Abstract
In patients with early breast cancer, the combination of different systemic treatment
strategies, including chemotherapy, endocrine therapy, targeted therapy, and more
recently also immunotherapy has demonstrated to significantly improve their survival
outcomes. However, this gain is often obtained at the cost of higher toxicity calling
for the need of increased attention toward survivorship-related issues, including
fertility preservation in young women. According to available guidelines, health care
providers should offer oncofertility counseling to all patients with cancer diagnosed
at reproductive age. Counselling should focus on the risk of gonadotoxicity of anticancer
treatments and on the access to fertility preservation techniques. However, several
surveys have demonstrated suboptimal implementation of these recommendations. This
review aims at summarizing the available evidence on oncofertility to guide health
care providers involved in the management of young women with breast cancer. Available
and effective options for fertility preservation include oocyte/embryo cryopreservation
or ovarian tissue cryopreservation. Patient, disease, and treatment characteristics
should be carefully considered when offering these strategies. Ovarian function preservation
with gonadotrophin-releasing hormone agonists during chemotherapy should be discussed
and offered to every premenopausal woman concerned about developing premature ovarian
insufficiency and independently of her wish to preserve fertility. Current available
data confirm that pregnancy occurring after proper treatment for breast cancer is
safe, both in terms of long-term clinical outcomes and for the babies. Fertility preservation
and pregnancy desire should be pivotal components of the multimodal management of
breast cancer in young women, and require a multidisciplinary approach based on close
collaborations between oncologists and fertility specialists.
Keywords
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References
- Cancer statistics, 2022.CA Cancer J Clin. 2022; 72: 7-33https://doi.org/10.3322/caac.21708
- ESO-ESMO 5th international consensus guidelines for breast cancer in young women (BCY5).Ann Oncol. 2022; 33 (S0923753422018580): 1097-1118https://doi.org/10.1016/j.annonc.2022.07.007
- Subtype-dependent relationship between young age at diagnosis and breast cancer survival.J Clin Oncol. 2016; 34: 3308-3314https://doi.org/10.1200/JCO.2015.65.8013
- Biology of breast cancer in young women.Breast Cancer Res. 2014; 16: 427https://doi.org/10.1186/s13058-014-0427-5
- ESMO Expert consensus statements on cancer survivorship: promoting high-quality survivorship care and research in Europe.Ann Oncol. 2022; 33 (S0923753422037929): 1119-1133https://doi.org/10.1016/j.annonc.2022.07.1941
- European Society for Medical Oncology (ESMO) position paper on supportive and palliative care.Ann Oncol. 2018; 29: 36-43https://doi.org/10.1093/annonc/mdx757
- Current state of the art in the adjuvant systemic treatment of premenopausal patients with early breast cancer.Clin Med Insights Oncol. 2020; 14117955492093181https://doi.org/10.1177/1179554920931816
- Management of young women with early breast cancer.ESMO Open. 2018; 3e000458https://doi.org/10.1136/esmoopen-2018-000458
- Controversies about fertility and pregnancy issues in young breast cancer patients: current state of the art.Curr Opin Oncol. 2017; 29: 243-252https://doi.org/10.1097/CCO.0000000000000380
- Quality of life, fertility concerns, and behavioral health outcomes in younger breast cancer survivors: a systematic review.J Natl Cancer Inst. 2012; 104: 386-405https://doi.org/10.1093/jnci/djr541
- Fertility preservation and post-treatment pregnancies in post-pubertal cancer patients: ESMO Clinical Practice Guidelines†.Ann Oncol. 2020; 31: 1664-1678https://doi.org/10.1016/j.annonc.2020.09.006
- How I perform fertility preservation in breast cancer patients.ESMO Open. 2021; 6100112https://doi.org/10.1016/j.esmoop.2021.100112
