Browsing by Author "Merino, Tomas"

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    A simple method to assess estrogen receptor gene (ESR1) amplification in paired biopsies from primary tumor and recurrence in breast cancer patients receiving endocrine therapy
    (2020) Maiz, Cristóbal; Oddó, David; Alfaro, Francisca; Villarroel, Alejandra; Acevedo, Francisco; Pérez Sepulveda, Alejandra; Muñiz, Sabrina; Silva, Fernando; Valdivia, Andrés; Merino, Tomas; Pinto, Mauricio P.; Sánchez, César
    Globally, Breast Cancer (BC) is the leading cause of cancer death among women. About 75% of patients are diagnosed with hormone-dependent tumors and are set to receive Endocrine Therapy (ET) targeting the estrogen receptor. Unfortunately, a significant proportion of these patients develops ET resistance. Still controversial, studies have proposed that Estrogen Receptor-Alpha Gene (ESR1) alterations may underlie ET resistance. Here, we describe the use of a Chromogenic in Situ Hybridization (CISH) assay for the assessment of ESR1 amplification in primary tumors and recurrences. This assay could be a useful clinical tool with therapeutic implications for estrogen receptor positive BC patients.
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    Abstract PS6-37: Clinical stage is the only predictor of survival in breast cancer patients with a complete pathological response
    (2021) Acevedo, Francisco; Walbaum, Benjamin; Merino, Tomas; Petric, Militza; Sanchez, Cesar
    INTRODUCTION In breast cancer (BC) patients, achieving a complete pathological response (pCR) after neoadjuvant chemotherapy (NCT) is associated with better prognosis. Despite this, some of these patients will experience recurrences of the disease and will eventually die of BC. We identified clinical factors that can affect recurrence and survival in BC patients who achieve pCR.METHODSRetrospective analysis of a Chilean BC database including patients treated in public and private hospitals in Santiago, Chile from 2010 to 2019. pCR was defined as the absence of residual invasive disease in the breast and in the axillary lymph nodes (ypT0/is N0) at the completion of the NCT. Invasive Disease-Free Survival (IDFS), Distant Disease-Free Survival (DDFS) and BC-specific survival (BCS) was measured from the time of diagnosis to the event or lost to follow-up. We performed Cox regression analysis to identify factors associated with prognosis.RESULTSFrom 855 patients who received NCT, 195 (22.8%) achieved pCR and were included in this study. Clinical characteristics are shown in table 1. 76 (37.9%) patients had hormone receptor positive (HR+) and 113 (57.4%) had Human epidermal growth factor 2 (HER2) positive tumors. 88.7% were treated with a regimen that included anthracyclines and taxanes. With a median follow-up of 36 months, three-year IDFS, DDFS and BCS and their 95% confidence intervals were 90.9% (84.7 - 94.6), 91.8% (86.0 - 95.3) and 93.8% (87.8 - 97.5); respectively. The stage at diagnosis was the only predictor associated with IDFS (Hazard ratio (HR) = 5.6; p = 0.02), DDFS (HR = 4.1, p = 0.07), and BCS (HR = 8.3, p = 0.04). Body mass index (BMI), age, hospital, HR or HER2 status, lymph node involvement, or the presence of an in-situ component, were not associated with prognosis in the multivariate analysis.CONCLUSIONThe clinical stage at diagnosis was the only predictor of survival in patients who achieved pCR after NCT. Short follow-up and few events may have affected these results. This data is consistent with previously published work. Table 1. Tumor and patient characteristicsMedian age49 (24 – 78)HospitalPublic57.4%Private43.6%BMIMedian27.2 (18.5 – 44.7)Overweight38.0%Obese31.9%Receptor StatusRH+/HER2-16.4%RH+/HER2+21.5%RH-/HER2+35.9%RH-/HER2-26.2%Clinical StageI2.1%II47.4%III50.5%Lymph Node +69.7%ypT0/N078.1%ChemotherapyAnthracycline5.1%Taxane6.2%Anthracycline-Taxane88.7% Citation Format: Francisco Acevedo, Benjamin Walbaum, Tomas Merino, Militza Petric, Cesar Sanchez. Clinical stage is the only predictor of survival in breast cancer patients with a complete pathological response [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 PS6-37.
