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预测年轻乳腺癌患者化疗及抗HER2治疗后的卵巢功能丧失情况。

Predicting ovarian function loss after chemotherapy and anti-HER2 therapy in young breast cancer patients.

作者信息

Lambertini Matteo, Allegranza Deirdre, Laubender Ruediger P, Harbeck Nadia, Swain Sandra M, Geyer Charles E, Slamon Dennis J, Bobba Gabriella, Lambertini Chiara, de Haas Sanne, Restuccia Eleonora, Vaz-Luis Ines, Cameron David A, Krop Ian E, Winer Eric P, Anderson Richard A

机构信息

Department of Internal Medicine and Medical Specialties (DIMI), School of Medicine, University of Genova, Genoa, Italy.

Department of Medical Oncology, U.O. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.

出版信息

J Natl Cancer Inst. 2025 Aug 12. doi: 10.1093/jnci/djaf198.

Abstract

BACKGROUND

The ability to predict ovarian function loss after anticancer treatment is important for appropriate oncofertility counselling and to aid in therapy decision-making for young women with early breast cancer (eBC).

METHODS

This biomarker analysis of the BETH (NCT00625898) and KAITLIN (NCT01966471) randomized trials investigated anti-Müllerian hormone (AMH) use, alone and combined with follicle stimulating hormone (FSH) and estradiol (E2), for predicting ovarian function loss following currently adopted chemotherapy and anti-HER2 therapy in premenopausal women with HER2-positive eBC.Serum samples were centrally tested measuring AMH, FSH and E2 using Roche Elecsys assays.

RESULTS

Among 194 included patients (BETH: n = 62; KAITLIN: n = 132), AMH values declined from baseline median 8.44 pmol/L to undetectable levels (<0.07 pmol/L) at end of therapy, with partial recovery at 36 months (median 0.14 pmol/L).AMH measured at baseline was predictive of ovarian loss (AUC = 0.784). Addition of age to AMH slightly improved AUC to 0.800. AMH measured at the end of therapy had AUC 0.741, which increased to 0.785 with addition of age. The combination of AMH at baseline and end of therapy increased prediction to 0.808 and with addition of age to 0.820. Addition of baseline FSH and E2 did not improve prediction in any analysis.

CONCLUSIONS

These results support the use of pretreatment measurement of AMH in predicting ovarian function loss in premenopausal women with HER2-positive eBC receiving chemotherapy and anti-HER2 therapy. Measurement of AMH at end of treatment was comparable to pretreatment and added slightly to the value of pretreatment sampling.

摘要

背景

预测抗癌治疗后卵巢功能丧失的能力对于进行适当的生育力保护咨询以及辅助早期乳腺癌(eBC)年轻女性的治疗决策非常重要。

方法

这项对BETH(NCT00625898)和KAITLIN(NCT01966471)随机试验的生物标志物分析,研究了抗苗勒管激素(AMH)单独使用以及与促卵泡生成素(FSH)和雌二醇(E2)联合使用,用于预测HER2阳性eBC绝经前女性在接受目前采用的化疗和抗HER2治疗后卵巢功能丧失的情况。血清样本在中心实验室使用罗氏电化学发光免疫分析法检测AMH、FSH和E2。

结果

在194例纳入患者中(BETH:n = 62;KAITLIN:n = 132),AMH值从基线中位数8.44 pmol/L下降至治疗结束时的不可检测水平(<0.07 pmol/L),在36个月时部分恢复(中位数0.14 pmol/L)。基线时测量的AMH可预测卵巢功能丧失(AUC = 0.784)。将年龄纳入AMH分析后,AUC略有提高至0.800。治疗结束时测量的AMH的AUC为0.741,加入年龄后增加至0.785。基线和治疗结束时的AMH联合使用可将预测能力提高至0.808,加入年龄后提高至0.820。在任何分析中,加入基线FSH和E2均未改善预测能力。

结论

这些结果支持在预测接受化疗和抗HER2治疗的HER2阳性eBC绝经前女性卵巢功能丧失时使用治疗前AMH测量。治疗结束时测量的AMH与治疗前相当,且略微增加了治疗前采样的价值。

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