育龄期女性乳腺癌病人生育力保存临床实践指南(2025版)

中华医学会外科学分会乳腺外科学组, 中国妇幼保健协会乳腺保健专业委员会

中国实用外科杂志 ›› 2025, Vol. 45 ›› Issue (12) : 1409-1412.

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中国实用外科杂志 ›› 2025, Vol. 45 ›› Issue (12) : 1409-1412. DOI: 10.19538/j.cjps.issn1005-2208.2025.12.12
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育龄期女性乳腺癌病人生育力保存临床实践指南(2025版)

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Clinical practice guidelines for fertility preservation in reproductive-age women with breast cancer (2025 edition)

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中华医学会外科学分会乳腺外科学组, 中国妇幼保健协会乳腺保健专业委员会. 育龄期女性乳腺癌病人生育力保存临床实践指南(2025版)[J]. 中国实用外科杂志. 2025, 45(12): 1409-1412 https://doi.org/10.19538/j.cjps.issn1005-2208.2025.12.12
Chinese Society of Breast Surgery, Chinese Society of Surgery, Chinese Medical Association, Committee of Breast Health, Chinese Maternal and Child Health Association. Clinical practice guidelines for fertility preservation in reproductive-age women with breast cancer (2025 edition)[J]. Chinese Journal of Practical Surgery. 2025, 45(12): 1409-1412 https://doi.org/10.19538/j.cjps.issn1005-2208.2025.12.12
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参考文献

