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Ovarian Function Suppression in Premenopausal Women with Early-Stage Breast Cancer

  • Breast Cancer (ML Telli, Section Editor)
  • Published:
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Opinion statement

Breast cancers arising in young women are biologically more aggressive, and most of these patients are candidates to receive aggressive treatments that include the use of chemotherapy. As most of these tumors express the hormone receptors (i.e., luminal disease), these patients are also candidates to adjuvant endocrine therapy. Chemotherapy-induced amenorrhea showed to be prognostic in young patients with luminal breast cancer. However, the role of ovarian function suppression (OFS) in addition to standard adjuvant treatments has been largely debated over the past years. Recently, several studies have provided important insights on the role of OFS. Currently, the use of tamoxifen alone without prior cytotoxic therapy can be considered a very effective treatment option in young patients with hormone receptor-positive breast cancer at low risk of relapse. On the other hand, for patients at higher risk of relapse as those who are candidates to (neo)adjuvant chemotherapy, OFS proved to be beneficial, and therefore luteinizing hormone-releasing hormone agonists (LHRHa) should be considered in addition to tamoxifen or aromatase inhibitors (AI). However, toxicity is considerable and patients should be actively engaged in decision-making. Finally, in young breast cancer patients who are candidates to (neo)adjuvant chemotherapy, loss of ovarian function and fertility may be a concern. Besides other techniques, recent results showed that temporary OFS with LHRHa during cytotoxic treatment can be considered a reliable strategy to preserve gonadal function and fertility. Despite the recent advances in the field, several gray zones remain unanswered: the role of OFS plus AI in women who remained premenopausal after 5 years of tamoxifen, the optimal extended approach in women treated with 5 years of OFS plus AI, and the role of temporary OFS with LHRHa during chemotherapy in the specific subgroup of patients with BRCA mutations and in women undergoing this strategy after prior embryo/oocyte cryopreservation.

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  1. DeSantis CE, Fedewa SA, Goding Sauer A, et al. Breast cancer statistics, 2015: convergence of incidence rates between black and white women. CA Cancer J Clin. 2016;66(1):31–42.

    Article  PubMed  Google Scholar 

  2. Azim HA, Partridge AH. Biology of breast cancer in young women. Breast Cancer Res. 2014;16(4):427.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Partridge AH. Chemotherapy in premenopausal breast cancer patients. Breast Care. 2015;10(5):307–10.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Partridge AH, Hughes ME, Warner ET, et al. Subtype-dependent relationship between young age at diagnosis and breast cancer survival. J Clin Oncol. 2016;34(27):3308–14.

    Article  PubMed  Google Scholar 

  5. Poggio F, Levaggi A, Lambertini M. Chemotherapy-induced premature ovarian failure and its prevention in premenopausal breast cancer patients. Expert Rev Quality Life Cancer Care. 2016;1(1):5–7.

    Article  Google Scholar 

  6. Lambertini M, Azim Jr HA. Adjuvant hormonal therapy in young breast cancer patients. Breast Cancer Management. 2014;3(1):1–4.

    Article  CAS  Google Scholar 

  7. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG), Davies C, Godwin J, et al. Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet. 2011;378(9793):771–84.

    Article  Google Scholar 

  8. •• Burstein HJ, Temin S, Anderson H, et al. Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: american society of clinical oncology clinical practice guideline focused update. J Clin Oncol. 2014;32(21):2255–69. ASCO guidelines on adjuvant endocrine therapy for breast cancer patients.

    Article  PubMed  PubMed Central  Google Scholar 

  9. 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(11):1151–6.

    Article  PubMed  PubMed Central  Google Scholar 

  10. •• 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(19):2500–10. ASCO guidelines on fertility preservation in cancer patients.

    Article  PubMed  Google Scholar 

  11. •• Peccatori FA, Azim Jr HA, Orecchia R, et al. Cancer, pregnancy and fertility: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24(Suppl 6):vi160–70. ESMO guidelines on fertility preservation in cancer patients.

    Article  PubMed  Google Scholar 

  12. • Lambertini M, Del Mastro L, Pescio MC, et al. Cancer and fertility preservation: international recommendations from an expert meeting. BMC Med. 2016;14(1):1. International recommendations on fertility preservation in cancer patients.

