Access disparities and underutilization of germline genetic testing in Chilean breast cancer patients.

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.

Obesity is associated with early recurrence on breast cancer patients that achieved pathological complete response to neoadjuvant chemotherapy.

Pathological complete response (pCR) after neoadjuvant chemotherapy (NCT) is associated with good long-term prognosis in breast cancer (BC) patients. However, some patients still recur and eventually die from this disease. For years, clinical stage at diagnosis has been consistently linked to recurrence and survival in the pCR setting. Herein, we aimed to identify other potential predictors of recurrence and survival in patients that achieved pCR. We performed a retrospective analysis of patients diagnosed between 2011 and 2020 in our center. We calculated overall survival (OS), invasive disease-free survival (IDFS), distant disease-free survival (DDFS), and BC-specific survival (BCSS). Among the 241 patients included into our study 36% were obese (Body Mass Index (BMI) > 29.9 kg/m2) and 47% were stage III. Multivariate analysis confirmed that obesity was a significant risk factor associated with early recurrence and poorer survival in these patients. In summary, obesity and clinical stage predict early recurrence and poorer survival in patients that achieved pCR after NCT. Pending further investigation and based on our findings we speculate that weight management could be beneficial for this subset of patients. To our knowledge, this is the first Latin American report linking obesity and recurrence within this setting.

Better overall survival in patients who achieve pathological complete response after neoadjuvant chemotherapy for breast cancer in a Chilean public hospital.

INTRODUCTION: There is extensive evidence associating the response to neoadjuvant chemotherapy (NeoCT) with breast cancer (BC) survival. However, to the author's knowledge, there is no published data in Chile. The objective of the study is to evaluate whether achieving pathological complete response (pCR) after NeoCT is associated with greater survival and lower risk of recurrence in a Chilean Public Health Service. METHODS: Retrospective analysis of a database. Patients with a diagnosis of Stages I-III BC who received NeoCT between 2009 and 2019 were included. Clinical and pathological information were extracted from the clinical records. BC subtypes were defined using hormone receptor (HR) information (HR: oestrogen and/or progesterone) and epidermal growth factor type 2 (HER2), being divided into four groups: HR+/HER2-, HR+/HER2+, HR-/HER2+, HR-/HER2-. pCR was defined as the absence of invasive cancer in the breast and axilla (ypT0/is N0) after NeoCT. RESULTS: Of 3,092 patients, 17.2% received NeoCT. Of these, 40.2% corresponded to HR+/HER2-, 20.9% HR+/HER2+, 18.2% HR-/HER2+ and 20.7% HR-/HER2-. Overall, 24.8% achieved pCR, being the lowest for HR+/HER2- (10.3%) and the highest for HR-/HER2+ (53.2%). In the multivariable analysis, family history, HER2+ and type of chemotherapy were associated with a greater probability of pCR. With a median follow-up of 40 months, the overall survival and metastasis-free survival (MFS) at 3 years were greater for the group with pCR compared to that which did not achieve it (90.5% versus 76.7%, p = 0.03 and 88.5% versus 71.4%, p = 0.003, respectively). The multivariable analysis confirmed this finding. Brain MFS was similar in both groups. CONCLUSION: NeoCT is associated with greater pCR in aggressive BC subtypes. In those, achieving pCR was associated with better survival in our study. To the author's knowledge, this is the first study which evaluates the relation between pCR and BC subtypes in a Chilean public hospital.

Caracterización de la incidencia del cáncer de mama en un servicio público de salud chileno en el período 2006-2015 / Characterization of incidence rates of breast cancer in public health service, period 2006-2015

OBJETIVO: El cáncer de mama constituye la primera causa de muerte oncológica en mujeres chilenas. Las tasas de incidencia solo han sido estimadas según el registro 2003-2007. Nuestro objetivo fue estimar las tasas de incidencia en un período de 10 años en un servicio de salud y caracterizar dicha población. MÉTODO: Se calcularon las tasas de incidencia del período 2006-2015, por método directo, y se analizó la tendencia por Prais-Winsten. Se caracterizó la población según la edad y la etapa al diagnóstico. RESULTADOS: De 2862 casos, la tasa de incidencia estandarizada promedio fue de 66,6 por 100.000 mujeres. En el período hubo una tendencia al alza del diagnóstico de 0,63/100.000 anualmente (p = 0,5; intervalo de confianza del 95%: −1,73 a 2,99). La mayor tasa de incidencia bruta fue en el grupo de 70 y más años (154,8/100.000). El 49% correspondieron a casos diagnosticados de 50 a 69 años. El 56% se diagnosticó precozmente; la etapa I tuvo la más alta tasa (15,8/100.000). CONCLUSIONES: En este estudio, las tasas de incidencia son mayores que las reportadas en informes nacionales previos. El diagnóstico es mayoritariamente en etapas precoces, lo que difiere del resto de los países de la región. Nuestros datos pueden aportar a mejorar las políticas públicas.

OBJECTIVE: Breast cancer is the leading cause of cancer death in Chilean women. Incidence rates have only been estimated based on population records (2003-2007). Our objective was to estimate the incidence rates in a 10-year period in a health service and portray in words this cohort. METHOD: Incidence rates were calculated between 2006-2015 by direct method and trends were analyzed with the Prais-Winsten model. The population was defined according to age and stage at diagnosis. RESULTS: Of a total of 2862 cases, the average incidence rate was 66.6 out of 100,000 women. Between 2006-2015, the trend rose in breast cancer diagnosis of 0.63/100,000 annually (p = 0.5; 95% confidence interval: −1.73, 2.99). The highest crude rate of incidence was in the group aged 70 and over (154.8/100,000). 49% correspond to cases diagnosed between 50 and 69 years. 56% were in early stages, stage I, being the most frequent (15.8/100,000). CONCLUSIONS: On this research the incidence rates were higher than the ones reported on previous national reports. Diagnosis is mostly in early stages which differs from other countries in the region, our data can help improve public health policies.

