Review Article

Fertility Preservation in Breast Cancer

Authors: Cristina O’Donoghue, MD, MPH, Gwendolyn P. Quinn, PhD, M. Catherine Lee, MD

Abstract

As more young women survive breast cancer, fertility preservation (FP) is an important component of care. This review highlights the importance of early pretreatment referral, reviews the risks of infertility associated with breast cancer treatment, and defines existing and emerging techniques for FP. The techniques reviewed include ovarian suppression, embryo cryopreservation, oocyte cryopreservation, and ovarian tissue cryopreservation and transplantation. The barriers women face, such as not being appropriately referred and the costs of treatment, also are addressed. Multidisciplinary, patient-centered care is essential to discussing FP with patients with breast cancer and ensuring appropriate care that includes quality of life in survivorship.

 

This content is limited to qualifying members.

Existing members, please login first

If you have an existing account please login now to access this article or view purchase options.

Purchase only this article ($25)

Create a free account, then purchase this article to download or access it online for 24 hours.

Purchase an SMJ online subscription ($75)

Create a free account, then purchase a subscription to get complete access to all articles for a full year.

Purchase a membership plan (fees vary)

Premium members can access all articles plus recieve many more benefits. View all membership plans and benefit packages.

References

1. Trivers KF, Fink AK, Partridge AH, et al. Estimates of young breast cancer survivors at risk for infertility in the U.S. Oncologist 2014;19:814-822.
 
2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin 2016;66:7-30.
 
3. Jemal A, Siegel R, Xu J, et al. Cancer statistics, 2010. CA Cancer J Clin 2010;60:277-300.
 
4. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin 2015;65:5-29.
 
5. 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;365:1687-1717.
 
6. Lee MC, Gray J, Han HS, et al. Fertility and reproductive considerations in premenopausal patients with breast cancer. Cancer Control 2010;17:162-172.
 
7. Soleimani R, Heytens E, Darzynkiewicz Z, et al. Mechanisms of chemotherapy-induced human ovarian aging: double strand DNA breaks and microvascular compromise. Aging (Albany NY) 2011;3:782-793.
 
8. Goodwin PJ, Ennis M, Pritchard KI, et al. Risk of menopause during the first year after breast cancer diagnosis. J Clin Oncol 1999;17:2365-2370.
 
9. Abusief ME, Missmer SA, Ginsburg ES, et al. The effects of paclitaxel, dose density, and trastuzumab on treatment‐ amenorrhea in premenopausal women with breast cancer. Cancer 2010;116:791-798.
 
10. Partridge AH, Ruddy KJ, Gelber S, et al. Ovarian reserve in women who remain premenopausal after chemotherapy for early stage breast cancer. Fertil Steril 2010;94:638-644.
 
11. Gracia CR, Sammel MD, Freeman E, et al. Impact of cancer therapies on ovarian reserve. Fertil Steril 2012;97:134-140.e1.
 
12. Partridge AH, Gelber S, Peppercorn J, et al. Fertility and menopausal outcomes in young breast cancer survivors. Clin Breast Cancer 2008;8:65-69.
 
13. Anderson RA, Themmen AP, Al-Qahtani A, et al. The effects of chemotherapy and long-term gonadotrophin suppression on the ovarian reserve in premenopausal women with breast cancer. Hum Reprod 2006;21:2583-2592.
 
14. Su HC, Haunschild C, Chung K, et al. Prechemotherapy antimullerian hormone, age, and body size predict timing of return of ovarian function in young breast cancer patients. Cancer 2014;120:3691-3698.
 
15. Anderson RA, Rosendahl M, Kelsey TW, et al. Pretreatment anti-Mullerian hormone predicts for loss of ovarian function after chemotherapy for early breast cancer. Eur J Cancer 2013;49:3404-3411.
 
16. Dillon KE, Sammel MD, Prewitt M, et al. Pretreatment antimüllerian hormone levels determine rate of posttherapy ovarian reserve recovery: acute changes in ovarian reserve during and after chemotherapy. Fertil Steril 2013;99:477-483.
 
17. Chai J, Howie AF, Cameron DA, et al. A highly-sensitive anti-Müllerian hormone assay improves analysis of ovarian function following chemotherapy for early breast cancer. Eur J Cancer 2014;50:2367-2374.
 
18. Dezellus A, Barriere P, Campone M, et al. Prospective evaluation of serum anti-Müllerian hormone dynamics in 250 women of reproductive age treated with chemotherapy for breast cancer. Eur J Cancer 2017;79:72-80.
 
