Stem cell markers: A guide to neoadjuvant therapy in breast carcinomas

Aim: This study aims to investigate potential associations between the stem cell population and the degree of tumor regression in breast carcinomas treated with neoadjuvant therapy. Settings and Design: The study included 92 patients with breast carcinoma who received neoadjuvant therapy. Tumor regression was defined based on Miller and Payne grading system. Patients with grade 1 or 2 regression on a 5-point scale were included in group 1 (n = 37), grade 3 regression in group 2 (n = 32), and grade 4 or 5 regression in group 3 (n = 23). Materials and Methods: Immunohistochemical staining was performed on paraffin block sections of every case using CD44, CD24, CD29, CD133, ID4, and ALDH1 antibodies to detect stem cells. Statistical Analysis Used: IBM Statistical Package for the Social Sciences (SPSS), version 23.0 (IBM Corp., Armonk, NY, USA) software was used for statistical analyses, and a P value less than 0.05 was considered statistically significant. Results: Histologically high-grade tumors are more common in the near-complete/complete response group (P = 0.004). HER2-positive tumors were more common in the complete/near-complete response group (P = 0.054). Tumor cells positive for stem cell markers CD44 and CD24 were more common in the poor response group (P = 0.027 and P = 0.001, respectively). CD29 expression was reduced in the posttreatment residual tumor tissue in the near-complete/complete response group. Conclusion: High CD44 and CD24 expression may be a predictor of poor response/nonresponse to neoadjuvant therapy in breast carcinomas. Background: In recent years, stem cells have been defined as the main cell population responsible for resistance to anticancer therapies.

Reconstrução de parede torácica em extensas ressecções oncológicas / Reconstruction of the chest wall in extensive oncological resections

Introdução: Apesar do avanço no diagnóstico e no tratamento das pacientes com neoplasia mamária, ainda há casos que se apresentam como doença localmente avançada. Nesse contexto, o controle oncológico requer ressecções extensas e complexos procedimentos reparadores. A participação do cirurgião plástico nas equipes multidisciplinares de tratamento oncológico tem apresentado importância crescente tanto nas etapas de planejamento como de execução. O objetivo é analisar prospectivamente casos de pacientes com extensas ressecções no tórax e reconstrução de parede torácica quanto aos seus resultados e complicações no período de 2014-2016. Métodos: Seguimento prospectivo por 6 meses de 15 casos de pacientes submetidas a extensas ressecções oncológicas no tórax e reconstrução por um mesmo cirurgião plástico em hospitais da rede pública de São Paulo-SP. Foram coletados os dados: idade, diagnóstico, queixa pré-operatória, extensão da área de ressecção e incidência de complicações locais. Resultados: As pacientes tinham idade média de 49,2 anos, a queixa mais comum era massa papável, o diagnóstico mais comum era neoplasia da mama (80%), a maioria das ressecções preservou o plano muscular e a área média de ressecção foi de 259,2 cm2. O retalho miocutâneo do grande dorsal em V-Y foi o mais utilizado, e o toracoabdominal foi o segundo. Epiteliólise foi detectada em 13,3% das pacientes e necrose parcial menor que 5% do retalho em 13,3%. Conclusão: Na presente casuística, as pacientes portadoras de neoplasias extensas no tórax representaram um desafio para a reconstrução local, necessitando de planejamento pré-operatório minucioso e com múltiplas opções. A participação do cirurgião plástico no tratamento desses casos contribuiu para redução de morbidade e demonstrou baixo índice de complicações.

Introduction: In spite of advances in the diagnosis and treatment of patients with breast cancer, there are still cases that present with locally advanced disease. In this context, cancer control requires extensive resections and complex repair procedures. The participation of the plastic surgeon in the multidisciplinary cancer treatment teams has been increasingly important in both the planning and execution stages. The aim of this study is to prospectively analyze patients who underwent extensive chest resections and thoracic wall reconstruction with regard to their results and complications in the period 2014-2016. Methods: Prospective 6-month follow-up of 15 patients who underwent extensive oncological resections in the chest and reconstruction by the same plastic surgeon in public hospitals of São Paulo was done. The following data were collected: age, diagnosis, preoperative complaint, extent of resection area, and incidence of local complications. Results: Patients had a mean age of 49.2 years, the most common complaint was a papillary mass, the most common diagnosis was breast cancer (80%), the most resection area preserved was the muscular plane, and the mean resection area was 259.2 cm2. The V-Y latissimus dorsi myocutaneous flap was the most used, and the thoracoabdominal flap was the second. Epitheliolysis was detected in 13.3% of the patients, and partial necrosis less than 5% of the flap in 13.3%. Conclusion: In the present study, patients with extensive cancers in the thorax presented a challenge for local reconstruction, requiring detailed preoperative planning and multiple options. The participation of the plastic surgeon in the treatment of these patients contributed to the reduction of morbidity rate and low rate of complications.