    Article  PubMed  PubMed Central  Google Scholar 

  13. • Paluch-Shimon S, Pagani O, Partridge AH, et al. Second international consensus guidelines for breast cancer in young women (BCY2). Breast. 2016;26:87–99. International recommendations on the management of breast cancer in young women.

    Article  PubMed  Google Scholar 

  14. Lambertini M, Poggio F, Vaglica M, et al. News on the medical treatment of young women with early-stage HER2-negative breast cancer. Expert Opin Pharmacother. 2016;17(12):1643–55.

    Article  CAS  PubMed  Google Scholar 

  15. Del Mastro L, Rossi G, Lambertini M, et al. New insights on the role of luteinizing hormone releasing hormone agonists in premenopausal early breast cancer patients. Cancer Treat Rev. 2016;42:18–23.

    Article  PubMed  Google Scholar 

  16. Tomasi-Cont N, Lambertini M, Hulsbosch S, et al. Strategies for fertility preservation in young early breast cancer patients. Breast. 2014;23(5):503–10.

    Article  PubMed  Google Scholar 

  17. Zhao J, Liu J, Chen K, et al. What lies behind chemotherapy-induced amenorrhea for breast cancer patients: a meta-analysis. Breast Cancer Res Treat. 2014;145(1):113–28.

    Article  CAS  PubMed  Google Scholar 

  18. Swain SM, Jeong J-H, Geyer CE, et al. Longer therapy, iatrogenic amenorrhea, and survival in early breast cancer. N Engl J Med. 2010;362(22):2053–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Giobbie-Hurder A, Gelber RD, Regan MM. Challenges of guarantee-time bias. J Clin Oncol. 2013;31(23):2963–9.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Lambertini M, Ceppi M, Cognetti F, et al. Dose-dense adjuvant chemotherapy in premenopausal breast cancer patients: a pooled analysis of the MIG1 and GIM2 phase III studies. Eur J Cancer. 2017;71:34–42.

  21. Griggs JJ, Somerfield MR, Anderson H, et al. American Society of Clinical Oncology endorsement of the cancer care Ontario practice guideline on adjuvant ovarian ablation in the treatment of premenopausal women with early-stage invasive breast cancer. J Clin Oncol. 2011;29(29):3939–42.

    Article  PubMed  Google Scholar 

  22. Love RR. Adjuvant surgical oophorectomy plus tamoxifen in premenopausal women with operable hormone receptor-positive breast cancer: a global treatment option. Clin Breast Cancer. 2016;16(4):233–7.

    Article  PubMed  Google Scholar 

  23. Love RR, Laudico AV, Van Dinh N, et al. Timing of adjuvant surgical oophorectomy in the menstrual cycle and disease-free and overall survival in premenopausal women with operable breast cancer. J Natl Cancer Inst. 2015;107(6):djv064.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Love RR, Hossain SM, Hussain MM, et al. Luteal versus follicular phase surgical oophorectomy plus tamoxifen in premenopausal women with metastatic hormone receptor-positive breast cancer. Eur J Cancer. 2016;60:107–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Hadji P, Coleman RE, Wilson C, et al. Adjuvant bisphosphonates in early breast cancer: consensus guidance for clinical practice from a European panel. Ann Oncol. 2016;27(3):379–90.

    Article  CAS  PubMed  Google Scholar 

  26. •• Burstein HJ, Lacchetti C, Anderson H, et al. Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: American Society of Clinical Oncology clinical practice guideline update on ovarian suppression. J Clin Oncol. 2016;34(14):1689–701. ASCO guidelines on ovarian suppression as adjuvant endocrine therapy for breast cancer patients.

    Article  CAS  PubMed  Google Scholar 

  27. Bellet M, Gray KP, Francis PA, et al. Twelve-month estrogen levels in premenopausal women with hormone receptor-positive breast cancer receiving adjuvant triptorelin plus exemestane or tamoxifen in the suppression of ovarian function trial (SOFT): the SOFT-EST substudy. J Clin Oncol. 2016;34(14):1584–93.

