AI and Ethics: A Systematic Review of the Ethical Considerations of Large Language Model Use in Surgery Research.

INTRODUCTION: As large language models receive greater attention in medical research, the investigation of ethical considerations is warranted. This review aims to explore surgery literature to identify ethical concerns surrounding these artificial intelligence models and evaluate how autonomy, beneficence, nonmaleficence, and justice are represented within these ethical discussions to provide insights in order to guide further research and practice. METHODS: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Five electronic databases were searched in October 2023. Eligible studies included surgery-related articles that focused on large language models and contained adequate ethical discussion. Study details, including specialty and ethical concerns, were collected. RESULTS: The literature search yielded 1179 articles, with 53 meeting the inclusion criteria. Plastic surgery, orthopedic surgery, and neurosurgery were the most represented surgical specialties. Autonomy was the most explicitly cited ethical principle. The most frequently discussed ethical concern was accuracy (n = 45, 84.9%), followed by bias, patient confidentiality, and responsibility. CONCLUSION: The ethical implications of using large language models in surgery are complex and evolving. The integration of these models into surgery necessitates continuous ethical discourse to ensure responsible and ethical use, balancing technological advancement with human dignity and safety.

Artificial-Intelligence-Based Clinical Decision Support Systems in Primary Care: A Scoping Review of Current Clinical Implementations.

Primary Care Physicians (PCPs) are the first point of contact in healthcare. Because PCPs face the challenge of managing diverse patient populations while maintaining up-to-date medical knowledge and updated health records, this study explores the current outcomes and effectiveness of implementing Artificial Intelligence-based Clinical Decision Support Systems (AI-CDSSs) in Primary Healthcare (PHC). Following the PRISMA-ScR guidelines, we systematically searched five databases, PubMed, Scopus, CINAHL, IEEE, and Google Scholar, and manually searched related articles. Only CDSSs powered by AI targeted to physicians and tested in real clinical PHC settings were included. From a total of 421 articles, 6 met our criteria. We found AI-CDSSs from the US, Netherlands, Spain, and China whose primary tasks included diagnosis support, management and treatment recommendations, and complication prediction. Secondary objectives included lessening physician work burden and reducing healthcare costs. While promising, the outcomes were hindered by physicians' perceptions and cultural settings. This study underscores the potential of AI-CDSSs in improving clinical management, patient satisfaction, and safety while reducing physician workload. However, further work is needed to explore the broad spectrum of applications that the new AI-CDSSs have in several PHC real clinical settings and measure their clinical outcomes.

Breast cancer survival after mammography dissemination in Brazil: a population-based analysis of 2,715 cases.

BACKGROUND: This study aims to assess breast cancer survival rates after one decade of mammography in a large urban area of Brazil. METHODS: It is a population-based retrospective cohort of women with breast cancer in Campinas, São Paulo, from 2010 to 2014. Age, vital status and stage were accessed through the cancer and mortality registry, and patients records. Statistics used Kaplan-Meier, log-rank and Cox's regression. RESULTS: Out of the 2,715 cases, 665 deaths (24.5%) were confirmed until early 2020. The mean age at diagnosis was 58.6 years. Women 50-69 years were 48.0%, and stage I the most frequent (25.0%). The overall mean survival was 8.4 years (8.2-8.5). The 5-year survival (5yOS) for overall, 40-49, 50-59, 60-69, 70-79 years was respectively 80.5%, 87.7%, 83.7%, 83.8% and 75.5%. The 5yOS for stages 0, I, II, III and IV was 95.2%, 92.6%, 89.4%, 71.1% and 47.1%. There was no significant difference in survival in stage I or II (p = 0.058). Compared to women 50-59 years, death's risk was 2.3 times higher for women 70-79 years and 26% lower for women 40-49 years. Concerning stage I, the risk of death was 1.5, 4.1 and 8.6 times higher, and 34% lower, respectively, for stage II, III, IV and 0. CONCLUSIONS: In Brazil, breast cancers are currently diagnosed in the early stages, although advanced cases persist. Survival rates may reflect improvements in screening, early detection and treatment. The results can reflect the current status of other regions or countries with similar health care conditions.

The impact of the COVID-19 pandemic on breast cancer screening and diagnosis in a Brazilian metropolitan area.

