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Purpose: This study was designed to identify genes that could predict response to doxorubicin-based primary chemotherapy in breast cancer patients.Experimental Design: Biopsy samples were obtained before primary treatment with doxorubicin and cyclophosphamide. RNA was extracted and amplified and gene expression was analyzed using cDNA microarrays.Results: Response to chemotherapy was evaluated in 51 patients, and based on Response Evaluation Criteria in Solid Tumors guidelines, 42 patients, who presented at least a partial response (≥30% reduction in tumor dimension), were classified as responsive. Gene profile of samples, divided into training set (n = 38) and independent validation set (n = 13), were at first analyzed against a cDNA microarray platform containing 692 genes. Unsupervised clustering could not separate responders from nonresponders. A classifier was identified comprising EMILIN1, FAM14B, and PBEF, which however could not correctly classify samples included in the validation set. Our next step was to analyze gene profile in a more comprehensive cDNA microarray platform, containing 4,608 open reading frame expressed sequence tags. Seven samples of the initial training set (all responder patients) could not be analyzed. Unsupervised clustering could correctly group all the resistant samples as well as at least 85% of the sensitive samples. Additionally, a classifier, including PRSS11, MTSS1, and CLPTM1, could correctly distinguish 95.4% of the 44 samples analyzed, with only two misclassifications, one sensitive sample and one resistant tumor. The robustness of this classifier is 2.5 greater than the first one.Conclusion: A trio of genes might potentially distinguish doxorubicin-responsive from nonresponsive tumors, but further validation by a larger number of samples is still needed.

Trios of genes sorted by Spread Error which best discriminate responders from nonresponders.

Breast cancer (BC) is mainly considered a disease in women, but male BC (MaBC) accounts for approximately 1.0% of BC diagnoses and 0.5% of malignant neoplasms in the western population. The stigmatization of MaBC, the fact that men are less likely to undergo regular health screenings, and the limited knowledge of health professionals about MaBC contribute to men being diagnosed at more advanced stages. The aim of this article is to increase the visibility of MaBC among urologists, who have more contact with male patients. This review highlights key points about the disease, the risk factors associated with MaBC, and the options for treatment. Obesity and increased population longevity are among the important risk factors for MaBC, but published studies have identified family history as extremely relevant in these patients and associated with a high penetrance at any age. There is currently no screening for MaBC in the general population, but the possibility of screening in men at high risk for developing BC can be considered. The treatment of MaBC is multidisciplinary, and, because of its rarity, there are no robust clinical studies evaluating the role of systemic therapies in the management of both localized and metastatic disease. Therefore, in current clinical practice, treatment strategies for men with breast cancer are extrapolated from information arising from studies in female patients.

To investigate the impact of response evaluation after neoadjuvant chemotherapy (NAC) in breast cancer patients, assessed by both magnetic resonance imaging (MRI) and pathology, on disease-free survival (DFS). This single-center, retrospective cohort study included consecutive breast cancer patients who underwent NAC and preoperative breast MRI. Resolution of invasive carcinoma in the breast and axilla was defined as complete pathological response (pCR). Radiological complete response (rCR) was defined as the absence of abnormal enhancement in the tumor site. Kaplan-Meier estimator was used to estimate the disease-free survival on 60 months. Cox regression analysis was used to estimate hazard ratio (HR) values. In total, 317 patients were included with a mean age of 47.3 years and a mean tumor size of 39.8 mm. The most common immunophenotype was luminal (44.9%), followed by triple-negative (26.8%). Overall, 126 patients (39.7%) had an rCR, while 119 (37.5%) had pCR; the radiological and pathological responses agreed in 252 cases (79.5%). During follow-up, patients who had rCR and pCR had a better DFS curve compared to patients with non-rCR and non-pCR, while those who had rCR or pCR presented an intermediate curve (Log-rank p = 0.003). Multivariate analysis showed a higher risk of recurrence in patients with non-rCR and non-pCR (HR: 5,626; p = 0.020) and those who had a complete response on MRI or pathology only (HR: 4,369; p = 0.067), when compared to patients with rCR and pCR. The association of MRI and pathological responses after NAC might better stratify the risk of recurrence and prognosis in breast cancer patients. • Association of response evaluation after neoadjuvant chemotherapy by pathology and MRI allows better stratification of prognosis. • Complete response to neoadjuvant chemotherapy on pathology and MRI was related to better disease-free survival. • Complete response on MRI or pathology only had a greater risk of recurrence.

Introduction: Phyllodes tumor (PT) of the breast, particularly malignant phyllodes tumor (mPT), is a rare fibroepithelial neoplasm. A complex diagnosis is based on pathologic, radiologic, and clinical findings, with controversies about what is the best therapeutic strategy. Objective: Our objective was to provide an overview of the clinical, pathologic, and therapeutic aspects of this rare tumor. Conclusions: mPT is a rare presentation of breast cancer and a challenge in clinical practice. A multidisciplinary approach should take into account some aspects like pathogenic mutations and hereditary syndromes. Oncologic surgery is the fundamental approach, and the use of adjuvant therapies is still controversial due to the lack of clinical trials. Treatment recommendations should be individualized according to patient risk and preferences. Prospective studies are fundamental to clarifying the best treatment for these tumors.

Background Cancer patients configure a risk group for complications or death by COVID‐19. For many of them, postponing or replacing their surgical treatments is not recommended. During this pandemic, surgeons must discuss the risks and benefits of treatment, and patients should sign a specific comprehensive Informed consent (IC). Objectives To report an IC and an algorithm developed for oncologic surgery during the COVID‐19 outbreak. Methods We developed an IC and a process flowchart containing a preoperative symptoms questionnaire and a PCR SARS‐CoV‐2 test and described all perioperative steps of this program. Results Patients with negative questionnaires and tests go to surgery, those with positive ones must wait 21 days and undergo a second test before surgery is scheduled. The IC focused both on risks and benefits inherent each surgery and on the risks of perioperative SARS‐CoV‐2 infections or related complications. Also, the IC discusses the possibility of sudden replacement of medical staff member(s) due to the pandemic; the possibility of unexpected complications demanding emergency procedures that cannot be specifically discussed in advance is addressed. Conclusions During the pandemic, specific tools must be developed to ensure safe experiences for surgical patients and prevent them from having misunderstandings concerning their care.

