Gil Facina

Effects of low dose tamoxifen on normal breast tissue from premenopausal women

The aim of this study was to determine the effects of low doses of tamoxifen (5 and 10mg/day) for 50 days compared with the standard dose (20 mg/day) on breast biomarkers measured in normal breast tissue from premenopausal patients. A randomised double-blind study was performed using tissue from 56 premenopausal women with a diagnosis of fibroadenoma of the breast. Excisional biopsy was performed on the 50th day of therapy. Normal breast tissue samples were collected during surgery. The patients were divided in groups: A (placebo, n=11); group B (5 mg, n=16), group C (10 mg, n=14) and group D (20 mg, n=15). In this cross-sectional study, differences in the expression of Oestrogen Receptor alpha (ERalpha), Progesterone Receptor (PR), Ki-67, apoptotic bodies and mitotic index between the different groups after treatment can be seen on the normal breast tissue. We believe that a lower dose of tamoxifen could reduce the side-effects associated with treatment without affecting its chemopreventive activity in the breast.

Association between estrogen receptor gene polymorphisms and breast density in postmenopausal women

Objectives The aim of this study was to evaluate the association between clinical characteristics and polymorphisms HaeIII, MspI and XbaI of the estrogen receptor gene α with postmenopausal mammographic density. Methods A prospective study was performed with 120 women who were not users of hormones and had no identified breast lesions. All of them underwent bilateral mammography; the radiological density was determined by three independent observers, with two subjective evaluations based on the ACR-BIRADS® classification of mammographic patterns, 2003, and one computerized evaluation using the gray-scale histogram tool of the Adobe Photoshop® 7.0 software. Peripheral blood samples were obtained for DNA extraction, performed according to the GFX® Kit protocol (Amersham-Pharmacia). Polymerase chain reaction restriction fragment length polymorphism was carried out for an analysis of the polymorphisms present in intron 1 (HaeIII and XbaI) and in exon 1 (MspI) of the estrogen receptor gene. Results There was a high degree of concordance among the observers in the determination of mammary density (Kappa, Pearson and Spearman, p < 0.001). The associations of clinical characteristics with mammary density were: age (p = 0.04), body mass index (p < 0.0001) and age at menarche (p = 0.02). The relationship between the allele distribution of the polymorphisms and density was: XbaI (p = 0.02), HaeIII (p = 0.65) and MspI (p = 0.65). Conclusions Our data suggested that the polymorphism XbaI may be strongly related to mammographic density.

Estrogenic activity of tamoxifen on normal mammary parenchyma in the luteal phase of the menstrual cycle

Objectives: Tamoxifen, an anti‐estrogenic drug used in the adjuvant treatment of breast cancer, deserves more investigation for the determination of its efficacy as a prophylactic agent against breast cancer in high risk women. Thus, the action of tamoxifen on the human mammary gland was studied by measuring the number of lysosomes in normal mammary epithelium during the administration of tamoxifen. Methods: Tamoxifen was administered only during the luteal phase of the menstrual cycle to avoid interference with corpus luteum formation. A fragment of breast tissue adjacent to a fibroadenoma was obtained during surgery from 35 premenopausal women aged 15 to 37 years who had been eumenorrheic for at least 6 months; 18 of these patients were treated with tamoxifen and 17 were used as controls. Lysosome counts were performed under the light microscope on slides submitted to the acid phosphatase cytochemical technique and the data were analyzed statistically by the Mann‐Whitney test. Results: The fragments from the group treated with tamoxifen showed a significant decrease in lysosome numbers. Conclusions: Tamoxifen administered after ovulation significantly decreases the number of lysosomes in the cells of normal mammary epithelium, demonstrating the antiestrogenic effect of the drug on this target tissue.

Immunohistochemical expression of E-cadherin in sclerosing adenosis, ductal carcinoma in situ and invasive ductal carcinoma of the breast

E‐cadherin (EC) is an important glycoprotein cell‐adhesion molecule that appears to play a significant role in the progression of breast lesions. The objective of this study was to evaluate EC expression in sclerosing adenosis, ductal carcinoma in situ and invasive ductal carcinoma. Samples of breast lesions from 44 women were used in this study, comprising cases of sclerosing adenosis (n = 11), ductal carcinoma in situ (DCIS) (n = 10) and invasive ductal carcinoma (n = 23). Immunohistochemical evaluation of EC expression was assessed semiquantitatively and considered negative (<10% of cells with stained cytoplasmic membranes), positive+ (10–50% of cells stained) or positive++ (> 50% of cells stained). Fishers exact test was used to compare the distribution of staining intensity in the lesions (P< 0.05). There was a progressive loss of EC expression from benign to malignant lesions. This difference was statistically significant when sclerosing adenosis was compared with DCIS (P < 0.0002), when sclerosing adenosis was compared with invasive ductal carcinoma (P < 0.008) and when DCIS was compared with invasive ductal carcinoma (P < 0.007). The present findings point to a significant association between reduced EC expression and the progression and aggressivity of breast lesions. Diagn. Cytopathol. 2010.