OBJECTIVES: To evaluate the performance of breast cancer screening and early diagnosis during the pandemic, compared to the pre-pandemic period.Setting: The public referral centre for screening in Campinas, São Paulo State, Brazil. METHODS: This is an audit study of performance screening and diagnostic indicators. Two periods were analysed: 2019, the pre-COVID period, and 2020, the COVID period. All women who underwent mammography in these periods were included. Indicators were compared between periods, and the US Breast Cancer Surveillance Consortium benchmarks were used as a reference. RESULTS: A comparison between the periods shows a reduction of 57.4% in screening and 4.4% in diagnosis using mammography. Cancer detection rate per 1000 screening mammograms dropped from 4.62 to 2.83 (p = 0.031), while it increased from 84.43 to 89.36 in diagnosis mammograms (p = 0.701), higher than the reference (34.4, p < 0.001). With regard to diagnosis, the proportion of minimal cancers was reduced (p = 0.005) and was lower than the reference (40.0%, p < 0.001), along with the proportion of node-negative invasive cancers (p < 0.001). The mean size of invasive tumours was similar in the two periods (32.50 mm and 33.40 mm, p = 0.808) but larger than the reference value (16.50 mm, p < 0.001). Recall rate was lower in the COVID period (22.55% vs. 27.37%, p = 0.015). CONCLUSION: The COVID pandemic caused an overall decrease in breast screening and detection of breast cancer cases, although the reduction in number of diagnosis mammograms performed was minimal. Tumour mean size was large in both periods, the pandemic highlighting a previous profile of detection at an advanced stage.

The COVID-19 Pandemic Impact on Breast Cancer Diagnosis: A Retrospective Study / O impacto da pandemia de COVID-19 no diagnóstico de câncer de mama: Um estudo retrospectivo

Abstract Objective This study aimed to evaluate the diagnostic profile of breast cancer cases during the coronavirus disease 2019 (COVID-19) pandemic compared with the previous year. Methods It is a retrospective study of cases diagnosed by a reference service in the public health system of Campinas, SP, Brazil. Two periods were analyzed: March to October 2019 (preCOVID period) and March to October 2020 (COVID-period). All women diagnosed during the periods were included. The Chi-Squared or Fisher exact and Mann-Whitney tests were used. Results In the preCOVID and COVID periods, breast cancers were diagnosed, respectively, in 115 vs 59 women, and the mean ages at diagnosis were 55 and 57 years (p = 0.339). In the COVID period, the family history of breast cancer was more observed (9.6% vs 29.8%, p < 0.001), cases were more frequently symptomatic (50.4% vs 79.7%, p < 0.001) and had more frequently palpable masses (56.5% vs 79.7%, p = 0.003). In symptomatic women, the mean number of days from symptom to mammography were 233.6 (458.3) in 2019 and 152.1 (151.5) in 2020 (p = 0.871). Among invasive tumors, the proportion of breast cancers in stages I and II was slightly higher in the COVID period, although not significantly (76.7% vs 82.4%, p = 0.428). Also in the COVID period, the frequency of luminal A-like tumors was lower (29.2% vs 11.8%, p = 0.018), of triple-negative tumors was twice as high (10.1% vs 21.6%, p = 0.062), and of estrogen receptor-positive tumors was lower (82.2% vs 66.0%, p = 0.030). Conclusion During the COVID-19 pandemic, breast cancer diagnoses were reduced. Cases detected were suggestive of a worse prognosis: symptomatic women with palpable masses and more aggressive subtypes. Indolent tumors were those more sensitive to the interruption in screening.

Resumo Objetivo Este estudo teve como objetivo avaliar o perfil diagnóstico dos casos de câncer de mama na pandemia de coronavirus disease 2019 (COVID-19) em comparação com o ano anterior. Métodos Este é um estudo retrospectivo de casos diagnosticados em um serviço de referência da rede pública de saúde de Campinas, SP, Brasil. Foram analisados dois períodos: de março a outubro de 2019 (período pré-COVID) e de março a outubro de 2020 (período COVID). Todas as mulheres diagnosticadas durante os períodos foram incluídas. Foram utilizados os testes do qui-quadrado ou exato de Fisher e Mann-Whitney. Resultados Nos períodos pré-COVID e COVID, o câncer de mama foi diagnosticado, respectivamente, em 115 e 59 mulheres, e a média de idade no diagnóstico foi de 55 e 57 anos (p = 0,339). No período COVID, foram mais frequentes a história familiar de câncer de mama (9,6% vs 29,8%, p < 0,001), casos sintomáticos (50,4% vs 79,7%, p < 0,001) e com massas palpáveis (56,5% vs 79,7%, p = 0,003). Nas mulheres sintomáticas, a média de dias desde os sintomas até a mamografia foi de 233,6 (458,3) no pré-COVID e 152,1 (151,5) no COVID (p = 0,871). Entre os tumores invasivos no período COVID, a proporção de cânceres nos estágios I e II foi ligeiramente maior, porém não significativa (76,7% vs 82,4%, p = 0,428). Ainda no período COVID, a frequência de tumores tipo luminal A-like foi menor (29,2% vs 11,8%, p = 0,018), de tumores triplo-negativos foi duas vezes maior (10,1% vs 21,6%, p = 0,062), e de tumores positivos para receptor de estrogênio foi inferior (82,2% vs 66,0%, p = 0,030). Conclusão Durante a pandemia de COVID-19, houve uma redução no diagnóstico de câncer de mama. Os casos detectados eram sugestivos de pior prognóstico: mulheres sintomáticas com massas palpáveis e subtipos mais agressivos. Os tumores indolentes foram os mais sensíveis à interrupção do rastreamento.

The COVID-19 Pandemic Impact on Breast Cancer Diagnosis: A Retrospective Study.

