Adjuvant nivolumab, capecitabine or the combination in patients with residual triple-negative breast cancer: the OXEL randomized phase II study.

Chemotherapy and immune checkpoint inhibitors have a role in the post-neoadjuvant setting in patients with triple-negative breast cancer (TNBC). However, the effects of nivolumab, a checkpoint inhibitor, capecitabine, or the combination in changing peripheral immunoscore (PIS) remains unclear. This open-label randomized phase II OXEL study (NCT03487666) aimed to assess the immunologic effects of nivolumab, capecitabine, or the combination in terms of the change in PIS (primary endpoint). Secondary endpoints included the presence of ctDNA, toxicity, clinical outcomes at 2-years and association of ctDNA and PIS with clinical outcomes. Forty-five women with TNBC and residual invasive disease after standard neoadjuvant chemotherapy were randomized to nivolumab, capecitabine, or the combination. Here we show that a combination of nivolumab plus capecitabine leads to a greater increase in PIS from baseline to week 6 (91%) compared with nivolumab (47%) or capecitabine (53%) alone (log-rank p = 0.08), meeting the pre-specified primary endpoint. In addition, the presence of circulating tumor DNA (ctDNA) is associated with disease recurrence, with no new safety signals in the combination arm. Our results provide efficacy and safety data on this combination in TNBC and support further development of PIS and ctDNA analyses to identify patients at high risk of recurrence.

Adjuvant nivolumab, capecitabine or the combination in patients with residual triple-negative breast cancer: the OXEL randomized phase II study.

Chemotherapy and immune checkpoint inhibitors have a role in the post-neoadjuvant setting in patients with triple-negative breast cancer (TNBC). However, the effects of nivolumab, a checkpoint inhibitor, capecitabine, or the combination in changing peripheral immunoscore (PIS) remains unclear. This open-label randomized phase II OXEL study (NCT03487666) aimed to assess the immunologic effects of nivolumab, capecitabine, or the combination in terms of the change in PIS (primary endpoint). Secondary endpoints include the presence of ctDNA, toxicity, clinical outcomes at 2-years and association of ctDNA and PIS with clinical outcomes. Forty-five women with TNBC and residual invasive disease after standard neoadjuvant chemotherapy were randomized to nivolumab, capecitabine, or the combination. Here we show that a combination of nivolumab plus capecitabine leads to a greater increase in PIS from baseline to week 6 (91%) compared with nivolumab (47%) or capecitabine (53%) alone (log-rank p = 0.08), meeting the pre-specified primary endpoint. In addition, the presence of circulating tumor DNA (ctDNA) was associated with disease recurrence, with no new safety signals in the combination arm. Our results provide efficacy and safety data on this combination in TNBC and support further development of PIS and ctDNA analyses to identify patients at high risk of recurrence.

Feasibility of Symptom Monitoring During the First Year of Endocrine Therapy for Early Breast Cancer Using Patient-Reported Outcomes Collected via Smartphone App.

PURPOSE: Treatment-associated symptoms drive early discontinuation of adjuvant endocrine therapy (ET) for breast cancer. We hypothesized that symptom monitoring with electronic patient-reported outcomes (ePROs) during adjuvant ET will enhance symptom detection, symptom management, and persistence. METHODS: Eligible patients were initiating ET for stage 0-III breast cancer. Participants completed ePRO surveys via smartphone at baseline and 1, 3, 6, and 12 months. Measures included Patient-Reported Outcomes Measurement Information System Anxiety, Depression, Fatigue, and Vaginal Discomfort; plus Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events items assessing joint pain, hot flashes, vaginal dryness, concentration problems, and memory problems. Scores surpassing prespecified thresholds triggered alerts, and recommended symptom management pathways were provided to clinicians. The primary objective was to evaluate feasibility, assessed by survey completion rates, with targets of >65% for the baseline survey and ≥1 follow-up survey during the first 6 months. Secondary objectives included 12-month ET discontinuation rate (target: ≤15%), describing symptoms and evaluating pathway implementation. RESULTS: Among 250 participants, 73.2% completed the baseline survey and 69.6% completed ≥1 follow-up survey during the first 6 months. Thirty-one percent of participants had ≥1 symptom alert at baseline and 74% had ≥1 symptom alert during follow-up. The proportions of participants for whom pathway-concordant symptom management was documented at each time point ranged from 12.8% to 36.6%. Twenty-eight participants (11.2%) discontinued ET by 12 months. CONCLUSION: Symptom monitoring with ePROs during adjuvant ET is feasible. Despite infrequent documentation of pathway-concordant symptom management after symptom alerts, ePROs were associated with favorable short-term ET persistence.

