Basal cell–like (triple-negative) breast cancer, a predictor of distant metastasis in African American women

Ihemelandu, Chukwuemeka; Naab, Tammey; Mezghebe, Haile M.; Makambi, Kepher H.; Siram, Suryanarayana M.; Leffall, LaSalle D.; DeWitty, Robert L.; Frederick, Wayne

doi:10.1016/j.amjsurg.2007.09.033

Cited by 34 publications

(27 citation statements)

References 21 publications

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“…Lastly, our data show treatment types did not affect OS or RFS in the basal cell-like or non-basal cell-like BC subtypes, which are consistent with other studies [30,31]. In our study, the selection of all patients' treatment types are based on the tumor size, tumor stage, and node status, and these variables were the independent prognostic factors for RFS or OS.…”

Section: Journal Of Surgical Oncologysupporting

confidence: 93%

Characteristics and prognosis for molecular breast cancer subtypes in Chinese women

Zhao¹,

Liu²,

Wang³

et al. 2009

Journal of Surgical Oncology

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Section: Journal Of Surgical Oncologysupporting

confidence: 93%

Characteristics and prognosis for molecular breast cancer subtypes in Chinese women

Zhao¹,

Liu²,

Wang³

et al. 2009

Journal of Surgical Oncology

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“…In addition, premenopausal African American patients have a significantly higher prevalence of triple-negative or basal-like breast tumors (negative for ER, PR, and HER-2, and positive for cytokeratin 5/6 and/or HER-1) compared with postmenopausal African American and non-African American populations (32,33). Interestingly, the triple-negative subgroup has been suggested as an independent predictor of distant breast cancer metastasis in African American women (34). Based on this study, BLID may be a unique prognostic marker for African American breast cancer patients.…”

Section: Discussionmentioning

confidence: 99%

The Proapoptotic Molecule BLID Interacts with Bcl-XL and Its Downregulation in Breast Cancer Correlates with Poor Disease-Free and Overall Survival

Broustas

Ross

Yang

et al. 2010

Clinical Cancer Research

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Purpose: BLID is a BH3-like motif containing apoptotic member of the Bcl-2 family of proteins. This study was designed to investigate the mechanism of BLID-induced apoptosis and to assess the significance of BLID expression in breast cancer.Experimental Design: The interaction between BLID and Bcl-X L was examined using in vitro transcription/translation, coimmunoprecipitation, and immunoflourescence assays. The relationship between BLID mRNA expression and pathologic measures in breast cancer specimens (n = 55) was examined using the publicly available ONCOMINE microarray database. Immunohistochemistry was done using formalinfixed, paraffin-embedded sections of 148 cases of invasive ductal breast carcinomas (IDC) and 58 cases of invasive lobular breast carcinomas, and breast tissue microarrays representing additional 437 cases (>85% IDC) with associated clinicopathologic database and long-term clinical follow-up (median 7 years).Results: BLID was found to interact with Bcl-X L , and the binding was enhanced in cancer cells exposed to doxorubicin or cisplatin. Exogenous expression of BLID correlated with activation of Bax and an increase in cytosolic cytochrome c. BLID mRNA expression was significantly reduced in grade 3 relative to grade 1 and 2 breast cancer (P = 0.023). Cytoplasmic BLID immunoreactivity was absent in IDC compared with invasive lobular breast carcinoma (P < 0.001). Lack of BLID expression was associated with younger age (median 40 years), African American ethnicity, tumor size, and triple-negative breast cancer (estrogen receptor negative, progesterone receptor negative, and human epidermal growth factor receptor 2 negative; all P < 0.005). Significant correlations were observed between BLID negativity and declines in overall, cause-specific, and local relapse-free survival (all P < 0.03). Multivariate analysis indicated that BLID is an independent prognostic factor of distant metastasis-free survival (hazard ratio, 0.302; 95% confidence interval, 0.160-0.570, P = 0.0002).Conclusion: BLID is a new binding partner of Bcl-X L and a significant prognostic factor in breast cancer. Clin Cancer Res; 16(11); 2939-48. ©2010 AACR.The Bcl-2 family of proteins plays a pivotal role in the control of cell death and response of cancer cells to antineoplastic drugs and γ-radiation (1, 2). The antiapoptotic members (e.g., Bcl-2, Bcl-X L , Mcl-1) share homology within three or four BH (Bcl-2 homology) domains (BH 1-4). The proapoptotic proteins contain either two or three BH domains (e.g., Bax, Bak) or only the short (9-16 amino acids) BH3 domain (BH3-only proteins, e.g., Bad, Puma, Noxa; ref. 3). Under unstimulated conditions, Bax and Bak are sequestered by one or more prosurvival members. Numerous landmark studies have shown that binding of a BH3-only apoptotic molecule to an antiapoptotic member is a critical step in the activation of Bax/Bak, release of cytochrome c, and activation of caspase-9 and caspase-3 (4, 5). More recently, a new class of proapoptotic molecules has emerged that contains a B...

