• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.3733-3736
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• 2016

HER2/neu is a well-established prognostic and predictive factor for invasive breast cancer. However, the role of HER2/neu in ductal breast carcinoma in situ (DCIS) is debated and recent data have suggested that it is mainly linked to in situ local recurrence. Although molecular data suggest that atypical ductal hyperplasia (ADH) and duct carcinoma in situ (DCIS) are related lesions, albeit with vastly different clinical implications, the role of HER2/neu expression in atypical ductal hyperplasia is not well defined either. The aim of this study was to evaluate over expression of HER2/neu in DCIS and cases of ADH in comparison with invasive breast carcinoma. Archival primary breast carcinoma paraffin blocks (n=15), DCIS only (n=10) and ductal epithelial hyperplasia and other breast benign lesions (n=25) were analyzed for HER2/neu immunoexpression. Follow up was available for 40% of the patients. HER2/neu was positive in 80%of both DCIS and invasive carcinoma, and 67% of atypical ductal hyperplasia (ADH) cases. Thus at least a subset of patients with preinvasive breast lesions were positive, which strongly suggests a role for Her2/neu in identifying high-risk patients for malignant transformation. Although these are preliminary data, which need further studies of gene amplification within these patients as well as a larger patient cohort with longer periods of follow up, they support the implementation of routine Her2/neu testing in patients diagnosed as pure DCIS and in florid ADH.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.5
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• pp.1707-1713
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• 2015

Eighty six cases of invasive ductal breast carcinomas were utilized to investigate GSTP1 polymorphisms in certain immunohistochemistry (IHC) subtypes of breast cancer with respect to ER, PR and HER2 expression. The frequency of wild allele homozygote, heterozygote and variant allele homozygote genotypes were 46.5%, 52.3% and 1.16% respectively; Whereas 54.3% of the control subjects were GSTP1 wild type allele homozygous, 40.0% were heterozygous and 5.71% mutant allele homozygous. There was dramatic inverted relation between positive IHC ER staining and increasing grade of tumors in general (100%, 88.6%, 40.4%) and especially among tumors with heterozygote genotype of GSTP1 (70%, 35.4%, 22.7). There was increase in positive IHC HER2 staining consistent with higher grades in general (20%, 29.6%, 50.0%), especially among tumors with GSTP1 wild allele homozygote genotype (5.0%, 9.1%, 31.8%). A remarkable reverse relation was also observed between the fraction of IHC hormone receptor phenotype ER+/PR+/ HER2- and increased grade of tumors (60.0%, 45.5%, and 27.3%) especially among tumors with GSTP1 heterozygote genotype, and a similar link was noted regarding ER+/PR-/ HER2- and tumor grade. There was increase in frequency of ER-/PR-/ HER2- (0.0%, 6.8%, and 18.2%) and ER-/PR-/ HER2+ (0.0%, 4.54%, and 40.9%) consistent with the higher grades of tumors in general and especially GSTP1 heterozygote genotype tumors. As a conclusion, there is no correlation between GSTP1 polymorphism and increased risk of breast cancer i.e. the mutant allele is randomly distributed in cancer and control cases. However, there is a link between GSTP1 genotypes and hormone receptor expression status and certain phenotypes of breast cancer, which may have clinical importance.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2973-2978
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• 2012

Background: Cancer stem cells (CSC) have been described in a variety of malignancies, including breast carcinomas. Among several markers, aldehyde dehydrogenase 1 (ALDH1) has been identified as reliable for breast cancer stem cells. Knockdown of BRCA1 in primary breast epithelial cells leads to an increase in cells expressing ALDH1. Methods: We examined 127 breast carcinomas for expression of ALDH1, using immunohistochemistry and correlated with clinicopathological parameters as well as the BRAC1 status. Results: Comparing the results for both ALDH1 and BRCA1 expression showed a significant inverse association between the two, indicating that reduced BRCA1 was more often seen in breast cancer cells expressing ALDH1 (p-value = 0.044). A total of 24/110 (22%) of tumours displayed the ALDH1 + / BRCA1 -/low phenotype, which showed a trend for a relation with a high grade (p-value= 0.056). Cytoplasmic expression of ALDH1 was not correlated with tumour characteristics. Conclusion: Taken together, our findings suggest that increased ALDH1 is inversely correlated with decreased BRCA1 in a series of unselected breast carcinomas. Therefore, ALDH1 positive (cancer stem) cells with reduced BRCA1 phenotype may indicate a subset of patients for whom specific targeting of the CSC marker ALDH1 and more aggressive adjuvant treatment is appropriate.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1215-1219
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• 2016

