Expanded Access Study of Palbociclib Plus Letrozole for Postmenopausal Women with HR+/HER2- Advanced Breast Cancer in Latin America for Whom Letrozole Therapy is Deemed Appropriate.

BACKGROUND AND OBJECTIVES: Palbociclib is a cyclin-dependent kinase 4/6 inhibitor that is approved in the United States for the treatment of hormone receptor‒positive (HR+)/human epidermal growth factor receptor‒2 negative (HER2-) advanced breast cancer (ABC). The objectives of this expanded access trial were to provide palbociclib in combination with letrozole to patients with HR+/HER2- ABC in Argentina, Brazil, Colombia, and Mexico who were candidates for letrozole therapy before commercial availability of palbociclib, and to evaluate the safety and tolerability of palbociclib plus letrozole. PATIENTS AND METHODS: Postmenopausal women aged ≥ 18 years with HR+/HER2- ABC were eligible to participate in this study. Patients received palbociclib 125 mg once daily (3/1 schedule) and letrozole 2.5 mg once daily (continuous schedule). Safety, objective response rate (ORR), and duration of treatment were evaluated. RESULTS: A total of 130 patients were treated with palbociclib plus letrozole (Argentina, n = 33; Brazil, n = 35; Colombia, n = 28; Mexico, n = 34). The most common treatment-emergent adverse events (TEAEs) of any grade were neutropenia (70.0%), leukopenia (34.6%), anemia (33.8%), decreased neutrophil count (27.7%), and thrombocytopenia (24.6%); 22.3% of patients required a palbociclib dose reduction due to adverse events (AEs). Serious AEs were reported in 32 patients (24.6%). The ORR was 24.8% (95% confidence interval 17.6‒33.2), and the median duration of treatment was 10.6 months (range 0.1‒29.3). CONCLUSION: Palbociclib in combination with letrozole was generally well tolerated with a clinically manageable safety profile; the observed ORR supported treatment benefit in Latin American women with HR+/HER2- ABC. TRIAL REGISTRY: ClinicalTrials.gov, NCT02600923.

This study was done to learn more about the safety of 2 medicines together for women with advanced breast cancer after menopause. All 130 women in the study had the most common kind of breast cancer and were from Argentina, Brazil, Colombia, and Mexico. Everyone took 2 oral medicines called palbociclib and letrozole during the study. The researchers looked for any side effects experienced by the women while taking these medicines together. Another goal of the study was to see how well the treatment worked. Blood tests showed 70.0% of women had a side effect where they had a lower number of a type of white blood cell called a neutrophil. In total, 34.6% of women had low levels of another white blood cell called a leukocyte. These blood test results can mean a person is more likely to get infections. Serious side effects were experienced by 24.6% of the women, which meant these were life-threatening, caused lasting problems, or they needed hospital care. To cope with their side effects, 22.3% of the women switched to a lower palbociclib dose; 24.8% of the women had an overall response, which meant they either had a decrease in their tumor size or all cancer signs disappeared from their body. The most common length of time in the study was 10.6 months and the longest time was 29.3 months. The results of this study support using palbociclib plus letrozole to treat women who live in Latin America with advanced breast cancer after menopause.

Results of a survey study on health professionals' perceptions of tumor boards in Brazil.

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.

Biomarker Data from the Phase III KATHERINE Study of Adjuvant T-DM1 versus Trastuzumab for Residual Invasive Disease after Neoadjuvant Therapy for HER2-Positive Breast Cancer.

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.

Impact of the COVID-19 Pandemic on Cancer Staging: An Analysis of Patients With Breast Cancer From a Community Practice in Brazil.