Background: Axillary lymph node status is one of the most important prognostic factors in breast cancer (BC). Neoadjuvant Chemotherapy (NACT) has been indicated for locally advanced tumors, and for HER2-positive and triple negative tumors larger than 2.0 and 1.0 cm, respectively, regardless of axillary status. This approach allows to assess biological response of the tumor, predicting prognosis and may permit more conservative surgeries in breast and axilla. However, there is no consensus about the best approach on management of axilla after NACT. Objective: To evaluate the rate of axillary downstaging after NACT in BC patients using a standardized protocol with a clip marker placement on positive lymph nodes prior to chemotherapy at a Cancer Center. Methods: This single-center, Institutional Review Board (IRB)-approved, retrospective study evaluated 471 BC patients who underwent NACT from January/2014 to December/2018. All included patients were evaluated for histological type, clinical T and N stages before NACT, modality of breast surgery (mastectomy vs. lumpectomy), type of axillary dissection (Axillary Lymph Node Dissection [ALND], sentinel lymph node biopsy [SLNB], or SLNB followed by ALND), placement or not of a clip marker in axillary lymph nodes before NACT, reason for the ALND and the pathological response by residual cancer burden (RCB) criteria. Patients were divided in two groups, before and after institution of a standardized protocol for axillary management after NACT in January/2017, which consists of: (1) biopsy of clinically suspect axillary lymph nodes before NACT, and placement of a clip marker in one positive lymph node in patients with 1-2 suspected lymph nodes (N1); (2) SLNB after NACT using blue dye and radioactive isotope injection; (3A) in the presence of clip marker in an axillary lymph node, confirmation of its extraction is performed through radiography of the surgical specimen and, (3B) in the absence of clip markers on axillary lymph nodes, removal of at least 03 sentinel lymph nodes should be performed; (4) no further axillary dissection is performed if all SLN are negative on frozen section analysis; any residual lymph node disease and/or absence of previously placed clip marker on SLNB specimen indicate ALND.Results: Patients’ mean age was 47 years (range 24-87 years), 67.2% (n=316) were cT2-T3, 83.5% (n=393) cN+ (N1 and N2), 62.6% (n = 295) had mastectomy. ALND was performed in 64.7% (n=303) patients, SLNB in 33.3% (n=156) and SLNB followed by ALND in 1.9% (n=9). In the subgroup of N+ patients (n=385), it was possible to perform SNB in 25.6% (n=98). 165 of 471 patients (35%) were included in standardized protocol for axillary management; the rate of SLNB in N+ patients was statistically higher in this group when compared to patients treated before the implementation of the protocol (34.4% vs. 22.8%; p=0.025).Conclusion: The results of the present study demonstrate a significant increase in sparing ALND after the implementation of a standardized protocol for management of axilla after NACT. However, further multi-institutional studies are still needed to support its widely adoption, as well as clinical trials to assess overall and disease-free survival in those patients who had omitted ALND after NACT. Citation Format: Marina de Paula Canal, Caroline Rocha, Marina Sonagli, Almir Bitencourt, Solange Sanches, Monique Tavares, Cynthia Osório, Fabiana Baroni Makdissi. Impact of a standardized protocol for management of axilla after neoadjuvant chemotherapy in breast cancer patients at a cancer center [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-44.

Background There are limited data on surgical complications for patients that have delayed surgery after severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. We aimed to analyze the surgical outcomes of patients submitted to surgery after recovery from SARS‐CoV‐2 infection. Methods Asymptomatic patients that had surgery delayed after preoperative reverse‐transcription polymerase chain reaction (RT‐PCR) for SARS‐CoV‐2 were matched in a 1:2 ratio for age, type of surgery and American Society of Anesthesiologists to patients with negative RT‐PCR for SARS‐CoV‐2. Results About 1253 patients underwent surgical procedures and were subjected to screening for SARS‐CoV‐2. Forty‐nine cases with a delayed surgery were included in the coronavirus disease (COVID) recovery (COVID‐rec) group and were matched to 98 patients included in the COVID negative (COVID‐neg) group. Overall, 22 (15%) patients had 30‐days postoperative complications, but there was no statistically difference between groups –16.3% for COVID‐rec and 14.3% for COVID‐neg, respectively (odds ratio [OR] 1.17:95% confidence interval [CI] 0.45–3.0; p = .74). Moreover, we did not find difference regarding grades more than or equal to 3 complication rates – 8.2% for COVID‐rec and 6.1% for COVID‐neg (OR 1.36:95%CI 0.36‐5.0; p = .64). There were no pulmonary complications or SARS‐CoV‐2 related infection and no deaths within the 30‐days after surgery. Conclusions Our study suggests that patients with delayed elective surgeries due to asymptomatic preoperative positive SARS‐CoV‐2 test are not at higher risk of postoperative complications.

Objective Cowden Syndrome belongs to a group of disorders that are associated with germline mutations in the tumor suppressor gene , phosphatase and tensin homolog (PTEN). The prevalence has been estimated to be 1 in 200,000–250,000. However, this prevalence may be underestimated due to many factors. Better understand Cowden Syndrome among our local population to provide genetic counseling and appropriate screening for different types of neoplasms associated to Cowden Syndrome. Material and methods Case series analysis based on data maintained by the Breast Cancer and Hereditary Cancer Departments of the AC Camargo Cancer Center, a large specialized hospital in Brazil. Results Five cases are presented according to their diagnostic criteria, cancer rates, and outcomes for Cowden Syndrome. Conclusion These cases highlight the need for a multi-institutional evaluation of Cowden Syndrome cases in order to better comprehend its prevalence in Brazil. To improve the outcome of patients with CS, a greater understanding of this syndrome is needed, as well as recognition of the value of periodic screening.

Objective: Loss-of-function germline mutation in BRCA1 increases breast cancer risk, especially in the triple-negative breast cancer (TNBC) subtype. BRCA1 impairment may confer benefit from the treatment with DNA damage-inducing drugs and PARP1 inhibitors. Patients who respond to neoadjuvant chemotherapy tend to have good outcomes. The aim of this study was to characterize the resistance to chemotherapy in patients with germline-characterized TNBC by investigating somatic mutations in ctDNA. Methods: Germline genetic testing was done using cancer-predisposing gene panels (26–126 genes) to classify TNBC as hereditary or sporadic. Somatic mutation identification in tumor (409 cancer-related gene panel) and screening of ctDNA in plasma samples during treatment were performed. Results: We enrolled 96 TNBC patients of which 88 were tested for germline variants: 23% (20/88) of cases were hereditary – BRCA1 (16%), BRCA2 (4%), PALB2 (1%), RAD51D (1%), and TP53 (1%). Tumor mutation burden (TMB) analysis (43 cases) showed that 11.6% had high and 89.4% had low TMB, not associated with hereditary status. We found, on average, 3 somatic variants per tumor (range 1–7) and used them as tumor marks for screening ctDNA in plasma. Somatic mutations in TP53 were identified in most tumors (71%). In ctDNA before treatment, detection of at least one tumor mutation was observed in 24 out of 30 patients (80%), and no association was observed between hereditary status and TMB score. Although ctDNA was not associated with the residual cancer burden score, ctDNA-positive patients were associated with clinical progression, either at baseline or during monitoring (post-neoadjuvant chemo), and ctDNA identification anticipated progression detected by imaging. Conclusion: Hereditary tumors, markedly due to germline variants in BRCA1, are frequent in TNBC. Tumor-mark identification using gene panels and ctDNA screening in plasma samples provide valuable information regarding the clinical progression of patients treated with preoperative chemotherapy.