Genetic Association Study of Angiotensin II Receptor Types 1 (A168G) and 2 (T1247G and A5235G) Polymorphisms in Breast Carcinoma among Brazilian Women

Background: Many types of cancer are associated with polymorphisms of the renin-angiotensin system. Our aim was to assess possible association between single-nucleotide polymorphisms (SNPs) of the angiotensin II receptor types 1 (A168G), and 2 (T1247G and A5235G) with breast cancer. Patients and Methods: 242 participating subjects were genotyped and allocated to case or control groups. Results: Genotype distribution (in %) was: for AGTR1 (A168G): AA, AG, GG = 61, 30, 09 for cases, and 69, 25, 06 for controls (p = 0.55); for AGTR2 (T1247G): TT, TG, GG = 84, 12, 04 for cases, and 81, 17, 02 for controls (p = 0.45); for AGTR2 (A5235G): AA, AG, GG = 32, 67, 01 for cases, and 53, 28, 19 for controls (p < 0.0001). Women carrying genotypes AA/AG in the intronic region of angiotensin II type 2 receptor had an 11-fold higher risk of breast cancer than GG carriers. Conclusions: Many types of cancer have been associated with polymorphisms of the renin-angiotensin system. For SNP A5235G, the GG genotype seems to be protective against breast cancer. The other 2 SNPs showed no association. However, SNPs T1247G and A5235G were associated with at least 1 clinical variable, with G being a predictor of better outcome. The use of SNPs A5235G and T1247G (the latter to a lesser degree) as genetic markers should be considered.

Application of a domicile-based exercise program for shoulder rehabilitation after breast cancer surgery

El objetivo de este estudio fue evaluar la efectividad de un programa de ejercicios para recuperacion de la amplitud de movimientos (ADM) del hombro. Se trata de una investigacion cuasi experimental desarrollada en el Ambulatorio de Mastologia de la Universidad Federal de Sao Paulo, en Brasil, de agosto de 2006 a junio de 2008, con 64 mujeres con cancer de mama, sometidas a cirugia. La intervencion consto de: evaluacion preoperatoria (ADM), orientacion verbal y escrita, demostracion y ejecucion de los ejercicios y reevaluaciones en los retornos al ambulatorio, hasta el 105o dia de posoperatorio (PO). Se constato un aumento significativo y continuo de la ADM, del 7oPO hasta el 105oPO. El tiempo minimo para la recuperacion fue 105 dias para las mujeres mastectomizadas y 75 para las sometidas a cuadrantectomia. Hubo adhesion satisfactoria de 78,6%. Se concluye que el programa domiciliario se mostro efectivo para la recuperacion de la ADM en esa poblacion, beneficiando mujeres que no podrian frecuentar un programa presencial.Descriptores: Neoplasias de la Mama; Rehabilitacion; Fisioterapia; Cuidados Posoperatorios; Enfermeria Oncologica.The aim of this study was to evaluate the effectiveness of an exercise program for the recuperation of the range of motion (ROM) of the shoulder. This is a quasi-experimental study developed at the Mastology Outpatient Clinic of the Federal University of São Paulo - Brazil, from August 2006 to June 2008, with 64 breast cancer patients undergoing surgery. The intervention consisted of: preoperative evaluation of the ROM, verbal and written guidance, demonstration and implementation of the exercises and revaluation at the outpatient follow-up appointments until the 105(th) postoperative day (PO). From the 7(th) PO a significant increase was observed in the ROM, which continued until the 105(th) PO. The minimum time for recovery was 105 days for the women undergoing mastectomy, and 75 days for those undergoing quadrantectomy. There was satisfactory adherence of 78.6% of the women. The domicile program was effective for the recovery of ROM in the study population, benefiting women who can not attend a presential program.

Analysis of human mammary fibroadenoma by Ki‐67 index in the follicular and luteal phases of menstrual cycle

Objectives:  Fibroadenoma is the most common benign mammary condition among women aged 35 or younger. Expression of Ki‐67 antigen has been used to compare proliferative activity of mammary fibroadenoma epithelium in the follicular and luteal phases of the menstrual cycle.

Effects of low-dose tamoxifen on breast cancer biomarkers Ki-67, estrogen and progesterone receptors.