    Article  CAS  PubMed  Google Scholar 

  28. Papakonstantinou A, Foukakis T, Rodriguez-Wallberg KA, Bergh J. Is estradiol monitoring necessary in women receiving ovarian suppression for breast cancer? J Clin Oncol. 2016;34(14):1573–9.

    Article  CAS  PubMed  Google Scholar 

  29. Pfeiler G, Königsberg R, Fesl C, et al. Impact of body mass index on the efficacy of endocrine therapy in premenopausal patients with breast cancer: an analysis of the prospective ABCSG-12 trial. J Clin Oncol. 2011;29(19):2653–9.

    Article  CAS  PubMed  Google Scholar 

  30. Dowsett M, Lønning PE, Davidson NE. Incomplete estrogen suppression with gonadotropin-releasing hormone agonists may reduce clinical efficacy in premenopausal women with early breast cancer. J Clin Oncol. 2016;34(14):1580–3.

    Article  CAS  PubMed  Google Scholar 

  31. LHRH-agonists in Early Breast Cancer Overview group, Cuzick J, Ambroisine L, 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;369(9574):1711–23.

    Article  Google Scholar 

  32. Jain S, Santa-Maria CA, Gradishar WJ. The role of ovarian suppression in premenopausal women with hormone receptor-positive early-stage breast cancer. Oncol Williston Park N. 2015;29(7):473–8. 481

    Google Scholar 

  33. • Partridge AH, Pagani O, Abulkhair O, et al. First international consensus guidelines for breast cancer in young women (BCY1). Breast. 2014;23(3):209–20. International recommendations on the management of breast cancer in young women.

    Article  PubMed  Google Scholar 

  34. Tevaarwerk AJ, Wang M, Zhao F, et al. Phase III comparison of tamoxifen versus tamoxifen plus ovarian function suppression in premenopausal women with node-negative, hormone receptor-positive breast cancer (E-3193, INT-0142): a trial of the Eastern Cooperative Oncology Group. J Clin Oncol. 2014;32(35):3948–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Francis PA, Regan MM, Fleming GF, et al. Adjuvant ovarian suppression in premenopausal breast cancer. N Engl J Med. 2015;372(5):436–46.

    Article  PubMed  Google Scholar 

  36. Ribi K, Luo W, Bernhard J, 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. J Clin Oncol. 2016;34(14):1601–10.

    Article  CAS  PubMed  Google Scholar 

  37. Phillips K-A, Regan MM, Ribi K, et al. Adjuvant ovarian function suppression and cognitive function in women with breast cancer. Br J Cancer. 2016;114(9):956–64.

    Article  CAS  PubMed  Google Scholar 

  38. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG), Dowsett M, Forbes JF, et al. Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials. Lancet. 2015;386(10001):1341–52.

    Article  Google Scholar 

  39. Cheung KL, Agrawal A, Folkerd E, et al. Suppression of ovarian function in combination with an aromatase inhibitor as treatment for advanced breast cancer in pre-menopausal women. Eur J Cancer. 2010;46(16):2936–42.

    Article  CAS  PubMed  Google Scholar 

  40. Carlson RW, Theriault R, Schurman CM, et al. Phase II trial of anastrozole plus goserelin in the treatment of hormone receptor-positive, metastatic carcinoma of the breast in premenopausal women. J Clin Oncol. 2010;28(25):3917–21.

    Article  CAS  PubMed  Google Scholar 

  41. Iwata H, Masuda N, Sagara Y, et al. Analysis of Ki-67 expression with neoadjuvant anastrozole or tamoxifen in patients receiving goserelin for premenopausal breast cancer. Cancer. 2013;119(4):704–13.

    Article  CAS  PubMed  Google Scholar 

  42. Rossi E, Morabito A, De Maio E, et al. Endocrine effects of adjuvant letrozole + triptorelin compared with tamoxifen + triptorelin in premenopausal patients with early breast cancer. J Clin Oncol. 2008;26(2):264–70.

    Article  CAS  PubMed  Google Scholar 

  43. Gnant M, Mlineritsch B, Schippinger W, et al. Endocrine therapy plus zoledronic acid in premenopausal breast cancer. N Engl J Med. 2009;360(7):679–91.

