Abstract:
BACKGROUND:We investigated the effect of basal protein expression on trastuzamab response in patients with HER2-positive (HER2(+)) breast cancer who received trastuzamab (T) and in HER2(+) breast cancer cell lines. PATIENTS AND METHODS:Expression of cytokeratin (CK) 5/6, CK14, and epidermal growth factor receptor (EGFR) was evaluated after immunohistochemical staining in paraffin-embedded tissue of 97 patients with stage I to III HER2(+) breast cancer treated with chemotherapy/T. Groups with and without basal protein expression were compared with respect to clinicopathologic parameters and survival. We treated 4 cell lines (2 basal-HER2 [HCC1569, HCC1954] and 2 nonbasal HER2 [BT474, SKBR3]) each with vehicle, T 20 μg/mL, paclitaxel 0.01 μM (P), and T with P (T + P). Cell viability was assessed and HER2 pathway suppression was compared between groups using immunoblot analysis. Mammosphere formation was used to assess breast cancer stem cell properties. RESULTS:EGFR expression was significantly associated with cancer-specific survival (CSS) (P = .05). CK5/6 expression strongly correlated with overall and disease-free survival, and CSS (P = .03, P = .04, and P = .03, respectively). Statistical significance was maintained for EGFR and CK5/6 after adjustment for covariates. CK14 was not associated with survival. All cell lines expressed similar levels of HER2. T and P alone inhibited proliferation of nonbasal cell lines; T + P had an additive cytotoxic effect. Basal cells were resistant to T, P inhibited proliferation, but T + P had no additive cytotoxic effect on cell growth in basal cells. Immunoblot analysis showed a significant decrease in phosphorylated Akt levels after treatment with T or T + P in nonbasal cells but not in basal cells. Akt blockade suppressed growth of basal and nonbasal HER2(+) cells. Furthermore, basal HER2 cell lines had increased mammosphere formation, which suggests increased stem cell properties compared with nonbasal HER2 cell lines. CONCLUSION:CK5/6 and EGFR expression are predictive of worse prognosis in HER2(+) breast cancer patients treated with T. Basal HER2 breast cancer cell lines are resistant to trastuzamab, which is mediated through the Akt pathway; AKT inhibition abrogates this resistance. Basal HER2 cell lines also have increased stem cell properties, which might play a role in the resistance pathway.
journal_name
Clin Breast Cancerjournal_title
Clinical breast cancerauthors
Chung A,Choi M,Han BC,Bose S,Zhang X,Medina-Kauwe L,Sims J,Murali R,Taguiam M,Varda M,Schiff R,Giuliano A,Cui Xdoi
10.1016/j.clbc.2015.06.001subject
Has Abstractpub_date
2015-12-01 00:00:00pages
448-457.e2issue
6eissn
1526-8209issn
1938-0666pii
S1526-8209(15)00117-2journal_volume
15pub_type
杂志文章abstract:UNLABELLED:This is a retrospective study on 40 breast cancer patients, of which 20 have bone metastases, 10 have visceral metastases, and 10 have no evidence of disease, aimed at evaluating the role of CXCR4 and the RANK/RANKL/OPG system to predict bone metastases. CXCR4 expression, alone or in combination with RANK, i...
journal_title:Clinical breast cancer
pub_type: 杂志文章
doi:10.1016/j.clbc.2011.05.001
更新日期:2011-12-01 00:00:00
abstract:BACKGROUND:Triple-negative breast carcinoma is defined by a primary tumor that is estrogen receptor negative, progesterone receptor negative, and HER2 negative. The current study was performed to determine the relationship of triple-negative tumor status to outcome after breast conservation treatment with radiation. P...
journal_title:Clinical breast cancer
pub_type: 杂志文章
doi:10.3816/CBC.2009.n.018
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abstract:BACKGROUND:Most investigations have compared triple-negative breast cancer (TNBC) to non-TNBC to elucidate clinical or epidemiologic differences between subtypes. We examined a contemporary cohort of patients with primary TNBC by detection and age at diagnosis within a population-based breast screening program to exami...
journal_title:Clinical breast cancer
pub_type: 杂志文章
doi:10.1016/j.clbc.2018.04.013
更新日期:2018-10-01 00:00:00
abstract:BACKGROUND:The diagnosis of breast cancer in young women (aged 18-45 years) has been increasing. Women are commonly left coping with treatment-related disabilities of the upper limb that can persist for > 2 years postoperatively. PATIENTS AND METHODS:A total of 59 young breast cancer patients (29 in the intervention g...