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    Dosimetric Evaluation of Cardiac Structures on Left Breast Cancer Radiotherapy: Impact of Movement, Dose Calculation Algorithm and Treatment Technique
    (2023) Wittwer, Esteban Barnafi; Rippker, Carolin; Caprile, Paola; Torres, Demetrio Elias; El Far, Rodrigo; Gago-Arias, Araceli; Merino, Tomas
    Background: Breast cancer is the most frequently diagnosed and leading cause of cancer-related deaths among females. The treatment of breast cancer with radiotherapy, albeit effective, has been shown to be toxic to the heart, resulting in an elevated risk of cardiovascular disease and associated fatalities. Methods: In this study, we evaluated the impact of respiratory move-ment, treatment plans and dose calculation algorithm on the dose de-livered to the heart and its substructures during left breast radiothera-py over a cohort of 10 patients. We did this through three image sets, four different treatment plans and the employment of three algorithms on the same treatment plan. The dose parameters were then employed to estimate the impact on the 9-year excess cumulative risk for acute cardiac events by applying the model proposed by Darby. Results: The left ventricle was the structure most irradiated. Due to the lack of four-dimensional computed tomography (4DCT), we used a set of images called phase-average CT that correspond to the average of the images from the respiratory cycle (exhale, exhale 50%, inhale, inhale 50%). When considering these images, nearly 10% of the heart received more than 5 Gy and doses were on av-erage 27% higher when compared to free breathing images. Deep inspiration breath-hold plans reduced cardiac dose for nine out of 10 patients and reduced mean heart dose in about 50% when com-pared to reference plans. We also found that the implementation of deep inspiration breath-hold would reduce the relative lifetime risk of ischemic heart disease to 10%, in comparison to 21% from the reference plan. Conclusion: Our findings illustrate the importance of a more accu-rate determination of the dose and its consideration in cardiologists' consultation, a factor often overlooked during clinical examination. They also motivate the evaluation of the dose to the heart substruc-tures to derive new heart dose constraints, and a more mindful and individualized clinical practice depending on the treatment employed.
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    First-line endocrine therapy for advanced breast cancer. A real-world study at a Latin American university health institution
    (TAYLOR & FRANCIS LTD, 2020) Walbaum, Benjamin; Acevedo, Francisco; Medina, Lidia; Bravo, M. Loreto; Merino, Tomas; Camus, Mauricio; Dominguez, Francisco; Mondaca, Sebastian; Galindo, Hector; Nervi, Bruno; Ibanez, Carolina; Madrid, Jorge; Pena, Jose; Koch, Erica; Garrido, Marcelo; Pinto, Mauricio P.; Sanchez, Cesar
    Objective: Clinical guidelines recommend the use of endocrine therapy (ET) in advanced hormone receptor positive (HR+) human epidermal growth factor receptor type 2 negative (HER2-) breast cancer (BC) patients in the absence of visceral disease or ET resistance. Furthermore, studies indicate similar response and survival rates using ET or cytotoxic chemotherapy (CT). Methods: Herein, we assessed clinical characteristics, type of systemic therapy and survival rates of advanced HR + HER2-BC patients in our database. Results: A total of 172 advanced HR + HER2-BC patients were treated at our institution between 1997 and 2019. Sixty percent received first-line ET (4% received combined ET). Median age of this subset was 55 years (range: 30-86). Similarly, the median age of patients that received CT was 54 years (range: 21-83). Over time, 30% of patients received ET in the 2000-2005 period; this increased to 70% in the 2016-2019 period (p = .045). Overall survival (OS) was 97 months and 51 months for patients treated with ET or CT, respectively (p = .002). Conclusions: To the best of our knowledge this is the first study assessing the use of ET in Chilean advanced HR + HER2-BC patients. Several patients in our institution receive CT without indication. The increase in ET usage over time can be attributed to better and faster immunohistochemical detection methods for Estrogen Receptor (ER), changes in educational and government policies, and a wider variety of ET options. Finally, clinical trials have failed to demonstrate a substantial benefit of CT over ET in this setting.
