Skip to main content

Advertisement

SpringerLink
Log in

Reproductive Considerations for Patients with Early-Onset Breast Cancer

  • Fertility Issues and Breast Cancer (J Jeruss, Section Editor)
  • Published:
Current Breast Cancer Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Early-onset breast cancer presents various challenges in regard to reproductive health. This review examines the current data pertaining to issues such as fertility preservation, preimplantation genetics, the impact of chemotherapy and endocrine therapy, contraception, and pregnancy in the young breast cancer population.

Recent Findings

Many breast cancer treatments such as chemotherapy and endocrine therapy can be gonadotoxic or teratogenic. Multiple fertility preservation options are now available to young breast cancer patients, including embryo and oocyte preservation, ovarian tissue preservation, and ovarian suppression with GnRH agonists. In patients with known cancer germline mutations, preimplantation genetic testing is an option.

Summary

Fertility preservation and other reproductive services are expanding and offer great promise to the early-onset breast cancer community. Providers must be knowledgeable about the various options in order to better empower patients.

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

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 2021. CA Cancer J Clin. 2021;71:7–33.

    Article  PubMed  Google Scholar 

  2. National Cancer Institute Cancer stat facts: female breast cancer.

  3. Lambertini M, Moore HCF, Leonard RCF, et al. Gonadotropin-Releasing Hormone Agonists During Chemotherapy for Preservation of Ovarian Function and Fertility in Premenopausal Patients With Early Breast Cancer: A Systematic Review and Meta-Analysis of Individual Patient-Level Data. J Clin Oncol. 2018;36:1981–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Poggio F, Lambertini M, Bighin C, et al. Potential Mechanisms of Ovarian Protection with Gonadotropin-Releasing Hormone Agonist in Breast Cancer Patients: A Review. Clin Med Insights Reprod Health. 2019;13:1179558119864584.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Partridge AH, Ruddy KJ, Gelber S, Schapira L, Abusief M, Meyer M, Ginsburg E. Ovarian reserve in women who remain premenopausal after chemotherapy for early stage breast cancer. Fertil Steril. 2010;94:638–44.

    Article  PubMed  Google Scholar 

  6. Kim J, Mersereau JE, Su HI, Whitcomb BW, Malcarne VL, Gorman JR. Young female cancer survivors’ use of fertility care after completing cancer treatment. Support Care Cancer. 2016;24:3191–9.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Donnez J, Dolmans M-M. Fertility Preservation in Women. N Engl J Med. 2017;377:1657–65.

    Article  PubMed  Google Scholar 

  8. Young K, Shliakhtsitsava K, Natarajan L, Myers E, Dietz AC, Gorman JR, Martínez ME, Whitcomb BW, Su HI. Fertility counseling before cancer treatment and subsequent reproductive concerns among female adolescent and young adult cancer survivors. Cancer. 2019;125:980–9.

    Article  PubMed  Google Scholar 

  9. Letourneau JM, Ebbel EE, Katz PP, Katz A, Ai WZ, Chien AJ, Melisko ME, Cedars MI, Rosen MP. Pretreatment fertility counseling and fertility preservation improve quality of life in reproductive age women with cancer. Cancer. 2012;118:1710–7.

    Article  PubMed  Google Scholar 

  10. Oktem O, Oktay K. Quantitative assessment of the impact of chemotherapy on ovarian follicle reserve and stromal function. Cancer. 2007;110:2222–9.

    Article  CAS  PubMed  Google Scholar 

  11. Chemaitilly W, Li Z, Krasin MJ, et al. Premature Ovarian Insufficiency in Childhood Cancer Survivors: A Report From the St. Jude Lifetime Cohort. J Clin Endocrinol Metab. 2017;102:2242–50.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Moravek MB, Appiah LC, Anazodo A, et al. Development of a Pediatric Fertility Preservation Program: A Report From the Pediatric Initiative Network of the Oncofertility Consortium. J Adolesc Health. 2019;64:563–73.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Moravek MB, Confino R, Smith KN, Kazer RR, Klock SC, Lawson AK, Gradishar WJ, Pavone ME. Long-term outcomes in cancer patients who did or did not pursue fertility preservation. Fertil Steril. 2018;109:349–55.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Logan S, Perz J, Ussher J, Peate M, Anazodo A. Clinician provision of oncofertility support in cancer patients of a reproductive age: A systematic review. Psychooncology. 2018;27:748–56.

