Evaluation of tumor infiltrating lymphocytes as a prognostic biomarker in patients with ductal carcinoma in situ of the breast.

PURPOSE: To assess the association between tumor-infiltrating lymphocytes (TILs) in ductal carcinoma in situ (DCIS) samples and disease recurrence. METHODS: This retrospective cohort study included women aged 18 years and older who underwent treatment between January 2007 and December 2020. Male patients, individuals diagnosed with invasive or microinvasive disease based on anatomopathological examination of surgical specimens, and those with a personal history of any other cancers were excluded. Additionally, the presence of "touching TILs" (lymphocytes in direct contact with tumor cells) and periductal desmoplasia were evaluated as complementary methods to represent the immunological microenvironment. The primary outcome was relapse-free survival based on TIL quantification adjusted for potential confounders. Pathologists assessed TILs in the sample with the highest tumor representation and quantified them as a percentage. Survival was evaluated using Kaplan‒Meier curves, log-rank tests, and Cox regression models. RESULTS: A total of 191 patients met the eligibility criteria. The mean follow-up duration was 77.2 months, with a recurrence rate of 9.2%. Patients with TILs ≥ 17% had a greater risk of recurrence (HR 2.97, 95% CI 1.17-7.51; p = 0.02). Additionally, focal necrosis (HR 6.4, 95% CI 1.39-34.71; p = 0.018) or comedonecrosis (HR 4.53, 95% CI 1.34-15.28; p = 0.015) were associated with increased recurrence risk. According to the multivariate model, comedonecrosis and TILs ≥ 17% were significantly associated with recurrence (p = 0.034 and p = 0.035, respectively). Regarding the evaluations of "touching TILs" and periductal desmoplasia, no statistical significance was found when assessing their association with disease recurrence. CONCLUSION: In our cohort, a high percentage of TILs (≥ 17%) and the presence of comedonecrosis were independently associated with DCIS recurrence.

Predictive value of ultrasound doppler parameters in neoadjuvant chemotherapy response of breast cancer: Prospective comparison with magnetic resonance and mammography.

BACKGROUND: Neoadjuvant chemotherapy (NACT) is a treatment option for breast cancer patients that allows for the assessment of tumor response during treatment. This information can be used to adjust treatment and improve outcomes. However, the optimal imaging modalities and parameters for assessing tumor response to NACT are not well established. METHODS: This study included 173 breast cancer patients who underwent NACT. Patients were imaged with ultrasound (US), mammography (MMG), and magnetic resonance imaging (MRI) at baseline, after two cycles of NACT, and before breast surgery. US parameters included lesion morphology, Doppler variables, and elastography measurements. MMG and MRI were evaluated for the presence of nodules and tumor dimensions. The pathological response to NACT was determined using the residual cancer burden (RCB) classification. RESULTS: The US parameter with the highest power for predicting pathological complete response (pCR) was shear wave elastography (SWE) maximum speed inside the tumor at baseline. For nonluminal tumors, the end diastolic velocity measured by US after two cycles of NACT showed the highest predictive value for pCR. Similarly, SWE maximum speed after two cycles of NACT had the highest discriminating power for predicting RCB-III in luminal tumors, while the same parameter measured at baseline was most predictive for nonluminal tumors. CONCLUSIONS: This study provides evidence that mid-treatment Doppler US and other imaging modalities can be used to predict the response to NACT in breast cancer patients. Functional parameters, such as blood flow velocities and SWE measurements, demonstrated superior predictive value for pCR, while morphological parameters had limited value. These findings have implications for personalized treatment strategies and may contribute to improved outcomes in the management of breast cancer.

Three-dimensional Simulation on Patient-reported Outcomes Following Oncoplastic and Reconstructive Surgery of the Breast: A Randomized Trial.

