Locally advanced breast cancer: breast-conserving surgery and other factors linked to overall survival after neoadjuvant treatment.

Background: Recent data suggest that breast-conserving surgery (BCS) may positively impact overall survival (OS) in early breast cancer. However, the role of BCS in locally advanced breast cancer (LABC) following neoadjuvant therapy (NAT) remains uncertain. Methods: We conducted a retrospective cohort study involving 530 LABC patients who underwent surgery after NAT between 2010 and 2015. Outcomes examined included OS, distant recurrence rates (DRR), and loco-regional recurrence rates (LRRs). Results: Among the 927 breast cancer patients who received NAT, 530 were eligible for our study. Of these, 24.6% underwent BCS, while 75.4% underwent mastectomy (MS). The median follow-up duration was 79 months. BCS patients exhibited a higher pathological complete response (PCR) rate compared to those who underwent MS (22.3% vs. 10%, p < 0.001). The 6-year OS rates for BCS and MS were 81.5% and 62%, respectively (p < 0.000). In multivariate OS analysis, MS was associated with worse outcomes (OR 1.678; 95% CI 1.069-2.635; p = 0.024), as was body mass index (BMI) (OR 1.031; 95% CI 1.006-1.058; p = 0.017), and stage IIIB or IIIC (OR 2.450; 95% CI 1.561-3.846; p < 0.000). Conversely, PCR (OR 0.42; 95% CI 0.220-0.801; p = 0.008) was associated with improved survival. DRR was significantly lower in BCS (15.4%) compared to MS (36.8%) (OR 0.298; 95% CI 0.177-0.504). LRRs were comparable between BCS (9.2%) and MS (9.5%) (OR 0.693; 95% CI 0.347-1.383). Conclusion: Our findings suggest that BCS is oncologically safe, even for patients with large lesions, and is associated with superior OS rates compared to MS. Additionally, lower BMI, lower pretreatment stage, and achieving PCR were associated with improved survival outcomes.

Long-Term Results of Intraoperative Radiation Therapy for Early Breast Cancer Using a Nondedicated Linear Accelerator.

Purpose: To present the long-term results of intraoperative radiation therapy (IORT) for early breast cancer using a nondedicated linear accelerator. Methods and Materials: The eligibility criteria were biopsy-proven invasive carcinoma, age ≥40 years, tumor size ≤3 cm, and N0M0. We excluded multifocal lesions and sentinel lymph node involvement. All patients had previously undergone breast magnetic resonance imaging. Breast-conserving surgery with margins and sentinel lymph node evaluation using frozen sections were performed in all cases. If there were no margins or involved sentinel lymph nodes, the patient was transferred from the operative suite to the linear accelerator room, where IORT was delivered (21 Gy). Results: A total of 209 patients who were followed up for ≥1.5 years from 2004 to 2019 were included. The median age was 60.3 years (range, 40-88.6), and the mean pT was 1.3 cm (range, 0.2-4). There were 90.5% pN0 cases (7.2% of micrometastases and 1.9% of macrometastases). Ninety-seven percent of the cases were margin free. The rate of lymphovascular invasion was 10.6%. Twelve patients were negative for hormonal receptors, and 28 patients were HER2 positive. The median Ki-67 index was 29% (range, 0.1-85). Intrinsic subtype stratification was as follows: luminal A, 62.7% (n = 131); luminal B, 19.1% (n = 40); HER2 enriched 13.4% (n = 28); and triple negative, 4.8% (n = 10). Within the median follow-up of 145 months (range, 12.8-187.1), the 5-year, 10-year, and 15-year overall survival rates were 98%, 94.7%, and 88%, respectively. The 5-year, 10-year, and 15-year disease-free rates were 96.3%, 90%, and 75.6%, respectively. The 15-year local recurrence-free rate was 76%. Fifteen local recurrences (7.2%) occurred throughout the follow-up period. The mean time to local recurrence was 145 months (range, 12.8-187.1). As a first event, 3 cases of lymph node recurrence, 3 cases of distant metastasis, and 2 cancer-related deaths were recorded. Tumor size >1 cm, grade III, and lymphovascular invasion were identified as risk factors. Conclusions: Despite approximately 7% of recurrences, we may infer that IORT may still be a reasonable option for selected cases. However, these patients require a longer follow-up as recurrences may occur after 10 years.

