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Purpose: In KATHERINE, adjuvant T-DM1 reduced risk of disease recurrence or death by 50% compared with trastuzumab in patients with residual invasive breast cancer after neoadjuvant therapy (NAT) comprised of HER2-targeted therapy and chemotherapy. This analysis aimed to identify biomarkers of response and differences in biomarker expression before and after NAT. Experimental Design: Exploratory analyses investigated the relationship between invasive disease-free survival (IDFS) and HER2 protein expression/gene amplification, PIK3CA hotspot mutations, and gene expression of HER2, PD-L1, CD8, predefined immune signatures, and Prediction Analysis of Microarray 50 intrinsic molecular subtypes, classified by Absolute Intrinsic Molecular Subtyping. HER2 expression on paired pre- and post-NAT samples was examined. Results: T-DM1 appeared to improve IDFS versus trastuzumab across most biomarker subgroups, except the HER2 focal expression subgroup. High versus low HER2 gene expression in residual disease was associated with worse outcomes with trastuzumab [HR, 2.02; 95% confidence interval (CI), 1.32–3.11], but IDFS with T-DM1 was independent of HER2 expression level (HR, 1.01; 95% CI, 0.56–1.83). Low PD-L1 gene expression in residual disease was associated with worse outcomes with trastuzumab (HR, 0.66; 95% CI, 0.44–1.00), but not T-DM1 (HR, 1.05; 95% CI, 0.59–1.87). PIK3CA mutations were not prognostic. Increased variability in HER2 expression was observed in post-NAT versus paired pre-NAT samples. Conclusions: T-DM1 appears to overcome HER2 resistance. T-DM1 benefit does not appear dependent on immune activation, but these results do not rule out an influence of the tumor immune microenvironment on the degree of response.

Ovarian function suppression (OFS) is a potentially life-saving treatment for young women diagnosed with high-risk hormonal-receptor (HR)+ early breast cancer (EBC), albeit one associated with significant side effects that may adversely affect quality of life. Of particular concern, this article raises a few borderline indications that were largely unaddressed in pivotal clinical trials but are still commonly encountered in daily practice. These, referred to here as 'borderline indications of OFS' remain a source of uncertainty for patients and physicians and are concisely addressed in this article.This article is about a treatment for breast cancer that is a type of drug-induced menopause. It is considered highly effective for young women diagnosed with a specific form of breast cancer. However, it often causes significant side effects. The author addresses several situations, commonly encountered in daily medical practice, in which the indication for this treatment is controversial.

The digital revolution is an ongoing process that has nevertheless profoundly affected century-old medical practice. Digitalization has many facets, ranging from telehealth to social media and even new instant communication devices, each of which affect both patients’ and physicians’ realities. Although the benefits of developments such as telehealth and novel applications of social media to medicine are more easily perceived by all stakeholders, they still have their own hurdles and risks, such as coldness and impersonal treatment in telehealth, and misinformation on social media. The widespread digitalization of health records has greatly facilitated patient access to health information, becoming a major patient empowerment tool; however, some forms of unrestricted access, such as to test results—in particular, prior to consultations—have unclear benefits to patients with cancer and have also become a hurdle for care teams. In addition, the advent of instant messaging, which is revolutionizing personal communication in many cultures, is gradually affecting patient-physician communication and, combined with unrestricted patient access to test results, is creating new challenges for physicians. How these transformations are affecting patients themselves and physicians’ well-being and mental health are matters addressed in this text. Last, to address potential biases in an article written by two oncologists, and in line with this year’s ASCO presidential theme of including a diversity of voices, we decided to give voice to patients with cancer by collecting the opinions of high-profile patient advocates about the controversial topics addressed in this text.

Background: Tumor boards (TB) are synonymous with quality of care but have been occasionally misunderstood and underutilized. This survey aimed to evaluate health professionals' perceptions of TBs in Brazil. Materials & methods: The survey was sent electronically. Results: Of 206 respondents, 67.8% attended TBs at least once and 82.4% dedicated at least 1 h weekly to them; 64.2% preferred a more “educational” model over case discussions only; 63.1% had institutional leadership capable of promoting multidisciplinarity; 21.1% and 32.7% of the physicians and nonphysicians, respectively, felt intimidated to express their opinions; 91.6% believed that TBs improve cancer outcomes. Postpandemic, 52.7% preferred a hybrid (virtual/face-to-face) model. Conclusion: This study provides a glimpse of the reality of TBs in Brazil, with potential implications for clinical practice.

HER2, PD-L1, and Five-Gene Signature Quartile Analysis. IDFS by HER2 gene expression quartile (A) in the trastuzumab arm; and (B) in the T-DM1 arm; (C) treatment effect on IDFS by HER2 gene expression quartile; (D) effect of HER2 gene expression quartile on IDFS; IDFS by PD-L1 gene expression quartile (E) in the trastuzumab arm; and (F) in the T-DM1 arm; (G) treatment effect on IDFS by PD-L1 gene expression quartile; (H) effect of PD-L1 gene expression quartile on IDFS; IDFS by five-gene signature (i.e., PD-L1/granzymeB/CD8/IFNγ/CXCL9) gene expression quartile (I) in the trastuzumab arm; and (J) in the T-DM1 arm; (K) treatment effect on IDFS by five-gene signature gene expression quartile; (L) effect of five-gene signature gene expression quartile expression on IDFS. Each expression quartile (quartile 2, quartile 3, and quartile 4) is compared to the lowest quartile (quartile 1). The analyses are unstratified and adjusted using a Cox regression model that includes percent tumor in marked area, clinical stage at presentation, hormone receptor status, type of preoperative HER2-directed therapy, and pathologic nodal status. HER2, human epidermal growth factor receptor 2; IDFS, invasive disease-free survival; IFNγ, interferon gamma; Q, quartile; T-DM1, trastuzumab emtansine.

Prognostic value for IDFS by treatment arm of biomarker gene expression levels (>median vs. ≤median and continuous) in post-NAT surgical RNA-evaluable tissue samples. Analysis is adjusted for tumor content. One sample could not be included because there was insufficient information on tumor content.

Purpose:In KATHERINE, adjuvant T-DM1 reduced risk of disease recurrence or death by 50% compared with trastuzumab in patients with residual invasive breast cancer after neoadjuvant therapy (NAT) comprised of HER2-targeted therapy and chemotherapy. This analysis aimed to identify biomarkers of response and differences in biomarker expression before and after NAT.Materials and Methods:Exploratory analyses investigated the relationship between invasive disease-free survival (IDFS) and HER2 protein expression/gene amplification, PIK3CA hotspot mutations, and gene expression of HER2, PD-L1, CD8, predefined immune signatures, and Prediction Analysis of Microarray 50 intrinsic molecular subtypes, classified by Absolute Intrinsic Molecular Subtyping. HER2 expression on paired pre- and post-NAT samples was examined.Results:T-DM1 appeared to improve IDFS versus trastuzumab across most biomarker subgroups, except the HER2 focal expression subgroup. High versus low HER2 gene expression in residual disease was associated with worse outcomes with trastuzumab [HR, 2.02; 95% confidence interval (CI), 1.32–3.11], but IDFS with T-DM1 was independent of HER2 expression level (HR, 1.01; 95% CI, 0.56–1.83). Low PD-L1 gene expression in residual disease was associated with worse outcomes with trastuzumab (HR, 0.66; 95% CI, 0.44–1.00), but not T-DM1 (HR, 1.05; 95% CI, 0.59–1.87). PIK3CA mutations were not prognostic. Increased variability in HER2 expression was observed in post-NAT versus paired pre-NAT samples.Conclusions:T-DM1 appears to overcome HER2 resistance. T-DM1 benefit does not appear dependent on immune activation, but these results do not rule out an influence of the tumor immune microenvironment on the degree of response.