Background: Three-dimensional (3D) imaging using computer simulations is an evolving technology. There is a lack of strong data on the use of this technology for oncoplastic (OP) and reconstructive surgery. Methods: A prospective, randomized, single-center trial including breast cancer patients undergoing OP or mastectomy with immediate breast reconstruction with implant (IBR) enrolled from November 2019 to October 2021 at the Hospital Nossa Senhora das Graças, Breast Unit in Curitiba, Brazil. Both patients undergoing OP and those in the IBR group were randomized to undergo 3D imaging and simulation of postoperative results (intervention group) or 3D imaging without simulation (control group). All patients were invited to complete a patient-reported outcome (BREAST-Q) expectations module and breast reconstruction or reduction/mastopexy module before and 6 months after surgery. Results: A total of 96 patients were enrolled. Sixty-nine patients (45 OP and 24 IBR) completed the pre- and postoperative questionnaires and were randomized for the simulation. Women in the OP group had higher expectations for breast appearance when clothed than those in the IBR implant group (93.4 ± 16.3 versus 82.9 ± 26.5; P = 0.03). The intervention group was more satisfied with information than the control group (P = 0.021). Both patients who underwent OP and IBR believed that the 3D simulation helped them understand the surgical process (86.6% and 75%, respectively). Conclusions: Preoperative 3D simulation significantly improved patient's satisfaction with information and did not decrease postoperative satisfaction with the outcomes. The incorporation of preoperative 3D simulation may be a valuable tool in breast reconstruction.

Prospective study: Impact of breast magnetic resonance imaging on oncoplastic surgery and on indications of mastectomy in patients who were previously candidates to breast conserving surgery.

Background: Routine use of magnetic resonance imaging (MRI) in the staging of patients with early breast cancer is still controversial. Oncoplastic surgery (OP) allows for wider resections without compromising the aesthetic results. This study aimed to assess the impact of preoperative MRI on surgical planning and on indications of mastectomy. Methods: Prospective study including T1-T2 breast cancer patients treated between January 2019 and December 2020 in the Breast Unit of the Hospital Nossa Senhora das Graças in Curitiba, Brazil. All patients had indication for breast conserving surgery (BCS) with OP and did a breast MRI after conventional imaging. Results: 131 patients were selected. Indication for BCS was based on clinical examination and conventional imaging (mammography and ultrasound) findings. After undergoing breast MRI, 110 patients (84.0%) underwent BCS with OP and 21 (16.0%) had their surgical procedure changed to mastectomy. Breast MRI revealed additional findings in 52 of 131 patients (38%). Of these additional findings, 47 (90.4%) were confirmed as invasive carcinoma. Of the 21 patients who underwent mastectomies, the mean tumor size was 2.9 cm (± 1,7cm), with all having additional findings on breast MRI (100% of the mastectomies group vs 28.2% of the OP, p<0.01). Of the 110 patients submitted to OP, the mean tumor size was 1,6cm (± 0,8cm), with only 6 (5.4%) presenting positive margins at the final pathology assessment. Conclusion: Preoperative breast MRI has an impact on the OP scenario, bringing additional information that may help surgical planning. It allowed selecting the group with additional tumor foci or greater extension to convert to mastectomy, with a consequent low reoperation rate of 5.4% in the BCS group. This is the first study to assess the impact of breast MRI in the preoperative planning of patients undergoing OP for the treatment of breast cancer.

Effects of preoperative magnetic resonance image on survival rates and surgical planning in breast cancer conservative surgery: randomized controlled trial (BREAST-MRI trial).

BACKGROUND: Breast magnetic resonance imaging (MRI) has high sensitivity in detecting invasive neoplasms. Controversy remains about its impact on the preoperative staging of breast cancer surgery. This study evaluated survival and surgical outcomes of preoperative MRI in conservative breast cancer surgery. METHODS: A phase III, randomized, open-label, single-center trial including female breast cancer participants, stage 0-III disease, and eligible for breast-conserving surgery. We compared the role of including MRI in preoperative evaluation versus radiologic exam routine with mammography and ultrasound in breast cancer conservative candidates. The primary outcome was local relapse-free survival (LRFS), and secondary outcomes were overall survival (OS), mastectomy rate, and reoperation rate. RESULTS: 524 were randomized to preoperative MRI group (n = 257) or control group (n = 267). The survival analysis showed a 5.9-years LRFS of 99.2% in MRI group versus 98.9% in control group (HR = 0.72; 95% CI 0.12-4.28; p = 0.7) and an OS of 95.3% in the MRI group versus 96.3% in the control group (HR = 1.37 95% CI 0.59-3.19; p = 0.8). Surgical management changed in 21 ipsilateral breasts in the MRI group; 21 (8.3%) had mastectomies versus one in the control group. No difference was found in reoperation rates, 22 (8.7%) in the MRI group versus 23 (8.7%) in the control group (RR = 1.002; 95% CI 0.57-1.75; p = 0.85). CONCLUSION: Preoperative MRI increased the mastectomy rates by 8%. The use of preoperative MRI did not influence local relapse-free survival, overall survival, or reoperation rates.