PURPOSE: A nationwide lockdown was enforced in Brazil starting in March 2020 because of the COVID-19 pandemic when cancer screening activities were reduced. In this study, we evaluated the impact of the COVID-19 pandemic on breast cancer (BC) diagnosis. METHODS: We extracted data from the medical records of patients age older than 18 years who were diagnosed with BC and started treatment or follow-up in private oncology institutions in Brazil between 2018 and 2021. The primary objective was to compare the stage distribution during the COVID-19 pandemic (2020-2021) with a historical prepandemic control cohort (2018-2019). Early BC was defined as stage I-II and advanced disease as stage IV. RESULTS: We collected data for 11,753 patients with an initial diagnosis of BC, with 6,493 patients in the pandemic (2020-2021) and 5,260 patients in the prepandemic period (2018-2019). We observed a lower prevalence of early-stage BC (63.6% v 68.4%) and a higher prevalence of advanced-stage BC (16.9 v 12.7%), after the onset of the pandemic (both P < .01). This pattern was similar for both estrogen receptor-positive/human epidermal growth factor receptor 2-negative and human epidermal growth factor receptor 2-positive tumors: significantly decreased in the early stage from 69% to 67% and 68% to 58%, respectively, and a considerable increase in advanced-stage disease from 13% to 15% and 13% to 20%, respectively. For triple-negative BC, there was a significantly higher percentage of patients with advanced-stage disease during the pandemic (17% v 11%). Overall, age 50 years or older and postmenopausal status were associated with a greater risk of advanced stage at diagnosis during the pandemic period. CONCLUSION: We observed a substantial increase in the number of cases of advanced-stage BC in Brazil during the COVID-19 pandemic.

Adjuvant trastuzumab emtansine in HER2-positive breast cancer patients with HER2-negative residual invasive disease in KATHERINE.

Following chemotherapy and human epidermal growth factor 2 (HER2)-targeted neoadjuvant therapy for HER2-positive early breast cancer, residual invasive breast cancer at surgery may be HER2-negative on retesting in some patients. We evaluated outcomes with T-DM1 and trastuzumab in patients randomized in the phase III KATHERINE trial based on HER2-positive central testing of the pre-treatment core biopsy with HER2-negative central testing on their corresponding surgical specimen after neoadjuvant treatment. In the 70/845 (8.3%) patients with HER2-negative residual disease on retesting at surgery, there were 11 IDFS events in the 42 trastuzumab-treated patients (26.2%) and none in the 28 T-DM1-treated patients, suggesting that T-DM1 should not be withheld in this patient population.

Telehealth, Social Media, Patient Empowerment, and Physician Burnout: Seeking Middle Ground.

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.

Gene expression signatures in early breast cancer: Better together with clinicopathological features.

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.

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

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

Pre-treatment MRI tumor features and post-treatment mammographic findings: may they contribute to refining the prediction of pathologic complete response in post-neoadjuvant breast cancer patients with radiologic complete response on MRI?

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Implementing multidisciplinary tumor boards in oncology: a narrative review.

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.

Is Independent Clinical Research Possible in Low- and Middle-Income Countries? A Roadmap to Address Persistent and New Barriers and Challenges.

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.

Integrating Adjuvant Radiation with Post-Neoadjuvant Therapies in Early Breast Cancer.

PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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.

Pathologic response at the epicenter of the treatment decision-making process in Human Epidermal Receptor-Type 2 overexpressing (Her2+) Early Breast Cancer (EBC): Challenges and opportunities for financially-constrained healthcare systems.

After more than two decades of intensive research, tremendous progress has been achieved in the management of Human Epidermal Receptor-2 overexpressing (Her2+) Early Breast Cancer (EBC). In the latest years, major clinical trials have explored the neoadjuvant scenario, in addition to the prognostic role of pathologic complete response (pCR) and the possibility of a 'tumor biology-driven' patient selection provided by the assessment pathologic response. However, the introduction of new agents has been a major burden for financially-constrained healthcare systems-which includes those from most emerging markets (currently representing 85% of the world population) but also, to some extent, public systems from welfare states. This manuscript addresses evidence-based opportunities to promote a more rational utilization of the available resources in Her2+ EBC, in addition to areas of interest for future research in cost-efficiency.