CHEST WALL RESECTION FOR LOCOREGIONAL RECURRENCE OF BREAST CANCER: A FEASIBLE AND EFFECTIVE / Ressecção da parede torácica para recidiva locorregional de câncer de mama: um método efetivo e reprodutível

Objective: The aim of this study was to evaluate survival after chest wall resection for breast cancer locoregional recurrence. Secondary endpoints were symptomatic control and safety of the procedure. Method: This was a retrospective review including all patients who underwent chest wall resection for breast cancer local recurrence at the Division of Thoracic Surgery of the School of Medicine of São Paulo University, from January 1998 to November 2011. Full thickness chest wall resection involving bones and/or soft tissues was performed to achieve macroscopical free margins. Results: Eighteen patients were included in this study with a mean followup of 83.5 months. The interval between mastectomy and chest wall recurrence (CWR) was 4.2 years (0.5 to 9 years). The resection was complete in 12 patients (66%) and incomplete in 6 (33%), in whose resection would involve amputation of an upper limb. Mean tumor size was 8.25 cm and resection of the costal arch was necessary in 10 patients. There was no operation death and after two years, 66% of patients were alive. Six patients died due to distant recurrence of breast cancer on patients who died to inflammatory acute abdomen. The mean survival among patients who died was 25.2 months (12 to 42 months). At the last follow up visit, eleven patients were alive. Conclusion: CWR for locally recurrent breast cancer is feasible and safe in selected patients, who did not develop metastatic disease, allowing good quality of life for a considerable period. Larger and prospective series are needed to endorse our findings.

Objetivo: O objetivo deste estudo foi avaliar a sobrevida após ressecção da parede torácica para recidiva locorregional de c âncer de mama. Desfechos secundários foram controle dos sintomas e a segurança do procedimento. Métodos: Estudo retrospectivo de todos os pacientes submetidos à ressecção da parede torácica para recidiva local do câncer de mama na Divisão de Cirurgia Torácica da Faculdade de Medicina da Universidade de São Paulo, de janeiro de 1998 a novembro de 2011. A ressecção da parede torácica foi realizada com espessura total podendo envolver ossos e/ou tecidos moles, a fim de atingir margens livres macroscópicas. Resultados: Dezoito pacientes foram incluídos neste estudo, com seguimento médio de 83,5 meses. O intervalo entre a mastectomia e a recidiva da parede torácica (RPT) foi de 4,2 anos (0,5 a 9 anos). A ressecção foi completa em 12 pacientes (66%) e incompleta em 6 (33%), cuja ressecção envolveria a amputação do membro superior. O tamanho médio do tumor foi de 8,25cm e a ressecção do arco costal foi necessária em 10 pacientes. Não houve óbito devido à operação e, após dois anos, 66% dos pacientes estavam vivos. Seis pacientes morreram devido à recorrência sistêmica do câncer de mama e uma paciente morreu devido a um abdome agudo inflamatório. A sobrevida média entre os pacientes que morreram foi de 25,2 meses (12 a 42 meses). Na última consulta de acompanhamento, onze pacientes estavam vivos. Conclusões: A RPT para a recidiva locorregional do câncer de mama é factível e segura em pacientes selecionados, que não desenvolveram doença metastática, permitindo boa qualidade de vida por um período considerável. São necessárias séries maiores e prospectivas para endossar nossas achados

Clinical impact of adjuvant radiation therapy delay after neoadjuvant chemotherapy in locally advanced breast cancer.

BACKGROUND: and Purpose: Post-operative radiation therapy (PORT) is usually indicated for patients with breast cancer (BC) after neoadjuvant chemotherapy (NAC) and surgery. However, the optimal timing to initiation of PORT is currently unknown. MATERIAL AND METHODS: We retrospectively evaluated data from patients with BC who received PORT after NAC and surgery at our institution from 2008 to 2014. Patients were categorized into three groups according to the time between surgery and PORT: <8 weeks, 8-16 weeks and >16 weeks. RESULTS: A total of 581 patients were included; 74% had clinical stage III. Forty-three patients started PORT within 8 weeks, 354 between 8 and 16 weeks and 184 beyond 16 weeks from surgery. With a median follow-up of 32 months, initiation of PORT up to 8 weeks after surgery was associated with better disease-free survival (DFS) (<8 weeks versus 8-16 weeks: HR 0.33; 95% CI 0.13-0.81; p = 0.02; <8 weeks versus >16 weeks: HR 0.38; 95% CI 0.15-0.96; p = 0.04) and better overall survival (OS) (<8 weeks versus 8-16 weeks: HR 0.22; 95% CI 0.05-0.90; p = 0.036; <8 weeks versus >16 weeks: HR 0.28; 95% CI 0.07-1.15; p = 0.08). CONCLUSION: PORT started up to 8 weeks after surgery was associated with better DFS and OS in locally-advanced BC patients submitted to NAC. Our findings suggest that early initiation of PORT is critically important for these patients. However, the low numbers of patients and events in this study prevent us from drawing firm conclusions.

