Browsing by Author "Merino Lara, Tomás Rodrigo"

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    Access disparities and underutilization of germline genetic testing in Chilean breast cancer patients
    (2023) Acevedo Claros, Francisco Nicolás; Walbaum García, Benjamín Vicente; Camus Appuhn, Mauricio Gonzalo; Manzor Véliz, Manuel; Muñiz Muñoz, María Sabrina; Medina Araya, Lidia; Petric Guajardo, Militza Paulina; Reyes, Paula; Domínguez, Francisco; Puschel Illanes, Klaus; Merino Lara, Tomás Rodrigo; Bravo, M. Loreto; Pinto, Mauricio P.; Ibáñez, Carolina; Hughes, Kevin; Sánchez Rojel, César Giovanni
    Purpose Latin American reports on genetic cancer risk assessments are scarce. In Chile, current breast cancer (BC) guidelines do not define strategies for germline genetic testing. Our study sought to quantify the disparities in access to genetic testing in Chilean BC patients, according to international standards and their clinical characteristics to explore improvement strategies.Methods Retrospective analysis of invasive BC databases including patients treated in a Public Hospital (PH) and in an Academic Private Center (AC) in Santiago, Chile between 2012 and 2021.Results Of 5438 BC patients, 3955 had enough data for National Comprehensive Cancer Network (NCCN) categorization. From these, 1911 (48.3%) fulfilled NCCN criteria for germline testing, of whom, 300 were tested for germline mutations and 268 with multigene panels. A total of 65 pathogenic variants were found in this subset. As expected, BRCA1/2 mutations were the most frequent (17.7%). Access to genetic testing was higher in AC versus PH (19.6% vs. 10.3%, p = 0.0001). Other variables associated with germline genetic testing were BC diagnosis after 2018, being 45 years old or younger at diagnosis, BC family history (FH), FH of ovarian cancer, non-metastatic disease, and triple-negative subtype.Conclusion In our cohort, 15% of BC patients who met NCCN criteria for germline testing were effectively tested. This percentage was even lower at the PH. Current recommendations encourage universal genetic testing for BC patients; however, our findings suggest that Chile is far from reaching such a goal and national guidelines in this regard are urgently needed. To our knowledge, this is the first study of its kind in Chile and Latin America.
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    Calorie Restriction and Time-Restricted Feeding: Effective Interventions in Overweight or Obese Patients Undergoing Radiotherapy Treatment with Curative Intent for Cancer
    (2024) Vega Huerta, Carmen Natalia; Barnafi Wittwer, Esteban Andrés; Sánchez Rojel, César Giovanni; Acevedo Claros, Francisco Nicolás; Walbaum García, Benjamín Vicente; Parada Daza, Alejandra Cristina; Rivas Segura, Nicolás Eduardo; Merino Lara, Tomás Rodrigo
    This study assesses the feasibility of calorie restriction (CR) and time-restricted feeding (TRF) in overweight and obese cancer patients who realized little to no physical activity undergoing curative radiotherapy, structured as a prospective, interventional, non-randomized open-label clinical trial. Of the 27 participants initially enrolled, 21 patients with breast cancer were selected for analysis. The participants self-selected into two dietary interventions: TRF, comprising a sugar and saturated fat-free diet calibrated to individual energy needs consumed within an 8 h eating window followed by a 16 h fast, or CR, involving a 25% reduction in total caloric intake from energy expenditure distributed across 4 meals and 1 snack with 55% carbohydrates, 15% protein, and 30% fats, excluding sugars and saturated fats. The primary goal was to evaluate the feasibility of these diets in the specific patient group. The results indicate that both interventions are effective and statistically significant for weight loss and reducing one’s waist circumference, with TRF showing a potentially stronger impact and better adherence. Changes in the LDL, HDL, total cholesterol, triglycerides, glucose and insulin were not statistically significant.
