Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Cancer Epidemiol Biomarkers Prev. 2022 Mar 1;31(3):561-568. doi: 10.1158/1055-9965.EPI-21-0940.
Breast cancers in recently postpartum women may have worse outcomes, but studies examining tumor molecular features by pregnancy recency have shown conflicting results.
This analysis used Carolina Breast Cancer Study data to examine clinical and molecular tumor features among women less than 50 years of age who were recently (≤10 years prior) or remotely (>10 years prior) postpartum, or nulliparous. Prevalence odds ratios (POR) and 95% confidence intervals (CI) were estimated using multivariable models.
Recently postpartum women (N = 618) were more frequently lymph node-positive [POR (95% CI): 1.66 (1.26-2.19)], estrogen receptor (ER)-negative [1.37 (1.02-1.83)], and IHC-based triple negative [1.57 (1.00-2.47)] compared with nulliparous (N = 360) women. Some differences were identified between recent versus remotely postpartum; smaller tumor size [0.67 (0.52-0.86)], p53 wildtype [0.53 (0.36-0.77)], and non-basal-like phenotype [0.53 (0.33-0.84)] were more common among recently postpartum. Recently postpartum (vs. nulliparous) had significant enrichment for adaptive immunity, T cells, B cells, CD8 T cells, activated CD8 T cells/natural killer (NK) cells, and T follicular helper (Tfh) cells and higher overall immune cell scores. These differences were attenuated in remotely (compared with recently) postpartum women.
These results suggest a dominant effect of parity (vs. nulliparity) and a lesser effect of pregnancy recency on tumor molecular features, although tumor immune microenvironments were altered in association with pregnancy recency.
Our study is unique in examining tumor immune microenvironment and RNA-based markers according to time since last childbirth. Future studies should examine the interplay between tumor features, postdiagnostic treatment, and outcomes among recently postpartum women. See related commentary by McDonald et al., p. 518.
最近分娩后的女性的乳腺癌可能预后更差,但研究妊娠时间对肿瘤分子特征的影响结果不一。
本研究利用卡罗莱纳乳腺癌研究的数据,对年龄小于 50 岁的最近(≤10 年前)、远(>10 年前)分娩或未生育的女性的临床和分子肿瘤特征进行分析。采用多变量模型估计优势比(POR)及其 95%置信区间(CI)。
最近分娩的女性(N=618)淋巴结阳性(POR(95%CI):1.66(1.26-2.19))、雌激素受体(ER)阴性(1.37(1.02-1.83))和 IHC 三阴性(1.57(1.00-2.47))的比例高于未生育的女性(N=360)。最近分娩与远分娩之间存在一些差异;肿瘤较小(0.67(0.52-0.86))、p53 野生型(0.53(0.36-0.77))和非基底样表型(0.53(0.33-0.84))在最近分娩的女性中更为常见。与未生育的女性相比,最近分娩的女性(与未生育的女性相比)适应性免疫、T 细胞、B 细胞、CD8 T 细胞、激活的 CD8 T 细胞/NK 细胞和滤泡辅助 T 细胞(Tfh)的丰度更高,总免疫细胞评分更高。这些差异在远(与最近)分娩的女性中减弱。
这些结果表明,与生育状态(而非未生育)相比,妊娠时间对肿瘤分子特征的影响较小,但与妊娠时间相关的肿瘤免疫微环境发生了改变。
本研究的独特之处在于根据上次分娩时间来检查肿瘤免疫微环境和基于 RNA 的标志物。未来的研究应该检查最近分娩后女性的肿瘤特征、诊断后治疗和结局之间的相互作用。见 McDonald 等人的相关评论,第 518 页。