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Reproductive potential and performance of fertility preservation strategies in BRCA-mutated breast cancer patients.
Annals of Oncology ( IF 56.7 ) Pub Date : 2018-01-01 , DOI: 10.1093/annonc/mdx639
M Lambertini 1, 2 , O Goldrat 3 , A R Ferreira 4 , J Dechene 3 , H A Azim 5 , J Desir 6 , A Delbaere 3 , M-D t'Kint de Roodenbeke 1 , E de Azambuja 1 , M Ignatiadis 1 , I Demeestere 3
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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 μg/l (IQR 1.0-2.7) and 2.6 µg/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 versus 9; P = 0.145) and to cryopreserve (3.5 versus 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 versus 0.14; P = 0.193) and per square millimeter (0.33 versus 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.

中文翻译:

BRCA突变的乳腺癌患者的生殖潜力和生育力保留策略的表现。

背景临床前证据表明,有害的BRCA突变可能对女性生育能力产生负面影响。然而,可获得有限且相当矛盾的临床数据。这项研究评估了BRCA突变的乳腺癌患者的生殖潜力和生育力保留策略的性能。患者和方法这是两项前瞻性研究的回顾性分析,该两项前瞻性研究调查了新诊断的早期乳腺癌患者的卵母细胞冷冻保存和卵巢组织冷冻保存。在当前的分析中,比较了具有或没有生殖系有害BRCA突变的患者的基线抗Mullerian激素(AMH)和冷冻保存策略的性能。结果在156例患者中,有101例具有BRCA状态,其中29例(18.6%)为BRCA突变,72例(46。1%)没有突变。整个队列的中位年龄为31岁(四分位间距(IQR)28-33)。在BRCA阳性和BRCA阴性人群中,AMH中位数分别为1.8μg/ l(IQR 1.0-2.7)和2.6μg/ l(IQR 1.5-4.1)(P = 0.109)。在接受卵母细胞冷冻保存的患者(N = 29)中,BRCA阳性队列中的女性比BRCA的女性趋于恢复(分别为6.5和9; P = 0.145)和冷冻保存(分别为3.5和6; P = 0.121)。 -阴性队列。在BRCA阳性和BRCA阴性人群中,不良反应率(即≤4个卵母细胞的回收率)分别为40.0%和11.1%(P = 0.147)。在接受卵巢组织冷冻保存的患者(N = 72)中,BRCA阳性队列中的女性每个卵母细胞的数量往往较低(0.08对0.14; P = 0。193)和每平方毫米(0.33对0.78; P = 0.153)。两名BRCA突变的患者在化疗后被移植,其中一名在足月健康婴儿中分娩。在上述任何结果中,均未观察到BRCA1和BRCA2突变患者之间的差异。结论在BRCA突变的乳腺癌患者中观察到一致的降低生殖潜能和冷冻保存策略的趋势。需要对这些结果进行独立验证。结论在BRCA突变的乳腺癌患者中观察到了一致的降低生殖潜能和冷冻保存策略的趋势。需要对这些结果进行独立验证。结论在BRCA突变的乳腺癌患者中观察到一致的降低生殖潜能和冷冻保存策略的趋势。需要对这些结果进行独立验证。
更新日期:2017-10-10
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