Correlation between Ki67 and histological grade in breast cancer patients treated with preoperative chemotherapy.

BACKGROUND AND AIM: Breast cancer (BC) is a heterogeneous disease and cell proliferation markers may help to identify subtypes of clinical interest. We here analyzed the correlation between cell proliferation determined by Ki67 and HG in BC patients undergoing preoperative chemotherapy (PCT). MATERIALS AND METHODS: We obtained clinical/pathological data from patients with invasive BC treated at our institution from 1999 until 2012. Expression of estrogen receptor (ER), progesterone receptor (PR), epidermal growth factor receptor type 2 (HER2) and Ki67 were determined by immuno-histochemistry (IHC). Clinicopathological subtypes were defined as: Luminal A, ER and/or PR positive, HER2 negative, HG 1 or 2; Luminal B, ER and/or PR positive, HER2 negative or positive and/or HG 3; triple negative (TN), ER, PR and HER2 negative independent of HG; HER2 positive, ER, PR negative and HER2 positive, independent of HG. By using Ki67, a value of 14% separated Luminal A and B tumors, independently of the histological grade. We analyzed correlations between Ki67 and HG, to define BC subtypes and their predictive value for response to PCT. RESULTS: 1,560 BC patients were treated in the period, 147 receiving PCT (9.5%). Some 57 had sufficient clinicopathological information to be included in the study. Median age was 52 years (26-72), with 87.7% invasive ductal carcinomas (n=50). We performed IHC for Ki67 in 40 core biopsies and 50 surgical biopsies, 37 paired samples with Ki67 before and after chemotherapy being available. There was no significant correlation between Ki67 and HG (p=0.237), both categorizing patients into different subtypes. In most cases Ki67 decreased after PCT (65.8%). Only 3 patients had pathologic complete response (cPR). CONCLUSIONS: In our experience we did not find associations between Ki67 and HG. Determination of clinicopathological luminal subtypes differs by using Ki67 or HG.

Porcentaje de subgraduación del puntaje de Gleason en la biopsia transrectal de pacientes candidatos a vigilancia activa / Percentage of Gleason score under grading in transrectal biopsies of patients candidates to active surveillance

La vigilancia activa (VA) constituye una alternativa de manejo válida para pacientes con cáncer de próstata que cumplen con ciertos criterios que incluyen las características anatomopatológicas de la biopsia preoperatoria transrectal. La subgraduación del puntaje de Gleason en la biopsia preoperatoria respecto de la biopsia definitiva se reporta en un 24-39 por ciento de los casos, lo que constituye un problema al momento de querer incluir a un paciente en un protocolo de vigilancia. El objetivo principal de este estudio consistió en determinar el porcentaje de subgraduación del score de Gleason en biopsias preoperatorias de pacientes que cumplían criterios para VA pero que fueron sometidos a prostatectomía radical y la relación con el número de punciones realizadas y el porcentaje de subgraduación. Se incluyó restrospectivamente a 167 pacientes sometidos a prostatectomía radical, que por sus características preoperatorias cumplían criterios para ingresar a un protocolo de VA. Se evaluó la concordancia entre las biopsias preoperatorias y definitivas y además la relación entre el número de punciones realizadas y el nivel de subgraduación. 52 pacientes (31,1 por ciento) tuvieron un puntaje de Gleason mayor a 6 (GS 7 n=49; GS 8 n=3) en la biopsia definitiva. El menor porcentaje de subgraduación (23.4 por ciento) se observó en el grupo de pacientes que se sometió a biopsias preoperatorias que incluyeron 15 o más punciones. La biopsia prostática preoperatoria presenta un significativo porcentaje de subgraduación respecto a la biopsia definitiva, que tiende a disminuir al aumentar el número de punciones realizadas. Estos factores deben ser considerados al momento de ofrecer al paciente su ingreso a un protocolo de VA.

Active surveillance (AS) is a validated alternative for the management of patients with prostate cancer that meet certain criteria including the histopathological characteristics of preoperative transrectal biopsy. The down-grading of preoperative Gleason score compared to postoperative biopsy is reported in 24-39 percent of cases, which represents a significative problem to include a patient in a AS protocol. The main objective of this study was to determine the percentage of down-grading Gleason score compared to postoperative biopsy is reported in 24-39 percent of cases, which represents a significative problem to include a patient in a AS protocol. The main objective of this study was to determine the percentage of down-grading of the preoperative Gleason score compared to the definitive score in biopsy specimens from patients that met criteria for AS but that were subjected to a radical prostatectomy, and the relation between the number of punctures and the percentage of downgrading. 167 patients subjected to radical prostatectomy were retrospectively included, all of them having preoperative characteristics that fulfilled the criteria for entry into an AS protocol. We evaluated the correlation between preoperative and postoperative biopsies. We also evaluated the relationship between the number of punctures and the percentage of down-grading in the preoperative biopsy. RESULTS: 52 patients (31.1 percent) were found to have a Gleason score higher than 6 (GS 7 n=49; GS 8 n=3) in the definitive biopsy. The lowest percentage of downgrading (23.4 percent) was observed in the group of patients with preoperative biopsies that included 15 or more punctures. The preoperative prostatic biopsy has a significant percentage of downgrading compared to the definitive biopsy, which tends to decrease with increasing the number of punctures. These factors must be considered when offering AS to a patient.