Prepectoral Direct-to-Implant Breast Reconstruction without Placement of Acellular Dermal Matrix or Mesh after Nipple-Sparing Mastectomy.

BACKGROUND: The aim of this study was to report the results of prepectoral direct-to-implant reconstruction in nipple-sparing mastectomy without acellular dermal matrices or mesh. METHODS: A multicenter cohort of patients undergoing prophylactic or therapeutic nipple-sparing mastectomy was included from 2013 to 2020. All sizes and types of breasts were included, except those with previously failed reconstruction, previous radiotherapy with severe skin damage, locally advanced breast cancer, gigantomasty, severe degree of ptosis, tumors close to the nipple-areola complex (<1 cm on magnetic resonance imaging), or combined autologous-based reconstruction. RESULTS: A total of 280 immediate breast reconstructions were performed in 195 patients. The mean age was 45 years and 32.8 percent of patients were postmenopausal. The mean follow-up period was 16.5 (±17.43) months. Eighty-five patients (43.6 percent) underwent bilateral mastectomy; 116 mastectomies (41.4 percent) were prophylactic and 164 (58.6 percent) were therapeutic. Sixty-eight reconstructions (24 percent) had at least one acute complication, the most common being implant explantation (9.2 percent), which was more frequent in smokers. Late complications included rippling (grades 3 and 4) in seven cases (3.8 percent) and capsular contracture (Baker II through IV) in 29 cases (15.7 percent) [22 Baker II (11.9 percent), six Baker III (3.3 percent), and one Baker IV (0.5 percent)]. One implant rotation was observed. No deformity animation was observed. Cosmetic results were considered good or excellent in 87.3 percent of patients. CONCLUSIONS: Overall complications were similar to those reported in acellular dermal matrices, mesh, or subpectoral series, except for a higher explantation rate. This technique is safe and economically advantageous, as it is a one-stage technique without acellular dermal matrices and mesh. These are preliminary data and larger and comparative studies are needed. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Breast Cancer Treatment Delay in SafetyNet Health Systems, Houston Versus Southeast Brazil.

BACKGROUND: Breast cancer outcomes among patients who use safety-net hospitals in the highly populated Harris County, Texas and Southeast Brazil are poor. It is unknown whether treatment delay contributes to these outcomes. METHODS: We conducted a retrospective cohort analysis of patients with non-metastatic breast cancer diagnosed between January 1, 2009 and December 31, 2011 at Harris Health Texas and Unicamp's Women's Hospital, Barretos Hospital, and Brazilian National Institute of Cancer, Brazil. We used Cox proportional hazards regression to evaluate association of time to treatment and risk of recurrence (ROR) or death. RESULTS: One thousand one hundred ninety-one patients were included. Women in Brazil were more frequently diagnosed with stage III disease (32.3% vs. 21.1% Texas; P = .002). Majority of patients in both populations had symptom-detected disease (63% in Brazil vs. 59% in Texas). Recurrence within 5 years from diagnosis was similar 21% versus 23%. Median time from diagnosis to first treatment defined as either systemic therapy (chemotherapy or endocrine therapy) or surgery, were comparable, 9.9 weeks versus 9.4 weeks. Treatment delay was not associated with increased ROR or death. Higher stage at diagnosis was associated with both increased ROR and death. CONCLUSION: Time from symptoms to treatment was considerably long in both populations. Treatment delay did not affect outcomes. IMPACT: Access to timely screening and diagnosis of breast cancer are priorities in these populations.

