• K. J. Ruddy
  • A. H. Partridge
Part of the Cancer Treatment and Research book series (CTAR, volume 151)


Breast cancer is the most common invasive cancer in women of childbearing age, and the most common cause of cancer-related death in young women. It is estimated that 1 in every 210 women under 40 years old will be diagnosed with breast cancer, and young women represent approximately 5% of new breast cancer patients in the United States [1]. This translates into more than 10,000 women diagnosed annually with breast cancer under age 40 in the United States alone, and over 50,000 young women diagnosed worldwide [1]. Young women with breast cancer face not only the anxieties associated with a potentially life-threatening illness and aggressive treatment, but also several unique medical and psychosocial issues. Future fertility, in particular, has been increasingly recognized as a major concern for many young breast cancer survivors [2, 3].


Breast Cancer Luteinizing Hormone Breast Cancer Survivor Ovarian Reserve Fertility Preservation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2007. CA Cancer J Clin. 2007;57:43–66.PubMedCrossRefGoogle Scholar
  2. 2.
    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(18):2917–31.Google Scholar
  3. 3.
    Partridge AH, Gelber S, Peppercorn J, et al. Web-based survey of fertility issues in young women with breast cancer. J Clin Oncol. 2004;22:4174–83.PubMedCrossRefGoogle Scholar
  4. 4.
    Pagani O, O'Neill A, Castiglione M, et al. Prognostic impact of amenorrhoea after adjuvant chemotherapy in premenopausal breast cancer patients with axillary node involvement: results of the International Breast Cancer Study Group (IBCSG) Trial VI. Eur J Cancer. 1998;34:632–40.PubMedCrossRefGoogle Scholar
  5. 5.
    Parulekar WR, Day AG, Ottaway JA, et al. Incidence and prognostic impact of amenorrhea during adjuvant therapy in high-risk premenopausal breast cancer: analysis of a National Cancer Institute of Canada Clinical Trials Group Study--NCIC CTG MA.5. J Clin Oncol. 2005;23:6002–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Goldhirsch A, Gelber RD, Castiglione M. The magnitude of endocrine effects of adjuvant chemotherapy for premenopausal breast cancer patients. The International Breast Cancer Study Group. Ann Oncol. 1990;1:183–8.PubMedGoogle Scholar
  7. 7.
    Louis J, Limarzi LR, Best WR. Treatment of chronic granulocytic leukemia with Myleran. Arch Int Med. 1956;97:299–308.CrossRefGoogle Scholar
  8. 8.
    Falcone T, Attaran M, Bedaiwy MA, et al. Ovarian function preservation in the cancer patient. Fertil Steril. 2004;81:243–57PubMedCrossRefGoogle Scholar
  9. 9.
    Marhhom E, Cohen I. Fertility preservation options for women with malignancies. Obstet Gynecol Surv. 2007;62:58–72.PubMedCrossRefGoogle Scholar
  10. 10.
    Di Cosimo S, Alimonti A, Ferretti G, et al. Incidence of chemotherapy-induced amenorrhea depending on the timing of treatment by menstrual cycle phase in women with early breast cancer. Ann Oncol. 2004;15:1065–71.PubMedCrossRefGoogle Scholar
  11. 11.
    Hrushesky WJ, Vyzula R, Wood PA. Fertility maintenance and 5-fluorouracil timing within the mammalian fertility cycle. Reprod Toxicol. 1999;13:413–20.PubMedCrossRefGoogle Scholar
  12. 12.
    Mehta RR, Beattie CW, Das Gupta TK. Endocrine profile in breast cancer patients receiving chemotherapy. Breast Cancer Res Treat. 1992;20:125–32PubMedCrossRefGoogle Scholar
  13. 13.
    Walshe JM, Denduluri N, Swain SM. Amenorrhea in premenopausal women after adjuvant chemotherapy for breast cancer. J Clin Oncol. 2006;24:5769–79.PubMedCrossRefGoogle Scholar
  14. 14.
    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;24:1045–51.PubMedCrossRefGoogle Scholar
  15. 15.
    Bines J, Oleske DM, Cobleigh MA. Ovarian function in premenopausal women treated with adjuvant chemotherapy for breast cancer. J Clin Oncol. 1996;14:1718–29.PubMedGoogle Scholar
  16. 16.
    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;21:2583–92.PubMedCrossRefGoogle Scholar
  17. 17.
    Kramer R, Tham YL, Sexton K, et al. Chemotherapy-induced amenorrhea is increased in patients treated wtih adjuvant doxorubicin and cyclophosphamide (AC) followed by a taxane (T). J Clin Oncol, ASCO Annual Meeting Proceedings 2005;23:651.Google Scholar
  18. 18.
