Division of Oncological Sciences, Oregon Health & Science University, Portland.
Knight Cancer Institute, Oregon Health & Science University, Portland.
JAMA Netw Open. 2022 Oct 3;5(10):e2236763. doi: 10.1001/jamanetworkopen.2022.36763.
Breast cancer diagnosed within 5 to 10 years after childbirth, called postpartum breast cancer (PPBC), is associated with increased risk for metastasis and death. Whether a postpartum diagnosis is an independent risk factor or a surrogate marker of cancer features associated with poor outcomes remains understudied.
To determine whether diagnostic temporal proximity to childbirth is associated with features of breast cancer associated with poor outcomes, including tumor stage, estrogen receptor (ER) status, and risk for distant metastasis and breast cancer-specific mortality, using a population database from the state of Utah.
DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study using the Utah Population Database (UPDB) included individuals with stage I to III breast cancer diagnosed at age 45 years or younger between 1996 and 2017, followed-up until February 2020. Participant data were analyzed from November 2019 to August 2022.
The primary exposures were no prior childbirth or time between most recent childbirth and breast cancer diagnosis. Patients were grouped by diagnoses within less than 5 years, 5 to less than 10 years, or 10 years or more since recent childbirth.
The 2 primary outcomes were distant metastasis-free survival and breast cancer-specific death. Cox proportional hazard models were used to investigate associations between exposures and outcomes adjusting for diagnosis year, patient age, tumor stage, and estrogen receptor (ER) status.
Of 2970 individuals with breast cancer diagnosed at age 45 years or younger (mean [SD] age, 39.3 [5.0] years; 12 Black individuals [0.4%], 2679 White individuals [90.2%]), breast cancer diagnosis within 5 years of recent childbirth was independently associated with approximately 1.5-fold elevated risk for metastasis (hazard ratio [HR], 1.5; 95% CI, 1.2-2.0) and breast cancer-specific death (HR, 1.5; 95% CI, 1.1-2.1) compared with nulliparous individuals. For cancers classically considered to have tumor features associated with good outcomes (ie, stage I or II and ER-positive), a postpartum diagnosis was a dominant feature associated with increased risk for metastasis and death (eg, for individuals with ER-positive disease diagnosed within <5 years of childbirth: age-adjusted metastasis HR, 1.5; 95% CI, 1.1-2.1; P = .01; age-adjusted death HR, 1.5; 95% CI, 1.0-2.1; P = .04) compared with nulliparous individuals. Furthermore, liver metastases were specifically increased in the group with diagnosis within 5 years postpartum and with positive ER expression (38 of 83 patients [45.8%]) compared with the nulliparous (28 of 77 patients [36.4%]), although the difference was not statistically significant. Overall, these data implicate parity-associated breast and liver biology in the observed poor outcomes of PPBC.
In this cohort study of individuals with breast cancer diagnosed at age 45 years or younger, a postpartum breast cancer diagnosis was a risk factor associated with poor outcomes. Irrespective of ER status, clinical consideration of time between most recent childbirth and breast cancer diagnosis could increase accuracy of prognosis in patients with young-onset breast cancer.
产后 5 至 10 年内诊断出的乳腺癌,称为产后乳腺癌(PPBC),与转移和死亡风险增加有关。产后诊断是否是转移风险增加和不良预后相关的癌症特征的独立危险因素还是替代标志物仍有待研究。
使用犹他州的人口数据库(UPDB),确定与不良预后相关的乳腺癌特征,包括肿瘤分期、雌激素受体(ER)状态以及远处转移和乳腺癌特异性死亡的风险,是否与产后诊断时间的接近程度有关。
设计、设置和参与者:这项基于人群的队列研究使用了 UPDB,纳入了 1996 年至 2017 年间 45 岁以下被诊断为 I 期至 III 期乳腺癌的个体,随访至 2020 年 2 月。参与者数据于 2019 年 11 月至 2022 年 8 月进行分析。
主要暴露因素是无生育史或最近一次分娩与乳腺癌诊断之间的时间。患者根据最近分娩后 5 年内、5 至 10 年内或 10 年或更长时间的诊断分组。
两个主要结局是远处无转移生存和乳腺癌特异性死亡。使用 Cox 比例风险模型,调整诊断年份、患者年龄、肿瘤分期和雌激素受体(ER)状态,调查暴露与结局之间的关系。
在 2970 名 45 岁以下被诊断为乳腺癌的个体中(平均[SD]年龄 39.3[5.0]岁;12 名黑人患者[0.4%],2679 名白人患者[90.2%]),与未生育的个体相比,产后 5 年内被诊断为乳腺癌与转移(风险比[HR],1.5;95%CI,1.2-2.0)和乳腺癌特异性死亡(HR,1.5;95%CI,1.1-2.1)的风险增加约 1.5 倍相关。对于传统上被认为具有良好预后肿瘤特征的癌症(即 I 期或 II 期和 ER 阳性),产后诊断是与转移和死亡风险增加相关的主要特征(例如,在产后 5 年内被诊断为 ER 阳性疾病的患者:年龄调整的转移 HR,1.5;95%CI,1.1-2.1;P=0.01;年龄调整的死亡 HR,1.5;95%CI,1.0-2.1;P=0.04),与未生育的个体相比。此外,与未生育的个体相比,产后 5 年内诊断并伴有 ER 阳性表达的患者(83 例患者中有 38 例[45.8%])发生肝转移的比例明显更高(83 例患者中有 28 例[36.4%]),尽管差异无统计学意义。总的来说,这些数据提示与生育相关的乳房和肝脏生物学在观察到的产后乳腺癌不良结局中起作用。
在这项对 45 岁以下被诊断为乳腺癌的个体的队列研究中,产后乳腺癌诊断是不良预后的一个危险因素。无论 ER 状态如何,最近一次分娩与乳腺癌诊断之间的时间考虑都可以提高年轻乳腺癌患者预后的准确性。