[1]
中华医学会外科学分会乳腺外科学组, 中国妇幼保健协会乳腺保健专业委员会. 中国育龄期女性乳腺癌病人生育力保存临床实践指南(2023版)[J]. 中国实用外科杂志, 2023, 43(2):136-138.DOI:10.19538/j.cjps.issn1005-2208.2023.02.03.
[2]
Su HI, Lacchetti C, Letourneau J, et al. Fertility preservation in people with cancer: ASCO guideline update[J]. J Clin Oncol, 2025, 43(12):1488-1515.DOI: 10.1200/JCO.24.02782.
To provide updated fertility preservation (FP) recommendations for people with cancer.A multidisciplinary Expert Panel convened and updated the systematic review.One hundred sixty-six studies comprise the evidence base.People with cancer should be evaluated for and counseled about reproductive risks at diagnosis and during survivorship. Patients interested in or uncertain about FP should be referred to reproductive specialists. FP approaches should be discussed before cancer-directed therapy. Sperm cryopreservation should be offered to males before cancer-directed treatment, with testicular sperm extraction if unable to provide semen samples. Testicular tissue cryopreservation in prepubertal males is experimental and should be offered only in a clinical trial. Males should be advised of potentially higher genetic damage risks in sperm collected soon after cancer-directed therapy initiation and completion. For females, established FP methods should be offered, including embryo, oocyte, and ovarian tissue cryopreservation (OTC), ovarian transposition, and conservative gynecologic surgery. In vitro maturation of oocytes may be offered as an emerging method. Post-treatment FP may be offered to people who did not undergo pretreatment FP or cryopreserve enough oocytes or embryos. Gonadotropin-releasing hormone agonist (GnRHa) should not be used in place of established FP methods but may be offered as an adjunct to females with breast cancer. For patients with oncologic emergencies requiring urgent oncologic therapy, GnRHa may be offered for menstrual suppression. Established FP methods in children who have begun puberty should be offered with patient assent and parent/guardian consent. The only established method for prepubertal females is OTC. Oncology teams should ensure prompt access to a multidisciplinary FP team. Clinicians should advocate for comprehensive FP services coverage and help patients access benefits.Additional information is available at www.asco.org/survivorship-guidelines.
[3]
Paluch-Shimon S, Cardoso F, Partridge AH, et al. ESO-ESMO fifth international consensus guidelines for breast cancer in young women(BCY5)[J]. Ann Oncol, 2022, 33(11):1097-1118.DOI:10.1016/j.annonc.2022.07.007.
The 5 International Consensus Symposium for Breast Cancer in Young Women (BCY5) took place virtually in October 2020, organized by the European School of Oncology (ESO) and the European Society of Medical Oncology (ESMO). Consensus recommendations for the management of breast cancer in young women were updated from BCY4 with incorporation of new evidence to inform the guidelines. Areas of research priorities, as well as specificities in different geographic and minority populations were identified. This manuscript summarizes the ESO-ESMO international consensus recommendations, which are also endorsed by the European Society of Breast Specialists (EUSOMA).Copyright © 2022 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.
[4]
Benvenuti C, Laot L, Grinda T, et al. Is controlled ovarian stimulation safe in patients with hormone receptor-positive breast cancer receiving neoadjuvant chemotherapy?[J]. ESMO Open, 2024, 9(2):102228. DOI: 10.1016/j.esmoop.2023.102228.
[5]
Marklund A, Lekberg T, Hedayati E, et al. Relapse rates and disease-specific mortality following procedures for fertility preservation at time of breast cancer diagnosis[J]. JAMA Oncol, 2022, 8(10):1438-1446.DOI:10.1001/jamaoncol.2022.3677.
Breast cancer (BC) is the most common indication for fertility preservation (FP) in women of reproductive age. Procedures for FP often include hormonal stimulation, but current data are scarce regarding whether using hormonal stimulation for FP is associated with any deterioration in BC prognosis.
[6]
Jr AH, Niman SM, Partridge AH, et al. Fertility preservation and assisted reproduction in patients with breast cancer interrupting adjuvant endocrine therapy to attempt pregnancy[J]. J Clin Oncol, 2024, 42(23):2822-2832.DOI:10.1200/JCO.23.02292.
We investigated time to pregnancy, efficacy and safety of fertility preservation, and assisted reproductive technologies (ARTs) in women with early hormone receptor–positive breast cancer (BC) desiring future pregnancy.
[7]
Arecco L, Blondeaux E, Bruzzone M, et al. Safety of fertility preservation techniques before and after anticancer treatments in young women with breast cancer: A systematic review and meta-analysis[J]. Human reproduction(Oxford,England), 2022, 37(5):954-968.DOI:10.1093/humrep/deac035.
[8]
Lee S, Ozkavukcu S, Heytens E, et al. Value of early referral to fertility preservation in young women with breast cancer[J]. J Clin Oncol, 2010, 28(31):4683-4686.DOI:10.1200/JCO.2010.30.5748.