Research Progress on the Relationship between Metabolic Syndrome and Triple-Negative Breast Cancer / 天津医药

Metabolic syndrome (MS) and breast cancer are common diseases of women. Triple negative breast cancer (TNBCs) is one type of breast cancer, which is of much attention in recent years. Important components of MS include central obesity, high blood sugar, high triglycerides and low level of high-density lipoprotein (HDL-C), which increased the inci-dence risk of TNBCs. Common biomarkers of MS including insulin, adiponectin and leptin play an important role in the oc-currence and development of breast cancer, especially TNBCs. Insulin-like growth factor-IImRNA binding protein 3 (IMP3, an oncofetal protein) may be TNBCs’new invasive cancer biomarkers. In this paper, the research progress on the relation-ship between MS and TNBCs is reviewed.

Ultrasonography and histology correlation in BI-RADS 4/5 small breast lesions among Thai patients.

Background: Ultrasonography is an important imaging tool in detection of small breast cancers, particularly in younger women with dense breasts. Among the ultrasonographic characteristics for the malignancy, it is unclear which are common or more predictive. Objective: Analyze breast ultrasonograms and determine the common and predictive characteristics of the BIRADS 4/5 small breast lesions that were correlated with histology-proved carcinoma among Thai patients. Methods: Data were collected retrospectively between November 2006 and September 2007 at King Chulalongkorn Memorial Hospital. Forty-five BI-RADS 4 or 5 small breast lesions from 41 patients were reviewed for ultrasonographic characteristics and for correlation between each of these features and histology-proved malignancy. Results: There were 15 out of 30 lesions of BI-RADS 4 and 14 out of 15 of BI-RADS 5 that were histologically proven breast carcinoma. The lesion dimension ranged from 0.27 cm to 1.5 cm (mean: 0.98 cm). The malignant signs that were common consisted of irregular shapes (70%) and posterior shadowing (35.6%). However, the most correlating signs for malignancy were vascularity of the lesion 100%, and spiculated margins 100%. The other characteristics for malignancy, in descending order, were marked hypoechoicity 88.9%, microcalcifications within mass 85.7%, echogenic halo 83.3%, shadowing 81.3%, branched pattern 77.8%, duct extension 75%, irregular shape72.2%, and taller than wide orientation 70%. Conclusion: Irregular shape and shadowing were the two most common malignant signs that characterized BIRADS 4, 5 small breast lesions by ultrasonography. However, the most predictive signs were increases in vascularity and spiculated margins.

Carcinomas mamários de tipo basal: perfil clínico-patológico e evolutivo / Basal-like breast cancers: clinicopathological features and outcome

OBJETIVO: Investigar a frequência de carcinomas mamários de fenótipo basal em uma série de tumores triplo-negativos (TTN), definidos pela negatividade para receptores de estrógeno (RE), de progesterona (RP) e HER2. MÉTODOS: Selecionamos 140 TTN, obtendo-se características clínico-patológicas e sobrevida. Microarranjo de tecido (2 cilindros de cada tumor) foi construído e submetido à imunoistoquímica para RE, RP, HER2, citoqueratinas (Cks) 5 e 14, EGFR, p63 e p53. Consideramos carcinomas de fenótipo basal os tumores negativos para RE, RP e HER2, e positivos para CK5. RESULTADOS: Encontramos 105 carcinomas de fenótipo basal entre 140 TTN (frequência=75 por cento). A idade média das pacientes foi de 54,8 anos, sendo que 34,3 por cento estavam na pré-menopausa. A maioria dos tumores foi classificada como carcinoma ductal invasor de alto grau. Os TTN exibiram positividade para CK5 (75,0 por cento), CK14 (29 por cento), EGFR (36,4 por cento), p63 (28,6 por cento) e p53 (67,1 por cento). Estadiamento avançado da doença foi observado em 52 pacientes (50 por cento), com diâmetro tumoral maior que 5 cm em 41 casos (39 por cento) e metástases axilares em 61 casos (59,2 por cento). Seguimento clínico foi obtido em 89 pacientes (média=51 meses). Destas, 45 pacientes (50,5 por cento) evoluíram sem doença; 6 (6,7 por cento) estavam vivas com doença e 38 (42,6 por cento) morreram pelo câncer. Recidiva sistêmica ocorreu em 42 pacientes (47,1 por cento), sendo pulmões, cérebro e ossos os principais sítios de metástases. As médias das sobrevidas global e livre de doença foram de 36 e 28 meses, respectivamente. CONCLUSÕES: Nosso estudo confirma comportamento clínico agressivo e elevada frequência dos carcinomas de fenótipo basal entre os TTN, semelhante ao descrito em casuísticas norte-americanas e europeias.