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    Moderate hypofractionated radiotherapy to the prostate bed with or without pelvic lymph nodes: a prospective trial
    (2024) Canales, Juan P.; Barnafi, Esteban; Salazar, Cristian; Reyes, Paula; Merino, Tomas; Calderon, David; Cortes, Analia
    Background: Hypofractionated radiotherapy in the treatment of prostate cancer has been widely studied. However, in the postoperative setting it has been less explored. The objective of this prospective study is to evaluate the safety and efficacy of hypofractionated radiotherapy in postoperative prostate cancer. Materials and methods: A prospective study was designed to include patients with prostate cancer with an indication of postoperative radiotherapy as adjuvant or salvage. A hypofractionated radiotherapy scheme of 51 Gy in 17 fractions was performed with the possibility of treating the pelvis at a dose of 36 Gy in 12 fractions sequentially. Safety was evaluated based on acute and late toxicity [according to the Radiation Therapy Oncology Group (RTOG) scale and Common Terminology Criteria Adverse Events (CTCAE) v4.03], International Prognostic Scoring System (IPSS) over time, and quality of life. Results: From August 2020 to June 2022, 31 patients completed treatment and were included in this report. 35.5% of patients received elective treatment of the pelvic nodal areas. Most patients reported minimal or low acute toxicity, with an acute gastrointestinal (GI) and genitourinary (GU) grade 3 or greater toxicity of 3.2% and 0%, respectively. The evolution in time of the IPSS remained without significant differences (p = 0.42). With the exception of a significant improvement in the domains of hormonal and sexual symptoms of the Expanded Prostate Cancer Index Composite (EPIC) questionnaire, the rest of the domains [EPIC, European Organization for Research and Treatment of Cancer (EORTC) Core quality of life questionnaire (C-30) and Prostate Cancer module (PR-25)] were maintained without significant differences over time. With a follow-up of 15.4 months, late GI and GU grade 2 toxicity was reported greater than 0% and 9.6%, respectively. Conclusions: Hypofractionated radiotherapy in postoperative prostate cancer appears to be safe with low reports of relevant acute or late toxicity. Further follow-up is required to confirm these results. Trial registration: The protocol was approved by the accredited Medical Ethical Committee of Pontificia Universidad Cat & oacute;lica de Chile. All participants accepted and wrote informed consent.
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    Needs and satisfaction levels of breast cancer patients
    (2024) Ramis, Sylvia; Acevedo, Francisco; Bravo, M. Loreto; Pena, Jose; Bravo, Paulina; Medina, Lidia; Muniz, Sabrina; Ibanez, Carolina; Walbaum, Benjamin; Merino, Tomas; Marin-Olivo, Erick; Pinto, Mauricio P.; Sanchez, Cesar
    Introduction. Knowing and satisfying the needs of breast cancer (BC) patients (P) and their caregivers (CG) during treatment can help to improve their quality of life. This study assessed the needs of BC-P, their CG and health professionals (HP) and their perception before and after an intervention aiming to improve healthcare. Methods. The study included an academic center (AC) and a public hospital (PH). Data were obtained from interviews, focus groups and self-completed surveys. A content analysis was performed using Nvivo software. Due to COVID19 restrictions, educational videos were delivered to HPs describing the identified needs. Finally, satisfaction surveys were applied to P and CG, before and after this intervention. Results. A total of 22 participants were interviewed (7P, 5CG and 10HP). Three main needs were identified: 1) Healthcare related needs, 2) Financial issues and 3) Social support. Subsequently, a satisfaction survey was applied to users (stage I; n=93) and the identified needs were used to design an intervention that consisted of educational videos directed towards HP. Following the intervention a second survey was applied (stage II; n=71). Both surveys revealed high levels of satisfaction among users. Following the second survey, we noticed the emergence of other needs, mainly related to nutrition and the improvement of facilities. Conclusions. This is the first study in Chile assessing BC-P needs from the perspective of P, their CG and HP. All participants indicated that information and social/financial support were the most relevant needs.
