The prognostic role of HER2 expression in ductal breast carcinoma in situ (DCIS); a population-based cohort study.
The prognostic role of HER2 expression in ductal breast carcinoma in situ (DCIS); a population-based cohort study.
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DOI：
10.1186/s12885-015-1479-3
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发表时间：
2015-06-11
期刊：
影响因子：
3.8
通讯作者：
Wärnberg F
中科院分区：
文献类型：
--
作者：
Borgquist S;Zhou W;Jirström K;Amini RM;Sollie T;Sørlie T;Blomqvist C;Butt S;Wärnberg F
HER2 是浸润性乳腺癌中公认的预后和预测因素。 HER2 在导管原位乳腺癌 (DCIS) 中的作用存在争议，最近的数据表明 HER2 主要与原位复发有关。我们的目的是研究 HER2 作为大型 DCIS 人群的预后因素并进行长期随访。 1986 年至 2004 年瑞典两个县诊断为原发性 DCIS 的所有 458 名患者均被纳入其中。使用银增强原位杂交 (SISH) 检测 HER2 基因扩增，并通过组织微阵列中的免疫组织化学 (IHC) 评估蛋白质表达。 HER2 阳性定义为 IHC 扩增的 HER2 基因和/或 HER2 3+。通过 Kaplan-Meier 生存分析和 Cox 比例风险回归模型评估与新同侧事件 (IBE) 和局部或远处浸润性乳腺癌复发 (IBCR) 相关的 HER2 状态。 75.5% 的原发性导管原位癌是通过筛查发现的。 78.6% 的患者进行了保乳手术 (BCS)，其中 44.0% 接受了术后放疗。没有患者接受辅助内分泌或化疗。大多数 DCIS 可以分类为 HER2 (N = 420 (91.7 %))； 132 名 HER2 阳性 (31%) 和 288 名 HER2 阴性 (69%)。 HER2 阳性与肿瘤体积大 (P = 0.002)、高级别 (P< 0.001) 以及 ER- 和 PR 阴性 (P< 0.001) 相关。在随访期间（平均 184 个月），在所有 458 例病例中发现了 106 个 IBCR 和 105 个 IBE，对应于 54 个原位复发和 51 个侵入性复发。 18 名女性死于乳腺癌，另有 114 名女性死于其他原因。与 HER2 阴性 DCIS 相比，HER2 阳性 DCIS 后发生 IBCR 的风险在统计学上显着降低（Log-Rank P = 0.03，(HR) 0.60 (95% CI 0.38–0.94)）。值得注意的是，这些曲线直到 10 年后才分离。在 ER 分层分析中，HER2 阳性 DCIS 与 ER 阴性 DCIS 女性较低的 IBCR 风险相关（Log-Rank P = 0.003），但与 ER 阳性 DCIS 女性无关。需要改进 DCIS 患者的预后工具来调整辅助治疗。在这里，我们证明原发性 DCIS 中的 HER2 阳性疾病与复发性浸润性乳腺癌的较低风险相关。
HER2 is a well-established prognostic and predictive factor in invasive breast cancer. The role of HER2 in ductal breast carcinoma in situ (DCIS) is debated and recent data have suggested that HER2 is mainly related to in situ recurrences. Our aim was to study HER2 as a prognostic factor in a large population based cohort of DCIS with long-term follow-up. All 458 patients diagnosed with a primary DCIS 1986–2004 in two Swedish counties were included. Silver-enhanced in situ hybridisation (SISH) was used for detection of HER2 gene amplification and protein expression was assessed by immunohistochemistry (IHC) in tissue microarrays. HER2 positivity was defined as amplified HER2 gene and/or HER2 3+ by IHC. HER2 status in relation to new ipsilateral events (IBE) and Invasive Breast Cancer Recurrences, local or distant (IBCR) was assessed by Kaplan-Meier survival analyses and Cox proportional hazards regression models. Primary DCIS was screening-detected in 75.5 % of cases. Breast conserving surgery (BCS) was performed in 78.6 % of whom 44.0 % received postoperative radiotherapy. No patients received adjuvant endocrine- or chemotherapy. The majority of DCIS could be HER2 classified (N = 420 (91.7 %)); 132 HER2 positive (31 %) and 288 HER2 negative (69 %)). HER2 positivity was related to large tumor size (P = 0.002), high grade (P < 0.001) and ER- and PR negativity (P < 0.001 for both). During follow-up (mean 184 months), 106 IBCRs and 105 IBEs were identified among all 458 cases corresponding to 54 in situ and 51 invasive recurrences. Eighteen women died from breast cancer and another 114 had died from other causes. The risk of IBCR was statistically significantly lower subsequent to a HER2 positive DCIS compared to a HER2 negative DCIS, (Log-Rank P = 0.03, (HR) 0.60 (95 % CI 0.38–0.94)). Remarkably, the curves did not separate until after 10 years. In ER-stratified analyses, HER2 positive DCIS was associated with lower risk of IBCR among women with ER negative DCIS (Log-Rank P = 0.003), but not for women with ER positive DCIS. Improved prognostic tools for DCIS patients are warranted to tailor adjuvant therapy. Here, we demonstrate that HER2 positive disease in the primary DCIS is associated with lower risk of recurrent invasive breast cancer.
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一种多基因表达测定法，以预测乳房原位导管癌的局部复发风险。
DOI：
10.1093/jnci/djt067
发表时间：
2013-05-15
期刊：
Journal of the National Cancer Institute
影响因子：
--
作者：
Solin LJ;Gray R;Baehner FL;Butler SM;Hughes LL;Yoshizawa C;Cherbavaz DB;Shak S;Page DL;Sledge GW Jr;Davidson NE;Ingle JN;Perez EA;Wood WC;Sparano JA;Badve S
通讯作者：
Badve S
影响因子：
8.4
作者：
Ringberg, A.;Nordgren, H.;Holmberg, L.
通讯作者：
Holmberg, L.
影响因子：
--
作者：
Francis, Glenn D.;Jones, Mark A.;Stein, Sandra R.
通讯作者：
Stein, Sandra R.
影响因子：
45.3
作者：
Silverstein, MJ;Lagios, MD;Waisman, JR
通讯作者：
Waisman, JR
DOI：
10.1186/bcr1613
发表时间：
2006
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Hannemann J;Velds A;Halfwerk JB;Kreike B;Peterse JL;van de Vijver MJ
通讯作者：
van de Vijver MJ