To determine whether early referral to reproductive specialists improves fertility preservation (FP) outcomes and reduces delay in adjuvant treatment in young women with breast cancer.A secondary analysis of a prospective database of patients with breast cancer undergoing ovarian stimulation (OS) for FP by oocyte or embryo cryopreservation was performed.Of the 154 patients, 93 met the inclusion criteria (mean age, 35.2 ± 4.4 years). Thirty-five of the 93 patients were referred before breast surgery (PreS), and 58 patients were referred after surgery (PostS). The time periods from initial diagnosis (ID) to initiation of OS (42.6 ± 27.7 days for PreS v 71.9 ± 30.7 days for PostS; P <.001) and from ID to initiation of chemotherapy (83.9 ± 24.3 days for PreS v 107.8 ± 42.9 days for PostS; P =.045) were significantly shorter for the PreS group versus the PostS group. Nine (25.7%) of 35 patients in the PreS group versus one (1.7%) of 58 patients in the PostS group were able to undergo two FP cycles (P <.001), resulting in an increased yield of oocytes in the PreS group (18.2% [93 of 511 oocytes] v 0.6% [five of 800 oocytes], respectively; P <.001) and embryos (17.2% [40 of 233 embryos] v 0.6% [two of 357 embryos], respectively; P <.001). Patients who had an oocyte retrieval within 5 weeks of the surgery were able to complete a second cycle within 9 weeks of the surgery.FP referral before breast surgery enables earlier initiation of cryopreservation cycles and chemotherapy and, when appropriate, multiple FP cycles. Women who can undergo multiple cycles may be at advantage for FP because of a larger number of oocytes or embryos cryopreserved. This is the first study demonstrating the benefit of early FP referral in patients with cancer.
[9]
ESHRE Guideline Group on Female Fertility Preservation,Anderson RA, Amant F, et al. ESHRE guideline: Female fertility preservation[J]. Hum Reprod Open, 2020, 2020(4): hoaa052. DOI: 10.1093/hropen/hoaa052.
[10]
Lambertini M, Blondeaux E, Bruzzone M, et al. Pregnancy after breast cancer: A systematic review and meta-analysis[J]. J Clin Oncol, 2021, 39(29):3293-3305.DOI: 10.1200/JCO.21.00535.
Many patients and physicians remain concerned about the potential detrimental effects of pregnancy after breast cancer (BC) in terms of reproductive outcomes and maternal safety. This systematic review and meta-analysis aimed at providing updated evidence on these topics.
[11]
Partridge AH, Niman SM, Ruggeri M, et al. Interrupting endocrine therapy to attempt pregnancy after breast cancer[J]. N Engl J Med, 2023, 388(18):1645-1656. DOI: 10.1056/NEJMoa2212856.
[12]
Anderson RA, Lambertini M, Hall PS, et al. Survival after breast cancer in women with a subsequent live birth: Influence of age at diagnosis and interval to subsequent pregnancy[J]. Eur J Cancer, 2022, 173:113-122.DOI: 10.1016/j.ejca.2022.06.048.
There remains a considerable concern among both patients and oncologists that having a live birth (LB) after breast cancer might adversely impact survival.analysis of survival in a national cohort of women with breast cancer diagnosed at age 20-39 years between 1981 and 2017 (n = 5181), and subsequent LB using Scottish Cancer Registry and national maternity records. Cases had at least one subsequent LB, each was matched with up to six unexposed cases without subsequent LB, accounting for guaranteed time bias.In 290 women with a LB after diagnosis, overall survival was increased compared to those who did not have a subsequent LB, HR 0.65 (95%CI 0.50-0.85). Women with subsequent LB who had not had a pregnancy before breast cancer showed increased survival (HR 0.56, 0.38-0.82). There was a progressively greater interaction of subsequent LB with survival with younger age, thus for women aged 20-25 years, HR 0.30 (0.12-0.74) vs. those aged 36-39, HR 0.89 (0.42-1.87). In women with LB within five years of diagnosis, survival was also increased (HR 0.66; 0.49-0.89). Survival following LB was similar to unexposed women by ER status (both positive and negative) and in those known to have been exposed to chemotherapy.This analysis provides further evidence that for the growing number of women who wish to have children after breast cancer, LB does not have a negative impact on overall survival. This finding was confirmed within subgroups, including the youngest women and those not previously pregnant.Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.
[13]
Arecco L, Blondeaux E, Bruzzone M, et al. Safety of pregnancy after breast cancer in young women with hormone receptor-positive disease: A systematic review and meta-analysis[J]. ESMO Open, 2023, 8(6):102031.DOI:10.1016/j.esmoop.2023.102031.
[14]
Peccatori FA, Niman SM, Partridge AH, et al. Breastfeeding after hormone receptor-positive breast cancer: Results from the POSITIVE trial[J]. J Clin Oncol, 2025, 43(24):2712-2719.DOI:10.1200/JCO-24-02697.