Background: Worldwide, breast cancer is the most common cancer among women and is a leading cause of cancer death. In the present study, we investigated the NQO1 C609T genotypic and allelic distribution in north Indian breast cancer patients. Materials and Methods: The genotypic distribution of the NQ01 C609T polymorphism was assessed in 100 invasive ductal carcinoma (IDC) breast cancer patients and 100 healthy controls using allele specific PCR (AS-PCR). Results: A lower frequency of the CC genotype was found in breast cancer patients (24%) than in the controls. On the other hand, TT genotype frequency was also found to be higher in female healthy controls (32%) than the female breast cancer patients (20%). The frequencies of all three genotypes CC, CT, TT in patients were 24%, 56% and 20% and in healthy controls 50%, 22% and 32% respectively. We did not find any significant correlation between the NQO1 C609T polymorphism and age group, grading, menopausal status and distant metastasis. A less significant association was found between the NQ01 C609T polymorphism and the stage of breast cancer (X2=5.931, P=0.05). Conclusions: The present study shows a strong association between NQO1 C609T polymorphism with the breast cancer risk in the north Indian breast cancer patients so that possible use as a risk factor should be further expel.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.717-722
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• 2013

Background: Breast cancer is the most common cancer among women worldwide. The aim of this study was to investigate the relationship between tumor size and axillary lymph node involvement (ALNI) in patients with invasive lesions, to find the best candidates for a full axillary dissection. Additionally, we evaluated the association between tumor size and invasive behavior. The study was based on data from 789 patients with histopathologically proven invasive breast cancer diagnosed in Shohada University hospital in Tehran, Iran (1993-2009). Cinical and histopathological characteristics of tumors were collected. Patients were divided into 6 groups according to primary tumor size: group I ($0.1-{\leq}1cm$), II ($1.1-{\leq}2cm$), III ($2.1-{\leq}3cm$), IV ($3.1-{\leq}4cm$), V ($4.1-{\leq}5cm$) and VI (>5cm). The mean(${\pm}SD$) size of primary tumor at the time of diagnosis was $3.59{\pm}2.69$ cm that gradually declined during the course of study. There was a significant correlation between tumor size and ALNI (p<0.001). A significant positive correlation between primary tumor size and involvement of surrounding tissue was also found (p<0.001). The mean number of LNI in group VI was significantly higher than other groups (p<0.05). We observed more involvement of lymph nodes, blood vessels, skin and areola-nipple tissue with increase in tumor size. We found 15.3% overall incidence of ALNI in tumors ${\leq}2cm$, indicating the need for more investigation to omit full axillary lymph node dissection with an acceptable risk for tumors below this diameter. While in patients with tumors ${\geq}2cm$, 84.3% of them had nodal metastases, so the best management for this group would be a full ALND. Tumor size is a significant predictor of ALNM and involvement of surrounding tissue, so that an exact estimation of the size of primary tumor is necessary prior to surgery to make the best decision for management of patients with invasive breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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• pp.2771-2776
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• 2014

Background: Breast cancer screening and higher quality mammography have resulted in an increase in the diagnosis of ductal carcinoma in situ worldwide. We compared the incidence and other factors in our cases of ductal carcinoma in situ between two recent decades. Materials and Methods: Medical records of cases of ductal carcinoma in situ who had been admitted to the surgery wards of the Cancer Institute of Tehran, Iran were evaluated from March 1993 to March 2003 as phase 1, and from April 2003 to April 2013 as phase 2. Results: Ratio of ductal carcinoma in situ to overall breast cancer was 1.27 and 3.93 in phases 1 and 2, respectively. Rates of excisional or incisional biopsies versus core needle biopsies and clinically versus mammographically detected cases as well as median size of tumors dropped between the 2 phases while a substantial rise in the number of patients attending for screening was seen in this time period. Surgical treatments followed a trend from modified radical mastectomy and axillary lymphatic dissection toward breast conserving surgery and sentinel node dissection or no axillary intervention. Conclusions: Our study shows a considerable trend toward earlier detection of breast cancer and evolution of treatment strategies toward standard less invasive surgery of DCIS in Iran.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1347-1350
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• 2016