    Fornier MN, Modi S, Panageas KS, et al. Incidence of chemotherapy-induced, long-term amenorrhea in patients with breast carcinoma age 40 years and younger after adjuvant anthracycline and taxane. Cancer. 2005;104:1575–9.PubMedCrossRefGoogle Scholar
  19. 19.
    Abusief ME, Missmer SA, Ginsburg ES, et al. Chemotherapy-related amenorrhea in women with early breast cancer: The effect of paclitaxel or dose density. Journal of Clinical Oncology, ASCO Annual Meeting Proceedings (Post-Meeting Edition). 2006;24:10506.Google Scholar
  20. 20.
    Byrne J, Fears TR, Gail MH, et al. Early menopause in long-term survivors of cancer during adolescence. Am J Obstet Gynecol. 1992;166:788–93.PubMedGoogle Scholar
  21. 21.
    Chiarelli AM, Marrett LD, Darlington G. Early menopause and infertility in females after treatment for childhood cancer diagnosed in 1964–1988 in Ontario, Canada. Am J Epidemiol. 1999;150:245–54.PubMedGoogle Scholar
  22. 22.
    Sklar CA, Mertens AC, Mitby P, et al. Premature menopause in survivors of childhood cancer: A report from the childhood cancer survivor study. J Natl Cancer Inst. 2006;98:890–6.Google Scholar
  23. 23.
    Partridge A, Gelber S, Gelber R, et al. Delayed premature menopause following chemotherapy for early stage breast cancer: Long-term results from IBCSG Trial V. Proc Am Soc Clin Oncol. 2005;23:50s (abstract 687)Google Scholar
  24. 24.
    Partridge A, Gelber S, Gelber R, et al. Age of menopause among women who remain premenopausal following treatment for early breast cancer: long-term results from International Breast Cancer Study Group Trials V and VI. Eur J Cancer. In pressGoogle Scholar
  25. 25.
    Goodwin PJ, Ennis M, Pritchard KI, et al. Risk of menopause during the first year after breast cancer diagnosis. J Clin Oncol. 1999;17:2365–70.PubMedGoogle Scholar
  26. 26.
    Weghofer A, Margreiter M, Fauster Y, et al. Age-specific FSH levels as a tool for appropriate patient counselling in assisted reproduction. Hum Reprod. 1005;20:2448.–52Google Scholar
  27. 27.
    Bath LE, Tydeman G, Critchley HOD, et al. Spontaneous conception in a young woman who had ovarian cortical tissue cryopreservation before chemotherapy and radiotherapy for a Ewing's sarcoma of the pelvis: Case report. Hum Reprod. 2004;19:2569–72.Google Scholar
  28. 28.
    Blumenfeld Z, Ritter M, Shen-Orr Z, et al. Inhibin A concentrations in the sera of young women during and after chemotherapy for lymphoma: Correlation with ovarian toxicity. Am J Reprod Immunol. 1998;39:33–40PubMedCrossRefGoogle Scholar
  29. 29.
    Blumenfeld Z. 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. 2002;187:93–105.PubMedCrossRefGoogle Scholar
  30. 30.
    van Rooij IA, Broekmans FJ, te Velde ER, et al. Serum anti-Mullerian hormone levels: A novel measure of ovarian reserve. Hum Reprod. 2002;17:3065–71PubMedCrossRefGoogle Scholar
  31. 31.
    Scheffer GJ, Broekmans FJ, Looman CW, et al. The number of antral follicles in normal women with proven fertility is the best reflection of reproductive age. Hum Reprod. 2003;18:700–6.PubMedCrossRefGoogle Scholar
  32. 32.
    Schmidt KL, Byskov AG, Nyboe Andersen A, et al. Density and distribution of primordial follicles in single pieces of cortex from 21 patients and in individual pieces of cortex from three entire human ovaries. Hum Reprod. 2003;18:1158–64.PubMedCrossRefGoogle Scholar
  33. 33.
    Cook CL, Siow Y, Taylor S, et al. Serum mullerian-inhibiting substance levels during normal menstrual cycles. Fertil Steril. 2000;73:859–61.PubMedCrossRefGoogle Scholar
  34. 34.
    Whitehead E, Shalet SM, Blackledge G, et al. The effect of combination chemotherapy on ovarian function in women treated for Hodgkin's disease. Cancer. 1983;52:988–93.PubMedCrossRefGoogle Scholar
  35. 35.
    Behringer K, Breuer K, Reineke T, et al. Secondary amenorrhea after Hodgkin's lymphoma is influenced by age at treatment, stage of disease, chemotherapy regimen, and the use of oral contraceptives during therapy: A report from the German Hodgkin's Lymphoma Study Group. J Clin Oncol. 2005;23:7555–64.Google Scholar
  36. 36.
