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乳腺癌易感基因突变的乳腺癌患者的潜在生育能力和保留生育能力措施的效果


  临床前证据表明,乳腺癌易感基因(BRCA)有害突变可能对女性生育能力产生负面影响。不过,现有临床数据较少而且互相矛盾。


  2017年10月10日,欧洲肿瘤内科学会和牛津大学出版社旗下《肿瘤学年鉴》在线发表比利时布鲁塞尔自由大学、朱尔博尔代研究中心、伊拉斯谟医院、葡萄牙里斯本大学、圣玛丽亚医院的研究报告,评定了BRCA突变乳腺癌患者的潜在生育能力和保留生育能力措施的效果。


  该回顾研究对新诊断早期乳腺癌患者卵母细胞冷藏和卵巢组织冷藏的两项前瞻研究进行分析。对有或无原始生殖细胞BRCA有害突变的患者抗输卵管激素基线水平和冷藏措施效果进行比较。


  结果,入组156例患者,整个队列中位年龄31岁(四分位距:28~33岁),其中已知BRCA状态101例:BRCA突变29例(18.6%),无突变72例(46.1%)。


  BRCA突变阳性、阴性队列的抗输卵管激素中位水平分别为1.8、2.6μg/L(四分位距:1.0~2.7、1.5~4.1,P = 0.109)。


  29例患者接受卵母细胞冷藏,BRCA突变阳性与阴性队列女性相比,获取卵母细胞(6.5比9,P = 0.145)和冷藏卵母细胞(3.5比6,P = 0.121)稍少。


  BRCA突变阳性、阴性队列的无效率(即获取卵母细胞≤4个)分别为40.0%、11.1%(P = 0.147)。


  72例患者接受卵巢组织冷藏,BRCA突变阳性与阴性队列女性相比,每片组织卵母细胞(0.08比0.14,P = 0.193)和每平方毫米卵母细胞(0.33比0.78;P = 0.153)稍少。


  两例BRCA突变患者化疗接受自体冷藏卵巢组织移植,其中一例分娩健康婴儿。


  BRCA1与BRCA2突变患者之间上述任何结局均未见显著差异。


  因此,BRCA突变与未突变的乳腺癌患者相比,生育能力降低和冷藏措施效果相似,不过需要对这些结果进行独立验证。



Ann Oncol. 2017 Oct 10. [Epub ahead of print]


Reproductive potential and performance of fertility preservation strategies in BRCA-mutated breast cancer patients.


Lambertini M, Goldrat O, Ferreira AR, Dechene J, Azim Jr HA, Desir J, Delbaere A, tKint de Roodenbeke MD, de Azambuja E, Ignatiadis M, Demeestere I.


Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium; CUB-Hopital Erasme, Université Libre de Bruxelles, Brussels, Belgium; Hospital de Santa Maria, Universiade de Lisboa, Lisbon, Portugal.


BACKGROUND: Preclinical evidence suggests a possible negative impact of deleterious BRCA mutations on female fertility. However, limited and rather conflicting clinical data are available. This study assessed the reproductive potential and performance of fertility preservation strategies in BRCA-mutated breast cancer patients.


PATIENTS AND METHODS: This was a retrospective analysis of two prospective studies investigating oocyte cryopreservation and ovarian tissue cryopreservation in newly diagnosed early breast cancer patients. In the current analysis, baseline anti-mullerian hormone (AMH) and performance of cryopreservation strategies were compared between patients with or without germline deleterious BRCA mutations.


RESULTS: Out of 156 patients included, 101 had known BRCA status of whom 29 (18.6%) were BRCA-mutated and 72 (46.1%) had no mutation. Median age in the entire cohort was 31 years (interquartile range [IQR] 28-33). Median AMH levels were 1.8 ug/L (IQR 1.0-2.7) and 2.6 ug/L (IQR 1.5-4.1) in the BRCA-positive and BRCA-negative cohorts, respectively (P=0.109). Among patients who underwent oocyte cryopreservation (N=29), women in the BRCA-positive cohort tended to retrieve (6.5 vs. 9; P=0.145) and to cryopreserve (3.5 vs. 6; P=0.121) less oocytes than those in the BRCA-negative cohort. Poor response rate (i.e. retrieval of≤4 oocytes) was 40.0% and 11.1% in the BRCA-positive and BRCA-negative cohorts, respectively (P=0.147). Among patients who underwent ovarian tissue cryopreservation (N=72), women in the BRCA-positive cohort tended to have a numerically lower number of oocytes per fragment (0.08 vs. 0.14; P=0.193) and per mm2 (0.33 vs. 0.78; P=0.153) than those in the BRCA-negative cohort. Two BRCA-mutated patients were transplanted after chemotherapy and one delivered at term a healthy baby. No difference between BRCA1- and BRCA2-mutated patients was observed in any of the above-mentioned outcomes.


CONCLUSION: A consistent trend for reduced reproductive potential and performance of cryopreservation strategies was observed in BRCA-mutated breast cancer patients. Independent validation of these results is needed.


KEYWORDS: BRCA1/2, fertility, anti-mullerian hormone, oocyte cryopreservation, ovarian tissue cryopreservation


DOI: 10.1093/annonc/mdx639