Clinicopathological Features Of Breast Cancer Research Articles

Keratin 17 is overexpressed and predicts poor survival in estrogen receptor–negative/human epidermal growth factor receptor-2–negative breast cancer

Clinicopathological features of breast cancer have limited accuracy to predict survival. By immunohistochemistry (IHC), keratin 17 (K17) expression has been correlated with triple-negative status (estrogen receptor [ER]/progesterone receptor/human epidermal growth factor receptor-2 [HER2] negative) and decreased survival, but K17 messenger RNA (mRNA) expression has not been evaluated in breast cancer. K17 is a potential prognostic cancer biomarker, targeting p27, and driving cell cycle progression. This study compared K17 protein and mRNA expression to ER/progesterone receptor/HER2 receptor status and event-free survival. K17 IHC was performed on 164 invasive breast cancers and K17 mRNA was evaluated in 1097 breast cancers. The mRNA status of other keratins (16/14/9) was evaluated in 113 ER-/HER2- ductal carcinomas. IHC demonstrated intense cytoplasmic and membranous K17 localization in myoepithelial cells of benign ducts and lobules and tumor cells of ductal carcinoma in situ. In ductal carcinomas, K17 protein was detected in most triple-negative tumors (28/34, 82%), some non-triple-negative tumors (52/112, 46%), but never in lobular carcinomas (0/15). In ductal carcinomas, high K17 mRNA was associated with reduced 5-year event-free survival in advanced tumor stage (n = 149, hazard ratio [HR] = 3.68, P = .018), and large (n = 73, HR = 3.95, P = .047), triple-negative (n = 103, HR = 2.73, P = .073), and ER-/HER2- (n = 113, HR = 2.99, P = .049) tumors. There were significant correlations among keratins 17, 16, 14, and 9 mRNA levels suggesting these keratins (all encoded on chromosome 17) could be coordinately expressed in breast cancer. Thus, K17 is expressed in a subset of triple-negative breast cancers, and is a marker of poor prognosis in patients with advanced stage and ER-/HER2- breast cancer.

Methylation in promoter regions of PITX2 and RASSF1A genes in association with clinicopathological features in breast cancer patients.

Breast cancer is a heterogeneous disease with very different responses to therapy and different length of survival. In many cases, however, the determination of the stage and histopathological characteristics of breast cancer is insufficient to predict prognosis and response to treatment for the vast heterogeneity of the disease. To understand the molecular signature of subtypes of breast cancer, we attempted to identify the methylation status of key tumour suppressor gene Ras association (RalGDS/AF-6) domain family member 1 isoform a (RASSF1A) and a member of the paired-like homeodomain transcription factor family which functions in left-right asymmetry development (PITX2) and to correlate results with known clinicopathological features of breast cancer. Formalin-fixed, paraffin-embedded (FFPE) tissues of breast carcinomas (n=149) were used for DNA extraction. DNA was modified by bisulphite conversion. Detection of the methylation level of the genes mentioned above was performed by methylation-sensitive high-resolution melting assay (MS-HRM). Based on MS-HRM results for RASSF1A and PITX2, we subdivided the samples into four groups according to methylation level (≤50% methylated, >50% methylated, 100% methylated and completely unmethylated alleles). All degrees of methylation status for both genes underwent analysis of dependence with known clinicopathological features, and we found significant associations. In 134 of 149 (89.9%) primary breast carcinomas, the RASSF1A promoter was methylated. Total hypermethylation of PITX2 was observed in 60 of 135 (44.4%) breast cancer cases. RASSF1A hypermethylation had significant association with increased age (p<0.05), tumour grade (p<0.0001) and stage (p<0.0001) in the 100% methylated group. There was significant association of PITX2 hypermethylation with tumour grade (p<0.0001) and stage (p<0.0001). Association between the methylation level of both investigated genes and tumour type was significant for ductal invasive carcinoma cases only (p<0.0001). This study shows different levels of heterogeneous methylation acquired by MS-HRM assay of the promoter region of RASSF1A and PITX2 and its relationship with clinicopathological features of 149 breast cancer patients. We noticed that immunohistopathological subtypes of breast cancer contain distinct promoter methylation patterns. All these data suggest that hypermethylation of the CpG island promoters of RASSF1A and PITX2 might play an essential role in the very early stages of breast cancer pathogenesis.

