, No. 1. P. 7–33.

7. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005. Vol. 365, No. 9472. P. 1687–1717.

8. Regan M.M. et al. Premenopausal endocrine-responsive early breast cancer: who receives chemotherapy? Ann Oncol. 2008. Vol. 19, No. 7. P. 1231–1241.

9. Bardia A., Hurvitz S. Targeted Therapy for Premenopausal Women with HR+, HER2– Advanced Breast Cancer: Focus on Special Considerations and Latest Advances. Clinical Cancer Research. 2018. Vol. 24, No. 21. P. 5206–5218.

10. Beatson G. T. On the Treatment of Inoperable Cases of Carcinoma of the Mamma: Suggestions for a New Method of Treatment, with Illustrative Cases. Trans Med Chir Soc Edinb. 1896. Vol. 15. P. 153–179.

11. Jensen E.V. From chemical warfare to breast cancer management. Nat Med. 2004. Vol. 10, No. 10. P. 1018–1021.

12. Ranu H.S., Burlin T.E., Hutton W.C. The effects of x-irradiation on the mechanical properties of skin. Phys Med Biol. 1975. Vol. 20, No. 1. P. 96–105.

13. Ward H.W. Anti-oestrogen therapy for breast cancer: A trial of tamoxifen at two dose levels. Br Med J. 1973. Vol. 1, No. 5844. P. 13–14.

14. Fisher B. et al. Treatment of lymph-node-negative, oestrogen-receptor-positive breast cancer: long-term findings from National Surgical Adjuvant Breast and Bowel Project randomised clinical trials. Lancet. 2004. Vol. 364, No. 9437. P. 858–868.

15. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005. Vol. 365, No. 9472. P. 1687–1717.

16. Bergman L. et al. Risk and prognosis of endometrial cancer after tamoxifen for breast cancer. Comprehensive Cancer Centres’ ALERT Group. Assessment of Liver and Endometrial cancer Risk following Tamoxifen. Lancet. 2000. Vol. 356, No. 9233. P. 881–887.

17. Cutuli B. et al. Adjuvant tamoxifen in breast-cancer-treatment in postmenopausal women – occurrence of thromboembolic complications. Oncol Rep. 1994. Vol. 1, No. 1. P. 59–63.

18. Fisher B. et al. Endometrial cancer in tamoxifen-treated breast cancer patients: findings from the National Surgical Adjuvant Breast and Bowel Project (NSABP) B‑14. J Natl Cancer Inst. 1994. Vol. 86, No. 7. P. 527–537.

19. Jordan V.C. Tamoxifen: Toxicities and drug resistance during the treatment and prevention of breast cancer. Annu Rev Pharmacol Toxicol. 1995. Vol. 35. P. 195–211.

20. Meisel J.L. et al. Evolution of Targeted Therapy in Breast Cancer: Where Precision Medicine Began. American Society of Clinical Oncology Educational Book. American Society of Clinical Oncology, 2018. No. 38. P. 78–86.

21. Coombes R. C. et al. A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. N Engl J Med. 2004. Vol. 350, No. 11. P. 1081–1092.

22. Baum M. et al. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial. Lancet. 2002. Vol. 359, No. 9324. P. 2131–2139.

23. Regan M.M. et al. Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1–98 randomised clinical trial at 8·1 years median follow-up. Lancet Oncol. 2011. Vol. 12, No. 12. P. 1101–1108.

24. Höffken K., Kath R. The role of LH-RH analogues in the adjuvant and palliative treatment of breast cancer. Recent Results Cancer Res. 2000. Vol. 153. P. 61–70.

25. Klijn J.G., de Jong F.H. Treatment with a luteinising-hormone-releasing-hormone analogue (buserelin) in premenopausal patients with metastatic breast cancer. Lancet. 1982. Vol. 1, No. 8283. P. 1213–1216.