journal_title:Clinical breast cancer
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clbc.2017.06.007
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abstract:INTRODUCTION:Ensuring guideline-concordant cancer care is a Department of Veterans Affairs (VA) priority, especially as the number of breast cancer patients at VA medical centers (VAMCs) grows. We assessed the utilization and clinical impact of the 21-gene Recurrence Score test, which predicts 10-year risk of breast ca...
journal_title:Clinical breast cancer
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doi:10.1016/j.clbc.2017.11.018
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abstract:BACKGROUND:The objective of the study was to compare the accuracy of different magnetic resonance (MR) sequences for measuring tumor size and to evaluate whether the imaging and histopathologic features affect the accuracy of the tumor size estimation on the MR sequence. PATIENTS AND METHODS:Eight hundred women were i...
journal_title:Clinical breast cancer
pub_type: 杂志文章
doi:10.1016/j.clbc.2016.07.007
更新日期:2016-12-01 00:00:00
abstract:INTRODUCTION:The purpose of this study was to investigate the impact of single nucleotide polymorphisms (SNPs) in the acylphosphatase 2 gene and the SNP-SNP interactions on breast cancer (BC) risk in Chinese Han women. PATIENTS AND METHODS:A logistic regression model was used to examine the association between SNPs an...
journal_title:Clinical breast cancer
pub_type: 杂志文章
doi:10.1016/j.clbc.2017.09.003
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abstract:BACKGROUND:Although magnetic resonance imaging (MRI) is a useful imaging modality for invasive cancer, its role in preoperative surgical planning for ductal carcinoma in situ (DCIS) has not been established. We sought to determine whether preoperative MRI affects surgical treatment and outcomes in women with pure DCIS....
journal_title:Clinical breast cancer
pub_type: 杂志文章
doi:10.3816/CBC.2011.n.006
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journal_title:Clinical breast cancer
pub_type: 杂志文章,多中心研究,随机对照试验
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journal_title:Clinical breast cancer
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clbc.2013.09.011
更新日期:2014-06-01 00:00:00
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journal_title:Clinical breast cancer
pub_type: 杂志文章
doi:10.1016/j.clbc.2015.12.001
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journal_title:Clinical breast cancer
pub_type: 杂志文章
doi:10.3816/CBC.2008.n.014
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journal_title:Clinical breast cancer
pub_type: 杂志文章
doi:10.1016/j.clbc.2017.07.014
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journal_title:Clinical breast cancer
pub_type: 杂志文章
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journal_title:Clinical breast cancer
pub_type: 杂志文章,评审
doi:10.3816/CBC.2005.n.022
更新日期:2005-08-01 00:00:00
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journal_title:Clinical breast cancer
pub_type: 杂志文章,评审
doi:10.1016/j.clbc.2020.01.002
更新日期:2020-08-01 00:00:00
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journal_title:Clinical breast cancer
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.3816/CBC.2009.n.008
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journal_title:Clinical breast cancer
pub_type: 杂志文章
doi:10.1016/j.clbc.2020.11.018
更新日期:2020-12-05 00:00:00
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journal_title:Clinical breast cancer
pub_type: 杂志文章
doi:10.1016/j.clbc.2011.04.004
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journal_title:Clinical breast cancer
pub_type: 杂志文章
doi:10.1016/j.clbc.2013.10.010
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journal_title:Clinical breast cancer
pub_type: 杂志文章,多中心研究
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journal_title:Clinical breast cancer
pub_type: 杂志文章
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journal_title:Clinical breast cancer
pub_type: 临床试验,杂志文章
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journal_title:Clinical breast cancer
pub_type: 杂志文章,评审
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journal_title:Clinical breast cancer
pub_type: 杂志文章
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更新日期:2007-12-01 00:00:00
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journal_title:Clinical breast cancer
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更新日期:2019-04-01 00:00:00
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journal_title:Clinical breast cancer
pub_type: 杂志文章,评审
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journal_title:Clinical breast cancer
pub_type: 杂志文章,评审
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journal_title:Clinical breast cancer
pub_type: 杂志文章
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更新日期:2017-02-01 00:00:00
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journal_title:Clinical breast cancer
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