We investigated breastfeeding patterns, behaviors, and association with breast cancer (BC) outcomes in women with early hormone receptor-positive (HR+) BC who had a live birth in the POSITIVE trial.POSITIVE is a prospective trial that demonstrated no increased short-term risk of BC events in women with early HR+ BC who interrupted endocrine therapy (ET) to attempt pregnancy. We describe the frequency, duration, and laterality of breastfeeding and estimate the cumulative incidence of BC events by breastfeeding status.At a median follow-up of 41 months, 317 patients had at least one live birth and 313 were eligible for this analysis. A total of 196 of 313 (62.6%) patients breastfed. A total of 130 of the 167 women (77.8%) who had breast-conserving surgery breastfed, and 90 of 130 (69.2%) breastfed from the unaffected breast only. Sixty-six of the 146 women (45.2%) who underwent unilateral mastectomy breastfed. The frequency of breastfeeding was higher in women older than 35 years (67.6% 55.7%) and in those without previous children (66.4% 48.5%). Over half (103 of 196, 52.6%) of women breastfed their first live birth for >4 months (median 4.4 months; 95% CI, 4.0 to 5.3). The cumulative incidence of a BC event at 24 months from first on-study live birth was 3.6% and 3.1% in the breastfeeding and nonbreastfeeding groups, respectively (0.5% difference; 95% CI, -4.3% to 5.2%).In POSITIVE, two thirds of women who gave birth after BC diagnosis breastfed, mostly for 4 months or more. In early follow-up, we did not observe differences in BC-related events in women who breastfed compared with those who did not. These results are key for women who wish to pursue pregnancy and breastfeeding after BC.
[15]
Lambertini M, Blondeaux E, Agostinetto E, et al. Pregnancy after breast cancer in young brca carriers: An international hospital-based cohort study[J]. JAMA, 2024, 331(1):49-59.DOI:10.1001/jama.2023.25463.
Young women with breast cancer who have germline pathogenic variants in BRCA1 or BRCA2 face unique challenges regarding fertility. Previous studies demonstrating the feasibility and safety of pregnancy in breast cancer survivors included limited data regarding BRCA carriers.To investigate cumulative incidence of pregnancy and disease-free survival in young women who are BRCA carriers.International, multicenter, hospital-based, retrospective cohort study conducted at 78 participating centers worldwide. The study included female participants diagnosed with invasive breast cancer at age 40 years or younger between January 2000 and December 2020 carrying germline pathogenic variants in BRCA1 and/or BRCA2. Last delivery was October 7, 2022; last follow-up was February 20, 2023.Pregnancy after breast cancer.Primary end points were cumulative incidence of pregnancy after breast cancer and disease-free survival. Secondary end points were breast cancer-specific survival, overall survival, pregnancy, and fetal and obstetric outcomes.Of 4732 BRCA carriers included, 659 had at least 1 pregnancy after breast cancer and 4073 did not. Median age at diagnosis in the overall cohort was 35 years (IQR, 31-38 years). Cumulative incidence of pregnancy at 10 years was 22% (95% CI, 21%-24%), with a median time from breast cancer diagnosis to conception of 3.5 years (IQR, 2.2-5.3 years). Among the 659 patients who had a pregnancy, 45 (6.9%) and 63 (9.7%) had an induced abortion or a miscarriage, respectively. Of the 517 patients (79.7%) with a completed pregnancy, 406 (91.0%) delivered at term (≥37 weeks) and 54 (10.4%) had twins. Among the 470 infants born with known information on pregnancy complications, 4 (0.9%) had documented congenital anomalies. Median follow-up was 7.8 years (IQR, 4.5-12.6 years). No significant difference in disease-free survival was observed between patients with or without a pregnancy after breast cancer (adjusted hazard ratio, 0.99; 95% CI, 0.81-1.20). Patients who had a pregnancy had significantly better breast cancer-specific survival and overall survival.In this global study, 1 in 5 young BRCA carriers conceived within 10 years after breast cancer diagnosis. Pregnancy following breast cancer in BRCA carriers was not associated with decreased disease-free survival.ClinicalTrials.gov Identifier: NCT03673306.
[16]
Magaton IM, Blondeaux E, Hamy AS, et al. Assisted reproductive technology in young BRCA carriers with a pregnancy after breast cancer: An international cohort study[J]. Eur J Cancer, 2025, 222:115434.DOI:10.1016/j.ejca.2025.115434.
[17]
Hartnett KP, Mertens AC, Kramer MR, et al. Pregnancy after cancer: Does timing of conception affect infant health?[J]. Cancer, 2018, 124(22):4401-4407.DOI:10.1002/cncr.31732.
The objective of this retrospective cohort study was to determine whether women who conceive soon after treatment for cancer have higher risks of adverse pregnancy outcomes.Vital records data were linked to cancer registry diagnosis and treatment information in 3 US states. Women who conceived their first pregnancy after diagnosis between ages 20 and 45 years with any invasive cancer or ductal carcinoma in situ were eligible. Log-binomial models were used to compare risks in cancer survivors who conceived in each interval to the risks in matched comparison births to women without cancer.Women who conceived ≤1 year after starting chemotherapy for any cancer had higher risks of preterm birth than comparison women (chemotherapy alone: relative risk [RR], 1.9; 95% confidence interval [CI], 1.3-2.7; chemotherapy with radiation: RR, 2.4; 95% CI, 1.6-3.6); women who conceived ≥1 year after starting chemotherapy without radiation or ≥2 years after chemotherapy with radiation did not. In analyses imputing the treatment end date for breast cancer survivors, those who conceived ≥1 year after finishing chemotherapy with or without radiation had no higher risks than women without cancer. The risk of preterm birth in cervical cancer survivors largely persisted but was somewhat lower in pregnancies conceived after the first year (for pregnancies conceived ≤1 year after diagnosis: RR, 3.5; 95% CI, 2.2-5.4; for pregnancies conceived >1 year after diagnosis: RR, 2.4; 95% CI, 1.6-3.5).In women who received chemotherapy, the higher risk of preterm birth was limited to those survivors who had short intervals between treatment and conception.Cancer 2018;124:000-000.© 2018 American Cancer Society.