Exposed Implant after Immediate Breast Reconstruction - Presentation and Analysis of a Clinical Management Protocol.

OBJECTIVE: Infection and exposure of the implant are some of the most common and concerning complications after implant-based breast reconstruction. Currently, there is no consensus on the management of these complications. The aim of the present study was to review our cases and to present a clinical protocol. METHODS: We conducted a retrospective review of consecutive patients submitted to implant-based breast reconstruction between 2014 and 2016. All patients were managed according to a specific and structured protocol. RESULTS: Implant exposure occurred in 33 out of 277 (11.9%) implant-based reconstructions. Among these, two patients had history of radiotherapy and had their implant removed; Delayed reconstruction with a myocutaneous flap was performed in both cases. Signs of severe local infection were observed in 12 patients, and another 5 presented with extensive tissue necrosis, and they were all submitted to implant removal; of them, 8 underwent reconstruction with a tissue expander, and 2, with a myocutaneous flap. The remaining 14 patients had no signs of severe infection, previous irradiation or extensive tissue necrosis, and were submitted to primary suture as an attempt to salvage the implant. Of these, 8 cases (57.1%) managed to keep the original implant. CONCLUSION: Our clinical protocol is based on three key points: history of radiotherapy, severe infection, and extensive tissue necrosis. It is a practical and potentially-reproducible method of managing one of the most common complications of implant-based breast reconstruction.

OBJECTIVO: Infecção e exposição da prótese são algumas das complicações mais comuns e preocupantes após reconstrução da mama com implantes. Atualmente, ainda não há consenso quanto ao manejo destas complicações. O objetivo deste estudo foi o de revisar os casos da nossa instituição e apresentar um protocolo clínico. MéTODOS: Realizou-se uma revisão retrospectiva de todos os casos consecutivos submetidos a reconstrução mamária imediata com prótese entre 2014 e 2016. Todos os casos foram conduzidos de acordo com um protocolo específico e estruturado. RESULTADOS: A exposição do implante ocorreu em 33 de 227 reconstruções (11,9%). Dentre estas, duas pacientes tinham histórico de radioterapia, e foram submetidas a remoção da prótese e posterior reconstrução com retalho miocutâneo. Sinais de infecção local grave foram observados em 12 pacientes, e, em 5, necrose extensa de tecido, e todas foram submetidas a remoção dos implantes; destas, 8 foram reconstruídas com expansor, e 2, com retalho miocutâneo. As 14 pacientes remanecentes não haviam sido submetidas previamente à radioterapia, não tinham sinais de infecção, nem necrose extensa; portanto, foram submetidas a sutura primária em uma tentativa de salvar a prótese. Dessas, 8 pacientes (57,1%) conseguiram manter os implantes originais. CONCLUSãO: Nosso protocolo clínico é baseado em três pontos principais: histórico de radioterapia, infecção grave, e necrose extensa de tecido. Ele constitui um método prático e potencialmente reprodutível de manejo de uma das complicações mais comuns da reconstrução mamária com implantes.

Exposed Implant after Immediate Breast Reconstruction - Presentation and Analysis of a Clinical Management Protocol / Exposição de prótese após reconstrução imediata da mama: apresentação e análise de protocolo clínico

Abstract Objective Infection and exposure of the implant are some of the most common and concerning complications after implant-based breast reconstruction. Currently, there is no consensus on the management of these complications. The aim of the present study was to review our cases and to present a clinical protocol. Methods We conducted a retrospective review of consecutive patients submitted to implant-based breast reconstruction between 2014 and 2016. All patients were managed according to a specific and structured protocol. Results Implant exposure occurred in 33 out of 277 (11.9%) implant-based reconstructions. Among these, two patients had history of radiotherapy and had their implant removed; Delayed reconstruction with a myocutaneous flap was performed in both cases. Signs of severe local infection were observed in 12 patients, and another 5 presented with extensive tissue necrosis, and they were all submitted to implant removal; of them, 8 underwent reconstruction with a tissue expander, and 2, with a myocutaneous flap. The remaining 14 patients had no signs of severe infection, previous irradiation or extensive tissue necrosis, and were submitted to primary suture as an attempt to salvage the implant. Of these, 8 cases (57.1%) managed to keep the Conclusion Our clinical protocol is based on three key points: history of radiotherapy, severe infection, and extensive tissue necrosis. It is a practical and potentially-reproducible method of managing one of the most common complications of implant-based breast reconstruction.