Demographic and socioeconomic factors in impacts of COVID-19 by regions in Brazil / Factores demográficos y socioeconómicos en impactos del COVID-19 por regiones en Brasil / Fatores demográficos e socioeconômicos nos impactos da COVID-19 por regiões do Brasil

Objective: assess which demographic and socioeconomic factors contribute to the different impacts of COVID-19 by regions in Brazil. Method: descriptive study with mathematic modeling (USA) were use to assess deaths and COVID-19 cases and also establish a standard relational relationship with demographic and socioeconomic factors across the country and by regions (2020 to 2023). The factors analyzed in the study: i) deaths and cases of COVID-19, ii) total population density per thousand kilometers, iii) isolation index, iv) population, v) Human Development Index - HDI, vi) population density, vii ) average water tariff, viii) urban water service tariff, ix) total water tariff, x) urban sewage service tariff referring to municipalities served with water, xi) service tariff of total sewage, referring to the municipalities served with water, xii) Gini index (income concentration level), xiii) 1st and 2nd dose of vaccine, and xiv) Gross Domestic Product. Results: the study reveals that COVID-19 cases/deaths are significantly correlated with GDP and inversely correlated with the vaccination rate. Conclusion: this study shows scientific evidence that supports the use of vaccination as a protective measure against COVID-19 mortality in Brazil.

Objetivo: avaliar os fatores demográficos e socioeconômicos que contribuem para os diferentes impactos da COVID-19 por regiões do Brasil. Método: estudo descritivo com modelo matemático (USA) foi utilizado para avaliar óbitos e casos de COVID-19 e também estabelecer uma relaçao padrão com fatores demográficos e socioeconômicos em todo o país e por regiões (2020a 2023). Os fatores analisados no estudo: i) óbitos e casos de COVID-19; ii) densidade populacional total por mil quilômetros; iii) índice de isolamento; iv) população; v) Índice de Desenvolvimento Humano; vi)densidade demográfica; vii) tarifa média de água; viii) tarifa de serviço de água urbana; ix) tarifa de água total; x) tarifa de serviço de esgoto urbano referente aos municípios atendidos com água; xi) tarifa de serviço de esgoto total referente aos municípios atendidos com água; xii) índice de Gini; xiii) 1ª e 2ª dose de vacina; e xiv) Produto Interno Bruto. Resultados: o estudo revela que casos/óbitos por COVID-19 são significativamente correlacionados com o PIB e inversamente correlacionados com a taxa de vacinação. Conclusão: este estudo mostra evidências científicas que apoiam o uso da vacinação como medida de proteção contra a mortalidade por COVID-19 no Brasil.

A survey on brazilian dentists' awareness, perception, and knowledge of bisphosphonates