[18]
Lambertini M, Peccatori FA, Demeestere I, et al. Fertility preservation and post-treatment pregnancies in post-pubertal cancer patients: ESMO Clinical Practice Guidelines[J]. Ann Oncol, 2020, 31(12):1664-1678.DOI:10.1016/j.annonc.2020.09.006.
[19]
National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology:Breast cancer, Version 4.2025[EB/OL].(2025-04-17)[2025-07-27]. https: //www.nccn.org/professionals/physician_gls/default.aspx
[20]
Kim HA, Lee JW, Nam SJ, et al. Adding ovarian suppression to tamoxifen for premenopausal breast cancer: A randomized phase Ⅲ trial[J]. J Clin Oncol, 2020, 38(5):434-443.DOI:10.1200/JCO.19.00126.
[21]
Donnez J, Dolmans MM. Fertility preservation in women[J]. N Engl J Med, 2017, 377(17):1657-1665.DOI: 10.1056/NEJMra1614676.
[22]
Newman LA, Shippee Rockefeller E, Yip CH. Safety of pregnancy after breast cancer in brca mutation carriers[J]. JAMA Surg, 2024, 159(5):482-483.DOI:10.1001/jamasurg.2024.0005.
[23]
Zagouri F, Dimopoulos MA, Andrikopoulou A. PARP inhibitors during conception and pregnancy in breast cancer[J]. Crit Rev Oncol Hematol, 2025, 210:104696.DOI:10.1016/j.critrevonc.2025.104696.
[24]
Practice Committee of the American Society for Reproductive Medicine. Fertility preservation in patients undergoing gonadotoxic therapy or gonadectomy: A committee opinion[J]. Fertil Steril, 2019, 112(6):1022-1033. DOI: 10.1016/j.fertnstert.2019.09.013.
Patients preparing to undergo gonadotoxic medical therapy, radiation therapy, or gonadectomy should be provided with prompt counseling regarding available options for fertility preservation for iatrogenic infertility. Fertility preservation can best be provided by comprehensive programs designed and equipped to confront the unique challenges facing these patients. This document replaces the document with a similar name, last published in 2013.Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
[25]
Lambertini M, Boni L, Michelotti A, et al. Long-term outcomes with pharmacological ovarian suppression during chemotherapy in premenopausal early breast cancer patients[J]. J Natl Cancer Inst, 2022, 114(3):400-408.DOI:10.1093/jnci/djab213.
Although use of gonadotropin-releasing hormone agonist (GnRHa) during chemotherapy is an established strategy to protect ovarian function in premenopausal breast cancer patients, no long-term safety data are available, raising some concerns in women with hormone receptor–positive disease. There are controversial data on its fertility preservation potential.
[26]
Moore HC, Unger JM, Phillips KA, et al. Goserelin for ovarian protection during breast-cancer adjuvant chemotherapy[J]. N Engl J Med, 2015, 372(10):923-932.DOI:10.1056/NEJMoa1413204.
[27]
Leonard RCF, Adamson DJA, Bertelli G, et al. GnRH agonist for protection against ovarian toxicity during chemotherapy for early breast cancer: The Anglo Celtic Group OPTION trial[J]. Ann Oncol, 2017, 28(8):1811-1816.DOI:10.1093/annonc/mdx184.
Chemotherapy-induced premature ovarian insufficiency (POI) impacts fertility and other aspects of women's health. The OPTION trial tested whether administration of a gonadotropin-releasing hormone agonist during chemotherapy for early breast cancer reduced the risk of POI.This was a prospective, randomized, parallel group study of the gonadotropin-releasing hormone agonist goserelin administered before and during chemotherapy for breast cancer with stage I-IIIB disease. The primary outcome was amenorrhoea between 12 and 24 months after randomization, supported by elevated follicle stimulating hormone concentrations to give an additional analysis as rate of POI.A total of 227 patients were randomized and the primary analysis was conducted on 202 patients. Goserelin reduced the prevalence of amenorrhoea between 12 and 24 months to 22% versus 38% in the control group (P = 0.015) and the prevalence of POI to 18.5% versus 34.8% in the control group (P = 0.048). Follicle stimulating hormone concentrations were also lower in all women treated with goserelin at both 12 and 24 months (P = 0.027, P = 0.001, respectively). The effect of goserelin was not statistically significant in women >40 years. Assessment of the ovarian reserve using anti-Müllerian hormone showed a marked fall in both groups during treatment to median values of 5% of pretreatment levels in the control group and 7% in the goserelin group, which were not significantly different between groups.This study shows that goserelin reduced the risk of POI in women treated with chemotherapy for early breast cancer, with particular efficacy in women aged ≤40 years old. The degree of ovarian protection also seems limited and the clinical significance for fertility and longer term prevention of estrogen deficiency-related outcomes needs to be determined.© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

基金

上海市卫生健康委员会联合上海市中医药管理局项目(ZXXT-202301)
上海市科学技术委员会项目(23ZR1408400)

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