Cancer characteristics in patients with schizophrenia: a 25-year retrospective analysis.

Schizophrenia is associated with higher cancer-related mortality, perhaps due to delayed diagnosis and limited access to treatment. The study aimed to compare patients diagnosed with cancer with and without schizophrenia to determine whether these groups differ in terms of oncological variables and survival outcomes. This was a retrospective, observational cohort study that included 30.990 patients diagnosed with cancer between 1997 and 2021. We performed univariate and bivariate analyses for the sociodemographic and clinical variables, and constructed Kaplan-Meier survival curves and used the log-rank test to perform the comparisons. All variables were compared for each cancer type. One hundred and sixty-two (0.52 %) patients had a confirmed diagnosis of schizophrenia (ICD-9 criteria). The mean age at diagnosis was significantly lower in the schizophrenia group. A significantly higher proportion of the schizophrenia group was diagnosed with cancer through the emergency department and a lower percentage through scheduled appointments. A smaller percentage of patients in the schizophrenia group received radical treatment for cancer. The mortality rate was higher in the schizophrenia group and median survival was lower. These findings suggest that cancer patients with schizophrenia have worse outcomes than patients without schizophrenia in terms of oncological variables and survival.

ctDNA dynamics and mechanisms of acquired resistance in patients treated with osimertinib with or without bevacizumab from the randomised phase II ETOP-BOOSTER trial.

BACKGROUND: ETOP 10-16 BOOSTER study was a randomised phase II trial of osimertinib and bevacizumab versus osimertinib in patients with an acquired EGFR T790M mutation. The mechanisms of acquired resistance to osimertinib and bevacizumab have not been described previously. METHODS: Next generation sequencing (Guardant360®) was conducted in serial plasma samples. The association between ctDNA and efficacy outcomes was explored and molecular alterations at progression were described. RESULTS: 136 patients (88% of 155 randomised) had plasma samples at baseline (68 per arm), 110 (71%) at week 9 and 65 (42%) at progression. In a multivariable model for progression-free survival (PFS), the treatment effect was found different by smoking status (interaction p=0.046), with the effect of smoking also different by baseline EGFR T790M (interaction p=0.033), while both TP53 at baseline and tissue EGFR Exon 21 L858R mutation were significantly associated with worse PFS outcome. Smokers (current/former) without baseline EGFR T790M showed a significant improvement in PFS under combination treatment, albeit with small numbers (p=0.015). Week-9 EGFR T790M clearance was associated with improved PFS in the osimertinib arm (p=0.0097). Acquired EGFR C797S mutations were detected in 22% and 13% of patients in the combination and osimertinib arm, respectively. CONCLUSIONS: The differential effect of treatment by smoking was not explained by TP53 mutation or other molecular alterations examined. Molecular mechanisms of acquired resistance were detected but no novel molecular alterations were identified in the combination arm.

Prognostic impact of tumor location and gene expression profile in sporadic desmoid tumor.

PURPOSE: Prognostic biomarkers remain necessary in sporadic desmoid tumor (DT) because the clinical course is unpredictable. DT location along with gene expression between thoracic and abdominal wall locations was analyzed. METHOD: Sporadic DT patients (GEIS Registry) diagnosed between 1982 and 2018 who underwent upfront surgery were enrolled retrospectively in this study. The primary endpoint was relapse-free survival (RFS). Additionally, the gene expression profile was analyzed in DT localized in the thoracic or abdominal wall, harboring the most frequent CTNNB1 T41A mutation. RESULTS: From a total of 454 DT patients, 197 patients with sporadic DT were selected. The median age was 38.2 years (1.8-89.1) with a male/female distribution of 33.5/66.5. Most of them harbored the CTNNB1 T41A mutation (71.6 %), followed by S45F (17.8 %) and S45P (4.1 %). A significant worse median RFS was associated with males (p = 0.019), tumor size ≥ 6 cm (p = 0.001), extra-abdominal DT location (p < 0.001) and the presence of CTNNB1 S45F mutation (p = 0.013). In the multivariate analysis, extra-abdominal DT location, CTNNB1 S45F mutation and tumor size were independent prognostic biomarkers for worse RFS. DTs harboring the CTNNB1 T41A mutation showed overexpression of DUSP1, SOCS1, EGR1, FOS, LIF, MYC, SGK1, SLC2A3, and IER3, and underexpression of BMP4, PMS2, HOXA9, and WISP1 in thoracic versus abdominal wall locations. CONCLUSION: Sporadic DT location exhibits a different prognosis in terms of RFS favoring the abdominal wall compared to extra-abdominal sites. A differential gene expression profile under the same CTNNB1 T41A mutation is observed in the abdominal wall versus the thoracic wall, mainly affecting the Wnt/ß-catenin, TGFß, IFN, and TNF pathways.