26. Puhalla S., Bhattacharya S., Davidson N.E. Hormonal therapy in breast cancer: A model disease for the personalization of cancer care. Mol Oncol. 2012. Vol. 6, No. 2. P. 222–236.

27. Belfiglio M. et al. Twelve-year mortality results of a randomized trial of 2 versus 5 years of adjuvant tamoxifen for postmenopausal early-stage breast carcinoma patients (SITAM 01). Cancer. 2005. Vol. 104, No. 11. P. 2334–2339.

28. Cardoso F. et al. Early breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†. Annals of Oncology. Elsevier, 2019. Vol. 30, No. 8. P. 1194–1220.

29. Robertson J.F. et al. Combined endocrine effects of LHRH agonist (Zoladex) and tamoxifen (Nolvadex) therapy in premenopausal women with breast cancer. Br J Surg. 1989. Vol. 76, No. 12. P. 1262–1265.

30. Cuzick J. et al. Use of luteinising-hormone-releasing hormone agonists as adjuvant treatment in premenopausal patients with hormone-receptor-positive breast cancer: a meta-analysis of individual patient data from randomised adjuvant trials. Lancet. 2007. Vol. 369, No. 9574. P. 1711–1723.

31. Gnant M.F.X. et al. Zoledronic acid prevents cancer treatment-induced bone loss in premenopausal women receiving adjuvant endocrine therapy for hormone-responsive breast cancer: a report from the Austrian Breast and Colorectal Cancer Study Group. J Clin Oncol. 2007. Vol. 25, No. 7. P. 820–828.

32. Partin J.F. Special Considerations in Patients with Early-Stage Breast Cancer and Survivors. Obstetrics and Gynecology Clinics of North America. 2022. Vol. 49, No. 1. P. 195–208.

33. Low-Risk Breast Cancer Survivors Experience Long-Term Symptoms and Concerns. P. 4.

34. Ekenga C.C. et al. Early-stage breast cancer and employment participation after two years of follow-up: A comparison with age-matched controls. Cancer. 2018. Vol. 124, No. 9. P. 2026–2035.

35. de Oliveira N.P.D. et al. Functional Disability in Women Submitted to Breast Cancer Treatment. Asian Pac J Cancer Prev. 2017. Vol. 18, No. 5. P. 1207–1214.

36. Rocca W.A. et al. Survival patterns after oophorectomy in premenopausal women: a population-based cohort study. The Lancet Oncology. Elsevier, 2006. Vol. 7, No. 10. P. 821–828.

37. Francis P. A. et al. Tailoring Adjuvant Endocrine Therapy for Premenopausal Breast Cancer. New England Journal of Medicine. Massachusetts Medical Society, 2018. Vol. 379, No. 2. P. 122–137.

38. Bernhard J. et al. Patient-reported outcomes with adjuvant exemestane versus tamoxifen in premenopausal women with early breast cancer undergoing ovarian suppression (TEXT and SOFT): a combined analysis of two phase 3 randomised trials. The Lancet Oncology. 2015. Vol. 16, No. 7. P. 848–858.

39. Ingle C. Meta-analysis of breast cancer outcomes in adjuvant trials of aromatase inhibitors versus tamoxifen. Journal of clinical… 2010.

40. Andriyanto D.R. et al. Comparison of outcomes in patients with luminal type breast cancer treated with a gonadotropin-releasing hormone analog or bilateral salpingo-oophorectomy: A cohort retrospective study. Annals of Medicine and Surgery. 2022. Vol. 77. P. 103614.

41. Suh K.J. et al. KoreaMed Synapse. Cancer Res Treat. Korean Cancer Association, 2017. Vol. 49, No. 4. P. 1153–1163.

42. Hsieh A.H.-C. et al. Goserelin toxicities and preferences for ovarian suppression method in pre-menopausal women with breast cancer. Internal Medicine Journal. 2016. Vol. 46, No. 10. P. 1153–1159.

