SpringerLink
Log in

Hereditary breast cancer and fertility preservation outcomes

  • Fertility Preservation
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

To determine the frequency of hereditary breast cancer associated with different mutated genes and to evaluate fertility preservation (FP) outcomes among young women with hereditary breast cancer when compared to non-hereditary breast cancer.

Material and methods

A retrospective cohort study of women with breast cancer who underwent fertility preservation treatment at our academic fertility center between 2005 and 2019. We included all women with breast cancer aged < 40 years who had a genetic testing and underwent fertility preservation before starting gonadotoxic therapy (n = 132). Our objective was to evaluate the total number of oocytes retrieved, mature oocytes MII, embryos (where appropriate), cryopreserved oocytes, and/or embryos.

Results

Of 132 women with breast cancer, 40 women were found to be genetically positive (31.4%), 31 women of 40 (77.5%) had a BRCA mutation, 3 (7.5%) had ATM, 2 (5%) had CHK2, and one (2.5%) for each of the following genes: PALP2, NF, MUTYH.c.536A, and TP53. There was no significant difference between the groups in the total number of eggs retrieved and the number of MII oocytes and cryopreserved oocytes. The numbers of fertilized oocytes and cryopreserved embryos in the hereditary (n = 40) and non-hereditary (n = 92) group were (5.15 ± 6.6 vs 2.90 ± 4.2, P = 0.054) and (3.35 ± 3.7 vs 1.9 ± 2.8, P = 0.046) respectively.

Conclusion

More than three quarters of positive mutated genes in women with breast cancer are BRCA mutations. Compared to those with non-hereditary breast cancer, women with hereditary breast cancer attained higher number of cryopreserved embryos.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Germany)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Code availability

Not applicable.

Abbreviations

AFC:

Antral follicle count

ATM:

Ataxia-telangiectasia mutated

BRCA:

Breast cancer gene

CP:

Clinical pregnancy

CHK2:

Checkpoint kinase 2

DOR:

Diminish ovarian reserve

ET:

Endometrial thickness

FET:

Frozen embryo transfer

FSH:

Follicle stimulating hormone

GnRH:

Gonadotropin releasing hormone

HRT:

Hormonal replacement treatment

HCG:

Human chorionic gonadotropin

IVF:

In vitro fertilization

IVM:

In vitro maturation

ICSI:

Intracytoplasmic sperm injection

LBR:

Live birth rate

NF1:

Neurofibromin 1

PALP2:

Partner and localizer of BRCA 2

PCOS:

Polycystic ovarian syndrome

References

  1. DeSantis CE, Ma J, Gaudet MM, Newman LA, Miller KD, Goding Sauer A, et al. Breast cancer statistics, 2019. CA Cancer J Clin. 2019;69(6):438–51. https://doi.org/10.3322/caac.21583.

    Article  PubMed  Google Scholar 

  2. Radecka B, Litwiniuk M. Breast cancer in young women. Ginekol Pol. 2016;87(9):659–63. https://doi.org/10.5603/GP.2016.0062.

    Article  PubMed  Google Scholar 

  3. McCray DK, Simpson AB, Flyckt R, Liu Y, O’Rourke C, Crowe JP, et al. Fertility in women of reproductive age after breast cancer treatment: practice patterns and outcomes. Ann Surg Oncol. 2016;23(10):3175–81. https://doi.org/10.1245/s10434-016-5308-y.

    Article  PubMed  Google Scholar 

  4. Vu JV, Llarena NC, Estevez SL, Moravek MB, Jeruss JS. Oncofertility program implementation increases access to fertility preservation options and assisted reproductive procedures for breast cancer patients. J Surg Oncol. 2017;115(2):116–21. https://doi.org/10.1002/jso.24418.

    Article  PubMed  Google Scholar 

  5. Apostolou P, Fostira F. Hereditary breast cancer: the era of new susceptibility genes. Biomed Res Int. 2013;2013: 747318. https://doi.org/10.1155/2013/747318.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Catana A, Apostu AP, Antemie R-G. Multi gene panel testing for hereditary breast cancer-is it ready to be used? Med Pharma Rep. 2019;92(3):220–5. https://doi.org/10.15386/mpr-1083.