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    Cáncer de mama Her2-positivo: Terapias sistémicas actuales y experiencia local
    (2023) Walbaum García, Benjamín Vicente; Acevedo Claros, Francisco Nicolás; Carrillo Barrientos, Diego Ignacio; Camus Appuhn, Mauricio Gonzalo; Manzor V., Manuel; Martinez R., Raúl; Veglia Q., Paulina; Murature S., Geraldine; Salvado U., Valentina; Muñiz Muñoz, María Sabrina; Merino Lara, Tomás Rodrigo; Sanchez Rojel, César Giovanni
    Breast cancer (BC) is the leading cause of cancer death for women both worldwide and in Chile. Based on clinical, histological, and molecular features, studies have identified four BC subtypes that correlate with treatment sensitivity. Human Epidermal growth factor Receptor type 2-positive (HER2+) BC re-presents 15%-25% of newly diagnosed breast neoplasms; HER2+ BC is characterized by its aggressive behavior, early recurrence, and higher risk of brain metastasis. In recent years, HER2-targeted therapies have become the mainstay of treatment and have redefined the natural history of this subtype, reducing relapse rates for early-stage patients and increasing survival in advanced-stage patients. Herein we review novel treatment strategies and their mechanisms of action, along with clinical and real-world data. We also provide a summary of currently available treatments for this subtype and our local experience regarding the management of this disease.
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    Clinical characteristics, risk factors, and outcomes in Chilean triple negative breast cancer patients: a real-world study
    (2023) Acevedo Claros, Francisco Nicolás; Walbaum, Benjamin; Medina, Lidia; Merino Lara, Tomás Rodrigo; Camus Appuhn, Mauricio Gonzalo; Puschel Illanes, Klaus; Ramírez Parada, Karol Lilia; Manzor, Manuel; Veglia, Paulina; Martinez, Raul; Guerra, Constanza; Navarro, Marisel; Bauerle, Catherine; Domínguez Covarrubias, Francisco José; Sánchez Rojel, César Giovanni
    Background Latin American (LA) studies on triple-negative breast cancer (TNBC) and their characteristics are scarce. This forces physicians to make clinical decisions based on data obtained from studies that include non-Hispanic patients. Our study sought to obtain local epidemiological data, including risk factors and clinical outcomes from a Chilean BC registry. Methods This was a retrospective population-cohort study that included patients treated at a community hospital (mid-low income) or an academic private center (high income), in the 2010-2021 period. Univariate and multivariate analyses were performed to identify prognostic factors associated with survival. Results 647 out of 5,806 BC patients (11.1%) were TNBC. These patients were younger (p = 0.0001) and displayed lower rates of screening-detected cases (p = 0.0001) compared to non-TNBC counterparts. Among TNBC patients, lower income (i. e., receiving treatment at a community hospital) was associated with poorer overall survival (HR: 1.53; p = 0.0001) and poorer BC specific survival (HR: 1.29; p = 0.004). Other risk factors showed no significant differences between TNBC and non-TNBC. As expected, 5-year OS was significantly shorter on TNBC versus non-TNBC patients (p = 0.00001). In our multivariate analyses TNBC subtype (HR: 2.30), locally advanced stage (HR: 7.04 for stage III), lower income (HR: 1.64), or non-screening detected BC (HR: 1.32) were associated with poorer OS. Conclusion To the best of our knowledge, this is the largest LA cohort of TNBC patients. Interestingly, the proportion of TNBC among Chileans was smaller compared to similar studies within LA. As expected, TNBC patients had poorer survival and higher risk for early recurrence versus non-TNBC. Other relevant findings include a higher proportion of premenopausal patients among TNBC. Also, mid/low-income patients that received medical attention at a community hospital displayed lower survival versus private health center counterparts.
