• Title, Summary, Keyword: Triple negative breast cancer

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Molecular Profiling of Breast Carcinoma in Almadinah, KSA: Immunophenotyping and Clinicopathological Correlation

  • Elkablawy, Mohamed A;Albasry, Abdelkader M;Hussainy, Akbar S;Nouh, Magdy M;Alhujaily, Ahmed
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.17
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    • pp.7819-7824
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    • 2015
  • Purpose: To subtype breast cancer (BC) in Saudi women according to the recent molecular classification and to correlate these subtypes with available clinicopathological parameters. Materials and Methods: Estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor (Her2/neu) immunostaining was semi-quantitatively assessed to define molecular subtypes of luminal A and B, HER-2 and triple negative (basal-like) in BC paraffin embedded sections from 115 Saudi female patients diagnosed between 2005 to 2015 at the Department of Pathology, King Fahd Hospital, Almadinah, Saudi Arabia. Results: The most common subtypes were luminal A (47%), followed by luminal B (27.8%) and basal like subtypes (18.3%), whereas HER-2 was the least common subtype (6.9%). Luminal A was predominantly found in the old age group, with low tumor grade (p<0.001) and small tumor size, whereas HER-2 and basal-like subtypes were significantly associated with young age, high tumor grade, lymph node metastasis and lymphovascular invasion (p<0.03, 0.004, 0.05 and 0.04 respectively). All subtypes showed advanced clinical stage at the time of presentation. Conclusions: Molecular subtypes of Saudi BC patients in Almadinah region are consistent with most of the worldwide subtyping. The biological behaviour of each molecular subtype could be expected based on its characteristic clinicopathological features. Along with other prognostic indicators, molecular subtyping would be helpful in predicting prognosis and management of our BC patients. We recommend screening and early diagnosis of BC in our population.

High Histologic Grade and High Ki-67 Expression Predict Phenotypic Alterations in Node Metastasis in Primary Breast Cancers

  • Mando, Pablo;Rizzo, Manglio;de la Puente, Constanza Perez;Maino, Mercedes;Ponce, Carolina;Pombo, Maria Teresa;Amat, Mora;Costanzo, Maria Victoria;Nervo, Adrian;Nadal, Jorge;Fabiano, Veronica;Loza, Jose;Loza, Carlos Martin;Colo, Federico;Reinaldo, Chacon
    • Journal of Breast Cancer
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    • v.20 no.2
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    • pp.170-175
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    • 2017
  • Purpose: Several studies have shown that estrogen receptor (ER) and progesterone receptor (PR) expression and human epidermal growth factor receptor 2 (HER2) expression may vary during tumoral progression. We aimed to describe and compare ER, PR, and HER2 expressions in primary breast tumors and synchronic axillary nodal metastases, and evaluate phenotypic correlations between them. Methods: Patients were identified prospectively through surgical procedures between September 2013 and July 2016. The status of ER, PR, HER2, and Ki-67 were pathologically analyzed in breast cancers and axillary nodal metastases; these patients were classified based on the breast cancer phenotypes into five subgroups. Results: Synchronic axillary nodal metastases were observed in 127 patients. In breast cancers and nodal metastases, correlation analyses of ER, PR, and Ki-67 expression showed a statistical dependence and concordance between these samples was unambiguously demonstrated through Bland-Altman plots for each determination. Primary breast tumors were classified as follows: luminal A, 41.6%; luminal B, 40.0%; luminal B/HER2, 9.6%; HER2, 2.4%; triple negative, 6.4%. Alterations in phenotype were observed in 28% of patients. The most frequent phenotypic alteration was from luminal B to A (36.4%). Ten cases (30.3%) showed alterations with therapeutic implications; six gained HER2 overexpression, and four, hormonal receptor (HR) expression. A moderate strength of agreement (Cohen's ${\kappa}$ coefficient, 0.59; 95% confidence interval, 0.48-0.71) was observed. In multivariate analyses, high histologic grade (odds ratio [OR], 2.79; p<0.047) and high Ki-67 expression (OR, 1.05; p<0.037) were independent factors predictive of phenotypic alterations. Conclusion: Strong correlations were observed in HR and Ki-67 expressions between primary breast tumors and axillary nodal metastases, and a moderate concordance was observed in their phenotypical characteristics. Nevertheless, alterations did exist, and one-third of these changes may have therapeutic implications. The nodal metastases of tumors with high grade and high Ki-67 expression may need to be analyzed, to obtain complete therapeutic information.

