Skip to main content

Advertisement

SpringerLink
Log in

Controversies in preservation of ovary function and fertility in patients with breast cancer

  • Review
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Improved treatment of breast cancer in premenopausal patients increased survival rates, but the therapy may influence fertility and ovarian function. Currently there is a big public and individual interest of breast cancer affected women in preservation of ovarian function and fertility. Chemotherapy induced amenorrhea (CIA) has many objective (osteoporosis, cardiovascular, urogenital atrophy, cognitive etc.) and subjective (hot flushes, sleep disturbances, change of mood etc.) consequences. In patients with breast cancer who wish to avoid a CIA and to preserve their fertility ovarian protection by GnRH agonists, cryopreservation of operative sampled ovarian tissue or obtained fertilized or non-fertilized eggs after stimulation and puncture or embryos after in vitro fertilization are technically possible. However there are no evidence-based recommendations for preservation of fertility or ovarian function in breast cancer patients. Except the cryopreservation of embryos all other procedures are experimental. It is also undefined who is going to carry the costs. Moreover, there are recent data that the reappearance of ovarian hormones may stimulate occult tumor cells in hormone sensitive breast cancer. Therefore it seems necessary to inform breast cancer patients about the possible negative effects of preservation of ovarian function.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Lee SJ, Schover LR, Partridge AH, Patrizio P, Wallace WH, Hagerty K, Beck LN, Brennan LV, Oktay K (2006) American Society of Clinical Oncology recommendations on fertility preservation in cancer patients. J Clin Oncol 24:2917–2931

    Article  PubMed  Google Scholar 

  2. Pritchard KI (2002) Adjuvant therapy for premenopausal women with breast cancer: is it time for another paradigm shift? J Clin Oncol 20:4611–4614

    PubMed  Google Scholar 

  3. Fornier MN, Modi S, Panageas KS, Norton L, Hudis C (2005) Incidence of chemotherapy-induced, long-term amenorrhea in patients with breast carcinoma age 40 years and younger after adjuvant anthracycline and taxane. Cancer 104:1575–1579

    Article  PubMed  CAS  Google Scholar 

  4. De Haes H, Olschewski M, Kaufmann M, Schumacher M, Jonat W, Sauerbrei W (2003) Quality of life in goserelin-treated versus cyclophosphamide + methotrexate + fluorouracil-treated premenopausal and perimenopausal patients with node-positive, early breast cancer: the zoladex early breast cancer research association trialists group. J Clin Oncol 21:4510–4516

    Article  PubMed  CAS  Google Scholar 

  5. Ganz PA, Greendale GA, Petersen L, Kahn B, Bower JE (2003) Breast cancer in younger women: reproductive and late health effects of treatment. J Clin Oncol 21:4184–4193

    Article  PubMed  Google Scholar 

  6. Ghidoni R, Boccardi M, Benussi L, Testa C, Villa A, Pievani M, Gigola L, Sabattoli F, Barbiero L, Frisoni GB, Binetti G (2006) Effects of estrogens on cognition and brain morphology: involvement of the cerebellum. Maturitas 54:222–228

    Article  PubMed  CAS  Google Scholar 

  7. Nystedt M, Berglund G, Bolund C, Fornander T, Rutqvist LE (2003) Side effects of adjuvant endocrine treatment in premenopausal breast cancer patients: a prospective randomized study. J Clin Oncol 21:1836–1844

    Article  PubMed  CAS  Google Scholar 

  8. Tchen N, Juffs HG, Downie FP, Yi QL, Hu H, Chemerynsky I, Clemons M, Crump M, Goss PE, Warr D, Tweedale ME, Tannock IF (2003) Cognitive function, fatigue, and menopausal symptoms in women receiving adjuvant chemotherapy for breast cancer. J Clin Oncol 21:4175–4183

    Article  PubMed  Google Scholar 

  9. EBCTCG (2005) Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 365:1687–1717

    Article  CAS  Google Scholar 

  10. Duffy CM, Allen SM, Clark MA (2005) Discussions regarding reproductive health for young women with breast cancer undergoing chemotherapy. J Clin Oncol 23:766–773

    Article  PubMed  Google Scholar 

  11. Holmberg L, Anderson H (2004) HABITS (hormonal replacement therapy after breast cancer–is it safe?), a randomised comparison: trial stopped. Lancet 363:453–455

