PURPOSE Breast cancer is the most common cancer and the leading cause of cancer-related death in women worldwide. The number of women living with metastatic breast cancer (MBC) in Brazil is unknown. The objective of this article was to use population-based data to estimate the prevalence of MBC in Brazil. METHODS Using 4 different sources and cancer registries (DataSUS, Registro Hospitalar de Câncer, the Brazilian National Health Agency, and the National Geography and Statistics Institute) with data from 2008 to 2018, we built a database that represents Brazilian MBC cases. The current number of women in the model living with MBC was considered the prevalence (recurrent or de novo), and new cases in the year 2018 represented the incidence. In each of these outcomes, we were able to separate our population on the basis of cancer subtype, age, and time from diagnosis. RESULTS We estimate that 44,642 women currently live with MBC in Brazil. This accounts for one in every 2,409 Brazilian women and approximately 41 women per 100,000. A total of 58% have hormone receptor–positive/human epidermal growth factor receptor 2–negative tumors, 25% are human epidermal growth factor receptor 2–positive, and 16% have triple-negative breast cancer. According to our methodology, the estimated median overall survival of Brazilian women after diagnosis of MBC is 26.2 months. CONCLUSION The significant number of patients living with MBC should inform and raise the interest of the many stakeholders involved. This collaborative effort is a clear requirement to improve the lives of these patients as well as to prepare for future challenges related to the trend of a progressive increase in MBC prevalence.

Purpose: A CDK4/6 inhibitor (CDK4/6i) combined with endocrine therapy is the standard of care for patients with hormone receptor-positive (HR+) and HER2-negative (HER2-) metastatic breast cancer (MBC). However, the incorporation of these agents into clinical practice remains challenging. This study aims to estimate the impact of the lack of access to ribociclib on mortality of premenopausal patients with MBC in Brazil. Methods: Based on published epidemiological studies and national cancer registries, we estimated the number of premenopausal patients with potential indication of ribociclib as first-line treatment for MBC. Efficacy estimates were based on results from the Monaleesa-7 trial. Our analysis is made under the unrealistic assumption that all premenopausal MBC patients would be candidates for the treatment. To estimate the number of yearly premature deaths that could be prevented, we considered the largest absolute effect on mortality when sequentially applying the observed hazard ratio. Results: We estimated an annual incidence of 4,294 premenopausal HR+, HER2-MBC patients in Brazil. Considering these patients, at 12, 24 and 60 months, the number of surviving subjects would be 3,504, 2,859 and 1,553 for endocrine therapy (ET) alone; and 3,717, 3,217 and 2,086 for ET plus ribociclib. The largest difference between both groups was observed at the end of the sixth year when the use of ribociclib would prevent 538 premature deaths (survival of 1,805 versus 1,267 patients by the 72nd month). Conclusion: We estimate that lack of access to CDK4/6i for patients with HR+, HER2-, MBC will cause the premature death of a significant number of premenopausal women with MBC. The unavailability of effective therapies has measurable consequences. Progress in this area demands a concerted effort to prevent further loss of lives.

INTRODUCTION Current definition of HER2-positive BC follows ASCO/CAP guidelines using immunohistochemistry (IHC) and/or in situ hybridization (ISH)-based techniques. However, HER2 expression can be variable in cells that lack ERBB2 amplification. For example, HER2-negative tumors can express some level of HER2 protein by IHC (i.e. 1+ or 2+ and a negative ISH result) and are identified as HER2-low. Others have no expression and are considered HER2-zero. Innovative therapies have shown promising activity in patients in HER2-low BC. The aim of this study is to evaluate the association of HER2-low and HER2-zero status with response to NACT in HER2-negative BC. METHODS Retrospective cohort of patients with HER2-negative BC treated with NACT in four institutions in Brazil. Protocols of diagnosis, treatment and follow-up were standardized and based on international guidelines. Tumors with HER2 IHC score 0 were classified as HER2-zero whereas tumors with HER2 score 1+ and those with HER2 score 2+ with FISH-negative were classified as HER2-low. Patients were treated with anthracycline- and taxane- based chemotherapy. The following clinicopathological data were evaluated, when available: age, ER, Ki67, tumor size, lymph node (LN) status and response to NACT according to pCR status and residual cancer burden (RCB) index. Primary objective was to evaluate the prevalences and compare pCR rates among HER2-zero and HER2-low cases. Secondary objectives were to perform the same comparison within the HR-positive (HR+) and HR-negative subgroups. Pearsons chi squared tests were performed and a p value of <0.05 was considered statistically significant. RESULTS 331 patients were included in this analysis. 63% were HR+and 37% were TNBC. 50% were HER2-zero and 50% HER-low (36% HER2 IHC 1+ and 14% HER2 IHC 2+/FISH-negative). Median age, initial tumor size, clinical LN status and Ki67 expression were similar among HER2-zero and HER2-low subgroups. In HR+ tumors, 42% (86/207) were HER2-zero and 58% (121/207) were HER2-low. In TNBC, 63% (78/124) were HER2-zero and 37% (46/124) were HER2-low (p<0.001, Pearsons chi squared test). The pCR rate was 26% (85/331) in the entire cohort. As expected, there was a higher rate of pCR in TNBC vs HR+ (50% vs 11%, p<0.001). We found a statistically significant difference in the pCR rates when comparing the HER2-zero versus HER2-low subgroups (31% vs 20%, p=0.03). However, this difference is mostly related to an imbalance between groups (HER2-zero subgroups had a higher proportion of TNBC). Among HR+ tumors, there was no difference in the pCR rates between HER2-zero and HER2-low subgroups (8% vs 13%, p=0.35). In TNBC, we identified an interesting but non-statistically significant difference in pCR in HER2-zero vs. HER2-low tumors (56% vs. 39%, p=0.09). In the TNBC cohort we identified a non-statistically significant difference in RCB 0-I in HER2-zero vs. HER2-low tumors (p=0.06). With a 30 month median follow-up, PFS and OS data are immature. CONCLUSION The distribution of HER2-zero and HER2-low cases is different in HR+ and TNBC. HER2-low is more frequent in HR+ and HER2-zero in TNBC. We identified a higher pCR rate in HER2-zero compared to HER2-low tumors, even though this difference is associated with an imbalance between the two groups. Still, we identified a trend to higher pCR rate in HER2-zero compared to HER2-low tumors even within the TNBC subgroup. Identification of HER2-low and HER2-zero tumors may have clinical implications that should be further explored. Citation Format: Tomas Reinert, Guilherme Parisotto Sartori, Alessandra AB Souza, Rodrigo Pellegrini, Mahira L Rosa, Nathalia Rossatto, Guilherme P Coelho, Isnard E Litvin, Felipe Zerwes, Eduardo Millen, Francisco P Cavalcante, Antonio L Frasson, Marcia S Graudenz, Carlos H Barrios. Prevalence of HER2-low and HER2-zero subgroups and correlation with response to neoadjuvant chemotherapy (NACT) in patients with HER2-negative breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS4-22.