Anti-cancer Effect of Apigenin on Human Breast Carcinoma MDA-MB-231 through Cell Cycle Arrest and Apoptosis

  • Lee, Hwan Hee;Cho, Hyosun
    • Microbiology and Biotechnology Letters
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    • v.47 no.1
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    • pp.34-42
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    • 2019
  • Apigenin, a common natural product that is found in many plants and vegetables, has been reported to have many biological activities, including antioxidative, anti-inflammatory, and anticancer effects. The triple-negative breast carcinoma cell line MDA-MB-231 is known to be highly invasive and resistant to chemotherapy. In this study, we investigated the anticancer effect of apigenin on human MDA-MB-231 cells. First, the cytotoxicity of apigenin toward MDA-MB-231 cells was analyzed by MTT assay. Then, the cell cycle and apoptotic effects of apigenin were examined, and the molecular mechanism underlying its anticancer activity was explored. Apigenin inhibited the growth of the cells in a dose-dependent manner, correlating with the cell cycle arrest at the G2-M phase as well as an increase of early apoptosis. The cell-cycle inhibitory effect was highly associated with the increased expression of p21 and decreased expression of CDK6, cyclin D1, and cyclin B1. The induction of apoptosis by apigenin was associated with the upregulated expression of cleaved PARP and cleaved caspase-3, -7, and -9.

Treatment Patterns and Outcomes in Elderly Patients with Metastatic Breast Cancer: A Multicenter Retrospective Study

  • Park, Jin Hyun;Choi, In Sil;Kim, Ki Hwan;Kim, Jin-Soo;Lee, Kyung-Hun;Kim, Tae-Yong;Im, Seock-Ah;Kim, Se Hyun;Kim, Yu Jung;Kim, Jee Hyun
    • Journal of Breast Cancer
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    • v.20 no.4
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    • pp.368-377
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    • 2017
  • Purpose: Currently, there is little information regarding optimal treatment for metastatic breast cancer (MBC) in elderly patients. In this retrospective study, we examined a cohort of elderly patients with MBC receiving a range of treatments, in terms of demographic and clinicopathologic characteristics, treatment patterns, and outcomes. Methods: Patients aged 65 years and older, and diagnosed with MBC between 2003 and 2015, were identified from the databases of three academic hospitals in South Korea. A total of 161 cases were eligible for inclusion. We assessed clinicopathologic features, treatment patterns, and outcomes, using the available electronic medical records. Based on age at MBC diagnosis, patients were divided into three groups: 65 to 69, 70 to 74, and ${\geq}75years$. Results: Most patients had received active treatment according to biologic subtype as in younger patients, although frequent dose modifications were observed during chemotherapy. The median overall survival (OS) for all patients was 30.3 months; age (${\geq}70years$), Eastern Cooperative Oncology Group (ECOG) performance status (PS) (${\geq}2$), triple-negative cancer, and number of metastatic sites (${\geq}2$) were significant poor prognostic factors for OS in multivariate analyses. All types of systemic treatments according to biologic subtype conferred more prolonged OS in patients receiving treatment. Patients aged ${\geq}75years$ were more likely to have a poor ECOG PS and advanced comorbidity, and tended to receive less intensive treatments compared to the other age groups. Conclusion: Elderly patients with MBC should not be excluded from receiving standard treatments prescribed for younger patients. Future research plans for elderly patients, especially aged ${\geq}75years$ with breast cancer, should include a geriatric assessment for identifying individuals at risk for treatment-related toxicity. Overall, this analysis will provide a better understanding of this population and help guide clinical care in real-world practice.

Silencing of Mutant p53 Leads to Suppression of Human Breast Xenograft Tumor Growth in vivo (돌연변이 p53 단백질의 Silencing에 의한 사람유방암세포의 in vivo 항 종양 효과)

  • Park, Won Ick;Park, Se-Ra;Park, Hyun-Joo;Bae, Yun-Hee;Ryu, Hyun Su;Jang, Hye-Ock;Bae, Moon-Kyoung;Bae, Soo-Kyung
    • KSBB Journal
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    • v.31 no.1
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    • pp.52-57
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    • 2016
  • Mutant p53 (R280K) is highly expressed in MDA-MB-231 triple-negative human breast cancer cells. Currently, we reported the role of mutant p53-R280K in mediating the survival of MDA-MB-231 cells in vitro. The present study was undertaken to determine whether mutant p53-R280K affects breast cancer cell growth in vivo. To this end, we used small interfering RNA to knockdown the level of mutant p53-R280K in MDA-MB-231 cells. Silencing of mutant p53-R280K in MDA-MB-231 cells causes substantial tumor regression of established xenografts in vivo. In xenograft model for breast cancer, silencing of mutant p53-R280K in MDA-MB-231 cells significantly inhibited the tumor growth. Moreover, TUNEL assay showed more occurrence of apoptotic cells in mutant p53-R280K silenced tumors compared to control. Our data indicate that mutant p53-R280K has an important role in mediating tumor growth of MDA-MB-231 cells in vivo. Taken together, this study suggests that endogenous mutant p53-R280K could be used as a therapeutic target for breast cancer cells harboring this TP53 missense mutation.

