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肿瘤床基质细胞中的雌激素受体阳性可预测乳腺癌新辅助化疗的反应。

Estrogen receptor positivity in stromal cells of the tumor bed predicts the response to neoadjuvant chemotherapy for breast carcinoma.

作者信息

Bayram Aysel, Bagbudar Sidar, Karanlık Hasan, Cabıoglu Neslihan, Aydıner Adnan, Onder Semen, Yavuz Ekrem

机构信息

Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, 34390, Faith, Istanbul, Turkey.

Department of Surgical Oncology Unit, Institute of Oncology, Istanbul University, Istanbul, Turkey.

出版信息

Breast Cancer Res Treat. 2025 Apr;210(3):627-633. doi: 10.1007/s10549-024-07601-6. Epub 2025 Jan 8.

DOI:10.1007/s10549-024-07601-6
PMID:39776012
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11953172/
Abstract

PURPOSE

This study aimed to determine estrogen receptor (ER) expression in stromal cells in postchemotherapy tumor bed (PCTB) and its relationship with tumor regression and tumor characteristics.

METHODS

The study included 490 breast cancer patients who received neoadjuvant chemotherapy (NAC). We performed ER in stromal cells in all resection specimens and available pre-treatment core biopsy materials of 299 patients immunohistochemically.

RESULTS

Two hundred and forty-two (49.4%) cases were negative for ER in the stromal cells of the PCTB, and 248 (50.6%) cases were positive. ER-positive stromal cells in the PCTB correlated with a higher regression rate (90.2 vs 68.6%) and lower mean residual cancer burden value (1.366 vs 2.424) compared to ER-negative cases (p < 0.001). Stromal ER positivity was more prevalent in cases achieving pathologic complete response (pCR) (68.1%) compared to those without pCR (39.8%, p < 0.001). ER positivity in stromal cells was more common in non-luminal tumors than in luminal ones. Multivariate analysis identified stromal ER positivity (OR: 3.059, 95% CI [1.947-4.807], p < 0.001), intrinsic subtype (Odds ratio (OR): 1.477, 95% confidence interval (CI) [1.102-1.980], p = 0.009), and Ki67 index (OR: 1.028, 95% CI [1.104-1.041], p < 0.001) as independent predictors of pCR. In core biopsies before NAC, 270 cases (90.3%) and 29 cases (9.7%) were negative and positive in stromal cells, respectively. Out of the cases with ER-negativity in stromal cells before NAC, 132 (48.9%) converted to ER positivity in stromal cells of PCTB and displayed a high regression rate (89.8%).

CONCLUSION

This is the first study regarding ER expression in the stroma of breast carcinoma that compares treatment response after NAC. We showed that the increase in ER positivity in the stromal cells of the PCTB is correlative with the complete response and tumor subtypes. In this manner, ER positivity in stromal cells will soon serve as a cornerstone for individualized treatment options.

摘要

目的

本研究旨在确定化疗后肿瘤床(PCTB)基质细胞中雌激素受体(ER)的表达及其与肿瘤消退和肿瘤特征的关系。

方法

该研究纳入了490例接受新辅助化疗(NAC)的乳腺癌患者。我们对299例患者的所有切除标本及可用的治疗前核心活检材料中的基质细胞进行了ER免疫组织化学检测。

结果

PCTB基质细胞中ER阴性的病例有242例(49.4%),阳性的有248例(50.6%)。与ER阴性病例相比,PCTB中ER阳性基质细胞与更高的消退率(90.2%对68.6%)和更低的平均残留癌负荷值(1.366对2.424)相关(p < 0.001)。与未达到病理完全缓解(pCR)的病例相比,达到pCR的病例中基质ER阳性更为普遍(68.1%对39.8%,p < 0.001)。基质细胞中ER阳性在非腔面肿瘤中比在腔面肿瘤中更常见。多因素分析确定基质ER阳性(比值比(OR):3.059,95%置信区间(CI)[1.947 - 4.807],p < 0.001)、内在亚型(OR:1.477,95% CI [1.102 - 1.980],p = 0.009)和Ki67指数(OR:1.028,95% CI [1.104 - 1.041],p < 0.001)是pCR的独立预测因素。在NAC前的核心活检中,基质细胞阴性的病例有270例(90.3%),阳性的有29例(9.7%)。在NAC前基质细胞ER阴性的病例中,有132例(48.9%)在PCTB的基质细胞中转变为ER阳性,并显示出较高的消退率(89.8%)。

结论

这是第一项关于乳腺癌基质中ER表达并比较NAC后治疗反应的研究。我们表明,PCTB基质细胞中ER阳性的增加与完全缓解和肿瘤亚型相关。通过这种方式,基质细胞中ER阳性将很快成为个体化治疗方案的基石。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c7f/11953172/6d6bf19752ee/10549_2024_7601_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c7f/11953172/6d6bf19752ee/10549_2024_7601_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c7f/11953172/6d6bf19752ee/10549_2024_7601_Fig1_HTML.jpg

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本文引用的文献

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FASEB J. 2022 Nov;36(11):e22597. doi: 10.1096/fj.202200164RR.
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Drug targeting to myofibroblasts: Implications for fibrosis and cancer.靶向肌成纤维细胞的药物:对纤维化和癌症的影响。
Adv Drug Deliv Rev. 2017 Nov 1;121:101-116. doi: 10.1016/j.addr.2017.07.010. Epub 2017 Jul 16.
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Tumor-associated fibroblasts predominantly come from local and not circulating precursors.
肿瘤相关成纤维细胞主要来源于局部而非循环前体细胞。
Proc Natl Acad Sci U S A. 2016 Jul 5;113(27):7551-6. doi: 10.1073/pnas.1600363113. Epub 2016 Jun 17.
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Key players in pancreatic cancer-stroma interaction: Cancer-associated fibroblasts, endothelial and inflammatory cells.胰腺癌-基质相互作用中的关键参与者:癌症相关成纤维细胞、内皮细胞和炎症细胞。
World J Gastroenterol. 2016 Mar 7;22(9):2678-700. doi: 10.3748/wjg.v22.i9.2678.
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Chemotherapy induces the cancer-associated fibroblast phenotype, activating paracrine Hedgehog-GLI signalling in breast cancer cells.化疗诱导癌症相关成纤维细胞表型,激活乳腺癌细胞中的旁分泌刺猬索尼克-胶质瘤相关蛋白信号通路。
Oncotarget. 2015 May 10;6(13):10728-45. doi: 10.18632/oncotarget.3828.
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TSPAN12 is a critical factor for cancer-fibroblast cell contact-mediated cancer invasion.四跨膜蛋白12是癌症-成纤维细胞接触介导的癌症侵袭的关键因素。
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