Racial Disparities in Pathological Complete Response Among Patients Receiving Neoadjuvant Chemotherapy for Early-Stage Breast Cancer.
Racial Disparities in Pathological Complete Response Among Patients Receiving Neoadjuvant Chemotherapy for Early-Stage Breast Cancer.
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DOI：
10.1001/jamanetworkopen.2023.3329
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发表时间：
2023-03-01
影响因子：
13.8
通讯作者：
Olopade, Olufunmilayo I.
中科院分区：
文献类型：
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作者：
Zhao, Fangyuan;Miyashita, Minoru;Hattori, Masaya;Yoshimatsu, Toshio;Howard, Frederick;Kaneva, Kristiyana;Jones, Ryan;Bell, Joshua S. K.;Fleming, Gini F.;Jaskowiak, Nora;Nanda, Rita;Zheng, Yonglan;Huo, Dezheng;Olopade, Olufunmilayo I.
乳腺癌患者对新辅助化疗的反应是否存在种族差异？造成这种差异的因素是什么？在这项690例早期乳腺癌患者的队列研究中，激素受体阴性/ERBB2+疾病的黑人患者获得病理完全缓解的几率明显低于白人患者。患有ERBB2+疾病的黑人患者比新一代肿瘤测序发现的白人患者更有可能发生MAPK通路改变。这些发现表明，不同乳腺癌亚型对新辅助化疗的反应存在种族差异，潜在的治疗靶点有待进一步研究。本队列研究探讨了乳腺癌患者在新辅助化疗（NACT）后病理完全缓解（pCR）是否存在种族差异，以及导致这种差异的因素。在乳腺癌患者中，发表的关于新辅助化疗（NACT）后实现病理完全缓解（pCR）的种族差异的研究结果不一致。调查在实现聚合酶链反应中是否存在种族差异以及造成这种差异的因素。正在进行的芝加哥多种族流行病学乳腺癌队列研究（ChiMEC）包括前瞻性确定的乳腺癌患者队列，在芝加哥大学医学院的单机构研究中确定了690名接受NACT治疗的I至III期乳腺癌患者。纳入2002年至2020年间诊断的患者（中位随访时间：5.4年）；新一代测序数据来自186例ChiMEC患者，包括原发和残留肿瘤样本。统计分析时间为2021年9月至2022年9月。人口统计学、生物学和治疗因素可能导致聚合酶链反应的差异。pCR被定义为乳腺和腋窝淋巴结中没有浸润性癌，而不考虑导管原位癌。该研究包括690例乳腺癌患者，平均（SD）年龄为50.1（12.8）岁。355例白人患者中有130例（36.6%）获得pCR， 269例黑人患者中有77例（28.6%,P = 0.04）获得pCR。未实现pCR与总生存率显著降低相关（校正风险比，6.10;95% CI, 2.80-13.32）。在激素受体阴性/ERBB2+亚型中，黑人患者获得pCR的几率明显低于白人患者（校正优势比为0.30；95% CI为0.11-0.81）。与ERBB2+疾病的白人患者相比，黑人患者更容易发生MAPK通路改变(30.0% [6 / 20]vs 4.6% [1 / 22]; P =。04)，抗erbb2治疗耐药的潜在机制。肿瘤突变负荷和若干基因（如FGF4、FGF3、CCND1、MCL1、FAT1、ERCC3、PTEN）的体细胞改变在原发肿瘤和残留肿瘤之间存在显著差异。在这项乳腺癌患者的队列研究中，种族差异对NACT的反应与生存差异有关，并且在不同的乳腺癌亚型中存在差异。这项研究强调了更好地了解原发性和残余肿瘤生物学的潜在益处。
Are there racial disparities in response to neoadjuvant chemotherapy among patients with breast cancer, and what factors contribute to them? In this cohort study of 690 patients with early-stage breast cancer, Black patients with hormone receptor–negative/ERBB2+ disease had significantly lower odds of achieving pathological complete response compared with White patients. Black patients with ERBB2+ disease were significantly more likely to have MAPK pathway alterations than White patients found with tumor next-generation sequencing. These findings suggest that racial disparities in response to neoadjuvant chemotherapy varied across different breast cancer subtypes and potential therapeutic targets should be further investigated. This cohort study examines whether racial disparities exist in achieving pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) and what factors contribute to them among patients with breast cancer. Among patients with breast cancer, inconsistent findings have been published on racial disparities in achieving pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT). To investigate whether racial disparities exist in achieving pCR and what factors contribute to them. Within the ongoing Chicago Multiethnic Epidemiologic Breast Cancer Cohort (ChiMEC), which consists of a prospectively ascertained cohort of patients with breast cancer, 690 patients with stage I to III breast cancer receiving NACT were identified for this single-institution study at the University of Chicago Medicine. Patients diagnosed between 2002 and 2020 (median follow-up: 5.4 years) were included; next-generation sequencing data on tumor-normal tissue pairs were available from 186 ChiMEC patients, including both primary and residual tumor samples. Statistical analysis was performed from September 2021 to September 2022. Demographic, biological, and treatment factors that could contribute to disparities in achieving pCR. pCR was defined as the absence of invasive cancer in the breast and axillary nodes, irrespective of ductal carcinoma in situ. The study included 690 patients with breast cancer, with a mean (SD) age of 50.1 (12.8) years. Among the 355 White patients, 130 (36.6%) achieved pCR compared to 77 of the 269 Black patients (28.6%; P = .04). Not achieving pCR was associated with significantly worse overall survival (adjusted hazard ratio, 6.10; 95% CI, 2.80-13.32). Black patients had significantly lower odds of achieving pCR compared with White patients in the hormone receptor–negative/ERBB2+ subtype (adjusted odds ratio, 0.30; 95% CI, 0.11-0.81). Compared with White patients with ERBB2+ disease, Black patients were more likely to have MAPK pathway alterations (30.0% [6 of 20] vs 4.6% [1 of 22]; P = .04), a potential mechanism of anti-ERBB2 therapy resistance. Tumor mutational burden and somatic alterations in several genes (eg, FGF4, FGF3, CCND1, MCL1, FAT1, ERCC3, PTEN) were significantly different between the primary and residual tumors. In this cohort study of patients with breast cancer, racial disparities in response to NACT were associated with disparities in survival and varied across different breast cancer subtypes. This study highlights the potential benefits of better understanding the biology of primary and residual tumors.
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影响因子：
45.3
作者：
Killelea, Brigid K.;Yang, Vicky Q.;Lannin, Donald R.
通讯作者：
Lannin, Donald R.
影响因子：
7.2
作者：
DEYO, RA;CHERKIN, DC;CIOL, MA
通讯作者：
CIOL, MA
影响因子：
3.1
作者：
Fei, Fei;Siegal, Gene P.;Wei, Shi
通讯作者：
Wei, Shi
影响因子：
28.4
作者：
Huo D;Hu H;Rhie SK;Gamazon ER;Cherniack AD;Liu J;Yoshimatsu TF;Pitt JJ;Hoadley KA;Troester M;Ru Y;Lichtenberg T;Sturtz LA;Shelley CS;Benz CC;Mills GB;Laird PW;Shriver CD;Perou CM;Olopade OI
通讯作者：
Olopade OI
DOI：
10.1093/jncimonographs/lgv004
发表时间：
2015-05-01
期刊：
Journal of the National Cancer Institute Monographs
影响因子：
--
作者：
Hayes, Daniel F.;Schott, Anne F.
通讯作者：
Schott, Anne F.