Analysis of RPL37A, MTSS1, and HTRA1 expression as potential markers for pathologic complete response and survival.

BACKGROUND: Non-metastatic locally advanced breast carcinoma (LABC) treatment involves neoadjuvant chemotherapy (NCT). We evaluated the association of clinical-pathological data and immunoexpression of hormone receptors, HER2 and Ki67, and new biomarkers, RPL37A, MTSS1 and HTRA1, with pathological complete response (PCR) or tumour resistance (stable disease or disease progression), disease-free survival (DFS) and cancer-specific survival (CSS). METHODS: This is a retrospective study of 333 patients with LABC who underwent NCT. Expression of MTSS1, RPL37A and HTRA1/PRSS11 was evaluated by immunohistochemistry in TMA slides. Cutoff values were established for low and high tumour expression. ROC plotter evaluated response to NCT. Chi-square test for factors related to PCR, and Kaplan-Meier test and Cox model for factors related to DFS and CSS were prformed. RESULTS: The mean follow-up was 70.0 months and PCR rate was 15.6%. At 120 months, DFS rate was 32.5% and CSS rate was 67.1%. In multivariate analysis, there was an association between: (1) necrosis presence, intense inflammatory infiltrate, ER absence, HER2 molecular subtype and high RPL3A expression with increased odds of PCR; (2) lymph node involvement (LNI), high Ki67, low RPL37A and high HTRA1 expression with increased risk for NCT non-response; (3) LNI, high proliferation, necrosis absence, low RPL37A and high HTRA1 expression with increased recurrence risk; (4) advanced LNI, ER negative tumours, high HTRA1, low RPL37A expression and desmoplasia presence with higher risk of cancer death. CONCLUSION: RPL37A is a potential biomarker for response to NCT and for prognosis. Additional studies evaluating HTRA1 and MTSS1 prognostic value are needed.

CAIX is a predictor of pathological complete response and is associated with higher survival in locally advanced breast cancer submitted to neoadjuvant chemotherapy.

BACKGROUND: Locally advanced breast cancer often undergoes neoadjuvant chemotherapy (NAC), which allows in vivo evaluation of the therapeutic response. The determination of the pathological complete response (pCR) is one way to evaluate the response to neoadjuvant chemotherapy. However, the rate of pCR differs significantly between molecular subtypes and the cause is not yet determined. Recently, the metabolic reprogramming of cancer cells and its implications for tumor growth and dissemination has gained increasing prominence and could contribute to a better understanding of NAC. Thus, this study proposed to evaluate the expression of metabolism-related proteins and its association with pCR and survival rates. METHODS: The expression of monocarboxylate transporters 1 and 4 (MCT1 and MCT4, respectively), cluster of differentiation 147 (CD147), glucose transporter-1 (GLUT1) and carbonic anhydrase IX (CAIX) was analyzed in 196 locally advanced breast cancer samples prior to NAC. The results were associated with clinical-pathological characteristics, occurrence of pCR, disease-free survival (DFS), disease-specific survival (DSS) and overall survival (OS). RESULTS: The occurrence of pCR was higher in the group of patients whith tumors expressing GLUT1 and CAIX than in the group without expression (27.8% versus 13.1%, p = 0.030 and 46.2% versus 13.5%, p = 0.007, respectively). Together with regional lymph nodes staging and mitotic staging, CAIX expression was considered an independent predictor of pCR. In addition, CAIX expression was associated with DFS and DSS (p = 0.005 and p = 0.012, respectively). CONCLUSIONS: CAIX expression was a predictor of pCR and was associated with higher DFS and DSS in locally advanced breast cancer patients subjected to NAC.

Effectiveness and Safety of Implant-Based Breast Reconstruction in Locally Advanced Breast Carcinoma: A Matched Case-Control Study.