197P - Effect of using different antihypertensive drugs on demographic and clinico-pathological characteristics of breast cancer

197P - Effect of using different antihypertensive drugs on demographic and clinico-pathological characteristics of breast cancer

Impact of the PARP1 rs1136410 and rs3219145 polymorphisms on susceptibility and clinicopathologic features of breast cancer in a Chinese population

Impact of the PARP1 rs1136410 and rs3219145 polymorphisms on susceptibility and clinicopathologic features of breast cancer in a Chinese population

198P - Effect of using different antidiabetic drugs on demographic and clinico-pathological characteristics of breast cancer

Approximately 20 % of patients diagnosed with breast cancer have also diabetes mellitus as a comorbid condition. There is growing evidence that the use of metformin in diabetic patients was associated with lower risks of cancer. In this study, we aimed to investigate retrospectively the demographic and clinicopathological characteristics of patients with different antidiabetics (AD) users at the time of breast cancer diagnosis. From 3890 breast cancer patients who were taking AD drugs more than 12 months at the time of breast cancer diagnosis were enrolled (n = 378). Patients were classified as Group 1 if they treated only with metformin, Group 2; another oral AD, Group 3; oral AD combination, Group 4; insulin plus oral AD and Group 5; if they treated with insulin only. Median age of 378 patients diagnosed with breast cancer and diabetes was 58 (23-92). The median follow-up of patients was 47 months. There were 128 patients (%38.8) in Group 1, 106 patients (%32.1) in Group 2, 13 patients (%3.9) in Group 3, 27 patients (%8.2) in Group 4 and 56 patients (%17.0) in Group 5. The 5 groups were well-balanced and there were no apparent differences in histological type, terms of baseline tumor size, grade, axillary lymph node involvement, extracapsular extension, perineural invasion, lymphovascular invasion, type of surgery, menopausal status, HER2 positivity and hormonal receptor status between 5 groups. Both estrogen and progesteron receptor positivity were same between 5 groups. Treatment patterns such as hormonal treatment, chemothearpy and radiotherapy were also similar. Similarly, distribution of TNM stages were same between groups. 5-year DFS rates were 81.9%, 77.3%, 79.3%, 72.5% and 61.9% in Groups 1-5, respectively (P = 0.06). 5-year OS rates were 89.3%, 92.5%, 92.9%, 81.8% ve 67.7% in Groups 1-5, respectively. (P = 0. 002). In our study, patients treated with insülin alone or combination have significantly worse OS and borderline significant worse DFS compared to diabetic breast cancer patients treated with oral AD medications. The insulin-sensitizing effect of metformin may play a major role in its anticancer activity. B

Prognostic value of microRNA-203a expression in breast cancer.

Tumor heterogeneity and the poor outcome of breast cancer (BC) patients have led researchers to define new markers of this disease. In recent years, microRNA expression patterns have proven to be valuable disease indicators. The level of miR-203a, in particular, was shown to be altered in different types of cancer. The objective of the present study was to assess the relationship between miR-203a expression and clinicopathological features of BC in a Portuguese cohort. The expression levels of miR‑203a were analyzed in 109formalin‑fixed paraffin-embedded paired normal and tumor tissue samples. Significant overexpression of miR‑203a in the tumor tissues was found (1.7-fold higher) compared to the expression in the normal adjacent tissues (p=0.003). In addition, several clinicopathological characteristics presented an association with higher miR-203a expression levels. Tumors with diameter ≤18.5mm (1.5-fold; p=0.019), tumors positive for estrogen receptor (fold-change,1.71; p=0.042), progesterone receptor (fold-change,1.50; p=0.046) and negative for HER2 (fold-change,1.50; p=0.016) and high Ki-67 index (fold-change,2.60; p=0.024) presented a significant difference in miR-203a expression compared with adjacent normal tissues. Tumors without invasion of lymph nodes also presented higher expression of miR-203a (fold-change,2.40; p=0.004). With regard to histological classification, ductal carcinomas insitu (fold-change, 2.20; p=0.028) and invasive carcinoma NOS (fold-change, 1.71; p=0.009) displayed significantly higher expression of miR-203a. Moreover, we found a significant downregulation of miR-203a with increased stage in invasive lobular carcinomas, suggesting that miR-203a could represent a potential marker to discriminate stages in invasive lobular carcinomas.