OBJECTIVE: This study aimed to evaluate the diagnostic profile of breast cancer cases during the coronavirus disease 2019 (COVID-19) pandemic compared with the previous year. METHODS: It is a retrospective study of cases diagnosed by a reference service in the public health system of Campinas, SP, Brazil. Two periods were analyzed: March to October 2019 (preCOVID period) and March to October 2020 (COVID-period). All women diagnosed during the periods were included. The Chi-Squared or Fisher exact and Mann-Whitney tests were used. RESULTS: In the preCOVID and COVID periods, breast cancers were diagnosed, respectively, in 115 vs 59 women, and the mean ages at diagnosis were 55 and 57 years (p = 0.339). In the COVID period, the family history of breast cancer was more observed (9.6% vs 29.8%, p < 0.001), cases were more frequently symptomatic (50.4% vs 79.7%, p < 0.001) and had more frequently palpable masses (56.5% vs 79.7%, p = 0.003). In symptomatic women, the mean number of days from symptom to mammography were 233.6 (458.3) in 2019 and 152.1 (151.5) in 2020 (p = 0.871). Among invasive tumors, the proportion of breast cancers in stages I and II was slightly higher in the COVID period, although not significantly (76.7% vs 82.4%, p = 0.428). Also in the COVID period, the frequency of luminal A-like tumors was lower (29.2% vs 11.8%, p = 0.018), of triple-negative tumors was twice as high (10.1% vs 21.6%, p = 0.062), and of estrogen receptor-positive tumors was lower (82.2% vs 66.0%, p = 0.030). CONCLUSION: During the COVID-19 pandemic, breast cancer diagnoses were reduced. Cases detected were suggestive of a worse prognosis: symptomatic women with palpable masses and more aggressive subtypes. Indolent tumors were those more sensitive to the interruption in screening.

OBJETIVO: Este estudo teve como objetivo avaliar o perfil diagnóstico dos casos de câncer de mama na pandemia de coronavirus disease 2019 (COVID-19) em comparação com o ano anterior. MéTODOS: Este é um estudo retrospectivo de casos diagnosticados em um serviço de referência da rede pública de saúde de Campinas, SP, Brasil. Foram analisados dois períodos: de março a outubro de 2019 (período pré-COVID) e de março a outubro de 2020 (período COVID). Todas as mulheres diagnosticadas durante os períodos foram incluídas. Foram utilizados os testes do qui-quadrado ou exato de Fisher e Mann-Whitney. RESULTADOS: Nos períodos pré-COVID e COVID, o câncer de mama foi diagnosticado, respectivamente, em 115 e 59 mulheres, e a média de idade no diagnóstico foi de 55 e 57 anos (p = 0,339). No período COVID, foram mais frequentes a história familiar de câncer de mama (9,6% vs 29,8%, p < 0,001), casos sintomáticos (50,4% vs 79,7%, p < 0,001) e com massas palpáveis (56,5% vs 79,7%, p = 0,003). Nas mulheres sintomáticas, a média de dias desde os sintomas até a mamografia foi de 233,6 (458,3) no pré-COVID e 152,1 (151,5) no COVID (p = 0,871). Entre os tumores invasivos no período COVID, a proporção de cânceres nos estágios I e II foi ligeiramente maior, porém não significativa (76,7% vs 82,4%, p = 0,428). Ainda no período COVID, a frequência de tumores tipo luminal A-like foi menor (29,2% vs 11,8%, p = 0,018), de tumores triplo-negativos foi duas vezes maior (10,1% vs 21,6%, p = 0,062), e de tumores positivos para receptor de estrogênio foi inferior (82,2% vs 66,0%, p = 0,030). CONCLUSãO: Durante a pandemia de COVID-19, houve uma redução no diagnóstico de câncer de mama. Os casos detectados eram sugestivos de pior prognóstico: mulheres sintomáticas com massas palpáveis e subtipos mais agressivos. Os tumores indolentes foram os mais sensíveis à interrupção do rastreamento.

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.

Potential impact of the z0011 trial on the omission of axillary dissection: a retrospective cohort study / Potencial impacto do estudo Z0011 na omissão da adenectomia axilar: Estudo de coorte retrospectiva

Abstract Objective To evaluate the number of patients with early-stage breast cancer who could benefit from the omission of axillary surgery following the application of the Alliance for Clinical Trials in Oncology (ACOSOG) Z0011 trial criteria. Methods A retrospective cohort study conducted in the Hospital da Mulher da Universidade Estadual de Campinas. The study population included 384 women diagnosed with early-stage invasive breast cancer, clinically negative axilla, treated with breast-conserving surgery and sentinel lymph node biopsy, radiation therapy, chemotherapy and/or endocrine therapy, from January 2005 to December 2010. The ACOSOG Z0011 trial criteria were applied to this population and a statistical analysis was performed to make a comparison between populations. Results A total of 384 patients underwent breast-conserving surgery and sentinel lymph node biopsy. Of the total number of patients, 86 women underwent axillary lymph node dissection for metastatic sentinel lymph nodes (SNLs). One patient underwent axillary node dissection due to a suspicious SLN intraoperatively, thus, she was excluded fromthe study. Among these patients, 82/86 (95.3%) had one to two involved sentinel lymph nodes andmet the criteria for the ACOSOG Z0011 trial with the omission of axillary lymph node dissection. Among the 82 eligible women, there were only 13 cases (15.9%) of lymphovascular invasion and 62 cases (75.6%) of tumors measuring up to 2 cm in diameter (T1). Conclusion The ACOSOG Z0011 trial criteria can be applied to a select group of SLNpositive patients, reducing the costs and morbidities of breast cancer surgery.

