Felipe Pereira Zerwes

Inducible heat shock protein 70 expression as a potential predictive marker of metastasis in breast tumors

Abstract Heat shock protein (Hsp)–peptide complexes purified from tumors can prime the immune system against tumor antigens, but how they contribute to the generation of immune responses against naturally occurring tumors is unknown. Murine tumors expressing high amounts of Hsp70 are preferentially rejected by the immune system, suggesting that low Hsp70 expression is advantageous for tumor growth in the host. To determine whether Hsp70 was differentially expressed in human tumors, inducible Hsp70 expression was quantitatively (by Western blot) and qualitatively (by immunohistology) analyzed in 53 biopsies of tumor and normal breast tissue. The mean expression of inducible Hsp70 was significantly higher in tumor compared with normal tissue (U = 899.0; P = 0.0033). However, a significant negative association of the amount of Hsp70 expressed by tumor tissue was found with metastasis (r2 = −0.309; P = 0.05). After 3 years, follow-up analysis determined that 7 of the 53 patients relapsed, and 5 died. Hsp70 expression in tumor (but not normal) cells was significantly lower in relapse patients and patients with metastatic disease than in patients with no relapse or metastasis. Together, these observations support the hypothesis that Hsp70 plays a role in tumor expansion in vivo, and tumors that downregulate it may be able to evade immunosurveillance and grow.

Bilateral giant juvenile fibroadenomas of the breasts—a rare indication for bilateral skin reducing mastectomy

Fibroadenoma is the most common benign tumor of the breast but giant juvenile fibroadenoma represent only 0.5% of all fibroadenomas and when bilateral are much more rare. We describe the case of a 25 years old girl that presented with bilateral giant juvenile fibroadenomas and was treated by bilateral skin reducing mastectomy using the inferior dermal flap, implant, and free nipple graft.

Immune risk profile of elderly women with breast cancer: the first 37 cases

AIMS: To evaluate the immune risk profile of elderly women with breast cancer and to assess whether this can be a reliable predictor to determine types of treatment and oncologic follow-up. METHODS: We assessed the CD4+/CD8+ ratio in peripheral blood cell, as well as serology for cytomegalovirus, of 37 women who were aged 60 years or more at the time they were diagnosed with breast cancer/. They all had surgical treatment at the Breast Center from Pontificia Universidade Catolica do Rio Grande do Sul. Those with positive serology for HIV, or immuno-suppressed due to organ transplant, as well as those who had neoadjuvant chemotherapy. Data was analyzed according to axillary involvement, tumor size, tumor immunohistochemical profile and occurrence of adverse events (axillary relapse, local relapse and/or metastases) RESULTS: The mean value of CD4+/CD8+ ratio was 1.72 (min. 1.1, max. 2.32) and cytomegalovirus serology was positive in all subjects. Comparing the groups, patients with positive axillary metastases (n=10) had a CD4+/CD8+ ratio greater than in those with negative axillary metastases (p=0.04). No statistically significant difference was detected regarding the size and immunohistochemical profile of the tumor. Two adverse events occurred at a mean follow-up of 14 months (one axillary relapse and one bone metastasis), when an increase in the CD4+/CD8+ ratio was observed. CONCLUSIONS: The CD4+/CD8+ ratio appear to increase in cases of breast cancer with worst prognosis. As far as was possible to search, these are the first data on CD4+ and CD8+ peripheral blood of elderly women with breast cancer. A longer follow-up will determine the value of these cells as a prognostic and/or predictive marker.

Skin Sparing Mastectomy and Adenomastectomy: Follow Up of the First 93 Cases

INTRODUCTION: Surgical treatment of breast cancer has evolved considerably in recent years with the development of the concepts of immediate breast reconstruction, prophylactic mastectomy and symetrization. Based on these concepts the techniques of skin-sparing mastectomy and adenomastectomy (subcutaneous mastectomy with nipple areola complex – NAC - preservation) are rising as important options in clinical practice. The published data shows good cosmetic results, although there are no randomized studies comparing the safety of this procedure in breast cancer patients. MATERIAL AND METHODS: The performance of skin-sparing mastectomy and adenomastectomy began in 2006 in Centro de Mama da PUC/RS, Brazil. The objectives of this study are to describe the sociodemographic profile, tumor characteristics and outcome of the first 93 cases operated between 2006 and 2010. Inclusion criteria were female gender, surgical conditions to preserve skin and / or NAC, obtain free surgical margins and desire of the patient. Follow up of the patients was filled in a form with demographic information, surgical, pathologic, adjuvant treatment and adverse events. RESULTS: As inclusion criteria, were selected to participate in this study 93 patients, mean age at diagnosis of 44.5 years (23-70 years). The mean follow-up was 62 months. The surgery was unilateral in 36 cases (38%) and bilateral in 57 cases (61%). of these, 14 patients (15%) underwent skin sparing mastectomy, 4 patients (5%) underwent bilateral different procedure (skin sparing mastectomy on one side and adenomastectomy on the other side); and most, 75 patients (80%), underwent a adeno-mastectomy. The immediate breast reconstruction was performed in all cases, using silicon prothesis in 72 (77%) and expanders in the others 21 patients (23%). Thirty one patients of our group were pTis. The others 62 patients (66%) presented with invasive lesions with an average tumor size of 2.3 cm (0.2 - 7.1 cm); Chemotherapy was neoadjuvant in 11 patients (17.7%) and adjuvant in 38 patients (61.2%). Hormone therapy was indicated in 52 cases (83.8%), 12 patients (19.3%) received anti-Her 2 therapy and radiotherapy was applied in 42 cases (67.7%). To evaluate the results of follow-up, 6 patients were excluded from analysis because the indication of the surgery was a recurrent tumor. So, 87 patients with a primary tumor at a mean follow up of 62 months were analised. In this period there were 5 (5.5%) local recurrences, 2 located in the NAC and 1 (1.1%) single distant metastase in the bone. All patients are alive. CONCLUSIONS: Skin-sparing mastectomy and adenomastectomy appears to be oncologically safe. In this study the overall recurrence rate is in keeping with previous studies. The role of postoperative radiotherapy to avoid local recurrence has to be defined in larger studies.