Background: Breast cancer prognosis is influenced by several histopathology and clinical factors including expression of Ki67 which may have a predictive role in lymph node negative breast cancer patients. The aim of this study was to assess Ki67 expression in breast cancers without axillary lymph node involvement and to evaluate its prognostic value with regard to disease-free survival. Materials and Methods: Subjects were selected from non-metastatic invasive breast cancer patients who were referred to the oncology department of Ghaem hospital during 1 April 2001 to 1 April 2008. Ki67 levels were measured using immunohistochemistry (IHC) and compared with clinicopathological features. The relation of Ki67 expression with disease-free survival was also analysed. Results: A total of 106 women with a mean age of 49 were examined. Some 94.3% were classified as having invasive ductal carcinomas and the mean tumour diameter at the time of diagnosis was 2.8 cm. Some 50.9% of cases were ER positive and 47.2% were PR positive. P53 expression was positive in 48.1% of the cases. According to the IHC results, only 8.5% of the patients were Her2/neu positive. Ki67 was positive in 66 (62.3%) with a significant relation to lower age (p=0.0229) and P53 positivity (p=0.005). After an average of 40-months follow up, 13 (12.3%) demonstrated recurrence, most commonly systemic. Of 13 cases with relapse, 10 patients (77%) were Ki67 positive. Conclusions: In our population Ki67 appeared to be an independent prognostic factor for three-year survival. However, we stress that a survival study with a bigger sample size would help to support this conclusion.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6529-6532
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• 2013

Background: Breast cancer is mostly the disease of postmenopausal women but very young affected women are seen more than occasionally in developing countries. We reviewed our cases of very young breast cancer in order to help in better understanding of such cases. Materials and Methods: The records of patients 25 years of age or less who had been admitted for breast cancer surgery in the Cancer Institute of Tehran from 1979 to 2012 were reviewed and relevant data were extracted. Results: From 5,265 cases of breast cancer, 62 patients had 25 years of age or less. There were 55 cases of breast adenocarcinoma, all female. More than 78% of the patients had presented with a palpable mass, the family history was positive in 2% of cases, and about 94% of the histologies were invasive ductal carcinoma. Gestational breast cancer constituted 10% of the cancers; another 10%were bilateral. The median size of the tumors was 5.72 centimeters, 63.2% of them had axillary lymphatic involvement, and more than half were negative for hormone receptors. Conclusions: Our study shows an incidence of 1.17% for very young breast cancer and a 10% rate of bilaterality which probably warrants special guidelines for contralateral screening. Cancer stage and features were poor in comparison with breast cancer in all ages.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.3
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• pp.1481-1488
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• 2014

Background: To avoid performing axillary lymph node dissection (ALND) for non-sentinel lymph node (SLN)-negative patients with-SLN positive axilla, nomograms for predicting the status have been developed in many centers. We created a new nomogram predicting non-SLN metastasis in SLN-positive patients with invasive breast cancer and evaluated 14 existing breast cancer models in our patient group. Materials and Methods: Two hundred and thirty seven invasive breast cancer patients with SLN metastases who underwent ALND were included in the study. Based on independent predictive factors for non-SLN metastasis identified by logistic regression analysis, we developed a new nomogram. Receiver operating characteristics (ROC) curves for the models were created and the areas under the curves (AUC) were computed. Results: In a multivariate analysis, tumor size, presence of lymphovascular invasion, extranodal extension of SLN, large size of metastatic SLN, the number of negative SLNs, and multifocality were found to be independent predictive factors for non-SLN metastasis. The AUC was found to be 0.87, and calibration was good for the present Ondokuz Mayis nomogram. Among the 14 validated models, the MSKCC, Stanford, Turkish, MD Anderson, MOU (Masaryk), Ljubljana, and DEU models yielded excellent AUC values of > 0.80. Conclusions: We present a new model to predict the likelihood of non-SLN metastasis. Each clinic should determine and use the most suitable nomogram or should create their own nomograms for the prediction of non- SLN metastasis.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.9
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• pp.4527-4531
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• 2016

Background: PTEN protein is one of the most important tumour suppressor factors which is detectable by immunohistochemistry. The goal of the present study was to investigate the prognostic role of PTEN gene expression in breast cancer patients. Materials and Methods: This descriptive-analytical study was conducted on 100 breast cancer patients referred to Sabzevar hospitals in the north-east of Iran between 2010 and 2011, who were followed up to 2015. PTEN gene expression in tissue samples was determined using specific monoclonal antibodies and data were analyzed using Chi-square test and Fisher's exact test. Patient survival was analyzed after 4 years of follow-up using the Cox regression model. Results: PTEN gene expression was evident in 70 of 100 cnacer samples but was found at high levels in all non-cancer samples. There was an inverse significant relationship between PTEN gene expression and tumour stage or tumour grade (p<0.001). The expression of PTEN in invasive ductal tumours was lower than in non-invasive tumours. There was also an inverse significant relationship between the hazard of death and PTEN gene expression (p<0.001). In addition, there was an inverse significant relationship between tumour stage and hazard of death (p<0.001). Conclusion: These findings indicate that lack of PTEN gene expression can be a sign of a worse prognosis and poor survival in breast cancer cases.