Resumo Objetivo Avaliar o número de pacientes com câncer de mama em estágio inicial que se beneficiariam da omissão da linfadenectomia axilar segundo o protocolo Z0011 da Alliance for Clinical Trials in Oncology (ACOSOG). Métodos Estudo de coorte retrospectiva conduzido no Hospital da Mulher da Universidade Estadual de Campinas. Foram incluídas mulheres diagnosticadas com carcinoma invasivo de mama em estágio inicial, com axila clinicamente negativa, tratadas com cirurgia conservadora e biópsia do linfonodo sentinela, radioterapia, quimioterapia e/ou hormonioterapia, de janeiro de 2005 a dezembro de 2010. Os critérios do estudo da ACOSOG Z0011 foram aplicados a essas mulheres e foi realizada uma análise estatística que comparou ambas as populações dos estudos. Resultados Foram estudadas 384 mulheres submetidas a cirurgia conservadora de mama e biópsia do linfonodo sentinela. Entre elas, 86 mulheres foram submetidas a linfadenectomia axilar por metástase presente no linfonodo sentinela. Uma paciente foi submetida a linfadenectomia axilar por ter um linfonodo palpável suspeito no intraoperatório, não incluída no estudo. Entre essas 86 pacientes, 82 (95,3%) tiveram de 1 a 2 linfonodos sentinela comprometidos e seriam elegíveis para omissão da linfadenectomia axilar pelos critérios do ACOSOG Z0011. Entre as 82 pacientes elegíveis, apenas 13 (15,9%) delas apresentaram tumores com invasão angiolinfática, e 62 (75,6%) dos tumores mediram até 2 cm (T1). Conclusão Os critérios do estudo ACOZOG Z0011 podem ser aplicados a um seleto grupo de pacientes com linfonodo sentinela positivo reduzindo os custos e a morbidade cirúrgica do tratamento do câncer de mama.

Potential Impact of the Z0011 Trial on the Omission of Axillary Dissection: A Retrospective Cohort Study.

OBJECTIVE: To evaluate the number of patients with early-stage breast cancer who could benefit from the omission of axillary surgery following the application of the Alliance for Clinical Trials in Oncology (ACOSOG) Z0011 trial criteria. METHODS: A retrospective cohort study conducted in the Hospital da Mulher da Universidade Estadual de Campinas. The study population included 384 women diagnosed with early-stage invasive breast cancer, clinically negative axilla, treated with breast-conserving surgery and sentinel lymph node biopsy, radiation therapy, chemotherapy and/or endocrine therapy, from January 2005 to December 2010. The ACOSOG Z0011 trial criteria were applied to this population and a statistical analysis was performed to make a comparison between populations. RESULTS: A total of 384 patients underwent breast-conserving surgery and sentinel lymph node biopsy. Of the total number of patients, 86 women underwent axillary lymph node dissection for metastatic sentinel lymph nodes (SNLs). One patient underwent axillary node dissection due to a suspicious SLN intraoperatively, thus, she was excluded from the study. Among these patients, 82/86 (95.3%) had one to two involved sentinel lymph nodes and met the criteria for the ACOSOG Z0011 trial with the omission of axillary lymph node dissection. Among the 82 eligible women, there were only 13 cases (15.9%) of lymphovascular invasion and 62 cases (75.6%) of tumors measuring up to 2 cm in diameter (T1). CONCLUSION: The ACOSOG Z0011 trial criteria can be applied to a select group of SLN-positive patients, reducing the costs and morbidities of breast cancer surgery.