Imaging and clinicopathological characteristics of breast cancer among women under the age of 40 years

Background: although breast cancer in young women is less common and often overlooked, it is still considered a major health concern.Objectives: to evaluate the demographic, clinical, radiological and histopathological characteristics of breast cancer among a sample of Iraqi women diagnosed under the age of 40 years.Patients and methods: a retrospective study enrolled 73 females below the age of 40 years with a history of breast cancer. All data was extracted from an established information system database designed by the Principal Investigator of the Iraqi National Breast Cancer Research Project under supervision of the International Agency for Research on Cancer (IARC) over a 4-years period from 2011 to 2014.Results: seventy three women under the age of 40 years with breast cancer were included in the study out of 625 diagnosed cases at different ages (11.68%). The age at presentation ranged from 25 to 39 years, the peak age frequency (63%) was recorded in the period between 35-39 years (n=46). Family history of breast cancer was noticed in approximately 31.5% of cases (n=23). Early menarche (less than 12 years old) was detected in 78.1% (n=57) of cases. On examination, 90.4% (n=66) of patients had painless palpable breast lump. By Sonography, the lesions were spiculated margins in 52% (n=38) of patients and echogenic halo around the mass was detected in 57.5% (n=42) of cases. Stage-II disease was recognized in 54.8%(n=40) of sample of the study and majority of the tumor (98.6%) were ductal in origin. According to Scarf- Bloom-Richardson method, 60.3% (n=44) of the tumors were moderately differentiated (i.e. grade- II). Eight patients (10.9%) were presented with triple receptor-negative breast cancer and recurrence of tumor was encountered in 17.8% (n=13) of cases.Conclusions: The current study suggest that breast cancer among young Iraqi women under 40 years had high incidence rate but might be less aggressive than what is reported in western countries despite of high recurrence rate.

Imaging and clinicopathological characteristics of breast cancer among women under the age of 40 years

Imaging and clinicopathological characteristics of breast cancer among women under the age of 40 years

A new marker for breast cancer diagnosis, human epididymis protein 4: A preliminary study.

Breast cancer is the most frequently diagnosed cancer type in women. Tumor markers have been widely used for assessing the treatment response and early diagnosis of recurrence. Human epididymis protein 4 (HE4) is expressed in ductal carcinoma of the breast tissue; however, its serum levels and their diagnostic and prognostic potential in breast cancer have not been investigated, which was therefore the aim of the present study. The serum levels of HE4 were determined in 36 breast cancer patients, 11 ovarian cancer patients and 16 healthy volunteers. The association between clinicopathological characteristics of breast cancer and serum HE4 levels was investigated. A significant difference in the median serum levels of HE4 was identified between breast cancer patients, ovarian cancer patients and healthy volunteers (P=0.013). The cutoff value for the prediction of breast cancer was determined at >13.24 pmol/l for HE4, with a sensitivity of 61.11%, specificity of 68.75%, positive predictive value of 81.48%, negative predictive value of 44.0% and accuracy of 63.46%. Furthermore, a positive correlation between the serum levels of HE4 and cancer antigen 15-3 was determined (r=0.399, P=0.026). To the best of our knowledge, the present study was the first to determine the diagnostic value of serum HE4 for breast cancer. A significant elevation of serum HE4 levels in patients with breast cancer compared with that in healthy controls was identified. HE4 may serve as a novel biomarker for the diagnosis of breast cancer.

