Lymphatic vascularization in primary breast cancer: her2 overexpressing tumors contain more lymphatics than steroid receptor positive, triple-positive and triple negative breast carcinomas

Aim: The present study was planned to analyze plasma levels of tumor necrosis factor (TNF) in invasive ductal primary breast cancer (BC) patients in a South Indian population. TNF alpha (TNF α) and TNF beta (TNF β) are produced during inflammation as proinflammatory cytokine markers. The plasma levels of TNF α and TNF β (lymphotoxin α) were correlated with clinicopathological features of BC. Materials and Methods: Blood samples were collected from patients before treatment. We analyzed plasma levels of TNF α, and TNF β in 70 female BC cases and 35 age-matched healthy controls using Millipore magnetic bead kits. Results: Plasma TNF α levels in BC cases were significantly elevated (median 10.1 pg/ml) when compared to the control groups. Plasma values of TNF α and TNF β both were significantly elevated in BC patients with hormone receptor negative cases. Plasma TNF α level was elevated in lymph node metastasis and triple negative BC. Plasma values of TNF α inversely correlated with estrogen receptor and progesterone receptor positivity. Conclusion: The plasma levels of TNF α were more significantly overexpressed than TNF β in BC patients. Further, the patients with aggressive cancer had higher levels of inflammation markers. The present study shows that TNF levels were elevated in hormone receptor negative and triple-negative cases.

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Docetaxel and cyclophosphamide as neoadjuvant chemotherapy in HER2- primary breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.26_suppl.141 ◽

2014 ◽

Vol 32 (26_suppl) ◽

pp. 141-141

Author(s):

Katsuhiko Nakatsukasa ◽

Tetsuya Taguchi ◽

Hiroshi Koyama ◽

Seiichi Imanishi ◽

Kouichi Sakaguchi ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Primary Breast Cancer ◽

Triple Negative ◽

Ductal Carcinoma ◽

Dose Intensity ◽

Completion Rate ◽

Luminal A ◽

Luminal B ◽

Triple Negative Subtype

141 Background: Recently, docetaxel plus cyclophosphamide (TC) has been established as a standard regimen for adjuvant chemotherapy in HER2- operable breast cancer. However, the efficacy and tolerability of TC as neoadjuvant chemotherapy (NAC) remains unclear. We performed a prospective study of TC NAC in HER2- primary breast cancer. Methods: Eligible patients had HER2- invasive breast cancer that measured more than 1cm, less than 7cm and N0~N1 clinically between July, 2011 and February, 2014. Four cycles of TC(75 and 600 mg/m2) were administered intravenously every 3 weeks as NAC. We investigated the pathological complete response(pCR) of primary breast tumors. pCR was defined as no histological evidence of invasive carcinoma, or the appearance of only ductal carcinoma in situ. The cut-off value of Ki67 index between luminal A and luminal B was defined 20%. Results: We enrolled 52 patients. The completion rate for 4 cycles of TC was 94.2% ( 49 of 52). Relative dose intensity was 99.1% for TC therapy. Forty nine patients were classified according to breast cancer subtype before the estimation. Overall pCR rate was 16.3 %( 8 of 49 ) . pCR rate for patients with luminal A ( ER+, Ki67 low and HER2- ), luminal B ( ER+, Ki67 high and HER2- ) and triple negative ( ER- and HER2- ) were 0%( 0 of 12 ), 4.3 %( 1 of 23 ) and 50.0 %( 7 of 14 ), respectively pCR was achieved in almost triple negative patients. Conclusions: The pCR rate of TC was not so high, regardless of the high completion rate. In this study, TC was effective against triple negative subtype, showing a high pCR rates, compared with luminal subtype. In conclusion, the efficacy of TC NAC in HER2- primary breast cancer is limited, and triple negative subtype might be the good target. Clinical trial information: UMIN000013261.

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Biological Characteristics and Clinical Outcome of Triple Negative Primary Breast Cancer in Older Women – Comparison with Their Younger Counterparts

PLoS ONE ◽

10.1371/journal.pone.0100573 ◽

2014 ◽

Vol 9 (7) ◽

pp. e100573 ◽

Cited By ~ 13

Author(s):

Binafsha M. Syed ◽

Andrew R. Green ◽

Christopher C. Nolan ◽

David A. L. Morgan ◽

Ian O. Ellis ◽

...

Keyword(s):

Breast Cancer ◽

Clinical Outcome ◽

Older Women ◽

Primary Breast Cancer ◽

Triple Negative ◽

Biological Characteristics

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p63/p73 expression mediates cisplatin sensitivity in a subset of triple-negative primary breast cancer: Implications for a new clinical trial

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.10522 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 10522-10522 ◽

Cited By ~ 4

Author(s):

S. J. Isakoff ◽

C. Leong ◽

N. Vidnovic ◽

M. P. DeYoung ◽

D. Sgroi ◽

...