    Ataya K, Rao LV, Lawrence E, et al. Luteinizing hormone-releasing hormone agonist inhibits cyclophosphamide-induced ovarian follicular depletion in rhesus monkeys. Biol Reprod. 1995;52:365–72.PubMedCrossRefGoogle Scholar
  37. 37.
    Letterie GS. Anovulation in the prevention of cytotoxic-induced follicular attrition and ovarian failure. Hum Reprod. 2004;19:831–7.PubMedCrossRefGoogle Scholar
  38. 38.
    Grundker C, Emons G. Role of gonadotropin-releasing hormone (GnRH) in ovarian cancer. Reprod Biol Endocrinol. 2003;1:65.PubMedCrossRefGoogle Scholar
  39. 39.
    Waxman JH, Ahmed R, Smith D, et al. Failure to preserve fertility in patients with Hodgkin's disease. Cancer Chemother Pharmacol. 1987;19:159–62PubMedCrossRefGoogle Scholar
  40. 40.
    Dann EJ, Epelbaum R, Avivi I, et al. Fertility and ovarian function are preserved in women treated with an intensified regimen of cyclophosphamide, adriamycin, vincristine and prednisone (Mega-CHOP) for non-Hodgkin lymphoma. Hum Reprod. 2005;20:2247–9.PubMedCrossRefGoogle Scholar
  41. 41.
    Blumenfeld Z, Eckman A. Preservation of fertility and ovarian function and minimization of chemotherapy-induced gonadotoxicity in young women by GnRH-a. J Natl Cancer Inst Monogr. 2005;40–3Google Scholar
  42. 42.
    Pereyra Pacheco B, Mendez Ribas JM, Milone G, et al. Use of GnRH analogs for functional protection of the ovary and preservation of fertility during cancer treatment in adolescents: A preliminary report. Gynecol Oncol. 2001;81:391–7Google Scholar
  43. 43.
    Recchia F, Sica G, De Filippis S, et al. Goserelin as ovarian protection in the adjuvant treatment of premenopausal breast cancer: A phase II pilot study. Anticancer Drugs. 2002;13:417–24.PubMedCrossRefGoogle Scholar
  44. 44.
    Fox KR, Scialla J, Moore H. Preventing chemotherapy-related amenorrhea using leuprolide during adjuvant chemotherapy for early-stage breast cancer [abstract 50]. Proc ASCO. 2003;22:13.Google Scholar
  45. 45.
    Danforth DR, Arbogast LK, Friedman CI. Acute depletion of murine primordial follicle reserve by gonadotropin-releasing hormone antagonists. Fertil Steril. 2005;83:1333–8PubMedCrossRefGoogle Scholar
  46. 46.
    Meirow D, Assad G, Dor J, et al. The GnRH antagonist cetrorelix reduces cyclophosphamide-induced ovarian follicular destruction in mice. Hum Reprod. 2004;19:1294–9.PubMedCrossRefGoogle Scholar
  47. 47.
    Morita Y, Perez GI, Paris F, et al. Oocyte apoptosis is suppressed by disruption of the acid sphingomyelinase gene or by sphingosine-1-phosphate therapy. Nat Med. 2000;6:1109–14.PubMedCrossRefGoogle Scholar
  48. 48.
    Pal L, Leykin L, Schifren JL, et al. Malignancy may adversely influence the quality and behaviour of oocytes. Hum Reprod. 1998;13:1837–40.PubMedCrossRefGoogle Scholar
  49. 49.
    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;18:90–5.PubMedCrossRefGoogle Scholar
  50. 50.
    Mitwally MF, Casper RF. Single-dose administration of an aromatase inhibitor for ovarian stimulation. Fertil Steril. 2005;83:229–31.PubMedCrossRefGoogle Scholar
  51. 51.
    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;23:4347–53.PubMedCrossRefGoogle Scholar
  52. 52.
    Kim SS, Radford J, Harris M, et al. Ovarian tissue harvested from lymphoma patients to preserve fertility may be safe for autotransplantation. Hum Reprod. 2001;16:2056–60.PubMedCrossRefGoogle Scholar
  53. 53.
    Donnez J, Dolmans MM, Demylle D, et al. Restoration of ovarian function after orthotopic (intraovarian and periovarian) transplantation of cryopreserved ovarian tissue in a woman treated by bone marrow transplantation for sickle cell anaemia: case report. Hum Reprod. 2006:21:183–8.Google Scholar
  54. 54.
    Donnez J, Dolmans MM, Demylle D, et al. Livebirth after orthotopic transplantation of cryopreserved ovarian tissue. Lancet. 2004;364:1405–10.PubMedCrossRefGoogle Scholar
  55. 55.
    Partridge A, Gelber S, Peppercorn J, et al. Fertility outcomes in young women with breast cancer: A web-based survey. Proc ASCO. 2004;23:538 [abstract #6085].Google Scholar
  56. 56.