EZH2 Protein Expression and Tumor Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer.

Introduction Neoadjuvant chemotherapy (NAC) is the standard treatment for locally advanced breast cancer. However, some tumors will not respond to this treatment due to histological and molecular features. The protein EZH2 (enhancer of zest homolog 2) is a histone methyltransferase that is correlated with poorly differentiated breast carcinomas and aggressive tumor behavior. Purpose The present study evaluated the association between EZH2 expression and response to NAC, and its correlation with HER2 overexpression, estrogen and progesterone receptors (ER, PR) and Ki-67 proliferation index. Methods A total of 60 patients with locally advanced breast cancer treated with NAC were selected for this study. Twenty-three paraffin blocks had not enough material for tissue resection, and were not evaluated. A tissue microarray based in immunohistochemistry (IHC) analysis of EZH2 was performed for the remaining 37 specimens. Patients were divided into two groups based on response to NAC. Results EZH2 expression was significantly associated with markers of poor prognosis such as ER negativity (p = 0.001), PR negativity (p = 0.042) and high Ki-67 proliferation index (p = 0.002). High EZH2 expression was not correlated with the response to NAC. Conclusions Our data suggested that EZH2 protein expression may not correlate with the clinical response to NAC. Other studies with more patients are needed to confirm this observation.

EZH2 Protein Expression and Tumor Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer / Expressão da proteína EZH2 e resposta tumoral à quimioterapia neoadjuvante no câncer de mama localmente avançado

Abstract Introduction Neoadjuvant chemotherapy (NAC) is the standard treatment for locally advanced breast cancer. However, some tumors will not respond to this treatment due to histological and molecular features. The protein EZH2 (enhancer of zest homolog 2) is a histone methyltransferase that is correlated with poorly differentiated breast carcinomas and aggressive tumor behavior. Purpose The present study evaluated the association between EZH2 expression and response to NAC, and its correlation with HER2 overexpression, estrogen and progesterone receptors (ER, PR) and Ki-67 proliferation index. Methods A total of 60 patients with locally advanced breast cancer treated with NAC were selected for this study. Twenty-three paraffin blocks had not enough material for tissue resection, and were not evaluated. A tissue microarray based in immunohistochemistry (IHC) analysis of EZH2 was performed for the remaining 37 specimens. Patients were divided into two groups based on response to NAC. Results EZH2 expression was significantly associated with markers of poor prognosis such as ER negativity (p = 0.001), PR negativity (p = 0.042) and high Ki-67 proliferation index (p = 0.002). High EZH2 expression was not correlated with the response to NAC. Conclusions Our data suggested that EZH2 protein expression may not correlate with the clinical response to NAC. Other studies with more patients are needed to confirm this observation.

Resumo Introdução A quimioterapia neoadjuvante é o tratamento padrão para os cânceres de mama localmente avançados. Entretanto, apenas uma porcentagem desses tumores irá responder ao tratamento, devido a características histológicas e moleculares. A proteína EZH2 (enhancer of zest homolog 2) é uma histona metiltransferase associada a tumores mal diferenciados e de comportamento agressivo. Objetivo O presente estudo teve como objetivo avaliar a associação entre a expressão da proteína EZH2 e a resposta à quimioterapia neoadjuvante, além da correlação dessa proteína com hiper-expressão de HER2, receptores de estrogênio e progesterona, e o marcador de proliferação Ki-67. Métodos Um total de 60 pacientes com câncer de mama localmente avançado tratadas com quimioterapia neoadjuvante foram selecionadas para esse estudo. Vinte e três blocos de parafina não continham material suficiente para ressecção e não foram avaliados. Foi realizado microarray baseado em análise imuno-histoquímica da proteína EZH2 para as 36 pacientes restantes. As pacientes foram divididas em dois grupos baseado na resposta à quimioterapia neoadjuvante. Resultados A expressão da proteína EZH2 foi significativamente associada com marcadores de pior prognóstico, como negatividade para receptor de estrogênio (p = 0,001) e progesterona (p = 0,042), além de alto Ki-67 (p = 0,002). Entretanto, a alta expressão da EZH2 não se correlacionou com a resposta à quimioterapia neoadjuvante. Conclusões Nossos dados sugerem que a expressão da proteína EZH2 pode não estar relacionada com a resposta clínica à quimioterapia neoadjuvante. Outros estudos com maior número de pacientes são necessários para confirmar esses achados.

