Leonardo Ribeiro Soares

Effect of Tamoxifen and Raloxifene on the Proliferative Activity of the Breast Epithelium in Premenopausal Women

Objectives To compare the effects of tamoxifen and raloxifene on the proliferative activity of normal breast tissue in premenopausal women as measured by Ki-67/MIB-1 expression. Study Design A total of 48 women with benign breast nodules and a recommendation for surgical removal of the lesion took part in this study. They were randomized to use tamoxifen or raloxifene for 22 days, after which they were submitted to surgery. During the surgical procedure, a 1-cm fragment of normal breast tissue was removed to study Ki-67 expression. Results The mean percentage ratios between immunolabeled and non-labeled cells were 2.02 ± 1.09 and 3.13 ± 3.23 for the tamoxifen and raloxifene groups, respectively. There was no statistically significant difference between the tamoxifen (n = 16) and raloxifene (n = 14) groups in relation to the immunohistochemical analysis of Ki-67 (P = 0.205). Conclusion The results of this study showed no difference between tamoxifen and raloxifene with respect to the potential of these drugs to reduce the proliferative activity of the normal breast epithelium in premenopausal women.

Effect of Ki-67 on Immunohistochemical Classification of Luminal A to Luminal B Subtypes of Breast Carcinoma.

It has recently been proposed to include an immunohistochemical marker of cell proliferation, Ki‐67, as an element with which to classify the molecular subtypes of breast cancer. The objective of this study was to evaluate the effect of the introduction of the Ki‐67 marker on the molecular classification of breast cancer by immunohistochemistry. This study was performed on 234 cases of invasive ductal carcinoma of the breast submitted to two immunohistochemical classification panels, one including Ki‐67 and the other not. The data obtained with the two classifications were correlated with well‐established prognostic factors such as histologic grade, the number of lymph nodes affected and tumor size. The molecular classification without Ki‐67 identified: 136 cases of luminal A (58.1%), 19 cases of luminal B (8.1%), 27 cases of human epidermal growth‐factor receptor 2 overexpressing (11.5%), 27 cases of basal‐like (11.5%), and 25 cases of nonbasal‐like triple‐negative tumors (10.7%). When Ki‐67 was included, this situation changed significantly, with the following cases being identified: 72 cases of luminal A (30.8%) and 83 cases of luminal B tumors (35.5%), resulting in a Kappa score of 0.216. Evaluation of correlations between the luminal A and luminal B tumor subtypes and the selected prognostic factors showed a statistically significant difference only when Ki‐67 was included and only with respect to histologic grade (p < 0.001). The new classification with Ki‐67 significantly altered the prevalence of the luminal A and luminal B subtypes and improved correlation with the histologic grade.

Visceral adiposity increases the risk of breast cancer: a case-control study

INTRODUCTION in recent decades, lifestyle changes in women involving physical inactivity, insulin resistance and body fat distribution have been associated with an increase in breast cancer. OBJECTIVE to assess whether insulin resistance, lipid profile, and visceral adiposity are associated with increased risk of breast cancer. METHODS a hospital-based case control study was conducted with 116 women newly diagnosed with breast cancer and 226 controls. Body mass index, waist circumference, total cholesterol, high-density lipoproteins (HDL), low-density lipoproteins (LDL), very-low-density lipoproteins (VLDL), triglycerides, glycated hemoglobin, HOMA-IR, HOMA-β, lipid accumulation product (LAP), and visceral adiposity index (VAI) were assessed. Logistic regression was adjusted for body mass index and age to quantify the association between breast cancer risk and insulinresistance, dyslipidemias, and visceral adiposity. RESULTS the case group had higher insulin resistance (p < 0.001), LAP (p = 0.012), and VAI (p = 0.004), and lower concentrations of HDL (p = 0.024) and HOMA-β(p = 0.010) compared to the control. Insulin resistance (OR = 3.00, 95% CI: 1.75-5.17, p < 0.001) and higher VAI (OR = 1.91, 95% CI: 1.17-3.13, p = 0.01) were associated with breast cancer, whereas the highest concentration of HDL reduces the chances of cancer by 53% (95% CI: 0.32-0.86, p = 0.026). In the multivariate analysis, only LAP and VAI were associated to breast cancer. CONCLUSIONS visceral fat accumulation increases the risk of breast cancer.