The healthcare industry compares unfavorably with other ultra-safe industries such as aviation and nuclear power plants, which address complexity by reducing the vulnerability of a single person and promoting teams and strong systems. A multidisciplinary tumor board (MTB) is an evidence-based organizational approach to implementing a more effective concept in oncology practice. Studies addressing the correlation between MTBs and cancer outcomes show promising results, and other potential benefits are also addressed. The objectives of this article are to define and characterize MTBs in modern oncology practice, review the current literature on MTBs effectiveness and address challenges to the implementation and maintenance of MTBs. In this commentary-type narrative review, the authors present their opinions and, whenever possible, substantiate recommendations by citing supportive literature.Lay abstract Compared with other ultra-safe industries such as aviation and nuclear power plants, the healthcare industry operates with lower safety standards. Multidisciplinary tumor boards (MTBs) are regular meetings of various specialist doctors and other health professionals involved in cancer care to discuss cases of patients with cancer. MTBs are considered valuable tools to promote the quality of care in oncology by reducing the vulnerability of a single person and promoting teams and strong systems. Studies have shown that MTBs correlate with better treatment results, and other potential benefits are also addressed. The objectives of this paper are to define and characterize MTBs in modern oncology practice, review the current literature on MTBs and address challenges to the implementation and maintenance of MTBs. The authors substantiate their views with literature citations where possible.

Radiologic complete response (rCR) in breast cancer patients after neoadjuvant chemotherapy (NAC) does not necessarily correlate with pathologic complete response (pCR), a marker traditionally associated with better outcomes. We sought to verify if data extracted from two important steps of the imaging workup (tumor features at pre-treatment MRI and post-treatment mammographic findings) might assist in refining the prediction of pCR in post-NAC patients showing rCR. A total of 115 post-NAC women with rCR on MRI (2010–2016) were retrospectively assessed. Pre-treatment MRI (lesion morphology, size, and distribution) and post-treatment mammographic findings (calcification, asymmetry, mass, architectural distortion) were assessed, as well as clinical and molecular variables. Bivariate and multivariate analyses evaluated correlation between such variables and pCR. Post-NAC mammographic findings and their correlation with ductal in situ carcinoma (DCIS) were evaluated using Pearson’s correlation. Tumor distribution at pre-treatment MRI was the only significant predictive imaging feature on multivariate analysis, with multicentric lesions having lower odds of pCR (p = 0.035). There was no significant association between tumor size and morphology with pCR. Mammographic residual calcifications were associated with DCIS (p = 0.009). The receptor subtype remained as a significant predictor, with HR-HER2 + and triple-negative status demonstrating higher odds of pCR on multivariate analyses. Multicentric lesions on pre-NAC MRI were associated with a lower chance of pCR in post-NAC rCR patients. The receptor subtype remained a reliable predictor of pCR. Residual mammographic calcifications correlated with higher odds of malignancy, making the correlation between mammography and MRI essential for surgical planning. Key Points • The presence of a multicentric lesion on pre-NAC MRI, even though the patient reaches a radiologic complete response on MRI, is associated with a lower chance of pCR. • Molecular status of the tumor remained the only significant predictor of pathologic complete response in such patients in the present study. • Post-neoadjuvant residual calcifications found on mammography were related to higher odds of residual malignancy, making the correlation between mammography and MRI essential for surgical planning.

Background In the KATHERINE study (NCT01772472), patients with residual invasive early breast cancer (EBC) after neoadjuvant chemotherapy (NACT) plus human epidermal growth factor receptor 2 (HER2)-targeted therapy had a 50% reduction in risk of recurrence or death with adjuvant trastuzumab emtansine (T-DM1) versus trastuzumab. Here, we present additional exploratory safety and efficacy analyses. Patients and methods KATHERINE enrolled HER2-positive EBC patients with residual invasive disease in the breast/axilla at surgery after NACT containing a taxane (± anthracycline, ± platinum) and trastuzumab (± pertuzumab). Patients were randomized to adjuvant T-DM1 (n = 743) or trastuzumab (n = 743) for 14 cycles. The primary endpoint was invasive disease-free survival (IDFS). Results The incidence of peripheral neuropathy (PN) was similar regardless of neoadjuvant taxane type. Irrespective of treatment arm, baseline PN was associated with longer PN duration (median, 105-109 days longer) and lower resolution rate (∼65% versus ∼82%). Prior platinum therapy was associated with more grade 3-4 thrombocytopenia in the T-DM1 arm (13.5% versus 3.8%), but there was no grade ≥3 hemorrhage in these patients. Risk of recurrence or death was decreased with T-DM1 versus trastuzumab in patients who received anthracycline-based NACT [hazard ratio (HR) = 0.51; 95% confidence interval (CI): 0.38-0.67], non-anthracycline-based NACT (HR = 0.43; 95% CI: 0.22-0.82), presented with cT1, cN0 tumors (0 versus 6 IDFS events), or had particularly high-risk tumors (HRs ranged from 0.43 to 0.72). The central nervous system (CNS) was more often the site of first recurrence in the T-DM1 arm (5.9% versus 4.3%), but T-DM1 was not associated with a difference in overall risk of CNS recurrence. Conclusions T-DM1 provides clinical benefit across patient subgroups, including small tumors and particularly high-risk tumors and does not increase the overall risk of CNS recurrence. NACT type had a minimal impact on safety.

Cancer is an increasing and significant problem for both high- and low- and middle-income countries. Basic, translational, and clinical research efforts have been instrumental in generating the outstanding improvements we have witnessed over the last few decades, answering important questions, and improving patient outcomes. Arguably, a substantial portion of currently ongoing research is sponsored by the pharmaceutical industy and specifically addresses questions under industry interests, most of which apply to high-income countries, leaving behind problems related to the much larger and underserved population of patients with cancer in low- and middle-income countries. In this scenario, discussing independent academic research is an important challenge, particularly for these countries. Although different countries and institutions face different problems while establishing independent research agendas, some generalizable barriers can be identified. A solid regulatory and ethical framework, a strong and sustainable technical supporting infrastructure, and motivated and experienced investigators are all paramount to build a viable and productive academic research program. Securing funding for research, although not the only hurdle, is certainly one of the most basic hurdles to overcome. Noticeably, and as an added impediment, public and governmental support for cancer research has been decreasing in high-income countries and is almost nonexistent in the rest of the world. We propose an initial careful diagnostic assessment of the research resource scenario of each institution/country and adjustment of the strategic development plan according to four different research resource restriction levels. Although not necessarily applicable to all situations, this model can be helpful if adjusted to each local or regional situation.

Purpose: The SARS-CoV-2 pandemic was declared a global public health emergency. Determinants of mortality in the general population are now clear, but specific data on patients with breast cancer (BC) remain limited, particularly in developing nations. Materials and methods: We conducted a longitudinal, multicenter cohort study in patients with BC and confirmed SARS-CoV-2 infection. The primary end point was the proportion of patients on treatment for severe SARS-CoV-2 infection (defined as need for hospitalization) or early death (within 30 days of diagnosis). Data were evaluated sequentially in the following way: i) univariate Fisher’s exact test; ii) multivariable logistic regression analysis; and iii) multivariable logistic regression. In items i and ii only those with P< 0.1 are considered significant and in stage iii only those with p< 0.05 were the final significant variables. We divided patients’ data into three major variable domains: a) signs and symptoms; b) comorbidities; and c) tumor and treatment characteristics; in item ii each variable domain was tested separately, finally, in item iii the significant variables of all domains were tested together and we called it the integrative step. Results: From April 2020 to June 2021, 413 patients with BC and COVID-19 were retrospectively registered, of which 288 (70%) had an identified molecular subtype and 273 (66%) had stage information. Most patients were on active systemic therapy or radiotherapy (73.2%), most of them in the curative setting (69.5%). The overall rate of severe SARS-CoV-2 was 19.7% (95% CI, 15.3-25.1). In the integrative multivariate analysis, factors associated with severe infection were metastatic setting, chronic pain, acute dyspnea, and cardiovascular comorbidities. Recursive partitioning modeling used acute dyspnea, metastatic setting, and cardiovascular comorbidities to predict non-progression to severe infection, yielding a negative predictive value of 84.9% (95% CI, 78.9%-88.3%). Conclusion: The rate of severe COVID-19 in patients with BC is influenced by prognostic factors that partially overlap with those reported in the general population. High-risk patients should be considered candidates to active preventive measures to reduce the risk of infection, close monitoring in the case of exposure or SARS-CoV-2 -related symptoms and prophylactic treatment once infected. Citation Format: Fanny Cascelli, Matheus Costa e Silva, Rodrigo Dienstmann, Bruno L. Ferrari, Carlos Gil Ferreira, Max S. Mano, Jorge Canedo, Diego Cunha, Daniel Luiz Gimenes, Aline Goncalves. Determinants of severe COVID-19 infection in Patients with Breast Cancer from a Community Oncology Practice in Brazil [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-03-36.