Objective: Aiming at the assistance of women with breast cancer, quality of life indicators can help in clinical practice, guide therapeutic intervention strategies, and evaluate the success of intervention after surgery and cancer treatment, in addition to defining parameters for actions. This perspective study is about the quality of life of patients treated for breast cancer at the Institution. However, as soon as the pandemic started, the need to readapt the way of filling out the questionnaires to an online model emerged. Our objective is to share the facilities and difficulties of online model research. Methods: Through the selection of patients for research that aimed to analyze the quality of life of patients with breast cancer, they were contacted by their registered e-mails in the institution system. Each patient received an explanation of the project through e-mail and the Free and Informed Consent Term (TCLE). After agreement, the survey link of the REDCap system directing the selected instrument to be filled in was sent. The analysis included a general questionnaire composed of demographic and clinical aspects (collected by electronic medical record data) and specific questionnaires. Results: In all, 477 e-mails were sent, 52 patients signed the TCLE (but 2 did not answer the research), 36 answered the questionnaires completely, and 14 incompletely. A total of 12 e-mails were returned (wrong e-mail address). Conclusion: During the pandemic period, new tools were incorporated in order to obtain data and maintain research. Moving to an online way brought the chance to keep studies, giving new possibilities to answer research remotely, but difficulties were added to this new kind of research. E-mail data, lack of explanation face-to-face, and the number of complete responses mainly in long questionnaires were some of the most tricky parts of this new way of study. Online strategy is a real option, but the success of the process depends on many variables.

Introduction: We are currently living in a state of pandemic by COVID-19, whose virus has high transmissibility and potential lethality. The World Health Organization recommended social isolation, and the Brazilian National Cancer Institute, following this guidance, proposed that the oncological treatment of low-to-moderate aggressive tumors be postponed, including breast cancer. In Brazil, the lockdown was a strategy to reduce the potential impact of the pandemic on health services; consequently, asymptomatic patients postponed their imaging tests this year. Considering this abrupt change in access to health care and in the routine of cancer screening, we theorize that the COVID-19 pandemic may have had a negative impact on diagnosis, treatment, and survival in breast cancer patients. Objective: The aim of this study was to analyze the staging at diagnosis of patients with breast cancer, before and during the pandemic, and to calculate if there was a statistical difference comparing the two groups studied. A secondary objective was to describe clinical and demographic characteristics. Methods: A single-center, cross-sectional analytical study with 1219 patients diagnosed with breast cancer (CID C50 or D05) treated at the Mastology Department of the AC Camargo Cancer Center from March 2019 to February 2021. The following epidemiological variables were evaluated: age at years at diagnosis, clinical staging at diagnosis (TNM 8th edition©), presence of comorbidities (risk group for severe COVID-19), family history of cancer, symptoms at diagnosis, and provenance. Descriptive variables and data analysis was performed using Pearson’s χ2 test or Fisher’s exact test. Results: In this study, 1002 patients were included, divided into two groups: prepandemic (574) and pandemic (428). Both groups had similar demographic and clinical characteristics. There was an increase in the frequency of symptomatic patients in the pandemic period 199 (46.5%) versus nonpandemic period 213 (37.1%) (p=0.003). Anatomical and clinical staging were similar between the groups, with no statistically significant difference. When analyzing the anatomical staging, comparing the prepandemic versus pandemic groups, we observed a higher frequency of tumors: T1 [262 (45.6%) vs. 170 (39.8%), p=0.376]; N0 [398 (69.2%) vs. 288 (67.4%), p=0.194]; M0 [552 (96.0%) vs. 415 (97.2%), p=0.614]. Regarding clinical staging, early malignant tumors (EC Tis, Ia–IIIa) were more frequent, corresponding to 521 (90.8%) prepandemic versus 390 (91.1%) pandemic (p=0.766). Conclusion: There was no significant variation between the groups in terms of staging at diagnosis, but more patients with symptoms related to breast cancer sought cancer care.

Introduction: Breast cancer is the second most common malignant neoplasm among women in Brazil and worldwide. It is considered pregnancy-associated when the malignant tumor occurs during pregnancy and up to the first year after delivery. However, current studies show an increased prevalence of these cases, and their causality is not yet well explained. Objective: The aim of this study was to perform a descriptive analysis of the profile of patients with breast cancer during pregnancy treated at our facility from 2010 to 2020. Methods: This retrospective cross-sectional study analyzed electronic health records from a database. The sample consisted of pregnant or postpartum patients diagnosed with breast cancer and treated at AC Camargo Cancer Center from 2010 to 2020. Variables were described based on absolute and relative frequency distributions. Statistical analysis was performed using the Mann-Whitney U test and the independent samples Kruskal-Wallis test. Results: The final sample comprised 44 patients. The mean age was 35 years. Most patients had no comorbidities, were married, white, and had access to the service through health insurance (95.5%). Ductal carcinoma was the most prevalent (84.1%). The main molecular subtypes were luminal B without HER2 expression (34.1%) and triple negative (25%). About 30% of the cases were associated with some genetic mutation. Most patients were diagnosed in the postpartum period (70.5%). Recurrence occurred in five cases. We found four cases of death, three of which had oncological causes. The comparative analysis of variables that could lead to worse prognosis, such as genetic mutation and molecular subtypes, did not indicate a higher recurrence of cases, since they were not statistically significant. Conclusion: The profile of patients with pregnancy-associated breast cancer treated at this cancer center partly follows the trend of other centers.

SUMMARY OBJECTIVE: The aim of this study was to perform dosimetric analysis of radiotherapy (RT) plans with or without elective nodal irradiation (ENI) and estimate whether the increase in mean doses (MDs) in the heart and lungs with ENI may lead to late side effects that may surpass the benefits of treatment. METHODS: The dosimetric analysis of 30 treatment plans was done with or without ENI. The planning and dose-volume histograms were analyzed, and the impact on the mortality of cardiovascular and lung cancer was estimated based on the correlation of the dosimetric data with data from population studies. RESULTS: RT with ENI increased the doses in the lungs and heterogeneity in the plans compared to breast-exclusive RT. When the increase in MDs is correlated with the increase of late side-effect risks, the most important effect of ENI is the increased risk of lung cancer, especially in patients who smoke (average increase in absolute risk=1.38%). The increase in the absolute risk of cardiovascular diseases was below 0.1% in the all the situations analyzed. CONCLUSIONS: ENI increases the heterogeneity and the doses at the lungs. When recommending ENI, the risks and benefits must be taken into account, considering the oncology factors and the plan of each patient. Special attention must be given to patients who smoke as ENI may lead to a significant increase in MD in the lung and the increased risk of radiation-induced lung cancer may surpass the benefits from this treatment.