Aim: The purpose of the study was to analyze the knowledge of dentists in Belo Horizonte, Brazil, about bisphosphonates and their clinical implications. Methods: A cross-sectional questionnaire-based study was conducted with a convenience sample of dentists in Belo Horizonte, in a period of 8 weeks. The questionnaire was self-applied and was structured with 10 items about the dentists' demographic characteristics, professional profile, and knowledge about bisphosphonates. Associations in the data were analyzed by with the Fischer's exact test with a significance level of 5%. Results: Of the 214 participating dentists, 163 (76.17%) were women, and 51 (23.83%) were men, with age ranged for 21 to 73 years (mean of 30 years) and mean of 6 years of professional activity. Nearly half (106/49.53%) reported having knowledge about bisphosphonates, and undergraduate courses were the primary source of such information (73/34.11%). Osteoporosis was the most identified indication for use (75/35.04%), although no participants correctly identified all indications. Regarding the drugs' side effects, only three dentists (1.40%) could correctly identify all responses, with bone necrosis being recognized by the majority (88/41.12%). Sodium alendronate (54/25.23%) and sodium ibandronate (15/7.01%) were the most identified examples of bisphosphonates. Last, only nine dentists (4.20%) could identify all examples of the drugs, and their capacity was associated with self-reported knowledge (p<0.05). Conclusions: More information about bisphosphonates should be disseminated in Belo Horizonte, ideally via better approaches in local undergraduate and postgraduate courses. Until then, knowledge of the basic aspects of bisphosphonates will remain limited

Integrating Immunotherapy in Early-Stage Triple-Negative Breast Cancer: Practical Evidence-Based Considerations.

The KEYNOTE-522 study is a practice-changing phase III randomized study that demonstrated that the addition of pembrolizumab to polychemotherapy improves outcomes in patients with high-risk early-stage triple-negative breast cancer (TNBC). This regimen is highly efficacious with unprecedented pathologic complete response (pCR) rates, and clinically meaningful improvements in event-free survival (EFS). However, the combination is also associated with significant high-grade treatment-related toxicity. The backbone regimen deviated from common practice, including the addition of carboplatin, lack of dose dense anthracyclines, and adjuvant capecitabine for residual disease, thus brining important questions regarding real-world translation of these results. This brief report practically addresses some of the most relevant questions physicians and patients face in optimizing care using the best available evidence.

Estudo de métodos naturais para redução de doenças fúngicas em sementes nativas da região Amazônica / Study of natural methods for reducing fungal diseases in native seeds in the Amazon region

Existe uma preocupação na produção de alimentos com a segurança sanitária desde o processo de cultivo até a sua expedição aos centros comerciais. Uma das maiores contaminações em sementes por suas características físicas e químicas, é a contaminação fúngica devida à acidez e umidade dos frutos. As doenças fúngicas entre elas, antracnose, vassoura de bruxa e podridão parda são consideradas importante doenças em pós colheita, ocorrendo, principalmente, sob condições de alta umidade relativa do ar e temperaturas elevadas (26ºC a 28ºC). Dentre as sementes da região Amazônica, destacam-se sementes de (cacau- Theobroma cacao L., pupunha- Bactris gasipaes, tucumã da Amazonas-Astrocaryum aculeatum), que apresentam problemas de contaminação fúngica durante o sistema de cultivo. Métodos de biocontroles com ação antimicrobiana: bactérias endofíticas, rizobactérias e fungo Trichoderma ssp, entre outros estão sendo estudados para a redução destas contaminações fúngicas em estudos in vitro e no campo. O objetivo deste trabalho é apresentar uma revisão bibliográfica sobre a utilização de métodos de biocontrole como uma alternativa promissora no manejo de doenças de plantas na fase de pós-colheita, com excelentes resultados em culturas de grande importância econômica. Assim novas alternativas ecologicamente sustentáveis demonstram a possibilidade de os produtos estudados serem utilizados no manejo da antracnose na pós-colheita.(AU)