Advanced non-squamous NSCLC with no actionable oncogenic driver in Spain: a cross-sectional descriptive analysis of data from the Thoracic Tumor Registry.

BACKGROUND: Non-small cell lung cancer (NSCLC) accounts for the vast majority of all diagnosed lung cancers. According to their histology, most NSCLCs are considered non-squamous cell carcinoma (NSCC), and up to 85% of the latter may lack either one of the two main actionable oncogenic drivers (i.e., EGFR mutations and ALK rearrangements). OBJECTIVE: Our analysis aimed to describe the clinical and epidemiological characteristics of Spanish patients suffering from NSCC with no actionable oncogenic driver in daily clinical practice. DESIGN: A retrospective, cross-sectional, descriptive analysis. METHODS: We analyzed the records of all Spanish patients with advanced NSCC diagnosed between January 2011 and January 2020 and included in the Spanish Thoracic Tumor Registry database. We evaluated the presence of metastasis and molecular profiling at the time of diagnosis and treatments received. We also assessed overall survival (OS) and progression-free survival (PFS) according to first-line treatment. RESULTS: One thousand seven hundred ninety-seven Spanish patients with NSCC were included. They were mainly men (73.2%), smokers (current [44.4%] and former [44.4%]) and presented adenocarcinoma histology (97.6%). Most patients had at least one comorbidity (80.4%) and one metastatic site (96.8%), and a non-negligible number of those tested were PD-L1 positive (35.2%). Notably, the presence of liver metastasis indicated a shorter median OS and PFS than metastasis in other locations (p < 0.001). Chemotherapy was more often prescribed than immunotherapy as first-, second-, and third-line treatment in that period. In first-line, the OS rates were similar in patients receiving either regimen, but PFS rates significantly better in patients treated with immunotherapy (p = 0.026). Also, a high number of patients did not reach second- and third-line treatment, suggesting the failure of current early diagnostic measures and therapies. CONCLUSIONS: This analysis of the most lethal tumor in Spain could highlight the strengths and the weaknesses of its clinical management and set the ground for further advances and research.

Exploring long-term breast cancer survivors' care trajectories using dynamic time warping-based unsupervised clustering.

OBJECTIVES: Long-term breast cancer survivors (BCS) constitute a complex group of patients, whose number is estimated to continue rising, such that, a dedicated long-term clinical follow-up is necessary. MATERIALS AND METHODS: A dynamic time warping-based unsupervised clustering methodology is presented in this article for the identification of temporal patterns in the care trajectories of 6214 female BCS of a large longitudinal retrospective cohort of Spain. The extracted care-transition patterns are graphically represented using directed network diagrams with aggregated patient and time information. A control group consisting of 12 412 females without breast cancer is also used for comparison. RESULTS: The use of radiology and hospital admission are explored as patterns of special interest. In the generated networks, a more intense and complex use of certain healthcare services (eg, radiology, outpatient care, hospital admission) is shown and quantified for the BCS. Higher mortality rates and numbers of comorbidities are observed in various transitions and compared with non-breast cancer. It is also demonstrated how a wealth of patient and time information can be revealed from individual service transitions. DISCUSSION: The presented methodology permits the identification and descriptive visualization of temporal patterns of the usage of healthcare services by the BCS, that otherwise would remain hidden in the trajectories. CONCLUSION: The results could provide the basis for better understanding the BCS' circulation through the health system, with a view to more efficiently predicting their forthcoming needs and thus designing more effective personalized survivorship care plans.

Effect of comorbidity and multimorbidity on adherence to follow-up recommendations among long-term breast cancer survivors.