BACKGROUND: Immediate implant-based breast reconstruction (IBBR) is rarely performed in patients with locally advanced breast carcinoma (LABC). It has not been considered the best indication, and the literature is scarce about this subject. PATIENTS AND METHODS: A retrospective matched case-control study was performed in patients with LABC submitted to neoadjuvant chemotherapy (NCT). Forty-eight patients undergoing immediate IBBR were matched with 96 patients undergoing conventional mastectomy. Patients were matched according to 2 models based on prognostic characteristics prior to NCT and response to NCT. Local recurrence and disease-free survival were compared between the groups. In the IBBR group, local complications were evaluated. RESULTS: In all, 196 patients were evaluated. The mean tumour size of IBBR patients was 5.8 cm. 83.3% (180/196) of the patients had clinical stage III. At a mean follow-up of 74.7 months, the local recurrence rate was 6.2% (3/48), 15.6% (15/96) and 13.7% (13/95) in the IBBR, model 1 and model 2 groups, respectively (p > 0.05). Disease-free survival was higher in the IBBR group than in the model 1 group (mean 88.8 vs. 73.7 months; p = 0.05). In the group submitted to IBBR, 14.6% (7/48) of patients presented loss of prosthesis and 48.8% (20/41) developed capsular contracture. CONCLUSION: Immediate IBBR may be a safe and effective surgical procedure in selected patients with LABC.

Breast-conserving surgery in locally advanced breast cancer submitted to neoadjuvant chemotherapy. Safety and effectiveness based on ipsilateral breast tumor recurrence and long-term follow-up.

OBJECTIVE:: To evaluate ipsilateral breast tumor recurrence after breast-conserving surgery for locally advanced breast cancer. METHODS:: A retrospective observational cohort study was performed in patients with locally advanced breast cancer submitted to breast-conserving surgery after neoadjuvant chemotherapy based on an adriamycin-cyclophosphamide-paclitaxel regimen. We evaluated the clinical, pathologic, immunohistochemistry, and surgical factors that contribute to ipsilateral breast tumor recurrence and locoregional recurrence. A Kaplan-Meier analysis and Cox model were used to evaluate the main factors related to disease-free survival. RESULTS:: Of the 449 patients who received neoadjuvant chemotherapy, 98 underwent breast-conserving surgery. The average diameter of the tumors was 5.3 cm, and 87.2% reached a size of up to 3 cm. Moreover, 86.7% were classified as clinical stage III, 74.5% had T3-T4 tumors, 80.5% had N1-N2 axilla, and 89.8% had invasive ductal carcinoma. A pathologic complete response was observed in 27.6% of the tumors, and 100.0% of samples had free margins. The 5-year actuarial overall survival rate was 81.2%, and the mean follow-up was 72.8 months. The rates of ipsilateral breast tumor recurrence and locoregional recurrence were 11.2% and 15.3%, respectively. Multifocal morphology response was the only factor related to ipsilateral breast tumor recurrence disease-free survival (p=0.04). A multivariate analysis showed that the pathologic response evaluation criteria in solid tumors (RECIST)-breast cutoff was the only factor related to locoregional recurrence disease-free survival (p=0.01). CONCLUSIONS:: Breast-conserving surgery is a safe and effective therapy for selected locally advanced breast tumors.

Breast-conserving surgery in locally advanced breast cancer submitted to neoadjuvant chemotherapy. Safety and effectiveness based on ipsilateral breast tumor recurrence and long-term follow-up