Prognostic and Clinicopathological Value of Programmed Death Ligand-1 in Breast Cancer: A Meta-Analysis.

Recently, the interest in programmed death ligand-1 (PD-L1) as a prognostic marker in several types of malignant tumors has increased. In the present meta-analysis, we aimed to explore the prognostic and clinicopathological value of PD-L1 in breast cancer. We searched Medline/PubMed, Web of Science, EMBASE, the Cochrane Library databases, and grey literature from inception until January 20, 2016. Studies concerning breast cancer that focused on PD-L1 expression and studies reporting survival data were included; two authors independently performed the data extraction. The pooled risk ratio (RR) and 95% confidence interval (CI) were assessed to determine the association between the clinicopathological parameters of patients and PD-L1 expression. Five studies involving 2061 patients were included in this meta-analysis. The results indicated that positive/higher PD-L1 expression was a negative predictor for breast cancer, with an RR of 1.64 (95% CI, 1.14–2.34) for the total mortality risk and an RR of 2.53 (95% CI, 1.78–3.59) for the mortality risk 10 years after surgery. Moreover, positive/higher PD-L1 expression was significantly associated with positive lymph node metastasis (RR, 1.33; 95% CI, 1.04–1.70), poor nuclear grade (RR, 1.24; 95% CI, 1.07–1.43), and negative estrogen receptor status (RR, 2.45; 95% CI, 1.31–4.60) in breast cancer patients. Our findings suggest that PD-L1 can serve as a significant biomarker for poor prognosis and the adverse clinicopathologic features of breast cancer and could facilitate the better management of individual patients.

Anti-hMAM monoclonal antibodies evaluated in breast and non-breast tissues for differential diagnosis implication.

Human mammaglobin (hMAM) is a breast tissue-specific marker that may have potency for the diagnosis of breast cancer. However, there is a lack of commercialization of anti-hMAM antibody made in China. Immunoreactivities of 2 self-made monoclonal anti-hMAM antibodies, MEF521 and MDA822, were evaluated by immunohistochemistry staining and compared with imported monoclonal antibody ab81611. A total of 48 cases of primary breast cancers, 36 cases of benign or normal breast tissues, 52 cases of lymph nodes or organ metastases from breast cancer, and 90 cases of non-breast primary carcinoma tissues were analyzed. All 3 anti-hMAM antibodies showed high positive expression of hMAM in primary breast cancers, benign, and normal breast tissues. The positive ratio for MEF521 (33.3%) or MDA822 (44.4%) was much higher than that of ab81611 (16.7%) in lymph node metastasis from breast cancer (p = 0.038). There was no correlation between hMAM expression and clinicopathologic features of breast cancer in the 3 groups of antibodies. In 90 cases of non-breast primary carcinoma tissues, no hMAM-positive ones were observed in the MEF521 or MDA822 group, but 48 (53.3%) in the ab81611 group were positive, indicating that breast tissue specificity of the 2 self-made anti-hMAM monoclonal antibodies much higher than that of ab81611 (p&lt;0.001). Our results showed that MDA822 and MEF521 are more specific to breast cancer as measured by means of immunohistochemistry. Therefore, the 2 self-made anti-hMAM antibodies may have good prospects for clinical application in the differential diagnosis of breast tumor and breast cancer metastases.

Clinicopathological significance of forkhead box protein A1 in breast cancer: A meta-analysis

The aim of the present study was to investigate the associations between the expression of forkhead box protein A1 (FOXA1) and differential clinicopathological characteristics in breast cancer using a meta-analysis method. Eligible studies that investigated the correlation between FOXA1 expression and the clinical characteristics of breast cancer were collected through searching numerous databases, including PubMed, EMBASE, the Chinese National Knowledge Infrastructure and the VIP database. In total, eight studies were included in the meta-analysis. Following a systematic analysis, the expression of FOXA1 was found to be significantly associated with the estrogen receptor α status, the progesterone receptor status, lymph node metastasis and the histological grade in breast cancer. However, no statistically significant association was observed between FOXA1 expression and the human epidermal growth factor receptor-2 status in breast cancer patients.