OBJECTIVES: To study the impact of comorbidities, multimorbidity, and multimorbidity clusters on adherence to recommended follow-up guidelines among long-term breast cancer survivors. STUDY DESIGN: Retrospective cohort study based on 2078 women diagnosed with breast cancer from 2000 to 2006 and followed up from 2012 to 2016. MAIN OUTCOME MEASURES: Adherence to breast cancer follow-up recommendations (annual medical visit and imaging) was determined. Comorbidities were classified as acute/chronic. Multimorbidity was defined as the presence of two or more chronic comorbidities aside from breast cancer. Five multimorbidity clusters were considered. Multivariate logistic regression models were fitted to determine the relationship between adherence to recommendations and the presence of comorbidities and multimorbidity, considering both sociodemographic and clinical characteristics. RESULTS: Overall adherence to recommendations was 79.5 %. Adherence was lower among long-term breast cancer survivors with no comorbidities (75.8 %). Among multimorbidity clusters, adherence was highest in the anxiety and fractures cluster (84.3 %) and was lowest in the musculoskeletal and cardiovascular cluster (76.4 %). In adjusted multivariate models, multimorbidity was associated with higher levels of adherence (OR = 1.52 95 %CI 1.16-1.99), and adherence was highest in the metabolic and degenerative cluster (OR = 2.2 95 %CI 1.4-3.5). CONCLUSION: Adherence to follow-up recommendations was higher among long-term breast cancer survivors with multimorbidity than among those without. Adherence also differed by multimorbidity cluster. These results suggest suboptimal adherence to the current follow-up recommendations in certain groups, suggesting the need to adapt clinical practice guidelines to reflect patients' comorbidities and different characteristics.

Evaluación de la estabilidad de parámetros hematológicos en muestras pediátricas bajo diferentes condiciones de almacenamiento determinados en un analizador Sysmex XN / Stability of hematological parameters in pediatric samples under different storage conditions using the Sysmex XN analyser / Avaliação de estabilidade de parâmetros hematológicos em amostras pediátricas sob diferentes condições de armazenamento determinados em um analisador Sysmex XN

Resumen Conocer la estabilidad de las muestras biológicas es esencial para obtener resultados confiables en el laboratorio de análisis clínicos. La Norma IRAM-ISO 15189:2023 establece que cada laboratorio debe estandarizar las condiciones de almacenamiento de las muestras. El objetivo de este trabajo fue determinar el tiempo y la temperatura óptimos para conservar muestras sanguíneas para la determinación de parámetros hematológicos en un analizador Sysmex XN 1000. Se procesaron muestras de sangre entera conservadas hasta 48 horas a temperatura ambiente y hasta 72 horas en heladera. De acuerdo a los resultados, para la determinación del hemograma, las muestras almacenadas a temperatura ambiente deben procesarse dentro de las 6-8 horas posextracción; los parámetros limitantes son aquellos influenciados por cambios en el volumen eritrocitario. En las muestras conservadas en heladera el análisis puede retrasarse hasta 48 horas y el recuento de plaquetas es el parámetro menos estable.

Abstract Knowing sample stability is essential to obtain reliable results in the clinical laboratory. The IRAM-ISO 15189:2023 Standard establishes that each laboratory must standardise the storage conditions of biological samples. This study was conducted to investigate the stability of haematological parameters using a Sysmex XN 1000 in samples stored for up to 48-72 hours at different temperatures. According to these results, the hematologic analytes should be processed in this laboratory within 6-8 hours after extraction if they are stored at room temperature. The limiting parameters are those influenced by changes in the erythrocyte volume. If storage is in a refrigerator, the analysis can be delayed up to 48 hours, being platelet count the limiting parameter.

Resumo Conhecer a estabilidade das amostras biológicas é essencial para obter resultados confiáveis no laboratório de exames clínicas. A Norma IRAM-ISO 15189:2023 estabelece que cada laboratório deve padronizar as condições de armazenamento das amostras. O objetivo deste trabalho foi determinar o tempo e a temperatura ideais para preservar amostras de sangue para a determinação de parâmetros hematológicos em um analisador em um Sysmex XN 1000. Para isso, foram processadas amostras de sangue total armazenadas por até 48 horas em temperatura ambiente e por até 72 horas em geladeira. De acordo com os resultados obtidos, para a determinação do hemograma, as amostras armazenadas em temperatura ambiente devem ser processadas dentro de 6-8 horas após a extração, sendo os parâmetros limitantes aqueles influenciados por alterações no volume eritrocitário. Nas amostras armazenadas em geladeira, a análise pode demorar até 48 horas, sendo a contagem de plaquetas o parâmetro menos estável.

SEOM-GEIS clinical guideline for gastrointestinal stromal tumors (2022).