43. Francis P.A. et al. Adjuvant ovarian suppression in premenopausal breast cancer. N Engl J Med. 2015. Vol. 372, No. 5. P. 436–446.

44. Pagani O. et al. Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. N Engl J Med. 2014. Vol. 371, No. 2. P. 107–118.

45. Regan M.M. et al. Adjuvant treatment of premenopausal women with endocrine-responsive early breast cancer: design of the TEXT and SOFT trials. Breast. 2013. Vol. 22, No. 6. P. 1094–1100.

46. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials. Lancet. 2015. Vol. 386, No. 10001. P. 1341–1352.

47. Bartlett J.M.S. et al. HER2 status predicts for upfront AI benefit: A TRANS-AIOG meta-analysis of 12,129 patients from ATAC, BIG 1–98 and TEAM with centrally determined HER2. Eur J Cancer. 2017. Vol. 79. P. 129–138.

48. Zhou Q. et al. Prognostic impact of chemotherapy-induced amenorrhea on premenopausal breast cancer: A meta-analysis of the literature. Menopause. 2015. Vol. 22, No. 10. P. 1091.

49. Sparano J.A. et al. Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer. New England Journal of Medicine. Massachusetts Medical Society, 2018. Vol. 379, No. 2. P. 111–121.

50. Piccart M. et al. 70-gene signature as an aid for treatment decisions in early breast cancer: updated results of the phase 3 randomised MINDACT trial with an exploratory analysis by age. The Lancet Oncology. Elsevier, 2021. Vol. 22, No. 4. P. 476–488.

51. Regan M.M. et al. Abstract GS2–05: Randomized comparison of adjuvant aromatase inhibitor exemestane (E) plus ovarian function suppression (OFS) vs tamoxifen (T) plus OFS in premenopausal women with hormone receptor-positive (HR+) early breast cancer (BC): update of the combined TEXT and SOFT trials. Cancer Research. 2022. Vol. 82, No. 4_Supplement. P. GS2–05GS2–05 p.

52. Bradley R. et al. Aromatase inhibitors versus tamoxifen in premenopausal women with oestrogen receptor-positive early-stage breast cancer treated with ovarian suppression: A patient-level meta-analysis of 7030 women from four randomised trials. The Lancet Oncology. Elsevier, 2022. Vol. 23, No. 3. P. 382–392.

53. Goss P.E. et al. Exemestane Versus Anastrozole in Postmenopausal Women with Early Breast Cancer: NCIC CTG MA.27 – A Randomized Controlled Phase III Trial. J Clin Oncol. 2013. Vol. 31, No. 11. P. 1398–1404.

54. Smith I. et al. Comparative Efficacy and Safety of Adjuvant Letrozole Versus Anastrozole in Postmenopausal Patients with Hormone Receptor-Positive, Node-Positive Early Breast Cancer: Final Results of the Randomized Phase III Femara Versus Anastrozole Clinical Evaluation (FACE) Trial.

55. Pan H. et al. 20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years. New England Journal of Medicine. Massachusetts Medical Society, 2017. Vol. 377, No. 19. P. 1836–1846.

56. Jiang M. et al. Adjuvant ovarian suppression for premenopausal hormone receptor-positive breast cancer: A network meta-analysis. Medicine. 2021. Vol. 100, No. 33. P. e26949.

57. Baek S.Y. et al. Adding ovarian function suppression to tamoxifen in young women with hormone-sensitive breast cancer who remain premenopausal or resume menstruation after chemotherapy: 8-year follow-up of the randomized ASTRRA trial. JCO. Wolters Kluwer, 2022. Vol. 40, No. 16_suppl. P. 506–506.

58. Buus R. et al. Molecular Drivers of Oncotype DX, Prosigna, EndoPredict, and the Breast Cancer Index: A TransATAC Study. JCO. Wolters Kluwer, 2021. Vol. 39, No. 2. P. 126–135.