Imaging and clinicopathological characteristics of breast cancer among women under the age of 40 years

Background: although breast cancer in young women is less common and often overlooked, it is still considered a major health concern.Objectives: to evaluate the demographic, clinical, radiological and histopathological characteristics of breast cancer among a sample of Iraqi women diagnosed under the age of 40 years.Patients and methods: a retrospective study enrolled 73 females below the age of 40 years with a history of breast cancer. All data was extracted from an established information system database designed by the Principal Investigator of the Iraqi National Breast Cancer Research Project under supervision of the International Agency for Research on Cancer (IARC) over a 4-years period from 2011 to 2014.Results: seventy three women under the age of 40 years with breast cancer were included in the study out of 625 diagnosed cases at different ages (11.68%). The age at presentation ranged from 25 to 39 years, the peak age frequency (63%) was recorded in the period between 35-39 years (n=46). Family history of breast cancer was noticed in approximately 31.5% of cases (n=23). Early menarche (less than 12 years old) was detected in 78.1% (n=57) of cases. On examination, 90.4% (n=66) of patients had painless palpable breast lump. By Sonography, the lesions were spiculated margins in 52% (n=38) of patients and echogenic halo around the mass was detected in 57.5% (n=42) of cases. Stage-II disease was recognized in 54.8% (n=40) of sample of the study and majority of the tumor (98.6%) were ductal in origin. According to Scarf-Bloom-Richardson method, 60.3% (n=44) of the tumors were moderately differentiated (i.e. grade- II). Eight patients (10.9%) were presented with triple receptor-negative breast cancer and recurrence of tumor was encountered in 17.8% (n=13) of cases.Conclusions: The current study suggest that breast cancer among young Iraqi women under 40 years had high incidence rate but might be less aggressive than what is reported in western countries despite of high recurrence rate.

السمات السريرية والتصويرية والمرضية لسرطان الثدي لدى النساء دون سن الاربعين

السمات السريرية والتصويرية والمرضية لسرطان الثدي لدى النساء دون سن الاربعين

Abstract P4-04-23: Clinical importance of S100A9 and S100A2 in breast cancer

Abstract Background: The most frequent cause of cancer deaths throughout the world is breast cancer (BC). Therefore, preventing, diagnosing and treating BC has gained importance. Calcium-binding S100 group proteins are coded in the chromosome 1q21 and have many members. It is claimed that S100A12 and S100A9 play an important role in the development of cancer. S100A12 is normally expressed in neutrophil granulocytes, and from lymphocytes and monocytes in small amounts. S100A12 is closely related to inflammation and vascular invasion by tumor cells, and causes excessive inflammation and vascular invasion causes tumor recurrence and metastasis. S100A9 protein is found in human epithelial cells and cytosols in phagocytes and regulates the motility of phagocytes and activity of target proteins through interaction with danger signal molecules. Furthermore, it has also been stated that it is possible that it regulates the cellular growth through interaction with p53 like other S100 proteins and can modulate metastasis of malignant tumors. In this study, we aimed at diagnostic and clinic-pathological importance of serum levels of S100A9 and S100A12 with known cytokin-like pro-inflammatory effects in BC. Material: A total number of 45 patients with breast cancer were first admitted in the study. Sixteen age-matched healty women were enrolled in to this study. All the samples were analyzed with enzyme-linked immunosorbent assay for serum S100A9 and S100A12 levels before starting the systemic chemotherapy. The characteristics of the breast cancer patients with respect to age, weight, height, menopausal status, histopathological type, tumor size, tumor lymph node metastasis, tumor grade, and estrogen receptor (ER) and progesterone receptor (PR) and HER2, lymphovascular invasion (LVI), perineural invasion (PNI) status and stage were collected for data analyses. Clinicopathologic characteristics of BC and other blood parameters were compared in relation with serum S100A9 and S100A12 levels. Results: While the serum S100A9 levels were found significantly higher as compared to healthy individuals (190.85±32.29 and 92.72±54, respectively) (p=0.001), it was observed that there were no differences in S100A12 (120.50±15.78 and 112.21±10.46, respectively) (p=0.056) levels. As regards the subgroup analysis in BC patients, no statistically significant results were found in body mass index, smoking, menopause status, histopathologic type, grade, biological subtype of BC, tumor size, presence of lymph node metastases, LVI, PNI and stage. As regards the blood parameters and serum S100 A9, while only statistically significant results were found with anemia (209.05±33.12 and 181.75±28.21, respectively) (p=0.005), no statistically significant results were found with leukocytosis, thrombocytosis and tumor markers. Conclusion: In this study, while we found the level of S100A9, which has a potential cytokine-like function in inflammation, significantly higher, we could not find any increase in S100A12 level. Therefore, it is possible that S100A9 can play a key role in inflammation-related BC. We therefore suggest that serum S100A9 can be the target marker in breast cancer both as a diagnostic tool and to suppress inflammation in treatment. Citation Format: Gunaldi M, Okuturlar Y, Üstüngüler A, Akarsu C, Kural A. Clinical importance of S100A9 and S100A2 in breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-04-23.

