中国早期乳腺癌卵巢功能抑制临床应用专家共识（2021年版）

卵巢功能抑制（ovarian function suppression,OFS）已经应用于乳腺癌治疗数十年,早期辅助治疗研究证实,单独进行OFS能够降低50岁以下乳腺癌患者的复发风险,改善生存情况。鉴于新的循证医学数据不断累积,中国抗癌协会乳腺癌专业委员会遂召集国内乳腺癌专家,在《中国早期乳腺癌卵巢功能抑制临床应用专家共识（2018年版）》的基础上共同商讨制订了《中国早期乳腺癌卵巢功能抑制临床应用专家共识（2021年版） 》。2021年版共识建议,将药物去势[促性腺激素释放激素激动剂（gonadotropin releasing hormone agonist,GnRHa）]作为绝经前激素受体阳性的早期乳腺癌OFS的首选。中高危绝经前激素受体阳性乳腺癌患者推荐接受OFS的内分泌治疗;低危患者推荐选择性雌激素受体调节剂（selective estrogen receptor modulators,SERM）单药治疗;使用芳香化酶抑制剂（aromatase inhibitor,AI）代替SERM治疗的绝经前患者,需要同时接受OFS治疗。关于OFS联合方案,对绝经前激素受体阳性早期乳腺癌的中危和高危患者,或亚群处理效果模式图（subpopulation treatment effect pattern plot,STEPP）分析的较高风险患者推荐OFS联合AI治疗,OFS联合SERM治疗也是合理的选择。对存在SERM禁忌证的任何风险级别患者,推荐OFS联合AI治疗。关于OFS的使用时机,建议根据激素受体阳性乳腺癌患者化疗前的卵巢功能状态,决定辅助内分泌治疗方案。如果考虑卵巢保护,推荐GnRHa同步化疗,不影响患者的生存获益;如果不考虑卵巢保护,推荐GnRHa可以在化疗结束后直接序贯使用。已接受化疗的患者不推荐确认卵巢功能状态后再使用GnRHa。GnRHa辅助内分泌治疗的标准疗程应为5年。完成5年联合OFS的内分泌治疗后,如未绝经且耐受性良好,推荐继续5年联合OFS的内分泌治疗或5年SERM治疗。低危选择OFS替代化疗的患者,可考虑OFS联合内分泌治疗时长为2年。推荐与患者充分沟通可能出现的不良事件,选用合适的药物去势治疗方案。合理的安全管理能够有效地缓解不良反应,增加患者治疗的依从性。对于接受药物去势的患者,不常规推荐在药物去势治疗过程中监测雌激素水平并根据检测报告来决定是否继续药物去势。但在药物去势后,怀疑不完全的卵巢功能抑制时[包括改变用法如注射人员缺乏相关经验、更换剂型或出现某些可能提示卵巢功能恢复的生理变化如月经恢复和（或）更年期症状的周期性波动时],可以进行雌激素水平检测。绝经前乳腺癌患者,无论激素受体阳性或阴性,推荐在（新）辅助化疗前和化疗过程中使用OFS药物保护卵巢功能,降低卵巢功能早衰的发生风险,减少生育能力损害。推荐化疗前2周开始使用GnRHa,每28 d 1次,直至化疗结束后2周给予最后一剂药物。此外共识还建议,激素受体阳性乳腺癌患者抗肿瘤药物的临床试验,应尽可能纳入绝经前女性,在雌激素充分抑制的前提下,探索抗肿瘤药物对肿瘤生物学特性和患者长期生活质量的影响。

Expert consensus on clinical applications of ovarian function suppression for Chinese women with early breast cancer 2021 CACA-CBCS

Ovarian function suppression(OFS)has been used in the treatment of breast cancer for decades.Early adjuvant treatment studies have confirmed that the application of OFS alone can reduce the recurrence risk of breast cancer patients under the age of 50 and improve their survival.With the emergence of new evidence-based medical data,the Breast Cancer Professional Committee of the China Anti-Cancer Association convened domestic clinical experts in the field of breast cancer treatment,who jointly discussed and formulated the"Chinese Consensus of Ovarian Function Suppression in Early Breast Cancer(2021 edition)"on the basis of the 2018 edition.Consensus suggests that gonadotropin-releasing hormone agonist(GnRHa)should be the first choice of OFS for premenopausal hormone receptor-positive(HR positive)early breast cancer.Medium-and high-risk premenopausal HR positive breast cancer patients are recommended for endocrine therapy including OFS;low-risk patients are recommended for selective estrogen receptor modulator(SERM)monotherapy;premenopausal patients who use aromatase inhibitor(AI)instead of SERM need to receive OFS at the same time.For the medium-and high-risk patients with premenopausal HR positive early breast cancer,or the medium/high-risk patients analyzed by subpopulation treatment effect pattern plot(STEPP),the combination of OFS and AI is recommended,and the combination of OFS and SERM is also an alternative choice.For patients with contraindications or at risk of contraindications to SERM,OFS combined with AI is recommended.The adjuvant endocrine therapy should be decided based on the status of ovarian function before adjuvant chemotherapy.If ovarian function protection is considered,GnRHa plus chemotherapy is recommended,which does not affect the survival benefits.If not,it is recommended that GnRHa can be used sequentially after chemotherapy.It is recommended that patients with confirmed ovarian function status after chemotherapy should not use GnRHa.The GnRHa adjuvant endocrine therapy should be used for 5 years.After 5 years,it is recommended to continue endocrine therapy combined with OFS for 5 years or 5 years of SERM therapy if the patients are still premenopausal and well tolerated.For low-risk patients who choose OFS instead of chemotherapy,OFS combined with endocrine therapy can be considered for 2 years.Full communication with patients based on adverse events of the OFS is needed before decision making.The sound management of adverse events will effectively relieve symptoms and increase the treatment compliance.For patients with OFS,it is not recommended to monitor estrogen levels routinely during the treatment and make decisions according to the test.However,when incomplete ovarian function suppression is suspected(including changes in usage such as unskilled injection,replacement of dosage forms,or indications of ovarian function recovery,such as menstrual recovery and/or the fluctuating perimenopausal symptoms),estrogen testing can be performed.For premenopausal patients,no matter HRs are positive or negative,it is recommended to use ovarian function suppression drugs before and during(neo)adjuvant chemotherapy to protect ovarian function and reduce the risk of ovarian function failure and impaired fertility.It is recommended to start using GnRHa 2 weeks before chemotherapy,once every 28 days,until 2 weeks after the last dose of chemotherapy.In addition,the consensus suggests that premenopausal patients with sufficient OFS should be included in the clinical trials so as to investigate the impact of HR positive breast cancer drugs on tumor biological characteristics and long-term quality of life.