Triple negative breast cancer: a study from the point of view of basal CK5/6 and HER-1

Pintens, S; Neven, Patrick; Drijkoningen, Maria; Belle, Vanya Van; Moerman, Philippe; Christiaens, Marie-Rose; Smeets, Ann; Wildiers, Hans; Bempt, Isabelle Vanden

doi:10.1136/jcp.2008.061358

Cited by 32 publications

(27 citation statements)

References 43 publications

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“…MBC has been reported as a distinct subgroup of basal breast cancer, with limited myoepithelial differentiation as shown by gene expression analysis [7]. CK5/6 protein is a member of the basal/myoepithelial cytokeratin family, and is frequently detected in triple-negative invasive breast cancer (60%∼72% positivity rate) [22]–[23]. In the current study, however, only 55% of triple-negative breast cancer cases were positive for CK5/6 protein expression.…”

Section: Discussioncontrasting

confidence: 53%

Clinicopathologic Characteristics of Typical Medullary Breast Carcinoma: A Retrospective Study of 117 Cases

et al. 2014

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PurposeThis study analyzed the clinicopathologic characteristics of typical medullary breast carcinoma (TMBC) in a cohort of Chinese patients.MethodsWe conducted a retrospective review of clinical data including general information, pathologic results, treatment regimens, and patient survival in cases of TMBC diagnosed between February 2004 and April 2011.ResultsA total of 117 patients were enrolled, with a median age of 52 years (range, 28∼92 years). Stage I and II disease accounted for 31.6% and 61.6% of the cases, respectively. Hormonal receptor negative disease (estrogen receptor negative, 68.4%; progestogen receptor negative, 86.3%) was more prevalent in this population. Human epidermal growth factor receptor-2 (HER-2) positivity was 20.5%, while equivocal and HER-2 negative cases represented 16.2% and 63.2% of the cohort. The triple-negative, luminal, and HER-2 overexpressing subtypes constituted 44.4%, 31.6%, and 15.4% of the cases, respectively. The various TMBC subtypes showed no differences regarding tumor size, rates of lymph node(s) metastasis, TNM staging, treatment regimens, and 2-year recurrence rates. However, patients with triple-negative disease were more likely to be younger, when compared to those with luminal disease (P = 0.002). At a median follow-up of 56 months (range, 2–112 months), the 2-year disease-free survival and overall survival rates were 99.1% and 98.2%, respectively.ConclusionEarly stage disease dominated the study cohort, and at two years after surgery, recurrence was extremely low. The heterogeneity of molecular subtypes was clearly shown, and no apparent differences were found among the clinicopathologic characteristics of the triple-negative, luminal, and HER-2 overexpressing subtypes.

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Section: Discussioncontrasting

confidence: 53%

Clinicopathologic Characteristics of Typical Medullary Breast Carcinoma: A Retrospective Study of 117 Cases

et al. 2014

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“…A well prognosis indicates that the patients survived without tumor and a worse prognosis indicates that the patients with cancer recurrence and/or who did not survive. TP53 mRNA expression levels tended to be higher in patients who had the worse prognosis than in patients who had a well prognosis (P = 0.05) 16.0 % of the cases presented EGFR (HER1) gene amplification and these were EGFR positive, but negative for CK5/6 expression [31]. Patients with CK5/6-negative but EGFR-positive TNBC may have to be classified as an independent subtype to consider the indication for EGFR inhibitors.…”

Section: Discussionmentioning

confidence: 97%

Immunohistochemical co-expression status of cytokeratin 5/6, androgen receptor, and p53 as prognostic factors of adjuvant chemotherapy for triple negative breast cancer