Increased Incidence of Breast Cancer in Postmenopausal Women with High Body Mass Index at the Modena Screening Program.

PurposeWe conducted a study to evaluate the relationship between body mass index (BMI) and the risk of breast cancer (BC) and outcome in a population of 14,684 women aged 55 to 69 years eligible to participate in the Mammography Screening Program (MSP) in the Province of Modena, Italy.MethodsThe study population was drawn from women who underwent mammography screening between 2004 and 2006 in the Province of Modena. Women were subdivided into obese, overweight, and normal-weight categories according to BMI and followed until July 31, 2010, to evaluate the BC incidence. The clinicopathological characteristics of BC were also evaluated in different groups of patients classified according to BMI. After BC diagnosis, patients were followed for a median period of 65 (range, 2–104) months. Second events (recurrences and second tumors) were recorded, and the 5-year event-free survival (EFS) was calculated.ResultsAfter a period of 73 months, 366 cases of BC were diagnosed. Compared with normal-weight women, obese women had a significantly higher incidence of BC (relative risk [RR], 1.32; p=0.040) (RR=1), larger tumors (27% of tumors were larger than T2 size), and more nodal involvement (38.5% of tumors were node-positive). Furthermore, a significantly higher rate of total events was seen in obese women compared with overweight and normal-weight patients, respectively (17.9% vs. 11.4% vs. 10.8%, p=0.032). The 5-year EFS was 89.0%, 89.0%, and 80.0% for normal-weight, overweight, and obese patients, respectively.ConclusionWe observed a significantly higher risk of BC in obese women among those eligible to participate in the MSP in the Province of Modena. Finally, obese women had more second events and poorer EFS compared to nono bese women.

Diagnostic importance of S100A9 and S100A12 in breast cancer.

