Raquel Mary Rodrigues Peres

Reduced prevalence of the C825T polymorphism of the G-protein beta subunit gene in women with breast cancer.

Objective To evaluate the prevalence of the C825T polymorphism in the GNB3 gene in women with and without breast cancer and its possible association with clinical or pathological features of breast disease. Subjects and methods We included 134 women with breast cancer and a control group of 129 healthy women. The case group responded to a questionnaire on lifestyle, reproductive factors and family history. Clinical data were also evaluated. The risk for cancer was calculated and PCR was carried out for the detection of the polymorphism. Statistical analysis was performed using the package R Environment, with confidence intervals of 95% and a significance level of 5% (P<0.05). Results The frequency of the TT genotype was significantly greater in women of the control group (30.2%) than women with breast cancer (14.9%) (p=0.02). The polymorphism was not associated with clinical features, age at diagnosis (p=0.07), age at menarche (p=0.17), and age at menopause (p=0.60). The TT genotype did not have a higher frequency in patients with high BMI (p=0.98). The risk for cancer showed no correlation with the presence of the polymorphism. Conclusions Our data indicate that the C825T polymorphism in the GNB3 gene has no relationship to the risk for breast cancer or the characteristics of the disease.

Functional Annotation of ESR1 Gene Fusions in Estrogen Receptor-Positive Breast Cancer.

SUMMARY RNA sequencing (RNA-seq) detects estrogen receptor alpha gene (ESR1) fusion transcripts in estrogen receptor-positive (ER+) breast cancer, but their role in disease pathogenesis remains unclear. We examined multiple ESR1 fusions and found that two, both identified in advanced endocrine treatment-resistant disease, encoded stable and functional fusion proteins. In both examples, ESR1-e6>YAP1 and ESR1-e6>PCDH11X, ESR1 exons 1–6 were fused in frame to C-terminal sequences from the partner gene. Functional properties include estrogen-independent growth, constitutive expression of ER target genes, and anti-estrogen resistance. Both fusions activate a metastasis-associated transcriptional program, induce cellular motility, and promote the development of lung metastasis. ESR1-e6>YAP1- and ESR1-e6>PCDH11X-induced growth remained sensitive to a CDK4/6 inhibitor, and a patient-derived xenograft (PDX) naturally expressing the ESR1-e6>YAP1 fusion was also responsive. Transcriptionally active ESR1 fusions therefore trigger both endocrine therapy resistance and metastatic progression, explaining the association with fatal disease progression, although CDK4/6 inhibitor treatment is predicted to be effective.

Expressão da proteína erbB-2 e dos receptores de hormônios na transição das regiões in situ para invasora de tumores da mama

PURPOSE to evaluate the expression of erbB-2 and of the estrogen and progesterone (ER/P) hormonal receptors in the transition regions between the in situ and the invasive fractions of ductal breast neoplasia (ISDC and IDC, respectively). METHODS Eighty-five cases of breast neoplasia, containing contiguous ISDC and IDC areas, were selected. Histological specimens from the ISDC and the IDC areas were obtained through the tissue microarray (TMA) technique. The erbB-2 and the ER/PR expressions were evaluated through conventional immunohistochemistry. The McNemars test was used for the comparative analysis of the expressions of erbB-2 protein and the ER/PR in the in situ and invasive regions of the tumors. The confidence intervals were set to 5% (p=0.05). Intraclass correlation coefficients (ICC) were calculated to assess the cross-tabulation agreement of the erbB-2 and the ER/PR expression in the ISDC and the IDC areas. RESULTS the erbB-2 expression has not differed between the ISDC and the IDC areas (p=0.38). Comparing the two areas in each case, there was agreement in the expression of erbB-2 (ICC=0.64), PR (ICC=0.71) and ER (ICC=0.64). Restricting the analysis to tumors with the in situ component harboring necrosis (comedo), the ICC for erbB-2 was 0.4, compared to 0.6 for the whole sample. In this select group, the ICC for PR/ER did not differ substantially from those obtained with the complete dataset: as for the ER, ICC=0.7 (versus 0.7 for the entire sample) and for PR, ICC=0.7 (versus 0.6 for the entire sample). CONCLUSIONS our findings suggest that the erbB-2 and the ER/PR expressions do not differ in the contiguous in situ and invasive components of breast ductal tumors.

Comparative evaluation of the erbB2 and hormone receptor status of neighboring invasive and in situ components of ductal carcinomas of the breast

BACKGROUND It remains unknown whether erbB2 expression and hormone receptor status predict the invasive potential of ductal carcinoma in situ (DCIS) of the breast. OBJECTIVES To examine erbB2 and estrogen/progesterone receptor (ER/PR) status in the precise areas where DCIS turns into invasive ductal carcinoma (IDC). SUBJECTS AND METHODS Eighty-seven cases of breast malignancies harboring contiguous regions of DCIS and IDC were selected. Separate histological samples from the DCIS and the neighboring IDC were obtained using tissue microarrays. The erbB2 and ER/PR statuses were assessed using immunohistochemistry (erbB2 and ER/PR) and fluorescence in situ hybridization (FISH - only erbB2). RESULTS The expression of erbB2 did not differ in the DCIS and IDC components of the breast tumors (p=0.35). There was good agreement in sample-by-sample comparisons of erbB2 (intraclass correlation coefficient [ICC]=0.78), PR (ICC=0.61) and ER (ICC=0.70) expression in the DCIS and IDC components. CONCLUSION Our findings suggest that the expressions of erbB2 and ER/PR do not differ in the contiguous regions from DCIS to IDC.

Molecular Subtypes of Breast Cancer Are Not Associated with the Clinical Under- or Overstaging of Breast Cancer

Purpose to evaluate the agreement between the clinical and pathological stagings of breast cancer based on clinical and molecular features. Methods this was a cross-sectional study, in which clinical, epidemiological and pathological data were collected from 226 patients who underwent surgery at the Prof. Dr. José Aristodemo Pinotti Womens Hospital (CAISM/Unicamp) from January 2008 to September 2010. Patients were staged clinically and pathologically, and were classified as: understaged, when the clinical staging was lower than the pathological staging; correctly staged, when the clinical staging was the same as the pathological one; and overstaged, when the clinical staging was greater than the pathological staging. Results understaged patients were younger (52.2 years; p < 0.01) and more symptomatic at diagnosis (p = 0.04) when compared with correctly or overstaged patients. Clinicopathological surrogate subtype, menopausal status, parity, hormone replace therapy and histology were not associated with differences in staging. Women under 57 years of age were clinically understaged mainly due to underestimation of T (tumor staging) (p < 0.001), as were the premenopausal women (p < 0.01). Patients whose diagnosis was made due to clinical complaints, and not by screening, were clinically understaged due to underestimation of N (lymph nodes staging) (p < 0.001). Conclusion the study shows that the clinicopathological surrogate subtype is not associated with differences in staging, while younger women diagnosed because of clinical complaints tend to have their breast tumors understaged during clinical evaluation.