Music Therapy Reduces Radiotherapy-Induced Fatigue in Patients With Breast or Gynecological Cancer: A Randomized Trial

Purpose: To investigate the influence of music therapy on the reduction of fatigue in women with breast or gynecological malignant neoplasia during radiotherapy, since it is one of the most frequent side effects of this type of treatment, and may interfere with self-esteem, social activities, and quality of life. Experimental Design: Randomized controlled trial (control group [CG] and music therapy group [MTG]) to assess fatigue, quality of life, and symptoms of depression in women undergoing radiotherapy using the Functional Assessment of Cancer Therapy: Fatigue (FACT-F) version 4, Functional Assessment of Cancer Therapy–General (FACT-G) version 4, and Beck Depression Inventory in 3 separate times, namely, during the first week of radiotherapy, on the week of the intermediary phase, and during the last week of radiotherapy. Individual 30- to 40-minute sessions of music therapy with the presence of a trained music therapist were offered to participants. Results: In this study, 164 women were randomized and 116 (63 CG and 53 MTG) were included in the analyses, with mean age of 52.90 years (CG) and 51.85 years (MTG). Participants in the MTG had an average of 10 music therapy sessions, totaling 509 sessions throughout the study. FACT-F results were significant regarding Trial Outcome Index (P = .011), FACT-G (P = .005), and FACT-F (P = .001) for the MTG compared with the CG. Conclusions: Individual music therapy sessions may be effective to reduce fatigue related to cancer and symptoms of depression, as well as to improve quality of life for women with breast or gynecological cancer undergoing radiotherapy. Further well-designed research studies are needed to adequately determine the effects of music therapy on fatigue.

The impact of mammography screening on the surgical treatment of breast cancer

Dear Editor, Marcon et al conducted a retrospective study in Switzerland and evaluated the impact of mammography screening on the surgical treatment of 262 women with breast cancer. Mastectomy was performed in 16/92 patients (17.4%) whose breast cancer was identified at screening and in 55/170 (32.3%) whose diagnosis was based on clinical findings. Conservative breast surgery was performed on 82.6% of the patients whose diagnosis was made at screening and on 67.6% of those whose diagnosis was clinical. In Brazil, despite the geographical and population differences, advancement in the surgical treatment of breast cancer has been similar. In a recent analysis of 193 596 breast surgeries performed within the Brazilian National Health Service between 2008 and 2014, a reduction was found in the number of simple mastectomies and of lymphadenectomies, while the rates of conservative surgery remained stable. Nevertheless, the overall rate of patients undergoing breast reconstruction increased from 15% in 2008% to 29.2% in 2014. This outcome may be a consequence of the cancer being diagnosed at earlier stages due to the increased coverage of mammography screening in Brazil. Among the limitations of the study conducted by Marcon et al, the small sample size and the fact that the surgeries evaluated were performed at a single treatment center merit particular attention. Therefore, the indications for surgery may reflect regional peculiarities and may not necessarily be a result of mammography screening. In Brazil, for example, a study conducted in a referral hospital for breast cancer treatment analyzed the 403 surgeries performed between 2002 and 2009 and found an annual increment of nine mastectomies (P = 0.04). Nevertheless, over the same period, there was an increase in the number of advanced cases of the disease in that hospital, which explains the differences between these findings and the nationwide patterns. Finally, the difficulties in accessing health care services found in some regions of Brazil should be emphasized, as well as the absence of an effective population‐based screening program. In 2013, the nationwide estimated mammography coverage within the public health care system was only 24.8%, ranging from 7.5% to 35.7% in the different states in the country. The barriers to mammography screening in Brazil include the limited access of the population to information and to health care services, the geographical distribution of mammography machines that tend to be concentrated in the major cities, the inadequate quality of mammography in some centers, and the delay in treatment following a diagnosis of breast cancer.5–7 Therefore, the consolidation of organized population‐based breast cancer screening and the elaboration of public policies for the management of breast cancer in Brazil will make the advances associated with the surgical treatment of the disease more effective.