- Prospective study of fertility concerns and preservation strategies in young women with breast cancer.J Clin Oncol. 2014; 32: 1151-1156https://doi.org/10.1200/JCO.2013.52.8877
- Pretreatment fertility counseling and fertility preservation improve quality of life in reproductive age women with cancer.Cancer. 2012; 118: 1710-1717https://doi.org/10.1002/cncr.26459
- Prospective study to optimize care and improve knowledge on ovarian function and/or fertility preservation in young breast cancer patients: Results of the pilot phase of the PREgnancy and FERtility (PREFER) study.Breast. 2018; 41: 51-56https://doi.org/10.1016/j.breast.2018.06.012
- The PREgnancy and FERtility (PREFER) study investigating the need for ovarian function and/or fertility preservation strategies in premenopausal women with early breast cancer.Front Oncol. 2021; 11690320https://doi.org/10.3389/fonc.2021.690320
- The use of fertility preservation services for cancer patients: a single institution experience.F&S Reports. 2022; 3 (S2666334122000800): 349-354https://doi.org/10.1016/j.xfre.2022.08.001
- Fertility preservation in patients of childbearing age treated for breast cancer: A nationwide cohort study.Breast. 2022; 64: 121-126https://doi.org/10.1016/j.breast.2022.05.006
- Pregnancy after breast cancer: a systematic review and meta-analysis.J Clin Oncol. 2021; 39: 3293-3305https://doi.org/10.1200/JCO.21.00535
- ESHRE guideline: female fertility preservation†.Hum Reprod Open. 2020; 2020: hoaa052https://doi.org/10.1093/hropen/hoaa052
- Early discontinuation of tamoxifen intake in younger women with breast cancer: Is it time to rethink the way it is prescribed?.Eur J Cancer. 2012; 48: 1939-1946https://doi.org/10.1016/j.ejca.2012.03.004
- Serum detection of nonadherence to adjuvant tamoxifen and breast cancer recurrence risk.J Clin Oncol. 2020; 38: 2762-2772https://doi.org/10.1200/JCO.19.01758
- Impact of fertility concerns on tamoxifen initiation and persistence.J Natl Cancer Inst. 2015; 107: djv202https://doi.org/10.1093/jnci/djv202
- Early discontinuation and non-adherence to adjuvant hormonal therapy are associated with increased mortality in women with breast cancer.Breast Cancer Res Treat. 2011; 126: 529-537https://doi.org/10.1007/s10549-010-1132-4
- The BCY3/BCC 2017 survey on physicians’ knowledge, attitudes and practice towards fertility and pregnancy-related issues in young breast cancer patients.Breast. 2018; 42: 41-49https://doi.org/10.1016/j.breast.2018.08.099
- Knowledge, practice, and attitudes of physicians in low- and middle-income countries on fertility and pregnancy-related issues in young women with breast cancer.JCO Glob Oncol. 2022; 8: e2100153https://doi.org/10.1200/GO.21.00153
- Awareness and practices of Arab oncologists towards oncofertility in young women with cancer.ecancer. 2022; 16: 1388https://doi.org/10.3332/ecancer.2022.1388
- Current awareness and attitude toward fertility preservation in Indonesia: a nationwide survey among health-care providers.J Hum Reprod Sci. 2021; 14: 81https://doi.org/10.4103/jhrs.jhrs_239_20
- Survey of professionals on breast cancer, fertility preservation and pregnancy in Argentina.ecancer. 2021; 15: 1183https://doi.org/10.3332/ecancer.2021.1183
- Anti-Müllerian hormone as a marker of ovarian reserve and premature ovarian insufficiency in children and women with cancer: a systematic review.Hum Reprod Update. 2022; 28: 417-434https://doi.org/10.1093/humupd/dmac004
- Risk of gonadotoxicity with immunotherapy and targeted agents remains an unsolved but crucial issue.Eur J Clin Invest. 2022; 52: e13779https://doi.org/10.1111/eci.13779
- The effects of paclitaxel, dose density, and trastuzumab on treatment-related amenorrhea in premenopausal women with breast cancer.Cancer. 2010; 116: 791-798https://doi.org/10.1002/cncr.24835
- Adjuvant anti-HER2 therapy, treatment-related amenorrhea, and survival in premenopausal HER2-positive early breast cancer patients.J Natl Cancer Inst. 2019; 111: 86-94https://doi.org/10.1093/jnci/djy094