OBJECTIVE: The aim of our study was to investigate basal phenotype in a series of triple-negative (estrogen and progesterone receptors-negative and HER2-negative) invasive mammary carcinomas. METHODS: We selected 140 previously tested triple-negative tumors. Clinical, histopathological and survival data were obtained. A tissue microarray containing 2 cylinders from each tumor was constructed and immunohistochemistry for estrogen receptor (ER), progesterone receptor (PR), HER2, cytokeratins (CK) 5 and 14, EGFR, p63, and p53 was performed. We considered basal like-cancers (BLC) those tumors that were ER/PR/HER2-negative and CK5-positive. RESULTS: We found 105 cases of BLC from 140 triple-negative tumors (frequency=75.0 percent). The mean age at diagnosis was 54.8 years-old and 34.3 percent were premenopausal women. The majority of tumors were high grade (83.7 percent) and of ductal/no-special-type (80.8 percent). Triple-negative tumors showed immunoreactivity for CK5 (75.0 percent), CK14 (29.0 percent), EGFR (28.6 percent), p63 (28.6 percent), and p53 (67.1 percent). Tumor size larger than 5cm was observed in 41 cases (39.0 percent) and axillary metastases were detected in 61 patients (59.2 percent). Follow-up was recorded for 89 patients (mean=51 months): 45 patients (50.5 percent) with no evidence of disease; 6 patients (6.7 percent) were alive with disease; and 38 patients (42.6 percent) died of the disease. Relapse was detected in 42 women (47.1 percent), lungs, brain, and bones being the most common sites of metastasis. The mean overall survival was 36 months and the mean disease-free interval was 28 months. CONCLUSION: Our findings confirmed that BLC are poor prognosis and highly-frequent carcinomas among triple-negative tumors, similar to data previously reported in North American and European patients.

Interval Breast Cancers: Comparisons with Screen Detected Cancers

PURPOSE: Although the screening with a mammography has been shown to reduce breast cancer mortality, it has limitations relating to its sensitivity and efficacy. Interval cancers are those that become symptomatic, and are detected between screening examinations. The success of a screening program in reducing the rate of mortality due to breast cancer relies on keeping the number of interval cancers at a minimum. This study was performed to review the mammographic features of interval cancers, and to compare their clinicopathological factors with those cancers detected by screening. METHODS: Of the 881 women who had operations for breast cancer performed between 1995 and 1999, we retrospectively analyzed the medical records and mammograms of 57 who received at least a mammogram before the diagnosis of their breast cancer. These patients were divided into an interval cancer group, who had symptoms, and a screen detected cancer group, who had not. The factors compared included the clinical, radiographic, histopathological, and immunohistochemical features. RESULTS: Interval cancers were more likely to have masses, than microcalcifications, in their mammographic features, and were more likely to be invasive and at a higher stage according to their histopathological features. The false negative rate was 48% for the screen detected cancers, and 35% for the interval cancers (P=0.414). HRT users had the higher false negative rate of 51.6% than the 26.9% for the nonuser (P=0.103). CONCLUSION: The interval cancers were found to be different from the screen detected cancers in terms of their radiological and pathological features. The standardization of screen interval, and additional magnification mammography, or ultrasonography may contribute to reduce false negative rates of mammography.

Microcalcification Classifications on Mammography and Breast Cancer Incidences / 대한암학회지

PURPOSE: Since needle localization biopsy was introduced, it is widely performed for nonpalpable microcalcified breast lesions, but there are many controversies in determining the disease characteristics and guidelines of the biopsy for microcalcifications detected mammographically in the absence of any palpable mass. This study was designed to detennine the breast cancers according to microcalcification types. MATERIALS AND METHODS: We reviewed 91 patients, who underwent breast biopsies between January 1995 and June 1998 for only microcalcified lesions detected by mammography at the Department of Surgery, Korea University Hospitals. Microcalcifications were defined as calcifications less than 1.0 mm. The needle localization biopsy was performed only on patients who were found to have five or more microcalcifications. We classified the mictocalcifications into three types; casting type, crushed-stone-like type, and amorphous type. RESULTS: The mean age was 49 years (25 82 years). Sixteen patients (17.6%) among the 91 patients were diagnosed with the breast cancer; four (22.2%) of 18 patients with casting type, eight (21.6%) of 37 patients with crushed-stone-like type, and four (11.1%) of 36 patients with amorphous type microcalcifications. Breast cancers were more prevalent in casting and crushed-stone-like types than in amorphous types. There was no difference in the size of microcalcifiations between benign and malignant lesions 13.11+-10.89 rnm vs 13.13+-9.51 mm. CONCLUSIONS: The patients who have more than 5 microcalcifications clustered within 1 cm circle detected at mammographic evaluation, especially in case of casting or crushed-stone-like type, should be advised to have localization biopsy to detect early breast cancer.