Bcl2 is an independent prognostic marker of triple negative breast cancer (TNBC) and predicts response to anthracycline combination (ATC) chemotherapy (CT) in adjuvant and neoadjuvant settings

Abdel-Fatah, Tma; Perry, Christina; Dickinson, P.; Ball, Graham; Moseley, Paul M.; Madhusudan, Srinivasan; Ellis, Ian O.; Chan, Sy

doi:10.1093/annonc/mdt277

Cited by 71 publications

(79 citation statements)

References 15 publications

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“…Patient demographics are summarized in Supplementary Table S3. This is a well-characterized series of patients with long-term follow-up that have been investigated in a wide range of biomarker studies (12)(13)(14)(15)(16)(17)(18)(19)(20). All patients were treated in a uniform way in a single institution with standard surgery (mastectomy or wide local excision) with radiotherapy.…”

Section: Blm Protein Expression In Breast Cancermentioning

confidence: 99%

“…The TMAs were immunohistochemically profiled for BLM and other biologic antibodies (Supplementary Table S4) as previously described (12)(13)(14)(15)(16)(17)(18)(19)(20). Immunohistochemical (IHC) staining was performed using the Thermo Scientific Shandon Sequenza chamber system (REF: 72110017), in combination with the Novolink Max Polymer Detection System (RE7280-K: 1,250 tests), and the Leica Bond Primary Antibody Diluent (AR9352), each used according to the manufacturer's instructions (Leica Microsystems).…”

Section: Tissue Microarrays and Immunohistochemistrymentioning

confidence: 99%

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Transcriptomic and Protein Expression Analysis Reveals Clinicopathological Significance of Bloom Syndrome Helicase (BLM) in Breast Cancer

Arora

Abdel-Fatah

Agarwal

et al. 2015

Molecular Cancer Therapeutics

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Bloom syndrome helicase (BLM) has key roles in homologous recombination repair, telomere maintenance, and DNA replication. Germ-line mutations in the BLM gene causes Bloom syndrome, a rare disorder characterized by premature aging and predisposition to multiple cancers, including breast cancer. The clinicopathologic significance of BLM in sporadic breast cancers is unknown. We investigated BLM mRNA expression in the Molecular Taxonomy of Breast Cancer International Consortium cohort (n ¼ 1,950) and validated in an external dataset of 2,413 tumors. BLM protein level was evaluated in the Nottingham Tenovus series comprising 1,650 breast tumors. BLM mRNA overexpression was significantly associated with high histologic grade, larger tumor size, estrogen receptor-negative (ER À ), progesterone receptor-negative (PR À ), and triple-negative phenotypes (ps < 0.0001). BLM mRNA overexpression was also linked to aggressive molecular phenotypes, including PAM50.Her2 (P < 0.0001), PAM50. Basal (P < 0.0001), and PAM50.LumB (P < 0.0001) and Genufu subtype (ER þ /Her2 À /high proliferation; P < 0.0001). PAM50. LumA tumors and Genufu subtype (ER þ /Her2 À /low proliferation) were more likely to express low levels of BLM mRNA (ps < 0.0001). Integrative molecular clusters (intClust) intClust.1 (P < 0.0001), intClust.5 (P < 0.0001), intClust.9 (P < 0.0001), and intClust.10 (P < 0.0001) were also more likely in tumors with high BLM mRNA expression. BLM mRNA overexpression was associated with poor breast cancer-specific survival (BCSS; ps < 0.000001). At the protein level, altered subcellular localization with high cytoplasmic BLM and low nuclear BLM was linked to aggressive phenotypes. In multivariate analysis, BLM mRNA and BLM protein levels independently influenced BCSS. This is the first and the largest study to provide evidence that BLM is a promising biomarker in breast cancer.

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Section: Blm Protein Expression In Breast Cancermentioning

confidence: 99%

Section: Tissue Microarrays and Immunohistochemistrymentioning

confidence: 99%

Transcriptomic and Protein Expression Analysis Reveals Clinicopathological Significance of Bloom Syndrome Helicase (BLM) in Breast Cancer

Arora

Abdel-Fatah

Agarwal

et al. 2015

Molecular Cancer Therapeutics

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“…In recent years, researchers have discovered from pathological typing that many kinds of molecules can be used as prognostic indicators of neoadjuvant chemotherapy of breast cancer. For instance, over-expression of FOXA1 protein and BCL-2 protein are deemed to be negatively correlated to prognosis of ER positive breast cancer and triple negative breast cancer (Abdel-Fatah et al, 2013;Xu et al, 2015), while over-expression of the LC3B protein is considered to have a positive correlation with the prognosis of locally advanced breast cancer (Chen et al, 2013).…”

Section: Molecular Index and Prognosismentioning

confidence: 99%

Use of liposomal doxorubicin for adjuvant chemotherapy of breast cancer in clinical practice