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    Oncological benefit versus cardiovascular risk in breast cancer patients treated with modern radiotherapy
    (2022) Acevedo, Francisco; Ip, Teresa; Orellana, María; Martínez, Gonzalo; Gabrielli, Luigi; Andia, Marcelo; Besa, Cecilia; Pinto, Mauricio P.; Sánchez, Cesar; Merino, Tomas
    Radiotherapy (RT) is an essential part of breast cancer (BC) treatments. Unfortunately, heart exposure to radiation can also impair the long-term survival of patients. Our study aimed to quantify the oncological benefit and the cardiovascular (CV) risk associated with modern RT in a real-world cohort of BC patients. Our descriptive study enrolled BC patients who received adjuvant RT. Ten-year overall survival (OS) was estimated using Predict® version 2.1 (National Health Service, London, UK). The basal risk of CV events was estimated using the American Heart Association (ACC/AHA) CV score. Treatment volumes and mean cardiac doses were obtained from RT treatment plan records. The increased risk of CV events due to RT was estimated using a model proposed by Darby. The risk of acute myocardial infarction or stroke mortality was estimated using HeartScore® (European Society of Cardiology, Brussels, Belgium). A total of 256 BC patients were included in the study. The average age of patients was 57 years old (range: 25–91); 49.6% had left BC. The mean cardiac dose was 166 cGy (interquartile range (IQR) 94–273); the estimated hazard ratio (HR) for CV disease was HR 1.12 (confidence interval (CI) 1.04–1.24). The estimated baseline 10-year CV risk was 5.6% (0.2 to 51.2); CV risk increased by 0.9% (range 0.02–35.47%) after RT. The absolute risk of 10-year mortality from CV disease was 2.5% (0.1–9); RT was associated with an estimated 4.9% survival benefit (3.73–6.07) against BC death and a 0.23% (0.17–0.29) estimated increase in CV mortality. Modern RT decreased 10-year BC mortality by 4% but increased CV mortality by 0.2% in this cohort. Our findings encourage the implementation of personalized adjuvant RT treatments that balance risks and benefits to improve long-term BC patient survival.
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    Pathological complete response to neoadjuvant chemotherapy, but not the addition of carboplatin, is associated with improved survival in Chilean triple negative breast cancer patients: a report of real world data
    (2021) Walbaum, Benjamin; Acevedo, Francisco; Median, Lidia; Bravo, M. Loreto; Merino, Tomas; Camus, Mauricio; Dominguez, Francisco; Mondaca, Sebastián; Galindo, Héctor; Nervi, Bruno; Ibañez, Carolina; Madrid, Jorge; Muñiz, Sabrina; Peña, José; Koch, Érica; Garrido, Marcelo; Pinto, Mauricio P.; Sánchez, César
    Background: Breast cancer (BC) is the leading cause of cancer death for Chilean women. About 11% of cases are triple-negative (TN) BC. These are characterised by poor prognosis, higher risk of early recurrence and visceral dissemination versus other BC subtypes. Current standard treatment for early-stage non-metastatic TNBC patients consists of neoadjuvant chemotherapy (NACT) followed by surgery and radiotherapy. Pathological complete response (pCR) to NACT is associated with an increase in survival rates. In general, NACT and adjuvant regimens involve similar cytotoxic drugs. Recent studies have postulated that the use of platinum compounds in TNBC would increase response rates. However, their effects on patient survival remain uncertain. Materials and methods: We retrieved and analysed medical records from a total of 156 Chilean stage I–III TNBC female patients that received NACT and compared survival rates using carboplatin (Cb)-containing versus non-Cb-containing regimens at two health cancer centres. Results: Median age was 51 years (range: 24–81); 13.5% (n = 21) received Cb-containing regimens, 80.1% (n = 125) received sequential anthracyclines plus taxanes; 29.5% (n = 46) of the total group achieved pCR, 28% for the standard treatment and 35% (n = 8) for the Cb-containing group (p = 0.59). We confirmed pCR was associated with prolonged overall survival, invasive and distant disease-free survival (Log-rank p = 0.0236). But the addition of Cb was not associated with differences in survival measures (Log-rank p = 0.5216). Conclusions: To the best of authors’ knowledge, this is the first report on real-world data in the Chilean population assessing the effect of Cb-containing NACT in TNBC. The authors’ results suggest no survival benefit by the addition of Cb to standard NACT. However, we confirm an increase in survival associated to pCR regardless of treatment.