Resumo Objectivo Infecção e exposição da prótese são algumas das complicações mais comuns e preocupantes após reconstrução da mama com implantes. Atualmente, ainda não há consenso quanto ao manejo destas complicações. O objetivo deste estudo foi o de revisar os casos da nossa instituição e apresentar um protocolo clínico. Métodos Realizou-se uma revisão retrospectiva de todos os casos consecutivos submetidos a reconstrução mamária imediata com prótese entre 2014 e 2016. Todos os casos foram conduzidos de acordo com um protocolo específico e estruturado. Resultados A exposição do implante ocorreu em 33 de 227 reconstruções (11,9%). Dentre estas, duas pacientes tinham histórico de radioterapia, e foram submetidas a remoção da prótese e posterior reconstrução com retalho miocutâneo. Sinais de infecção local grave foram observados em 12 pacientes, e, em 5, necrose extensa de tecido, e todas foram submetidas a remoção dos implantes; destas, 8 foram recons truídas com expansor, e 2, com retalho miocutâneo. As 14 pacientes remanecentes não haviam sido submetidas previamente à radioterapia, não tinham sinais de infecção, nem necrose extensa; portanto, foram submetidas a sutura primária em uma tentativa de salvar a prótese. Dessas, 8 pacientes (57,1%) conseguiram manter os implantes originais. Conclusão Nosso protocolo clínico é baseado em três pontos principais: histórico de radioterapia, infecção grave, e necrose extensa de tecido. Ele constitui um método prático e potencialmente reprodutível de manejo de uma das complicações mais comuns da reconstrução mamária com implantes.

Marking axillary nodes with 4% carbon microparticle suspension before neoadjuvant chemotherapy improves sentinel node identification rate and axillary staging.

BACKGROUND AND OBJECTIVES: Marking positive lymph nodes (LNs) before neoadjuvant chemotherapy (NAC) may improve the accuracy of sentinel lymph node biopsy (SLNB). The aim of this study was to determine the feasibility of marking LNs with 4% carbon microparticle suspension (CMS) before NAC and to evaluate if this technique would improve the SLNB identification rate. METHODS: A prospective study of patients with cT1-T4, cN1-N2 breast cancer who underwent US-guided fine-needle aspiration biopsy (FNAB) of suspected LNs and concomitant marking with 4% CMS was performed. After NAC, LNs marked with 4% CMS and those marked with Patent Blue V dye (PBV) were identified and resected. RESULTS: Of the 123 patients included, 74 (60.1%) had positive LNs at FNAB. During axillary surgery, 4% CMS was identified in 121 of 123 patients (98.3%) and blue sentinel LNs in 91% (112 of 123 patients) (P = .0103). Comparing isolated results of PBV and 4%CMS + PBV, the association was better in identifying positive LNs (72.2% vs 97.7%) (P = .02). CONCLUSION: The association of 4% CMS and PBV is feasible and significantly increased the identification rate of positive LNs. 4% CMS may play an important role as a complementary technique in patients submitted to NAC.

Levonorgestrel-releasing intrauterine system and breast cancer risk: A systematic review and meta-analysis.