SPECT-CT-Guided Thoracoscopic Biopsy of Sentinel Lymph Nodes in the Internal Mammary Chain in Patients With Breast Cancer: A Pilot Study.

OBJECTIVE: The objective of this study was to determine the impact of the use of single-photon emission computed tomography fused with computed tomography (SPECT-CT) on thoracoscopic biopsy of sentinel lymph nodes (SLNs) in the internal mammary chain in patients with breast cancer by evaluating resultant changes in staging and their clinical implications. METHODS: Between September 2010 and January 2014, we performed lymphoscintigraphy-assisted thoracoscopic biopsy of the internal mammary chain SLN in 20 patients with breast cancer. Single-photon emission computed tomography fused with computed tomography was also used in 13 of these patients. The sentinel nodes were surgically identified with the aid of a gamma probe. RESULTS: Sentinel lymph nodes were identified surgically in 19 of 20 patients. In the 13 patients in whom SPECT-CT was used, it readily identified SLNs, especially when they were located over an intercostal space. Change of staging occurred in three patients (15%), two of whom accordingly received adjuvant radiotherapy to the internal thoracic chain. CONCLUSIONS: Compared with lymphoscintigraphy alone, the use of SPECT-CT improves localization of the SLN in the internal mammary chain, allowing more accurate planning of each individual's treatment.

MRI to Predict Nipple Involvement in Breast Cancer Patients.

OBJECTIVE: The selection of breast cancer patients as candidates for nipple-sparing mastectomy (NSM) is dependent on the preoperative detection of neoplastic involvement of the nipple-areola complex (NAC). This cross-sectional study was designed to evaluate the accuracy of preoperative breast MRI as a noninvasive method to predict neoplastic involvement of the nipple. MATERIALS AND METHODS: We included 165 female breast cancer patients with a surgical plan that included total mastectomy or breast conservation surgery with the removal of the NAC. All patients underwent MRI before surgery on a 1.5-T unit with a 4-channel in vivo dedicated surface breast coil. One radiologist who was blinded to the results of the histologic evaluations of the specimens evaluated the MRI studies. RESULTS: Of the 170 mastectomy specimens evaluated, 37 (21.8%) had neoplastic involvement of the NAC. The MRI findings of enhancement between the index lesion and the NAC and of nipple retraction were considered statistically significant predictors of nipple involvement in breast cancer patients (p < 0.01 and p = 0.01, respectively). The negative predictive value of the combination of these MRI findings was 83.3%. CONCLUSION: Breast MRI is a safe noninvasive method to preoperatively evaluate breast cancer patients eligible for NSM with a high specificity and a high negative predictive value when enhancement between the index lesion and the nipple and nipple retraction are analyzed.

Feasibility of two schedules of weekly paclitaxel in HER2-negative early breast cancer in a Brazilian community setting.

BACKGROUND: Weekly paclitaxel has been shown more effective and less toxic than the conventional three-weekly administration. The GEICAM 9906 demonstrated effectiveness and safety of a dose-dense schedule of 100 mg/m(2) of paclitaxel given over 8 weeks (w). This schedule has been adopted at our institution in 2009 for HER2-negative disease, and herein, we present the first off-trial experience and compare its safety profile with that of a historical cohort of patients treated with the conventional 80 mg/m(2) over 12 w schedule. METHODS: Retrospective single-center chart review of patients with locally advanced breast cancer treated with (neo)adjuvant paclitaxel-based therapy from 2008 to 2012 with (1) 80 mg/m(2) for 12 w or (2) 100 mg/m(2) for 8 w. Adverse events were graded according to common terminology criteria for adverse events (CTCAE) 4.0. RESULTS: A total of 326 patients were analyzed. Median age was 52 (±10.9). Seventy and 256 patients received schedule (1) and (2), respectively. No significant difference was observed in the incidence of grade (G) 3/4 toxicity: pneumonitis (2.8 vs 0.3 % p = 0.097); neuropathy (2.8 vs 0.7 % p = 0.303); hand-foot syndrome (1.4 vs 0.3 % p = 0.538); anemia (0 vs 0.6 % p = 0.624); and neutropenia (5.7 vs 6.2 % p = 0.408). Also, no significant difference was seen when comparing all grades toxicity. Schedule (2) had higher dose intensity: 97.72 vs 77.07 mg/m(2) per week (p < 0.0001). CONCLUSIONS: Weekly paclitaxel given according to GEICAM 9906 is pragmatic and well tolerated, with safety profile consistent with the conventional schedule. In addition to being convenient to patients, it may also be cost-effective because of a lower number of clinic visits and infusions.

