Daling Janet R, Malone Kathleen E, Doody David R, Anderson Benjamin O, Porter Peggy L
Fred Hutchinson Cancer Research Center, Divisions of Public Health Sciences, Seattle, Washington 98109-1024, USA.
Cancer Epidemiol Biomarkers Prev. 2002 Mar;11(3):235-41.
Young women with breast cancer have been reported to have an increased risk of dying from their disease if they have given birth in <2 years before diagnosis. The prognostic factors associated with the tumors of these women have not been thoroughly studied. We examined the tumors of the women who had a recent birth and compared the tumor characteristics with those of women who were nulliparous or had given birth > or =5 years before diagnosis. A follow-up study was conducted of 1174 women <45 years old whose invasive ductal breast cancer was diagnosed from January 1983 to December 1992 in three counties of western Washington. These women had participated previously in a population-based, case-control study. Mean follow-up time was 105.4 months. Histological slides were collected for 79.1% of the tumors and reviewed by the study pathologist. Using immunoperoxidase assays, tumor tissue was tested for prognostic markers for 70.4% of the tumors from the women. Cox proportional hazards models were used to estimate the relative risk of dying from breast cancer associated with reproductive events. Logistic regression was used to obtain estimates of the association between various reproductive factors and tumor characteristics. At the end of follow-up, 48.2% of the women (n = 83) whose last birth occurred in < 2 years of diagnosis had died, compared with 23.3% of nulliparous women (n = 189) and 24.4% of the women (n = 661) whose last birth was > or =5 years before diagnosis. The tumors of the women with a recent birth (<2 years before diagnosis) were more likely to be progesterone receptor negative, odds ratio (OR) = 2.2, 95% confidence interval (CI) = 1.2-3.9, to be p53 positive, OR = 2.6, 95% CI = 1.5-4.7, to be of high histological grade, OR = 5.9, 95% CI = 1.7-20.1, to have high mitotic count, OR = 2.2, 95% CI = 1.4-4.4, to be node positive, OR = 2.1, 95% CI = 1.3-3.5, to have a high S phase fraction, OR = 2.3, 95% CI = 1.1-4.8, and to have a high American Joint Committee on Cancer stage (III+), OR = 2.8, 95% CI 1.3-5.8, compared with the tumors of nulliparous women. After adjusting for tumor characteristics and treatment, the risk of mortality associated with a birth in < 2 years of diagnosis of breast cancer remained an independent predictor of mortality, hazard radio (HR) = 2.7, 95% CI = 1.6-4.3. Our study provides evidence that reproductive factors influence the biological behavior of breast cancer in young women and prognosis. Clinicians need to be aware that women who have delivered a child in < 2 years before diagnosis are at increased risk of having tumors with especially adverse prognostic profiles and have a poorer survival rate than women who are nulliparous or whose last birth was some years in the past.
据报道，患有乳腺癌的年轻女性若在诊断前不到2年生育，死于该病的风险会增加。与这些女性肿瘤相关的预后因素尚未得到充分研究。我们检查了近期生育女性的肿瘤，并将肿瘤特征与未生育女性或在诊断前5年及以上生育女性的肿瘤特征进行了比较。对1983年1月至1992年12月在华盛顿州西部三个县诊断为浸润性导管乳腺癌的1174名45岁以下女性进行了随访研究。这些女性此前参与了一项基于人群的病例对照研究。平均随访时间为105.4个月。79.1%的肿瘤收集了组织学切片，并由研究病理学家进行复查。使用免疫过氧化物酶测定法，对70.4%的女性肿瘤组织进行了预后标志物检测。采用Cox比例风险模型估计与生殖事件相关的死于乳腺癌的相对风险。使用逻辑回归来估计各种生殖因素与肿瘤特征之间的关联。随访结束时，最后一次生育发生在诊断前不到2年的女性中有48.2%（n = 83）死亡，未生育女性中有23.3%（n = 189）死亡，最后一次生育发生在诊断前5年及以上的女性中有24.4%（n = 661）死亡。与未生育女性的肿瘤相比，近期生育（诊断前不到2年）女性的肿瘤更可能孕激素受体阴性，优势比（OR）= 2.2，95%置信区间（CI）= 1.2 - 3.9；p53阳性，OR = 2.6，95% CI = 1.5 - 4.7；组织学分级高，OR = 5.9，95% CI = 1.7 - 20.1；有丝分裂计数高，OR = 2.2，95% CI = 1.4 - 4.4；淋巴结阳性，OR = 2.1，95% CI = 1.3 - 3.5；S期分数高，OR = 2.3，95% CI = 1.1 - 4.8；美国癌症联合委员会分期高（III +），OR = 2.8，95% CI 1.3 - 5.8。在调整肿瘤特征和治疗因素后，与乳腺癌诊断前不到2年生育相关的死亡风险仍然是死亡的独立预测因素，风险比（HR）= 2.7，95% CI = 1.6 - 4.3。我们的研究提供了证据表明生殖因素会影响年轻女性乳腺癌的生物学行为和预后。临床医生需要意识到，在诊断前不到2年分娩的女性患具有特别不良预后特征肿瘤的风险增加，并且其生存率低于未生育女性或最后一次生育发生在数年前的女性。