OBJETIVO: Avaliar o número de pacientes com câncer de mama em estágio inicial que se beneficiariam da omissão da linfadenectomia axilar segundo o protocolo Z0011 da Alliance for Clinical Trials in Oncology (ACOSOG). MéTODOS: Estudo de coorte retrospectiva conduzido no Hospital da Mulher da Universidade Estadual de Campinas. Foram incluídas mulheres diagnosticadas com carcinoma invasivo de mama em estágio inicial, com axila clinicamente negativa, tratadas com cirurgia conservadora e biópsia do linfonodo sentinela, radioterapia, quimioterapia e/ou hormonioterapia, de janeiro de 2005 a dezembro de 2010. Os critérios do estudo da ACOSOG Z0011 foram aplicados a essas mulheres e foi realizada uma análise estatística que comparou ambas as populações dos estudos. RESULTADOS: Foram estudadas 384 mulheres submetidas a cirurgia conservadora de mama e biópsia do linfonodo sentinela. Entre elas, 86 mulheres foram submetidas a linfadenectomia axilar por metástase presente no linfonodo sentinela. Uma paciente foi submetida a linfadenectomia axilar por ter um linfonodo palpável suspeito no intraoperatório, não incluída no estudo. Entre essas 86 pacientes, 82 (95,3%) tiveram de 1 a 2 linfonodos sentinela comprometidos e seriam elegíveis para omissão da linfadenectomia axilar pelos critérios do ACOSOG Z0011. Entre as 82 pacientes elegíveis, apenas 13 (15,9%) delas apresentaram tumores com invasão angiolinfática, e 62 (75,6%) dos tumores mediram até 2 cm (T1). CONCLUSãO: Os critérios do estudo ACOZOG Z0011 podem ser aplicados a um seleto grupo de pacientes com linfonodo sentinela positivo reduzindo os custos e a morbidade cirúrgica do tratamento do câncer de mama.

Real-world data on neoadjuvant endocrine therapy in ER-positive/HER2-negative breast cancer.

PURPOSE: Neoadjuvant endocrine therapy (NET) has been shown to be effective in ER-positive/HER2-negative breast cancer in clinical trials. However, adoption in clinical practice is still limited. Real-world data may provide useful insights into effectiveness, toxicities and quality of care, potentially rendering clinical trial results to the real-world setting. Our purpose was to report real-world data of a cohort of postmenopausal patients submitted to NET. METHODS: This prospective cohort study evaluated 146 postmenopausal female patients with ER-positive/HER2-negative breast cancer treated with NET at three tertiary hospitals between 2016 and 2018. Clinicopathological information were collected prospectively. Preoperative Endocrine Prognostic Index (PEPI) score was calculated for tumors submitted to at least 16 weeks of NET. RESULTS: Median age was 67 years old, and 87.8% had stage I-II disease. Most tumors had histological grade II (76.1%). Median pretreatment Ki67 expression was 10%. Aromatase inhibitor was used in 99.5% of patients, and median treatment duration was 21.0 weeks. No tumor progressed during NET. Breast-conserving surgery was performed in the majority of patients (63.0%), as well as sentinel lymph-node biopsy (76.7%). Pathological complete response rate was 1.0%. 43 patients (29.5%) had PEPI score 0, and 26% had PEPI scores 4-5. Posttreatment Ki67 median expression was 3.0%, and only five tumors (3.4%) showed marked increase in Ki67 expression during treatment. Seven patients (4.8%) had HER2-positive residual disease, and were treated with adjuvant chemotherapy plus trastuzumab. CONCLUSIONS: Our real-world data shows that NET is effective and safe in postmenopausal patients with ER-positive/HER2-negative breast cancer. Postmenopausal status and low-risk luminal tumor features (luminal A-like) should be used as selection criteria to ensure the best results with NET.

Breast Cancer in Men: Clinical and Pathological Analysis of 817 Cases.

The objective of the current study was to describe breast cancer cases in men according to age, stage, and histology, calculating risks compared to women. It is a retrospective cross-sectional study of all breast cancer cases of the Hospital Cancer Registry of São Paulo state, Brazil, 2000-2015. Variables were age, sex, stage, and histology. Absolute numbers and proportions, Mann-Whitney test and prevalence ratio with 95% confidence interval were used. The study included 93,737 cases, of which 817 were males. The mean age at diagnosis was 60.3 years in men and 56.2 years in women (p < .001). Stage II was the most common in both sexes (33.9% in men and 36.5% in women). Men had a higher frequency of stage III than women (PR 1.18, 95% CI 1.01-1.37). Stage 0 was significantly more common in women (PR 0.69, 95% CI 0.51-0.94). Ductal carcinoma and its variants were the most common histological types in both sexes (88.7% in men and 89.0% in women). Men had a higher frequency of rarer histological types such as papillary (PR 2.17, 95% CI 1.36-3.44) and sarcomas (PR 4.10, 95% CI 1.86-9.01). In conclusion, in men, breast cancer diagnosis occurred in more advanced ages and stages. Invasive ductal carcinoma was the primary histological type observed, although rarer types were more frequent.

ESR1 Mutations Are Not a Common Mechanism of Endocrine Resistance in Patients With Estrogen Receptor-Positive Breast Cancer Treated With Neoadjuvant Aromatase Inhibitor Therapy.