    Article  CAS  PubMed  Google Scholar 

  44. Gnant M, Mlineritsch B, Stoeger H, 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;12(7):631–41.

    Article  CAS  PubMed  Google Scholar 

  45. Gnant M, Mlineritsch B, Stoeger H, et al. Zoledronic acid combined with adjuvant endocrine therapy of tamoxifen versus anastrozol plus ovarian function suppression in premenopausal early breast cancer: final analysis of the Austrian Breast and Colorectal Cancer Study Group Trial 12. Ann Oncol. 2015;26(2):313–20.

    Article  CAS  PubMed  Google Scholar 

  46. Pagani O, Regan MM, Walley BA, et al. Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. N Engl J Med. 2014;371(2):107–18.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Bernhard J, Luo W, Ribi K, 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. Lancet Oncol. 2015;16(7):848–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Regan MM, Pagani O, Francis PA, et al. Predictive value and clinical utility of centrally assessed ER, PgR, and Ki-67 to select adjuvant endocrine therapy for premenopausal women with hormone receptor-positive, HER2-negative early breast cancer: TEXT and SOFT trials. Breast Cancer Res Treat. 2015;154(2):275–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Regan MM, Francis PA, Pagani O, et al. Absolute benefit of adjuvant endocrine therapies for premenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative early breast cancer: TEXT and SOFT trials. J Clin Oncol. 2016;34(19):2221–31.

    Article  PubMed  Google Scholar 

  50. Woodruff TK, Smith K, Gradishar W. Oncologists’ role in patient fertility care: a call to action. JAMA Oncol. 2016;2(2):171–2.

    Article  PubMed  PubMed Central  Google Scholar 

  51. 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(9):2224–35.

    Article  CAS  PubMed  Google Scholar 

  52. Lambertini M, Peccatori FA, Moore HC, Del Mastro L. Reply to the letter to the editor "Can ovarian suppression with gonadotropin releasing hormone analogs (GnRHa) preserve fertility in cancer patients?" by Rodriguez-Wallberg et al. Ann Oncol. 2016;27(3):548–9.

  53. Lambertini M, Poggio F, Levaggi A, Del Mastro L. Protecting ovaries during chemotherapy through gonad suppression: a systematic review and meta-analysis. Obstet Gynecol. 2015;126(4):901.

    Article  PubMed  Google Scholar 

  54. Del Mastro L, Lambertini M. Temporary ovarian suppression with gonadotropin-releasing hormone agonist during chemotherapy for fertility preservation: toward the end of the debate? Oncologist. 2015;20(11):1233–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Moore HCF, Unger JM, Phillips K-A, et al. Goserelin for ovarian protection during breast-cancer adjuvant chemotherapy. N Engl J Med. 2015;372(10):923–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Lambertini M, Boni L, Michelotti A, et al. Ovarian suppression with triptorelin during adjuvant breast cancer chemotherapy and long-term ovarian function, pregnancies, and disease-free survival: a randomized clinical trial. JAMA. 2015;314(24):2632–40.

    Article  CAS  PubMed  Google Scholar 

  57. 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(3):269–76.

    Article  CAS  PubMed  Google Scholar 

  58. 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(12):2408–19.

    CAS  PubMed  Google Scholar 

  59. • Coates AS, Winer EP, Goldhirsch A, et al. Tailoring therapies-improving the management of early breast cancer: St Gallen international expert consensus on the primary therapy of early breast cancer 2015. Ann Oncol. 2015;26(8):1533–46. St. Gallen recommendations on the management of early stage breast cancer.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. • National Comprehensive Cancer Network (NCC) Guidelines—breast cancer. Available at: http://www.nccn.org/professionals/physician_gls/pdf/breast.pdf. NCCN guidelines on the management of breast cancer.

  61. • Lambertini M, Cinquini M, Moschetti I, et al. Temporary ovarian suppression during chemotherapy to preserve ovarian function and fertility in breast cancer patients: a GRADE approach for evidence evaluation and recommendations by the Italian Association of Medical Oncology. Eur J Cancer. 2017;71:25–33. Italian Association of Medical Oncology recommendations on the use of temporary ovarian suppression during chemotherapy to preserve ovarian function and fertility in breast cancer patients.