The most frequent cause of cancer deaths throughout the world is breast cancer (BC). Therefore, preventing, diagnosing and treating BC has gained importance. S100 protein probably plays an important role in carcinogenesis, cancer development, and metastasis. In this study, we aimed at diagnostic and clinic-pathological importance of serum levels of S100A9 and S100A12 with known cytokine-like pro-inflammatory effects in BC. Serum samples were collected with BC and the control group consisting of healthy individuals. All the samples were analyzed with enzyme-linked immunosorbent assay for serum S100A9 and S100A12 levels before starting the systemic chemotherapy. Clinicopathological characteristics of BC and other blood parameters were compared in relation with serum S100A9 and S100A12 levels. While the serum S100A9 levels were found significantly higher as compared to healthy individuals (190.85±32.29 and 92.72±54, respectively) (p=0.001), it was observed that there were no differences in S100A12 (120.50±15.78 and 112.21±10.46, respectively) (p=0.056) levels. As regards the subgroup analysis in BC patients, no statistically significant results were found in body mass index (BMI), smoking, menopause status, histopathologic type, grade, and biological subtype of BC, tumor size, presence of lymph node metastases, lymphovascular invasion (LVI), perineural invasion (PNI) and stage. As regards the blood parameters and serum S100 A9, while only statistically significant results were found with anemia (209.05±33.12 and 181.75±28.21, respectively) (p=0.005), no statistically significant results were found with leukocytosis, thrombocytosis and tumor markers. In this study, while we found the level of S100A9, which has a potential cytokine-like function in inflammation, significantly higher, we could not find any increase in S100A12 level. Therefore, it is possible that S100A9 can play a key role in inflammation-related BC. Despite of there are no significance relationship between S100A9 and S100A12 clinicopathological features of BC, the determination of S100A9 levels contributes to diagnosis the of BC patients. In future, we suggest that serum S100A9 is investigated as a diagnostic tool even the target marker in BC to suppress inflammation in treatment.

Ovarian Metastasis of Breast Cancer Is Associated With Specific Characteristics

Introduction: Breast cancer (BC) demonstrates a nonrandom, organotropic metastatic spread pattern. BC subtypes are associated with distinct patterns of metastasis in bone, liver, lung, and brain. However, the clinicopathologic characteristics of BC with ovarian metastasis (OM) have not been well established. The purpose of this retrospective study is to provide the features of BC with OM to help monitor early …

Effects of HER2 genetic polymorphisms on its protein expression in breast cancer

Background and purposesHER2 protein expression has been considered to be an important prognostic factor in breast cancer patients. Although the molecular mechanism of HER2 protein expression is currently unknown, single nucleotide polymorphisms (SNPs) of the HER2 gene may have some effects on its own expression. Here, we performed a trial to study the association between HER2 genetic polymorphisms and its protein expression in breast cancer. MethodsThree SNPs in the HER2 gene were genotyped in 303 breast cancer patients using the Sequenom Mass ARRAY system. HER2 protein expression, ER, PR, P53, and Ki67 status was detected by immunohistochemistry. A Pearson’s chi-square test was used to analyze the associations of the polymorphisms with its protein expression, corresponding with clinicopathological characteristics of breast cancer. ResultsUnder the codominant model, rs1058808 and rs2517956 polymorphisms were associated with HER2 protein expression in breast cancer (p=0.007; p=0.008, respectively). For SNP rs1058808, patients with genotypes CG and GG were more likely to have high HER2 protein expression than patients with genotype CC (p=0.007). No significant associations could be found between the three SNPs and breast cancer patients’ clinical stage, tumor size, histological grade, lymph node metastasis, ER, PR, Ki67 and P53 status (p>0.05). ConclusionsHER2 rs1058808 and rs2517956 polymorphisms are associated with its protein expression in breast cancer. Our study might provide new insights into the mechanisms of HER2 protein expression.

Evaluation of CYP17A1 and LEP Gene Polymorphisms in Breast Cancer

Background: Polymorphisms of estrogen synthesis- and adiposity-related genes can contribute to the development of breast cancer. The purpose of the current study was to analyze the association between CYP17A1 T27C (rs743572) and LEP -2548G>A (rs7799039) gene polymorphisms and breast cancer. Material and Methods: 199 breast cancer patients and 197 healthy controls were included in the study. The CYP17A1 and LEP gene polymorphisms were determined using polymerase chain reaction-based restriction fragment length polymorphism analysis. Results: No statistically significant association was found between these polymorphisms and breast cancer risk among a Turkish population. However, stratified analysis of these polymorphisms in relation to different clinicopathological characteristics of breast cancer revealed an association between breast cancer diagnosis and the CYP17A1 T27C polymorphism (p = 0.024). Conclusion: Our study suggests no strong association between the CYP17A1 T27C and LEP -2548G>A polymorphisms and the incidence of breast cancer in Turkish women. The potential association between CYP17A1 T27C and the type of breast cancer deserves further consideration.