Abdominal Adiposity and Physical Inactivity Are Positively Associated with Breast Cancer: A Case-Control Study

Objective To examine whether breast cancer is associated with body composition and level of physical activity, considering the menstrual status. Methods This was a case-control study with 116 women recently diagnosed with breast cancer and 226 controls. Body composition was assessed by dual-energy X-ray absorptiometry, and cardiometabolic risk was assessed by conicity index and waist-to-height ratio. The short version of the International Physical Activity Questionnaire was used to estimate the level of physical activity. All analyses were adjusted for age and BMI. Results The total body fat percentage, android body fat, android-gynoid ratio, and waist circumference were positively associated (p < 0.05), whereas the percentage of lean body mass (p <0.05) and the level of physical activity (p < 0.01) were inversely associated with breast cancer in premenopausal women. Among postmenopausal women, physical activity decreased the chance of developing breast cancer by 49% (95% CI = 0.29 to 0.92, p = 0.02). Conclusion A low percentage of lean body mass and high abdominal adiposity in the premenopausal period increase the chances of developing breast cancer. Regular physical activity is inversely associated with breast cancer in pre- and postmenopausal women.

Complete axillary dissection without drainage for the surgical treatment of breast cancer: a randomized clinical trial

OBJECTIVE: This randomized clinical trial evaluated the possibility of not draining the axilla following axillary dissection. METHODS: The study included 240 breast cancer patients who underwent axillary dissection as part of conservative treatment. The patients were divided into two groups depending on whether or not they were subjected to axillary drainage. ClinicalTrials.gov: NCT01267552. RESULTS: The median volume of fluid aspirated was significantly lower in the axillary drainage group (0.00 ml; 0.00 – 270.00) compared to the no drain group (522.50 ml; 130.00 - 1148.75). The median number of aspirations performed during conservative breast cancer treatment was significantly lower in the drainage group (0.5; 0.0 - 4.0) compared to the no drain group (5.0; 3.0 - 7.0). The total volume of serous fluid produced (the volume of fluid obtained from drainage added to the volume of aspirated fluid) was similar in the two groups. Regarding complications, two cases (2.4%) of wound dehiscence occurred in the drainage group compared to 13 cases (13.5%) in the group in which drainage was not performed, with this difference being statistically significant. Rates of infection, necrosis and hematoma were similar in both groups. CONCLUSION: Safety rates were similar in both study groups; hence, axillary dissection can feasibly be performed without drainage. However, more needle aspirations could be required, and there could be more cases of wound dehiscence in patients who do not undergo auxiliary drainage.

The accuracy of the SONOBREAST statistical model in comparison to BI-RADS for the prediction of malignancy in solid breast nodules detected at ultrasonography

OBJECTIVE The objective of the present study was to compare the accuracy of SONOBREAST for the prediction of malignancy in solid breast nodules detected at ultrasonography with that of the BI-RADS system and to assess the agreement between these two methods. STUDY DESIGN This prospective study included 274 women and evaluated 500 breast nodules detected at ultrasonography. The probability of malignancy was calculated based on the SONOBREAST model, available at www.sonobreast.com.br, and on the BI-RADS system, with results being compared with the anatomopathology report. RESULTS The lesions were considered suspect in 171 cases (34.20%), according to both SONOBREAST and BI-RADS. Agreement between the methods was perfect, as shown by a Kappa coefficient of 1 (p<0.001). SONOBREAST and BI-RADS proved identical insofar as sensitivity (95.40%), specificity (78.69%), positive predictive value (48.54%), negative predictive value (98.78%) and accuracy (81.60%) are concerned. With respect to the categorical variables (BI-RADS categories 3, 4 and 5), the area under the receiver operating characteristic (ROC) curve was 94.41 for SONOBREAST (range 92.20-96.62) and 89.99 for BI-RADS (range 86.60-93.37). CONCLUSIONS The accuracy of the SONOBREAST model is identical to that found with BI-RADS when the same parameters are used with respect to the cut-off point at which malignancy is suspected. Regarding the continuous probability of malignancy with BI-RADS categories 3, 4 and 5, SONOBREAST permits a more precise and individualized evaluation.