Breast carcinoma is the most common malignancy among women and it has a major impact on mortality. Studies of primary chemoprevention with tamoxifen have generated high expectations and considerable success rates. The efficacy of lower doses of tamoxifen is similar to that seen with a standard dose of the drug, and there has been a reduction in healthcare costs and side effects.The immune reaction to monoclonal antibody Ki-67 (MIB-1) and the expression of estrogen receptors (1D5) and progesterone receptors (PgR 636) in breast carcinoma were studied in patients treated with 10 mg of tamoxifen for a period of 14 days.A prospective randomized clinical trial was conducted with 38 patients divided into two groups: Group A: N = 20 (control group-without medication) and Group B: N = 18 (tamoxifen/10 mg/day for 14 days). All patients signed an informed consent term previously approved by both institutions. Patients underwent incisional biopsy before treatment and 14 days later a tumor tissue sample was obtained during surgical treatment. Positivity was quantitatively assessed, counting at least 1.000 cells per slide. For statistical data analysis, a Wilcoxon non-parametric test was used, and α was set at 5%.Both groups (A and B) were considered homogeneous regarding control variables. In Group A (control), there was no statistically significant reduction in Ki-67 (MIB-1) (p = 0.627), estrogen receptor (1D5) (p = 0.296) and progesterone receptor positivity (PgR 636) (p = 0.381).In Group B (tamoxifen 10 mg/day), the mean percentage of nuclei stained by Ki-67 (MIB-1) was 24.69% before and 10.43% after tamoxifen treatment. Mean percentage of nuclei stained by estrogen receptor (1D5) was 59.53% before and 25.99% after tamoxifen treatment. Mean percentage of nuclei stained by progesterone receptor (PgR 636), was 59.34 before and 29.59% after tamoxifen treatment. A statistically significant reduction was found with the three markers (p < 0.001).Tamoxifen significantly reduced monoclonal antibody Ki-67 (MIB-1), estrogen receptor (1D5) and progesterone receptor positivity (PgR 636) in the breast epithelium of carcinoma patients treated with a 10 mg dose of tamoxifen for 14 days.

Interface between breast cancer cells and the tumor microenvironment using platelet-rich plasma to promote tumor angiogenesis - influence of platelets and fibrin bundles on the behavior of breast tumor cells

Cancer progression is associated with an evolving tissue interface of direct epithelial-tumor microenvironment interactions. In biopsies of human breast tumors, extensive alterations in molecular pathways are correlated with cancer staging on both sides of the tumor-stroma interface. These interactions provide a pivotal paracrine signaling to induce malignant phenotype transition, the epithelial-mesenchymal transition (EMT). We explored how the direct contact between platelets-fibrin bundles primes metastasis using platelet-rich plasma (PRP) as a source of growth factors and mimics the provisional fibrin matrix between actively growing breast cancer cells and the tumor stroma. We have demonstrated PRP functions, modulating cell proliferation that is tumor-subtype and cancer cell-type-specific. Epithelial and stromal primary cells were prepared from breast cancer biopsies from 21 women with different cancer subtypes. Cells supplemented with PRP were immunoblotted with anti-phospho and total Src-Tyr-416, FAK-Try-925, E-cadherin, N-cadherin, TGF-β, Smad2, and Snail monoclonal antibodies. Breast tumor cells from luminal B and HER2 subtypes showed the most malignant profiles and the expression of thrombin and other classes of proteases at levels that were detectable through FRET peptide libraries. The angiogenesis process was investigated in the interface obtained between platelet-fibrin-breast tumor cells co-cultured with HUVEC cells. Luminal B and HER2 cells showed robust endothelial cell capillary-like tubes ex vivo. The studied interface contributes to the attachment of endothelial cells, provides a source of growth factors, and is a solid substrate. Thus, replacement of FBS supplementation with PRP supplementation represents an efficient and simple approach for mimicking the real multifactorial tumor microenvironment.

Structure and process of nursing care for prevention of surgical site infection: observational study

High rates of infection can reflect the quality of the service. Two previous studies in the same place reported an overall surgical site infection incidence of 14,1% and 22%, what motivated this research. The aim of this study was to analyze the structure and nursing process and its possible relationship with the prevention and control of surgical site infection (SSI). It is a descriptive, observational and documentary analysis study performed in a large general teaching Hospital in Sao Paulo from August 2007 to March 2008 . The data were collected from institutional documents and trough directed observation of the nursing practice . The results showed that the normative documents are in accord with the current evidence. However, the structure issues present limitations with negative impact for the prevention of SSI. The nursing processes accomplished partially to the recommended standards , the hand washing, appropriate use of antibiotics and accomplishment of postoperative dressing’s present improvement opportunities that could positively impact the surgical site infection’s rates. These results point out the need of review the nursing process and the adequacy of some structural issues in order to achieve the standards for prevention and control of the surgical site infection.