Introduction: Mutations in the ESR1 gene (ESR1m) are important mechanisms of resistance to endocrine therapy in estrogen receptor-positive (ER+) metastatic breast cancer and have been studied as a potential therapeutic target, as well as a predictive and prognostic biomarker. Nonetheless, the role of ESR1m as a possible mechanism of primary endocrine resistance, as well as whether it also occurs in tumors that are resistant to ET administered in early-stage disease as (neo)adjuvant, has not been adequately studied. In this study, we evaluated the prevalence of ESR1m in tumor samples from patients with ER+ breast cancer resistant to neoadjuvant aromatase inhibitor therapy. Methods: We followed a prospective cohort of patients with ER+ HER2- stages II and III breast cancer treated with neoadjuvant endocrine therapy (NET). Tumor samples from patients with a pattern of primary endocrine resistance [defined as a Preoperative Endocrine Prognostic Index (PEPI) score of ≥4] were identified and analyzed for the presence of ESR1m. Results: One hundred twenty-seven patients were included in the cohort, of which 100 (79%) had completed NET and underwent surgery. Among these patients, the PEPI score ranged from 0 to 3 in 70% (70/100), whereas 30% (30/100) had a PEPI score of 4 or more. Twenty-three of these patients were included in the analysis. ESR1 mutations were not identified in any of the 23 patients with early-stage ER+ breast cancer resistant to NET. Discussion: Growing evidence supports the notion that there are different mechanisms for primary and secondary endocrine resistance. Our study suggests that ESR1 mutations do not evolve rapidly and do not represent a common mechanism of primary endocrine resistance in the neoadjuvant setting. Therefore, ESR1m should be considered a mechanism of acquired endocrine resistance in the context of advanced disease. Further research should be conducted to identify factors associated with intrinsic resistance to ET.

Background parenchymal enhancement: behavior during neoadjuvant chemotherapy for breast cancer and relationship with a pathological complete response.

OBJECTIVE: To evaluate background parenchymal enhancement (BPE) and its characteristics, as well as its behavior before and after neoadjuvant chemotherapy (NAC), in both breasts of patients with unilateral breast cancer. MATERIALS AND METHODS: This was a retrospective, cross-sectional observational study involving a consecutive sample of women with invasive breast cancer who underwent breast magnetic resonance imaging (MRI) between July 2007 and July 2017, as well as undergoing dynamic contrast-enhanced MRI before and after NAC. In both breasts, we evaluated the BPE in accordance with the Breast Imaging Reporting and Data System. We applied logistic regression analysis, and values of p < 0.05 were considered significant. RESULTS: We evaluated 150 women. The mean age was 45.2 years (range, 20-74 years). The variables correlating independently with a high pre-NAC BPE, in the affected and contralateral breasts, were being under 50 years of age (odds ratio [OR] = 6.55; 95% confidence interval [95% CI]: 2.32-18.46, for both breasts) and a post-NAC BPE reduction (OR = 17.75; 95% CI: 4.94-63.73 and OR = 18.47; 95% CI: 5.19-66.49, respectively). CONCLUSION: Patients with invasive unilateral breast cancer who have a high pre-NAC BPE in both breasts tend to be under 50 years of age and to show a post-NAC reduction in BPE.

OBJETIVO: Avaliar o realce de fundo do parênquima (RFP), suas características e seu comportamento pré- e pós-quimioterapia neoadjuvante (QTN) em ambas as mamas em pacientes com câncer de mama unilateral. MATERIAIS E MÉTODOS: Estudo observacional transversal retrospectivo realizado em um serviço acadêmico e um centro especializado em mamas, que incluiu mulheres com câncer de mama invasivo submetidas a QTN e que realizaram exames de ressonância magnética (RM) das mamas com contraste antes e depois da quimioterapia, entre julho de 2007 e julho de 2017. Os exames foram realizados de acordo com protocolo padronizado. O RFP foi avaliado em ambas as mamas de acordo com o ACR BI-RADS, 5ª edição. Foi aplicada análise de regressão logística. O nível de significância adotado para os testes estatísticos foi p < 0,05. RESULTADOS: Foram analisadas 150 mulheres. A idade média foi de 45,2 anos (20­74 anos). Na análise de regressão multivariada, apenas a idade inferior a 50 anos e redução do RFP correlacionaram-se independentemente com o nível alto de RFP em ambas as mamas: mamas afetadas (odds ratio [OR]: 6,55; intervalo de confiança 95% [IC 95%]: 2,32­18,46 e OR: 17,75; IC 95%: 4,94­63,73, respectivamente); mamas contralaterais (OR: 6,55; IC: 95% 2,32­18,46 e OR: 18,47; IC 95%: 5,19­66,49, respectivamente). CONCLUSÃO: Idade abaixo de 50 anos e redução do RFP pós-QTN correlacionaram-se independentemente com maior RFP pré-QTN em ambas as mamas em pacientes com câncer de mama invasivo unilateral submetidas a QTN.