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    High linoleic acid levels in red blood cells predict a poor response to neoadjuvant chemotherapy in human epidermal growth factor receptor type 2-positive breast cancer patients
    (2024) Rodrigo Valenzuela; Walbaum García, Benjamín Vicente; Farías Castro, Camila ; Acevedo Claros, Francisco Nicolás; Vargas Añazco, Catalina Andrea; Bennett Lason, José Tomás; Bravo, M. Loreto; Pinto, Mauricio P.; Medina Araya, Lidia Marjorie; Merino Lara, Tomás Rodrigo; Ibáñez Cáceres, Carolina; Parada Daza, Alejandra Cristina; Sánchez Rojel, César Giovanni
    Objective Polyunsaturated fatty acids are categorized as ω-3 or ⍵-6. Previous studies demonstrate that breast cancers display a high expression of fatty acid synthase and high fatty acid levels. Our study sought to determine if changes in plasma or red blood cell membrane fatty acid levels were associated with the response to preoperative (neoadjuvant) chemotherapy in non-metastatic breast cancer patients.MethodsOur prospective study assessed fatty acid levels in plasma and red blood cell membrane. Response to neoadjuvant chemotherapy was evaluated by the presence or absence of pathologic complete response and/or residual cancer burden.ResultsA total of 28 patients were included. First, patients who achieved pathologic complete response had significantly higher neutrophil-to-lymphocyte ratio versus no pathologic complete response (P = 0.003). Second, total red blood cell membrane polyunsaturated fatty acids were higher in the absence of pathologic complete response (P = 0.0028). Third, total red blood cell membrane ⍵-6 polyunsaturated fatty acids were also higher in no pathologic complete response (P < 0.01). Among ⍵-6 polyunsaturated fatty acids, red blood cell membrane linoleic acid was higher in the absence of pathologic complete response (P < 0.01). Notably, plasma polyunsaturated fatty acid, ⍵-6, and linoleic acid levels did not have significant differences. A multivariate analysis confirmed red blood cell membrane linoleic acid was associated with no pathologic complete response; this was further confirmed by receiver operating characteristic analysis (specificity = 92.3%, sensitivity = 76.9%, and area under the curve = 0.855).ConclusionsPending further validation, red blood cell membrane linoleic acid might serve as a predictor biomarker of poorer response to neoadjuvant chemotherapy in non-metastatic human epidermal growth factor receptor type 2–positive breast cancer. Measuring fatty acids in red blood cell membrane could offer a convenient, minimally invasive strategy to identifying patients more likely to respond or those with chemoresistance.
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    Palbociclib in advanced stage hormone receptor-positive breast cancer: real- world data from a Chilean multicentre registry
    (2023) Walbaum García, Benjamín Vicente; Reyes, José Miguel ; Rodríguez, Pablo ; Muñiz Muñoz, María Sabrina; Medina Araya, Lidia Marjorie; Ibáñez Cáceres, Carolina; Merino Lara, Tomás Rodrigo; Pinto, Mauricio ; Bravo, María Loreto ; Acevedo Claros, Francisco Nicolás; Bennett Laso, José Tomás; Sánchez Rojel, César Giovanni
    Background The addition of cyclin-dependent kinases inhibitors (CDKi) to endocrine therapy (ET) as the first- or second line treatment improves progression-free and overall survival (OS) in hormone receptor-positive, HER2 negative (HR+/HER2-) advanced stage breast cancer (ABC). Our study compared survival rates and prognostic factors in Chilean patients that used palbociclib as first or subsequent (≥second) lines of treatment in a real-world setting.Methods Our retrospective population-cohort study included HR+/HER2- ABC patients. We calculated 5-year OS and performed a multivariate analysis to determine prognostic factors.Results A total of 106 patients were included. Median age was 49 years (19–86), 28.3% (30) had de novo stage IV disease; 63% received palbociclib with ET as first line, 54% of them with aromatase inhibitor over fulvestrant. Median OS for the entire cohort was 99 months and 5-year OS was 69%. Patients that received first line palbociclib had a 5-year OS of 89% versus 43% for ET monotherapy or ≥second line palbociclib (p = 0.0062). Multivariate analysis showed that the year at diagnosis and CDKi timing (first line versus ≥second line) were significantly associated with OS.Conclusion Our real-world data show that first-line CDKi + ET provides a statistically significant benefit in OS versus ≥second line in HR+/HER2- ABC patients.