Gastrointestinal stromal tumor (GIST) is the most common malignant neoplasm of mesenchymal origin, and a paradigmatic model for a successful rational development of targeted therapies in cancer. The introduction of tyrosine kinase inhibitors with activity against KIT/PDGFRA in both localized and advanced stages has remarkably improved the survival in a disease formerly deemed resistant to all systemic therapies. These guidelines are elaborated by the conjoint effort of the Spanish Society of Medical Oncology (SEOM) and the Spanish Sarcoma Research Group (GEIS) and provide a multidisciplinary and updated consensus for the diagnosis and treatment of GIST patients. We strongly encourage that the managing of these patients should be performed within multidisciplinary teams in reference centers.

Reference values of EORTC QLQ-C30, EORTC QLQ-BR23, and EQ-5D-5L for women with non-metastatic breast cancer at diagnosis and 2 years after.

PURPOSE: To obtain reference norms of EORTC QLQ-C30, EORTC QLQ-BR23, and EQ-5D-5L, based on a population of Spanish non-metastatic breast cancer patients at diagnosis and 2 years after, according to relevant demographic and clinical characteristics. METHODS: Multicentric prospective cohort study including consecutive women aged ≥ 18 years with a diagnosis of incident non-metastatic breast cancer from April 2013 to May 2015. Health-related quality of life (HRQoL) questionnaires were administered between diagnosis and beginning the therapy, and 2 years after. HRQoL differences according to age, comorbidity and stage were tested with ANOVA or Chi Square test and multivariate linear regression models. RESULTS: 1276 patients were included, with a mean age of 58 years. Multivariate models of EORTC QLQ-C30 summary score and EQ-5D-5L index at diagnosis and at 2-year follow-up show the independent association of comorbidity and tumor stage with HRQoL. The standardized multivariate regression coefficient of EORTC QLQ-C30 summary score was lower (poorer HRQoL) for women with stage II and III than for those with stage 0 at diagnosis (- 0.11 and - 0.07, p < 0.05) and follow-up (- 0.15 and - 0.10, p < 0.01). The EQ-5D-5L index indicated poorer HRQoL for women with Charlson comorbidity index ≥ 2 than comorbidity 0 both at diagnosis (- 0.13, p < 0.001) and follow-up (- 0.18, p < 0.001). Therefore, we provided the reference norms at diagnosis and at the 2-year follow-up, stratified by age, comorbidity index, and tumor stage. CONCLUSION: These HRQoL reference norms can be useful to interpret the scores of women with non-metastatic breast cancer, comparing them with country-specific reference values for this population.

Molecular Divergence upon EGFR-TKI Resistance Could Be Dependent on the Exon Location of the Original EGFR-Sensitizing Mutation.

Tumor molecular profiling upon disease progression enables investigations of the tumor evolution. Next-generation sequencing (NGS) of liquid biopsies constitutes a noninvasive readily available source of tumor molecular information. In this study, 124 plasma samples from advanced EGFR-positive NSCLC patients, treated with a first-line EGFR tyrosine kinase inhibitor (EGFR-TKI) were collected upon disease progression. The circulating cell-free DNA (cfDNA) was sequenced using the Oncomine Pan-Cancer Cell-Free Assay™. Excluding EGFR mutations, the most frequently mutated gene was TP53 (57.3%), followed by APC (11.3%), FGFR3 (7.3%), and KRAS (5.6%). Different molecular alterations were observed upon disease progression depending on the location of the original EGFR-sensitizing mutation. Specifically, the detection of the p.T790M mutation was significantly associated with the presence of exon 19 mutations in EGFR (Fisher p-value: 0.028). All KRAS activating mutations (n = 8) were detected in tumors with EGFR mutations in exons 18 and 21 (Fisher p-value < 0.001). Similarly, mutations in NRAS and HRAS were more frequently detected in samples from tumors harboring mutations in exons 18 or 21 (Fisher p-value: 0.050 and Fisher p-value: 0.099, respectively). In conclusion, our data suggest that the mechanisms underlying EGFR-TKI resistance could be dependent on the exon location of the original EGFR-sensitizing mutation.

Impact of Detection Mode in a Large Cohort of Women Taking Part in a Breast Screening Program.