Background parenchymal enhancement: behavior during neoadjuvant chemotherapy for breast cancer and relationship with a pathological complete response / Realce de fundo do parênquima: comportamento durante quimioterapia neoadjuvante para câncer de mama e relação com resposta patológica completa

Abstract Objective: To evaluate background parenchymal enhancement (BPE) and its characteristics, as well as its behavior before and after neoadjuvant chemotherapy (NAC), in both breasts of patients with unilateral breast cancer. Materials and Methods: This was a retrospective, cross-sectional observational study involving a consecutive sample of women with invasive breast cancer who underwent breast magnetic resonance imaging (MRI) between July 2007 and July 2017, as well as undergoing dynamic contrast-enhanced MRI before and after NAC. In both breasts, we evaluated the BPE in accordance with the Breast Imaging Reporting and Data System. We applied logistic regression analysis, and values of p < 0.05 were considered significant. Results: We evaluated 150 women. The mean age was 45.2 years (range, 20-74 years). The variables correlating independently with a high pre-NAC BPE, in the affected and contralateral breasts, were being under 50 years of age (odds ratio [OR] = 6.55; 95% confidence interval [95% CI]: 2.32-18.46, for both breasts) and a post-NAC BPE reduction (OR = 17.75; 95% CI: 4.94-63.73 and OR = 18.47; 95% CI: 5.19-66.49, respectively). Conclusion: Patients with invasive unilateral breast cancer who have a high pre-NAC BPE in both breasts tend to be under 50 years of age and to show a post-NAC reduction in BPE.

Resumo Objetivo: Avaliar o realce de fundo do parênquima (RFP), suas características e seu comportamento pré- e pós-quimioterapia neoadjuvante (QTN) em ambas as mamas em pacientes com câncer de mama unilateral. Materiais e Métodos: Estudo observacional transversal retrospectivo realizado em um serviço acadêmico e um centro especializado em mamas, que incluiu mulheres com câncer de mama invasivo submetidas a QTN e que realizaram exames de ressonância magnética (RM) das mamas com contraste antes e depois da quimioterapia, entre julho de 2007 e julho de 2017. Os exames foram realizados de acordo com protocolo padronizado. O RFP foi avaliado em ambas as mamas de acordo com o ACR BI-RADS, 5ª edição. Foi aplicada análise de regressão logística. O nível de significância adotado para os testes estatísticos foi p < 0,05. Resultados: Foram analisadas 150 mulheres. A idade média foi de 45,2 anos (20-74 anos). Na análise de regressão multivariada, apenas a idade inferior a 50 anos e redução do RFP correlacionaram-se independentemente com o nível alto de RFP em ambas as mamas: mamas afetadas (odds ratio [OR]: 6,55; intervalo de confiança 95% [IC 95%]: 2,32-18,46 e OR: 17,75; IC 95%: 4,94-63,73, respectivamente); mamas contralaterais (OR: 6,55; IC: 95% 2,32-18,46 e OR: 18,47; IC 95%: 5,19-66,49, respectivamente). Conclusão: Idade abaixo de 50 anos e redução do RFP pós-QTN correlacionaram-se independentemente com maior RFP pré-QTN em ambas as mamas em pacientes com câncer de mama invasivo unilateral submetidas a QTN.

Prognostic assessment of breast carcinoma submitted to neoadjuvant chemotherapy with pathological non-complete response.

BACKGROUND: Breast cancer with pathological non-complete response (non-pCR) after neoadjuvant chemotherapy (NAC) has a worse prognosis. Despite Neo-Bioscore has been validated as an independent prognostic model for breast cancer submitted to NAC, non-pCR carcinoma was not assessed in this setting. METHODS: This is a retrospective trial that included women with localized breast cancer who underwent NAC and had non-pCR carcinoma in surgical specimen between 01/01/2013 to 12/31/2015 with a three-year follow-up. Survival analysis was performed by Kaplan-Meier estimator and hazard ratio (HR) set by log-rank test for the primary and secondary endpoints, respectively Disease-Free Survival (DFS) and Overall Survival (OS). According to Neo-Bioscore, the proposed prognostic model named Clustered Neo-Bioscore was classified into low (0-3), low-intermediate (4-5), high-intermediate (6) and high (7) risk. The prognostic accuracy for recurrence risk was assessed by time-dependent receiver operating characteristic (time-ROC) methodology. Multivariate Cox regression assessed the menopausal status, histological grade, Ki-67, estrogen receptor, HER2, tumor subtype, pathological and clinical stages. Confidence interval at 95% (CI95%) and statistical significance at set 2-sided p-value less than 0.05 were adopted. RESULTS: Among the 310 women enrolled, 267 patients (86.2%) had non-pCR carcinoma presenting size T3/T4 (63.3%), node-positive axilla (74.9%), stage III (62.9%), Ki-67 ≥ 20% (71.9%) and non-luminal A (78.3%). Non-pCR carcinoma presented worse DFS-3y (HR = 3.88, CI95% = 1.18-11.95) but not OS-3y (HR = 2.73, CI95% = 0.66-11.40). Clustered Neo-Bioscore discerned the recurrence risk for non-pCR carcinoma: low (DFS-3y = 0.86; baseline), low-intermediate (DFS-3y = 0.70; HR = 2.61), high-intermediate (DFS-3y = 0.13, HR = 14.05), and high (DFS-3y = not achieved; HR = 22.19). The prognostic accuracy was similar between Clustered Neo-Bioscore and Neo-Bioscore (0.76 vs 0.78, p > 0.05). Triple-negative subtype (HR = 3.6, CI95% = 1.19-10.92) and pathological stages II (HR = 5.35, CI95% = 1.19-24.01) and III (HR = 6.56, CI95% = 1.29-33.32) were prognoses for low-intermediate risk, whereas pathological stage III (HR = 13.0, CI95% = 1.60-106.10) was prognosis for low risk. CONCLUSIONS: Clustered Neo-Bioscore represents a novel prognostic model of non-pCR carcinoma undergoing NAC with a more simplified and appropriate score pattern in the assessment of prognostic factors.