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    Suboptimal use of ovarian function suppression in very young women with early breast cancer: a real-world data study
    (2024) Heredia Castro, Ana Manuela; Walbaum García, Benjamín Vicente; Vidal, María ; Itriago Giménez, Laura Morella; Camus Appuhn, Mauricio Gonzalo; Domínguez Covarrubias, Francisco José; Manzor, Manuel ; Martínez, Raúl ; Murature, Geraldine ; Muñiz Muñoz, María Sabrina; Navarro, Marisel ; Guerra, Constanza ; Merino Lara, Tomás Rodrigo; Medina Araya, Lidia Marjorie; Ibáñez Cáceres, Carolina; Ramírez Parada, Karol Lilia; Acevedo Claros, Francisco Nicolás; Sánchez Rojel, César Giovanni
    Purpose The incidence of breast cancer in young women (BCYW) has increased in recent decades. Malignant disease in this subset is characterized by its aggressiveness and poor prognosis. Ovarian function suppression (OFS) in these patients improves survival especially in hormone receptor-positive (HR +) cases. The Regan Composite Risk (RCR) is a prognostic tool to identify high-risk HR + BC candidates for OFS. Our study sought to characterize a Chilean cohort of early HR + BCYW assessing the use of OFS and its related prognosis and the utility of RCR in our patients.MethodsThis was a retrospective population cohort study that included ≤ 35-year-old early HR + /human epidermal growth factor receptor 2 -negative (HER2-) BC patients treated between 2001 and 2021. Analysis included clinical-pathological characteristics, treatment strategies, and survival. Also, we evaluated the association between RCR and survival.ResultsA total of 143 patients were included into our study, representing 2.9% of all early BC cases in our registry. Median age was 31 years old (range: 19–35). Most patients (93%) received endocrine therapy (ET). Of these, 18% received OFS. No survival differences were observed among treatment strategies. Median RCR score for patients treated with CT plus ET was significantly higher vs. ET alone (2.95 vs. 1.91; p = 0.0001). Conversely, patients treated with tamoxifen alone had significantly lower RCR scores vs. OFS (2.72 vs. 3.14; p = 0.04). Higher RCR scores were associated with poorer overall survival.ConclusionLess than 20% of very young women with early HR + /HER2-BC in our cohort received OFS, in most cases, this involved surgical oophorectomy. RCR score was higher in patients that underwent CT and OFS and was associated with survival, regardless of treatment. We confirm the RCR score as a valuable prognostic tool to identify high-risk BC patients who could benefit from OFS.
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    Upper-Limb Disability and the Severity of Lymphedema Reduce the Quality of Life of Patients with Breast Cancer-Related Lymphedema
    (2023) Ramírez Parada, Karol Lilia; González Santos, Angela ; Riady Aleuy, Layla ; Pinto, Mauricio P.; Ibáñez Cáceres, Carolina; Merino Lara, Tomás Rodrigo; Acevedo Claros, Francisco Nicolás; Walbaum García, Benjamín Vicente; Fernández Verdejo, Rodrigo ; Sánchez Rojel, César Giovanni
    Breast cancer-related lymphedema (BCRL) is characterized by arm swelling, pain, and discomfort, reducing the quality of life (QoL) of affected individuals. BRCL is caused via the blockage or disruption of the lymphatic vessels following cancer treatments, leading to an accumulation of fluid in the affected arm. While current BCRL rehabilitation treatments seek to reduce arm swelling, our study aimed to examine the impact of both the magnitude of lymphedema (ΔVolume) and arm disability on three dimensions of QoL: social, physical, and psychological. Using the Disabilities of the Arm, Shoulder, and Hand questionnaire (DASH) and the Upper Limb Lymphedema 27 questionnaire (ULL) in a group of 30 patients, we found that the magnitude of lymphedema (ΔVolume) was associated with the social dimension of QoL (r = 0.37, p = 0.041), but not with other dimensions. On the other hand, arm disability was associated with all evaluated dimensions of QoL (social, physical, and psychological: p < 0.001, p = 0.019, and p = 0.050 (borderline), respectively). These findings suggest that BCRL rehabilitation strategies should not only aim to reduce the magnitude of lymphedema but should also seek to improve or preserve arm functionality to enhance the QoL of BCRL patients.