INTRODUCTION: Epidemiological studies have shown that some hormonal contraceptive methods are associated with increased breast cancer risk, especially if used over long periods. Our objective was to conduct a systematic review and meta-analysis of the literature on the risk of breast cancer development in women using the 52-mg levonorgestrel-releasing intrauterine system (LNG-IUS). MATERIAL AND METHODS: We performed a thorough review of peer-reviewed publications from 10 January 1999, through 31 July 2019, using combinations of search terms for breast cancer risk and LNG-IUS in the Medline, EMBASE, LILACS (Latin American and Caribbean Health Sciences Literature), and Scielo databases. This review was registered in PROSPERO (CRD42017059076). Studies reporting breast cancer risk estimates among healthy users of LNG-IUS were included according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analysis) criteria. Two authors performed data extraction, and a third author resolved disagreements. The quality of evidence was evaluated using the Downs and Black instrument. A funnel plot was generated, and a linear regression test of funnel plot asymmetry was used to assess publication bias. Finally, we performed a random-effects model (owing to high study heterogeneity) meta-analysis of seven suitable studies, stratified by the age distribution of patients (<50 years, ≥50 years, and mixed). RESULTS: We identified 96 studies and manually cross-referenced and excluded duplicate articles. Seventy articles were excluded on the basis of the inclusion and exclusion criteria, resulting in the assessment of 26 full-text articles. Eight articles were considered adequate for inclusion in this systematic review, and seven studies were included in the meta-analysis. Three publications were case-control studies and five were cohort studies. According to the Downs and Black instrument, 5 studies were rated as "good" and 3 studies were deemed "fair". Our meta-analysis results indicated increased breast cancer risk in LNG-IUS users: for all women, odds ratio (OR) = 1.16 (95% CI 1.06-1.28, I2  = 78%, P < .01); for women aged <50 years, OR = 1.12 (95% CI 1.02-1.22, I2  = 66%, P = .02); and for women aged ≥50 years, OR = 1.52 (95% CI 1.34-1.72, I2  = 0%, P = .84). CONCLUSIONS: Current evidence suggests that LNG-IUS users have an increased breast cancer risk regardless of age and indication. The effect of LNG-IUS on breast cancer risk seems to be larger in older users. However, our systematic review detected methodological issues across the available studies, and confounding factors may be responsible for at least a fraction of the risk effects associated with LNG-IUS use. Nevertheless, users of LNG-IUS should be aware of these trends. We believe that caution is needed, and risks should be balanced against proven health benefits (eg effective treatment of heavy menstrual bleeding and avoidance of surgical interventions), when prescribing LNG-IUS for long periods of use, especially in women with other known breast cancer risk factors such as old age, obesity, and familial predisposition.

Trends in breast cancer surgery in private patients under opportunistic screening / Tendências na cirurgia de câncer de mama em pacientes de um serviço privado sob rastreio oportunístico

Objective: This study aims to determine the evolution of staging and surgical treatment in patients with breast cancer in a private clinic over the last 40 years. Methods: Retrospective descriptive observational study, through statistical analysis of the medical records of 2105 patients treated at a private clinic in Curitiba, Paraná, between 1977 and 2017. Results: Data analyzed from 2,105 patients diagnosed with breast cancer revealed that, over time, radical surgeries predominated when compared to conservative ones. However, when analyzed proportionally over the years, it is possible to observe an inversion of the surgical modalities. It was demonstrated that from 1977 to 2017, there was a 273% increase in the number of conservative surgeries and a 45.5% decrease in mastectomies. In addition to this data, there was a decrease in the number of axillary emptying and, consequently, of positive sentinel lymph nodes. In addition, tumors diagnosed early (T1) have increased over the years. Conclusion: Patients had an early diagnosis of the disease, resulting in less invasive surgical treatments and, consequently, lower morbidity and mortality.

Objetivo: A pesquisa visa determinar a evolução do estadiamento e do tratamento cirúrgico em pacientes com câncer de mama em uma clínica privada, nos últimos 40 anos. Métodos: Estudo observacional descritivo retrospectivo, por meio da análise estatística dos prontuários de 2105 pacientes atendidas em clínica privada em Curitiba, Paraná, entre 1977 e 2017. Resultados: Dados analisados de 2.105 pacientes diagnosticadas com câncer de mama revelaram que, ao longo do tempo, as cirurgias radicais predominaram quando comparadas às cirurgias conservadoras. No entanto, quando analisadas proporcionalmente ao longo dos anos, é possível constatar uma inversão das modalidades cirúrgicas. Demonstrou-se que de 1977 a 2017, houve aumento de 273% do número das cirurgias conservadoras e queda de 45,5% das mastectomias. Associado a esse dado, notou-se diminuição do número de esvaziamento axilar e consequentemente de linfonodos sentinela positivos. Além disso, os tumores diagnosticados em fase inicial (T1) aumentaram ao longo dos anos. Conclusão: As pacientes tiveram um diagnóstico em estadiamento mais precoce da doença, proporcionando tratamentos cirúrgicos menos invasivos e, consequentemente, menor morbidade.