OBJECTIVE: To evaluate ipsilateral breast tumor recurrence after breast-conserving surgery for locally advanced breast cancer. METHODS: A retrospective observational cohort study was performed in patients with locally advanced breast cancer submitted to breast-conserving surgery after neoadjuvant chemotherapy based on an adriamycin-cyclophosphamide-paclitaxel regimen. We evaluated the clinical, pathologic, immunohistochemistry, and surgical factors that contribute to ipsilateral breast tumor recurrence and locoregional recurrence. A Kaplan-Meier analysis and Cox model were used to evaluate the main factors related to disease-free survival. RESULTS: Of the 449 patients who received neoadjuvant chemotherapy, 98 underwent breast-conserving surgery. The average diameter of the tumors was 5.3 cm, and 87.2% reached a size of up to 3 cm. Moreover, 86.7% were classified as clinical stage III, 74.5% had T3-T4 tumors, 80.5% had N1-N2 axilla, and 89.8% had invasive ductal carcinoma. A pathologic complete response was observed in 27.6% of the tumors, and 100.0% of samples had free margins. The 5-year actuarial overall survival rate was 81.2%, and the mean follow-up was 72.8 months. The rates of ipsilateral breast tumor recurrence and locoregional recurrence were 11.2% and 15.3%, respectively. Multifocal morphology response was the only factor related to ipsilateral breast tumor recurrence disease-free survival (p=0.04). A multivariate analysis showed that the pathologic response evaluation criteria in solid tumors (RECIST)-breast cutoff was the only factor related to locoregional recurrence disease-free survival (p=0.01). CONCLUSIONS: Breast-conserving surgery is a safe and effective therapy for selected locally advanced breast tumors.

The role of oncoplastic breast conserving treatment for locally advanced breast tumors. A matching case-control study.

BACKGROUND: Breast conserving surgery (BCS) after neoadjuvant chemotherapy (NC) in patients with locally advanced breast cancer (LABC) is an infrequent procedure. In these patients the association with BCS and oncoplastic surgery (OS) is reported as a possible procedure in case-series, but there are limited case-control studies. METHODS: A matched case-control study evaluated LABC submitted to NC and BCS. We evaluated 78 patients submitted to doxorubicin-cyclophosphamide regimen followed by paclitaxel regimen. The match case-control proportion was 2:1 and the patients were selected by tumor size, clinical T stage and year of diagnosis. RESULTS: 52 underwent classic BCS and 26 OS. The average size tumor was 5.25 cm and 88.5% of the tumors were larger than 3 cm. The clinical and pathological group characteristics were similar, except the weight of surgical specimens (p = 0.004), and surgical margins (p = 0.06), which were higher in OS group. The rate of complete pathologic response was 26.9%. 97.4% received postoperative radiotherapy. At 67.1 months of follow up, 10.2% had local recurrence (LR) and 12.8% locoregional recurrence (LRR) and 19.2% died because disease progression. The overall survival at 60 months was 81.7%. After surgery the disease free-survival at 60 months was 76.5%. The was no difference between groups related to pathologic response (p = 0.42), LR (p = 0.71), LRR (p = 1.00), overall survival (p = 0.99) and disease specific survival (p = 0.87). CONCLUSION: This study corroborates the fact that OS is a safety procedure for LABC, offering the similar oncologic results observed in patients submitted to classic BCS.

Invasive thymoma in a child: a rare case report.

Thymomas are neoplasms of the anterior mediastinum and generally occur between the fourth and sixth decades of life. In children, they are rare, with few reported cases. We describe a 9-year-old boy with invasive thymoma treated successfully by surgery alone. The patient was previously healthy and under treatment for a community-acquired pneumonia. A chest radiograph showed an opacity at the left lung base, and thoracic computed tomographic scan showed a mass with thick walls and liquid content situated in the lingula with no cleavage plane with the mediastinum. The patient underwent a left anterolateral thoracotomy, which showed a mass extending from the anterior mediastinum, infiltrating the left upper lobe of lung, phrenic nerve, and pericardium. A left upper lobectomy and resection of the mediastinal mass and lymph nodes were carried out. The pathologic analysis showed it to be a type B3 fusiform-cell thymoma, infiltrating the left upper lobe and 1 peribronchial lymph node. A multidisciplined tumor group decided to observe the patient and followed with thoracic computed tomographic scans every 3 months. After 2 years of follow-up, the patient has no evidence of recurrent disease.