Breast necrosis induced by the use of coumadin: case report and review of literature / Necrose mamária induzida pelo uso de cumarínico: relato de caso e revisão da literatura

The coumadin-induced skin necrosis is rare and occurs more frequently in the breasts, thighs and buttocks. We describe the first case of coumadin necrosis of the breast in Brazil in a 62-year-old patient.

A necrose cutânea induzida por cumarínicos é um evento raro e ocorre com maior frequência nas mamas, coxas e nádegas. Descrevemos o primeiro caso de necrose cumarínica das mamas no Brasil em paciente de 62 anos.

Criteria for prediction of metastatic axillary lymph nodes in early-stage breast cancer.

PURPOSE: To estimate the likelihood of axillary lymph node involvement for patients with early-stage breast cancer, based on a variety of clinical and pathological factors. METHODS: A retrospective analysis was done in hospital databases from 1999 to 2007. Two hundred thirty-nine patients were diagnosed with early-stage breast cancer. Predictive factors, such as patient age, tumor size, lymphovascular invasion, histological grade and immunohistochemical subtype were analyzed to identify variables that may be associated with axillary lymph node metastasis. RESULTS: Patients with tumors that are negative for estrogen receptor, progesterone receptor, and HER2 had approximately a 90% lower chance of developing lymph node metastasis than those with luminal A tumors (e.g., ER+ and/or PR+ and HER2-) - Odds Ratio: 0.11; 95% confidence interval: 0.01-0.88; p=0.01. Furthermore, the risk for lymph node metastasis of luminal A tumors seemed to decrease as patient age increased, and it was directly correlated with tumor size. CONCLUSION: The molecular classification of early-stage breast cancer using immunohistochemistry may help predicting the probability of developing axillary lymph node metastasis. Further studies are needed to optimize predictions for nodal involvement, with the aim of aiding the decision-making process for breast cancer treatment.

Criteria for prediction of metastatic axillary lymph nodes in early-stage breast cancer / Critérios para predição de metástases axilares em câncer de mama em estádio clínico inicial

PURPOSE: To estimate the likelihood of axillary lymph node involvement for patients with early-stage breast cancer, based on a variety of clinical and pathological factors. METHODS: A retrospective analysis was done in hospital databases from 1999 to 2007. Two hundred thirty-nine patients were diagnosed with early-stage breast cancer. Predictive factors, such as patient age, tumor size, lymphovascular invasion, histological grade and immunohistochemical subtype were analyzed to identify variables that may be associated with axillary lymph node metastasis. RESULTS: Patients with tumors that are negative for estrogen receptor, progesterone receptor, and HER2 had approximately a 90% lower chance of developing lymph node metastasis than those with luminal A tumors (e.g., ER+ and/or PR+ and HER2-) - Odds Ratio: 0.11; 95% confidence interval: 0.01-0.88; p=0.01. Furthermore, the risk for lymph node metastasis of luminal A tumors seemed to decrease as patient age increased, and it was directly correlated with tumor size. CONCLUSION: The molecular classification of early-stage breast cancer using immunohistochemistry may help predicting the probability of developing axillary lymph node metastasis. Further studies are needed to optimize predictions for nodal involvement, with the aim of aiding the decision-making process for breast cancer treatment. .

