Correlació entre resposta radiològica i resposta patològica en pacients amb càncer de mama tractades amb quimioteràpia neoadjuvant

En pacients amb càncer de mama la ressonància magnètica és superior a altres exploracions per a monitoritzar la resposta a la quimioteràpia neoadjuvant. Analitzem la correlació entre resposta completa radiològica(RCr) valorada amb RM i resposta completa patològica (RCp), globalment i en funció dels diferents immunofenotips

Alkylphenolic compounds and risk of breast and prostate cancer in the MCC-Spain study

BACKGROUND: Alkylphenolic compounds are chemicals with endocrine disrupting properties that have been widely used in industry with important changes in their usage over time. Few epidemiologic studies have evaluated the effect of alkylphenolic compounds on human health. OBJECTIVES: We investigated whether occupational exposure to alkylphenolic compounds is associated with breast and prostate cancer. METHODS: We carried out a population-based case-control study including 1513 incident cases of breast cancer, 1095 of prostate cancer, and 3055 controls, frequency matched by sex, age and region. Occupational exposure to alkylphenolic compounds was estimated using a recently developed job-exposure matrix, which considered different scenarios of exposure and different subtypes of alkylphenolic compounds. RESULTS: History of occupational exposure to alkylphenolic compounds was modestly associated with breast cancer (OR = 1.23; 95% CI = 1.01-1.48). Within the different scenarios, the occupational use of domestic tensioactives was positively associated with breast cancer (OR = 1.28; 95% CI = 1.02-1.60), while occupational exposure in other scenarios showed mostly a suggestion of a similar positive associations. Exposure to nonylphenol ethoxylates was positively associated with breast cancer (OR = 1.21; 95% CI = 1.00-1.47), while exposure to other compounds was uncommon. In general, we did not observe associations between alkylphenolic compounds and prostate cancer, except for a positive association among men occupationally exposed to cosmetic, hair and personal hygiene products. CONCLUSIONS: Our findings suggest a modest association between breast cancer risk and occupational exposure to alkylphenolic compounds, and no associations between these compounds and prostate cancer risk. These findings warrant further corroboration in other studies.This work was partially funded by the public grants from the Catalan Government (2014SGR756, 2017SGR1085, 2017SGR733, SLT006/17/76), and European Regional Development Fund-ERDF, by the “Accion Transversal del Cancer”, approved on the Spanish Ministry Council on the 11th October 2007, by the Instituto de Salud Carlos IIIFEDER (PI08/1770, PI08/0533, PI08/1359, PS09/00773-Cantabria, PS09/01286-León, PS09/01903-Valencia, PS09/02078-Huelva, PS09/01662-Granada, PI11/01403, PI11/01889-FEDER, PI11/00226, PI11/01810, PI11/02213, PI12/00488, PI12/00265, PI12/01270, PI12/00715, PI12/00150, PI14/01219, PI14/0613, PI15/00069, PI15/00914, PI15/01032, PI11/01810, PI14/01219, PI11/02213, PIE16/00049, PI17/01179), by the Fundación Marqués de Valdecilla (API 10/09), by the Red Temática de Investigación del Cáncer (RTICC) del ISCIII (RD12/0036/0036), by the Junta de Castilla y León (LE22A10-2), by the Consejería de Salud of the Junta de Andalucía (PI-0571-2009, PI0306-2011, salud201200057018tra), by the Conselleria de Sanitat of the Generalitat Valenciana (AP_061/10), by the Recercaixa (2010ACUP/00310), by the Regional Government of the Basque Country, by the Consejería de Sanidad de la Región de Murcia, by the European Commission grants FOOD-CT-2006-036224-HIWATE, by the Spanish Association Against Cancer (AECC) Scientific Foundation, by the Catalan Government-Agency for Management of University and Research Grants (AGAUR) grants 2014SGR647 and 2014SGR850. ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya

Perinatal and childhood factors and risk of breast cancer subtypes in adulthood.

