Decanter Christine, Dassonneville Audrey, D'Orazio Emmanuelle, Behal Hélène, Gagez Anne-Laure, Mailliez Audrey, Pigny Pascal
Service d'Assistance Médicale à la Procréation et de Préservation de Fertilité, CHU Lille, 59037, Lille, France.
Univ. Lille, CANTHER, Inserm UMR 1277, 59045, Lille, France.
J Assist Reprod Genet. 2025 Apr 12. doi: 10.1007/s10815-025-03475-9.
The impact of a germline BRCA1/2 pathogenic variant (gBRCApv) on baseline or late post-treatment AMH concentrations in breast cancer patients has been extensively studied, yielding mixed conclusions. However, whether the AMH decline during neo-adjuvant chemotherapy reflects differences in chemotherapy susceptibility between gBRCApv carriers and non-carriers remains unexplored.
A monocentric, retrospective, longitudinal study was conducted on breast cancer patients carrying a gBRCApv (n = 12) or wild-type (WT) (n = 35) who received a neo-adjuvant sequential chemotherapy (CT) with anthracyclines followed by taxanes. Serum AMH levels were measured at baseline (AMH0) and at three time points during CT by a hypersensitive assay. Tumor size change was assessed via imaging. The impact of genetic status on AMH decline was evaluated using a linear mixed model with post hoc analysis.
The change of AMH concentrations from baseline to the end of CT tended to be influenced by the genetic status (BRCA * time interaction, p = 0.058). The slope between AMH0 and the end of anthracyclines (after log transformation) was steeper in gBRCApv than in WT patients (mean (SE): - 5.54 (0.63) vs - 3.97 (0.62); p = 0.023). Tumor size change was positively and significantly correlated with the change in AMH levels (AMH MidCT-AMH0) in gBRCApv patients (r = 0.93, p < 0.001) but not in WT patients (r = - 0.05; p = 0.84).
Germline BRCA1/2 status influences AMH decline during neo-adjuvant CT with drugs inducing DNA lesions. AMH decay is positively related to tumor size change assessed by imaging in gBRCApv patients. However, no conclusions can be drawn regarding the relationship with treatment response assessed by histological criteria.
种系BRCA1/2致病变异（gBRCApv）对乳腺癌患者基线或治疗后晚期抗缪勒管激素（AMH）浓度的影响已得到广泛研究，但结论不一。然而，新辅助化疗期间AMH的下降是否反映了gBRCApv携带者和非携带者在化疗敏感性上的差异仍未得到探索。
对携带gBRCApv（n = 12）或野生型（WT）（n = 35）的乳腺癌患者进行了一项单中心、回顾性、纵向研究，这些患者接受了以蒽环类药物随后紫杉烷类药物的新辅助序贯化疗（CT）。在基线（AMH0）和CT期间的三个时间点通过超敏测定法测量血清AMH水平。通过影像学评估肿瘤大小变化。使用线性混合模型并进行事后分析评估基因状态对AMH下降的影响。
从基线到CT结束时AMH浓度的变化倾向于受基因状态影响（BRCA*时间交互作用，p = 0.058）。gBRCApv患者中，从AMH0到蒽环类药物治疗结束时（对数转换后）的斜率比WT患者更陡（均值（标准误）：-5.54（0.63）对-3.97（0.62）；p = 0.023）。gBRCApv患者中肿瘤大小变化与AMH水平变化（AMH MidCT - AMH0）呈正且显著相关（r = 0.93，p < 0.001），而WT患者中则无相关性（r = -0.05；p = 0.84）。
种系BRCA1/2状态影响使用诱导DNA损伤药物进行新辅助CT期间的AMH下降。在gBRCApv患者中，AMH衰减与通过影像学评估的肿瘤大小变化呈正相关。然而，关于与组织学标准评估的治疗反应之间的关系尚无定论。