Globalization and digitization have brought in unprecedented changes in the leadership-organization-environment equation. Managing this equation is complex because it is not confined by clear, known boundaries. Today's leadership, in this situation, faces three major challenges: One, they confront problems that are occurring rapidly, are complex in nature, and may be unclear as not having experienced by them before. Two, they have to make quick decisions, in spite of "complexity, novelty and ambiguity" (Lord & Maher, 19901). Three, they have to take risk, keeping in mind "negative consequences of a solution with respect to other on-solving efforts and broader system goals (Mumford & Peterson, 19992). This article addresses the primary, fundamental issue of leadership competencies, which Prof. Fadil Çitaku’s Leadership Competency Model (2012) and currently published Leadership Competency Model Drenica (Çitaku and Ramadani, 2020) propose, and the Leadership Style befitting to the organizational structure that Prof. Don Zilloux, the author of The Results-Focused Organization (2011) elucidates. Additionally, in this study a large body of evidence-based literature have been reviewed to highlight the newest outcomes from the Science of Leadership regarding Leadership, Risk-Taking and Decision-Making.

Breast cancer (BC) is a highly heterogeneous disease, characterized by a variety of subtypes with distinct biological, molecular, and clinical behavior. Standard clinicopathological and tumor biology information (as assessed by gene expression signatures-GES), have provided enhanced prognostic and predictive information in both node-negative(N0) and positive(N +), hormonal receptor positive/human epidermal growth factor 2 negative (HR+/HER2-) early breast cancer (EBC). Herein, we comprehensively review the clinical data of 5 commonly used GES, namely, Oncotype DX(ODX)®; MammaPrint (MP)®; Prosigna®; Breast Cancer Index (BCI)® and Endopredict® - with sections specifically addressing the role of GES in special histologic subtypes, premenopausal women, late recurrence and adjuvant treatment de-escalation.

Trastuzumab emtansine (T-DM1), given postoperatively for 14 cycles to patients with human epidermal growth factor receptor 2-positive (HER2-positive) early breast cancer (EBC) who failed to achieve a pathological complete response after standard chemotherapy and HER2 blockade, represents probably the greatest progress in the management of this aggressive form of breast cancer since the adjuvant trastuzumab pivotal trials. This article addresses the rationale behind the conception of the KATHERINE trial, T-DM1’s structure and pharmacokinetics data, clinical efficacy data of the KATHERINE trial and of other EBC trials with T-DM1, safety aspects, implications of the KATHERINE trial results to clinical practice and future perspectives in the management of HER2-positive EBC.

Background The phase 3 KATHERINE trial demonstrated significantly improved invasive disease–free survival with adjuvant trastuzumab emtansine (T‐DM1) versus trastuzumab in patients with HER2‐positive early breast cancer and residual invasive disease after neoadjuvant chemotherapy plus HER2‐targeted therapy. Methods Patients who received taxane‐ and trastuzumab‐containing neoadjuvant therapy (with/without anthracyclines) and had residual invasive disease (breast and/or axillary nodes) at surgery were randomly assigned to 14 cycles of adjuvant T‐DM1 (3.6 mg/kg intravenously every 3 weeks) or trastuzumab (6 mg/kg intravenously every 3 weeks). The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Core 30 (QLQ‐C30) and breast cancer module (QLQ‐BR23) were completed at screening, at day 1 of cycles 5 and 11, within 30 days after study drug completion, and at 6‐ and 12‐month follow‐up visits. Results Of patients who were randomly assigned to T‐DM1 (n = 743) and trastuzumab (n = 743), 612 (82%) and 640 (86%), respectively, had valid baseline and ≥1 postbaseline assessments. No clinically meaningful changes (≥10 points) from baseline in mean QLQ‐C30 and QLQ‐BR23 scores occurred in either arm. More patients receiving T‐DM1 reported clinically meaningful deterioration at any assessment point in role functioning (49% vs 41%), appetite loss (38% vs 28%), constipation (47% vs 38%), fatigue (66% vs 60%), nausea/vomiting (39% vs 30%), and systemic therapy side effects (49% vs 36%). These differences were no longer apparent at the 6‐month follow‐up assessment, except for role functioning (23% vs 16%). Conclusion These data suggest that health‐related quality of life was generally maintained in both study arms over the course of treatment., Patient‐reported outcomes are reported from the randomized, phase 3 KATHERINE trial, which demonstrated significantly improved invasive disease–free survival with adjuvant T‐DM1 compared with trastuzumab in patients who had residual invasive disease following neoadjuvant chemotherapy plus HER2‐targeted therapy. Patients who are treated with T‐DM1 have a greater incidence of any grade and grade ≥3 adverse events compared with trastuzumab‐treated patients; however, these adverse events appear to have a minimal impact on patient‐reported quality of life.

INTRODUCTION: The evaluation of an individual with risk of hereditary breast cancer is based on the patient's family history and the characteristics of the neoplasia. BRCA1 and BRCA 2 are the most common genes associated with hereditary predisposition for breast or ovarian cancer. The evaluation of an individual with risk of hereditary breast cancer is key to identify patients with indication to BRCA test. Recent studies in US suggests that 31 to 34% of patients with breast cancer should be referred for genetic evaluation. In Brazil, the proportion of BC patients with indication to genetic evaluation is unknown. OBJECTIVE: To describe the prevalence of breast cancer patients enrolled in the AMAZONA III study with indication for genetic evaluation considering the criteria for hereditary breast and ovarian cancer syndrome (HBOC). METHOD: We evaluated the database of the AMAZONA III observational, prospective cohort study which included 2950 patients newly diagnosed with BC in the period of 2016-18 within 23 Brazilian sites. The criteria used to select patients who should be referred for genetic testing were extracted from the National Comprehensive Cancer Network (NCCN) guideline 2018. The characteristics of interest were summarized through descriptive statistics. RESULTS: A total of 1094 (37%) BC patients had at least one criteria for HBOC syndrome test. The most common criteria for testing was age equal or inferior 45 years (27%), BC diagnosis under 50 years and family history of breast cancer (13.5%). From the 2950 enrolled patients, 651 (22%) had the information about whether an evaluation of BRCA test was performed. Of them only 45 (6.9%) performed BRCA test, one patient from public health system and the others from private health system and from those tested 18 (40%) had an identified pathogenic mutation. CONCLUSION: A high proportion of patients diagnosed with BC in Brazil have a criteria for HBOC syndrome testing. Nonetheless a few patients have access to genetic counseling and BRCA test, especially in the public health system. Therefore its critical to implement health policies to facilitate the access to specialized care in hereditary cancer. Frequency of each criteria regarding all 2950 patientsTotal - n (%)Missing - n (%) Citation Format: Alessandra BorbaAnton de Souza, Daniela Rosa, Antonio LuiZ Frasson, Felipe Pereira Zerwes, Nathalia Cunha Rossato, Patricia Asthon-Prolla, Sergio Simon, Jose Bines, Carlos Barrios, Alessandra Morelle, Carlos AlbertoSampaio Filho, Max Mano, Rafaela Gomes, Gustavo Werutsky. Prevalence of patients with indication of genetic evaluation for hereditary breast and ovarian syndrome in the Brazilian cohort study - AMAZONA III [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-09-11.