There is a concern in food production with health security from cultivation process to its dispatch to redistribution centers. One of the biggest contaminations in seeds due to their physical and chemical characteristics, is the fungal contamination due to the acidity and humidity of the fruits. Fungal diseases including anthracnose, bruca's broom and brownrot are considered important diseases in post-harvest, occurring mainly under conditions of high relative humidity and high temperatures (26ºC to 28ºC). Among the seeds of the Amazon region, seeds of de (cacau- Theobroma cacao L., pupunha- Bactris gasipaes, tucumã da Amazonas- Astrocaryum aculeatum ), that present problems fungals contamination during in their growing cultures sistems. Biocontrol methods with antimicrobial action: endophytic bacteria, rhizobacteria and the fungus Trichoderma ssp, among others, are being studied to reduce these fungal contaminations in in vitro and field studies. The objective of this work is to present a bibliographic review on the use of biocontrol methods as an alternative that is promising in the management of plant diseases in the post-harvest phase, with excellent results in crops of great economic importance. Thus, new ecologically sustainable alternatives demonstrate the possibility of the studied products to be used in the management of anthracnose in the post-harvest period.(AU)

Profile of Margetuximab: Evidence to Date in the Targeted Treatment of Metastatic HER2-positive Breast Cancer.

Human epidermal growth factor receptor 2 (HER2) positive breast cancer accounts for about 20% of all breast cancers and this subtype has been historically associated with worse prognosis. Margetuximab is a chimeric and Fc-engineered monoclonal antibody directed to HER2 that can enhance the activation of the innate and adaptive immune responses while maintaining trastuzumab's antiproliferative effects. Margetuximab in combination with chemotherapy was approved by the US FDA in December 2020 for patients with metastatic HER2+ breast cancer who have received two or more HER2-targeted regimens. This approval was based on the results of the SOPHIA trial that showed a modest improvement in progression-free survival with margetuximab and chemotherapy compared to trastuzumab and chemotherapy. Ongoing studies are assessing the role of margetuximab in other settings and diseases such as early stage breast cancer and gastrointestinal malignancies. Here we review the rationale for the development of margetuximab, previous and ongoing clinical trials and current role in clinical practice.

Association of treatment-emergent symptoms identified by patient-reported outcomes with adjuvant endocrine therapy discontinuation.

Many patients discontinue endocrine therapy for breast cancer due to intolerance. Identification of patients at risk for discontinuation is challenging. The minimal important difference (MID) is the smallest change in a score on a patient-reported outcome (PRO) that is clinically significant. We evaluated the association between treatment-emergent symptoms detected by worsening PRO scores in units equal to the MID with discontinuation. We enrolled females with stage 0-III breast cancer initiating endocrine therapy in a prospective cohort. Participants completed PROs at baseline, 3, 6, 12, 24, 36, 48, and 60 months. Measures included PROMIS pain interference, fatigue, depression, anxiety, physical function, and sleep disturbance; Endocrine Subscale of the FACT-ES; and MOS-Sexual Problems (MOS-SP). We evaluated associations between continuous PRO scores in units corresponding to MIDs (PROMIS: 4-points; FACT-ES: 5-points; MOS-SP: 8-points) with time to endocrine therapy discontinuation using Cox proportional hazards models. Among 321 participants, 140 (43.6%) initiated tamoxifen and 181 (56.4%) initiated aromatase inhibitor (AI). The cumulative probability of discontinuation was 23% (95% CI 18-27%) at 48 months. For every 5- and 4-point worsening in endocrine symptoms and sleep disturbance respectively, participants were 13 and 14% more likely to discontinue endocrine therapy respectively (endocrine symptoms HR 1.13, 95% CI 1.02-1.25, p = 0.02; sleep disturbance HR 1.14, 95% CI 1.01-1.29, p = 0.03). AI treatment was associated with greater likelihood of discontinuation than tamoxifen. Treatment-emergent endocrine symptoms and sleep disturbance are associated with endocrine therapy discontinuation. Monitoring for worsening scores meeting or exceeding the MID on PROs may identify patients at risk for discontinuation.

Olaparib Use in Patients With Metastatic Breast Cancer Harboring Somatic BRCA1/2 Mutations or Mutations in Non-BRCA1/2, DNA Damage Repair Genes.