    Article  PubMed  CAS  Google Scholar 

  12. Ataya K, Rao LV, Lawrence E, Kimmel R (1995) Luteinizing hormone-releasing hormone agonist inhibits cyclophosphamide-induced ovarian follicular depletion in rhesus monkeys. Biol Reprod 52:365–372

    Article  PubMed  CAS  Google Scholar 

  13. Chemaitilly W, Mertens AC, Mitby P, Whitton J, Stovall M, Yasui Y, Robison LL, Sklar CA (2006) Acute ovarian failure in the childhood cancer survivor study. J Clin Endocrinol Metab 91:1723–1728

    Article  PubMed  CAS  Google Scholar 

  14. Sklar CA, Mertens AC, Mitby P, Whitton J, Stovall M, Kasper C, Mulder J, Green D, Nicholson HS, Yasui Y, Robison LL (2006) Premature menopause in survivors of childhood cancer: a report from the childhood cancer survivor study. J Natl Cancer Inst 98:890–896

    Article  PubMed  Google Scholar 

  15. Petrek JA, Naughton MJ, Case LD, Paskett ED, Naftalis EZ, Singletary SE, Sukumvanich P (2006) Incidence, time course, and determinants of menstrual bleeding after breast cancer treatment: a prospective study. J Clin Oncol 24:1045–1051

    Article  PubMed  Google Scholar 

  16. Muller H (1990) Effects of adjuvant chemotherapy of breast cancer on gonadal function. Zentralbl Gynakol 112:795–801

    PubMed  CAS  Google Scholar 

  17. Kauff ND, Satagopan JM, Robson ME, Scheuer L, Hensley M, Hudis CA, Ellis NA, Boyd J, Borgen PI, Barakat RR, Norton L, Castiel M, Nafa K, Offit K (2002) Risk-reducing salpingo-oophorectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med 346:1609–1615

    Article  PubMed  Google Scholar 

  18. Rebbeck TR, Lynch HT, Neuhausen SL, Narod SA, Van’t Veer L, Garber JE, Evans G, Isaacs C, Daly MB, Matloff E, Olopade OI, Weber BL (2002) Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. N Engl J Med 346:1616–1622

    Article  PubMed  Google Scholar 

  19. Cuzick J (2006) The impact of LHRH agonists on breast cancer recurrence and mortality: an overview of the randomized trials. Breast Cancer Res Treat 100(Suppl. 1):S10

    Google Scholar 

  20. EBCTCG (2000) Ovarian ablation for early breast cancer. Cochrane Database Syst Rev: CD000485

  21. Gnant M, Greil R, Kubista E, Menzel C, Schippinger W, Seifert B, Haider K, Jakesz R (2006) The impact of treatment-induced amenorrhea on survival of premenopausal patients with endocrine-responsive breast cancer: 10-year result of ABCSG-05 (CMF vs. goserelin + tamoxifen). Breast Cancer Res Treat 100(Suppl 1):S10

    Google Scholar 

  22. Love RR, Duc NB, Allred DC, Binh NC, Dinh NV, Kha NN, Thuan TV, Mohsin SK, Roanh lD, Khang HX, Tran TL, Quy TT, Thuy NV, The PN, Cau TT, Tung ND, Huong DT, Quang lM, Hien NN, Thuong L, Shen TZ, Xin Y, Zhang Q, Havighurst TC, Yang YF, Hillner BE, DeMets DL (2002) Oophorectomy and tamoxifen adjuvant therapy in premenopausal Vietnamese and Chinese women with operable breast cancer. J Clin Oncol 20:2559–2566

    Article  PubMed  Google Scholar 

  23. Klijn JG, Blamey RW, Boccardo F, Tominaga T, Duchateau L, Sylvester R (2001) Combined tamoxifen and luteinizing hormone-releasing hormone (LHRH) agonist versus LHRH agonist alone in premenopausal advanced breast cancer: a meta-analysis of four randomized trials. J Clin Oncol 19:343–353

    PubMed  CAS  Google Scholar 

  24. Beatson GT (1896) On the treatment of inoperable cases of carcinoma of the mamma. Suggestions for a new method of treatment with illustrative cases. Lancet 2:104–107

    Article  Google Scholar 

  25. Davis AL, Klitus M, Mintzer DM (2005) Chemotherapy-induced amenorrhea from adjuvant breast cancer treatment: the effect of the addition of taxanes. Clin Breast Cancer 6:421–424