Background: Patients with HER2-positive early breast cancer with residual invasive disease after neoadjuvant chemotherapy (NACT) + HER2-targeted therapy have a higher risk of recurrence and death than those with pathologic complete response. In the phase III KATHERINE study, adjuvant T-DM1 reduced the risk of recurrence or death by 50% vs H in this population. Data from KATHERINE subgroups are reported here, including patients treated with non-anthracycline (AC) vs AC based NACT, patients with small tumors (cT1cN0) who typically do not receive neoadjuvant treatment, and patients with particularly higher-risk tumors defined by nodal involvement and hormone-receptor status. Methods: Eligible patients had HER2-positive early breast cancer, received taxane- and H-containing neoadjuvant therapy ± AC followed by surgery, and had residual invasive disease in the breast and/or axillary nodes. Patients received 14 cycles of adjuvant T-DM1 (3.6 mg/kg IV q3w) or H (6 mg/kg IV q3w) and endocrine and/or radiation therapy per local standards. The primary endpoint was invasive disease-free survival (IDFS), defined as time from randomization to the first occurrence of ipsilateral locoregional or contralateral invasive breast cancer recurrence, distant recurrence, or death from any cause. In this exploratory analysis, efficacy subpopulations were derived from the intent-to-treat population and safety data were reported for patients who received ≥1 dose of study treatment. Results: In the non-AC v AC based NACT analysis (N=1486), some patient characteristics were imbalanced. For non-AC/AC based NACT, respectively, these included: region (North America; 60.6% v 11.0%), race (Asian; 12.8% v 7.4%), ECOG PS 1 (28.0% v 15.7%); neoadjuvant HER2-based therapy (H + pertuzumab; 46.6% v 9.8%), and neoadjuvant carboplatin/cisplatin (78.7 v 2.3%). Benefit was observed with T-DM1 regardless of neoadjuvant AC use (Table). The all-grade incidence of selected AEs with T-DM1 including hepatotoxicity, peripheral neuropathy, hemorrhage, IRR/hypersensitivity, and cardiac dysfunction was similar between non-AC and AC NACT groups. There was a small increase in the non-AC group in all-grade thrombocytopenia (32.5% v 27.4%) and pulmonary toxicity (6.7% vs 1.7%). There was an increased incidence of grade ≥3 AEs (39.9% vs 21.7%) in the non-AC vs the AC group with T-DM1 which was likely driven by an increase in thrombocytopenia (10.4% v 4.3%) and peripheral sensory neuropathy (4.3% vs 0.5%). However, the percentage of patients with AEs leading to T-DM1 withdrawal in the non-AC vs AC groups (19.6% v 17.5%) was similar, as was the percentage with AEs leading to T-DM1 dose reduction (14.1% v 11.6%). In patients with cT1N0 tumors (n=77), baseline characteristics were well-balanced for H v T-DM1. There were only 6 IDFS events in this subgroup overall; none were observed with T-DM1 (Table). In the analysis of particularly higher-risk tumors, all subgroups showed a benefit with T-DM1; the number of patients was small in some subgroups (Table). Conclusions: T-DM1 provides clinical benefit regardless of prior non-AC vs AC based NACT, and in subgroups with small or particularly higher-risk tumors. There was an increased incidence of grade ≥3 AEs with T-DM1 in the non-AC vs the AC group but these did not result in increased treatment discontinuation and were likely driven by the imbalance in prior therapy. Table 1. Risk of IDFS event in patients treated with non-AC versus AC based NACT, patients with small tumors, and patients with particularly higher-risk tumors.Unstratified hazard ratio of IDFS (95% confidence interval [CI])Patients treated with non-AC vs AC based NACT (N=1,486)Non-AC-based NACT: H (n=179) vs T-DM1 (n=164)0.43 (0.22–0.82)AC-based NACT: H (n=564) vs T-DM1 (n=579)0.51 (0.38–0.67)Patients with small (cT1cN0) tumors (N=77)H (n=32) vs T-DM1 (n=45)6 events with H; 0 events with T-DM1(hazard ratio not applicable due to zero events in T-DM1 arm)Tumor subgroups defined by nodal and HR status (N=957)Inoperable; any HR or ypN statusH (n=190)T-DM1 (n=185)3-year IDFS event-free rate, % (95% CI)60.2 (52.7–67.8)76.0 (70.0–82.4)Unstratified hazard ratio (95% CI)0.54 (0.37–0.80)Operable; ypN positive and HR negativeH (n=52)T-DM1 (n=58)3-year IDFS event-free rate, % (95% CI)69.5 (56.1–82.9)76.0 (64.5–87.5)Unstratified hazard ratio (95% CI)0.72 (0.35–1.50)Operable; ypN positive and HR positiveH (n=167)T-DM1 (n=168)3-year IDFS event-free rate, % (95% CI)77.2 (70.2–84.1)91.4 (86.6–96.2)Unstratified hazard ratio (95% CI)0.43 (0.25–0.75)Operable; ypN0 and HR negativeH (n=68)T-DM1 (n=69)3-year IDFS event-free rate, % (95% CI)77.2 (66.5–87.9)91.1 (84.3–97.9)Unstratified hazard ratio (95% CI)0.43 (0.17–1.06) Citation Format: Max S Mano, Sibylle Loibl, Eleftherios P. Mamounas, Gunter von Minckwitz, Chiun-Sheng Huang, Michael Untch, Norman Wolmark, Irene L. Wapnir, Youngsen Yang, Alison K. Conlin, Sherko Kümmel, Mahasti Saghatchian, Michael P. DiGiovanna, Claudia Strunk, Martina Zimovjanova, Chunyan Song, Haying Liu, David Tesarowski, Steven Blotner, Lisa H. Lam, Melanie Smitt, Charles E. Geyer Jr. Adjuvant trastuzumab emtansine (T-DM1) vs trastuzumab (H) in patients with residual invasive disease after neoadjuvant therapy for HER2-positive breast cancer: KATHERINE subgroup analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-14-01.

Background: Oncotype DX Recurrence Score (ODXRS) is a 21-gene test that has been validated as an assay to effectively predict recurrence and chemotherapy benefit for hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) and lymph node negative (pN0) breast cancer. It has also been used in patients with 1-3 positive lymph nodes (pN1) in clinical practice. Methods: A single-institution retrospective study was conducted to include all patients who had an ODXRS test in our cancer center from 2005 to 2019. Clinical and pathology data were extracted from electronic charts. The predicted ODXRS was recorded and correlated with selected clinicopathological characteristics potentially related to a high-risk profile. A multivariate logistic regression model was performed to identify independent predictors of high-risk ODXRS (≥26) and ROC analysis was done to provide performance of the final model, found through exhaustive screening using Information Criteria (AIC). Associations with p Results: Two hundred and seventy-five patients with estrogen receptor positive, HER2 negative, pN0 or pN1 breast cancer were included. Median age was 55 years (range, 29 - 79). The ODXRS was low (25) in 58 (21.1%), 178 (64.7%) and 39 (14.2%) patients, respectively. On univariate and multivariate analyses, progesterone receptor negative status (p Conclusions: In our study, a prediction model based on progesterone receptor status, histological grade and KI-67 proliferation rate can be used to predict high-risk ODXRS. In resource-constrained healthcare systems, such model might help identify high-risk patients who would benefit from adjuvant chemotherapy without incurring the costs of the ODXRS test. Multivariable logistic regression Models for predicting High-Risk (>25) scores.Clinical and pathological variablesUnivariate OR (95%CI) pMultivariate OR (95%CI) pPatient age ≤ 50> 501.16 (0.58-2.36)0.682Multifocal tumorAbsent Present1.78 (0.81-3.70)0.1332.38 (0.86-6.34)0.085HistologyDuctalLobular1.14 (0.43 – 2.69)0.778Other0.65 (0.18 – 1.79)0.447T staging T1T2/31.25 (0.53-2.72)0.595N stagingN0N1 0.62 (0.20-1.55)0.347High-grade histologyG1/2G310.44 (3.97-28.25) Citation Format: Leandro JonataCarvalho Oliveira, Thais BacciliCury Megid, Marina Sahade, Andrea Kazumi Shimada, Daniele Xavier Assad, Joao Vicente Horvat, Antonildes Nascimento Assunção, Artur Katz, Max Senna Mano. Prediction of the high-risk oncotype Dx recurrence score from clinicopathologic factors: A report from a cancer reference center in Brazil [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-47.

