Marcos Desidério Ricci

Triple-negative and luminal A breast tumors: differential expression of miR-18a-5p, miR-17-5p, and miR-20a-5p

New concepts in epigenetics, microRNAs, and gene expression analysis have significantly enhanced knowledge of cancer pathogenesis over the last decade. MicroRNAs (miRNAs) are a class of non-coding RNAs that regulate gene expression by base pairing with target messenger RNAs (mRNAs), resulting in the repression of translation or the degradation of mRNA. To compare the carcinogenic process in tumors with different prognoses, we used real-time RT-PCR to evaluate the miRNA expression profiles of 24 triple-negative breast invasive ductal carcinoma, 20 luminal A breast invasive ductal carcinoma, and 13 normal breast parenchyma controls. We extracted total RNA from tissues fixed in formol and embedded in paraffin (FFPE). Results revealed the upregulation of miR-96-5p (9.35-fold; p = 0.000115), miR-182-5p (7.75-fold; p = 0.000033), miR-7-5p (6.71-fold; p = 0.015626), and miR-21-5p (6.10-fold; p = 0.000000) in tumors group. In addition, the expression of miR-125b-5p (4.49-fold; p = 0.000000) and miR-205-5p (4.36-fold; p = 0.006098) was downregulated. When the expression profiles of triple-negative and luminal A tumors were compared, there was enhanced expression of miR-17-5p (4.27-fold; p = 0.000664), miR-18a-5p (9.68-fold; p = 0.000545), and miR-20a-5 (4.07-fold; p = 0.001487) in the triple-negative tumors compared with luminal A. These data suggest that there is a similar regulation of certain miRNAs in triple-negative and luminal A tumors. However, it is possible that differences in the expression of miR-17-92 cluster will explain the phenotypic differences between these molecular tumor subtypes.

Analysis by MRI of residual tumor after radiofrequency ablation for early stage breast cancer.

OBJECTIVE The objective of our study was to evaluate the effectiveness of MRI in the detection of possible residual lesions after radiofrequency ablation (RFA) in the treatment of breast cancer. SUBJECTS AND METHODS We prospectively evaluated 14 patients who had undergone ultrasound-guided core biopsies diagnostic of invasive ductal carcinoma (IDC; range of diameters, 1.0-3.0 cm) and then ultrasound-guided percutaneous RFA with sentinel node biopsy as the primary treatment. Breast MRI was performed 1 week before RFA to evaluate tumor extension and again 3 weeks after RFA to verify the presence of possible residual lesions. Conventional surgical resection of the tumors was performed 1 week after RFA. The MRI findings were compared with histopathologic analyses to confirm the presence or absence of residual tumor. RESULTS There was no residual enhancement in seven lesions on the postablation breast MRI scans. These findings were confirmed by negative histopathologic findings in the surgical specimens. The MRI scans of five patients showed small areas of irregular enhancement that corresponded to residual lesions. In the two remaining patients, we observed enhancement of almost the entire lesion, indicating that RFA had failed. CONCLUSION Breast MRI is effective in detecting residual lesions after RFA in patients with IDC.

Optimizing the nipple-areola sparing mastectomy with double concentric periareolar incision and biodimensional expander-implant reconstruction: Aesthetic and technical refinements

Although the biodimensional anatomical expander-implant system (BEIS) is a reliable technique, little information has been available regarding outcome following nipple-areola sparing mastectomy (NSM). To perform the resection of glandular tissue, while improving the surgical access and maintaining the nipple-areola vascularization we have developed a new approach for NSM based on the double concentric periareolar incision (DCPI). The purpose of this study is to analyze the feasibility, surgical planning and its outcome following NSM. 18 patients underwent NSM reconstructions. Mean time of follow-up was 29 months. The technique was indicated in patients with small/moderate volume breasts. Flap complications were evaluated and information on aesthetic results and patient satisfaction were collected. 83.3% had tumors measuring 2cm or less (T1) and 72.1% were stage 0 and I. All patients presented peripherally tumors located (at least 5cm from the nipple). Skin complications occurred in 11.1%. One patient (5.5%) presented small skin necrosis and a wound dehiscence was observed in one patient (5.5%). The aesthetic result was good/very good in 94.4 percent and the majority of patients were very satisfied/satisfied. No local recurrences were observed. All complications except one were treated by a conservative approach. DCPI-BEIS is a simple and reliable technique for NSM reconstruction. The success depends on patient selection, coordinated planning with the oncologic surgeon and careful intra-operative and post-operative management.