Is the combination of fat grafts and platelet rich plasma effective in rats

PURPOSE: To investigate if the association of fat grafts and platelet-rich plasma (PRP) improves graft viability in female rats. METHODS: This is an experimental, randomized and blinded study, which involved 47 rats. Fat was harvested from the inguinal region and grafted to the cranial region. The experimental group consisted of PRP-enriched fat grafts (n=22) whilst the control group consisted of fat graft only (n=25). After a 100-day period, the animals were euthanised and the fat grafts were analyzed using scores from 0 (absent) to 4 (abundant), in optical microscopy by two independent and blinded pathologists. RESULTS: Regarding fat graft cell viability, the PRP group scored moderate/abundant in 63% of cases and the fat graft only group scored absent/slight in 72% of cases (p=0.03). The PRP group also presented lower fat necrosis scores when compared to the fat graft only group (p=0.03). Tumors (dermoid cysts) within the fat grafts were observed in three animals in which the grafts were mixed with PRP. CONCLUSION: Platelet-rich plasma improves the viability and integration of fat grafts in rats, but more studies are needed to fully understand the exact mechanisms that lead to this improvement and assess the safety of the method for use in humans.

Doença de Paget da mama: experiência de um centro universitário

Objetivo: Determinar a prevalencia de doenca de Paget da mama (DPM) entre os casos de carcinomas ductais diagnosticados em um centro universitario, entre 2003 e 2007, descrever as caracteristicas clinicas e analisar a sobrevida desses casos. Metodos: Estudo de coorte retrospectiva, por meio da revisao de prontuarios medicos. Foi realizada analise de frequencia para todas as variaveis e utilizada curva de Kaplan-Meier para a representacao da sobrevida global. Resultados: De 278 casos de carcinomas ductais de mama, houve 14 casos de DPM, determinando prevalencia de 5,0%. Um caso foi excluido da analise por apresentar dados incompletos. A media de idade ao diagnostico foi de 57,1 (±11,2) anos. Dos casos analisados, 11 (84,6%) apresentavam tumor palpavel, e 9 (69,3%), lesao do complexo areolo-papilar (CAP). Apenas um caso nao foi submetido a mastectomia, por obito durante quimioterapia neoadjuvante. Radioterapia foi realizada em 6 casos (46,2%), quimioterapia, em 11 casos (84,6%), e endocrinoterapia, em 6 casos (46,2%). A imunoistoquimica identificou 5 casos (38,5%) com expressao de receptores hormonais e 12 casos (92,3%) com superexpressao de HER2. A sobrevida global das pacientes foi de 61,5 (±13,4) meses e nao houve recidiva local apos um tempo medio de seguimento de 75,8 meses. Conclusao: Observou-se prevalencia de DPM associada a carcinomas invasores com estadio clinico avancado, o que possivelmente ocasionou sobrevida global inferior a observada em estudos previos para a regiao. Objective: To determine the prevalence of Pagets disease of the breast (PD) among cases of ductal carcinomas diagnosed in a university hospital between 2003 and 2007; describe clinical characteristics and analyze the survival of these cases. Methods: Retrospective cohort study, by reviewing medical records. Frequency analysis was performed for all variables and used Kaplan-Meier curve for the representation of overall survival. Results: In 278 cases of breast ductal carcinoma, 14 cases were PD determining prevalence of 5.0%. A case was excluded from analysis because of incomplete data. The mean age at diagnosis was 57.1 (±11.2) years. Of the cases analyzed, 11 (84.6%) had palpable tumor and 9 (69.3%) presented lesion of the nipple-areola complex. Only one case was not submitted to mastectomy because she died during neoadjuvant chemotherapy. Radiotherapy was performed in six cases (46.2%); chemotherapy in eleven cases (84.6%); endocrinoterapia in six cases (46.2%). Immunohistochemistry identified five cases (38.5%) with expression of hormone receptors and twelve patients (92.3%) with overexpression of HER2. The overall survival of patients was 61.5 (±13.4) months, and there was no local recurrence after a mean follow-up of 75.8 months. Conclusion: There was a prevalence of Pagets disease of the breast associated with invasive carcinomas with advanced clinical stages; which possibly resulted in overall survival rate lower than that observed in other studies for the region.