BACKGROUND: Poly-ADP ribose polymerase (PARP) inhibitors (PARPi) are active in patients with germline BRCA1/2 (gBRCA1/2)-mutated breast cancer, accounting for 5% to 10% of all breast cancers. Another 5% to 10% harbor somatic BRCA1/2 (sBRCA1/2) mutations or mutations in non-BRCA1/2, homologous recombination repair (HRR) genes but until recently, there were no data for the use of PARPi in these patients. This study examines the use of olaparib in patients with metastatic breast cancer harboring sBRCA1/2 or germline or somatic non-BRCA1/2, HRR mutations and demonstrates potential activity of PARPi in this setting. METHODS: In this retrospective, single institution study, patients who were treated with off-label, off-protocol olaparib for metastatic breast cancer harboring sBRCA1/2 or germline or somatic non-BRCA1/2, HRR mutations were identified. The primary aim was to describe these patients' demographics, tumor characteristics, mutations, safety and tolerability, response rates, progression free survival, PARPi-associated survival and subsequent treatment. RESULTS: Seven patients were treated off-label, off-trial with olaparib for sBRCA1/2-mutated cancers (n = 4) or non-BRCA1/2, HRR-mutated cancers (n = 3). All patients with sBRCA1/2-mutated cancers responded to PARP inhibition; patients with non-BRCA1/2, HRR-mutated cancers did not respond. The median progression free survival in patients with a sBRCA1/2 mutation was 6.5 months (range 5-9 months) vs. 3 months (range 2-4 months) in patients with non-BRCA1/2, HRR mutations. CONCLUSION: This single institution experience adds to recent larger reports confirming evidence for PARPi therapy in patients with metastatic breast cancer harboring sBRCA1/2 mutations. No activity was observed in patients with either germline or somatic non-BRCA1/2, HRR-mutated cancers.

Estudo de métodos naturais para redução de doenças fúngicas em sementes nativas da região amazônica / Study of natural methods for reducing fungal diseases in native seeds in the amazon region

Existe uma preocupação na produção de alimentos com a segurança sanitária desde o processo de cultivo até a sua expedição aos centros comerciais. Uma das maiores contaminações em sementes por suas características físicas e químicas, é a contaminação fúngica devida à acidez e umidade dos frutos. As doenças fúngicas entre elas, antracnose, vassoura de bruxa e podridão parda são consideradas importante doenças em pós colheita, ocorrendo, principalmente, sob condições de alta umidade relativa do ar e temperaturas elevadas (26ºC a 28ºC). Dentre as sementes da região Amazônica, destacam-se sementes de (cacau- Theobroma cacao L., pupunha- Bactris gasipaes, tucumã da Amazonas-Astrocaryum aculeatum), que apresentam problemas de contaminação fúngica durante o sistema de cultivo. Métodos de biocontroles com ação antimicrobiana: bactérias endofíticas, rizobactérias e fungo Trichoderma ssp, entre outros estão sendo estudados para a redução destas contaminações fúngicas em estudos in vitro e no campo. O objetivo deste trabalho é apresentar uma revisão bibliográfica sobre a utilização de métodos de biocontrole como uma alternativa promissora no manejo de doenças de plantas na fase de pós-colheita, com excelentes resultados em culturas de grande importância econômica. Assim novas alternativas ecologicamente sustentáveis demonstram a possibilidade de os produtos estudados serem utilizados no manejo da antracnose na pós-colheita

There is a concern in food production with health security from cultivation process to its dispatch to redistribution centers. One of the biggest contaminations in seeds due to their physical and chemical characteristics, is the fungal contamination due to the acidity and humidity of the fruits. Fungal diseases including anthracnose, bruca's broom and brownrot are considered important diseases in post-harvest, occurring mainly under conditions of high relative humidity and high temperatures (26ºC to 28ºC). Among the seeds of the Amazon region, seeds of de (cacau- Theobroma cacao L., pupunha- Bactris gasipaes, tucumã da Amazonas- Astrocaryum aculeatum ), that present problems fungals contamination during in their growing cultures sistems. Biocontrol methods with antimicrobial action: endophytic bacteria, rhizobacteria and the fungus Trichoderma ssp, among others, are being studied to reduce these fungal contaminations in in vitro and field studies. The objective of this work is to present a bibliographic review on the use of biocontrol methods as an alternative that is promising in the management of plant diseases in the post-harvest phase, with excellent results in crops of great economic importance. Thus, new ecologically sustainable alternatives demonstrate the possibility of the studied products to be used in the management of anthracnose in the post-harvest period