et al. 2015

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Triple negative breast cancer (TNBC) is immunohistochemically characterised by the lack of expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor type 2 (HER2). TNBC is known for its poor prognosis and high recurrence probability. There is no effective targeted treatment for TNBC, but only adjuvant chemotherapies. There are two TNBC subtypes, basal-like and non-basal-like, which are defined based on positive cytokeratin (CK) 5/6 and/or epidermal growth factor receptor (EGFR) expression. In particular, CK5/6 expression is reported to correlate with TNBC recurrence. TNBC lacks ER-α expression, but some TNBCs are known to express the androgen receptor (AR). Moreover, although p53 accumulation is detected in various malignant tumors, its influence on adjuvant chemotherapy for patients with TNBC remains unclear. The aim of this study was to assess the combined immunohistochemical expression of CK 5/6, AR, and p53 as a potential prognostic marker of adjuvant chemotherapy for patients with TNBC. The expression of CK5/6, AR, and p53 in formalin-fixed and paraffin-embedded (FFPE) surgical sections from 52 patients with TNBC was analysed by immunohistochemistry (IHC) and the co-expression patterns in individual cells were investigated by immunofluorescent (IF) staining. Low AR expression was correlated with high clinical stage (P < 0.05) and low nuclear grade (P < 0.05). The expression of CK5/6 and p53 did not correlate with clinicopathological features. Patients who needed adjuvant chemotherapy presented the worst prognosis. In particular, when the IHC expression pattern was CK5/6 (-), AR (-), and p53 (+), the disease free survival (DFS) and overall survival (OS) were the worst. On the other hand, patients with AR (+) and p53 (-) TNBC presented a good prognosis. The analysis of the co-expression status of these three markers showed that no cells presented both AR and CK5/6 expression. Furthermore, TP53 mRNA expression was higher in patients with AR-negative TNBC (P < 0.05) and in patients with the worst prognosis (P < 0.05) than in the other patients. These results suggested that, in patients with CK5/6-negative TNBC, AR expression correlated with good prognosis, but p53 accumulation correlated with poor prognosis. The present IHC markers allowed us to predict the post-surgery prognosis of patients with TNBC. In conclusion, TNBCs are heterogeneous. Patients with the CK5/6 (-), AR (-), and p53 (+) TNBC subtype, evaluated by IHC, presented the worst prognosis. These IHC markers will be helpful to follow patients with TNBC.

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“…Activating EGFR mutations have been reported in cancers such as non-small cell lung cancer (NSCLC) and head and neck cancers and are predictive of response to gefitinib or erlotinib therapy [13-15]. EGFR protein is expressed in 30% to 52% of triple negative breast cancers [7,16,17] and up to 60% of the closely related basal-like breast cancers and is associated with poor prognosis [18-21]. These observations are the basis for a number of ongoing clinical trials which are exploring the role of monoclonal antibodies against EGFR such as cetuximab and EGFR tyrosine kinase inhibitors such as erlotinib in triple negative breast cancer.…”

Section: Introductionmentioning

confidence: 99%

Mutations in the epidermal growth factor receptor (EGFR) gene in triple negative breast cancer: possible implications for targeted therapy

et al. 2011

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IntroductionTriple negative breast cancer is associated with poorer prognosis and unresponsiveness to endocrine and anti-HER2 directed agents. Despite emerging data supporting the use of polyADP-ribose polymerase (PARP) inhibitors, complete and durable responses are rare and exploration of additional targeted therapies is needed. Epidermal growth factor receptor (EGFR) is expressed in triple negative breast cancer and several clinical trials are testing the role of anti-EGFR directed therapy. However, the rate of EGFR mutations is poorly defined. We, therefore, sought to characterize EGFR mutations in triple negative breast cancers.MethodsSeventy samples were randomly chosen from a cohort of 653 triple negative breast tumours for EGFR mutation analysis. These samples were immunostained for EGFR protein expression and consisted of negatively stained and positively stained cases. DNA was extracted from paraffin blocks and polymerase chain reaction was performed to amplify exon regions 18 to 21 of the EGFR gene. Direct sequencing of the purified PCR products was performed.ResultsEGFR mutations were found in 8 of 70 samples (11.4%). Mutations were predominantly exon 19 deletions (4 of 70 samples, 5.7%), which clustered in the region spanning codons 746 to 759 within the kinase domain of EGFR. Two types of exon 19 deletions were seen: a 15 nucleotide deletion (del E746-A750) (2 of 70 samples) and a 24 nucleotide deletion (del S752 - I759) (2 of 70 samples). Other exon 19 mutations observed were the inversion of the complementary strand (1 of 70 samples). Exon 21 mutations included missense substitution, L858R (1 of 70 samples) and T847I (2 of 70 samples). Mutations observed were independent of EGFR protein expression determined by immunohistochemical staining.ConclusionsThis study is among the first to document the presence and estimate the prevalence of EGFR mutations in triple negative breast cancer. These findings have potential implications for the design of clinical trials involving anti-EGFR directed therapy which currently do not select for patients based on presence of activating EGFR mutations, which may hence be underpowered to detect significant benefit in unselected populations. More complete sampling of EGFR mutation status in triple negative breast cancer is needed to determine the true mutation rate.

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Triple negative breast cancer: a study from the point of view of basal CK5/6 and HER-1

Cited by 32 publications

References 43 publications

Clinicopathologic Characteristics of Typical Medullary Breast Carcinoma: A Retrospective Study of 117 Cases

Clinicopathologic Characteristics of Typical Medullary Breast Carcinoma: A Retrospective Study of 117 Cases

Immunohistochemical co-expression status of cytokeratin 5/6, androgen receptor, and p53 as prognostic factors of adjuvant chemotherapy for triple negative breast cancer

Mutations in the epidermal growth factor receptor (EGFR) gene in triple negative breast cancer: possible implications for targeted therapy

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