    Article  PubMed  CAS  Google Scholar 

  26. Colleoni M, Gelber S, Goldhirsch A, Aebi S, Castiglione-Gertsch M, Price KN, Coates AS, Gelber RD (2006) Tamoxifen after adjuvant chemotherapy for premenopausal women with lymph node-positive breast cancer: International Breast Cancer Study Group Trial 13–93. J Clin Oncol 24:1332–1341

    Article  PubMed  CAS  Google Scholar 

  27. Braverman AS, Sawhney H, Tendler A, Patel N, Rao CS (2002) Pre-menopausal serum estradiol levels may persist after chemotherapy-induced amenorrhea in breast cancer. Proc Am Soc Clin Oncol 21:42a (abstr 164)

    Google Scholar 

  28. Baum M, Houghton J, Odling-Smee W, Rutqvist LE, Fornander T, Nordenskjold B, Nicolucci A, Mark RJ (2001) Adjuvant treatment of premenopausal breast cancer with zoladex and tamoxifen: results from randomized trials by the Cancer Research Campaign (CRC) Breast Cancer Trials Group, The Stockholm Breast Cancer Study Group, The South East Sweden Breast Cancer Group and Gruppo Interdisciplinare Valutazione Intervention Oncologica (GIVIO). Breast 10(Suppl 1):P64

    Google Scholar 

  29. Castiglione-Gertsch M, O’Neill A, Price KN, Goldhirsch A, Coates AS, Colleoni M, Nasi ML, Bonetti M, Gelber RD (2003) Adjuvant chemotherapy followed by goserelin versus either modality alone for premenopausal lymph node-negative breast cancer: a randomized trial. J Natl Cancer Inst 95:1833–1846

    PubMed  Google Scholar 

  30. Davidson NE, O’Neill A, Vukov A, Osborne CK, Martino S, White D, Abeloff MD (2003) Effect of chemohormonal therapy in premenopausal node positive , receptor positive breast cancer: an Eastern Cooperative Oncology Group Phase III Intergroup trial (E5188, Int-0101). J Clin Oncol (Proc Am Soc Clin Oncol) 21:15 (abstr)

    Google Scholar 

  31. Walshe JM, Denduluri N, Swain SM (2006) Amenorrhea in premenopausal women after adjuvant chemotherapy for breast cancer. J Clin Oncol 24:5769–5779

    Article  PubMed  CAS  Google Scholar 

  32. Vanhuyse M, Fournier C, Bonneterre J (2005) Chemotherapy-induced amenorrhea: influence on disease-free survival and overall survival in receptor-positive premenopausal early breast cancer patients. Ann Oncol 16:1283–1288

    Article  PubMed  CAS  Google Scholar 

  33. Jonat W, Kaufmann M, Sauerbrei W, Blamey R, Cuzick J, Namer M, Fogelman I, de Haes JC, de Matteis A, Stewart A, Eiermann W, Szakolczai I, Palmer M, Schumacher M, Geberth M, Lisboa B (2002) Goserelin versus cyclophosphamide, methotrexate, and fluorouracil as adjuvant therapy in premenopausal patients with node-positive breast cancer: The Zoladex Early Breast Cancer Research Association Study. J Clin Oncol 20:4628–4635

    Article  PubMed  CAS  Google Scholar 

  34. Borde F, Chapelle-Marcilac IFP, Hery M, Bonneterre J, Kerbrat P (2003) Role of chemo-induced amenorrhea in premenopausale, node-positive, operable breast cancer patients: 9-year follow-up results of French Adjuvant Study Group (FASG) data base. Breast Cancer Res Treat 82(Suppl 1):30

    Google Scholar 

  35. http://www.bqs-qualitaetsreport.de/. BQS. (2007)

  36. Del Mastro L, Venturini M (2006) Fertility preservation strategies for breast cancer patients. J Clin Oncol 24:4220–4221

    Article  PubMed  Google Scholar 

  37. Ives A, Saunders C, Bulsara M, Semmens J (2006) Pregnancy after breast cancer: population based study. BMJ 334:166–167

    Google Scholar 

  38. Blakely LJ, Buzdar AU, Lozada JA, Shullaih SA, Hoy E, Smith TL, Hortobagyi GN (2004) Effects of pregnancy after treatment for breast carcinoma on survival and risk of recurrence. Cancer 100:465–469

    Article  PubMed  Google Scholar 

  39. Mueller BA, Simon MS, Deapen D, Kamineni A, Malone KE, Daling JR (2003) Childbearing and survival after breast carcinoma in young women. Cancer 98:1131–1140