BACKGROUND: Accumulated exposure to hormones and growth factors during early life may influence the future risk of breast cancer (BC). This study examines the influence of childhood-related, socio-demographic and anthropometric variables on BC risk, overall and by specific pathologic subtypes. METHODS: This is a case-control study where 1539 histologically-confirmed BC cases (23-85 years) and 1621 population controls, frequency matched by age, were recruited in 10 Spanish provinces. Perinatal and childhood-related characteristics were directly surveyed by trained staff. The association with BC risk, globally and according to menopausal status and pathologic subtypes, was evaluated using logistic and multinomial regression models, adjusting for tumor specific risk factors. RESULTS: Birth characteristics were not related with BC risk. However, women with high socioeconomic level at birth presented a decreased BC risk (OR=0.45; 95% CI=0.29-0.70), while those whose mothers were aged over 39 years at their birth showed an almost significant excess risk of hormone receptor positive tumors (HR+) (OR=1.35; 95% CI=0.99-1.84). Women who were taller than their girl mates before puberty showed increased postmenopausal BC risk (OR=1.26; 95% CI=1.03-1.54) and increased HR+ BC risk (OR=1.26; 95% CI=1.04-1.52). Regarding prepubertal weight, while those women who were thinner than average showed higher postmenopausal BC risk (OR=1.46; 95% CI=1.20-1.78), associated with HR+ tumors (OR=1.34; 95% CI=1.12-1.61) and with triple negative tumors (OR=1.56; 95% CI=1.03-2.35), those who were heavier than average presented lower premenopausal BC risk (OR=0.64; 95% CI=0.46-0.90) and lower risk of epidermal growth factor receptor positive tumors (OR=0.61; 95% CI=0.40-0.93). CONCLUSION: These data reflect the importance of hormones and growth factors in the early stages of life, when the mammary gland is in development and therefore more vulnerable to proliferative stimuli.The authors acknowledge funds provided by the Spanish Ministry of Economy and Competitiveness (Carlos III Institute of Health; PI12/00488, PI12/00265, PI12/01270, PI12/00715, PI12/00150, PI08/1770, PI08/0533, PI08/1359, PS09/00773, PS09/01286, PS09/01903, PS09/02078, PS09/01662, PI11/01403, PI11/01889, PI11/00226, PI11/01810, PI11/02213, PI14/01219 and Rio Hortega CM13/00232), the Catalan Government 2009SGR1489 & 2014SGR756-F, and, by the Fundación Marqués de Valdecilla (API 10/09), by the ICGC International Cancer Genome Consortium CLL, by the Junta de Castilla y León (LE22A10-2), by the Consejería de Salud of the Junta de Andalucía (PI-0571), by the Conselleria de Sanitat of the Generalitat Valenciana (AP 061/10), by the Recercaixa (2010ACUP 310), by the Regional Government of the Basque Country by European Commission grants FOOD-CT-2006-036224-HIWATE, and by the Spanish Association Against Cancer (AECC) Scientific Foundation

Perinatal and childhood factors and risk of breast cancer subtypes in adulthood.