OBJETIVO: Estimar a probabilidade de acometimento linfonodal em pacientes com câncer de mama inicial, baseado em fatores clínicos e patológicos. MÉTODOS: Foi realizada uma análise retrospectiva de 1999 a 2007 dos bancos de dados do hospital. Um total de 239 pacientes foram diagnosticados com câncer de mama em estádio inicial. Fatores preditivos como idade, tamanho do tumor, presença de invasão linfovascular, grau histológico e subtipo imunoistoquímico foram analisados para identificar possíveis variáveis associadas com a presença de metástases axilares. RESULTADOS: Pacientes com tumores negativos para receptor de estrogênio, receptor de progesterona e HER2 tiveram aproximadamente 90% menos chance de terem metástases axilares do que pacientes com tumores luminais A (por exemplo, ER+ e/ou PR+ e HER2-) - Odds Ratio: 0,11; intervalo de confiança de 95%: 0,01-0,88; p=0,013. Além disso, o risco de metástases axilares para tumores luminais A diminuiu com o aumento da idade e se correlacionou diretamente com o tamanho do tumor. CONCLUSÃO: A classificação molecular do câncer de mama em estádio inicial utilizando a imunoistoquímica pode ajudar a predizer a probabilidade de encontrar metástases axilares. Novos estudos são necessários para otimizar essa predição, auxiliando no processo de decisão do tratamento relacionado ao câncer de mama. .

Breast necrosis induced by the use of coumadin: case report and review of literature.

The coumadin-induced skin necrosis is rare and occurs more frequently in the breasts, thighs and buttocks. We describe the first case of coumadin necrosis of the breast in Brazil in a 62-year-old patient.

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 patient's 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 patient's 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.

Variations in the body mass index in Brazilian women undergoing adjuvant chemotherapy for breast cancer / Variações no índice de massa corpórea em mulheres brasileiras submetidas à quimioterapia adjuvante por câncer de mama

PURPOSE: To evaluate variations in the body mass index in patients undergoing adjuvant chemotherapy for breast cancer, and to associate these changes with patient's 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 patient's 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. .

OBJETIVO: Avaliar variações no índice de massa corpórea em pacientes que estão passando por quimioterapia devido ao câncer de mama, e relacionar tais alterações com a idade da paciente e o regime de quimioterapia. MÉTODOS: Estudo de coorte retrospectivo que correlacionou variações no índice de massa corpórea pré- e pós-quimioterapia com a idade da paciente e o regime de quimioterapia. Foram excluídas as pacientes que receberam terapia hormonal prévia, seja como tamoxifeno ou inibidores da aromatase. Os dados de 196 pacientes com estágio I a III de câncer de mama foram selecionados, e elas foram tratadas por cirurgia radical ou conservadora que receberam quimioterapia adjuvante no Instituto do Câncer do Estado de São Paulo, Brasil. RESULTADOS: Antes da quimioterapia adjuvante, 67,8% das pacientes foram classificadas com sobrepeso ou obesas de acordo com seus índices de massa corpórea. Aproximadamente 66,3% (IC95% 59,7–73,0) das pacientes exibiram aumento no índice de massa corpórea após a quimioterapia adjuvante. A média de idade das pacientes foi de 56,3± 11,3 anos. Pacientes que apresentaram aumento no índice de massa corpórea eram mais jovens do que aquelas que não apresentaram aumento algum (54,7±11,1 versus 59,3±11,2 anos; p=0,007). As pacientes foram tratadas com os seguintes regimes de quimioterapia: doxorrubicina, ciclofosfamida e paclitaxel (AC-T, 129 pacientes, 65,8%); 5-fluoracil, doxorrubicina e ciclofosfamida (36 pacientes, 18,4%); ciclofosfamida, metotrexato e 5-fluoracil (16 pacientes, 8,2%); docetaxel e ciclofosfamida (7 pacientes, 3,6%) e outros regimes (8 pacientes, 4,1%). O regime AC-T mostrou uma relação significativa com o aumento do índice de massa corpórea (p<0,001 por ANOVA). CONCLUSÕES: A maioria das pacientes ...

Intraoperative radiation therapy in early breast cancer using a linear accelerator outside of the operative suite: an "image-guided" approach.

