Immunohistochemical (IHC) sub-classification of 105 triple negative breast cancers (TNBC).

e12577 Background: Molecular data have shown that TNBC was a heterogeneous group of tumors. The objective was to evaluate prognosis of IHC sub-classification adapted from molecular model. Methods: We used IHC sub-classification based on positivity for androgen receptor (AR) (Roche, SP 107), cytokeratine 5/6 (CK) (Dako, D5/16B4) and Epidermal growth factor receptor (EGFR) (Biosd, 31G7). Samples with more than 10% AR nuclear immunostaining were considered positive. Threshold for CK and EGFR was 1%. We distinguished 4 groups of tumors: AR phenotype (AR+, EGFR-, CK5/6-), basal-like phenotype (AR-, EGFR+/-, CK5/6 +/-), triple-negative phenotype (AR-, EGFR-, CK5/6-) and mixed group (AR+, EGFR+/-, CK5/6 +/-). Tissue micro-array blocks were constructed with samples from a retrospective cohort treated in adjuvant setting for non metastatic TNBC in a single institution from 2003 to 2013. Survival data were estimated by the Kaplan-Meier method and compared by the log-rank test in univariate analysis. Multivariate analysis including tumor size (T), lymph nodes status (N) and lymphovascular invasion (LVI) was performed using Cox model. Results: 105 patients were followed-up for a median period of 56.3 months [6-155]. Median age was 54 years [29-80]. 57.1% were stage pT1, 41.9% were pN+ and 37,1% presented LVI. 11 patients were classified as AR phenotype, 35 as basal-like, 46 as triple-negative phenotype and 13 as mixed group. 18 patients developed metastases: 3/11 AR, 5/35 basal-like, 6/46 triple-negative and 4/13 mixed group. No difference was observed between TNBC subgroups in terms of disease free survival DFS (p = .98) and overall survival OS (p = .86). T, N and LVI were the only prognostic factors (p = .05, p = .05 and p = .046 respectively). Conclusions: We found no impact of IHC sub-classification of TNBC. Correlation between IHC and molecular biology is in progress.

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Pathological response rates in 710 operable breast cancer (BC) patients treated by neoadjuvant chemotherapy (NCT), according to immunohistochemichal subtypes of tumours

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.10579 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 10579-10579

Author(s):

P. J. Chollet ◽

C. Abrial ◽

O. Tacca ◽

I. Raoelfils ◽

M. Leheurteur ◽

...

Keyword(s):

Triple Negative ◽

Residual Disease ◽

Disease Free Survival ◽

Conservative Surgery ◽

Median Number ◽

Pathological Response ◽

Pathological Review ◽

Median Diameter ◽

Triple Negative Phenotype ◽

Negative Phenotype

10579 Background: Pathological responses rates were studied in 710 women with stage II-III operable BC treated between 1982 and 2004. A pathological review was conducted to assess the residual disease in breast and nodes according to Chevallier's classification (Am J Clin Oncol 1993) and patients repartited according to 3 tumour phenotypes: Her2+ (Her2+ phenotype), Her2-HR+ (Hormonal Receptor; luminal phenotype) and Her2-HR- (triple negative phenotype). Methods: Median diameter of the invasive tumour was 40 mm [10–130]. 555 (78%) patients had a canalar, 90 (13%) a lobular, 18 (2.5%) a mixed or invasive carcinoma, 36 (5%) neoplasic cells only and 11 (1.5%) another carcinoma. 25.6% of the tumours were grade III SBR. The median number of NCT courses was 6 [1–9] followed by a surgery for 92%, a radiotherapy for 95%, an adjuvant chemotherapy for 17% and/or an hormonotherapy for 52%. A breast evaluation was realized before, during and after NCT. Results: Overall response rate was 68% (16% complete). The complete pathological response (pCR) rate was 14.2% according to Chevallier's classification. On 656 patients operated, 470 (72%) had a conservative surgery. On 520 patients with an axillary dissection, 272 (52.3%) had involved nodes. After a median follow-up of 93 months, Disease-Free Survival (DFS) and Overall Survival (OS) at 120 months were 54.9% and 66.5%, respectively. According to tumour's phenotype, the pCR rate (Chevallier's classes 1+2) was: 24.5% in Her2+ phenotype, 14.8% in triple negative phenotype and 4.4% in luminal phenotype. These results showed that: -the pCR was three-fold more frequent in Her-2+ phenotype than in luminal one (p = 3.5.10-5) -the pCR was two-fold more frequent in triple negative phenotype than in luminal one (p = 3.10-3) -no significant pCR difference was found between Her2+ phenotype and triple negative one Furthermore, a significantly better DFS was found for luminal phenotype; DFS was intermediate for triple negative phenotype, and lower for Her2+ phenotype. Conclusions: The pCR rates were higher in Her2+ phenotype and in triple negative one. It is important to note that, in this series, most Her2+ patients did not receive any Herceptin treatment. No significant financial relationships to disclose.

