Implementing Standard Diagnosis and Treatment for Locally Advanced Breast Cancer Through Global Research in Latin America: Results From a Multicountry Pragmatic Trial.

PURPOSE: Breast cancer mortality rates in Latin America (LA) are higher than those in the United States, possibly because of advanced disease presentation, health care disparities, or unfavorable molecular subtypes. The Latin American Cancer Research Network was established to address these challenges and to promote collaborative clinical research. The Molecular Profiling of Breast Cancer Study (MPBCS) aimed to evaluate the clinical characteristics and treatment outcomes of LA participants with locally advanced breast cancer (LABC). PATIENTS AND METHODS: The MPBCS enrolled 1,449 participants from Argentina, Brazil, Chile, Mexico, and Uruguay. Through harmonized procedures and quality assurance measures, this study evaluated clinicopathologic characteristics, neoadjuvant chemotherapy response, and survival outcomes according to residual cancer burden (RCB) and the type of surgery. RESULTS: Overall, 711 and 480 participants in the primary surgery and neoadjuvant arms, respectively, completed the 5-year follow-up period. Overall survival was independently associated with RCB (worse survival for RCBIII-adjusted hazard ratio, 8.19, P < .001, and RCBII [adjusted hazard ratio, 3.69, P < .008] compared with RCB0 [pathologic complete response or pCR]) and type of surgery (worse survival in mastectomy than in breast-conserving surgery [BCS], adjusted hazard ratio, 2.97, P = .001). The hormone receptor-negative-human epidermal growth factor receptor 2-positive group had the highest proportion of pCR (48.9%). The analysis of the ASCO Quality Oncology Practice Initiative breast module revealed high compliance with pathologic standards but lower adherence to treatment administration standards. Notably, compliance with trastuzumab administration varied widely among countries (33.3%-88.7%). CONCLUSION: In LABC, we demonstrated the survival benefit of BCS and the prognostic effect of the response to available neoadjuvant treatments despite an important variability in access to key treatments. The MPBCS represents a significant step forward in understanding the real-world implementation of oncologic procedures in LA.

Impact of Lung Cancer on Health-Related Quality of Life, Financial Toxicity, and Household Economics in Patients From the Public and the Private Healthcare Sector in Argentina.

OBJECTIVES: Non-small cell lung cancer (NSCLC) is Argentina's first cause of cancer death. Most patients have an advanced stage at diagnosis, with poor expected survival. This study aimed to characterize the health-related quality of life (HRQOL) and economic impact of patients treated in the private healthcare sector and compare it with that of the public sector. METHODS: We undertook an observational cross-sectional study that extended a previous study to a referral private center in Argentina. Outcomes included the EuroQol EQ-5D-3L (to assess HRQOL), Comprehensive Score for Financial Toxicity (financial toxicity instrument), Work Productivity and Activity Impairment - General Health (to assess productivity loss), and out-of-pocket expenses in adults diagnosed of NSCLC. RESULTS: We included 30 consecutive patients from a private healthcare center (July 2021 to March 2022), totaling 131 patients (n = 101 from previous public study). The whole sample had low quality of life and relevant economic impact. Patients in the private healthcare sector showed lower disease severity and higher educational level and household income. In addition, private healthcare system patients showed higher utility (0.77 vs 0.73; P < .05) and lower impairment of daily activities (41% vs 59%; P = .01). Private health system patients also showed lower financial toxicity as measured by the Comprehensive Score for Financial Toxicity score (23.9 vs 20.14; P < .05) but showed no differences when financial toxicity was assessed as a dichotomic variable. CONCLUSIONS: Although patients with NSCLC treated in a private healthcare center in Argentina showed a relevant HRQOL and economic impact, this impact was smaller than the one observed in publicly funded hospitals.

The Transcriptomic Portrait of Locally Advanced Breast Cancer and Its Prognostic Value in a Multi-Country Cohort of Latin American Patients.

Purposes: Most molecular-based published studies on breast cancer do not adequately represent the unique and diverse genetic admixture of the Latin American population. Searching for similarities and differences in molecular pathways associated with these tumors and evaluating its impact on prognosis may help to select better therapeutic approaches. Patients and Methods: We collected clinical, pathological, and transcriptomic data of a multi-country Latin American cohort of 1,071 stage II-III breast cancer patients of the Molecular Profile of Breast Cancer Study (MPBCS) cohort. The 5-year prognostic ability of intrinsic (transcriptomic-based) PAM50 and immunohistochemical classifications, both at the cancer-specific (OSC) and disease-free survival (DFS) stages, was compared. Pathway analyses (GSEA, GSVA and MetaCore) were performed to explore differences among intrinsic subtypes. Results: PAM50 classification of the MPBCS cohort defined 42·6% of tumors as LumA, 21·3% as LumB, 13·3% as HER2E and 16·6% as Basal. Both OSC and DFS for LumA tumors were significantly better than for other subtypes, while Basal tumors had the worst prognosis. While the prognostic power of traditional subtypes calculated with hormone receptors (HR), HER2 and Ki67 determinations showed an acceptable performance, PAM50-derived risk of recurrence best discriminated low, intermediate and high-risk groups. Transcriptomic pathway analysis showed high proliferation (i.e. cell cycle control and DNA damage repair) associated with LumB, HER2E and Basal tumors, and a strong dependency on the estrogen pathway for LumA. Terms related to both innate and adaptive immune responses were seen predominantly upregulated in Basal tumors, and, to a lesser extent, in HER2E, with respect to LumA and B tumors. Conclusions: This is the first study that assesses molecular features at the transcriptomic level in a multicountry Latin American breast cancer patient cohort. Hormone-related and proliferation pathways that predominate in PAM50 and other breast cancer molecular classifications are also the main tumor-driving mechanisms in this cohort and have prognostic power. The immune-related features seen in the most aggressive subtypes may pave the way for therapeutic approaches not yet disseminated in Latin America. Clinical Trial Registration: ClinicalTrials.gov (Identifier: NCT02326857).

Adjuvant therapy in non-small cell lung cancer: is targeted therapy joining the standard of care?

INTRODUCTION: Surgical resection is the standard of care  (SOC) in non-small cell lung cancer (NSCLC) for early-stage. The 5-year overall survival (OS) rates with the use of adjuvant chemotherapy remain low. In advance NSCLC, tailored strategies have become the gold standard. We hope to translate these benefits into preventing recurrences and increasing survival in early-stage NSCLC. AREAS COVERED: EGFR mutated populations are the most common druggable molecular drivers in advance NSCLC. EGFR tyrosine kinase inhibitors (TKIs) are the SOC in this setting, and we discuss their emerging role as adjuvant therapy. EXPERT OPINION: The results of the first adjuvant clinical trial with TKIs showed increased DFS in patients with early-stage NSCLC. Despite that using osimertinib (Osm) as an adjuvant treatment seems promising, several open questions need to be answered. If Osm reaches a significant advantage in OS, undergoing 3 years of treatment is worthwhile, but if there is not an OS benefit then maybe DFS is not enough. In the meantime, should we treat patients with Osm as adjuvant therapy until the OS data is available? There is not an easy answer, but most of us are in favor of giving Osm a chance until we have definitive data or better options in early-stage NSCLC.