    Article  CAS  PubMed  Google Scholar 

  15. •• Practice Committee of the American Society for Reproductive Medicine. Electronic address: asrm@asrm.org. Fertility preservation in patients undergoing gonadotoxic therapy or gonadectomy: a committee opinion. Fertil Steril. 2019;112:1022–33 The ASRM Committee Opinion is an excellent summary of fertility options for patients undergoing gonadotoxic therapy.

    Article  Google Scholar 

  16. Lambertini M, Del Mastro L, Pescio MC, et al. Cancer and fertility preservation: international recommendations from an expert meeting. BMC Med. 2016;14:1.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Marklund A, Eloranta S, Wikander I, Kitlinski ML, Lood M, Nedstrand E, Thurin-Kjellberg A, Zhang P, Bergh J, Rodriguez-Wallberg KA. Efficacy and safety of controlled ovarian stimulation using GnRH antagonist protocols for emergency fertility preservation in young women with breast cancer-a prospective nationwide Swedish multicenter study. Hum Reprod. 2020;35:929–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Rodgers RJ, Reid GD, Koch J, Deans R, Ledger WL, Friedlander M, Gilchrist RB, Walters KA, Abbott JA. The safety and efficacy of controlled ovarian hyperstimulation for fertility preservation in women with early breast cancer: a systematic review. Hum Reprod. 2017;32:1033–45.

    Article  CAS  PubMed  Google Scholar 

  19. Argyle CE, Harper JC, Davies MC. Oocyte cryopreservation: where are we now? Hum Reprod Update. 2016;22:440–9.

    Article  CAS  PubMed  Google Scholar 

  20. Zhang X, Niu J, Che T, Zhu Y, Zhang H, Qu J. Fertility preservation in BRCA mutation carriers-efficacy and safety issues: a review. Reprod Biol Endocrinol. 2020;18:11.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Kasum M, von Wolff M, Franulić D, Čehić E, Klepac-Pulanić T, Orešković S, Juras J. Fertility preservation options in breast cancer patients. Gynecol Endocrinol. 2015;31:846–51.

    PubMed  Google Scholar 

  22. Kotsopoulos J, Librach CL, Lubinski J, et al. Infertility, treatment of infertility, and the risk of breast cancer among women with BRCA1 and BRCA2 mutations: a case-control study. Cancer Causes Control. 2008;19:1111–9.

    Article  PubMed  Google Scholar 

  23. Turan V, Bedoschi G, Emirdar V, Moy F, Oktay K. Ovarian Stimulation in Patients With Cancer: Impact of Letrozole and BRCA Mutations on Fertility Preservation Cycle Outcomes. Reprod Sci. 2018;25:26–32.

    Article  CAS  PubMed  Google Scholar 

  24. Wald K, Cakmak H, Mok-Lin E, Cedars M, Rosen M, Letourneau J. Back-to-back random-start ovarian stimulation prior to chemotherapy to maximize oocyte yield. J Assist Reprod Genet. 2019;36:1161–8.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Levine JM, Kelvin JF, Quinn GP, Gracia CR. Infertility in reproductive-age female cancer survivors. Cancer. 2015;121:1532–9.

    Article  PubMed  Google Scholar 

  26. Roness H, Kashi O, Meirow D. Prevention of chemotherapy-induced ovarian damage. Fertil Steril. 2016;105:20–9.

    Article  CAS  PubMed  Google Scholar 

  27. Oktay K, Harvey BE, Partridge AH, Quinn GP, Reinecke J, Taylor HS, Wallace WH, Wang ET, Loren AW. Fertility Preservation in Patients With Cancer: ASCO Clinical Practice Guideline Update. J Clin Oncol. 2018;36:1994–2001.

    Article  PubMed  Google Scholar 

  28. Shapira M, Dolmans M-M, Silber S, Meirow D. Evaluation of ovarian tissue transplantation: results from three clinical centers. Fertil Steril. 2020;114:388–97.

    Article  PubMed  Google Scholar 

  29. Somigliana E, Terenziani M, Filippi F, Bergamini A, Martinelli F, Mangili G, Peccatori F, Vercellini P. Chemotherapy-related damage to ovarian reserve in childhood cancer survivors: interpreting the evidence. J Assist Reprod Genet. 2019;36:341–8.

