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美国人群中的化生性乳腺癌:种族差异、辅助放化疗的生存获益以及基于基因组图谱的未来个性化治疗

Metaplastic Breast Carcinoma in U.S. Population: Racial Disparities, Survival Benefit of Adjuvant Chemoradiation and Future Personalized Treatment with Genomic Landscape.

作者信息

Ullah Asad, Khan Jaffar, Yasinzai Abdul Qahar Khan, Tracy Katharine, Nguyen Tena, Tareen Bisma, Garcia Andrea Agualimpia, Heneidi Saleh, Segura Sheila E

机构信息

Department of Pathology, Immunology, and Microbiology, Vanderbilt University, Nashville, TN 37232, USA.

Department of Pathology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

出版信息

Cancers (Basel). 2023 May 28;15(11):2954. doi: 10.3390/cancers15112954.

Abstract

PURPOSE

In this population-based study, we aim to identify factors that are influential on the survival outcome in MBC and investigate novel molecular approaches in personalized disease management.

METHODS

The data of this study were collected from the SEER database from 2000-2018. A total of 5315 cases were extracted from the database. The data were evaluated for demographics, tumor characteristics, metastasis, and treatment. Survival analysis was completed by using SAS software for multivariate analysis, univariate analysis, and non-parametric survival analysis. The molecular data with the most common mutations in MBC were extracted from the Catalogue of Somatic Mutations in Cancer (COSMIC) database.

RESULTS

The mean age at the time of presentation was 63.1 with a standard deviation (SD) of 14.2 years. Most patients were White (77.3%) with 15.7% Black patients, 6.1% Asian or Pacific Islander, and 0.5% American Indian. Histologically, most of the reported tumors were grade III (74.4%); 37% of the cases were triple negative (ER-, PR- and HER2-), whereas the hormone status was unknown in 46% of the cases. Spread was localized in 67.3% of patients while 26.3% had regional spread and 6.3% had distant metastases. Most tumors were unilateral (99.9%) and between 20-50 mm in size (50.6%). The lungs were the most common site for distant metastasis at diagnosis (3.42%) followed by bone (1.94%), liver (0.98%), and brain (0.56%). A combination of surgery, chemotherapy, and radiation therapy was the most common treatment with a cause-specific survival rate of 78.1% (95% CI = 75.4-80.4). The overall survival rate at 5 years was 63.6% (95% confidence interval (CI) = 62.0-65.1) with a cause-specific survival of 71.1% (95% CI = 69.5-72.6). Cause-specific survival was found to be 63.2% (95% CI = 58.9-67.1) in Black patients as compared to 72.4% (95% CI = 70.1-74.1) in White patients. Black patients also presented with higher rates of grade III disease, distant metastasis, and larger tumor size. On multivariate analysis, age > 60, grade III+, metastasis, and tumor size > 50 mm were associated with worse survival. The most common mutations in MBC identified in COSMIC data were TP53, PIK3CA, LRP1B, PTEN, and KMT2C.

CONCLUSION

Though rare, MBC is aggressive, with poor prognosis associated with high-grade tumors, metastasis, tumor size over 50 mm, and advanced age at the time of presentation. Overall, Black women had worse clinical outcomes. MBC is difficult to treat and carries a poor prognosis that affects various races disproportionately. Continued enhancement of treatment strategies to foster more individualized care as well as continued enrollment in clinical trials are needed to improve outcomes among patients with MBC.

摘要

目的

在这项基于人群的研究中,我们旨在确定影响转移性乳腺癌(MBC)生存结局的因素,并研究个性化疾病管理中的新型分子方法。

方法

本研究的数据收集自2000年至2018年的监测、流行病学和最终结果(SEER)数据库。共从该数据库中提取了5315例病例。对数据进行了人口统计学、肿瘤特征、转移情况和治疗方面的评估。使用SAS软件完成生存分析,包括多变量分析、单变量分析和非参数生存分析。从癌症体细胞突变目录(COSMIC)数据库中提取MBC中最常见突变的分子数据。

结果

就诊时的平均年龄为63.1岁,标准差(SD)为14.2岁。大多数患者为白人(77.3%),黑人患者占15.7%,亚洲或太平洋岛民占6.1%,美国印第安人占0.5%。组织学上,报告的大多数肿瘤为III级(74.4%);37%的病例为三阴性(雌激素受体阴性、孕激素受体阴性和人表皮生长因子受体2阴性),而46%的病例激素状态未知。67.3%的患者转移局限,26.3%有区域转移,6.3%有远处转移。大多数肿瘤为单侧(99.9%),大小在20至50毫米之间(50.6%)。诊断时,肺是最常见的远处转移部位(3.42%),其次是骨(1.94%)、肝(0.98%)和脑(0.56%)。手术、化疗和放疗联合是最常见的治疗方法,特定病因生存率为78.1%(95%置信区间[CI]=75.4 - 80.4)。5年总生存率为63.6%(95%置信区间[CI]=62.0 - 65.1),特定病因生存率为71.1%(95%置信区间[CI]=69.5 - 72.6)。黑人患者的特定病因生存率为63.2%(95%置信区间[CI]=58.9 - 67.1),而白人患者为72.4%(95%置信区间[CI]=70.1 - 74.1)。黑人患者III级疾病、远处转移和肿瘤较大的发生率也较高。多变量分析显示,年龄>60岁、III级以上、转移和肿瘤大小>50毫米与较差的生存相关。在COSMIC数据中确定的MBC最常见突变是TP53、PIK3CA、LRP1B、PTEN和KMT2C。

结论

尽管罕见,但MBC具有侵袭性,预后不良与高级别肿瘤、转移、肿瘤大小超过50毫米以及就诊时年龄较大有关。总体而言,黑人女性的临床结局较差。MBC难以治疗,预后不良,对不同种族的影响不成比例。需要持续加强治疗策略以促进更个性化的护理,并继续招募患者参加临床试验,以改善MBC患者的结局。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/447e/10251813/cb29bc6b989f/cancers-15-02954-g001.jpg

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