Introduction: Neoadjuvant chemotherapy in addition to increasing the rate of breast conservation, offers a invaluable opportunity to monitor individual tumor response which may be related to survival outcomes. In view of this, neoadjuvant treatment has been increasingly used.However, several distinct strategies and protocols are employed in this scenario, depending on the histological subtype and local preferences, and there is no clear definition of which one is the best. Most of the published series are from developed countries. Here we describe results of neoadjuvant therapy for non metastaic breast cancer treated in a single Brazilian cancer center.Objective: To evaluate the clinical and pathological characteristics and survival outcomes of breast cancer patients treated with neoadjuvant chemotherapy diagnosed in a single specialized Brazilian institution. Method: This is an observational, retrospective cohort, which included patients diagnosed with invasive breast cancer (stage I to III) submitted to neoadjuvant chemotherapy between January 2007 and December 2018.Results: We evaluated 685 patients with a median age of 46 years, 23.9% were younger than 40 years of age, 64.2% were premenopausal, 24% had a mutation in the BRCA1/2 gene and 70% were treated in the private.Regarding staging, 2.2% had stage I disease, 33.9% stage II, and 63.9% stage III. Approximately 95% of patients received anthracycline-containing regimens. Among patients with ERBB2+ tumors, 97.1% received an anthracycline regimen and 30.3% received double anti-HER2 blockade. Eleven percent of patients with triple-negative triple tumors received carboplatin, and only 0.5% of the hormone receptor positive patients received neoadjuvant hormone therapy. Forty percent of the patients demonstrated complete clinical response and only 30% of thenderwent conservative surgery. Thirty-seven percent had complete pathological response (RCB-0), 13.1% had minimal residual disease (RCB-1,) 40% had moderate to extensive residual disease (RCB-2 and RCB-3), and 0, 8% presented disease progression. The RCB-0 rate was 45.7% for AC dense dose and 31.9% AC for conventional dose (p=0.001). Regardless of hormonal status, in the subgroup with ERBB2 + tumors, the rate of RCB-0 was 61% for those who received HER2 double-blockade versus 55.1% for those who received anti-HER2 monotherapy (p=0.049). Nineteen percent of the patients progressed during the follow-up, with 17% having locoregional progression. In the last follow-up, 70% of the patients were alive without disease, with a median cancer-specific survival (CSS) of 133 months. The median CSS was 129 months among luminal tumors, 116 months for triple-positive, 117 months for triple-negative, and 91 months for HER2 super-expressors (p=0.008). The median SCC of the patients that achieved RCB-0 was 116 months, 89 months for those who had RCB-III, and 27 months for those who presented disease progression (p=0.004). CSS was the same for patients who received or not anthracycline and for those who were treated or not with dense dose schedules. Twenty percent of patients with triple-negative tumors received carboplatin, 52% had RCB-0 versus 34% for those who did not receive carboplatin (p=0.002), however, we did not observe any difference in CSS between these groups (p=0.109). Patients with triple-negative tumors were the only ones in which we observed a direct association between achieving RCB-0 and better CSS and progression-free survival (PFS) (p=0.001 for both). Conclusion: The administration of dose-dense anthracycline, of carboplatin and of anti-HER2 double-blockade increased the rate of RCB-0, nevertheless, this did not translate into improved CSS. Achiving complete pathological response in the triple-negative subtype was was associated with improved CSS and PFS. Citation Format: Monique Celeste Tavares, Marcelle G Cesca, Fernanda A Oliveira, Poliana Andrade, Camilla A Fogassa, Rafaela Pirolli, Bruna R Mattos, Mariana P Xerfan, Sinara Figueiredo, Fernando AB Campos, Vinicius F Calsavara, Solange M Sanches, Fabiana B Makdissi, Cynthia A Bueno, Marina Sonagli, Marina Canal, Vladmir CC Lima. Neoadjuvant therapy outcomes in non metastatic invasive breast carcinomas - Results from a large Brazilian cohort [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-16-30.

Background Whole breast irradiation reduces loco-regional recurrence and risk of death in patients submitted to breast-conserving treatment. Data show that radiation to the index quadrant alone may be enough in selected patients. Aim To report the experience with intra-operative radiotherapy (IORT) with Electron-beam Cone in Linear Accelerator (ELIOT) and the results in overall survival, local control and late toxicity of patients submitted to this treatment. Materials and Methods 147 patients treated with a median follow up of 6.9 years (0.1⿿11.5 years). The actuarial local control and overall survival probabilities were estimated using the Kaplan Meier method. All tests were two-sided and p ⿤ 0.05 was considered statistically significant. Results Overall survival of the cohort in 5 years, in the median follow up and in 10 years was of 98.3%, 95.1% and 95.1%, respectively, whereas local control in 5 years, in the median follow up and in 10 years was of 96%, 94.9% and 89.5%, respectively. Two risk groups were identified for local recurrence depending on the estrogen or progesterone receptors, axillary or margin status and lymphovascular invasion (LVI) (p = 0.016). Conclusions IORT is a safe and effective treatment. Rigorous selection is important to achieve excellent local control results.

Introduction: The axillary lymph node status is one of the most important prognostic factors in breast cancer. For locally advanced tumors, neoadjuvant chemotherapy favors higher rates of breast lumpectomy and downstaging tumor burden of axilla. The aim of this study was to evaluate the use of a standardized image-guided protocol after neoadjuvant chemotherapy to enable sentinel node dissection in patients with axillary downstaging, avoiding axillary dissection. Methods: Retrospective cohort study of data collected from medical records of patients who underwent neoadjuvant chemotherapy in a single center, from January 2014 to December 2018. The protocol comprises the placement of a metal clip in positive axillary lymph node, in patients with up to two clinically abnormal lymph nodes presented on imaging. After neoadjuvant chemotherapy, and once a radiologic complete response was achieved, sentinel node dissection was performed using blue dye and radiotracer. Axillary dissection were avoided in patients whose clipped sentinel node were negative for metastasis and in patients with three identified and negative sentinel node dissection. Results: A total of 471 patients were analyzed for this study: 303 before and 165 after the implementation of the protocol; 3 cases were excluded. The rate of sentinel node dissection in clinical nodes positive patients was statistically higher in this group when compared to patients treated before the protocol implementation (22.8% vs. 40.8%; p=0.001). Patients with triple negative and HER2-positive tumors underwent sentinel node dissection more frequently when compared to luminal tumors (p=0.03). After multivariate analysis, the variables that were associated with a greater chance of performing sentinel node dissection were clinical staging, type of surgery performed and implementation of the axillary assessment protocol. Conclusions: The results showed that the use of an easily and accessible image-guided protocol can improve sentinel node dissection in selected patients, even if the lymph node was positive previously to neoadjuvant treatment.