    Ives A, Saunders C, Bulsara M, et al. Pregnancy after breast cancer: Population based study. BMJ.2007;334:194.PubMedCrossRefGoogle Scholar
  57. 57.
    Hawkins MM. Pregnancy outcome and offspring after childhood cancer. BMJ. 1994;309:1034.PubMedCrossRefGoogle Scholar
  58. 58.
    Kroman N, Jensen MB, Melbye M, et al. Should women be advised against pregnancy after breast-cancer treatment? Lancet. 1997;350:319–22.PubMedCrossRefGoogle Scholar
  59. 59.
    Sankila R, Heinavaara S, Hakulinen T. Survival of breast cancer patients after subsequent term pregnancy: “Healthy mother effect”. Am J Obstet Gynecol. 1994;170:818–23.PubMedGoogle Scholar
  60. 60.
    von Schoultz E, Johansson H, Wilking N, et al. Influence of prior and subsequent pregnancy on breast cancer prognosis. J Clin Oncol. 1995;13:430–4.Google Scholar
  61. 61.
    Petrek JA. Pregnancy safety after breast cancer. Cancer. 1994;74:528–31.PubMedCrossRefGoogle Scholar
  62. 62.
    Gemignani ML, Petrek JA. Pregnancy After Breast Cancer. Cancer Control. 1999;6:272–6.PubMedGoogle Scholar
  63. 63.
    Velentgas P, Daling JR, Malone KE, et al. Pregnancy after breast carcinoma: Outcomes and Influence on Mortality. Cancer. 1999;85:2424–32.PubMedCrossRefGoogle Scholar
  64. 64.
    Dow KH. Having children after breast cancer. Cancer Pract. 1994;2:407–13.PubMedGoogle Scholar
  65. 65.
    Higgins S, Haffty BG. Pregnancy and lactation after breast-conserving therapy for early stage breast cancer. Cancer. 1994;73:2175–80.PubMedCrossRefGoogle Scholar
  66. 66.
    Gelber S, Coates AS, Goldhirsch A, et al. Effect of pregnancy on overall survival after the diagnosis of early-stage breast cancer. J Clin Oncol. 2001;19:1671–5.PubMedGoogle Scholar
  67. 67.
    Upponi SS, Ahmad F, Whitaker IS, et al. Pregnancy after breast cancer. Eur J Cancer. 2003;39:736–41.PubMedCrossRefGoogle Scholar
  68. 68.
    Mueller BA, Simon MS, Deapen D, et al. Childbearing and survival after breast carcinoma in young women. Cancer. 2003;98:1131–40.PubMedCrossRefGoogle Scholar
  69. 69.
    Blakely LJ, Buzdar AU, Lozada JA, et al. Effects of pregnancy after treatment for breast carcinoma on survival and risk of recurrence. Cancer. 2004;100:465–9.PubMedCrossRefGoogle Scholar
  70. 70.
    Sankila R, Heinavaara S, Hakulinen T. Survival of breast cancer patients after subsequent term pregnancy: “Healthy mother effect”. Am J Obstet Gynecol. 1994;170:818–23.PubMedGoogle Scholar
  71. 71.
    Yuri T, Tsukamoto R, Miki K, et al. Biphasic effects of zeranol on the growth of estrogen receptor-positive human breast carcinoma cells. Oncol Rep. 2006;16:1307–12.PubMedGoogle Scholar
  72. 72.
    Duffy CM, Allen SM, Clark MA. Discussions regarding reproductive health for young women with breast cancer undergoing chemotherapy. J Clin Oncol. 2005;23:766–73.PubMedCrossRefGoogle Scholar
  73. 73.
    Thewes B, Meiser B, Taylor A, et al. Fertility- and menopause-related information needs of younger women with a diagnosis of early breast cancer. J Clin Oncol. 2005;23:5155–65.PubMedCrossRefGoogle Scholar
  74. 74.
    Burstein HJ, Winer EP. Primary care for survivors of breast cancer. N Engl J Med. 2000;343:1086–94.PubMedCrossRefGoogle Scholar
  75. 75.
    Martin M, Pienkowski T, Mackey J, et al. Adjuvant docetaxel for node-positive breast cancer. N Engl J Med. 2005;352:2302–13.PubMedCrossRefGoogle Scholar
  76. 76.
    Castelo-Branco C, Nomdedeu B, Camus A, et al. Use of gonadotropin-releasing hormone agonists in patients with Hodgkin's disease for preservation of ovarian function and reduction of gonadotoxicity related to chemotherapy. Fertil Steril. 2007;87:702–5.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Brigham and Women’s Hospital, Harvard Medical SchoolDana-Farber Cancer InstituteBostonUSA
  2. 2.Dana-Farber Cancer InstituteBostonUSA

Personalised recommendations