Background: Recent medical literature reports that mastectomy rates are increasing in early breast cancer. The reasons for this have not yet been elucidated and appear to be complex and can be related to: availability of immediate reconstruction, expertise of the surgeon, increment of genetic tests and beliefs, unwillingness or impossibility of receipting radiotherapy, and information of the patients themselves. The present study aimed to demonstrate mastectomy rates throughout the years from a single Brazilian institution and to correlate it with age, neoadjuvant therapies and tumor staging. Methods: A retrospective analysis of breast cancer surgeries from patients treated at Hospital Sírio-Libanês cancer center from 2005 to 2018 was performed. The institutional database electronically of physically registered in this period included pathology, radiology, and clinical information. Chi-squared coefficient of correlation was applied for categorical variables analysis of association, and for significant findings a multivariate regression analysis was performed. All statistical analyses were performed in STATA version 15.1C. Results: Medical records from 2,942 patients treated were analyzed. 1,798 mastectomies (including nipple-sparing mastectomies and skin-sparing mastectomies) were performed against 1,144 conservative surgeries (61.11% x 38.89%). The range of mastectomy rates varied from 73.04% (2007) to 48.8% (2018) and mastectomy rates showed a slight decrease (53.84% in 2005 and 48.14% in 2018). Type of surgery (conservative, mastectomy, skin-sparing mastectomy) was associated with neoadjuvant treatment (p Conclusions: These results demonstrate that our mastectomy rates, differently from global trends, did not increase through the past 15 years. These findings are probably related to impossibility of genetic tests in this population, accurate diagnostic techniques and the achievement of higher response rates with neoadjuvant treatment. Interestingly, breast-conserving surgery rates were inversely correlated with older age, which can reflect an individualized therapeutic approach among a subgroup of patients potentially vulnerable to chemo-related toxicity. Citation Format: Thatyane EspósitoGallo Cunha, Thamyse FernandaSá Dassie, Julianne MariaSilva Lima, Max Senna Mano, Lincon Jo Mori, Samir Abdallah Hanna, Sandro ViniciusMachado Melo, Gustavo Nader Marta, Felipe EduardoMartins Andrade. Mastectomy rates in a single Brazilian institution through the past 15 years: Are we following the global trend? [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-20-29.

PURPOSE Physicians rarely receive formal training in leadership skills. Çitaku and colleagues have identified a set of leadership competencies (LCs) providing validity evidence in North American (NA) and European Union (EU) medical education institutions. We aim to apply this same survey to a sample of Latin American (LA) medical leaders from the oncology community and related areas, compare the results with those of the previous survey, and perform subgroup analyses within the LA cohort. METHODS The survey was sent to nearly 8,000 physicians of participating professional organizations. In addition to the 63 questions, we also collected data on the type of institution, country, specialty, sex, age, years of experience in oncology, and leadership position. RESULTS The 217 LA respondents placed the highest value on task management competencies (91.37% reported these as important or very important v 87.0% of NA/EU respondents; P < .0001), followed by self-management (87.45% of LA respondents v 87.55% of NA/EU respondents; P = not significant [NS]), social responsibility (86.83% of LA respondents v 87.48% of NA/EU respondents; P = NS), innovation (86.69% of LA respondents v 85.31% of NA/EU respondents; P = NS), and leading others (83.31% of LA respondents v 84.71% of NA/EU respondents; P = NS). Social responsibility, which was first in importance in the NA/EU survey, was only third in the LA survey. Subgroup analyses showed significant variations in the ratings of specific LCs within the LA population. CONCLUSION LCs valued by LA leaders somewhat differ from those valued by their NA and EU counterparts, implying that cultural aspects might influence the perception of desired LCs. We also detected variations in the responses within the LA population. Our data indicate that current physician leadership training programs should be tailored to suit specific needs and cultural aspects of each region. Further validity studies of this instrument with other samples and cultures are warranted.

Radiologic complete response (rCR) in breast cancer patients after neoadjuvant chemotherapy (NAC) does not necessarily correlate with pathologic complete response (pCR), a marker traditionally associated with better outcomes. We sought to verify if data extracted from two important steps of the imaging workup (tumor features at pre-treatment MRI and post-treatment mammographic findings) might assist in refining the prediction of pCR in post-NAC patients showing rCR.A total of 115 post-NAC women with rCR on MRI (2010-2016) were retrospectively assessed. Pre-treatment MRI (lesion morphology, size, and distribution) and post-treatment mammographic findings (calcification, asymmetry, mass, architectural distortion) were assessed, as well as clinical and molecular variables. Bivariate and multivariate analyses evaluated correlation between such variables and pCR. Post-NAC mammographic findings and their correlation with ductal in situ carcinoma (DCIS) were evaluated using Pearson's correlation.Tumor distribution at pre-treatment MRI was the only significant predictive imaging feature on multivariate analysis, with multicentric lesions having lower odds of pCR (p = 0.035). There was no significant association between tumor size and morphology with pCR. Mammographic residual calcifications were associated with DCIS (p = 0.009). The receptor subtype remained as a significant predictor, with HR-HER2 + and triple-negative status demonstrating higher odds of pCR on multivariate analyses.Multicentric lesions on pre-NAC MRI were associated with a lower chance of pCR in post-NAC rCR patients. The receptor subtype remained a reliable predictor of pCR. Residual mammographic calcifications correlated with higher odds of malignancy, making the correlation between mammography and MRI essential for surgical planning. Key Points • The presence of a multicentric lesion on pre-NAC MRI, even though the patient reaches a radiologic complete response on MRI, is associated with a lower chance of pCR. • Molecular status of the tumor remained the only significant predictor of pathologic complete response in such patients in the present study. • Post-neoadjuvant residual calcifications found on mammography were related to higher odds of residual malignancy, making the correlation between mammography and MRI essential for surgical planning.

BACKGROUND: Breast cancer (BC) in young women is uncommon and often more aggressive. There are disparities in terms of screening coverage, diagnostic features and access to optimal treatment among young BC patients worldwide. To better understand this scenario through real world data we performed a sub-analysis of AMAZONA III study. METHODS: The AMAZONA III study (GBECAM 0115) is a prospective registry that included 2950 women newly diagnosed with invasive BC in Brazil during the period of January 2016 to March 2018 within 22 sites. Of them, 2888 patients had valid data regarding age at diagnosis and complete baseline information. For the purpose of comparisons of epidemiologic and clinicopathologic features at the time of diagnosis of BC, patients were divided in two groups: women aged ≤40 years (Group 1) and >40 years (Group 2). Quantitative variables were expressed with mean, while categorical variables were described as their count and percentage and compared using the chi-square test. RESULTS: Of 2888 women, 486 (17%) were ≤40 years of age. No differences were found between ethnicity, performance status, body mass index, personal income, health insurance and family history of cancer between the two groups. Young women had higher educational level (p Breast cancer features by age groups at diagnosis in Brazilian women.InformationGroup 1 (≤40 years)Group 2 (> 40 years)p-valueN: 2888486 (16.83%)2402 (83.17%) Stage at diagnosis p< 0.001I76 (19.2%)541 (27.8%) II156 (39.4%)816 (41.9%) III146 (36.8%)489 (25.1%) IV19 (4.6%)101 (5.2%) Tumor size p< 0.001T1114 (27.1%)749 (36.9%) T2141 (33.6%)764 (37.6%) T3101 (24.1%)282 (13.9%) T464 (15.2%)235 (11.6%) Tumor grade p < 0.001Grade 146 (10.7%)381 (17.9%) Grade 2198 (46.2%)1150 (52.0%) Grade 3185 (43.1%)641 (30.1%) Molecular Subtype p < 0.001Luminal A106 (30.6%)957 (51.3%) Luminal B - HER 2 negative55 (15.8%)212 (11.4%) Luminal B- HER 2 positive79 (22.8%)298 (16.0%) HER 2 positive27 (7.8%)135 (7.2%) Triple negative80 (23.0%)264 (14.1%) Citation Format: Franzoi MA, Rosa D, Barrios C, Bines J, Cronemberger E, Queiroz G, Cordeiro de Lima VC, Junior R, Couto J, Emerenciano K, Resende H, Crocamo S, Reinert T, Van Evyl B, Neron Y, Dybal V, Lazaretti N, Costamilan RdC, de Andrade D, Mathias C, Zerwes Vacaro G, Borges G, Silva K, Werutsky G, Morelle A, Sampaio Filho CA, Mano M, Zaffaroni F, Simon S, Liedke PE. Advanced stage at diagnosis and worse clinicopathologic features in young woman with breast cancer. A sub-analysis of Brazilian population through the AMAZONA III study (GBECAM 0115) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-08-27.

