Triple-negative breast cancer: immunohistochemical correlation with basaloid markers and prognostic value of survivin

Dogu, Gamze Gokoz; Özkan, Metin; Öztürk, Figen; Dikilitaş, Mustafa; Er, Özlem; Öztürk, Ahmet

doi:10.1007/s12032-009-9166-3

Cited by 32 publications

(26 citation statements)

References 14 publications

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“…Basal-like breast cancers usually show high p53 protein expression [53,57,58], or a high rate of p53 gene mutations [2,31,59], and high expression of EGFR [27,31,56,57,60]. Also they may be associated with germ-line BRCA1 mutations [45,61] and often express genes associated with proliferation, such as those coding for cyclin E1 and proliferating cell nuclear antigen (PCNA) [2,48,62].…”

Section: Metastasis and Pattern Of Recurrencementioning

confidence: 99%

Triple-Negative Breast Cancer: Clinical and Histological Correlations

Elsawaf

Sinn²

2011

Breast Care

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Triple-negative breast cancer (TNBC) is characterized by the lack of estrogen and progesterone receptors and the lack of HER2 expression or amplification. Much interest has recently been focused on these triple-negative (TN) subtypes because they may be aggressive and are more likely to recur and metastasize than other subtypes of breast cancer. TNBC accounts for approximately 10–24% of all breast cancer cases, and typically it occurs in younger patients and in patients with BRCA1 mutation. There is a substantial heterogeneity of TNBCs both at the morphological and the molecular level, but there are also common features, such as low tumor grade and accelerated tumor proliferation. Morphologically, TNBC may present as invasive ductal, metaplastic, medullary, apocrine, or other types. Molecularly, they are most frequently associated with a basal phenotype, but there is a distinct subgroup of cancers that are not of basal type and belong to the claudin-low or molecular-apocrine type. The basal phenotype is frequently associated with the loss of BRCA1.

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Section: Metastasis and Pattern Of Recurrencementioning

confidence: 99%

Triple-Negative Breast Cancer: Clinical and Histological Correlations

Elsawaf

Sinn²

2011

Breast Care

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“…Increased survivin expression is observed in breast cancer cells, while no survivin transcripts are detectable in normal breast tissue. Retrospective analyses revealed that up-regulation of survivin correlates with decreased survival rates, increased relapse, and a higher frequency of metastases in breast cancer patients (9)(10)(11). Also, survivin is highly expressed in most cancer cell lines, where its expression confers resistance to apoptosis induced by various chemotherapeutic agents (12,13).…”

Section: Introductionmentioning

confidence: 99%

YM155, a selective survivin suppressant, inhibits tumor spread and prolongs survival in a spontaneous metastatic model of human triple negative breast cancer

Yamanaka

2011

Int J Oncol

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Abstract. Metastatic triple negative breast cancer [TNBC, with negative expression of estrogen and progesterone receptors and no overexpression of HER2/neu (ErbB-2)] remains a major therapeutic challenge because of its poor overall prognosis and lack of optimal targeted therapies. Survivin has been implicated as an important mediator of breast cancer cell growth and dysfunctions in apoptosis, and its expression correlates with a higher incidence of metastases and patient mortality; thus, survivin is an attractive target for novel anticancer agents. In previous studies, we identified YM155 as a small molecule that selectively suppresses survivin expression. YM155 inhibits the growth of a wide range of human cancer cell lines. Tumor regression induced by YM155 is associated with decreased intratumoral survivin expression, increased apoptosis and a decreased mitotic index. In the present study, we evaluated the antitumor efficacy of YM155 both in vitro and in vivo using preclinical TNBC models. We found that YM155 suppressed survivin expression, including that of its splice variants (survivin 2B, δEx3 and 3B), resulting in decreased cellular proliferation and spontaneous apoptosis of human TNBC cells. In a mouse xenograft model, continuous infusion of YM155 led to the complete regression of subcutaneously established tumors. Furthermore, YM155 reduced spontaneous metastases and significantly prolonged the survival of animals bearing established metastatic tumors in the MDA-MB-231-Luc-D3H2-LN orthotopic model. These results suggest that the survivin-suppressing activity of YM155 may offer a novel therapeutic option for patients with metastatic TNBC. IntroductionBreast cancer is one of the leading causes of cancer death worldwide (1). For patients with local disease, breast cancer is potentially curable by surgical resection combined with adjuvant therapy, including radiation, anti-estrogen therapy and Her2-targeting agents. However, management of metastatic breast cancer is far less successful than treatment of local disease. Despite the recent progress in molecular-targeted therapies, metastatic breast cancer remains the principal cause of breast cancer death and is a major therapeutic challenge for selecting optimal treatment (2).Recent molecular characterization of genetic signatures for patient stratification revealed that triple negative breast cancer (TNBC), with negative expression both of estrogen and progesterone receptors and no overexpression of the Her2 protein, is a high-risk factor with limited therapeutic options. Retrospective studies suggest that TNBC patients represent ~15% of total breast cancers, and that this cancer type may be more aggressive, with rapid tumor growth, a high incidence of metastasis, an increased possibility of distant recurrence, and a higher mortality rate than other breast cancers (3-5). Metastatic TNBC patients have a higher response rate than patients with hormone receptor-positive breast cancer at the initial stage of chemotherapy (6,7). However, the median overall surviva...

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“…Some data on Survivin expression and expression of molecular markers have been reported previously. In 1 study, no prognostic impact of Survivin expression was observed in patients with EGFR and cytokeratin 5/6 expressing tumors; however, the sample size of 30 patients was too small to definitively demonstrate an effect [22]. In another study, Survivin was reported to be highly expressed in breast cancer, was detected in 90% of 420 breast cancer cases, and correlated with HER2 expression; however, the other molecular subtypes of breast cancer, such as the basal-like and the luminal subtypes, were not evaluated [35].…”

Section: Discussionmentioning

confidence: 85%

“…Some studies suggest that high levels of cytoplasmic Survivin and low levels of nuclear Survivin are associated with poor clinical outcome [19], whereas others suggest the opposite [20,21] or report no correlation. The predictive value of Survivin expression in basal-like and triple-negative tumors [22] is currently under investigation. Previous studies have not examined the prognostic impact of Survivin in breast tumors inclusive of all molecular subtypes.…”

Section: Introductionmentioning

confidence: 99%