assay. To estimate the analytical performance of Ventana ALK and OFA in an orthogonal analysis; a total of 50 samples (22 Ventana ALK and OFA negatives, 9 Ventana ALK+, 7 OFA+, and 12 Ventana ALK and OFA positives) were analyzed using a qPCR based EML4-ALK fusion gene detection kit (AmoyDx) as benchmark. Results: The frequencies of ALK fusions detected were 3,76% and 3,69% by Ventana ALK and OFA respectively, with 57,1% of samples giving discordant results between Ventana ALK and OFA techniques. The orthogonal analysis revealed that both, Ventana ALK and OFA, have a sensitivity of 75% [CI95%:51-91]. However, OFA presents higher specificity than Ventana ALK (96% vs. 88%). This difference has a post hoc statistical power of 97%. While Ventana ALK test can detect only the aberrant ALK accumulation, by using NGS it was possible to establish that the most common ALK gene fusion was between exon 20 of ALK and 6 of EML4. Conclusion: Considering this analysis a preliminary assessment, when OFA and Ventana ALK are compared using "real world" lung adenocarcinoma samples, OFA presents an advantage against Ventana ALK test in specificity. Also, NGS can detect multiple mutations at the same time using a small amount of sample. The use of this technique unlocks the possibility to identify patients that can be treated using targeted therapies.

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Introduction: Cancer is the second leading cause of death in the world, and it is expected to be the main cause by the year 2030. Current trends of higher incidence and the introduction of new treatments lead to the challenge of treating more people with increasing costs per capita. In Brazil, current and future challenges are even more significant because of the limited resources destined for healthcare. Methods:We propose a methodology to compare cost-effectiveness performance with a regression of cancer lethality against the resources available for different nations, using the gross domestic product and the mortality-to-incidence ratio. Our objective is to evaluate and compare outcomes observed in Brazil.Results: According to our methodology, Brazil is performing well in breast and prostate cancer (observed lethality 9% and 15% lower than expected, respectively). It performs close to expected in colon (0.8% higher) and cervix (2% higher). However, lung cancer had a higher lethality than expected (6.5% higher). We also found that breast, prostate and cervical cancers are the primary sites more related to income. Lung cancer had the weakest relationship with resources. Conclusion:Brazil has different cost-effectiveness results in the management of cancer depending on the primary site. Also, national income has a significant and heterogeneous effect on the lethality of different tumour types. This economic analysis is important for low-to middle-income countries seeking to evaluate cancer outcomes in limited-resource settings.

BACKGROUND: Immune checkpoint inhibitors (ICI) have shown clinical benefit among patients with advanced kidney cancer. Their cost burden hardens its access, especially in low- and middle-income countries. To set solutions, the impact of geographical and socioeconomic differences in the clinical outcomes and survival of renal cell carcinoma (RCC) patients needs to be explored. OBJECTIVE: This review aimed to understand if geographical differences affected the clinical outcomes of RCC patients receiving immunotherapy. METHODS: This study reviewed 45 studies that examined the OS and PFS of RCC patients undergoing ICI (2010–2020) selected from a 3028-study database search conducted on PubMed and grey literature. The selected studies were divided into groups: Asia, multicentric studies, Europe and Anglo-America. The lethality and income of the geographical locations were measured and discussed. RESULTS: Weighted average (WAVG) of mPFS and mOS were 8,47 months, and 40,6 months in Asia. The WAVG of mOS were 12.2 months, and 20.22 months in the Anglo-American population (15 studies; 943 patients). In multicentric studies (4 studies; 1834 patients) the WAVG mPFS was 10,06. European group (13 studies; 3143 patients) had 6.1 and 20.24 months mPFS and mOS, respectively. The exploratory analysis on income and RCC lethality has shown an absolute decline of 8.7% (CI 10.1 to 7.3% - p <  0.05) in RCC lethality, when income is raised by 100% . CONCLUSION: Clinical benefit from ICI varies across the globe. A wide access to ICI, and evaluation of biological aspects of the disease will allow a better understanding of the impact of geographic regions in the clinical outcome of patients receiving ICI and the etiology of potential differences.

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