BACKGROUND: Accumulated exposure to hormones and growth factors during early life may influence the future risk of breast cancer (BC). This study examines the influence of childhood-related, socio-demographic and anthropometric variables on BC risk, overall and by specific pathologic subtypes. METHODS: This is a case-control study where 1539 histologically-confirmed BC cases (23-85 years) and 1621 population controls, frequency matched by age, were recruited in 10 Spanish provinces. Perinatal and childhood-related characteristics were directly surveyed by trained staff. The association with BC risk, globally and according to menopausal status and pathologic subtypes, was evaluated using logistic and multinomial regression models, adjusting for tumor specific risk factors. RESULTS: Birth characteristics were not related with BC risk. However, women with high socioeconomic level at birth presented a decreased BC risk (OR=0.45; 95% CI=0.29-0.70), while those whose mothers were aged over 39 years at their birth showed an almost significant excess risk of hormone receptor positive tumors (HR+) (OR=1.35; 95% CI=0.99-1.84). Women who were taller than their girl mates before puberty showed increased postmenopausal BC risk (OR=1.26; 95% CI=1.03-1.54) and increased HR+ BC risk (OR=1.26; 95% CI=1.04-1.52). Regarding prepubertal weight, while those women who were thinner than average showed higher postmenopausal BC risk (OR=1.46; 95% CI=1.20-1.78), associated with HR+ tumors (OR=1.34; 95% CI=1.12-1.61) and with triple negative tumors (OR=1.56; 95% CI=1.03-2.35), those who were heavier than average presented lower premenopausal BC risk (OR=0.64; 95% CI=0.46-0.90) and lower risk of epidermal growth factor receptor positive tumors (OR=0.61; 95% CI=0.40-0.93). CONCLUSION: These data reflect the importance of hormones and growth factors in the early stages of life, when the mammary gland is in development and therefore more vulnerable to proliferative stimuli.The authors acknowledge funds provided by the Spanish Ministry of Economy and Competitiveness (Carlos III Institute of Health; PI12/00488, PI12/00265, PI12/01270, PI12/00715, PI12/00150, PI08/1770, PI08/0533, PI08/1359, PS09/00773, PS09/01286, PS09/01903, PS09/02078, PS09/01662, PI11/01403, PI11/01889, PI11/00226, PI11/01810, PI11/02213, PI14/01219 and Rio Hortega CM13/00232), the Catalan Government 2009SGR1489 & 2014SGR756-F, and, by the Fundación Marqués de Valdecilla (API 10/09), by the ICGC International Cancer Genome Consortium CLL, by the Junta de Castilla y León (LE22A10-2), by the Consejería de Salud of the Junta de Andalucía (PI-0571), by the Conselleria de Sanitat of the Generalitat Valenciana (AP 061/10), by the Recercaixa (2010ACUP 310), by the Regional Government of the Basque Country by European Commission grants FOOD-CT-2006-036224-HIWATE, and by the Spanish Association Against Cancer (AECC) Scientific Foundation

Increased fracture risk in women treated with aromatase inhibitors versus tamoxifen: beneficial effect of bisphosphonates

Aromatase inhibitors have been associated with accelerated bone loss and an increased risk of osteoporotic fractures. Currently, bisphosphonates are recommended to reduce fracture risk in these patients. The aim of this study is to evaluate the fracture risk in breast cancer patients receiving aromatase inhibitors, compared to tamoxifen users, and to assess the effectiveness of oral bisphosphonates in reducing fracture risk. We performed an observational cohort study up to 10 years of follow-up. Data were extracted from primary care records in a population database. Women diagnosed with breast cancer between 2006 and 2015 and treated with tamoxifen or aromatase inhibitors (n = 36,472) were stratified according to low (without osteoporosis diagnosis nor bisphosphonates exposure) or high (with osteoporosis and/or treated with bisphosphonates) fracture risk. Cox models were used to calculate hazard ratios (HR [95% CI]) of fracture from the propensity score-matched patients. Sensitivity analyses account for competing risk of death were performed (subdistribution hazard ratio [SHR] [95% CI]). In postmenopausal women, fracture risk in aromatase inhibitor users showed an HR 1.40 [95% CI,1.05 to 1.87] and SHR 1.48 [95% CI, 1.11 to 1.98], compared to tamoxifen. Observing aromatase inhibitors patients at high risk of fracture, bisphosphonate-treated patients had an HR 0.73 [95% CI, 0.51 to 1.04] and SHR 0.69 [95% CI, 0.48 to 0.98] compared to nontreated. In conclusion, fracture risk in postmenopausal women during aromatase inhibitor treatment, in real-life conditions, was >40% compared to tamoxifen, corroborating previous randomized controlled trials results. In high-risk patients, bisphosphonate users had lower significant fracture incidence during aromatase inhibitor therapy than nonbisphosphonate users. Monitoring fracture risk and related risk factors in aromatase inhibitor patients is advisable. © 2019 American Society for Bone and Mineral Research

