BackgroundNeurofibromatosis type 1 (NF1) is a cancer predisposing syndrome. Studies suggest that women < 50 years old (y.o.) with NF1 have an increased breast cancer (BC) incidence and BC associated mortality. However, this has not been widely recognized secondary to small study populations.MethodsA systematic literature review was conducted through database searches for BC and NF1: 3456 articles identified, 166 reviewed, 58 used for descriptive analysis and 4 utilized for meta-analysis. Fisher’s exact tests, Kaplan-Meier curves and random-effects meta-analysis models were used for analysis.ResultsTwo hundred eighty-six cases of NF1 and female BC were identified with a median age of 46 years at diagnosis; 53% were < 50. Peak age of BC diagnosis was between 34 to 44 years. Women < 50 y.o. presented with more advanced disease vs. those ≥50 (56% vs. 22% stage III-IV, respectively; p = 0.005). Median survival for the entire cohort was 5 years vs. the reported median BC survival of over 20 years in the general population using the SEER database. Median age at BC death was 48.5 years; 64% of deceased patients were < 50. Meta-analysis of a total of 4178 women with NF1 revealed a BC standardized incidence ratio (SIR) of 3.07 (95%CI 2.16–4.38) for women with NF1 vs. the general population. Women < 50 y.o. demonstrated a higher SIR of 5.08 (95%CI 3.77–6.81) compared to 1.92 (95%CI 1.40–2.63) if ≥50 y.o.ConclusionsThis systematic literature review and meta-analysis suggests that women with NF1 < 50 y.o. have a five-fold increased risk of BC, present with more advanced disease, and may have an increased BC related mortality. Increased awareness and implementation of recent National Comprehensive Cancer Network early BC screening guidelines for this high-risk patient population is essential. Additional evaluation on the influence of NF1 gene mutations identified in patients undergoing hereditary cancer genetic testing on breast cancer risk in individuals without clinical evidence of NF1 is needed.

中文翻译：

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1型神经纤维瘤病女性患乳腺癌的风险增加：文献的荟萃分析和系统评价

背景1型神经纤维瘤病（NF1）是一种癌症易感综合征。研究表明，患有 NF1 的 < 50 岁 (yo) 女性乳腺癌 (BC) 发病率和 BC 相关死亡率增加。然而，这在小型研究人群中并未得到广泛认可。方法通过数据库搜索 BC 和 NF1 进行系统文献回顾：确定 3456 篇文章，166 篇评论，58 篇用于描述性分析，4 篇用于荟萃分析。采用Fisher精确检验、Kaplan-Meier曲线和随机效应荟萃分析模型进行分析。结果286例NF1和女性BC确诊，诊断时中位年龄46岁；53% < 50。BC 诊断的高峰年龄在 34 至 44 岁之间。< 50 岁的女性比 50 岁的女性患有更严重的疾病。≥50 人（分别为 56% 和 22% III-IV 期；p = 0.005）。整个队列的中位生存期为 5 年，而使用 SEER 数据库的普通人群中报告的 BC 中位生存期超过 20 年。BC 死亡的中位年龄为 48.5 岁；64% 的已故患者年龄小于 50。对 4178 名 NF1 女性的荟萃分析显示，NF1 女性与普通人群的 BC 标准化发病率 (SIR) 为 3.07 (95% CI 2.16–4.38)。< 50 岁的女性表现出更高的 SIR 为 5.08 (95%CI 3.77–6.81)，而 1.92 (95%CI 1.40–2.63) 如果 ≥ 50 岁结论本系统文献回顾和荟萃分析表明，NF1 < 50 岁的女性BC 的风险增加五倍，出现更晚期的疾病，并且可能增加 BC 相关的死亡率。提高对这一高危患者群体的近期国家综合癌症网络早期 BC 筛查指南的认识和实施至关重要。需要进一步评估在接受遗传性癌症基因检测的患者中发现的 NF1 基因突变对没有 NF1 临床证据的个体患乳腺癌风险的影响。