Analysis of the concordance rates between core needle biopsy and surgical excision in patients with breast cancer

OBJECTIVE To evaluate whether immunohistochemical marker studies performed on core needle biopsy (CNB) specimens accurately reflect the marker status of the tumor obtained from final surgical specimen. METHODS This was a retrospective study that used the database of the Division of Mastology of the Hospital das Clínicas, São Paulo, Brazil. Sixty-nine patients submitted to ultrasound-guided CNB diagnosed with breast cancer were retrospectively analyzed. Immunohistochemistry (IHC) on core biopsy specimens was compared to that of excisional biopsy regarding estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 gene (HER2), p53, and Ki67. The analysis of the concordance between CNB and surgical biopsy was performed using the kappa (k) coefficient (95% CI). RESULTS A perfect concordance between the labeling in the surgical specimens and the preoperative biopsies in p53 (k = 1.0; 95% CI: 0.76-1.0) was identified. There was an almost perfect concordance for ER (k = 0.89; 95% CI: 0.65-1.0) and a substantial concordance for PR (k = 0.70; 95% CI: 0.46-0.93). HER2 (k = 0.61; 95% CI: 0.38-0.84) and Ki-67 (k = 0.74; 95% CI: 0.58-0.98) obtained a substantial concordance this analysis. CONCLUSION The results of this study indicate that the immunohistochemical analysis of ER, PR, Ki-67, and p53 from core biopsy specimens provided results that accurately reflect the marker status of the tumor. The concordance rate of HER2 was less consistent; although it produced substantial concordance, values were very close to moderate concordance.

Immediate effects of intraoperative evaluation of surgical margins over the treatment of early infiltrating breast carcinoma

Aims and Background Local recurrences in patients submitted to conservative breast treatment for early infiltrating breast carcinomas occur in 5–10% of the cases and are caused mainly by inadequate local resection and remaining residual malignant tissue. The present study was carried out to analyze the effect of intraoperative evaluation of surgical margins and its influence on the immediate surgical management of patients with early breast carcinomas (T1–T2) scheduled to undergo quadrantectomy. Methods A total of 102 cases were studied. After a classical quadrantectomy, intraoperative evaluation of surgical margins was done by means of macroscopic, cytological and histopathologic analysis. The margins of the resected tissue were examined to assure they were clear or to orient a wider resection. Results In 64 cases (62.7%), the extent of the quadrant resection was considered adequate and the margins were clear. In 38 cases (37.3%), surgical margins were considered inadequate. An enlarged quadrantectomy was immediately performed in 33 patients (32.4%) and mastectomies in 5 (4.9%). Conclusions Intraoperative evaluation of surgical margins frequently modifies the surgical management of patients who were initially prepared to be submitted to a quadrantectomy, indicating the need for further resection in the form of an enlarged quadrantectomy or mastectomy.

Bilateral Reduction Mammaplasty for Immediate Breast Conservation Surgery Reconstruction and Intraoperative Radiotherapy: A Preliminary Report

BackgroundBreast conservation surgery and postoperative radiotherapy are widely accepted as the treatment of choice for patients with early breast cancer. Despite its oncologic benefits, the radiotherapy may cause unpredictable outcomes in soft tissues, especially in patients undergoing breast reconstruction. Described recently, intraoperative irradiation (IORT) has been indicated for selected patients as an alternative to radiotherapy with fewer adverse local effects. Clinical use of reduction mammaplasty (RM) techniques in oncologic breast surgery has been described previously. However, no previous studies have mentioned its application after breast conservation surgery and IORT.MethodsThe authors used RM to reconstruct a partial breast tissue defect secondary to breast conservation surgery followed by IORT treatment in a 46-year-old patient with an 11-mm invasive ductal carcinoma between the superior internal quadrants of the right breast.ResultsSatisfactory breast volume and shape were achieved, and no immediate or late complications were observed. After 2 postoperative years, no evidence of fat necrosis, tumor recurrence, or tissue volume loss was observed.ConclusionThe initial data indicate that RM in the setting of breast conservation surgery reconstruction and IORT is feasible. With appropriate patient selection, respecting indications and limitations, RM has its place among the various reconstructive techniques. Additional studies with larger clinical series and longer follow-up periods are necessary to analyze the precise IORT effects in patients submitted to immediate breast conservation surgery reconstruction.

Improved frozen section examination of the retroareolar margin for prediction of nipple involvement in breast cancer.

INTRODUCTION In this prospective ex vivo study, we propose a new technique for the intraoperative examination of retroareolar tissue and describe both surgical excision and pathological methods. We performed a nipple-sparing mastectomy simulation in patients selected to total mastectomy, in order to evaluate the accuracy of these new technique. MATERIALS AND METHODS A total of 158 total mastectomy specimens from patients affected by ductal carcinoma in situ (n = 15) or invasive ductal carcinoma (stages I, II, or IIIA) (n = 143) were examined. To obtain the entire sample area, the terminal retroareolar milk duct bunch was isolated. Fragments approximately 1.5 cm in length were excised and sectioned in parallel at the base of the nipple using a cold bistoury. Three transverse histological sections (4 μm each) at 200 μm intervals that included the entire isolated fragments were subjected to frozen section examination. The sections were stained with hematoxylin-eosin and were evaluated. The remainder of each fragment was embedded in paraffin and 4 μm sections were subsequently stained with hematoxylin-eosin and examined. RESULTS There were two false-negative (1.3%) and five false-positive (3.1%) findings among the frozen and paraffin sections analyzed. A statistical analysis of the frozen section examinations showed a sensitivity of 92.0%, a specificity of 96.2%, a positive predictive value of 82.1%, a negative predictive value of 98.4%, and an accuracy of 95.4%. CONCLUSION The frozen section examination technique described here detected nipple involvement in breast cancer with greater accuracy than the frozen section usually performed by most surgeons.