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“…Since being identified, TNBC has attracted increasing attention from oncologists due to its relatively poor clinical outcome and lack of molecules for targeted therapies. It has been reported that the prognosis for patients having TNBC is worse than those with HER2 overexpressing breast cancer (3,4). The main reason for its poor prognosis is thought to be the high rate of brain or viscera metastasis, and patients with such metastasis will die within a short period of time after diagnosis (3)(4)(5)11,12).…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that the prognosis for patients having TNBC is worse than those with HER2 overexpressing breast cancer (3,4). The main reason for its poor prognosis is thought to be the high rate of brain or viscera metastasis, and patients with such metastasis will die within a short period of time after diagnosis (3)(4)(5)11,12). Based on the clinical metastatic characteristics of TNBC, the objective of this study was to establish a xenograft model of human brain metastatic TNBC cells in nude mice for the investigation of molecular mechanisms underlying the high propensity of TNBC cells to transfer to the brain and for the detection of potential molecular targets for treatment of brain metastatic cancers.…”

Section: Discussionmentioning

confidence: 99%

“…The poor prognoses of TNBC patients mostly originate from high frequencies of distant organ metastasis, especially brain and viscera metastasis. The mortality rate of TNBC patients with brain metastasis is nearly as high as 100% in the first 3 months of the metastasis (3)(4)(5). The outcome of TNBC patients can be greatly improved if the high metastatic capacity of TNBC cells, especially to the brain, can be efficiently eliminated by 'targeted' therapy.…”

Section: Introductionmentioning

confidence: 99%

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Establishment of a bioluminescent MDA-MB-231 cell line for human triple-negative breast cancer research

et al. 2012

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Abstract. The aim of this study was to establish a bioluminescent MDA-MB-231 cell line stably expressing luciferase and green fluorescent protein for the generation of a xenografted model of human triple-negative breast cancer (TNBC) in nude mice. Lentivirus vectors carrying eGFP, firefly luc2 and neo fusion genes were used to transduce the MDA-MB-231 human TNBC cells in vitro. After 8 weeks of G418 selection, eGFP and luc2 expression was determined using a fluorescence microscope and a Xenogen IVIS200 bioluminescent imaging system, respectively. The MTT, transwell invasion and wound healing assays were performed to confirm whether cellular proliferation, invasion and migration were altered by lentiviral infection. Cells were orthotopically implanted into female BALB/c nude mice to test the sensitivity and stability of reporter gene expression. Growth of the tumors was monitored with the in vivo imaging system once a week until they were large enough for experiments. The tumor tissues were resected for histology, and cancer cells were harvested for culture. The lentivirus-transduced MDA-MB-231 cells could stably express luc2 and eGFP, and the luciferase activity reached 9689 photons/sec/cell. Meanwhile, no significant difference in biological activities was observed between the lentivirus-transduced MDA-MB-231 cells and parental cells. An orthotopically implanted tumor model of human TNBCs was successfully established in BALB/c nude mice. Lentiviruses may be ideal carriers for luciferase genes due to their highly efficient infectivity and stable transgene expression. The modified MDA-MB-231 cell line stably expressing luciferase could be detected, allowing for immediate and sensitive detection of metastasis sites in nude mice. As the eGFP and luc2 combination are superior to single reporter genes in their ability to mark cells in vivo and in vitro, these cells may provide a visualizable, convenient and sensitive platform for research on the mechanisms of metastasis and the development of new antitumor drugs for human TNBC.

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Basal cell–like (triple-negative) breast cancer, a predictor of distant metastasis in African American women

Cited by 34 publications

References 21 publications

Characteristics and prognosis for molecular breast cancer subtypes in Chinese women

Characteristics and prognosis for molecular breast cancer subtypes in Chinese women

The Proapoptotic Molecule BLID Interacts with Bcl-XL and Its Downregulation in Breast Cancer Correlates with Poor Disease-Free and Overall Survival

Establishment of a bioluminescent MDA-MB-231 cell line for human triple-negative breast cancer research

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