  62. Azim HA, Davidson NE, Ruddy KJ. Challenges in treating premenopausal women with endocrine-sensitive breast cancer. Am Soc Clin Oncol Educ Book. 2016;35:23–32.

    Article  PubMed  Google Scholar 

  63. Montemurro F, Del Mastro L, De Laurentiis M, Puglisi F. Endocrine therapy in premenopausal women with breast cancer: a critical appraisal of current evidence. Expert Rev Anticancer Ther. 2016;16(2):211–8.

    Article  CAS  PubMed  Google Scholar 

  64. Mathew A, Davidson NE. Adjuvant endocrine therapy for premenopausal women with hormone-responsive breast cancer. Breast. 2015;24(Suppl 2):S120–5.

    Article  PubMed  Google Scholar 

  65. He W, Fang F, Varnum C, et al. Predictors of discontinuation of adjuvant hormone therapy in patients with breast cancer. J Clin Oncol. 2015;33(20):2262–9.

    Article  PubMed  Google Scholar 

  66. Llarena NC, Estevez SL, Tucker SL, Jeruss JS. Impact of fertility concerns on tamoxifen initiation and persistence. J Natl Cancer Inst. 2015;107(10).

  67. Pagani O, Ruggeri M, Manunta S, et al. Pregnancy after breast cancer: are young patients willing to participate in clinical studies? Breast. 2015;24(3):201–7.

    Article  PubMed  Google Scholar 

  68. Pan H, Gray RG, Davies C, et al. Predictors of recurrence during years 5–14 in 46,138 women with ER+ breast cancer allocated 5 years only of endocrine therapy (ET). J Clin Oncol 2016;34(suppl):abstract 505.

  69. Copson E, Eccles B, Maishman T, et al. Prospective observational study of breast cancer treatment outcomes for UK women aged 18–40 years at diagnosis: the POSH study. J Natl Cancer Inst. 2013;105(13):978–88.

    Article  CAS  PubMed  Google Scholar 

  70. Davies C, Pan H, Godwin J, et al. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet. 2013;381(9869):805–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Goss PE, Ingle JN, Martino S, et al. Impact of premenopausal status at breast cancer diagnosis in women entered on the placebo-controlled NCIC CTG MA17 trial of extended adjuvant letrozole. Ann Oncol. 2013;24(2):355–61.

    Article  CAS  PubMed  Google Scholar 

  72. Ruddy KJ, DeSantis SD, Barry W, et al. Extended therapy with letrozole and ovarian suppression in premenopausal patients with breast cancer after tamoxifen. Clin Breast Cancer. 2014;14(6):413–6.

    Article  CAS  PubMed  Google Scholar 

  73. Goss PE, Ingle JN, Pritchard KI, et al. Extending aromatase-inhibitor adjuvant therapy to 10 years. N Engl J Med. 2016;375(3):209–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Azim Jr HA, Kroman N, Paesmans M, et al. Prognostic impact of pregnancy after breast cancer according to estrogen receptor status: a multicenter retrospective study. J Clin Oncol. 2013;31(1):73–9.

    Article  PubMed  Google Scholar 

  75. Lambertini M, Del Mastro L. Fertility preservation in BRCA-mutated breast cancer patients. Breast Cancer Manag. 2016;5(2):61–8.

    Article  CAS  Google Scholar 

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Correspondence to Matteo Lambertini MD.

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Matteo Lambertini acknowledges the support from the European Society for Medical Oncology (ESMO) for a Translational Research Fellowship at the Institut Jules Bordet. Lucia Del Mastro received honoraria from Takeda and personal fees from Ipsen and Takeda outside the submitted work. Giulia Viglietti declares that she has no conflict of interest. Noam F. Pondé declares that he has no conflict of interest. Cinzia Solinas declares that she has no conflict of interest. Evandro de Azambuja declares that he has no conflict of interest.

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Lambertini, M., Del Mastro, L., Viglietti, G. et al. Ovarian Function Suppression in Premenopausal Women with Early-Stage Breast Cancer. Curr. Treat. Options in Oncol. 18, 4 (2017). https://doi.org/10.1007/s11864-017-0442-8

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