Analysis of the concordance rates between core needle biopsy and surgical excision in patients with breast cancerAnálise das taxas de concordância entre a biópsia com agulha grossa e a excisão cirúrgica em pacientes com câncer de mama

OBJECTIVE To evaluate whether immunohistochemical marker studies performed on core needle biopsy (CNB) specimens accurately reflect the marker status of the tumor obtained from final surgical specimen. METHODS This was a retrospective study that used the database of the Division of Mastology of the Hospital das Clínicas, São Paulo, Brazil. Sixty-nine patients submitted to ultrasound-guided CNB diagnosed with breast cancer were retrospectively analyzed. Immunohistochemistry (IHC) on core biopsy specimens was compared to that of excisional biopsy regarding estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 gene (HER2), p53, and Ki67. The analysis of the concordance between CNB and surgical biopsy was performed using the kappa (k) coefficient (95% CI). RESULTS A perfect concordance between the labeling in the surgical specimens and the preoperative biopsies in p53 (k = 1.0; 95% CI: 0.76-1.0) was identified. There was an almost perfect concordance for ER (k = 0.89; 95% CI: 0.65-1.0) and a substantial concordance for PR (k = 0.70; 95% CI: 0.46-0.93). HER2 (k = 0.61; 95% CI: 0.38-0.84) and Ki-67 (k = 0.74; 95% CI: 0.58-0.98) obtained a substantial concordance this analysis. CONCLUSION The results of this study indicate that the immunohistochemical analysis of ER, PR, Ki-67, and p53 from core biopsy specimens provided results that accurately reflect the marker status of the tumor. The concordance rate of HER2 was less consistent; although it produced substantial concordance, values were very close to moderate concordance.

The biopsychosocial spiritual model applied to the treatment of women with breast cancer, through RIME intervention (relaxation, mental images, spirituality).

This postdoctoral study on the application of the RIME intervention in women that had undergone mastectomy and were in treatment, aimed to promote psychospiritual and social transformations to improve the quality of life, self-esteem and hope. A total of 28 women participated and were randomized into two groups. Brief Psychotherapy (PB) (average of six sessions) was administered in the Control Group, and RIME (three sessions) and BP (average of five sessions) were applied in the RIME Group. The quantitative results indicated a significant improvement (38.3%) in the Perception of Quality of Life after RIME according to the WHOQOL, compared both to the BP of the Control Group (12.5%), and the BP of the RIME Group (16.2%). There was a significant improvement in Self-esteem (Rosenberg) after RIME (14.6%) compared to the BP of the Control Group (worsened 35.9%), and the BP of the RIME Group (8.3%). The improvement in well-being, considering the focus worked on (Visual Analog Scale), was significant in the RIME Group (bad to good), as well as in the Control Group (unpleasant to good). The qualitative results indicated that RIME promotes creative transformations in the intrapsychic and interpersonal dimensions, so that new meanings and/or new attitudes emerge into the consciousness. It was observed that RIME has more strength of psychic structure, ego strengthening and provides a faster transformation that BP, therefore it can be indicated for crisis treatment in the hospital environment.

Variations in the body mass index in Brazilian women undergoing adjuvant chemotherapy for breast cancer.

PURPOSE To evaluate variations in the body mass index in patients undergoing adjuvant chemotherapy for breast cancer, and to associate these changes with patients age and adjuvant chemotherapy regimen. METHODS We performed a retrospective cohort study in order to correlate any variation in the body mass index before and after adjuvant chemotherapy with patients age and adjuvant chemotherapy regimen. Patients who received any form of prior hormone therapy, such as tamoxifen or aromatase inhibitors, were excluded. We selected data for 196 patients with stage I to III breast cancer who were treated by radical or conservative surgery and received adjuvant chemotherapy at the Cancer Institute of the State of São Paulo, Brazil. RESULTS Before adjuvant chemotherapy, 67.8% of patients were classified as overweight or obese according to their body mass indices. Around 66.3% (95% CI 59.7-73.0) of the patients exhibited an increase in the body mass index after adjuvant chemotherapy. The average age of all patients was 56.3±11.3 years. Participants whose body mass index increased were younger than those with no increase (54.7±11.1 versus 59.3±11.2 years; p=0.007). Patients were treated with the following adjuvant chemotherapy regimens: doxorubicin, cyclophosphamide, and paclitaxel (AC-T, 129 patients, 65.8%); 5-fluoracil, doxorubicin, and cyclophosphamide (36 patients, 18.4%); cyclophosphamide, methotrexate, and 5-fluoracil (16 patients, 8.2%); docetaxel and cyclophosphamide (7 patients, 3.6%); and other regimen (8 patients, 4.1%). The AC-T regimen showed a statistically significant association with increase in the body mass index (p<0.001 by ANOVA). CONCLUSIONS Most patients with breast cancer showed an increase in the body mass index after adjuvant chemotherapy, especially after the AC-T chemotherapy regimen.