Lack of Mutations in Protein Tyrosine Kinase Domain Coding Exons 19 and 21 of the EGFR Gene in Oral Squamous Cell Carcinomas

  • Mehta, Dhaval Tushar;Annamalai, Thangavelu;Ramanathan, Arvind
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.11
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    • pp.4623-4627
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    • 2014
  • Background: The epidermal growth factor receptor (EGFR) plays a vital role in the activation and inactivation of receptor tyrosine kinases. Mutations in exons 19 and 21 of EGFR are commonly found to be associated with non small cell lung carcinoma and triple negative breast cancer, enhancing sensitivity to EGFR targeting chemotherapeutic agents. Since amplification and prolonged activation of EGFR molecules have been identified in oral squamous cell carcinomas (OSCC), we investigated whether OSCCs carried mutations in exons 19 and 21 of EGFR to their incidence. Materials and Methods: Tumor chromosomal DNA isolated from forty surgically excised oral squamous cell carcinoma tissues was subjected to PCR amplification with intronic primers flanking exons 19 and 21 of the EGFR gene. The PCR amplicons were subsequently subjected to direct sequencing to elucidate the mutation status. Results: Data analysis of the EGFR exon 19 and 21 coding sequences did not show any mutations in the forty OSCC samples that were analyzed. Conclusions: To the best of our knowledge, this is the first study to have investigated the genetic status of exons 19 and 21 of EGFR in Indian OSCCs and identified that mutation in EGFR exon 19 and 21 may not contribute towards their genesis. The absence of mutations also indicates that oral cancerous lesions may not be as sensitive as other cancers to chemotherapeutic agents targeting EGFR.

Incorporating Risk Factors to Identify the Indication of Post-mastectomy Radiotherapy in N1 Breast Cancer Treated with Optimal Systemic Therapy: A Multicenter Analysis in Korea (KROG 14-23)

  • Park, Hae Jin;Shin, Kyung Hwan;Kim, Jin Ho;Ahn, Seung Do;Kim, Ja Young;Park, Won;Kim, Yong Bae;Kim, Yeon-Joo;Kim, Jin Hee;Kim, Kyubo;Park, Kyung Ran;Shin, Hyun Soo;Jeong, Bae Kwon;Lee, Sun Young;Kim, Suzy
    • Cancer Research and Treatment
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    • v.49 no.3
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    • pp.739-747
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    • 2017
  • Purpose In a recent meta-analysis, post-mastectomy radiotherapy (PMRT) reduced any first recurrence (AFR) and improved survival in N1 and N2 patients. We investigated risk factors for AFR in N1 after optimal systemic therapy without PMRT, to define a subgroup of patients who may benefit from PMRT. Materials and Methods One thousand three hundred eighty-two pT1-2N1M0 breast cancer patients treated with mastectomy without PMRT between 2005 and 2010 were retrospectively analyzed. Only 0.6% had no systemic therapy. Results After a median follow-up of 5.9 years, there were 173 AFR (53 loco-regional recurrence [LRR] without distant metastases [DM], 38 LRR with DM, and 82 DM without LRR). The 5-year LRR and AFR rates were 6.1% and 12.0%, respectively. Multivariate analysis revealed that close resection margin (p=0.001) was the only independent risk factor for LRR. Multivariate analysis for AFR revealed that age < 35 years (p=0.025), T2 stage (p=0.004), high tumor grade (p=0.032), close resection margin (p=0.035), and triple-negative biological subtype (p=0.031) were independent risk factors. Two or three positive lymph nodes (p=0.078) were considered a marginally significant factor. When stratified by these six factors, the 5-year LRR rates were 3.6% with 0-1 (n=606), 7.5% with 2-3 (n=655), and 12.7% with 4-6 (n=93) risk factors. The 5-year AFR rates were 7.1% with 0-1, 15.0% with 2-3, and 24.5% with 4-6 risk factors. Conclusion Patients with pT1-2N1M0 breast cancer who underwent mastectomy and optimal systemic therapy showed excellent loco-regional control and disease control. The patients with four or more risk factors may benefit from PMRT, and those with two or three risk factors merit consideration of PMRT.