59. Arboleda B. et al. Ovarian Function Suppression: A Deeper Consideration of the Role in Early Breast Cancer and its Potential Impact on Patient Outcomes: A Consensus Statement from an International Expert Panel. The Oncologist. 2022. P. oyac101.

60. Bui K.T. et al. Ovarian suppression for adjuvant treatment of hormone receptor-positive early breast cancer. Cochrane Database of Systematic Reviews. John Wiley & Sons, Ltd, 2020. No. 3.

61. Ribi K. et al. Adjuvant Tamoxifen Plus Ovarian Function Suppression Versus Tamoxifen Alone in Premenopausal Women with Early Breast Cancer: Patient-Reported Outcomes in the Suppression of Ovarian Function Trial. JCO. Wolters Kluwer, 2016. Vol. 34, No. 14. P. 1601–1610.

62. Adjuvant bisphosphonate treatment in early breast cancer: Meta-analyses of individual patient data from randomised trials. The Lancet. 2015. Vol. 386, No. 10001. P. 1353–1361.

63. Imam B. et al. Role of Bisphosphonates in Postmenopausal Women with Osteoporosis to Prevent Future Fractures: A Literature Review. Cureus. Vol. 11, No. 8. P. e5328.

64. Black D.M., Rosen C.J. Clinical Practice. Postmenopausal Osteoporosis. N Engl J Med. 2016. Vol. 374, No. 3. P. 254–262.

65. Arul Vijaya Vani S. et al. Effects of vitamin D and calcium supplementation on side effects profile in patients of breast cancer treated with letrozole. Clinica Chimica Acta. 2016. Vol. 459. P. 53–56.

66. Datta M., Schwartz G.G. Calcium and Vitamin D Supplementation and Loss of Bone Mineral Density in Women Undergoing Breast Cancer Therapy. Crit Rev Oncol Hematol.2013. Vol. 88, No. 3. P. 10.1016/j.critrevonc.2013.07.002.

67. Thornton H. Calcium, vitamin D and Aromatase inhibitors. 2022.

68. Eisen A. et al. Use of Adjuvant Bisphosphonates and Other Bone-Modifying Agents in Breast Cancer: ASCO-OH (CCO) Guideline Update. JCO. Wolters Kluwer, 2022. Vol. 40, No. 7. P. 787–800.

69. Uehara M. et al. Relationship between bone mineral density and ovarian function and thyroid function in perimenopausal women with endometriosis: a prospective study. BMC Women’s Health. 2022. Vol. 22, No. 1. P. 134.

70. Gnant M. et al. Adjuvant endocrine therapy plus zoledronic acid in premenopausal women with early-stage breast cancer: 62-month follow-up from the ABCSG‑12 randomised trial. Lancet Oncol. 2011. Vol. 12, No. 7. P. 631–641.

71. Ruddy K.J. et al. Prospective study of fertility concerns and preservation strategies in young women with breast cancer. J Clin Oncol. 2014. Vol. 32, No. 11. P. 1151–1156.

72. Lambertini M. et al. Long-term Safety of Pregnancy Following Breast Cancer According to Estrogen Receptor Status. JNCI: Journal of the National Cancer Institute. 2018. Vol. 110, No. 4. P. 426–429.

73. Lambertini M. et al. The BCY3/BCC2017 survey on physicians’ knowledge, attitudes and practice towards fertility and pregnancy-related issues in young breast cancer patients. The Breast. 2018. Vol. 42. P. 41–49.

74. Partridge A.H. et al. Who are the women who enrolled in the POSITIVE trial: A global study to support young hormone receptor positive breast cancer survivors desiring pregnancy. The Breast. 2021. Vol. 59. P. 327–338.

75. Tang S. et al. Long-term comparisons of the efficacy, safety, and pregnancy outcomes of adjuvant tamoxifen plus ovarian function suppression in premenopausal Han and Zhuang Chinese patients with hormone receptor-positive early breast cancer. J Int Med Res. 2019. Vol. 47, No. 2. P. 641–652.