Predictors of Pathological Complete Response in Women with Clinical Complete Response to Neoadjuvant Chemotherapy in Breast Carcinoma.

OBJECTIVE: There is insufficient information on predictors of pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast carcinoma that also presented clinical complete response (cCR) evaluated in breast, axilla and breast and axilla. METHODS: This retrospective study included 310 women with breast carcinoma who received NAC from 1/1/13 to 12/31/15 with follow-up until 8/31/16. The factors analyzed to predict pCR and cCR were menopausal status, Ki67, estrogen receptor, histologic grade, molecular subtype, tumor size, axilla status, and stage. RESULTS: The cCR/pCR rates were 53.2/16.5% (breast), 76.3/36.8% (axilla) and 50.6/13.9% (breast and axilla). Molecular subtype and HER2-positive were independent predictors to confirm pCR in women with cCR, mainly triple negative (TN) in breast (OR 22.81, 95% CI 7.13-72.96) and breast and axilla (OR 36.06, 95% CI 8.77-148.26), but not in axilla. Ki67 ≥50% expression was predictor of cCR in breast (OR 2.00, 95% CI 1.31-3.06) and breast and axilla (OR 1.67, 95% CI 1.10-1.45). CONCLUSION: TN subtype and HER2-positive were the main independent predictors of pCR in women who also had cCR to NAC in breast and breast and axilla, but none was predictor in axilla. The Ki67 ≥50% was the independent predictor of cCR in breast and breast and axilla.

18F-Fluoride PET/CT tumor burden quantification predicts survival in breast cancer.

PURPOSE: In bone-metastatic breast cancer patients, there are no current imaging biomarkers to identify which patients have worst prognosis. The purpose of our study was to investigate if skeletal tumor burden determined by 18F-Fluoride PET/CT correlates with clinical outcomes and may help define prognosis throughout the course of the disease. RESULTS: Bone metastases were present in 49 patients. On multivariable analysis, skeletal tumor burden was significantly and independently associated with overall survival (p < 0.0001) and progression free-survival (p < 0.0001). The simple presence of bone metastases was associated with time to bone event (p = 0.0448). MATERIALS AND METHODS: We quantified the skeletal tumor burden on 18F-Fluoride PET/CT images of 107 female breast cancer patients (40 for primary staging and the remainder for restaging after therapy). Clinical parameters, primary tumor characteristics and skeletal tumor burden were correlated to overall survival, progression free-survival and time to bone event. The median follow-up time was 19.5 months. CONCLUSIONS: 18F-Fluoride PET/CT skeletal tumor burden is a strong independent prognostic imaging biomarker in breast cancer patients.

Selecting postoperative adjuvant systemic therapy for early stage breast cancer: A critical assessment of commercially available gene expression assays.

Risk stratification of patients with early stage breast cancer may support adjuvant chemotherapy decision-making. This review details the development and validation of six multi-gene classifiers, each of which claims to provide useful prognostic and possibly predictive information for early stage breast cancer patients. A careful assessment is presented of each test's analytical validity, clinical validity, and clinical utility, as well as the quality of evidence supporting its use.

Multiple desmoid tumors in a patient with Gardner's syndrome - Report of a case.

INTRODUCTION: Desmoid tumor (DT) is a common manifestation of Gardner's Syndrome (GS), although it is a rare condition in the general population. DT in patients with GS is usually located in the abdominal wall and/or intra-abdominal cavity. PRESENTATION OF CASE: We report a case of a 32 years-old female patient with familial adenomatous polyposis (FAP), who was already submitted to total colectomy and developed multiple DT, located in the abdominal wall and in the left breast. The patient underwent several surgical procedures, with a multidisciplinary team of surgeons. Wide surgical resections of the left breast and the abdominal wall tumors were performed in separate steps. Polypropylene mesh reconstruction and muscle flaps were needed to cover the defects of the thoracic and abdominal walls. After partial necrosis of the adipose-cutaneous flap in the abdomen that required a new skin graft, she had a satisfactory outcome with complete healing of the surgical incisions. DISCUSSION: DT is frequent in GS, however, breast localization is very rare, with few cases reported in the literature. Recurrence of DT is not negligible, even after a wide surgical resection. GS patients must be followed up closely, and clinical examination, associated with imaging studies, should be performed to detect any signs of tumor. CONCLUSION: DT represents one of the most significant causes of the morbidity and mortality that affects FAP patients following colectomy. In general, the surgical procedures to excise DT are highly complex, requiring a multidisciplinary team.