Diagnosing molecular subtypes of breast cancer by means of Raman spectroscopy.

OBJECTIVES: Raman spectroscopy has been used to discriminate human breast cancer and its different tumor molecular subtypes (luminal A, luminal B, HER2, and triple-negative) from normal tissue in surgical specimens. MATERIALS AND METHODS: Breast cancer and normal tissue samples from 31 patients were obtained by surgical resection and submitted for histopathology. Before anatomopathological processing, the samples had been submitted to Raman spectroscopy (830 nm, 25 mW excitation laser parameters). In total, 424 Raman spectra were obtained. Principal component analysis (PCA) was used in an exploratory analysis to unveil the compositional differences between the tumors and normal tissues. Discriminant models were developed to distinguish the different cancer subtypes by means of partial least squares (PLS) regression. RESULTS: PCA vectors showed spectral features referred to the biochemical constitution of breast tissues, such as lipids, proteins, amino acids, and carotenoids, where lipids were decreased and proteins were increased in breast tumors. Despite the small spectral differences between the different subtypes of tumor and normal tissues, the discriminant model based on PLS was able to discriminate the spectra of the breast tumors from normal tissues with an accuracy of 97.3%, between luminal and nonluminal subtypes with an accuracy of 89.9%, between nontriple-negative and triple-negative with an accuracy of 94.7%, and each molecular subtype with an accuracy of 73.0%. CONCLUSION: PCA could reveal the compositional difference between tumors and normal tissues, and PLS could discriminate the Raman spectra of breast tissues regarding the molecular subtypes of cancer, being a useful tool for cancer diagnosis.

Correlação entre as medidas antropométricas e o comprometimento linfonodal de pacientes pós-menopausadas com câncer de mama / Correlation between anthropometric measurements an lymph node metastases in postmenopausal women with breast cancer

Introdução: Diversos estudos epidemiológicos observaram que mulheres obesas na pós-menopausa apresentam aumento de risco e mortalidade do câncer de mama. Apesar de não haver consenso, alguns estudos demonstraram maior grau de comprometimento dos linfonodos axilares nessas pacientes, o que pode contribuir para o pior prognóstico da doença nesse grupo. Objetivo: Avaliar a correlação entre as medidas antropométricas e o grau de comprometimento linfonodal axilar em pacientes pós-menopausadas com câncer de mama hormônio-responsivo. Métodos: Estudo prospectivo analítico com 57 mulheres com carcinoma ductal invasivo no estágio II, na pós-menopausa, com receptores hormonais positivos (receptor estrogênico e/ou receptor de progesterona - RE/RP), tratadas nos hospitais São Paulo e Pérola Byington. Logo após o diagnóstico foram realizadas as medidas antropométricas (IMC, CA, CQ e RCQ) das pacientes e, após o tratamento cirúrgico e avaliação histopatológica dos linfonodos axilares, realizou-se o estudo estatístico. Resultados: Observou-se associação significativa entre o número de linfonodos acometidos e o sobrepeso (IMC> 25 kg/m2) (p = 0,0329). Cerca de 64% das pacientes com mais de três linfonodos acometidos apresentaram IMC> 25 kg/m2. Entretanto, não houve diferença estatística entre as medidas antropométricas e a positividade dos linfonodos axilares de forma global. Conclusão: O número de linfonodos axilares comprometidos foi maior em pacientes com índice de massa corpórea entre 25 e 30 kg/m2.

Introduction: Several epidemiological studies have shown an increased risk and mortality in breast cancer of obese postmenopausal women. The higher number of lymph node metastases in these patients could contribute to poor prognosis. Objective: To evaluate the correlation between the anthropometric measurements and lymph node metastases in postmenopausal women with breast cancer expressing hormone receptors (ER/PgR). Methods: Prospective study with 57 women with invasive ductal carcinoma, stage II and estrogen receptor and/or progesterone receptor (ER/PgR) positivity treated in São Paulo and Pérola Byington Hospital. Anthropometric datawere obtained after the diagnoses, and statistical analysis was done after surgery treatment and definitive pathology results of axillary lymph nodes dissection. Results: There was a significant association (p = 0.0329) between the number of axillary lymph node metastases and overweight (BMI > 25 kg/m2). Almost 64% of patients with more than three lymph node metastases had more than 25 kg/m2. However, there were no statistical significance between the correlation of anthropometric measurements and the global number of axillary lymph node metastases. Conclusion: The number of axillary lymph node metastases was higher in patients with body mass index between 25 and 30 kg/m2.