Objective: The aim of this study was to evaluate the existing survival rate and clinical-pathological differences among patients with breast cancer detected by mammographic screening. Materials and Methods: This multicenter cohort study examined 1,248 patients who took part in a national screening program for the early detection of breast cancer over an eight-year period. Results: Of the two patient subgroups (interval and screening), we found significant differences in the distribution of prognostic factors, with interval cases presenting at a lower mean age (p = 0.002), with higher percentages of human epidermal growth factor receptor 2 (HER-2) or triple negative and lower percentages of luminal A or luminal B carcinomas (p = 0.001), advanced stages (p<0.001), lower hormone receptor expression (p<0.001), poorer differentiation (p<0.001) and lower survival (p<0.001). Among the screening group, patients with tumors detected during the first screening round had a significantly lower mean age (p<0.001), a lower frequency of comorbidities (p = 0.038) and a lower tendency (p<0.1) to be diagnosed as triple negative breast carcinomas than incident cases. Conclusion: Our results highlight that breast tumors detected during the first screening round are frequently characterized by a more benign phenotype than the rest of the screening subgroups, which could be of help when stratifying the risk of death and selecting the best treatment option for each patient.

Adherence of long-term breast cancer survivors to follow-up care guidelines: a study based on real-world data from the SURBCAN cohort.

PURPOSE: To identify adherence to follow-up recommendations in long-term breast cancer survivors (LTBCS) of the SURBCAN cohort and to identify its determinants, using real-world data. METHODS: We conducted a retrospective study using electronic health records from 2012 to 2016 of women diagnosed with incident breast cancer in Spain between 2000 and 2006 and surviving at least 5 years. Adherence to basic follow-up recommendations, adherence according to risk of recurrence, and overall adherence were calculated based on attendance at medical appointments and imaging surveillance, by year of survivorship. Logistic regression models were fitted to depict the association between adherence and its determinants. RESULTS: A total of 2079 LTBCS were followed up for a median of 4.97 years. Of them, 23.6% had survived ≥ 10 years at baseline. We estimated that 79.5% of LTBCS were overall adherent to at least one visit and one imaging test. Adherence to recommendations decreased over time and no differences were found according to recurrence risk. Determinants of better overall adherence were diagnosis in middle age (50-69 years old), living in a more-deprived area, having fewer years of survival, receiving primary treatment, and being alive at the end of follow-up. CONCLUSION: We identified women apparently not complying with surveillance visits and tests. Special attention should be paid to the youngest and eldest women at diagnosis and to those with longer survival.

Long-Term Risk of Breast Cancer after Diagnosis of Benign Breast Disease by Screening Mammography.

Assessing the long-term risk of breast cancer after diagnosis of benign breast disease by mammography is of utmost importance to design personalised screening strategies. We analysed individual-level data from 778,306 women aged 50-69 years with at least one mammographic screening participation in any of ten breast cancer screening centers in Spain from 1996 to 2015, and followed-up until 2017. We used Poisson regression to compare the rates of incident breast cancer among women with and without benign breast disease. During a median follow-up of 7.6 years, 11,708 (1.5%) women had an incident of breast cancer and 17,827 (2.3%) had a benign breast disease. The risk of breast cancer was 1.77 times higher among women with benign breast disease than among those without (95% CI: 1.61 to 1.95). The relative risk increased to 1.99 among women followed for less than four years, and remained elevated for two decades, with relative risk 1.96 (95% CI: 1.32 to 2.92) for those followed from 12 to 20 years. Benign breast disease is a long-term risk factor for breast cancer. Women with benign breast disease could benefit from closer surveillance and personalized screening strategies.

Use of health services among long-term breast cancer survivors in Spain: longitudinal study based on real-world data.

PURPOSE: This study aimed to evaluate health service utilization in Spain among long-term breast cancer survivors and to compare it with that among women with no history of breast cancer. METHODS: Study based on the SURBCAN cohort includes a sample of long-term breast cancer survivors and a sample of women without breast cancer from 5 Spanish regions. Healthcare utilization was assessed through primary care, hospital visits, and tests during the follow-up period (2012 to 2016) by using electronic health records. Annual contact rates to healthcare services were calculated, and crude and multivariate count models were fitted to estimate the adjusted relative risk of healthcare services use. RESULTS: Data were obtained from 19,328 women, including 6512 long-term breast cancer survivors. Healthcare use was higher among breast cancer survivors (20.9 vs 16.6; p < 0.0001) and decreased from >10 years of survival. Breast cancer survivors who underwent a mastectomy were more likely to have a primary care visit (RR = 3.10 95% CI 3.08-3.11). Five to ten years survivors were more likely to have hospital inpatient visits and imaging test compared to women without breast cancer (RRa = 1.35 95% CI 1.30-1.39 and RRa = 1.27 95% CI 1.25-1.29 respectively). CONCLUSION: This study shows higher use of health services in long-term breast cancer survivors than in women without breast cancer regardless of survival time. IMPLICATIONS FOR CANCER SURVIVORS: These results help to estimate the health resources needed for the growing group of breast cancer survivors and to identify risk factors that drive higher use of health services.