BACKGROUND Breast cancer (BC) is the most common tumor in women in Brazil with about 60 thousand new cases estimated per year. In low and middle-income countries, patients with BC are diagnosed with more advanced stages as compared with high-income countries. In Brazil, disparities in access to new therapies are recognized; previous data suggests worse survival of BC patients treated in the public system. The aim of AMAZONA III study (GBECAM 0115) is to describe the current status of BC care in Brazil. Here we report patients data at baseline. METHODS The AMAZONA III is a prospective BC registry that included women 18 years or older with newly diagnosed stage I to IV BC from 22 sites in Brazil in the period of January 2016 to March 2018. All patients provided written informed consent; data was collected from interview and medical charts, comprising clinical-demographic variables, initial treatment and a planned follow-up for 5 years. BC subtypes were defined by hormone receptor (HR) expression, HER2 status and grade according to von Minckwitz G. et al 2012. Here we present a descriptive analysis of the patients' baseline characteristics. Continuous variables are shown as mean (standard-deviation) and categorical variables by its absolute and relative frequencies. The study is registered in clinicaltrials.gov NCT02663973. RESULTS A total of 2950 patients were included in the study. Median age at diagnosis was 53 years old (8.4% 50 years), 58.6% were white, 34.4% had brown skin-color, 83% had children before BC diagnosis (median of 1 child/patient) and 63.1% had public health insurance. In terms of method of detection 34% were screen-detected whereas 66% were symptomatic, the last was even higher (70%) in patients in younger than 50 years. The distribution of BC stage at diagnosis was I (26.4%), II (41.6%), III (27%) and IV (5%). The most common histologies were ductal (80.9%) and lobular carcinoma (6.9%). The pathological characteristics were HR positive in 78.0%, HER-2 positive in 23.4% and grade 2 in 51%. BC subtypes were as follows: Luminal A 48%, Luminal B 12%, Luminal HER2 positive 17%, Non-luminal HER2 positive 7.3% and Triple negative 15.5%. DISCUSSION Breast cancer is diagnosed at an earlier age among Brazilian patients. The majority of patients were detected through symptomatic BC and therefore a significant proportion is still diagnosed in stages III and IV. Among other factors, these findings could have a significant impact in treatment outcomes. Further analysis of this large cohort of patients will help to identify other important elements and direct future strategies for breast cancer control. TRIAL REGISTRY: NCT02663973 KEYWORDS: Breast Cancer; Epidemiology; Treatment; Brazil Citation Format: Rosa D, Barrios C, Bines J, Werustky G, Cronemberger E, Queiroz GS, Lima VC, Freitas-Júnior R, Couto J, Emerenciano K, Resende H, Crocamo S, Reinert T, Van Eyil B, Néron Y, Dybal V, Lazaretti N, Costamilan RC, Andrade DA, Mathias C, Vacaro GZ, Borges G, Torres KL, Morelle A, Sampaio Filho CA, Mano M, Zaffaroni F, Simon S. Current status of clinical and pathological characteristics of breast cancer patients in Brazil: Results of the AMAZONA III study (GBECAM 0115) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-08-29.

e13022 Background: Breast cancer is a leading death cause of women in Brazil. There are increased concerns with limited access to innovative therapies and the effectiveness of these agents outside clinical trials. This study aims to assess practice patterns and real-world outcomes of patients with HER2+ metastatic breast cancer (MBC) treated in the largest network of community oncology practices of Brazil after the introduction of pertuzumab and T-DM1 in routine care. Methods: De-identified electronic medical records from Oncoclínicas Group were aggregated in a cloud-based central database that allows technology-based abstraction, whereby trained data curators qualify the information using mCODE standards. We included data from all patients with a confirmed diagnosis of HER2+ MBC treated from 2014 to 2021. The primary objective was median overall survival (OS) from diagnosis of metastatic disease and other endpoints included adoption of pertuzumab-based regimen and T-DM1 in the palliative setting and their median Time to Treatment Discontinuation (TTD) in a real-world scenario. Results: Out of 21,559 patients with BC in our database, 6,215 had HER2+ disease and 1,250 had MBC treated with at least one palliative anti-HER2 therapy. Median age at diagnosis was 56 years, 29% had de novo metastatic disease, 81% received 2nd line therapy and 47% a 3rd line or beyond. With a median follow-up of 2 years, median OS was 49 months (CI95% 44-59). We found a ten-fold increase in the proportion of patients receiving pertuzumab or T-DM1 in the last two years when compared to 2014-2015. Overall, 62% received a pertuzumab-based regimen, mostly in the 1st line (76%), with median TTD of 9.9 months (CI95% 9-13). T-DM1 was accessible to 22% of the patients, mostly in 2nd (28%) or 3rd line and beyond (50%), with median TTD of 10.2 months (CI95% 9-13). Conclusions: In the largest Brazilian real-world study of patients with HER2+ MBC treated in the private health system, we found similar outcomes as those reported in North-American and European cohorts, both in terms of OS and TTD with standard-of-care therapies. Adoption of pertuzumab and T-DM1 was fast, but there are still gaps in access and the need to optimize clinical positioning of new anti-HER2 therapies recently approved for clinical use.

e18822 Background: Oncotype DX (ODX) is a validated tool for the prediction of risk of recurrence and benefit of chemotherapy (CH) in both node negative (N0) and positive (N1), hormone receptor positive (HR+), HER2 negative (HER2-) early breast cancer (eBC). Due to limited access to novel genomic assays in Brazil, treatment decisions remain largely driven by traditional clinicopathologic risk factors. ODX has been reported to be cost-effective, but limited data is available considering the reality of middle-income countries such as Brazil. We aim to evaluate the cost-effectiveness of ODX across strata of clinical risk groups using data from a large dataset of patients from various Brazilian institutions. Methods: Clinicopathologic and ODX information were analyzed for patients with T1-T3, N0-N1, HR+/HER2- eBC who had an ODX performed between 2005 and 2020. Projections of CH indication by clinicopathologic criteria were based on binary clinical risk categorization based on the Adjuvant! algorithm, as used in the MINDACT study. The ODX score was correlated with the indication of CH according to TAILORx and RxPONDER data. Two decision-tree models were developed. In the first model, low and high clinical risk patients were included the model. In the second model, only high clinical risk patients were included. The cost for ODX and CH (U$2,846 and U$14,464, respectively) were based on the Brazilian private medicine perspective. Uncertainty was assessed using deterministic and probabilistic sensitivity analyses. Results: Six hundred and forty-five patients were analyzed. 411 patients (63.7%) had low clinical risk and 234 patients (36.3%) had high clinical risk disease. The ODX indicated low (< 11), intermediate (11-25) and high (> 25) risk in 119 (18.4%), 415 (64.3%) and 111 (17.2%) patients, respectively. Among 645 patients analyzed in the first model, 234 (36.2%) had clinical and 198 (30.6%) had genomic indication for CH, respectively. In this model, ODX was modestly effective (5.6% reduction in CH indication) though with an incremental cost of US$ 2,040 per patient. Among 234 patients analyzed in the second model (high clinical risk only), 99 (42.3%) patients had genomic indication of CH. In this model, ODX led to a 57.7% reduction in CH indication and reduced costs by US$5,491 per patient (table). The results remained robust in the 1,000 probabilistic simulations. Conclusions: Our study suggests that ODX is cost-saving for patients with high clinical risk HR+/HER2- eBC in the perspective of the Brazilian private health system. Its incorporation into routine practice should be strongly considered by health care providers.[Table: see text]

10559 Background: As a reaction to the COVID-19 pandemic, a nation-wide lockdown was enforced in Brazil in March 2020, cancer care was impacted, and cancer screening reduced. Therefore, an increase in cancer diagnoses at more advanced stages was expected. In this study, we extracted data from our nationwide real-world database to evaluate the impact of the COVID-19 pandemic on the stage at diagnosis of breast cancer (BC) cases. Methods: We explored curated electronic medical record data of female patients, over 18 years of age, diagnosed with BC and with established disease stage based on the AJCC 8th edition, who started treatment or follow-up in the Oncoclínicas (OC) between Jan 1, 2018, and Dec 31, 2021. The primary objective was to compare stage distribution at first visit during COVID-19 pandemic (2020-2021) with a historical control cohort from a period prior to the pandemic (2018-2019). We investigated stage distribution according to age at diagnosis and tumor ER/HER2 subtype in univariate models. Associations were considered significant if they had a minimum significance (P < 0.1 in Chi-square test). The historical numbers of patients with BC at OC make it possible to identify differences in the prevalence of stages in the order of 5% comparing pre and post pandemic periods with a statistical power greater than 80%. Results: We collected data for 11,752 patients with initial diagnosis of BC, with 6,492 patients belonging to the pandemic (2020-2021) and 5,260 patients to the pre-pandemic period (2018-2019). For both ER+/ HER2- and HER2+ tumors, there was a lower percentage of patients with early-stage (defined as stage I-II) in the years 2020-2021 vs 2018-2019 and a considerable increase in advanced-stage disease (defined as stage IV). For triple negative BC (TNBC), there was a significant higher percentage of patients with advanced-stage disease in the pandemic vs pre-pandemic period (table 1). Age over 50 years was associated with a greater risk of advanced stage at diagnosis after the onset of the pandemic, with an absolute increase of 7% (P two-sided