19. Ruddy KJ, O’Neill A, Miller KD, et al. Biomarker prediction of chemotherapy-related amenorrhea in premenopausal women with breast cancer participating in E5103. Breast Cancer Res Treat 2014;144:591-597.
 
20. Bines J, Oleske DM, Cobleigh MA. Ovarian function in premenopausal women treated with adjuvant chemotherapy for breast cancer. J Clin Oncol 1996;14:1718-1729.
 
21. Torino F, Barnabei A, De Vecchis L, et al. Chemotherapy-induced ovarian toxicity in patients affected by endocrine-responsive early breast cancer. Crit Rev Oncol Hematol 2014;89:27-42.
 
22. Lambertini M, Del Mastro L, Pescio MC, et al. Cancer and fertility preservation: international recommendations from an expert meeting. BMC Med 2016;14:1.
 
23. Lee SJ, Schover LR, Partridge AH, et al. American Society of Clinical Oncology recommendations on fertility preservation in cancer patients. J Clin Oncol 2006;24:2917-2931.
 
24. Oktay K, Sönmezer M. Chemotherapy and amenorrhea: risks and treatment options. Curr Opin Obstet Gynecol 2008;20:408-415.
 
25. Zavos A, Valachis A. Risk of chemotherapy-induced amenorrhea in patients with breast cancer: a systematic review and meta-analysis. Acta Oncol 2016;55:664-670.
 
26. Petrek JA, Naughton MJ, Case LD, et al. Incidence, time course, and determinants of menstrual bleeding after breast cancer treatment: a prospective study. J Clin Oncol 2006;24:1045-1051.
 
27. Poorvu PD, Gelber SI, Rosenberg SM, et al. Treatment-related amenorrhea among young women one year following diagnosis of early-stage breast cancer. Chicago: Paper presented at: American Society of Clinical Oncology meeting, May 29-June 2, 2015.
 
28. Walshe JM, Denduluri N, Swain SM. Amenorrhea in premenopausal women after adjuvant chemotherapy for breast cancer. J Clin Oncol 2006;24:5769-5779.
 
29. Swain SM, Jeong JH, Geyer CE, Jr et al. Longer therapy, iatrogenic amenorrhea, and survival in early breast cancer. N Engl J Med 2010;362:2053-2065.
 
30. Wapnir IL, Anderson SJ, Mamounas EP, et al. Prognosis after ipsilateral breast tumor recurrence and locoregional recurrences in five National Surgical Adjuvant Breast and Bowel Project node-positive adjuvant breast cancer trials. J Clin Oncol 2006;24:2028-2037.
 
31. Waks AG, Partridge AH. Fertility preservation in patients with breast cancer: necessity, methods, and safety. J Natl Compr Canc Netw 2016;14:355-363.
 
32. Ruddy KJ, Gelber SI, Tamimi RM, et al. Prospective study of fertility concerns and preservation strategies in young women with breast cancer. J Clin Oncol 2014;32:1151-1156.
 
33. Oktay K, Kim JY, Barad D, et al. Association of BRCA1 mutations with occult primary ovarian insufficiency: a possible explanation for the link between infertility and breast/ovarian cancer risks. J Clin Oncol 2010;28:240-244.
 
34. Lambertini M, Ginsburg ES, Partridge AH. Update on fertility preservation in young women undergoing breast cancer and ovarian cancer therapy. Curr Opin Obstet Gynecol 2015;27:98-107.
 
35. Loren AW, Mangu PB, Beck LN, et al. Fertility preservation for patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 2013;31:2500-2510.
 
36. National Comprehensive Cancer Network. Breast cancer. https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf. Accessed September 10, 2016.
 
37. Lewis JD, Silva C, Quinn GP, et al. Factors affecting uptake of fertility preservation in breast cancer. Breast Res 2014;1:7.
 
38. Quinn GP, Vadaparampil ST, Lee JH, et al. Physician referral for fertility preservation in oncology patients: a national study of practice behaviors. J Clin Oncol 2009;27:5952-5957.
 
39. Quinn GP, Vadaparampil ST, Gwede CK, et al. Discussion of fertility preservation with newly diagnosed patients: oncologists’ views. J Cancer Surviv 2007;1:146-155.
 
40. Goldfarb SB, Kamer SA, Oppong BA, et al. Fertility preservation for the young breast cancer patient. Ann Surg Oncol 2016;23:1530-1536.
 