Introduction: Breast cancer is the most common cancer in women worldwide, whose treatment is increasingly effective with survival above 90% in initial tumors, while it ranges from 20% to 40.8% in metastatic tumors. However, metastatic breast cancer persists and the survival of these women and treatments remain a challenge for oncology. Objective: To analyze the prognostic factors associated with the survival of patients with metastatic de novo breast cancer. Material and Methods: This is a retrospective cohort of women with stage IV (metastatic) breast cancer, conducted from January 1, 2000 to 31 December 2012, treated at the AC Camargo Cancer Center. The overall 5-year survival (OS) by using the Kaplan– Meier product-limit estimator and the differences between the curves and Cox multiple regression by using log-Rank method were observed. Results: Out of 265 patients analyzed, 182 (68.7 %) were alive at the end of the follow-up. The 5-year survival rate was 29.9%. There was a significant difference in survival rates, according to the categorized age (≤50 years, 51–70 years, and ≥71 years; p

Introduction: Nipple-Sparing Mastectomy (NSM) is increasingly indicated for therapeutic and prophylactic purposes due to better cosmetic results with nipple maintenance. Postoperative complications have not been compared among patients who have undergone simultaneous therapeutic and contralateral prophylactic NSM. The aim of the present study was to evaluate the incidence and risk factors for postoperative complications in bilateral/unilateral NSMs, and therapeutic and/or prophylactic NSMs. Methods: Retrospective study of patients who underwent NSM between 2007 and 2017 at A.C. Camargo Cancer Center. Results: Among 290 patients, 367 NSMs were performed, 64 simultaneous therapeutic and contralateral prophylactic NSM. The latter were associated with more postoperative complications (OR=3.42; p=0.002), mainly skin flap necrosis (OR=3.79; p=0.004), hematoma (OR=7.1; p=0.002), wound infection (OR=3.45; p=0.012), and nipple-areola complex (NAC) loss (OR=9.63; p=0.003). Of the 367 NSMs, 213 were unilateral NSMs, which were associated with lower rates of postoperative complications (OR=0.44; p=0.003), especially skin flap necrosis (OR=0.32; p=0.001), hematoma (OR=0.29; p=0.008), wound infection (OR=0.22; p=0.0001), and reoperation (OR=0.38; p=0.008). Obesity was related to more postoperative complications (OR=2.55; p=0.01), mainly hematoma (OR=3.54; p=0.016), reoperation (OR=2.68; p=0.023), and NAC loss (OR=3.54; p=0.016). Patients’ age (p=0.169), their smoking status (p=0.138), breast ptosis (0.189), previous chest radiotherapy (p 1), or previous breast surgery (p=0.338) were not related to higher chances of postoperative complications. Conclusions: Results suggest that performing therapeutic and contralateral prophylactic NSM as separated procedures may represent a good strategy for minimizing postoperative complications.

Pleomorphic adenoma (PA) is a common tumor of the salivary gland, but rarely occurs in the breast. PA of the breast is a benign tumor that usually presents as a periareolar nodule. Core-needle biopsies may yield misdiagnosis with complex fibroadenoma, phyllodes tumor and metaplastic breast cancer due to the mixture of stromal and epithelial elements. We present a case of PA of the breast suspected after core-needle biopsy, but confirmed after surgical excision. The importance to make a correct diagnosis consists in avoid extensive unnecessary surgery, such as mastectomy, since PA can be treated with local surgical resection.

Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer defined by the lack of expression of estrogen receptor, progesterone receptors, and of the human epithelial growth factor receptor 2. Neoadjuvant chemotherapy has proven efficacy in the treatment of TNBC, and a pathological complete response (pCR) is predictive of improved long-term survival. The immune response exerts a vital role in response to neoadjuvant chemotherapy, as indicated by the relation between the percentage of stromal tumor-infiltrating lymphocytes (TILs) in pre-treated tumor tissue samples and the likelihood of achieving pCR. Despite this, the relationship between the systemic immune response and the tumor microenvironment is unclear. In this prospective study, we determined the systemic plasma immune profile of TNBC patients before treatment using a panel of 27 immune mediators and measured the percentage of TILs from the same patients. Patients who demonstrated pCR had significantly higher systemic immune mediators; GM-CSF, FGF-basic, VEGF, IL-2, and IL-5, than the non-responders. Moreover, responders displayed a strong positive correlation between the cytokines IFN-γ and IL-7 with the percentage of TILs, while non-responders had a negative or no correlation. Finally, systemic immune mediator levels before treatment predict pCR (AUC range 0.64 - 0.71), and the combination of immune mediators and TILs improved pCR prediction (AUC 0.71 - 0.82). In conclusion, increased systemic immune mediators reflect increased TILs percentage and act as potential predictive biomarkers of pCR for TNBC patients submitted to neoadjuvant chemotherapy.

Sentinel lymph node biopsy has been developed as the standard of treatment in breast cancer. Status of axillary sentinel lymph node is known to be a significant prognostic factor. Nevertheless, involvement of an intramammary lymph node with metastasis in breast cancer is a rare radiological and clinical presentation, and with extracapsular extravasation even more uncommon. Historically, reported series of patients with intramammary lymph node diagnosed by final histological examination are small in number and clinical significance of metastasis is still unclear. Here, we report a case of conservative breast cancer surgery with 3 intramammary sentinel lymph nodes containing metastasis and extracapsular extravasation. After multidisciplinary consensus, the patient was surgically reapproached with mastectomy. Even though the 3 intramammary sentinel lymph nodes were positive for metastases, pathology examination did not reveal any signs of malignancy in the mastectomy specimen.

Introduction: Adenomastectomy (AM) consists of the almost complete removal of the mammary gland, but preserving the skin envelope and areolar-papillary complex (APC). This technique was initially indicated to women with family history of breast cancer and for treating fibrocystic breast disease. Currently, it can be carried out in a prophylactic manner in patients with genetic mutations associated with higher risks of breast cancer, and in a therapeutic manner for the treatment of tumors smaller than 3 cm, which are peripheral or more than 2 cm away from the APC, with negative retroareolar margin intraoperative freezing. Among the advantages of keeping the APC in AM are the cosmetic results, which favor self-image and self-esteem. Objectives: to assess the incidence of prophylactic AM (PAM) and therapeutic AM (TAM) and relate the PAM with the presence of family history of neoplasms, genetic changes that present high risk for breast cancer or desire of the patient (absence of these criteria). Methods: retrospective study of patients submitted to AM at A.C. Camargo between 2007 and 2017. Results: two-hundred and ninety patients were included, of which 77 were submitted to bilateral AM (154 AM), and 213 patients, to unilateral AM, accounting for 367 AM. Between 2007 and 2009, 116 PAM and 20 TAM were performed; between 2010 and 2013, 40 PAM and 32 TAM; and between 2014 and 2017, 71 PAM and 88 TAM. The indications of PAM were: between 2007 and 2009, 7 PAM were owed to pathogenic mutations, 50 were due to “family history of high risk”, and 58 due to the patient’s desire; between 2010 and 2013, 14 were caused by pathogenic mutations, 12 by “family history of high risk”, and 14 by the patient’s desire; between 2014 and 2017, 45 were owed to pathogenic mutations, 18 to “family history of high risk”, and 8 to the desire of the patient. Conclusions: it is observed that between 2007 and 2017 there was a progressive increase in the incidence of TAM, especially after 2010; simultaneously, there was a reduction in PAM, and they were finally equivalent in 2017. It is possible to observe that the reduction in the incidence of PAM in the first triennium was owed to the reduction in indications of PAM, based only on family history or on the patient’s desire. The recapture of PAM occurred with the increasing number of diagnosis of hereditary syndromes. At the end of the decade, most of the PAMs were performed due to the presence of pathogenic mutations, as advised by NCCN®.