Estudo do biomarcador p16 no carcinoma de mama de mulheres submetidas à endocrinoterapia primária de curta duração com tamoxifeno e anastrol / Study of p16 biomarker after short-period primary endocrinotherapy with tamoxifen and anastrozole in postmenopausal women with breast carcinoma

Frequentes deleções e mutações têm sido descritas no gene p16 em diversos tipos de tumores, mas pouco se sabe sobre o valor preditivo do p16 na hormonioresistência ao tratamento do câncer de mama. Objetivos: Estudar a expressão do p16 e dos receptores de estrogênio e progesterona (RE e RP) em pacientes com carcinoma de mama RE e/ ou RP (+) após curto período (26 dias) de tratamento com tamoxifeno, anastrozol e placebo. Métodos: Estudo prospectivo randomizado duplo-cego realizado com 58 pacientes na pós-menopausa diagnosticadas com carcinoma ductal invasivo de mama nos estádios II e III, que no período pré-operatório foram subdivididas em três grupos: P (placebo, n = 25), T (tamoxifeno 20 mg/dia, n = 15) e A (anastrozol 1 mg/dia, n = 18). A biópsia foi realizada no momento do diagnóstico e após a cirurgia definitiva (26° dia). Realizou-se o estudo semiquantitativo utilizando-se os critérios de Allred. Resultados: A positividade do p16 variou de 22 para 17%, respectivamente no pré e no pós-tratamento com anastrozol; variou de 8 para 4% no grupo placebo e não houve variação, com 7% de positividade no grupo que recebeu tamoxifeno. A comparação entre grupos e tempos não apresentou relação significativa para o p16 (p = 0,17). Não foi encontrada correlação entre a positividade do p16 e o status hormonal (RE e RP). Conclusão: Não houve diferença estatística significativa entre os três grupos estudados. Outros biomarcadores deverão ser pesquisados para se identificar precocemente a hormônio-resistência e a especificidade terapêutica.

Common deletions and mutations have been described in the p16 gene in various tumor types, but little is known about the predictive value of p16 in hormonioresistência the treatment of breast cancer. Objectives: To study the expression of p16 and estrogen receptor and progesterone (ER and PR) in patients with breast carcinoma ER and / or PR (+) after a short period (26 days) of treatment with tamoxifen, anastrozole and placebo. Methods: A prospective randomized double-blind study conducted with 58 postmenopausal patients diagnosed with invasive ductal breast carcinoma in stages II and III than in preoperative period were divided into three groups: P (placebo, n = 25) T (tamoxifen 20 mg / day, n = 15) and A (anastrozole 1 mg / day, n = 18). A biopsy was performed at diagnosis and after definitive surgery (26 days). We carried out the study using semiquantitative criteria Allred. Results: The positivity of p16 ranged from 22 to 17%, respectively, before and after treatment with anastrozole; ranged from 8 to 4% in the placebo group and no variation, with 7% positivity in the group receiving tamoxifen. The comparison between groups and time showed no significant relationship to the p16 (p = 0.17). No correlation was found between the positivity of p16 and hormonal status (ER and PR). Conclusion: There was no statistically significant difference among the three groups. Other biomarkers should be investigated for the early identification of resistance to hormone therapy and specificity.

Correlation Between Anthropometric Measures and Biomarker Changes After Neoadjuvant Therapy With Tamoxifen or Anastrozole in Postmenopausal Women With Breast Cancer.

BACKGROUND: Epidemiological studies have reported positive associations between anthropometric measures and risk for developing breast cancers that express hormone receptors and associated mortality. However, the impact of nutritional status on the molecular response to endocrine therapy has yet to be described. METHODS: Body mass index (BMI), waist circumference (WC), hip circumference (HP), and waist-to-hip ratio (WHR) were measured in patients with invasive ductal carcinoma (IDC) before and after neoadjuvant treatment with either tamoxifen or anastrozole, and a possible correlation with prognostic factors, as estrogen receptor (ER), progesterone receptor (PgR), and proliferative index (Ki-67), was analyzed. Fifty-seven patients with palpable ER-positive IDC were randomized into three neoadjuvant treatment groups and received anastrozole or placebo or tamoxifen for twenty-one days. Biomarker status was obtained by comparing the immunohistochemical evaluation of samples collected before and after treatment, using the Allred scoring system. Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS). RESULTS AND CONCLUSIONS: After treatment, the anastrozole group showed reduced ER and PgR expression (p < 0.05), and both the anastrozole and tamoxifen groups showed lower Ki-67 status. A significant reduction in PgR positivity (p < 0.05) was found in women with large WC and HC who were treated with anastrozole. Reduction in PgR positivity also tended to be associated with BMI (p = 0.09) in the anastrozole group. BMI, WC, HC and WHR correlated neither with biomarker levels in the tamoxifen and placebo groups nor with ER and Ki-67 status in the anastrozole group after primary endocrine treatment.