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Outcome of operable breast cancer with triple negative phenotype

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e11621 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e11621-e11621

Author(s):

Y. Izarzugaza ◽

P. Khosravi-Shahi ◽

A. Soria Lovelle ◽

G. Pérez Manga

Keyword(s):

Breast Cancer ◽

Adjuvant Chemotherapy ◽

Triple Negative ◽

Ductal Carcinoma ◽

Disease Free Survival ◽

Her 2 ◽

First Recurrence ◽

Triple Negative Phenotype ◽

Worse Prognosis ◽

Negative Phenotype

e11621 Background: Breast cancer(BC)is the most frequent neoplasm in women. Triple negative phenotype(TNP)is characterized by lack of expression of estrogen receptor(ER),progesterone receptor(PgR) and Her-2, and it is associated with a worse prognosis. Patients and Method: We conducted a retrospective study of consecutive cases of BC with TNP by immunohistochemistry(IHC),treated in our center within the last 5 years,with primary endpoint of analyzing the disease-free-survival (DFS).Second endpoints of the study were overall survival (OS),place of the first recurrence and cause of death. Results: After reviewing 295clinical histories of localized BC(with available ER,PgR and Her-2 by IHC),we found a total of 24 patients(p)with TNP(Prevalence=8.14%[95CI%: 5.3–11.9%].Ps characteristics:median age=50 years(26–74);premenopausal=55%;tumor grade:G3=40%;G2=60%;85.7% had high Ki-67(>40%);63.2% had stageIIB-III;median tumoral size=2.1cm;node positive=80%(25% with 4 or more positive nodes);96% was ductal carcinoma;56.5% was treated with mastectomy;78% with radiotherapy.Eighty-three percent of ps were treated with neoadjuvant and/or adjuvant chemotherapy with anthracyclines and taxanes:34.8% with adjuvant chemotherapy (AC60/600x4–>Paclitaxel-175x4);21.7% with neoadjuvant ATX(doxorubicin, docetaxel and capecitabine);and 26.1% with neoadjuvant AT(doxorubicin and docetaxel), and only 4 ps with adjuvant CMFx6.With a median follow-up of 36 months(m),median DSF was 42 m(95%CI: 33–51),and the probability of DSF at 3y was 67%.Median OS was 82m(95%CI: 41–123),with a probability at 5y of 52%.Thirty-eight percent(9/24)of ps had an event(3 recurrences and 6 deaths),and 100%of the deaths were caused by tumoural progression. Deaths according to the chemotherapy:75%(3/4 patients)in CMF group vs 15%(3/20)in anthracycline and taxane group(P=0.040; Fisher test).Mainly localization of the first recurrence was multiple in the 44.4%of the cases, followed by the liver(22.2%),lung(11.11%),bone(11.11%)and brain (11.11%). Conclusions: Our study confirmed the worse prognosis associated with triple negative BC.This subtype of BC must be treated with the most active cytostatic drugs in the adjuvant setting. No significant financial relationships to disclose.

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High Expression of H3K9me3 Is a Strong Predictor of Poor Survival in Patients With Salivary Adenoid Cystic Carcinoma

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2012-0704-oa ◽

2013 ◽

Vol 137 (12) ◽

pp. 1761-1769 ◽

Cited By ~ 20

Author(s):

Ronghui Xia ◽

Rongrui Zhou ◽

Zhen Tian ◽

Chunye Zhang ◽

Lizhen Wang ◽

...