    Article  PubMed  Google Scholar 

  40. Velentgas P, Daling JR, Malone KE, Weiss NS, Williams MA, Self SG, Mueller BA (1999) Pregnancy after breast carcinoma: outcomes and influence on mortality. Cancer 85:2424–2432

    Article  PubMed  CAS  Google Scholar 

  41. Goldhirsch A, Glick JH, Gelber RD, Coates A, Senn HJ (2005) Meeting highlights: international expert consensus on the primary therapy of early breast cancer 2005. Ann Oncol 16:1569–1583

    Article  PubMed  CAS  Google Scholar 

  42. Blumenfeld Z (2002) Preservation of fertility and ovarian function and minimalization of chemotherapy associated gonadotoxicity and premature ovarian failure: the role of inhibin-A and -B as markers. Mol Cell Endocrinol 187:93–105

    Article  PubMed  CAS  Google Scholar 

  43. Franke HR, Smit WM, Vermes I (2005) Gonadal protection by a gonadotropin-releasing hormone agonist depot in young women with Hodgkin’s disease undergoing chemotherapy. Gynecol Endocrinol 20:274–278

    Article  PubMed  CAS  Google Scholar 

  44. Fox K, Scialla J, Moore H (2003) Preventing chemotherapy-related amenorrhea using leuprolide during adjuvant chemotherapy for early-stage breast cancer. Proc Am Soc Clin Oncol 22:13

    Google Scholar 

  45. Recchia F, Saggio G, Amiconi G, Di Blasio A, Cesta A, Candeloro G, Rea S (2006) Gonadotropin-releasing hormone analogues added to adjuvant chemotherapy protect ovarian function and improve clinical outcomes in young women with early breast carcinoma. Cancer 106:514–523

    Article  PubMed  CAS  Google Scholar 

  46. Del Mastro L, Catzeddu T, Boni L, Bell C, Sertoli MR, Bighin C, Clavarezza M, Testa D, Venturini M (2006) Prevention of chemotherapy-induced menopause by temporary ovarian suppression with goserelin in young, early breast cancer patients. Ann Oncol 17:74–78

    Article  PubMed  Google Scholar 

  47. Urruticoechea A, Walsh G, Rigg A, Dowsett M, Smith IE (2004) Ovarian function protection with goserelin during adjuvant chemotherapy in pre-menopausal women with early breast cancer. Breast Cancer Res Treat 88(Suppl 1):S229

    Google Scholar 

  48. Oktay K, Buyuk E, Libertella N, Akar M, Rosenwaks Z (2005) Fertility preservation in breast cancer patients: a prospective controlled comparison of ovarian stimulation with tamoxifen and letrozole for embryo cryopreservation. J Clin Oncol 23:4347–4353

    Article  PubMed  CAS  Google Scholar 

  49. Oktay K, Hourvitz A, Sahin G, Oktem O, Safro B, Cil A, Bang H (2006) Letrozole reduces estrogen and gonadotropin exposure in women with breast cancer undergoing ovarian stimulation before chemotherapy. J Clin Endocrinol Metab 91:3885–3890

    Article  PubMed  CAS  Google Scholar 

  50. Sonmezer M, Oktay K (2006) Fertility preservation in young women undergoing breast cancer therapy. Oncologist 11:422–434

    Article  PubMed  CAS  Google Scholar 

  51. Donnez J, Dolmans MM, Demylle D, Jadoul P, Pirard C, Squifflet J, Martinez-Madrid B, van Langendonckt A (2004) Livebirth after orthotopic transplantation of cryopreserved ovarian tissue. Lancet 364:1405–1410

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Gynecology and Obstetrics, University of Rostock, Klinikum Südstadt Rostock, Südring 81, 18059, Rostock, Germany

    Bernd Gerber, Max Dieterich & Toralf Reimer

  2. Fertility Center, University of Rostock, Klinikum Südstadt Rostock, Rostock, Germany

    Heiner Müller

Authors
  1. Bernd Gerber
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Max Dieterich
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Heiner Müller
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Toralf Reimer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bernd Gerber.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gerber, B., Dieterich, M., Müller, H. et al. Controversies in preservation of ovary function and fertility in patients with breast cancer. Breast Cancer Res Treat 108, 1–7 (2008). https://doi.org/10.1007/s10549-007-9572-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-007-9572-1

Keywords

Search

Navigation