    Article  PubMed  Google Scholar 

  30. Shandley LM, Fothergill A, Spencer JB, Mertens AC, Cottrell HN, Howards PP. Impact of cancer treatment on risk of infertility and diminished ovarian reserve in women with polycystic ovary syndrome. Fertil Steril. 2018;109:516–525.e1.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Palinska-Rudzka KE, Ghobara T, Parsons N, Milner J, Lockwood G, Hartshorne GM. Five-year study assessing the clinical utility of anti-Müllerian hormone measurements in reproductive-age women with cancer. Reprod Biomed Online. 2019;39:712–20.

    Article  CAS  PubMed  Google Scholar 

  32. Dillon KE, Sammel MD, Prewitt M, Ginsberg JP, Walker D, Mersereau JE, Gosiengfiao Y, Gracia CR. Pretreatment antimüllerian hormone levels determine rate of posttherapy ovarian reserve recovery: acute changes in ovarian reserve during and after chemotherapy. Fertil Steril. 2013;99:477–83.

    Article  CAS  PubMed  Google Scholar 

  33. Clark RA, Mostoufi-Moab S, Yasui Y, et al. Predicting acute ovarian failure in female survivors of childhood cancer: a cohort study in the Childhood Cancer Survivor Study (CCSS) and the St Jude Lifetime Cohort (SJLIFE). Lancet Oncol. 2020;21:436–45.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Green DM, Nolan VG, Goodman PJ, et al. The cyclophosphamide equivalent dose as an approach for quantifying alkylating agent exposure: a report from the Childhood Cancer Survivor Study. Pediatr Blood Cancer. 2014;61:53–67.

    Article  CAS  PubMed  Google Scholar 

  35. Oncofertility Decision Tool Web Portal. In: The Oncofertility Consortium. https://oncofertility.northwestern.edu/resources/oncofertility-decision-tool-web-portal. Accessed 10 Oct 2021

  36. Fertility Risk Chart for Women. In: Livestrong. https://www.livestrong.org/content/fertility-risk-chart-women. Accessed 10 Oct 2021

  37. National Comprehensive Cancer Network (Version 1.2022) Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic.

  38. Sciorio R, Anderson RA. Fertility preservation and preimplantation genetic assessment for women with breast cancer. Cryobiology. 2020;92:1–8.

    Article  CAS  PubMed  Google Scholar 

  39. • Vuković P, Peccatori FA, Massarotti C, Miralles MS, Beketić-Orešković L, Lambertini M. Preimplantation genetic testing for carriers of BRCA1/2 pathogenic variants. Crit Rev Oncol Hematol. 2021;157:103201 Vukovick et al., 2021 provides a comprehensive overview of reproductive considerations for BRCA mutation carriers and touches on the ethical implications of PGT.

    Article  PubMed  Google Scholar 

  40. Wallis JM. Is it ever morally permissible to select for deafness in one’s child? Med Health Care Philos. 2020;23:3–15.

    Article  PubMed  Google Scholar 

  41. Schuurman TN, Witteveen PO, van der Wall E, Passier JLM, Huitema ADR, Amant F, Lok CAR. Tamoxifen and pregnancy: an absolute contraindication? Breast Cancer Res Treat. 2019;175:17–25.

    Article  CAS  PubMed  Google Scholar 

  42. Cullins SL, Pridjian G, Sutherland CM. Goldenhar’s syndrome associated with tamoxifen given to the mother during gestation. JAMA. 1994;271:1905–6.

    Article  CAS  PubMed  Google Scholar 

  43. Berger JC, Clericuzio CL. Pierre Robin sequence associated with first trimester fetal tamoxifen exposure. Am J Med Genet A. 2008;146A:2141–4.

    Article  PubMed  Google Scholar 

  44. Tewari K, Bonebrake RG, Asrat T, Shanberg AM. Ambiguous genitalia in infant exposed to tamoxifen in utero. Lancet. 1997;350:183.

    Article  CAS  PubMed  Google Scholar 

  45. Koca E, Kuzan TY, Babacan T, Turkbeyler IH, Furkan S, Altundag K. Safety of tamoxifen during pregnancy: 3 case reports and review of the literature. Breast Care. 2013;8:453–4.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Shandley LM, Spencer JB, Fothergill A, Mertens AC, Manatunga A, Paplomata E, Howards PP. Impact of tamoxifen therapy on fertility in breast cancer survivors. Fertil Steril. 2017;107:243–252.e5.