    Article  Google Scholar 

  7. Wendt C, Margolin S. Identifying breast cancer susceptibility genes - a review of the genetic background in familial breast cancer. Acta Oncol. 2019;58(2):135–46. https://doi.org/10.1080/0284186X.2018.1529428.

    Article  CAS  PubMed  Google Scholar 

  8. Shapira M, Raanani H, Feldman B, Srebnik N, Dereck-Haim S, Manela D, et al. BRCA mutation carriers show normal ovarian response in in vitro fertilization cycles. Fertil Steril. 2015;104(5):1162–7. https://doi.org/10.1016/j.fertnstert.2015.07.1162.

    Article  CAS  PubMed  Google Scholar 

  9. Oktay K, Turan V, Bedoschi G, Pacheco FS, Moy F. Fertility preservation success subsequent to concurrent aromatase inhibitor treatment and ovarian stimulation in women with breast cancer. J Clin Oncol. 2015;33(22):2424–9. https://doi.org/10.1200/JCO.2014.59.3723.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Giuliano AE, Connolly JL, Edge SB, Mittendorf EA, Rugo HS, Solin LJ, et al. Breast cancer-major changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017;67(4):290–303. https://doi.org/10.3322/caac.21393.

    Article  PubMed  Google Scholar 

  11. Huang JY, Chian RC, Gilbert L, Fleiszer D, Holzer H, Dermitas E, et al. Retrieval of immature oocytes from unstimulated ovaries followed by in vitro maturation and vitrification: a novel strategy of fertility preservation for breast cancer patients. Am J Surg. 2010;200(1):177–83. https://doi.org/10.1016/j.amjsurg.2009.04.004.

    Article  PubMed  Google Scholar 

  12. Rodriguez-Wallberg KA, Eloranta S, Krawiec K, Lissmats A, Bergh J, Liljegren A. Safety of fertility preservation in breast cancer patients in a register-based matched cohort study. Breast Cancer Res Treat. 2018;167(3):761–9. https://doi.org/10.1007/s10549-017-4555-3.

    Article  PubMed  Google Scholar 

  13. Dunn L, Fox KR. Techniques for fertility preservation in patients with breast cancer. Curr Opin Obstet Gynecol. 2009;21(1):68–73. https://doi.org/10.1097/GCO.0b013e32831e13b9.

    Article  PubMed  Google Scholar 

  14. Son WY, Chung JT, Chian RC, Herrero B, Demirtas E, Elizur S, et al. A 38 h interval between hCG priming and oocyte retrieval increases in vivo and in vitro oocyte maturation rate in programmed IVM cycles. Hum Reprod. 2008;23(9):2010–6. https://doi.org/10.1093/humrep/den210.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Chian RC, Tan SL. Maturational and developmental competence of cumulus-free immature human oocytes derived from stimulated and intracytoplasmic sperm injection cycles. Reprod Biomed Online. 2002;5(2):125–32. https://doi.org/10.1016/s1472-6483(10)61614-8.

    Article  CAS  PubMed  Google Scholar 

  16. Churpek JE, Walsh T, Zheng Y, Moton Z, Thornton AM, Lee MK, et al. Inherited predisposition to breast cancer among African American women. Breast Cancer Res Treat. 2015;149(1):31–9. https://doi.org/10.1007/s10549-014-3195-0.

    Article  CAS  PubMed  Google Scholar 

  17. Wong ESY, Shekar S, Met-Domestici M, Chan C, Sze M, Yap YS, et al. Inherited breast cancer predisposition in Asians: multigene panel testing outcomes from Singapore. NPJ Genom Med. 2016;1:15003. https://doi.org/10.1038/npjgenmed.2015.3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Rotman G, Shiloh Y. ATM: from gene to function. Hum Mol Genet. 1998;7(10):1555–63. https://doi.org/10.1093/hmg/7.10.1555.

    Article  CAS  PubMed  Google Scholar 

  19. McClain MR, Palomaki GE, Nathanson KL, Haddow JE. Adjusting the estimated proportion of breast cancer cases associated with BRCA1 and BRCA2 mutations: public health implications. Genet Med. 2005;7(1):28–33. https://doi.org/10.1097/01.gim.0000151155.36470.ff.