Keyword(s):

Breast Cancer ◽

Cell Lines ◽

Triple Negative Breast Cancer ◽

Primary Breast Cancer ◽

Triple Negative ◽

Response Rate ◽

Breast Cancer Cell Lines ◽

Mcf10a Cell ◽

Primary Tumors ◽

Cisplatin Sensitivity

10522 Background: Triple-negative breast cancer (ER-, PgR- and HER2-negative) has a poor prognosis relative to other subtypes, even with the best available chemotherapy. We recently reported that in squamous cell cancers, p63 promotes survival by direct interaction with and inhibition of p73-dependent apoptosis. We now report on the role of p63/p73 in triple-negative breast cancer. Methods: We performed quantitative RT-PCR on primary breast cancer specimens to determine the expression of specific p63 and p73 isoforms. Cell culture experiments used MCF7, HCC-1937, MDA-MB-468, T47D, and MCF10A cell lines. Lentiviral p63 and p73 shRNA were used for knockdown experiments. Chemotherapy dose-response curves were generated using MTT assay. Results: In primary tumors, ΔNp63 and TAp73 isoforms are expressed exclusively within a subset of triple-negative tumors in which p53 mutations are commonly found. Knockdown of p63 in triple-negative cell lines, but not the ER-positive MCF7 line, induced apoptosis which was specifically dependent on p73 expression. Breast cancer cell lines expressing p63/p73 exhibited p73-dependent sensitivity to cisplatin. Knockdown of p73 resulted in a 10–100 fold increase in the IC50 of cisplatin, but no change in doxorubicin or paclitaxel sensitivity. Exogenous p73 expression in MCF10A cells, which have high levels of p63 but no p73, confers increased sensitivity to cisplatin. Conclusion: These results show that p63/p73expression promotes survival in a subset of breast cancers, and they provide a mechanism for cisplatin sensitivity. These findings suggest that p63/p73 expression may serve as a biomarker to predict cisplatin sensitivity in triple-negative breast cancer. Based on these results, we are conducting a phase II study of 39 patients evaluating cisplatin as first line therapy for metastatic triple-negative breast cancer. The primary endpoints are overall objective response rate and response rate in low versus high p63/p73 expressing subgroups. No significant financial relationships to disclose.

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P4-07-03: Identification of Triple-Negative Primary Breast Cancer Xenograft Models with High Numbers of Circulating and Disseminated Tumor Cells.

10.1158/0008-5472.sabcs11-p4-07-03 ◽

2011 ◽

Author(s):

M Giuliano ◽

PI Christiny ◽

X Zhang ◽

S Mao ◽

A Contreras ◽

...

Keyword(s):

Breast Cancer ◽

Tumor Cells ◽

Primary Breast Cancer ◽

Triple Negative ◽

Disseminated Tumor Cells ◽

Breast Cancer Xenograft ◽

Xenograft Models

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VGLL1 expression is associated with a triple-negative basal-like phenotype in breast cancer

Endocrine Related Cancer ◽

10.1530/erc-13-0485 ◽

2014 ◽

Vol 21 (4) ◽

pp. 587-599 ◽

Cited By ~ 33

Author(s):

María Ángeles Castilla ◽

María Ángeles López-García ◽

María Reina Atienza ◽

Juan Manuel Rosa-Rosa ◽

Juan Díaz-Martín ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative ◽

Tissue Microarrays ◽

The Cancer Genome Atlas ◽

Luminal Progenitor ◽

Breast Carcinomas ◽

Luminal A ◽

Her2 Positive ◽

Cancer Subtypes ◽

Grade 3

Vestigial-like 1 (VGLL1) is a poorly characterized gene encoding a transcriptional co-activator structurally homologous toTAZandYAPthat modulates the Hippo pathway inDrosophila. In this study, we examined the expression ofVGLL1and its intronic miRNA, miR-934, in breast cancer.VGLL1and miR-934 expression miRNA profiling was carried out on frozen samples of grade 3 invasive ductal carcinomas. VGLL1 protein was also examined in 433 sporadic andBRCA1-associated breast carcinomas on tissue microarrays. RNA-seq data from The Cancer Genome Atlas (TCGA) was used to confirm differences inVGLL1and miR-934 expression in different breast cancer subtypes, and to correlate their expression with that of other genes and miRNAs. Of 28 miRNAs differentially expressed in estrogen receptor (ER)-positive and ER-negative grade 3 breast carcinomas, miR-934 was most strongly upregulated in ER-negative carcinomas, and its expression was correlated with that ofVGLL1. NuclearVGLL1expression was observed in 13% of sporadic breast carcinomas, and whileVGLL1was only occasionally found in luminal A (0.70%) and B (5.60%) carcinomas, it was often expressed in HER2-positive (17%), triple-negative (TN) breast carcinomas (>40%) andBRCA1-associated TN carcinomas (>50%). These findings were confirmed in the TCGA dataset, which revealed positive associations with luminal progenitor genes (GABRP,SLC6A14,FOXC1,PROM1, andBBOX1) and strong negative correlations with ER-associated genes (ESR1,C6ORF211,GATA3, andFOXA1). Moreover,VGLL1expression was associated with reduced overall survival. In conclusion,VGLL1and miR-934 are mainly expressed in sporadic andBRCA1-associated TN basal-like breast carcinomas, and their coordinated expression, at least partially mediated by the direct modulation ofESR1, might be involved in the maintenance of a luminal progenitor phenotype.