PURPOSE: To present local control, complications, and cosmetic outcomes of intraoperative radiation therapy (IORT) for early breast cancer, as well as technical aspects related to the use of a nondedicated linear accelerator. METHODS AND MATERIALS: This prospective trial began in May of 2004. Eligibility criteria were biopsy-proven breast-infiltrating ductal carcinoma, age >40 years, tumor <3 cm, and cN0. Exclusion criteria were in situ or lobular types, multicentricity, skin invasion, any contraindication for surgery and/or radiation therapy, sentinel lymph node involvement, metastasis, or another malignancy. Patients underwent classic quadrantectomy with intraoperative sentinel lymph node and margins evaluation. If both free, the patient was transferred from operative suite to linear accelerator room, and IORT was delivered (21 Gy). Primary endpoint: local recurrence (LR); secondary endpoints: toxicities and aesthetics. Quality assurance involved using a customized shield for chest wall protection, applying procedures to minimize infection caused by patient transportation, and using portal films to check collimator-shield alignment. RESULTS: A total of 152 patients were included, with at least 1 year follow-up. Median age (range) was 58.3 (40-85.4) years, and median follow-up time was 50.7 (12-110.5) months. The likelihood of 5-year local recurrence was 3.7%. There were 3 deaths, 2 of which were cancer related. The Kaplan-Meier 5-year actuarial estimates of overall, disease-free, and local recurrence-free survivals were 97.8%, 92.5%, and 96.3%, respectively. The overall incidences of acute and late toxicities were 12.5% and 29.6%, respectively. Excellent, good, fair, and bad cosmetic results were observed in 76.9%, 15.8%, 4.3%, and 2.8% of patients, respectively. Most treatments were performed with a 5-cm collimator, and in 39.8% of the patients the electron-beam energy used was ≥12 MeV. All patients underwent portal film evaluation, and the shielding was repositioned in 39.9% of cases. No infection or anesthesia complications were observed. CONCLUSIONS: Local control with IORT was adequate, with low complication rates and good cosmetic outcomes. More than one-third of patients benefited from the "image-guidance" approach, and almost 40% benefited from the option of higher electron beam energies.

Intraoperative full-dose of partial breast irradiation with electrons delivered by standard linear accelerators for early breast cancer.

Purpose. To assess feasibility, efficacy, toxicity, and cosmetic results of intraoperative radiotherapy (IORT) with electrons delivered by standard linear accelerators (Linacs) during breast conserving surgeries for early infiltrating breast cancer (BC) treatment. Materials and Methods. A total of 152 patients with invasive ductal carcinoma (T ≤ 3.0 cm) at low risk for local relapses were treated. All had unicentric lesions by imaging methods and negative sentinel node. After a wide local excision, 21 Gy were delivered on the parenchyma target volume with electron beams. Local recurrences (LR), survival, toxicity, and cosmetic outcomes were analyzed. Results. The median age was 58.3 years (range 40-85); median follow-up was 50.7 months (range 12-101.5). There were 5 cases with LR, 2 cases with distant metastases, and 2 cases with deaths related to BC. The cumulative incidence rates of LR, distant metastases, and BC death were 3.2%, 1.5%, and 1.5%, respectively. Complications were rare, and the cosmetic results were excellent or good in most of the patients. Conclusions. IORT with electrons delivered by standard Linacs is feasible, efficient, and well tolerated and seems to be beneficial for selected patients with early infiltrating BC.

Thoracoscopic approach of the internal thoracic lymphatic chain.

OBJECTIVE: Few studies to date have evaluated the videothoracoscopic approach of the internal thoracic lymphatic chain. However, the histological evaluation of lymph nodes is essential for patients with breast cancer who show lymph node uptake at scintigraphy in the preoperative period and also for patients with lymphoma who have exclusive uptake in these lymph nodes at positron emission tomography for recurrence assessment. Our goal was to evaluate the safety and the change in oncologic approach through this minimally invasive technique. METHODS: This is a review of the prospectively collected data in a group of patients undergoing thoracoscopic biopsy of the thoracic lymphatic chain in patients with breast cancer and lymphoma carried out in our institution between September 2010 and June 2012. The analyzed variables include age, histological type, operated hemithorax, number of resected lymph nodes, neoplastic involvement of the resected lymph nodes, duration of chest tube drainage, length of hospital stay, and perioperative mortality. Complications such as subcutaneous emphysema and necessity for blood transfusion were also evaluated. RESULTS: Thoracoscopic biopsy was successfully performed in 16 patients, of whom 14 had breast cancer and 2 had lymphoma. The surgical biopsy results changed the treatment in the two patients with lymphoma and avoided radiotherapy in the eight patients with breast cancer who did not have metastases. CONCLUSIONS: The use of the thoracoscopic assessment of the internal thoracic lymphatic chain seems safe and resulted in therapy modification in more than half of our patients, suggesting that it is an effective technique for staging in selected breast cancer and lymphoma cases.

Radicality effect of adding an interpectoral to a subpectoral approach for dissection of level III axillary lymph nodes in breast cancer.