- Chemotherapy-related amenorrhea after adjuvant paclitaxel–trastuzumab (APT trial).Breast Cancer Res Treat. 2015; 151: 589-596https://doi.org/10.1007/s10549-015-3426-z
- Chemotherapy-related amenorrhea (CRA) after adjuvant ado-trastuzumab emtansine (T-DM1) compared to paclitaxel in combination with trastuzumab (TH) (TBCRC033: ATEMPT Trial).Breast Cancer Res Treat. 2021; 189: 103-110https://doi.org/10.1007/s10549-021-06267-8
- Preimplantation genetic testing for carriers of BRCA1/2 pathogenic variants.Crit Rev Oncol Hematol. 2021; 157103201https://doi.org/10.1016/j.critrevonc.2020.103201
- Impairment of BRCA1-related DNA double-strand break repair leads to ovarian aging in mice and humans.Sci Transl Med. 2013; 5https://doi.org/10.1126/scitranslmed.3004925
- Do BRCA1/2 mutation carriers have an earlier onset of natural menopause?.Menopause. 2016; 23: 903-910https://doi.org/10.1097/GME.0000000000000633
- Antimüllerian hormone levels are lower in BRCA2 mutation carriers.Fertil Steril. 2017; 107: 1256-1265.e6https://doi.org/10.1016/j.fertnstert.2017.03.018
- BRCA carriers have similar reproductive potential at baseline to noncarriers: comparisons in cancer and cancer-free cohorts undergoing fertility preservation.Fertil Steril. 2019; 111: 363-371https://doi.org/10.1016/j.fertnstert.2018.10.014
- BRCA mutation carriers do not have compromised ovarian reserve.Int J Gynecol Cancer. 2014; 24: 233-237https://doi.org/10.1097/IGC.0000000000000058
- Reproductive potential and performance of fertility preservation strategies in BRCA-mutated breast cancer patients.Ann Oncol. 2018; 29: 237-243https://doi.org/10.1093/annonc/mdx639
- Association of Germline BRCA pathogenic variants with diminished ovarian reserve: a meta-analysis of individual patient-level data.J Clin Oncol. 2021; 39: 2016-2024https://doi.org/10.1200/JCO.20.02880
- Adjuvant olaparib for patients with BRCA1 - or BRCA2 -mutated breast cancer.N Engl J Med. 2021; 384: 2394-2405https://doi.org/10.1056/NEJMoa2105215
- Fertility Preservation in Women.N Engl J Med. 2017; 377: 1657-1665https://doi.org/10.1056/NEJMra1614676
- Methods of controlled ovarian stimulation for embryo/oocyte cryopreservation in breast cancer patients.Expert Rev Qual Life Cancer Care. 2017; 2: 47-59https://doi.org/10.1080/23809000.2017.1270760
- Clinical application of oocyte vitrification: a systematic review and meta-analysis of randomized controlled trials.Fertil Steril. 2011; 96: 277-285https://doi.org/10.1016/j.fertnstert.2011.06.030
- Double ovarian stimulation (DuoStim) protocol for fertility preservation in female oncology patients.Hum Fertil. 2017; 20: 248-253https://doi.org/10.1080/14647273.2017.1287433
- Fertility preservation: ovarian response to freeze oocytes is not affected by different malignant diseases—an analysis of 992 stimulations.J Assist Reprod Genet. 2018; 35: 1713-1719https://doi.org/10.1007/s10815-018-1227-0
- Efficacy and safety of ovarian stimulation before chemotherapy in 205 cases.Fertil Steril. 2010; 94: 2871-2873https://doi.org/10.1016/j.fertnstert.2010.06.054
- Elective and Onco-fertility preservation: factors related to IVF outcomes.Hum Reprod. 2018; 33: 2222-2231https://doi.org/10.1093/humrep/dey321
- Oocyte vitrification versus ovarian cortex transplantation in fertility preservation for adult women undergoing gonadotoxic treatments: a prospective cohort study.Fertil Steril. 2018; 109: 478-485.e2https://doi.org/10.1016/j.fertnstert.2017.11.018
- Fertility preservation success subsequent to concurrent aromatase inhibitor treatment and ovarian stimulation in women with breast cancer.J Clin Oncol. 2015; 33: 2424-2429https://doi.org/10.1200/JCO.2014.59.3723
- Safety of fertility preservation techniques before and after anticancer treatments in young women with breast cancer: a systematic review and meta-analysis.Hum Reprod. 2022; 37: 954-968https://doi.org/10.1093/humrep/deac035