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

Diagnostic accuracy of shear wave elastography - Virtual touch™ imaging quantification in the evaluation of breast masses: Impact on ultrasonography's specificity and its ultimate clinical benefit.

OBJECTIVES: To evaluate the diagnostic performance and the clinical benefit of Shear-Wave Elastography - Virtual Touch™ Imaging Quantification (SWE-VTIQ) as a complement to ultrasonography (US). METHODS: From October 2016 through Jun 2017, B-mode US and SWE-VTIQ were prospectively performed in 396 breast masses in 357 women who consented to undergo this study. Quantitative elastography values were recorded: Vmax (maximum elasticity), Vmean (median elasticity), Vratio(max) (ratio of Vmax and surrounding parenchyma) and Vratio(mean) (ratio of Vmean and surrounding parenchyma). The histopathology of the lesions was considered the reference standard for benign or malignant definition. The performance of the four elastographic parameters was evaluated trough sensitivity, specificity and AUC. The parameter with the best performance was tested in six different diagnostic approaches defined based on clinical practice. RESULTS: Of the 396 masses, 122 (30.8%) were benign and 274 (69.2%) were malignant. All SWE parameters were significantly higher in malignant masses (all p < 0.01). Vmax and Vratio(max) performed significantly better then Vratio(mean) (p = 0.01 and p = 0.03, respectively). SWE-VTIQ improved US specificity in all diagnostic approaches, except when applied to BI-RADS 3 lesions. SWE-VTIQ reduced the false positive rate in 25% if applied only to BI-RADS 4A masses, maintaining a high sensitivity (98.9%, 95% confidence interval 97.1-100%) and a negative predictive value of 95.5%. When applied to BI-RADS 4A and 4B masses, SWE-VTIQ reduced the false positive rate in 54.4%. However, 13 malignant cases would be missed in this approach (4.7% of all malignant cases). CONCLUSIONS: SWE-VTIQ increases US specificity when applied to BI-RADS 4 A lesions, significantly reducing unnecessary interventions and preserving the diagnosis of malignant lesions. When applied also to BI-RADS® 4B lesions, SWE-VTIQ increases the number of false negative cases, which should be evaluated with caution.

Development of a Model to Predict Invasiveness in Ductal Carcinoma In Situ Diagnosed by Percutaneous Biopsy-Original Study and Critical Evaluation of the Literature.

BACKGROUND: Approximately 30% of ductal carcinoma in situ (DCIS) cases have an invasive component discovered on the final analysis that could affect surgical management. The aims of the present study were to determine the risk factors associated with the underestimation of DCIS and to develop a model to predict the probability of invasiveness. MATERIALS AND METHODS: A retrospective analysis was performed on the data for all patients with a diagnosis of DCIS found by percutaneous biopsy from January 2008 to February 2016. Thirteen potential predictors of invasiveness were examined. The statistical analysis of the present study was improved using Nagelkerke's R2, the area under the receiving operating characteristic (AUC) curve, and the Hosmer-Lemeshow goodness-of-fit test. RESULTS: Of 354 biopsy specimens deemed to be DCIS on initial biopsy, 100 (28.2%) were recategorized as invasive carcinoma after surgery. On multivariate analysis, the strongest predictors of invasiveness were comedonecrosis, size on mammography, suspected microinvasion, histologic grade, and younger patient age. The model had a good discriminative ability, with an AUC of 0.764. The overall performance of the model was fair, with a Nagelkerke's R2 of 40.9%. A separate analysis performed on 274 specimens obtained through vacuum-assisted biopsy revealed different variables were associated with underestimation; however, a similar AUC (0.743) and Nagelkerke's R2 (45.7%) were obtained. CONCLUSION: Our model had the best AUC for predicting DCIS invasiveness reported to date. However, further statistical analysis showed only a fair overall performance. The currently known clinical, radiographic, and pathologic features might be insufficient to identify which patients with DCIS have underestimated disease.

