Clinical consideration of two key questions in assessing menopausal status of female breast cancer patients

doi:10.19401/j.cnki.1007-3639.2024.07.001

Abstract

Abstract:

Endocrine therapy plays a crucial role in hormone receptor-positive breast cancer and is closely related to the patient’s menopausal status. This manuscript aimed to explore two key questions in assessing menopausal status of breast cancer patients. Firstly, for premenopausal patients receiving ovarian function suppression (OFS) therapy, persistently elevated estradiol (E2) levels post-treatment may be attributed to either “true” or “pseudo” elevation, with caution needed due to potential interference from endocrine therapy drugs such as fulvestrant, abemaciclib, exemestane and tamoxifen. Secondly, when determining whether patients under OFS therapy have reached physiological menopause, factors such as the impact of chemotherapy on menopausal status and the complexity of hormone levels around menopause need to be considered. It is recommended to consider switching treatments based on the patient’s age and original endocrine therapy, and to regularly monitor levels of estradiol and follicle-stimulating hormone (FSH). In challenging cases, a comprehensive evaluation can be conducted by incorporating markers such as anti-Mullerian hormone (AMH), inhibin B (INHB) and androgen.

Key words: Breast cancer, Menopausal status, Ovarian function suppression, Clinical considerations

CLC Number:

R737.9

ZHANG Jian. Clinical consideration of two key questions in assessing menopausal status of female breast cancer patients[J]. China Oncology, 2024, 34(7): 619-627.

Figures/Tables 3

Tab. 1

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References 33

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研究名称/研究者	绝经/卵巢逃逸的定义
SOFT-EST研究^[3]	将E2>2.72 pg/mL作为OFS联合AI内分泌治疗去势逃逸的界值；将E2>21 pg/mL作为OFS联合TAM内分泌治疗去势逃逸的界值；检测次数≥2次。
Smith等^[4]	将绝经定义为E2始终<10 pmol/L（2.72 pg/mL）（连续监测6个月）。
MONALEESA-7研究^[5]	将绝经定义为E2<10 pg/mL和（或）FSH>40 U/L或符合中心实验室绝经前激素参考值。
Faqehi等^[6]	将卵巢逃逸定义为E2>20 pg/mL。
Schmid等^[7]	将卵巢逃逸定义为连续2次测量的E2>30 pg/mL。
Masuda等^[8]	评估不同剂型OFS时将卵巢逃逸定义为E2>30 pg/mL。
中国回顾性研究^[9]	将卵巢逃逸定义为至少出现1次E2≥30 pg/mL。
中国单中心研究^[10]	采用西门子吖啶酯化学发光法检测，E2<50 pg/mL、FSH>10 mU/mL且符合2011年《中国绝经前女性乳腺癌患者辅助治疗后绝经判断标准及芳香化酶临床应用共识（草案修正案）》^[11]提出的绝经标准时，可初步考虑符合绝经标准，并继续进行连续监测。

分析方法	分析仪器	定义	优势	劣势
质谱分析法	GC-MS/MS	GC-MS/MS，基于气相色谱的分离作用，与质谱通过电子冲击或化学电离实现的分析作用^[18]。	灵敏度高（检测下限通常为10 pmol/L或更低），特异度高，分析通量大，可同时定性定量分析^[12]，对于E2测定具有卓越的灵敏度^[19]。	仪器成本较高，设备普及率较低^[9]。
	LC-MS/MS	通过色谱柱固定相与待测物的相互作用实现结构分离，通过离子化测定质荷比实现分析^[18]。		仪器成本较高，设备普及率较低^[9]。
免疫分析法	放射免疫分析法	基于抗体抗原相互作用，使用放射性闪烁计数定量检测^[18]。	具有一定的灵敏度和准确度（绝经前妇女群体^[12]），有商业化试剂盒，成本较低，临床普及率高^[9]。	在激素测定中可能受到结构相似物质干扰，出现假阳性结果^[12]，在低浓度下缺乏特异性，可能导致E2定量不可靠^[19]。
	酶联免疫分析法	基于抗体抗原相互作用，通过培养已知能够产生可测量产物的底物，实现定量检测^[18]。
	化学发光免疫分析法/电化学发光免疫分析法	基于抗体抗原相互作用，通过直接化学发光标志物实现分析，或由电启动的电化学发光剂产生光信号实现分析^[20]。

指南	指南中绝经状态的判断
2024年V4版NCCN指南^[2]	满足以下任意一条^*： ⑴ 先前双侧卵巢切除术； ⑵ 年龄≥60岁； ⑶ 年龄<60岁，无化疗、TAM、托瑞米芬或卵巢功能抑制剂治疗史，闭经≥12个月，E2和FSH处于绝经后水平； ⑷ 年龄<60岁，化疗诱发的闭经≥12个月，FSH和E2处于绝经后水平； ⑸ 年龄<60岁，使用TAM，FSH和E2水平处于绝经后水平。
《中国绝经前女性乳腺癌患者辅助治疗后绝经判断标准及芳香化酶临床应用共识（草案修正案）》^[11]	化疗后或服用SERM药物期间：50岁及以上患者停经至少12个月/45~50岁患者停经至少24个月，并且至少3次连续测量E2和FSH处于绝经后水平（FSH>40 U/L，E2<30 pg/mL）。
《中国抗癌协会乳腺癌诊治指南与规范（2024年版）》^[29]	满足以下任意一条^#： ⑴ 双侧卵巢切除术后； ⑵ 年龄≥60岁； ⑶ 年龄<60岁，自然停经≥12个月，在近1年内未接受化疗、TAM、托瑞米芬或卵巢去势治疗的情况下，FSH和E2处于绝经后水平； ⑷ 年龄<60岁，正在服用TAM或托瑞米芬，FSH和E2处于绝经后水平。
《中国临床肿瘤学会（CSCO）乳腺癌诊疗指南（2024）》^[30]	满足以下任意一条： ⑴ 双侧卵巢切除术后 ⑵ 年龄≥60岁； ⑶ 停经≥12个月，在近1年未接受化疗、三苯氧胺、托瑞米芬或卵巢去势治疗的情况下，FSH和E2处于绝经后水平； ⑷ 年龄<60岁，正在服用三苯氧胺或托瑞米芬，连续2次测量FSH和E2处于绝经后水平。
《中国绝经管理与绝经激素治疗指南2023版》^[31]	40岁以上的女性停经12个月，排除妊娠及其他可能导致闭经的疾病后，即可临床诊断为绝经。