Introduction: Breast cancer screening has enhanced early–stage diagnosis by detection of impalpable tumors which require histopathological evaluation. Main percutaneous biopsy types are core-needle biopsy (CNB) and vacuum-assisted biopsy (VAB). CNB is less invasive and related to less bleeding and pain. VAB allows larger tissue samples and permits metal clip placement in biopsy bed for posterior localization in case of surgery. Access to VAB is restricted in Brazil due to its high costs. Objectives: To evaluate the agreement between pathological results of ultrasound (US) guided CNB with metal clip placement and surgery and settle false negative rates (FNR), sensibility, specificity, and accuracy of this method, for breast lesions < 20 mm. Methods: 388 US-guided CNB were retrospectively reviewed. Results: Surgical excision was performed in 317 patients. Overall FNR was 9.8%, (5.2% for lesions 10–20 mm), sensibility 90.2% (94.8% for lesions 10–20 mm), specificity 94.9% (94.1% for lesions 10–20 mm), and accuracy 91.1% (94.7% for lesions 10–20 mm). Cost of VAB varies from 2.2 to 12.5 times US-guided CNB. With metal clip placement, VAB costs 1.95 to 5.2 times US-guided CNB. Conclusions: For lesions that can be identified in US, CNB with metal clip placement has high sensitivity, specificity, and accuracy, as well as low FNR.

The purpose of this study was to evaluate the capacity of diffusion-weighted magnetic resonance imaging (DW-MRI) for early prediction of pathological response in breast cancer patients undergoing neoadjuvant chemotherapy (NCT). This prospective unicentric study evaluated 62 patients who underwent NCT. MRI was performed prior to the start of treatment (MR1), after the first NCT cycle (MR2), and upon completion of NCT (MR3). Pathological response was used as the gold-standard. Patients’ median age was 45.5 years and the median tumor size was 40 mm. Twenty-four (38.7%) tumors presented complete pathological response (pCR). The percent increase in apparent diffusion coefficient (ADC) value between MR1 and MR2 was higher in the pCR group (p

Objective: To assess the impact of magnetic resonance imaging (MRI) on the locoregional staging of breast cancer. Materials and Methods: We evaluated 61 patients with breast cancer who underwent pre-treatment breast MRI, between August 2015 and April 2016. An experienced breast surgeon determined the surgical treatment, on the basis of the findings of conventional imaging examinations, and made a subsequent treatment recommendation based on the MRI findings, then determining whether the MRI changed the approach, as well as whether it had a positive or negative impact on the treatment. Results: The mean age was 50.8 years (standard deviation, 12.0 years). The most common histological type was invasive breast carcinoma of no special type (in 68.9%), and the most common molecular subtype was luminal B (in 45.9%). Breast MRI modified the therapeutic management in 23.0% of the cases evaluated, having a positive impact in 82.7%. Conclusion: Breast MRI is an useful tool for the locoregional staging of breast cancer, because it provides useful information that can have a positive impact on patient treatment. Resumo Objetivo: Avaliar o impacto do uso da ressonância magnética (RM) no estadiamento pré-operatório do câncer de mama. Materiais e Métodos: Foram avaliadas 61 pacientes com carcinoma mamário submetidas a RM das mamas, no período de agosto de 2015 a abril de 2016. Um mastologista foi questionado sobre a conduta terapêutica indicada diante dos dados da paciente e dos exames convencionais e, após realização da RM, foi novamente questionado sobre a conduta para determinar se houve mudança e impacto no tratamento. Resultados: A média de idade das pacientes foi 50,8 anos (desvio-padrão: 12,0), o tipo histológico mais frequente foi carcinoma mamário invasivo tipo não especial (68,9%) e o imunofenótipo mais prevalente foi luminal B (45,9%). A RM das mamas mudou a conduta terapêutica em 23% dos casos, com impacto positivo em 82,7%. Conclusão: A RM das mamas é instrumento útil no estadiamento locorregional do câncer de mama, sendo capaz de adicionar informações que tenham impacto positivo no tratamento.

The detection of germline mutations in BRCA1 and BRCA2 is essential to the formulation of clinical management strategies, and in Brazil, there is limited access to these services, mainly due to the costs/availability of genetic testing. Aiming at the identification of recurrent mutations that could be included in a low-cost mutation panel, used as a first screening approach, we compiled the testing reports of 649 probands with pathogenic/likely pathogenic variants referred to 28 public and private health care centers distributed across 11 Brazilian States. Overall, 126 and 103 distinct mutations were identified in BRCA1 and BRCA2, respectively. Twenty-six novel variants were reported from both genes, and BRCA2 showed higher mutational heterogeneity. Some recurrent mutations were reported exclusively in certain geographic regions, suggesting a founder effect. Our findings confirm that there is significant molecular heterogeneity in these genes among Brazilian carriers, while also suggesting that this heterogeneity precludes the use of screening protocols that include recurrent mutation testing only. This is the first study to show that profiles of recurrent mutations may be unique to different Brazilian regions. These data should be explored in larger regional cohorts to determine if screening with a panel of recurrent mutations would be effective., This work was supported in part by grants from Barretos Cancer Hospital (FINEP - CT-INFRA, 02/2010), Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, 2013/24633-2 and 2103/23277-8), Fundação de Apoio à Pesquisa do Rio Grande do Norte (FAPERN), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS), Ministério da Saúde, the Breast Cancer Research Foundation (Avon grant #02-2013-044) and National Institute of Health/National Cancer Institute (grant #RC4 CA153828-01) for the Clinical Cancer Genomics Community Research Network. Support in part was provided by grants from Fundo de Incentivo a Pesquisa e Eventos (FIPE) from Hospital de Clínicas de Porto Alegre, by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, BioComputacional 3381/2013, Rede de Pesquisa em Genômica Populacional Humana), Secretaria da Saúde do Estado da Bahia (SESAB), Laboratório de Imunologia e Biologia Molecular (UFBA), INCT pra Controle do Câncer and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). RMR and PAP are recipients of CNPq Productivity Grants, and Bárbara Alemar received a grant from the same agency, info:eu-repo/semantics/publishedVersion

Immediate breast reconstruction with skin graft is still little mentioned in the literature. Follow-up studies regarding the technique aspects are particularly scarce. The objective was to detail immediate breast reconstruction using autologous skin graft.Patients (n = 49) who underwent mastectomies and autologous immediate breast reconstruction with skin graft associated with a breast implant at A. C. Camargo Hospital (São Paulo, Brazil) between January 2007 and July 2010 were included. Information on clinical data, technique details and clinical outcome were prospectively collected. Following mastectomy, the autologous full-thickness skin graft was obtained through an inframammary fold incision along the contralateral breast in most patients. The skin graft was placed on the surface of the pectoralis major muscle after adjustments to conform to the mastectomy defect. A minimum of 10-month follow-up period was established.Patients' age ranged from 35 to 55 years and all received a silicone gel textured surface implant to obtain the necessary breast mound. The mean surgical time was 45 min, and the mean amount of skin resection was 4.5 cm in the largest diameter. Follow-up ranged from 10 to 35 months (median 23). All patients had silicone-gel textured surface implants to perform the breast mound reconstruction. No complications were observed in 87.8% of reconstructions. Forty-six patients (94%) had no complaints about the donor-site aesthetics. The result was a breast mound with a central ellipse of healed skin graft. Three (6%) poor results were observed. Thirty-six patients (67%) reported the results as good or very good.Our results lead us to conclude that autologous skin graft provided a reliable option in immediate breast reconstruction to skin-sparing mastectomy defects. The technique accomplished a single-stage implant breast reconstruction when there is inadequate skin coverage.