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    Retrospective study on disparities in time-to-treatment by health insurance system in Chilean breast cancer patients
    (2025) Acevedo, Johanna; Ip, Teresa; Maureira, Lea; Sánchez Rojel, César Giovanni; Osorio, Claudia; Carvajal, Claudia; Araos, Rafael; Letelier, Hernan; Acevedo, Francisco; Merino, Tomas
    Breast cancer is the most common malignancy in the Americas, and the second leading cause of cancer death. Disparities in the time to treatment can significantly impact patient outcomes and typically affect lower socioeconomic individuals and/or ethnic minorities. Our study sought to evaluate disparities in time to treatment at three health institutions in Chile according to their type of health insurance (public or private). METHODS Our study analyzed a database of breast cancer patients diagnosed between 2017 and 2018. Analyses included descriptive statistics and a linear regression model that incorporated clinical and demographic variables. Additionally, using a proportional risks model, we analyzed the association between clinical variables and mortality. RESULTS Public health insurance (National Health Fund, FONASA) was associated with longer time-to-treatment and extended treatment times versus private health insurance (Social Security Institutions, ISAPRE; p < 0.0001). As expected, a more advanced stage at diagnosis was associated with lower survival. Our proportional risks model found that age was a predictor of breast cancer mortality in stage II patients. Also, total treatment time significantly increased the risk of breast cancer mortality in stage I patients. Conversely, total treatment time did not affect mortality on stages II or III. CONCLUSIONS We found significant disparities in the time to treatment of Chilean breast cancer patients using FONASA versus private ISAPRE. FONASA patients experience delays in the initiation of treatment and longer total treatment times compared to their private insurance counterparts. Finally, longer time-to-treatment was associated with more advanced stages and increased mortality.
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    Screen-detected breast cancer is associated with better prognosis and survival compared to self-detected/symptomatic cases in a Chilean cohort of female patients
    (2021) Walbaum, Benjamin; Puschel, Klaus; Medina, Lidia; Merino, Tomas; Camus, Mauricio; Razmilic, Dravna; Navarro, Maria Elena; Dominguez, Francisco; Cordova‑Delgado, Miguel; Pinto, Mauricio P.; Acevedo, Francisco; Sánchez, César
    Purpose The implementation of national breast cancer (BC) screening programs in Latin America has been rather inconsistent. Instead, most countries have opted for “opportunistic” mammogram screenings on the population at risk. Our study assessed and compared epidemiological, clinical factors, and survival rates associated with BC detected by screening (SDBC) or self-detected/symptomatic (non-SDBC) in Chilean female patients. Methods Registry-based cohort study that included non-metastatic BC (stage I/II/III) patients diagnosed between 1993 and 2020, from a public hospital (PH) and a private university cancer center (PC). Epidemiological and clinical data were obtained from medical records. Results A total of 4559 patients were included. Most patients (55%; n = 2507) came from PH and were diagnosed by signs/ symptoms (non-SDBC; n = 3132, 68.6%); these patients displayed poorer overall (OS) and invasive disease-free survival (iDFS) compared to SDBC. Importantly, the proportion of stage I and “luminal” BC (HR + /HER2 −) were significantly higher in SDBC vs. non-SDBC. Finally, using a stage/subset-stratified age/insurance-adjusted model, we found that nonSDBC cases are at a higher risk of death (HR:1.75; p < 0.001). In contrast, patients with PC health insurance have a lower risk of death (HR: 0.60; p < 0.001). Conclusion We confirm previous studies that report better prognosis/survival on SDBC patients. This is probably due to a higher proportion of stage I and luminal-A cases versus non-SDBC. In turn, the survival benefit observed in patients with PC health insurance might be attributed to a larger proportion of SDBC. Our data support the implementation of a systematic BC screening program in Chile to improve patient prognosis and survival rates.
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    Survival rates of advanced estrogen-receptor positive breast cancer. Analysis of 211 cases
    (2020) Sanchez, Cesar; Dominguez, Francisco; Galindo, Hector; Camus, Mauricio; Oddo, David; Villarroel, Alejandra; Razmilic, Dravna; Pena, Jose; Elena Navarro, Maria; Medina, Lidia; Merino, Tomas; Briones, Juan; Acevedo, Francisco
    Background: About 80% of breast cancer (BC) cases express estrogen receptor (ER), which has been correlated with good prognosis and response to estrogen deprivation Aim: To characterize ER positive advanced BC (ABC) patients treated at our institution assessing the impact of clinical presentation (stage IV, de novo disease at diagnosis versus systemic recurrence) and BC subtype on survival rates. Material and Methods: We evaluated 211 ER+ advanced BC (ABC) patients, treated between 1997 and 2017. Results: The median overall survival (OS) was 37 months. Median OS for the period 1997/2006 and 2007/2017 were 33 and 42 months, respectively (p = 0.47). Luminal A, ABC stage IV disease at diagnosis displayed better OS rates than Luminal B stage IV tumors (100 and 32 months respectively, p < 0.01). Conclusions: Clinical presentation (stage IV vs. systemic recurrence) and tumor subtype are key determinants of OS in ABC.