Yale University School of Medicine, New Haven, CT, USA.
Foundation Medicine Inc., Cambridge, MA, USA.
Breast Cancer Res Treat. 2024 Feb;204(1):181-185. doi: 10.1007/s10549-023-07179-5. Epub 2023 Nov 24.
Approximately 5% of breast cancers each year are diagnosed in young women < 40 years who tend to have worse clinical outcomes. We compared genomic alterations using comprehensive genomic profiling (CGP) of tumor tissue among very young women (< 30 years) and young women (30-39 years) compared to women ≥ 40 years at diagnosis.
2049 advanced breast cancer cases were submitted to Foundation Medicine within a 22-month window for CGP. Hybrid-capture based CGP was performed to evaluate all classes of genomic alterations. Tumor mutational burden was determined on at least 0.8 Mbp of sequenced DNA and microsatellite instability was determined on at least 95 loci. Immunocyte PD-L1 expression was determined by immunohistochemistry.
Of the total cases, 28 (1.37%) were < 30 years, 159 (7.76%) were 30-39 years, and 1862 (90.87%) were ≥ 40 at time of diagnosis. Breast tumors were less likely to be estrogen receptor positive in younger women (54% of < 30 years, p > 0.05; 60% of 30-39 years, p < 0.001; 69.4% of ≥ 40 years) and more likely to be triple negative (43%, p = 0.05; 33%, p = 0.05; 26.1% respectively). Young women had higher rates of BRCA1 mutations (17.9% <30 years, p < 0.001; 10.1% 30-39 years, p < 0.001; 2.6% ≥40 years), but lower rates of CDH1 (7.1% <30 years, p > 0.05; 5.0% 30-39 years, p < 0.001; 15.4% ≥40 years) and PIK3CA mutations (17.9% <30 years, p = 0.02; 17.6% 30-39 years, p < 0.001; 40.0% ≥40 years).
Our findings contribute to the growing literature demonstrating unique genetic profiles among young women diagnosed with breast cancer, compared to older women.
每年约有 5%的乳腺癌在 40 岁以下的年轻女性中被诊断出来，这些年轻女性的临床结局往往更差。我们比较了非常年轻的女性（<30 岁）和年轻的女性（30-39 岁）与诊断时≥40 岁的女性之间肿瘤组织的综合基因组分析（CGP）中的基因组改变。
在 22 个月的时间窗口内，2049 例晚期乳腺癌病例被提交给 Foundation Medicine 进行 CGP。基于杂交捕获的 CGP 用于评估所有类别的基因组改变。肿瘤突变负担在至少 0.8 Mbp 的测序 DNA 上确定，微卫星不稳定性在至少 95 个位点上确定。免疫细胞 PD-L1 表达通过免疫组化确定。
在总病例中，28 例（1.37%）<30 岁，159 例（7.76%）30-39 岁，1862 例（90.87%）诊断时≥40 岁。年轻女性的雌激素受体阳性肿瘤较少（<30 岁的为 54%，p>0.05；30-39 岁的为 60%，p<0.001；≥40 岁的为 69.4%），三阴性乳腺癌的比例更高（43%，p=0.05；33%，p=0.05；分别为 26.1%）。年轻女性 BRCA1 突变的发生率更高（<30 岁的为 17.9%，p<0.001；30-39 岁的为 10.1%，p<0.001；≥40 岁的为 2.6%），但 CDH1 突变的发生率更低（<30 岁的为 7.1%，p>0.05；30-39 岁的为 5.0%，p<0.001；≥40 岁的为 15.4%）和 PIK3CA 突变的发生率更低（<30 岁的为 17.9%，p=0.02；30-39 岁的为 17.6%，p<0.001；≥40 岁的为 40.0%）。
我们的研究结果有助于增加关于年轻女性乳腺癌独特的遗传特征的文献，与老年女性相比，年轻女性的遗传特征存在差异。