Mammographic features of benign breast lesions and risk of subsequent breast cancer in women attending breast cancer screening.

OBJECTIVES: To evaluate the mammographic features in women with benign breast disease (BBD) and the risk of subsequent breast cancer according to their mammographic findings. METHODS: We analyzed data from a Spanish cohort of women screened from 1995 to 2015 and followed up until December 2017 (median follow-up, 5.9 years). We included 10,650 women who had both histologically confirmed BBD and mammographic findings. We evaluated proliferative and nonproliferative BBD subtypes, and their mammographic features: architectural distortion, asymmetries, calcifications, masses, and multiple findings. The adjusted hazard ratios (aHR) and 95% confidence intervals (95% CI) for breast cancer were estimated using a Cox proportional hazards model. We plotted the adjusted cumulative incidence curves. RESULTS: Calcifications were more frequent in proliferative disease with atypia (43.9%) than without atypia (36.8%) or nonproliferative disease (22.2%; p value < 0.05). Masses were more frequent in nonproliferative lesions (59.1%) than in proliferative lesions without atypia (35.1%) or with atypia (30.0%; p value < 0.05). Multiple findings and architectural distortion were more likely in proliferative disease (16.1% and 4.7%) than in nonproliferative disease (12.8% and 1.9%). Subsequent breast cancer occurred in 268 (2.5%) women. Compared with women who had masses, the highest risk of subsequent breast cancer was found in those with architectural distortions (aHR, 2.21; 95% CI, 1.16-4.22), followed by those with multiple findings (aHR, 1.89; 95% CI, 1.34-2.66), asymmetries (aHR, 1.66; 95% CI, 0.84-3.28), and calcifications (aHR, 1.60; 95% CI, 1.21-2.12). CONCLUSION: BBD subtypes showed distinct mammographic findings. The risk of subsequent breast cancer was high in those who have shown architectural distortion, multiple findings, asymmetries, and calcifications than in women with masses. KEY POINTS: • The presence of mammographic findings in women attending breast cancer screening helps clinicians to assess women with benign breast disease (BBD). • Calcifications were frequent in BBDs with atypia, which are the ones with a high breast cancer risk, while masses were common in low-risk BBDs. • The excess risk of subsequent breast cancer in women with BBD was higher in those who showed architectural distortion compared to those with masses.

Differences in breast cancer-risk factors between screen-detected and non-screen-detected cases (MCC-Spain study).

PURPOSE: The variation in breast cancer (BC)-risk factor associations between screen-detected (SD) and non-screen-detected (NSD) tumors has been poorly studied, despite the interest of this aspect in risk assessment and prevention. This study analyzes the differences in breast cancer-risk factor associations according to detection method and tumor phenotype in Spanish women aged between 50 and 69. METHODS: We examined 900 BC cases and 896 controls aged between 50 and 69, recruited in the multicase-control MCC-Spain study. With regard to the cases, 460 were detected by screening mammography, whereas 144 were diagnosed by other means. By tumor phenotype, 591 were HR+, 153 were HER2+, and 58 were TN. Lifestyle, reproductive factors, family history of BC, and tumor characteristics were analyzed. Logistic regression models were used to compare cases vs. controls and SD vs. NSD cases. Multinomial regression models (controls used as a reference) were adjusted for case analysis according to phenotype and detection method. RESULTS: TN was associated with a lower risk of SD BC (OR 0.30 IC 0.10-0.89), as were intermediate (OR 0.18 IC 0.07-0.44) and advanced stages at diagnosis (OR 0.11 IC 0.03-0.34). Nulliparity in postmenopausal women and age at menopause were related to an increased risk of SD BC (OR 1.60 IC 1.08-2.36; OR 1.48 IC 1.09-2.00, respectively). Nulliparity in postmenopausal women was associated with a higher risk of HR+ (OR 1.66 IC 1.15-2.40). Age at menopause was related to a greater risk of HR+ (OR 1.60 IC 1.22-2.11) and HER2+ (OR 1.59 IC 1.03-2.45) tumors. CONCLUSION: Reproductive risk factors are associated with SD BC, as are HR+ tumors. Differences in BC-risk factor associations according to detection method may be related to prevailing phenotypes among categories.