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Prognostic significance of p53 overexpression in primary breast cancer; a novel luminometric immunoassay applicable on steroid receptor cytosols

British Journal of Cancer ◽

10.1038/bjc.1995.195 ◽

1995 ◽

Vol 71 (5) ◽

pp. 1013-1017 ◽

Cited By ~ 35

Author(s):

A Borg ◽

J Lennerstrand ◽

M Stenmark-Askmalm ◽

M Fernö ◽

A Brisfors ◽

...

Keyword(s):

Breast Cancer ◽

Primary Breast Cancer ◽

Prognostic Significance ◽

Steroid Receptor ◽

P53 Overexpression

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Clinical pathological and epidemiological study of triple negative breast cancer

International Journal of Research in Medical Sciences ◽

10.18203/2320-6012.ijrms20172465 ◽

2017 ◽

Vol 5 (6) ◽

pp. 2657

Author(s):

Arun Ajay ◽

Priya Radhakrishnan

Keyword(s):

Breast Cancer ◽

Triple Negative ◽

Ductal Carcinoma ◽

Tertiary Care ◽

High Rate ◽

Care Hospital ◽

Breast Carcinomas ◽

Significant Difference ◽

Her 2 ◽

Epidemiological Characteristics

Background: Worldwide breast cancer is the most frequently diagnosed life threatening cancer in women and a leading cause of cancer death among women. In Kerala, India around 30% of cancer-affected women have carcinoma breast. Breast carcinomas which do not express estrogen (ER), progesterone (PR), and human epidermal growth factor receptor 2 (HER-2/neu) receptors are known as triple negative breast carcinomas (TNBC). They are extremely aggressive with poor prognosis. Here the authors described the clinical pathological and epidemiological characters of triple negative breast carcinomas in a tertiary care hospital in Kerala, India and compare with non-TNBC.Methods: It was a cross sectional comparative study. Clinical, pathological and epidemiological characteristics of 75 cases of TNBC were compared with that of 225 cases of non-TNBC presented in Department of General Surgery, Government medical college, Kozhikode, Kerala, India between a period from March 2014 to October 2015 (20 months). Patients were recruited after obtaining an informed consent. ER, PR, HER-2/neu status were determined by immunohistochemical staining. Data obtained were statistically analyzed using SPSS software.Results: Triple negative breast carcinoma was significantly associated with a younger age (mean age 43.67 years), early age of menarche. Commonly seen in premenopausal age group (78.7%). Patients with the triple-negative carcinoma had relatively large tumors (mean size 4.45cm compared to 3.14cm) and a high rate of node positivity (86.67%). More advanced stage at diagnosis with high grade tumor characteristics. Most common histopathology was invasive ductal carcinoma (98.7%) but no statistical difference was noted with non-TNBC.Conclusions: No significant difference was noted between TNBC and non TNBC on comparing family history, parity, age at 1st child birth, OCP use. The outcome of the disease following treatment was unable to study due to short time frame of the study.

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PROGNOSTIC VALUE OF TUMOR STROMA RATIO IN TRIPLE NEGATIVE BREAST CANCER

Wiadomości Lekarskie ◽

10.36740/wlek202103201 ◽

2021 ◽

Vol 74 (3) ◽

pp. 565-571

Author(s):

Liubov M. Zakhartseva ◽

Mariia A. Yanovytska

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Triple Negative Breast Cancer ◽

Prognostic Value ◽

Triple Negative ◽

Disease Free Survival ◽

Tumor Stroma ◽

Breast Carcinomas ◽

Free Survival ◽

Disease Free

The aim: The purpose of this study is to investigate prognostic value of tumor stroma ratio in triple negative breast carcinomas. Materials and methods: This cohort retrospective study included a total number of 232 previously untreated operational materials with primary stage I-III triple negative breast cancer. The median follow-up period was 3.8 years for overall survival and 3.2 years for disease-free survival. Tumor stroma ratio was evaluated by two pathologists (Kappa coefficient was 0.71 and 0.84, respectively). Results: Kaplan-Meier curves with logrank test statistically significantly showed relationship between tumor stroma ratio and both overall and disease-free survival. The Cox proportional hazards model showed tumor stroma ratio is a strong independent prognostic factor for triple negative breast carcinomas with hazard ratios of 2.11 (p=0.002) for overall survival and 1.83 (p=0.004) for disease-free survival in multivariate analysis. Conclusions: Triple negative breast tumors with high stroma ratio have worse overall and disease-free survival compared to low stroma ratio tumors. Investigation of tumor stroma ratio doesn't require any additional costs and slide preparation. It can be added to routine breast cancer investigation to expand knowledge about cancer prognosis.

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