Sentinel lymph node biopsy (SLNB) is an appropriate method for the evaluation of axillary status in cases of early breast cancer. We report our experience in treating cases evaluated using SLNB. We analyzed a total of 1192 cases assessed by means of SLNB from July 1999 to December 2007. SLNB processing was successfully completed in 1154 cases with the use of blue dye or radiolabeled 99mTc-Dextran-500, or both. Of these 1154 patients, 857 were N0(i-) (no regional lymph node metastasis, negative immunohistochemistry, IHC), 96 were N0(i+) (no regional lymph node metastasis histologically, positive IHC, no IHC cluster greater than 0.2 mm) and 201 were N1mi (greater than 0.2 mm, none greater than 2.0 mm). Most of the tumors (70%) were invasive ductal carcinomas and tumors were staged as T1 in 770 patients (65%). A total of 274 patients underwent SLNB and axillary dissections up to April 2003. The inclusion criteria were tumor size equal to or less than 3 cm in diameter, no clinically palpable axillary lymph nodes, no neoadjuvant therapy. In 19 cases, the SLN could not be identified intraoperatively. A false-negative rate of 11% and a negative predictive value of 88.2% were obtained for the 255 assessable patients. The overall concordance between SLNB and axillary lymph node status was 92%. SLNB sensitivity for nodes was 81% and specificity was 100%. The higher sensitivity, specificity, accuracy, and lower false-negative rates of SLNB suggest that this method may be an appropriate alternative to total axillary dissection in early breast cancer patients.

Introdução: Os cânceres de mama subtipos Luminal A e B (HER2 negativo) podem apresentar prognóstico variável, a depender do índice de proliferação, avaliado pelo Ki67. As células malignas e as células estromais adjacentes (fibroblastos e células de resposta imune ) podem interagir tanto pelo contato célula a célula como por fatores secretados por elas, ambas influenciando no comportamento tumoral. Já foi demonstrado que as células estromais podem aumentar a proliferação das células do câncer da mama. Objetivo: Nosso objetivo foi avaliar o perfil de expressão gênica de células do estroma em câncer de mama luminal A e luminal B e analisar se este se correlaciona com o prognóstico da doença. Pacientes e Métodos/ Resultados: Amostras de tumores de 11 pacientes na pós menopausa foram analisadas, todas elas HER2 negativas. A expressão de Ki67 foi = 30 % em outras 6 amostras(Luminal B ). Células estromais foram microdissecadas para a extração de RNA, que posteriormente foi hibridizado na plataforma de microarray Agilent G485 -1A GE 8x60K. Após a normalização, 50 % dos genes com a maior variância foram selecionados para análise por SAM duas classes desemparelhado (software TMEV ) e aceitando FDR 14.1%, 35 sequências foram identificadas como diferencialmente expressas, incluindo 16 genes conhecidos, entre as células estromais das amostras de Luminal A versos Luminal B, todos mais expressos nas amostras B. Dentre as funções biológicas enriquecidas em genes diferencialmente expressos encontram-se regulação positiva do sistema imune, incluindo genes como ZAP70 (proteína quinase 70kDa associada a cadeia zeta (TCR)), CD38 (molécula CD38); UBASH3A (ubiquitina associada e SH3 domínio que contém A); PLA2G7 (fosfolipase A2, grupo VII (fator acetil ativador de plaquetas no plasma)); NCR3 (citotoxicidade natural, provocando receptor 3). Nosso próximo passo foi avaliar se a expressão de alguns genes selecionados estava associada com prognóstico de tumores luminais. Para tal selecionamos amostras de outro grupo de 89 pacientes com seguimento de pelo menos 5 anos, cujos tumores eram ER(+), HER2(-), para análise de expressão proteica em Tissue microarray. Caracterizamos os fibroblastos destas amostras com 3 marcadores de fibroblastos: actina de músculo liso (AML), S100A4 e caveolina-1 (CAV1) e analisamos a marcação da proteína ZAP70. Correlacionamos a expressão proteica de todos os marcadores com as características anatomopatológicas da amostra. Observamos que fibroblastos de todas as amostras de tumor de mama expressam AML, S100A4 e CAV1, em diferentes proporções, entretanto não detectamos diferença entre os tumores luminais A e B. Também não obsevamos diferença de expressão de AML, S100A4 e CAV1 em relação a grau histológico, comprometimento linfonodal e estadiamento clínico. Nestas amostras não detectamos expressão proteica de ZAP70 em fibroblastos tumorais. Conclusão: Houve expressão diferencial de 16 genes relacionados a processos imunes, todos eles mais expressos em células estromais de tumores Luminal B em relação a luminal A Introduction: Luminal breast cancer subtypes A and B (HER2 negative) may present a variable prognosis, depending on tumor proliferation index, evaluated by Ki67 expression. Malignant cells and adjacent stromal cells (fibroblasts and immune response cells) may interact by both cell contact and secreted factors and influence tumor behavior. It was shown that stromal cells may enhance breast cancer cells proliferation. Objective: Our aim was to evaluate stromal cells gene expression profile in luminal A and luminal B tumors and to evaluate whether selected transcripts expressed in stromal cells may be associated with prognosis in breast cancer. Material/ Methods and Results: Hormone receptor positive tumor samples from 11 post menopausal patients were analyzed, all of them Her2 negative. Ki67 expression = 30% (luminal B) in six samples. Stromal cells were microdissected for RNA extraction, which was hybridized in Agilent G485-1A GE 8x60K microarray platform. After normalization, 50% of the genes with the highest variance were selected for further analysis by two class unpaired SAM (TMEV software) and accepting FDR 14,1%, 35 sequences, including 16 known genes, were found differentially expressed between stromal cells from luminal A vs luminal B breast cancer samples, all of them more expressed in luminal B. Among biological functions enriched in genes found differentially expressed were positive regulation of immune system process, including genes as: ZAP70 (zeta-chain (TCR) associated protein kinase 70kDa); CD38 (CD38 molecule); UBASH3A (ubiquitin associated and SH3 domain containing A); PLA2G7 (phospholipase A2, group VII (platelet-activating factor acetylhydrolase, plasma); NCR3 (natural cytotoxicity triggering receptor 3). Our next step was evaluate whether expression of selected genes was associated with prognosis in another group of patients. Tumor samples from 89 patients with at least 5 years of follow up, all of them estrogen receptor positive and HER2 negative, were selected. Tissue microarray was prepared with stromal tumor compartment from paraffin embedded tumor samples. Fibroblasts were characterized for the expression of 3 fibroblasts markers (alfa-SMA, alpha smooth muscel actin; S100A4 and CAV1, caveolin 1), and ZAP70. Correlation of expression of these markers with prognostic variables was determined. Expression of alfa-SMA, S100A4 and CAV1 was detected in fibroblasts from all tumor samples in different proportions, however no differential expression was observed between luminal A and B tumors. Neither difference was detected on the expression of these proteins in relation with histological grade, lymph node involvement and clinical stage. Conclusion: A differential expression of 16 genes involved in immune process was found, all of them more expressed in fibroblasts from luminal B as compared with luminal A tumors