    Article  CAS  PubMed  Google Scholar 

  47. Machado F, Rodríguez JR, León JPH, Rodríguez JR, Parrilla JJ, Abad L. Tamoxifen and endometrial cancer. Is screening necessary? A review of the literature. Eur J Gynaecol Oncol. 2005;26:257–65.

    CAS  PubMed  Google Scholar 

  48. McGonigle KF, Shaw SL, Vasilev SA, Odom-Maryon T, Roy S, Simpson JF. Abnormalities detected on transvaginal ultrasonography in tamoxifen-treated postmenopausal breast cancer patients may represent endometrial cystic atrophy. Am J Obstet Gynecol. 1998;178:1145–50.

    Article  CAS  PubMed  Google Scholar 

  49. Buonomo B, Brunello A, Noli S, Miglietta L, Del Mastro L, Lambertini M, Peccatori FA. Tamoxifen Exposure during Pregnancy: A Systematic Review and Three More Cases. Breast Care. 2020;15:148–56.

    Article  PubMed  Google Scholar 

  50. von Schoultz E, Johansson H, Wilking N, Rutqvist LE. Influence of prior and subsequent pregnancy on breast cancer prognosis. J Clin Oncol. 1995;13:430–4.

    Article  Google Scholar 

  51. Braems G, Denys H, De Wever O, Cocquyt V, Van den Broecke R. Use of tamoxifen before and during pregnancy. Oncologist. 2011;16:1547–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Fraser HM. GnRH analogues for contraception. Br Med Bull. 1993;49:62–72.

    Article  CAS  PubMed  Google Scholar 

  53. Sweeney C, Giuliano AR, Baumgartner KB, Byers T, Herrick JS, Edwards SL, Slattery ML. Oral, injected and implanted contraceptives and breast cancer risk among U.S. Hispanic and non-Hispanic white women. Int J Cancer. 2007;121:2517–23.

    Article  CAS  PubMed  Google Scholar 

  54. Althuis MD, Brogan DD, Coates RJ, Daling JR, Gammon MD, Malone KE, Schoenberg JB, Brinton LA. Breast cancers among very young premenopausal women (United States). Cancer Causes Control. 2003;14:151–60.

    Article  PubMed  Google Scholar 

  55. Cooper JA, Rohan TE, Cant EL, Horsfall DJ, Tilley WD. Risk factors for breast cancer by oestrogen receptor status: a population-based case-control study. Br J Cancer. 1989;59:119–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Dolle JM, Daling JR, White E, Brinton LA, Doody DR, Porter PL, Malone KE. Risk factors for triple-negative breast cancer in women under the age of 45 years. Cancer Epidemiol Biomarkers Prev. 2009;18:1157–66.

    Article  PubMed  PubMed Central  Google Scholar 

  57. •• Trussell J, Aiken ARA, Micks E, Guthrie KA. Efficacy, safety, and personal considerations. In: Hatcher RA, Nelson AL, Trussell J, Cwiak C, Cason P, Policar MS, Edelman A, ARA A, Marrazzo J, Kowal D, editors. Contraceptive technology: Ayer Company Publishers, Inc; 2018. Trussell et al., 2018 provides up-to-date estimates on contraception failure rates. This may be useful for physicians as they counsel their patients on the effectiveness of each method.

    Google Scholar 

  58. Lambertini M, Kroman N, Ameye L, et al. Long-term Safety of Pregnancy Following Breast Cancer According to Estrogen Receptor Status. J Natl Cancer Inst. 2018;110:426–9.

    Article  PubMed  Google Scholar 

  59. Lambertini M, Ameye L, Hamy A-S, et al. Pregnancy After Breast Cancer in Patients With Germline BRCA Mutations. J Clin Oncol. 2020;38:3012–23.

    Article  PubMed  Google Scholar 

  60. Valentini A, Lubinski J, Byrski T, et al. The impact of pregnancy on breast cancer survival in women who carry a BRCA1 or BRCA2 mutation. Breast Cancer Res Treat. 2013;142:177–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Hartman EK, Eslick GD. The prognosis of women diagnosed with breast cancer before, during and after pregnancy: a meta-analysis. Breast Cancer Res Treat. 2016;160:347–60.