41. Snyder KA, Pearse W. Discussing fertility preservation options with patients with cancer. JAMA 2011;306:202-203.
 
42. Duffy CM, Allen SM, Clark MA. Discussions regarding reproductive health for young women with breast cancer undergoing chemotherapy. J Clin Oncol 2005;23:766-773.
 
43. Letourneau JM, Ebbel EE, Katz PP, et al. Pretreatment fertility counseling and fertility preservation improve quality of life in reproductive age women with cancer. Cancer 2012;118:1710-1717.
 
44. Quinn GP, Block RG, Clayman ML, et al. If you did not document it, it did not happen: rates of documentation of discussion of infertility risk in adolescent and young adult oncology patients’ medical records. J Oncol Pract 2015;11:137-144.
 
45. Lee MC, Bhati RS, von Rottenthaler EE, et al. Therapy choices and quality of life in young breast cancer survivors: a short-term follow-up. Am J Surg 2013;20:625-631.
 
46. Practice Committee of American Society for Reproductive Medicine. Fertility preservation in patients undergoing gonadotoxic therapy or gonadectomy: a committee opinion. Fertil Steril 2013;100:1214-1223.
 
47. Roberts JE, Oktay K. Fertility preservation: a comprehensive approach to the young woman with cancer. J Natl Cancer Inst Monogr 2005;:57-59.
 
48. Shapira M, Raanani H, Meirow D. IVF for fertility preservation in breast cancer patients-efficacy and safety issues. J Assist Reprod Genet 2015;32:1171-1178.
 
49. Centers for Disease Control and Prevention. 2014 assisted reproductive technology national summary report. https://www.cdc.gov/art/pdf/2014-report/art-2014-national-summary-report.pdf. Published October 2016. Accessed July 23, 2017.
 
50. Cardozo ER, Thomson AP, Karmon AE, et al. Ovarian stimulation and in-vitro fertilization outcomes of cancer patients undergoing fertility preservation compared to age matched controls: a 17-year experience. J Assist Reprod Genet 2015;32:587-596.
 
51. Dolmans MM, Hollanders de Ouderaen S, Demylle D, et al. Utilization rates and results of long-term embryo cryopreservation before gonadotoxic treatment. J Assist Reprod Genet 2015;32:1233-1237.
 
52. von Wolff M, Thaler CJ, Frambach T, et al. Ovarian stimulation to cryopreserve fertilized oocytes in cancer patients can be started in the luteal phase. Fertil Steril 2009;92:1360-1365.
 
53. Oktay K, Buyuk E, Davis O, et al. Fertility preservation in breast cancer patients: IVF and embryo cryopreservation after ovarian stimulation with tamoxifen. Hum Reprod 2003;18:90-95.
 
54. Cobo A, Meseguer M, Remohí J, et al. Use of cryo-banked oocytes in an ovum donation programme: a prospective, randomized, controlled, clinical trial. Hum Reprod 2010;25:2239-2246.
 
55. Oktay K, Buyuk E, Libertella N, et al. Fertility preservation in breast cancer patients: a prospective controlled comparison of ovarian stimulation with tamoxifen and letrozole for embryo cryopreservation. J Clin Oncol 2005;23:4347-4353.
 
56. Azim AA, Costantini-Ferrando M, Oktay K. Safety of fertility preservation by ovarian stimulation with letrozole and gonadotropins in patients with breast cancer: a prospective controlled study. J Clin Oncol 2008;26:2630-2635.
 
57. Oktay K, Kim J, Bedoschi G, et al. Safety of letrozole-gonadotropin controlled ovarian stimulation protocol in women with breast cancer undergoing fertility preservation before or after tumor resection via embryo or oocyte cryopreservation: a prospective cohort study. Cancer Res 2015;75(9 Suppl): P5-15-02.
 
58. Oktay K, Turan V, Bedoschi G, et al. Fertility preservation success subsequent to concurrent aromatase inhibitor treatment and ovarian stimulation in women with breast cancer. J Clin Oncol 2015;33:2424-2429.
 
59. Practice Committees of American Society for Reproductive Medicine, Society for Assisted Reproductive Technology. Mature oocyte cryopreservation: a guideline. Fertil Steril 2013;99:37-43.
 
60. Cobo A, Rubio C, Gerli S, et al. Use of fluorescence in situ hybridization to assess the chromosomal status of embryos obtained from cryopreserved oocytes. Fertil Steril 2001;75:354-360.
 