- Efficacy and safety of controlled ovarian stimulation with or without letrozole co-administration for fertility preservation: a systematic review and meta-analysis.Front Oncol. 2020; 10574669https://doi.org/10.3389/fonc.2020.574669
- Practical recommendations for fertility preservation in women by the FertiPROTEKT network. Part II: fertility preservation techniques.Arch Gynecol Obstet. 2018; 297: 257-267https://doi.org/10.1007/s00404-017-4595-2
- Update on fertility preservation from the Barcelona International Society for Fertility Preservation–ESHRE–ASRM 2015 expert meeting: indications, results and future perspectives.Fertil Steril. 2017; 108: 407-415.e11https://doi.org/10.1016/j.fertnstert.2017.05.024
- Transplantations of frozen-thawed ovarian tissue demonstrate high reproductive performance and the need to revise restrictive criteria.Fertil Steril. 2016; 106: 467-474https://doi.org/10.1016/j.fertnstert.2016.04.031
- Children born after autotransplantation of cryopreserved ovarian tissue. A review of 13 live births.Ann Med. 2011; 43: 437-450https://doi.org/10.3109/07853890.2010.546807
- Outcomes of transplantations of cryopreserved ovarian tissue to 41 women in Denmark.Hum Reprod. 2015; 30: 2838-2845https://doi.org/10.1093/humrep/dev230
- Implementing the hub and spoke model for the oncofertility units.Breast. 2019; 48: 100https://doi.org/10.1016/j.breast.2019.09.002
- Fertility preservation for girls and young women with cancer: population-based validation of criteria for ovarian tissue cryopreservation.Lancet Oncol. 2014; 15: 1129-1136https://doi.org/10.1016/S1470-2045(14)70334-1
- Transplantation of frozen-thawed ovarian tissue: an update on worldwide activity published in peer-reviewed papers and on the Danish cohort.J Assist Reprod Genet. 2018; 35: 561-570https://doi.org/10.1007/s10815-018-1144-2
- Autotransplantation of cryopreserved ovarian tissue in cancer survivors and the risk of reintroducing malignancy: a systematic review.Hum Reprod Update. 2013; 19: 483-506https://doi.org/10.1093/humupd/dmt020
- Fertility and pregnancy issues in BRCA -mutated breast cancer patients.Cancer Treat Rev. 2017; 59: 61-70https://doi.org/10.1016/j.ctrv.2017.07.001
- 86 successful births and 9 ongoing pregnancies worldwide in women transplanted with frozen-thawed ovarian tissue: focus on birth and perinatal outcome in 40 of these children.J Assist Reprod Genet. 2017; 34: 325-336https://doi.org/10.1007/s10815-016-0843-9
- Reproductive issues in carriers of germline pathogenic variants in the BRCA1/2 genes: an expert meeting.BMC Med. 2021; 19: 205https://doi.org/10.1186/s12916-021-02081-7
- Ovarian protection with gonadotropin-releasing hormone agonists during chemotherapy in cancer patients: from biological evidence to clinical application.Cancer Treat Rev. 2019; 72: 65-77https://doi.org/10.1016/j.ctrv.2018.11.006
- Ovarian function and fertility preservation in breast cancer: should gonadotropin-releasing hormone agonist be administered to all premenopausal patients receiving chemotherapy?.Clin Med Insights Reprod Health. 2019; 13117955811982839https://doi.org/10.1177/1179558119828393
- Severe ovarian hyperstimulation syndrome associated with long-acting GnRH agonist in oncofertility patients.J Assist Reprod Genet. 2021; 38: 751-756https://doi.org/10.1007/s10815-020-02051-7
- P-464 Long-acting GnRH agonist ovulation trigger to avoid ovarian hyperstimulation and to combine oocyte cryopreservation with ovarian suppression during chemotherapy.Hum Reprod. 2022; 37 (deac107.436)https://doi.org/10.1093/humrep/deac107.436
- ESO–ESMO 4th international consensus guidelines for breast cancer in young women (BCY4).Ann Oncol. 2020; 31: 674-696https://doi.org/10.1016/j.annonc.2020.03.284
- Fertility preservation in patients with cancer: ASCO clinical practice guideline update.J Clin Oncol. 2018; 36: 1994-2001https://doi.org/10.1200/JCO.2018.78.1914
- 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: 25-33https://doi.org/10.1016/j.ejca.2016.10.034
