孕期、产后与未孕女性乳腺癌结局
2021年7月27日，施普林格自然旗下《乳腺癌研究与治疗》在线发表加拿大森尼布鲁克奥德特癌症中心、多伦多大学、麦克马斯特大学的研究报告，对孕期女性、产后女性、未孕女性的乳腺癌临床病理特征和结局进行了比较，并探讨了产后乳腺癌相关不良预后因素。
该研究对加拿大森尼布鲁克奥德特癌症中心前瞻数据库2008年2月～2015年1月被诊断为乳腺癌的233例年龄≤40岁女性截至2020年7月的随访数据进行分析。利用卡方检验或均值秩检验对孕期、产后和未孕患者的临床病理特征和结局进行比较。通过生存曲线对无复发生存、无远处复发生存和总生存进行推算。利用对数秩检验对生存曲线进行比较。利用单因素比例风险回归模型分析对临床结局有潜在预后影响的因素，利用前向逐步选择过程构建多因素比例风险回归模型。如有可能，评定雄激素受体、转录因子GATA3、细胞程序死亡配体PD-L1状态、肿瘤浸润淋巴细胞。回顾提取治疗前的中性粒细胞和淋巴细胞计数。
结果，产后≤2年女性与未孕对照女性相比，淋巴结阳性率和乳腺癌分级较高，雌激素受体阴性乳腺癌比例显著较高。
中位随访7.2年，总生存率和无复发生存率由高到低依次为：未孕对照患者、产后>2年患者、产后≤2年患者、孕期患者，但是相差不大，无统计学意义。
产后≤2年患者与未孕对照患者相比：雄激素受体表达显著较低、PD-L1表达较高、间质肿瘤浸润淋巴细胞表达较高。
因此，该单中心小样本前瞻随访研究结果表明，产后乳腺癌患者与未孕对照患者相比，无复发生存率和总生存率较低，但不显著。产后乳腺癌与未孕乳腺癌相比，PD-L1和间质肿瘤浸润淋巴细胞表达较高，表明术后辅助免疫治疗可能对产后乳腺癌亚组有效。
Breast Cancer Res Treat. 2021 Jul 27. Online ahead of print.
Clinical outcomes and prognostic biomarkers among pregnant, post-partum and nulliparous women with breast cancer: a prospective cohort study.
Katarzyna J. Jerzak, Nechama Lipton, Sharon Nofech-Mozes, Dina Boles, Elzbieta Slodkowska, Gregory R. Pond, Ellen Warner.
Sunnybrook Odette Cancer Centre, Toronto, Canada; University of Toronto, Toronto, Canada; McMaster University, Hamilton, Canada.
PURPOSE: To compare clinical-pathologic characteristics and outcomes of pregnancy-associated, post-partum and nulliparous breast cancer patients and explore mediators of the poor prognosis associated with post-partum breast cancer.
METHODS: A prospective database of 233 women≤40 years of age diagnosed with breast cancer between February 2008 and January 2015 was analysed. Clinical-pathologic characteristics and outcomes among pregnant, post-partum and nulliparous patients were compared using chi-square or Kruskal-Wallis tests. The Kaplan-Meier method was used to estimate disease-free survival, distant disease-free survival and overall survival. Survival curves were compared using the log-rank test. Univariable Cox proportional hazards regression models were used to evaluate factors that were potentially prognostic for the clinical outcomes of interest; a multivariable Cox model was constructed using a forward stepwise selection process. Androgen receptor, GATA3, PDL1 status and the presence/absence of tumour-infiltrating lymphocytes were assessed when possible. Pre-treatment neutrophil and lymphocyte counts were abstracted retrospectively. Statistical significance was defined as a p value≤0.05.
RESULTS: Women≤2 years post-partum had a numerically higher incidence of lymph node-positive and high-grade disease and were significantly more likely to have estrogen receptor-negative breast cancer compared to nulliparous controls. With a median follow-up of 7.2 years, increasingly poor outcomes were observed among nulliparous (longest overall survival), >2 years post-partum, ≤2 years post-partum and pregnant (shortest overall survival) patients, but these differences were not statistically significant. The≤2 years post-partum group had significantly lower androgen receptor expression, a strong trend toward higher PDL1 expression and a higher expression of stromal tumour-infiltrating lymphocytes compared to nulliparous women.
CONCLUSIONS: post-partum breast cancer patients had numerically lower disease-free survival and overall survival compared to nulliparous controls. Higher PDL1 and stromal tumour-infiltrating lymphocytes in post-partum breast cancer suggest that adjuvant immunotherapy may be effective in the post-partum breast cancer subgroup.
KEYWORDS: Breast cancer; Pregnancy; Post-partum; Biomarkers
DOI: 10.1007/s10549-021-06327-z