Because of the strong prognostic value of pathologic complete response (pCR) in early breast cancer (EBC), patients who fail to achieve this outcome have increasingly been eligible to a new treatment modality, namely post-neoadjuvant systemic therapy (PNT). However, adjuvant radiation therapy (RT) retains a crucial role in EBC, and also needs to be timely administered to patients. To address how modern PNT optimally integrates with adjuvant RT is therefore the purpose of this review. How PNT administration optimally integrates with adjuvant RT has varied depending on the type of systemic therapy employed. The introduction of novel “targeted” agents has created new challenges, as for many of them limited information is available on the feasibility of concurrent systemic and RT administration or their optimal sequencing. PNT and RT are both of utmost importance to the management of EBC and need to be timely and safely administered to patients. The optimal strategy to integrate these modalities may vary according to the type of PNT agent and other factors.

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.

I was already in my early 40 s when I realised I was a financial illiterate. This happened in the wake of a little professional crisis—when I also envisioned a risk of getting exhausted from my work schedule (which at the time involved 7/8 periods of oncology clinics) before being able to achieve my financial independence. This concept—potentially unfamiliar to many physicians—means the time point where the wealth you have accumulated allows you to continue living on revenues for the rest of your life, without counting on further income from work. Importantly, this does not necessarily mean retirement, but instead breaking free to do only the type of work that gives you true pleasure. For some, this could mean continue to run clinics 7/8 periods; for others, shifting to a 1/8 schedule and taking the rest of the time for academic activities; or instead, working part time and using the free time to run a parallel activity, such as a passion you never had time to enjoy. Physicians should be extremely cautious in assuming they will be willing or able to run busy patient clinics until the late years of their careers and make plans to achieve their financial independence as early as possible (I personally recommend by age 50–55 years). However, reality shows a different story. For instance, in a recent survey of 20.329 US physicians, 53% said they did not have a goal for how much they wanted to save by a certain age.1 The financial life cycle can be simplified as follows: an average person works hard and saves little until age 40 years, then continues to work hard from age 40–60 years, usually being able to accumulate wealth; by …

Background Takotsubo syndrome (TTS), also known as stress cardiomyopathy, apical ballooning syndrome and broken heart syndrome, is characterized by acute-onset chest pain, electrocardiographic (ECG) abnormalities and reversible left ventricular (LV) disfunction in the absence of a culprit obstructive lesion in the coronary arteries; therefore, myocardial infarction is the most important differential diagnosis. Usually induced by emotional/physical stress, its treatment consists in hemodynamic support until complete and spontaneous recovery occurs, which is generally achieved within a few days to weeks. Cervical malignancies are an important public health issue in low/middle-income countries and, in the setting of locally advanced disease, concurrent chemoradiation followed by brachytherapy is considered the standard treatment, harboring curative potential. Case report We report a case of a 38-year-old woman who underwent concurrent chemoradiotherapy and developed cardiopulmonary arrest in ventricular fibrillation during a brachytherapy session. Complementary tests disclosed altered ECG and cardiac biomarkers, no evidence of coronary artery obstruction, as well as LV disfunction consistent with TTS on echocardiogram and cardiac MRI. After few days of supportive therapy, complete recovery of heart function was observed. Conclusions Especially for cancer patients, who usually experience intense emotional/physical stress intrinsically associated with their diagnosis and aggressive treatments, considering TTS as a differential diagnosis is warranted. Intracavitary brachytherapy procedure may represent a trigger for TTS.

In Brazil, the available cancer registries are deficient in number and quality and, hence, little information is known regarding sociodemographic, clinicopathological characteristics, treatment patterns, and outcomes of breast cancer (BC) patients. We performed the AMAZONA III/ GBECAM 0115 study and in this analysis, we describe patients’ characteristics at diagnosis and their association with health insurance type. This is a prospective cohort study developed in 23 sites in Brazil including women with newly diagnosed invasive BC from January 2016 to March 2018. In order to compare healthcare insurance type, we considered patients who were treated under the Brazilian public health system as publicly insured, and women who had private insurance or paid for their treatment as privately insured. A total of 2950 patients were included in the study. Median age at diagnosis was 53.9 years; 63.1% were publicly insured. The majority of patients (68.6%) had stage II–III breast cancer and ductal carcinoma histology (80.9%). The most common breast cancer subtype was luminal A-like (48.0%) followed by luminal B-HER2 positive-like (17.0%) and triple-negative (15.6%). Luminal A was more frequent in private (53.7% vs. 44.2%, p

Metastases are rare in early breast cancer (EBC), and international guidelines recommend against routine systemic staging for asymptomatic patients. However, imaging exams remain widely employed in the clinical practice. The aim of the present study is to evaluate the value of imaging for systemic staging in EBC. A retrospective analysis of newly-diagnosed breast cancer (BC) patients was performed. Clinical data including BC subtype, stage, presence of symptoms at diagnosis and instrumental procedures performed for staging were recorded. A total of 753 patients were included, with a median age of 57 years. The majority of the patients underwent at least 1 imaging procedure (91%); had invasive ductal carcinoma (83.5%); histological grade 2 (51.4%); stage II (61.8%); and luminal subtype (67.9%). Among the 685 (91%) patients who underwent any radiologic staging, distant metastases (DMs) were detected in 32 (4.7%). In the univariate analyses, stage IIb and pathological lymph node involvement (pN1) showed a statistically significant association with the presence of DMs, versus only a trend for triple negative and human epidermal growth factor receptor 2 (Her2) positive subtype. In an exploratory analysis performed in this same subgroup, when unfavorable biology (triple negative or Her2 positive) was present, patients had a DM rate of 14.4%, one of the highest reported at this stage of the disease. Early breast cancer has a low prevalence of DM at the initial evaluation, and systemic staging of asymptomatic, unselected patients is not warranted as a routine practice. However, we have identified subgroups of patients to whom a full staging could be indicated. Metástases são de ocorrência rara no câncer de mama precoce, e as diretrizes internacionais não recomendam o estadiamento sistêmico de rotina para pacientes assintomáticos. Apesar disso, exames de imagem continuam sendo largamente empregados na prática clínica. O objetivo do presente estudo é avaliar o valor do estadiamento por imagem no câncer de mama precoce. MéTODOS: Análise retrospectiva de pacientes recém-diagnosticados com câncer de mama. Foram registrados os dados clínicos dos pacientes, incluindo subtipo da neoplasia de mama, estadiamento, presença de sintomas no momento do diagnóstico e procedimentos de estadiamento. Um total de 753 pacientes foram incluídos, com idade média de 57 anos. Grande parte deles se submeteu a pelo menos um exame de imagem (91%); tinha carcinoma ductal invasivo (83,5%); grau histológico 2 (51,4%); estádio II (61,8%); e subtipo luminal (67,9%). Entre os 685 (91%) pacientes que realizaram algum exame de imagem, metástases à distância foram detectadas em 32 (4,7%). Na análise univariada, estádio IIb e acometimento linfonodal (pN1) tiveram uma associação estatisticamente significativa com a presença de metástase, enquanto os subtipos triplo negativo e receptor tipo 2 do fator de crescimento epidérmico humano (Her2) positivo demonstraram apenas uma tendência para a identificação de metástases. Na análise exploratória deste mesmo subgrupo, diante da presença de biologia desfavorável (triplo negativo e Her2 positivo), os pacientes apresentaram uma taxa de metástase à distância de 14,4%, uma das mais altas relatadas nesse estádio. CONCLUSãO: Neoplasia de mama precoce apresenta baixa baixa prevalência de metástase à distância no momento do diagnóstico, e o estadiamento sistêmico de rotina de pacientes assintomáticos e não selecionados não é justificável. Contudo, identificamos subgrupos de pacientes para os quais o estadiamento completo poderia ser indicado.