AIMS AND BACKGROUND: The extent of axillary lymph node dissection for breast cancer treatment is tailored to each patient. When the surgeon assumes that full dissection, including level III, is needed, there are basically two ways for reaching the apical nodes while preserving the pectoralis muscles: a subpectoral approach, below the joined pectoralis muscles, and another that includes an additional interpectoral dissection between the muscles. We conducted a study to evaluate the radicality of dissection using these two approaches. METHODS: To determine whether the harvest of level III axillary lymph nodes is equivalent with the different approaches, we prospectively studied 75 patients with breast cancer. Careful axillary lymph node dissection was done to as radical an extent as possible, first below the lateral edge of the joined pectoralis muscles (subpectoral approach) and sequentially after opening the space between the muscles (additional interpectoral approach). The number of patients with extra level III nodes retrieved by the addition of an interpectoral dissection as well as the number of complementary nodes obtained in such patients were determined. RESULTS: We excised 1701 axillary lymph nodes in 75 patients (mean, 22.7). Using first the subpectoral approach, we resected 259 level III nodes in 68 patients (mean, 3.8); in 56 patients, we removed 132 additional level III nodes using the supplementary interpectoral approach (mean, 2.4). In 7 patients (9.3%), we found at least one metastatic node with the interpectoral approach. Two of these patients had positive level III nodes that were discovered only by addition of the interpectoral dissection. CONCLUSIONS: The dissection of level III axillary nodes is more radical when an additional interpectoral dissection is performed after a subpectoral approach has been used. The exclusive subpectoral approach frequently leaves residual nodes at the apex of the axilla.

Metástase oculta em linfonodo sentinela no câncer de mama em estádios iniciais / Occult metastasis in sentinel lymph node in early-stage breast cancer

OBJETIVO: a identificação e biópsia do linfonodo sentinela (LS) no câncer de mama em estádio inicial vêm substituindo a dissecção axilar total. Neste estudo, será apresentada a técnica de processamento do LS, visando o diagnóstico de metástase oculta com base no exame histológico e imuno-histoquímico. MÉTODOS: entre os anos de 2002 e 2005, 266 linfonodos sentinelas foram dissecados em 170 pacientes com câncer de mama em estádio inicial. Foram incluídos apenas os linfonodos considerados negativos durante análise intra-operatória por citologia. Os linfonodos foram seccionados tranversalmente em quatro ou cinco fatias e incluídos em parafina. Em cada bloco de parafina, dois cortes histológicos com 4 µm de espessura foram montados em lâminas para microscopia de luz e corados pela técnica da hematoxilina-eosina e imunoperoxidase (citoqueratina AE1/AE3). RESULTADOS: a avaliação histológica convencional identificou metástase no LS de 22 pacientes (12,9 por cento). Em seis destas (3,5 por cento), o acometimento foi do tipo micrometástase. Já a metástase oculta diagnosticada exclusivamente pela imuno-histoquímica ocorreu em 16 pacientes (9,4 por cento). Em 11 destas (6,5 por cento) foram detectadas células tumorais isoladas e em cinco (2,9 por cento), micrometástases. CONCLUSÕES: a associação do exame histológico de parafina e imuno-histoquímica aumenta a capacidade de identificar metástase oculta no LS de pacientes com câncer de mama em estádios iniciais.

PURPOSE: sentinel lymph node biopsy in early-stage breast cancer patients has been substituting the total axillary lymph node is presented dissection. The technique of processing the sentinel lymph node and the aim of this study was to investigate the efficacy of occult metastasis identification based on the standard histological and immunohistochemical examination. METHODS: between 2002 and 2005, 266 sentinel lymph nodes were harvested from axillary biopsy of 170 patients with early stage breast cancer. All lymph nodes were considered to be negative according to standard intra-operative cytological assessment. Lymph nodes were transversally sectioned in four or five slices and embedded in paraffin blocks. Two paraffin-embedded tissue sections with 4 µm in thickness were mounted on glass slides and stained with hematoxylin-eosin and immunoperoxidase (cytokeratin AE1/AE3) techniques. RESULTS: standard histological examination identified metastasis in 22 patients (12.9 percent) and micrometastatic disease was observed in six of these patients (3.5 percent). The immunohistochemical examination identified metastatic disease in 16 patients (9.4 percent). Among them, isolated tumor cells were observed in 11 (6.5 percent) and micrometastases were identified in five (2.9 percent). CONCLUSIONS: the association of the standard histological examination and immunohistochemical technique increases the chances of sentinel lymph node metastasis identification.