Prognostic Utility of Breast Cancer Index to Stratify Distant Recurrence Risk in Invasive Lobular Carcinoma.

PURPOSE: The prognostic utility of Breast Cancer Index (BCI) for risk assessment of overall (0-10 years), early (0-5 years), and late (5-10 years) distant recurrence (DR) in hormone receptor-positive (HR+) invasive lobular carcinoma (ILC) was evaluated. EXPERIMENTAL DESIGN: BCI gene expression analysis was performed blinded to clinical outcome utilizing tumor specimens from patients with HR+ ILC from a multi-institutional cohort. The primary endpoint was time to DR. Kaplan-Meier analyses of overall, early, and late DR risk were performed, and statistical significance was evaluated by log-rank test and Cox proportional hazards regression. The prognostic contribution of BCI in addition to clinicopathologic factors was evaluated by likelihood ratio analysis. RESULTS: Analysis of 307 patients (99% ER+, 53% T1, 42% N+, 70% grade II) showed significant differences in DR over 10 years based on BCI risk categories. BCI low- and intermediate-risk patients demonstrated similar DR rates of 7.6% and 8.0%, respectively, compared with 27.0% for BCI high-risk patients. BCI was a significant independent prognostic factor for overall 10-year DR [HR = 4.09; 95% confidence interval (CI), 2.00-8.34; P = 0.0001] as well as for both early (HR = 8.19; 95% CI, 1.85-36.30; P = 0.0042) and late (HR = 3.04; 95% CI, 1.32-7.00; P = 0.0224) DR. In multivariate analysis, BCI remained the only statistically significant prognostic factor for DR (HR = 3.49; 95% CI, 1.28-9.54; P = 0.0150). CONCLUSIONS: BCI is an independent prognostic factor for ILC and significantly stratified patients for cumulative risk of 10-year, early, and late DR. BCI added prognostic value beyond clinicopathologic characteristics in this distinct subtype of breast cancer.

Role of Platinums in Triple-Negative Breast Cancer.

PURPOSE OF REVIEW: Platinum compounds are used in the treatment of various types of cancer. Here, we review the current role of cisplatin and carboplatin in the treatment of early stage and advanced triple-negative breast cancer (TNBC), and the use of biomarkers in predicting response to platinum therapy. RECENT FINDINGS: Addition of carboplatin to a neoadjuvant chemotherapy regimen can result in improvement in the pathological complete response rates. The long-term benefit of the addition of carboplatin to standard chemotherapy regimens remains unproven. Single-agent platinum is an option in the treatment of advanced breast cancer. BRCA1/2 mutations predicted benefit from platinums in advanced, but not early stage breast cancer. There are yet no biomarkers to predict response to platinum in sporadic TNBC. Platinum compounds are an option in the treatment of TNBC. Identification of biomarkers to select tumors most likely to derive benefit from these agents is still needed. Ongoing trials are exploring the role of platinum in the adjuvant setting and in combination with other agents, including immune checkpoint inhibitors.