- Early breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.Ann Oncol. 2019; 30: 1674https://doi.org/10.1093/annonc/mdz189
- Customizing local and systemic therapies for women with early breast cancer: the St. Gallen International Consensus Guidelines for treatment of early breast cancer 2021.Ann Oncol. 2021; 32: 1216-1235https://doi.org/10.1016/j.annonc.2021.06.023
- 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: 1981-1990https://doi.org/10.1200/JCO.2018.78.0858
- Long-term outcomes with pharmacological ovarian suppression during chemotherapy in premenopausal early breast cancer patients.J Natl Cancer Inst. 2022; 114: 400-408https://doi.org/10.1093/jnci/djab213
- 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: 1689-1701https://doi.org/10.1200/JCO.2015.65.9573
- Improving adjuvant endocrine treatment tailoring in premenopausal women with hormone receptor–positive breast cancer.J Clin Oncol. 2020; 38: 1258-1267https://doi.org/10.1200/JCO.19.02242
- Longer therapy, iatrogenic amenorrhea, and survival in early breast cancer.N Engl J Med. 2010; 362: 2053-2065https://doi.org/10.1056/NEJMoa0909638
- Fertility preservation: a pilot study to assess previsit patient knowledge quantitatively.Fertil Steril. 2011; 95: 1913-1916https://doi.org/10.1016/j.fertnstert.2011.02.016
- Long-term safety of pregnancy following breast cancer according to estrogen receptor status.J Natl Cancer Inst. 2018; 110: 426-429https://doi.org/10.1093/jnci/djx206
- Survival after breast cancer in women with a subsequent live birth: influence of age at diagnosis and interval to subsequent pregnancy.Eur J Cancer. 2022; 173: 113-122https://doi.org/10.1016/j.ejca.2022.06.048
- Pregnancy after breast cancer in patients with germline BRCA mutations.J Clin Oncol. 2020; 38: 3012-3023https://doi.org/10.1200/JCO.19.02399
- Estimation of historical control rate for a single arm de-escalation study – Application to the POSITIVE trial.Breast. 2020; 53: 1-7https://doi.org/10.1016/j.breast.2020.05.012
- Pregnancy after breast cancer: Are young patients willing to participate in clinical studies?.Breast. 2015; 24: 201-207https://doi.org/10.1016/j.breast.2015.01.005
- Who are the women who enrolled in the POSITIVE trial: a global study to support young hormone receptor positive breast cancer survivors desiring pregnancy.Breast. 2021; 59: 327-338https://doi.org/10.1016/j.breast.2021.07.021
Partridge AH, Niman SM, Ruggeri M, et al. GS4-09 Pregnancy outcome and safety of interrupting therapy for women with endocrine responsIVE breast cancer: primary results from the POSITIVE Trial (IBCSG 48-14 /BIG 8-13). Presented at the 2022 San Antonio Breast Cancer Symposium.
- Pregnancy after breast cancer: results from a prospective cohort of young women with breast cancer.Cancer. 2021; 127: 1021-1028https://doi.org/10.1002/cncr.33342
- Contraceptive Use in Premenopausal Women With Early Breast Cancer.JAMA Netw Open. 2022; 5e2233137https://doi.org/10.1001/jamanetworkopen.2022.33137
- Beyond fertility preservation: role of the oncofertility unit in the reproductive and gynecological follow-up of young cancer patients.Hum Reprod. 2019; 34: 1462-1469https://doi.org/10.1093/humrep/dez108
- Gender-specific aspects related to type of fertility preservation strategies and access to fertility care.ESMO Open. 2020; 5e000771https://doi.org/10.1136/esmoopen-2020-000771
- Fertility, sexuality and cancer in young adult women.Curr Opin Oncol. 2019; 31: 259-267https://doi.org/10.1097/CCO.0000000000000540
- Evidence-based approaches for the management of side-effects of adjuvant endocrine therapy in patients with breast cancer.Lancet Oncol. 2021; 22: e303-e313https://doi.org/10.1016/S1470-2045(20)30666-5
Article info
Publication history
Published online: January 13, 2023
Accepted:
January 10,
2023
Received in revised form:
December 23,
2022
Received:
September 16,
2022
Identification
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© 2023 Elsevier Inc. All rights reserved.