Keyword(s):

Adenoid Cystic Carcinoma ◽

Distant Metastasis ◽

Survival Data ◽

Histone H3 ◽

Disease Free Survival ◽

Rank Test ◽

Free Survival ◽

Salivary Adenoid Cystic Carcinoma ◽

Adenoid Cystic ◽

Disease Free

Context.—Histone methylation and acetylation play important roles in the carcinogenesis and progression of cancer. Objective.—To investigate whether histone modifications influence the prognosis of patients with salivary adenoid cystic carcinoma (ACC). Design.—The expression of histone H3 lysine 9 trimethylation (H3K9me3) and histone H3 lysine 9 acetylation (H3K9Ac) was assessed by immunohistochemistry in 66 specimens of primary ACC. Tests were used to determine the presence of any correlation between H3K9me3 and H3K9Ac levels and clinicopathologic parameters. Log-rank test and Cox proportional hazards regression models were used to analyze the survival data. Results.—H3K9me3 expression was positively correlated with solid pattern tumors (P = .002) and distant metastasis (P = .001). Solid pattern tumors had lower H3K9Ac expression levels than cribriform-tubular pattern tumors (P = .03). Patients whose tumors showed high H3K9me3 expression and a solid pattern had a significantly poorer overall survival (OS) (P < .001 and P < .001, respectively) and disease-free survival (P < .001 and P = .01, respectively). Low H3K9Ac expression was correlated with poor OS (P = .05). The multivariate analysis indicated that high levels of H3K9me3 expression and solid pattern tumors were independent prognostic factors that significantly influenced OS (P = .004 and P = .04, respectively). H3K9me3 expression was identified as the only independent predictor of disease-free survival (P = .006). Conclusions.—Our results suggest that high levels of H3K9me3 expression are predictive of rapid cell proliferation and distant metastasis in ACC. Compared with histologic patterns, H3K9me3 might be a better predictive biomarker for the prognosis of patients with salivary ACC.

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Antiangiogenic therapy for breast cancer with triple negative phenotype

Modern Oncology ◽

10.26442/18151434.2021.1.200763 ◽

2021 ◽

Vol 23 (1) ◽

pp. 88-92

Author(s):

Inna P. Ganshina ◽

Kristina A. Ivanova ◽

Olga O. Gordeeva ◽

Aleksandr V. Arkhipov ◽

Liudmila G. Zhukova

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Malignant Tumors ◽

Antiangiogenic Therapy ◽

Treatment Strategies ◽

Her 2 ◽

Triple Negative Phenotype ◽

The Impact ◽

Negative Phenotype

Triple-negative breast cancer is 1024% of all cases of breast cancer and is characterized by the absence of estrogen, progesterone, and HER-2 receptors in the tumor. The therapy of this illness is a difficult clinical case. In contrast to hormone-positive and HER-2-positive phenotypes, in which we successfully use targeted drugs (antiestrogens and anti-HER-2 drugs), for triple-negative breast cancer we have not had such targets for a long time. Thus, despite the impressive results of immunotherapy of triple-negative breast cancer, there remains a fairly large group of patients with negative PD-L1 status, for whom it is necessary to develop other treatment strategies. One of the approaches in the treatment of malignant tumors includes not the impact on tumor cells, but the process of angiogenesis. Antiangiogenic drugs have positively proven themselves in the treatment of a large number of malignant tumors but are underestimated for breast cancer (including triple-negative phenotype). The use of bevacizumab in combinations with cytostatic drugs in breast cancer therapy (including triple-negative breast cancer) has been studied in a large number of clinical trials but was undeservedly forgotten in some countries due to the revoked FDA registration. This review presents the role of bevacizumab in the treatment of patients with triple-negative breast cancer and suggests the conditions when the administration of this drug is justified and leads to better results.

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Development of cytotoxic chemotherapy in metastatic breast cancer with a triple-negative phenotype

Modern Oncology ◽

10.26442/1815-1434_2016.2.34-38 ◽

2016 ◽

Vol 18 (2) ◽

pp. 34-38

Author(s):

E.V. Karabina ◽

◽

L.G. Zhukova ◽

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Triple Negative ◽

Metastatic Breast ◽

Cytotoxic Chemotherapy ◽

Triple Negative Phenotype ◽

Negative Phenotype

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Long interspersed nuclear element 1 hypomethylation has novel prognostic value and potential utility in liquid biopsy for oral cavity cancer

Biomarker Research ◽

10.1186/s40364-020-00235-y ◽

2020 ◽

Vol 8 (1) ◽

Cited By ~ 1

Author(s):

Kiyoshi Misawa ◽

Satoshi Yamada ◽

Masato Mima ◽

Takuya Nakagawa ◽

Tomoya Kurokawa ◽

...