Lazer e a opção decolonial: diálogos teóricos e possibilidades de construções contra-hegemônicas / Leisure and the decolonial option: theoretical dialogues and possibilities of contra hegemonic constructions

Atentas à necessidade de olhar o lazer a partir de uma perspectiva outra, assumimos a opção decolonial movidas por nossas experiências de pesquisa. Apresentamos nesse ensaio argumentos conceituais do debate decolonial construídos na América Latina a partir de uma incursão teórica. Nosso olhar parte de estudos, concluídos e em andamento, com mulheres em situação de rua, mulheres negras, povos indígenas e sobre as manifestações culturais do Festejo do Tambor Mineiro e do BoiBumbá de Parintins. Essas experiências empíricas nos movem a um pensar outro que confronte as estruturas hegemônicas coloniais. A partir da discussão sobre temporalidade, cultura e educação dentro de uma perspectiva contra-hegemônica, buscamos construir pontes entre o campo de lazer e a decolonialidade. Assim, ressaltamos a necessidade de lançar um olhar a partir das práticas sociais, especificamente nossos contextos de pesquisa, e fazer ressoar vozes e perspectivas de mundo que operam com outras lógicas para nos orientar e fornecer contribuições na direção de um lazer decolonial ou ainda de uma possível construção decolonial do lazer.

Aware of the need to look at leisure from another perspective, we assume the decolonial option promoted by our research experiences. In this essay we present conceptual arguments of the decolonial debate built in Latin America from a theoretical incursion. Our view is based on studies, concluded and in progress with women on the street, black women, indigenous peoples and cultural manifestations of the Festejo do Tambor Mineiro and Boi-Bumbá de Parintins. These empirical experiences take us to a different thought that confronts the colonial hegemonic structures. From the discussion on temporality, culture and education in a hegemonic perspective, we seek to build bridges between the field of leisure and decoloniality. Thus, we emphasize the need to take a look at social practices, specifically our research contexts, and make voices and perspectives of the world resonate that work with other logics to guide us and provide contributions towards decolonial leisure or even a possible decolonial construction of leisure.

Long-term follow-up assessment of cardiac safety in SAFE-HEaRt, a clinical trial evaluating the use of HER2-targeted therapies in patients with breast cancer and compromised heart function.

PURPOSE: HER2-targeted therapies are associated with cardiotoxicity which is usually asymptomatic and reversible. We report the updated cardiac safety assessment of patients with compromised heart function receiving HER2-targeted therapy for breast cancer, enrolled in the SAFE-HEaRt trial, at a median follow-up of 3.5 years. METHODS: Thirty patients with stage I-IV HER2-positive breast cancer receiving trastuzumab with or without pertuzumab, or ado-trastuzumab emtansine (T-DM1), with asymptomatic LVEF (left ventricular ejection fraction) 40-49%, were started on cardioprotective medications, with the primary endpoint being completion of HER2-targeted therapy without cardiac events (CE) or protocol-defined asymptomatic worsening of LVEF. IRB-approved follow-up assessment included 23 patients. RESULTS: Median follow-up as of June 2020 is 42 months. The study met its primary endpoint with 27 patients (90%) completing their HER2-targeted therapies without cardiac issues. Of the 23 evaluable patients at long-term f/u, 14 had early stage breast cancer, and 9 had metastatic disease, 8 of whom remained on HER2-targeted therapies. One patient developed symptomatic heart failure with no change in LVEF. There were no cardiac deaths. The mean LVEF improved to 52.1% from 44.9% at study baseline, including patients who remained on HER2-targeted therapy, and those who received prior anthracyclines. CONCLUSIONS: Long-term follow-up of the SAFE-HEaRt study continues to provide safety data of HER2-targeted therapy use in patients with compromised heart function. The late development of cardiac dysfunction is uncommon and continued multi-disciplinary oncologic and cardiac care of patients is vital for improved patient outcomes.

Selection of Optimal Adjuvant Chemotherapy and Targeted Therapy for Early Breast Cancer: ASCO Guideline Update.