A expressão de E-caderina (Ecad) pode ser regulada pré ou pós transcricionalmente por Snail e Hakai, respectivamente. Nosso objetivo foi determinar a expressão de Ecad, Snail e Hakai, em células epiteliais (CE) de tecido tumoral e peritumoral de pacientes com carcinoma ductal invasivo da mama e correlacionar sua expressão ao comprometimento linfonodal axilar (LN+). As CE de amostras de tecidos de 45 pacientes (52% LN+) foram extraídas por método imunomagnético, o RNA foi extraído por RT-PCR em tempo real e utilizou-se primers específicos para a moléculas. A expressão de Ecad, Snail e Hakai não variou entre o tecido tumoral e peritumoral e não houve correlação com comprometimento linfonodal E-cadherin (Ecad) expression may be transcriptionally or post-transcriptionally regulated by Snail and Hakai. Our aim was to determine the expression of Ecad, Snail and Hakai, in epithelial cells (EC) obtained from tumor and its adjacent tissue from women with invasive ductal breast carcinoma (IDC) and evaluate their correlation to the axillary's lymph node (LN+) involvement. Tissue from 45 patients (52% LN+) had their EC recovered by immunomagnetic antibody process, RNA was extracted and real-time RT-PCR was performed using specific primers. Ecad, Snail and Hakai mRNA expression did not vary between tumoral and peritumoral samples and their expression was not correlated to LN involvement

Purpose: This study was designed to identify genes that could predict response to doxorubicin-based primary chemotherapy in breast cancer patients. Experimental Design: Biopsy samples were obtained before primary treatment with doxorubicin and cyclophosphamide. RNA was extracted and amplified and gene expression was analyzed using cDNA microarrays. Results: Response to chemotherapy was evaluated in 51 patients, and based on Response Evaluation Criteria in Solid Tumors guidelines, 42 patients, who presented at least a partial response (≥30% reduction in tumor dimension), were classified as responsive. Gene profile of samples, divided into training set (n = 38) and independent validation set (n = 13), were at first analyzed against a cDNA microarray platform containing 692 genes. Unsupervised clustering could not separate responders from nonresponders. A classifier was identified comprising EMILIN1, FAM14B, and PBEF, which however could not correctly classify samples included in the validation set. Our next step was to analyze gene profile in a more comprehensive cDNA microarray platform, containing 4,608 open reading frame expressed sequence tags. Seven samples of the initial training set (all responder patients) could not be analyzed. Unsupervised clustering could correctly group all the resistant samples as well as at least 85% of the sensitive samples. Additionally, a classifier, including PRSS11, MTSS1, and CLPTM1, could correctly distinguish 95.4% of the 44 samples analyzed, with only two misclassifications, one sensitive sample and one resistant tumor. The robustness of this classifier is 2.5 greater than the first one. Conclusion: A trio of genes might potentially distinguish doxorubicin-responsive from nonresponsive tumors, but further validation by a larger number of samples is still needed.

Introdução: A anemia é uma complicação comum em pacientes com câncer, especialmente naqueles em quimioterapia (QT). Existem poucas estratégias de tratamento para combater a anemia associada ao câncer (AAC). No entanto, pouco tem sido explorado em relação ao efeito do ferro intravenoso (IV) como uma estratégia única para o controle e tratamento da anemia. Objetivos: avaliar a efetividade da suplementação de ferro IV na prevenção da anemia em pacientes submetidos à QT para câncer de mama (CM) não metastático. O objetivo secundário foi a eficácia do Fe IV na redução da necessidade de uso de agentes estimuladores de eritropoiese (AEE) e transfusão de sangue. Métodos: Estudo prospectivo, randomizado, aberto, que incluiu 45 pacientes com CM submetidas a quimioterapia neo ou adjuvante. As pacientes foram selecionadas para o grupo de tratamento com Fe IV nos primeiros 4 ciclos de QT ou para o grupo controle (GC), de maio/10 a setembro/15. Resultados: Todos os parâmetros basais, como nível de hemoglobina (Hb), funções hepática e renal e do metabolismo do ferro, estavam dentro dos valores de referência. Houve redução da Hb inicial em 70% dos pacientes no grupo do Fe e em 82,6% nos pacientes no GC (p não significativo). No entanto, embora a queda de Hb tenha ocorrido, o nível mais baixo foi de 9,4, e nenhuma transfusão de sangue ou o uso de AEE foi necessário. Além disso, houve um bom perfil de tolerância no braço investigacional. Conclusão: A suplementação de Fe IV não foi eficaz na prevenção de AAC no presente estudo. No entanto, esse resultado não invalida novos estudos em diferentes populações e/ou com diferentes esquemas que explorem essa estratégia de tratamento Introduction: Anemia is a common complication in cancer patients, especially those on chemotherapy (CT). There are few treatment strategies to combat cancer-associated anemia (CAA). However, little has been explored regarding the effect of intravenous (IV) iron as a unique strategy for the control and treatment of anemia. Objectives: to evaluate the effectiveness of iron supplementation in the prevention of anemia in patients undergoing CT for non-metastatic breast cancer. The secondary endpoint was the effectiveness of iron in reducing the need for ESA use and blood transfusion. Methods: A prospective, randomized, open-label study including 45 BC patients undergoing neo or adjuvant chemotherapy. Patients were selected for the IV iron treatment group in the first 4 cycles of CT or for the control group, from May/10 to September/15. Results: All baseline parameters as hemoglobin (Hb) level, liver functions and renal and the iron metabolism, were within normal reference values. There was a reduction in initial Hb in 70% of patients in the iron group and in 82.6% in patients without iron. However, even though the Hb drop occurred, the lowest level was 9.4, and no blood transfusion or ESA was required in any of the cases. In addition, there was a good tolerance profile in the investigation arm. Conclusion: IV iron supplementation was not effective in the prevention of CAA in the present study. However, this result does not invalidate further studies in different populations and with different schedules that explore this treatment strategy