Background Anthracycline (ANT) chemotherapy is associated with cardiotoxicity. Prevention with β-blockers remains controversial. Objectives This prospective, randomized, double-blind, placebo-controlled study sought to evaluate the role of carvedilol in preventing ANT cardiotoxicity. Methods The authors randomized 200 patients with HER2-negative breast cancer tumor status and normal left ventricular ejection fraction (LVEF) referred for ANT (240 mg/m2) to receive carvedilol or placebo until chemotherapy completion. The primary endpoint was prevention of a ≥10% reduction in LVEF at 6 months. Secondary outcomes were effects of carvedilol on troponin I, B-type natriuretic peptide, and diastolic dysfunction. Results Primary endpoint occurred in 14 patients (14.5%) in the carvedilol group and 13 patients (13.5%) in the placebo group (p = 1.0). No differences in changes of LVEF or B-type natriuretic peptide were noted between groups. A significant difference existed between groups in troponin I levels over time, with lower levels in the carvedilol group (p = 0.003). Additionally, a lower incidence of diastolic dysfunction was noted in the carvedilol group (p = 0.039). A nonsignificant trend toward a less-pronounced increase in LV end-diastolic diameter during the follow-up was noted in the carvedilol group (44.1 ± 3.64 mm to 45.2 ± 3.2 mm vs. 44.9 ± 3.6 mm to 46.4 ± 4.0 mm; p = 0.057). Conclusions In this largest clinical trial of β-blockers for prevention of cardiotoxicity under contemporary ANT dosage, the authors noted a 13.5% to 14.5% incidence of cardiotoxicity. In this scenario, carvedilol had no impact on the incidence of early onset of LVEF reduction. However, the use of carvedilol resulted in a significant reduction in troponin levels and diastolic dysfunction. (Carvedilol Effect in Preventing Chemotherapy-Induced Cardiotoxicity [CECCY]; NCT01724450)

The percentage of women in leadership positions is increasing and advancing towards gender parity. However, the number of female leaders is still low when compared to male leaders. We endeavored to examine by means of a literature review the impact of Emotional Intelligence (EI) on women´s leadership since we found that EI is a key factor in predicting effective leadership traits. We also found there is a social perception that women tend to be seen as more emotional and empathic than men. We review the definitions of leadership and EI and explore the link between EI, leadership and women. Several leadership scholars and psychologists argue that EI is an important foundation for leadership effectiveness. We review the literature about how men and women compare in their EI attributes. When it comes to learning EI, men and women have the same opportunities to acquire a greater EI through reflection and experience. However, we highlight the necessity for increasing the number of women in leadership positions by enhancing and supporting women’s leadership competencies. Moreover, we emphasize the importance of building EI in order to achieve effective leadership.

Background Randomised clinical trials (RCT) are considered a gold standard generating efficacy and safety data supporting drug approval. However, real world data (RWD) reflecting health care delivery is becoming increasingly important. RWD on patient profiles and patterns of care in MBC are scarce in developing countries. As an example, observational studies suggest that despite guideline recommendations clearly indicating ET for hormone receptor positive MBC, a considerable proportion of patients in clinical practice begin chemotherapy in early lines of therapy. This pragmatic information addresses the uptake and applicability of the RCT results and should be able to help informing health care planning complementing RCT generated data. The objective of this study is to describe patient characteristics and evaluate actual physician-reported treatments for MBC in Brazil. Methods This analysis addresses the first 362 patients included in LACOG-0312, a retrospective study planning to recruit over 700 patients (cut-off date April 30th 2016) with recurrent locally advanced or MBC diagnosed in 2012 in 18 institutions across Brazil. Patient characteristics, type of health insurance coverage, treatment and survival outcome were analysed. Results Median age at BC diagnosis was 53 years and 37% were premenopausal. Regarding the educational level, 63.2% had completed elementary (primary) schooling, 75.7% were covered by the public health system while 24.3% had some form of private coverage. 70% of patients had hormone receptor positive (HR+) and 18% had HER2 positive tumors. Median disease free survival time from surgery was 29 months. Interestingly, 30% of patients underwent a biopsy of a metastatic site. Of the 362 patients, 349 (96.9%) received some form of palliative systemic therapy. Median time from diagnosis of metastatic disease to first-line therapy initiation was 46 days but a significant difference was noted between patients with public versus private health insurance (50 vs. 33 days p=0.012). Half of the patients received at least 3 lines of therapy (chemo or endocrine) to a maximum of 9 lines. In patients with HR+ tumors, endocrine therapy was administered in 47% in first, 65% in second and 61% in third-line, respectively. Median overall survival (OS) from diagnosis of metastatic disease was 34 months (CI 95%: 25.7-44.3) and no differences in OS were observed between patients with public or private coverage (34 months vs. 35 months p=0.808). Causes of death were cancer in 85.2% of patients and treatment toxicity in 3.6%. Conclusion Our study included a population with predominantly low educational level and mostly public health insurance. This likely corresponds to the majority of cases and reflects cancer care patterns in Brazil and many developing countries. A considerable proportion of patients were premenopausal at MBC diagnosis. More than half of HR+ patients received at least 3 lines of endocrine therapy although 54% of them had chemotherapy as the first systemic treatment. Patients from the public health system experienced a delay in starting first-line therapy but this didn't seem to jeopardize cancer outcomes in this setting. Citation Format: Barrios CH, Uema D, Cronenberger E, Lima V, Bines J, de Sant'ana RO, Batista ML, Dybal V, Liedke P, Beato C, Nerón YV, Giacomazzi J, dos Santos L, Ismael G, Azambuja A, Andrade D, Rosa DD, Borges G, Mano M, Martinez-Mesa J, Zaffaroni F, Werutsky G. Real World data and patterns of care of metastatic breast cancer (MBC) in Brazil: First results of LACOG 0312 retrospective study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-16-04.

PURPOSE: Breast cancer (BC) in young women is uncommon and tends to present with more aggressive characteristics. To better understand and characterize this scenario in Brazil through real-world data, we performed a subanalysis of AMAZONA III study (ClinicalTrials.gov identifier: NCT02663973). METHODS: The AMAZONA III study (GBECAM 0115) is a prospective registry that included 2,950 women newly diagnosed with invasive BC in Brazil from January 2016 until March 2018 at 22 sites. Valid data were obtained from 2,888 patients regarding age at diagnosis and complete baseline information. To compare epidemiologic and clinicopathological features at the time of diagnosis, patients with BC were divided into two groups according to age: ≤ 40 years and > 40 years. Quantitative variables were described as means, and categorical variables were described as frequencies and percentages and compared using the Pearson's χ2 test. RESULTS: Of 2,888 women diagnosed with BC, 486 (17%) were ≤ 40 years old. Young women had higher educational level, most were employed and a significant number were married (P < .001 for all associations). Younger patients were more symptomatic at BC diagnosis (P < .001), and they also presented more frequently with stage III, T3/T4, grade 3 tumors, HER-2-positive, luminal B, and triple-negative subtypes. CONCLUSION: Brazilian women younger than age 40 years have unfavorable clinicopathological features of BC at diagnosis, with more aggressive subtypes and advanced stage when compared with older women. These differences are not explained by socioeconomic or ethnic imbalances. The causes of a higher prevalence of BC among young women in Brazil deserve additional investigation., SCOPUS: ar.j, info:eu-repo/semantics/published

Purpose The purpose of the present study was to test the hypothesis that doxorubicin (DX) and cyclophosphamide (CY) adjuvant chemotherapy (CHT) acutely impairs neurovascular and hemodynamic responses in patients with breast cancer. Methods Sixteen women (age: 47.0±2.0 years; body mass index: 24.2±1.5 Kg.m−2) with stage II–III breast cancer and indication for adjuvant CHT underwent two experimental sessions, saline (SL) and CHT. In the CHT session, DX (60 mg/m2) and CY (600mg/m2) were administered in 45 min. In the SL session, a matching SL volume was infused in 45 min. Muscle sympathetic nerve activity (MSNA, microneurography), calf blood flow (CBF, plethysmography) and calf vascular conductance (CVC), heart rate (HR, electrocardiography) and beat-to-beat blood pressure (BP) (Finger plethysmography) were measured before, during and after each session. Blood samples (5 mL) were collected before and after both sessions for assessment of circulating endothelial microparticles (EMPs, flow cytometry), a surrog...