PURPOSE: The aim of this work is to update key recommendations of the ASCO guideline adaptation of the Cancer Care Ontario guideline on the selection of optimal adjuvant chemotherapy regimens for early breast cancer and adjuvant targeted therapy for breast cancer. METHODS: An Expert Panel conducted a targeted systematic literature review guided by a signals approach to identify new, potentially practice-changing data that might translate into revised guideline recommendations. RESULTS: The Expert Panel reviewed abstracts from the literature review and identified one article for inclusion that reported results of the phase III, open-label KATHERINE trial. In the KATHERINE trial, patients with stage I to III human epidermal growth factor receptor 2 (HER2)-positive breast cancer with residual invasive disease in the breast or axilla after completing neoadjuvant chemotherapy and HER2-targeted therapy were allocated to adjuvant trastuzumab emtansine (T-DM1; n = 743) or to trastuzumab (n = 743). Invasive disease-free survival was significantly higher in the T-DM1 group than in the trastuzumab arm (hazard ratio, 0.50; 95% CI, 0.39 to 0.64; P < .001), and risk of distant recurrence was lower in patients who received T-DM1 than in patients who received trastuzumab (hazard ratio, 0.60; 95% CI, 0.45 to 0.79). Grade 3 or higher adverse events occurred in 190 patients (25.7%) who received T-DM1 and in 111 patients (15.4%) who received trastuzumab. RECOMMENDATIONS: Patients with HER2-positive breast cancer with pathologic invasive residual disease at surgery after standard preoperative chemotherapy and HER2-targeted therapy should be offered 14 cycles of adjuvant T-DM1, unless there is disease recurrence or unmanageable toxicity. Clinicians may offer any of the available and approved formulations of trastuzumab, including trastuzumab, trastuzumab and hyaluronidase-oysk, and available biosimilars.Additional information can be found at www.asco.org/breast-cancer-guidelines.

Extended Endocrine Therapy for Early-Stage Breast Cancer: How Do We Decide?

PURPOSE OF REVIEW: While the majority of hormone receptor-positive breast cancers are diagnosed at an early stage, a significant proportion of patients will develop disease recurrence, especially late disease recurrence, despite current therapeutic approaches. In this review, we examine the data pertaining to the choice of endocrine and extended endocrine therapy, outline how to identify patients that may benefit from extended therapy, and discuss prognostic tools to assist with patient selection. RECENT FINDINGS: The risk of breast cancer recurrence persists after 5 years, is cumulative, and is indefinite. In attempts to mitigate these risks, studies have evaluated the use of extended endocrine therapy. Overall survival benefit has been demonstrated with extended tamoxifen, whereas extended aromatase inhibitors have shown modest disease-free survival benefit. Therapeutic approaches for individual patients will depend on the perceived risk of recurrence, likely benefit of extended therapy, tolerability of current endocrine therapy, and patient preference.

Management of Breast Cancer During the COVID-19 Pandemic: A Stage- and Subtype-Specific Approach.

The COVID-19 pandemic has rapidly changed delivery of cancer care. Many nonurgent surgeries are delayed to preserve hospital resources, and patient visits to health care settings are limited to reduce exposure to SARS-CoV-2. Providers must carefully weigh risks and benefits of delivering immunosuppressive therapy during the pandemic. For breast cancer, a key difference is increased use of neoadjuvant systemic therapy due to deferral of many breast surgeries during the pandemic. In some cases, this necessitates increased use of genomic tumor profiling on core biopsy specimens to guide neoadjuvant therapy decisions. Breast cancer treatment during the pandemic requires multidisciplinary input and varies according to stage, tumor biology, comorbidities, age, patient preferences, and available hospital resources. We present here the Johns Hopkins Women's Malignancies Program approach to breast cancer management during the COVID-19 pandemic. We include algorithms based on tumor biology and extent of disease that guide management decisions during the pandemic. These algorithms emphasize medical oncology treatment decisions and demonstrate how we have operationalized the general treatment recommendations during the pandemic proposed by national groups, such as the COVID-19 Pandemic Breast Cancer Consortium. Our recommendations can be adapted by other institutions and medical oncology practices in accordance with local conditions and resources. Guidelines such as these will be important as we continue to balance treatment of breast cancer against risk of SARS-CoV-2 exposure and infection until approval of a vaccine.