Relation between Ki-67, ER, PR, Her2/neu, p21, EGFR, and TOP II-α Expression in Invasive Ductal Breast Cancer Patients and Correlations with Prognosis

  • Yan, Jian;Liu, Xiao-Long;Han, Lu-Zhe;Xiao, Gang;Li, Ning-Lei;Deng, Yi-Nan;Yin, Liang-Chun;Ling, Li-Juan;Yu, Xiao-Yuan;Tan, Can-Liang;Huang, Xiao-Ping;Liu, Li-Xin
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.2
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    • pp.823-829
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    • 2015
  • The aim of the present study was to investigate the expression of the transcription factor Ki-67, ER, PR, Her2/neu, p21, EGFR, and TOP II-${\alpha}$ in the tumor tissue of patients with invasive ductal carcinoma(IDC); in addition, we examined correlations between these markers. Two hundred and sixteen IDC patients, who were not previously been treated with chemo- or radiotherapy, were included in the study. All tumors were grade I-III. Expression of molecular markers was determined by immunohistochemical analysis on paraffin-embedded tissue sections. Follow-up data were collected for 3 months to 10 years and analyzed for tumor recurrence, survival time, and prognostic risk factors. We determined Ki-67 expression correlates with the expression of ER, PR, HER-2, EGFR, and TOP-${\alpha}$, as well as lymph node involvement, high tumor grade, lymphovascular invasion, high tumor stage, and high TNM stage in IDC. Positive Ki-67 expression was a risk factor for rapid tumor recurrence and may help tumor progression, leading to poor prognosis in IDC. Ki-67 was directly correlated with EGFR, TOP II-${\alpha}$, lymph node involvement, high tumor grade, lymphovascular invasion, high tumor stage, and high TNM stage in the hormone receptor subtypes of breast cancer. In triple negative breast cancer, Ki-67 correlated with TOP II-${\alpha}$. Expression of Ki-67 correlated with that of ER, PR, HER-2, EGFR, TOP II-${\alpha}$, and p21. In addition, the biomarker Ki-67 has a role as a prognostic factor and indicates a poor prognosis in IDC.

Association of Histopathological Markers with Clinico-Pathological Factors in Mexican Women with Breast Cancer

  • Bandala, Cindy;De la Garza-Montano, Paloma;Cortes-Algara, Alfredo;Cruz-Lopez, Jaime;Dominguez-Rubio, Rene;Gonzalez-Lopez, Nelly Judith;Cardenas-Rodriguez, Noemi;Alfaro-Rodriguez, A;Salcedo, M;Floriano-Sanchez, E;Lara-Padilla, Eleazar
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.18
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    • pp.8397-8403
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    • 2016
  • Background: Breast cancer (BCa) is the most common malignancy in Mexican women. A set of histopathological markers has been established to guide BCa diagnosis, prognosis and treatment. Nevertheless, in only a few Mexican health services, such as that of the Secretariat of National Defense (SEDENA for its acronym in Spanish), are these markers commonly employed for assessing BCa. The aim of this study was to explore the association of Ki67, TP53, HER2/neu, estrogenic receptors (ERs) and progesterone receptors (PRs) with BCa risk factors. Materials and Methods: Clinical histories provided background patient information. Immunohistochemical (IHC) analysis was conducted on 48 tissue samples from women diagnosed with BCa and treated with radical mastectomy. The Chi square test or Fisher exact test together with the Pearson and Spearman correlation were applied. Results: On average, patients were $58{\pm}10.4$ years old. It was most common to find invasive ductal carcinoma (95.8%), histological grade 3 (45.8%), with a poor Nottingham Prognostic Index (NPI; 80.4%). ERs and PRs were associated with smoking and alcohol consumption, metastasis at diagnosis and Ki67 expression (p<0.05). PR+ was also related to urea and ER+ (p<0.05). Ki67 was associated with TP53 and elevated triglycerides (p<0.05), and HER2/neu with ER+, the number of pregnancies and tumor size (p<0.05). TP53 was also associated with a poor NPI (p<0.05) and CD34 with smoking (p<0.05). The triple negative status (ER-/PR-/HER2/neu-) was related to smoking, alcohol consumption, exposure to biomass, number of pregnancies, metastasis and a poor NPI (p<0.05). Moreover, the luminal B subty was associated with histological type (p=0.007), tumor size (p=0.03) and high cholesterol (p=0.02). Conclusions: Ki67, TP53, HER2/neu, ER and PR proved to be related to several clinical and pathological factors. Hence, it is crucial to determine this IHC profile in women at risk for BCa. Certain associations require further study to understand physiological/biochemical/molecular processes.