Power Doppler Ultrasonography and Shear Wave Elastography as Complementary Imaging Methods for Suspected Local Breast Cancer Recurrence.

OBJECTIVES: To prospectively investigate the diagnostic accuracy and clinical consequences of power Doppler morphologic criteria and shear wave elastography (SWE) as complementary imaging methods for evaluation of suspected local breast cancer recurrence in the ipsilateral breast or chest wall. METHODS: Thirty-two breast masses with a suspicion of local breast cancer recurrence on B-mode ultrasonography underwent complementary power Doppler and SWE evaluations. Power Doppler morphologic criteria were classified as avascular, hypovascular, or hypervascular. Shear wave elastography was classified according to a 5-point scale (SWE score) and SWE maximum elasticity. Diagnostic accuracy was assessed by the sensitivity, specificity, and area under the curve. A decision curve analysis assessed clinical consequences of each method. The reference standard for diagnosis was defined as core needle or excisional biopsy. RESULTS: Histopathologic examinations revealed 9 (28.2%) benign and 23 (71.8%) malignant cases. Power Doppler ultrasonography (US) had sensitivity of 34.8% (95% confidence interval [CI], 6.6%-62.9%) and specificity of 45.4% (95% CI, 19.3%-71.5%). The SWE score (≥3) had sensitivity of 87.0% (95% CI, 66.4%-97.2%) and specificity of 44.4% (95% CI, 13.7%-78.8%). The SWE maximum elasticity (velocity > 6.5cm/s) had sensitivity of 87% (95% CI, 66.4%-97.2%) and specificity of 77.8% (95% CI, 40.0% to 97.2%). The areas under the curves for the SWE score and SWE maximum elasticity were 0.71 (95% CI, 0.53-0.87) and 0.82 (95% CI, 0.64-0.93), respectively (P = .32). CONCLUSIONS: Power Doppler US is unsuitable for discrimination between local breast cancer recurrence and fibrosis. Although the SWE score and SWE maximum elasticity can make this discrimination, the use of these methods to determine biopsy may lead to poorer clinical outcomes than the current practice of performing biopsies of all suspicious masses.

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.

Predictive factors for positive surgical margins in the treatment of breast ductal carcinoma in situ.

CONTEXT: Surgery is the main form of treatment for ductal carcinoma in situ (DCIS) of the breast. Among other factors, treatment success requires that the surgical margins are free of disease, to reduce the risk of recurrence. AIMS: The purpose of this study was to analyze factors that might be associated with positive margins in patients diagnosed with DCIS. SETTINGS AND DESIGN: A retrospective analysis was performed of hospital databases from the year 2006 to 2014, to identify patients with an initial diagnosis of DCIS made by percutaneous biopsy. SUBJECTS AND METHODS: Age, the presence of disease symptoms, lesion size on mammogram, and the presence of estrogen receptors, and their relationship to the surgical margins were evaluated in 249 patients. STATISTICAL ANALYSIS USED: Shapiro and Wilcoxon-Mann-Whitney tests were used to verify that the data were normally distributed. Chi-squared test was used to verify the independence of the variables. RESULTS: Lesions measuring 1.55 cm or greater had a relative risk of positive margins after conservative surgery of 1.39 (95% confidence interval [95% CI]: 1.02-1.90). The presence of symptoms had a relative risk of positive margins after conservative surgery of 1.54 (95% CI: 1.17-2.02). CONCLUSION: Lesions measuring 1.55 cm or greater and the presence of symptoms are risk factors for positive margins in the treatment of ductal carcinoma in situ. Therefore, these patients need a better surgical planning in order to reduce the risk of positive margins. There is a clear need for large prospective studies to validate our findings and define other factors that might contribute to the success of surgical resection for ductal carcinoma in situ.

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.