Expression of androgen receptor and its regulatory molecule Lin28 in non-luminal subtype breast cancer.

Androgen receptor (AR) was associated with favourable outcome in luminal breast cancer. However, the role of AR in non-luminal breast cancer remains inconclusive. The aim of the present study was to evaluate the clinical significance of the AR and its regulatory pathway in non-luminal subtypes of breast cancer. In total, 284 breast cancer patients were recruited from January 2007 to January 2016. Tissue microarrays were constructed from archival paraffin blocks and assessed for AR and its regulatory molecule, Lin28, by immunohistochemistry. The association between AR and Lin28 expression and clinicopathological parameters was analyzed. Results showed that AR and Lin28 were co-expressed. No association between these proteins and clinicopathological parameters, and survival outcome was found. However, a higher proportion of the patients with AR and Lin28 expression were observed in HER2 subtype. In conclusion, Lin28 may be a novel marker for prognosis and targeted for treatment in HER2 subtype breast cancer.

Gail Model Underestimates Breast Cancer Risk in Thai Population.

Background: The Gail model is the most widely used method for breast cancer risk estimation. This model has been studied and verified for its validity in many groups but there has yet to be a study to validate the Gail model in a Thai population. This study aims to evaluate whether the Gail model can accurately calculate the risk of breast cancer among Thai women. Methods: The subjects were recruited from the Division of Head, Neck, and Breast Surgery, Department of Surgery, Siriraj Hospital. The patients attending the division were asked to enroll in the study and complete questionnaires. Gail model scores were then calculated. Relationships between parameters were examined using the Pearson's chi-square test, Fisher's exact test, and independent-samples t-test. Results: There were 514 women recruited. Age, parity, age at first-live birth, and history of atypical ductal hyperplasia (ADH) were significant risk factors for breast cancer. The 5-year and lifetime risk score for breast cancer calculated by the Gail model were not significantly different between the patient and the control subjects. The proportions of the subjects with lifetime risk ≥20% were significantly higher in breast cancer patients (p=0.049). Conclusion: The Gail model underestimated the risk of breast cancer in Thai women. Calibration of the model is still required before adoption in Thai population.

Nomogram to predict non-sentinel lymph node status using total tumor load determined by one-step nucleic acid amplification: first report from Thailand.

BACKGROUND: Axillary staging is a significant prognostic factor often used to determine the treatment course for breast cancer. One-step nucleic acid amplification (OSNA) is now the most accepted method for intra-operative assessment of sentinel lymph nodes (SLN) as it can semi-quantitatively determine the tumor burden in these SLN. Axillary lymph node dissection (ALND) may be omitted in patients with limited disease in the axilla. The objective was to create nomogram for prediction of non-sentinel lymph node (NSLN) status using OSNA to avoid unnecessary ALND. PATIENTS AND METHODS: Patients with invasive breast cancer T1-T3 and clinically negative axillary lymph nodes underwent SLN biopsy assessed by OSNA. The patients with positive SLN underwent ALND. Correlations between total tumor load (TTL), clinicopathological parameters, and NSLN status were analyzed by Chi square statistic and logistic regression. Model discrimination was evaluated using receiver-operating characteristic (ROC) analysis. RESULTS: The total number of patients who underwent SLN biopsies was 278. There were 89 patients with positive SLN. NSLNs were positive in 40 patients. Larger tumor size, presence of lymphovascular invasion (LVI) and higher log TTL were independent factors that predicted positive NSLN. TTL can discriminate NSLN status with area under the ROC curve of 0.789 (95% CI 0.686-0.892). Two nomograms using different parameters obtained pre- and post-operatively can predict NSLN involvement with better area under the ROC curve (0.801, 95% CI 0.702-0.900 and 0.849, 95% CI 0.766-0.932, respectively). CONCLUSIONS: Nomograms using results obtained via OSNA can predict NSLN status, as well as aid in deciding to omit the use of ALND.

Association of Estrogen Receptor Alpha and Interleukin 6 Polymorphisms with Lymphovascular Invasion, Extranodal Extension, and Lower Disease-Free Survival in Thai Breast Cancer Patients.

Breast cancer is the most frequent type of cancer diagnosed among women worldwide and also in Thailand. Estrogen and estrogen receptors exert important roles in its genesis and progression. Several cytokines have been reported to be involved in the microenvironment that promotes distant metastasis via modulation of immune and inflammatory responses to tumor cells. Estrogen receptor genetic polymorphisms and several cytokines have been reported to be associated with breast cancer susceptibility and aggressiveness. To investigate roles of genetic polymorphisms in estrogen receptor alpha (ESR1) and interleukin 6 (IL6), breast cancer patients and control subjects were recruited from the Division of Head, Neck and Breast Surgery (Siriraj Hospital, Bangkok, Thailand). Polymorphisms in ESR1 (rs3798577) and IL6 (rs1800795 and rs1800797) were evaluated by real-time PCR in 391 breast cancer patients and 79 healthy controls. Associations between genetic polymorphisms and clinicopathological data were determined. There was no association between genetic polymorphisms and breast cancer susceptibility. However the ESR1 rs3798577 CT genotype was associated with presence of lymphovascular invasion (OR=2.07, 95%CI 1.20-3.56, p=0.009) when compared to the TT genotype. IL6 rs1800795 CC genotype was associated with presence of extranodal extension (OR= 2.30, 95%CI 1.23-4.31, p=0.009) when compared to the GG genotype. Survival analysis showed that IL6 rs1800797 AG or AA genotypes were associated with lower disease-free survival. These findings indicate that polymorphisms in ESR1 and IL6 contribute to aggressiveness of breast cancer and may be used to identify high risk patients.