    Article  CAS  PubMed  Google Scholar 

  62. Pregnancy Outcome and Safety of Interrupting Therapy for Women with Estrogen Responsive Breast Cancer (POSITIVE). In: NIH U.S. National Library of Medicine: ClinicalTrials.gov. https://clinicaltrials.gov/show/NCT02308085. Accessed 10 Oct 2021

  63. Omesi L, Narayan A, Reinecke J, Schear R, Levine J. Financial Assistance for Fertility Preservation Among Adolescent and Young Adult Cancer Patients: A Utilization Review of the Sharing Hope/LIVESTRONG Fertility Financial Assistance Program. J Adolesc Young Adult Oncol. 2019;8:554–9.

    Article  PubMed  Google Scholar 

  64. Options for Women. In: Alliance for Fertility Preservation. https://www.allianceforfertilitypreservation.org/index.htm. Accessed 10 Oct 2021

  65. In: The Oncofertility Consortium. http://oncofertility.northwestern.edu/. Accessed 10 Oct 2021

  66. Liu Q, Yao S, Zhao H, Hu Q, Kwan ML, Roh JM, Ambrosone CB, Kushi LH, Liu S, Zhu Q. Early-onset triple-negative breast cancer in multiracial/ethnic populations: Distinct trends of prevalence of truncation mutations. Cancer Med. 2019;8:1845–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Eaglehouse YL, Georg MW, Shriver CD, Zhu K. Racial Differences in Time to Breast Cancer Surgery and Overall Survival in the US Military Health System. JAMA Surg. 2019;154:e185113.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Williams DR, Mohammed SA, Shields AE. Understanding and effectively addressing breast cancer in African American women: Unpacking the social context. Cancer. 2016;122:2138–49.

    Article  PubMed  Google Scholar 

  69. Yedjou CG, Sims JN, Miele L, Noubissi F, Lowe L, Fonseca DD, Alo RA, Payton M, Tchounwou PB. Health and Racial Disparity in Breast Cancer. Adv Exp Med Biol. 2019;1152:31–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Walsh SM, Zabor EC, Stempel M, Morrow M, Gemignani ML. Does race predict survival for women with invasive breast cancer? Cancer. 2019;125:3139–46.

    Article  CAS  PubMed  Google Scholar 

  71. McGee SA, Durham DD, Tse C-K, Millikan RC. Determinants of breast cancer treatment delay differ for African American and White women. Cancer Epidemiol Biomarkers Prev. 2013;22:1227–38.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Jones T, Lockhart JS, Mendelsohn-Victor KE, et al. Use of Cancer Genetics Services in African-American Young Breast Cancer Survivors. Am J Prev Med. 2016;51:427–36.

    Article  PubMed  Google Scholar 

  73. Jackson-Bey T, Morris J, Jasper E, Velez Edwards DR, Thornton K, Richard-Davis G, Plowden TC. Systematic review of racial and ethnic disparities in reproductive endocrinology and infertility: where do we stand today? F&S Reviews. 2021;2:169–88.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Cancer Genetics & Breast Health, Department of Obstetrics and Gynecology, University of Michigan, L4204 UH South, 1500 E. Medical Center Dr., SPC 5276, Ann Arbor, MI, 48109-5276, USA

    Versha Pleasant & Mark D. Pearlman

  2. Audobon Fertility, New Orleans, LA, USA

    Nicole Ulrich

  3. Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Department of Urology, University of Michigan, Ann Arbor, MI, USA

    Nicole Ulrich, Mark D. Pearlman & Molly B. Moravek

Authors
  1. Versha Pleasant
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nicole Ulrich
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mark D. Pearlman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Molly B. Moravek
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Versha Pleasant.

Ethics declarations

Conflict of Interest

Versha Pleasant currently works as a consultant for InheRET Inc. She does not hold stocks or shares in this company. She does not hold any leadership or board positions.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Fertility Issues and Breast Cancer

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pleasant, V., Ulrich, N., Pearlman, M.D. et al. Reproductive Considerations for Patients with Early-Onset Breast Cancer. Curr Breast Cancer Rep 14, 37–45 (2022). https://doi.org/10.1007/s12609-022-00445-3

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12609-022-00445-3

Keywords

Search

Navigation