61. Parmegiani L, Cognigni G, Bernardi S, et al. Efficiency of aseptic open vitrification and hermetical cryostorage of human oocytes. Reprod Biomed Online 2011;23:505-512.
 
62. Ubaldi F, Anniballo R, Romano S, et al. Cumulative ongoing pregnancy rate achieved with oocyte vitrification and cleavage stage transfer without embryo selection in a standard infertility program. Hum Reprod 2010;25:1199-1205.
 
63. Borini A, Levi Setti PE, Anserini P, et al. Multicenter observational study on slow-cooling oocyte cryopreservation: clinical outcome. Fertil Steril 2010;94:1662-1668.
 
64. Noyes N, Porcu E, Borini A. Over 900 oocyte cryopreservation babies born with no apparent increase in congenital anomalies. Reprod Biomed Online 2009;18:769-776.
 
65. Munhoz RR, Pereira AA, Sasse AD, et al. Gonadotropin-releasing hormone agonists for ovarian function preservation in premenopausal women undergoing chemotherapy for early-stage breast cancer: a systematic review and meta-analysis. JAMA Oncol 2016;2:65-73.
 
66. Turner NH, Partridge A, Sanna G, et al. Utility of gonadotropin-releasing hormone agonists for fertility preservation in young breast cancer patients: the benefit remains uncertain. Ann Oncol 2013;24:2224-2235.
 
67. Lambertini M, Ceppi M, Poggio F, et al. Ovarian suppression using luteinizing hormone-releasing hormone agonists during chemotherapy to preserve ovarian function and fertility of breast cancer patients: a meta-analysis of randomized studies. Ann Oncol 2015;26:2408-2419.
 
68. Moore HC, Unger JM, Phillips KA, et al. Goserelin for ovarian protection during breast-cancer adjuvant chemotherapy. N Engl J Med 2015;372:923-932.
 
69. Del Mastro L, Boni L, Michelotti A, et al. Effect of the gonadotropin-releasing hormone analogue triptorelin on the occurrence of chemotherapy-induced early menopause in premenopausal women with breast cancer: a randomized trial. JAMA 2011;306:269-276.
 
70. Gerber B, von Minckwitz G, Stehle H, et al. Effect of luteinizing hormone-releasing hormone agonist on ovarian function after modern adjuvant breast cancer chemotherapy: the GBG 37 ZORO study. J Clin Oncol 2011;29:2334-2341.
 
71. Donnez J, Dolmans M-M, Demylle D, et al. Livebirth after orthotopic transplantation of cryopreserved ovarian tissue. Lancet 2004;364:1405-1410.
 
72. Salama M, Woodruff TK. New advances in ovarian autotransplantation to restore fertility in cancer patients. Cancer Metastasis Rev 2015;34:807-822.
 
73. Meirow D, Levron J, Eldar-Geva T, et al. Pregnancy after transplantation of cryopreserved ovarian tissue in a patient with ovarian failure after chemotherapy. N Engl J Med 2005;353:318-321.
 
74. Prasath EB, Chan ML, Wong WH, et al. First pregnancy and live birth resulting from cryopreserved embryos obtained from in vitro matured oocytes after oophorectomy in an ovarian cancer patient. Hum Reprod 2014;29:276-278.
 
75. Robertson AD, Missmer SA, Ginsburg ES. Embryo yield after in vitro fertilization in women undergoing embryo banking for fertility preservation before chemotherapy. Fertil Steril 2011;95:588-591.
 
76. Lee S, Heytens E, Moy F, et al. Determinants of access to fertility preservation in women with breast cancer. Fertil Steril 2011;95:1932-1936.
 
77. Goodman LR, Balthazar U, Kim J, et al. Trends of socioeconomic disparities in referral patterns for fertility preservation consultation. Hum Reprod 2012;27:2076-2081.
 
78. Walgreens. Fertility Preservation Program. https://www.walgreens.com/topic/specialty-pharmacy/fertility-services.jsp. Accessed November 30, 2016.
 
79. The Oncofertility Consortium. http://oncofertility.northwestern.edu/events/2016-oncofertility-consortium-conference. Accessed July 23, 2017.
 
80. Miller CL, Specht MC, Skolny MN, et al. Sentinel lymph node biopsy at the time of mastectomy does not increase the risk of lymphedema: implications for prophylactic surgery. Breast Cancer Res Treat 2012;135:781-789.