Keyword(s):

Oral Cavity ◽

Real Time ◽

Oral Cavity Cancer ◽

Univariate Analysis ◽

Disease Free Survival ◽

Inverse Correlation ◽

Predictive Biomarker ◽

Rank Test ◽

Dna Hypomethylation ◽

Prognostic Implications

Abstract Background New biomarkers are urgently needed to improve personalized treatment approaches for head and neck squamous cell carcinoma (HNSCC). Global DNA hypomethylation has wide-ranging functions in multistep carcinogenesis, and the hypomethylation of long interspersed nucleotide element-1 (LINE-1) is related to increased retrotransposon activity and induced genome instability. However, little information is available regarding LINE-1 hypomethylation and its prognostic implications in HNSCC. Methods In this study, we analyzed LINE-1 hypomethylation levels in a well-characterized dataset of 317 primary HNSCC tissues and 225 matched pairs of normal mucosa tissues, along with five oral cavity cancer (OCC) circulating tumor DNA (ctDNA) samples using quantitative real-time methylation and unmethylation PCR. The analysis was performed according to various clinical characteristics and prognostic implications. Results The results demonstrated that LINE-1 hypomethylation levels were significantly higher in the HNSCC tissues than in corresponding normal tissues from the same individuals (P < 0.001). Univariate analysis revealed that high levels of LINE-1 hypomethylation were correlated with poor disease-free survival (DFS; log-rank test, P = 0.038), whereas multivariate analysis demonstrated that they were significant independent prognostic factor for DFS (hazard ratio: 2.10, 95% confidence interval: 1.02–4.36; P = 0.045). Moreover, samples with high LINE-1 hypomethylation levels exhibited the greatest decrease in 5-hydroxymethylcytosine (5-hmC) levels and increase in tumor-suppressor gene methylation index (P = 0.006 and P < 0.001, respectively). Further, ctDNA studies also showed that LINE-1 hypomethylation had high predictive ability in OCC. Conclusions LINE-1 hypomethylation is associated with a higher risk of early OCC relapse, and is hence, a potential predictive biomarker for OCC. Furthermore, 5-hmC levels also exhibited predictive potential in OCC, based on their inverse correlation with LINE-1 hypomethylation levels. LINE-1 hypomethylation analysis, therefore, has applications in determining patient prognosis and real-time surveillance of disease recurrence, and could serve as an alternative method for OCC screening.

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Expression of L1CAM and KI-67 in Endometrial Cancer of Egyptian Females: Clinical Impact and Survival

Tumori Journal ◽

10.1177/0300891620914173 ◽

2020 ◽

Vol 106 (1_suppl) ◽

pp. 36-36

Author(s):

Fatma Gharib ◽

Dareen Abd elaziz mohamed ◽

Basma Saed Amer

Keyword(s):

Endometrial Cancer ◽

Endometrial Adenocarcinoma ◽

Univariate Analysis ◽

Disease Free Survival ◽

Rank Test ◽

Significant Heterogeneity ◽

Ki 67 ◽

Free Survival ◽

Disease Free ◽

L1cam Expression

Introduction: Endometrial adenocarcinoma is characterized by a good prognosis. However, the disease response shows a significant heterogeneity. Treatment of endometrial cancer (EC) is still based on clinico-pathological parameters, which have limited role in risk stratification. There is a need for more determinant markers, such as L1 Cell Adhesion Molecule (L1CAM), to identify patients at higher risk of relapse and tailor a more convenient treatment. L1CAM has a capacity to enhance cell motility and promote tumor invasion in different malignancies. In Egypt, the incidence rate of EC is growing over time. Especially in Elgharbiah governorate (home of this study). L1CAM expression and Ki-67 was reported and compared with other clinico-pathological criteria. Method: Seventy-six female patients of endometrial carcinomas were involved in this prospective study. The patients were treated and followed up at Tanta University Hospitals in the period between January 2015 to April 2019. L1CAM expression and Ki-67 was detected by immuno-histochemical exam and compared with other clinico-pathological criteria. Survival was assessed and compared by Kaplan-Meier curves and log-rank test. Results: Positive L1CAM expression was detected in 17 patients (22.4%) and was significantly correlated with unfavorable prognostic factors such as higher stage and grade ( P= 0.021 and P =0.001 respectively), lympo-vascular invasion ( P <0.001), non-endometroid type ( P <0.027) and Ki-67 ( P= 0.003). Univariate analysis revealed that: positive L1CAM; higher tumor grade; high stage; and non-endometrioid type were significantly associated with shorter disease-free survival (DFS) but no significant correlation was detected between Ki-67 and DFS. In multivariate analysis, positive L1CAM remained statistically significant with DFS [P =0.045; 95%CI (1.028:11.17); HR=3.38]. Conclusion: Our study indicates that L1CAM expression and Ki-67 are significantly associated with poor tumor characteristics. L1CAM is significantly associated with shorter disease-free survival and may be a helpful tool as a part of a simple clinical molecular classification for EC.

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