    Article  CAS  PubMed  Google Scholar 

  20. Shao D, Cheng S, Guo F, Zhu C, Yuan Y, Hu K, et al. Prevalence of hereditary breast and ovarian cancer (HBOC) predisposition gene mutations among 882 HBOC high-risk Chinese individuals. Cnacer Sci. 2020;111(2):647–57.

    Article  CAS  Google Scholar 

  21. van Tilborg TC, Derks-Smeets IA, Bos AM, Oosterwijk JC, van Golde RJ, de Die-Smulders CE, et al. Serum AMH levels in healthy women from BRCA1/2 mutated families: are they reduced? Hum Reprod. 2016;31(11):2651–9. https://doi.org/10.1093/humrep/dew242.

    Article  CAS  PubMed  Google Scholar 

  22. Wang YA, Jian JW, Hung CF, Peng HP, Yang CF, Cheng HS, et al. Germline breast cancer susceptibility gene mutations and breast cancer outcomes. BMC Cancer. 2018;18(1):315. https://doi.org/10.1186/s12885-018-4229-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Son KA, Lee DY, Choi D. Association of BRCA mutations and anti-mullerian hormone level in young breast cancer patients. Front Endocrinol (Lausanne). 2019;10:235. https://doi.org/10.3389/fendo.2019.00235.

    Article  Google Scholar 

  24. Lin W, Titus S, Moy F, Ginsburg ES, Oktay K. Ovarian aging in women with BRCA germline mutations. J Clin Endocrinol Metab. 2017;102(10):3839–47. https://doi.org/10.1210/jc.2017-00765.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Oktay K, Kim JY, Barad D, Babayev SN. 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(2):240–4. https://doi.org/10.1200/JCO.2009.24.2057.

    Article  CAS  PubMed  Google Scholar 

  26. Gunnala V, Fields J, Irani M, D’Angelo D, Xu K, Schattman G, et al. BRCA carriers have similar reproductive potential at baseline to noncarriers: comparisons in cancer and cancer-free cohorts undergoing fertility preservation. Fertil Steril. 2019;111(2):363–71. https://doi.org/10.1016/j.fertnstert.2018.10.014.

    Article  CAS  PubMed  Google Scholar 

  27. Volodarsky-Perel A, Cohen Y, Arab S, Son WY, Suarthana E, Dahan MH, et al. Effects of cancer stage and grade on fertility preservation outcome and ovarian stimulation response. Hum Reprod. 2019;34(3):530–8. https://doi.org/10.1093/humrep/dey382.

    Article  CAS  PubMed  Google Scholar 

  28. Young SR, Pilarski RT, Donenberg T, Shapiro C, Hammond LS, Miller J, et al. The prevalence of BRCA1 mutations among young women with triple-negative breast cancer. BMC Cancer. 2009;9:86. https://doi.org/10.1186/1471-2407-9-86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The author would like to thank Nancy Lamothe for managing the database, and all nurses, physicians, and medical health workers at the MUHC-Reproductive center.

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, McGill University, 888 Boulevard de Maisonneuve East, suite # 200, Montreal, QC, H2l 4S8, Canada

    Suha Arab, Togas Tulandi & William Buckett

  2. Obstetrics and Gynecology Department, King Abdulaziz University Hospital, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia

    Suha Arab

Authors
  1. Suha Arab
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Togas Tulandi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. William Buckett
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

S. Arab was involved in study design, data collection, data analysis, and writing the manuscript; W. Buckett participated in study design, data analysis, editing the manuscript, and review; T. Tulandi was involved in data analysis, interpretation, and editing the manuscript.

Corresponding author

Correspondence to Suha Arab.

Ethics declarations

Ethical approval

Research and Ethics Board (MUHC REB) approved the study (REB #2020-6219).

Consent to participate

Not applicable.

Consent for publication

Not applicable.

Conflict of interests

The authors declare no competing interests.

Additional information

Publisher's note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Arab, S., Tulandi, T. & Buckett, W. Hereditary breast cancer and fertility preservation outcomes. J Assist Reprod Genet 39, 1163–1168 (2022). https://doi.org/10.1007/s10815-022-02486-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10815-022-02486-0

Keywords

Search

Navigation