Zhao

Ding

Shen

et al. 2017

J. Zhejiang Univ. Sci. B

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Breast cancer is one of the malignant tumors with the highest morbidity and mortality. It is helpful to reduce the rate of tumor recurrence and metastasis by treating breast cancer with adjuvant chemotherapy, so as to increase the cure rate or survival of patients. In recent years, liposomes have been regarded as a kind of new carrier for targeted drugs. Being effective for enhancing drug efficacy and reducing side effects, they have been widely used for developing anticancer drugs. As a kind of anthracycline with high anticancer activity, doxorubicin can treat or alleviate a variety of malignant tumors effectively when it is used on its own or in combination with other anticancer drugs. Although liposomal doxorubicin has been extensively used in the adjuvant chemotherapy of breast cancer, its exact therapeutic efficacy and side effects have not been definitely proven. Various clinical studies have adopted different combined regimes, dosages, and staging, so their findings differ to certain extent. This paper reviews the clinical application of liposomal doxorubicin in the adjuvant chemotherapy of breast cancer and illustrates therapeutic effects and side effects of pegylated liposomal doxorubicin (PLD) and non-PLD (NPLD) in clinical research, in order to discuss the strategies for applying these drugs in such adjuvant chemotherapy, looking forward to providing references for related research and clinical treatment in terms of dosage, staging, combined regimes, and analysis methods and so on.

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“…Prior to 1989, patients did not receive adjuvant chemotherapy (ACT). Since 1989, adjuvant therapy was scheduled on the basis of the Nottingham Prognostic Index (NPI), ER-a, and menopausal status (3). Patients with NPI scores <3.4 (low risk) did not receive ACT.…”

Section: Study Populationsmentioning

confidence: 99%

“…The management of TNBC remains a significant clinical challenge, and is hindered by the inability of these tumors to respond to traditional hormone therapies and targeted agents. Research efforts to discover specific prognostic and predictive molecular signatures that can guide individualized therapy for this subgroup of breast cancer patients are therefore urgently needed (3).…”

Section: Introductionmentioning

confidence: 99%

HAGE in Triple-Negative Breast Cancer Is a Novel Prognostic, Predictive, and Actionable Biomarker: A Transcriptomic and Protein Expression Analysis

Abdel-Fatah

McArdle

Agarwal

et al. 2016

Clinical Cancer Research

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Purpose: The expression of HAGE as a novel prognostic and predictive tool was assessed in 1,079 triple-negative breast cancers (TNBC).Experimental Design: HAGE protein expression was investigated in an early primary TNBC (EP-TNBC; n ¼ 520) cohort who received adjuvant chemotherapy (ACT) and in a locally advanced primary TNBC cohort who received anthracycline combination Neo-ACT (n ¼ 110; AC-Neo-ACT). HAGE-mRNA expression was evaluated in the METABRIC-TNBC cohort (n ¼ 311) who received ACT and in a cohort of patients with TNBC who received doxorubicin/cyclophosphamide Neo-ACT, followed by 1:1 randomization to ixabepilone (n ¼ 68) or paclitaxel (n ¼ 64) as part of a phase II clinical trial. Furthermore, a cohort of 128 tumors with integrated HAGE gene copy number changes, mRNA, and protein levels were analyzed.Results: In patients with EP-TNBC, who were chemotherapy-na€ ve, high HAGE protein expression (HAGE þ ) was associated with a higher risk of death [HR, 1.3; 95% confidence interval (CI), 1.2-1.5; P ¼ 0.000005] when compared with HAGE À cases. Patients who received ACT and expressed mRNA-HAGE þ were at a lower risk of death than those who were mRNA-HAGE À (P ¼ 0.004). The expression of HAGE was linked to the presence of tumor-infiltrating lymphocytes (TIL), and both features were found to be independent predictors for pathologic complete response (pCR, P < 0.001) and associated with prolonged survival (P < 0.01), following AC-Neo-ACT. In patients with residual disease, HAGE þ had a 2-fold death risk increase (P ¼ 0.018) compared with HAGE À .Conclusions: HAGE expression is a potential prognostic marker and a predictor of response to anthracycline treatment in TNBC. A prospective clinical trial to examine the therapeutic value of HAGE for TNBC cases is warranted.

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Bcl2 is an independent prognostic marker of triple negative breast cancer (TNBC) and predicts response to anthracycline combination (ATC) chemotherapy (CT) in adjuvant and neoadjuvant settings

Cited by 71 publications

References 15 publications

Transcriptomic and Protein Expression Analysis Reveals Clinicopathological Significance of Bloom Syndrome Helicase (BLM) in Breast Cancer

Transcriptomic and Protein Expression Analysis Reveals Clinicopathological Significance of Bloom Syndrome Helicase (BLM) in Breast Cancer

Use of liposomal doxorubicin for adjuvant chemotherapy of breast cancer in clinical practice

HAGE in Triple-Negative Breast Cancer Is a Novel Prognostic, Predictive, and Actionable Biomarker: A Transcriptomic and Protein Expression Analysis

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