Correlació entre resposta radiològica i resposta patològica en pacients amb càncer de mama tractades amb quimioteràpia neoadjuvant

En pacients amb càncer de mama la ressonància magnètica és superior a altres exploracions per a monitoritzar la resposta a la quimioteràpia neoadjuvant. Analitzem la correlació entre resposta completa radiològica(RCr) valorada amb RM i resposta completa patològica (RCp), globalment i en funció dels diferents immunofenotips

Análisis genético de enzimas de la vía esteroidal asociadas a efectos adversos musculoesqueléticos de los inhibidores de la aromatasa

Objetives: Identify putative functional variants in the CYP11A1 and CYP17A1 genes associated with musculoskeletal effects (accelerated bone mass loss and arthralgia) derived from treatment with aromatase inhibitors (AI). Material and methods: The B-ABLE cohort is a prospective study of postmenopausal women with breast cancer undergoing AI treatment. Bone mineral density in the lumbar spine and femoral neck was measured by densitometry and joint pain using visual analogue scale. From single-nucleotide polymorphisms (SNPs) in genes CYP11A1 (rs4077581, rs11632698 and rs900798) and CYP17A1 (rs4919686, rs4919683, rs4919687, rs3781287, rs10786712, rs6163, rs743572), previously associated with musculoskeletal events, haplotypes were constructed for each pacient from the cohort, and those haplotypes that showed greatest phenotypic differences were chosen (p<0.05). Within each haplotype, patients with extreme phenotypes were chosen for the sequencing of respective genes and identifying functional genetic variants. Finally, a multiple linear regression analysis was carried out considering the models of dominant, recessive and additive genetic inheritance. Results: No mutation was found in coding regions. A genetic variant (D15S520), in the basal promoter region of gene CYP11A1, was found associated with femoral neck bone loss at 24 month of AI treatment. Conclusions: Variants in regulatory regions of the CYP11A1 gene could modulate the expression of this gene, thus explaining part of the phenotypic variability found in bone loss of patients undergoing AI treatment.Objetivos: Identificar putativas variantes funcionales en los genes CYP11A1 y CYP17A1 asociadas a efectos musculoesqueléticos (pérdida acelerada de la masa ósea y artralgias) derivados del tratamiento con inhibidores de la aromatasa (IA). Material y métodos: La cohorte B-ABLE es un estudio prospectivo de mujeres postmenopáusicas con cáncer de mama en tratamiento con IA. La densidad mineral ósea en columna lumbar y cuello femoral se midió mediante densitometría, y el dolor articular mediante escala analógica visual. A partir de polimorfismos de cambio de un nucleótido (SNPs) en los genes CYP11A1 (rs4077581, rs11632698 y rs900798) y CYP17A1 (rs4919686, rs4919683, rs4919687, rs3781287, rs10786712, rs6163, rs743572), asociados previamente con eventos musculoesqueléticos, se construyeron los haplotipos para cada paciente de la cohorte, y se seleccionaron aquellos que mostraron mayor diferencia fenotípica (p<0,05). Dentro de cada haplotipo, se eligieron aquellas pacientes con fenotipos extremos para la secuenciación de los respectivos genes y la identificación de variantes genéticas funcionales. Finalmente, se realizó un análisis de regresión lineal múltiple contemplando los modelos de herencia genética dominante, recesivo y aditivo. Resultados: No se encontró ninguna mutación en las regiones codificantes. En la región del promotor basal del gen CYP11A1 se encontró una variante genética (D15S520) asociada a la pérdida de masa ósea del cuello de fémur a los 24 meses de tratamiento con IA. Conclusiones: Variantes en regiones reguladoras del gen CYP11A1 podrían modular la expresión de este gen, explicando así parte de la variabilidad fenotípica encontrada en la pérdida de hueso de las pacientes en tratamiento con IA

Thromboembolic, cardiovascular and overall mortality risks of aromatase inhibitors, compared with tamoxifen treatment: an outpatient-register-based retrospective cohort study

Background: Tamoxifen (TAM) and aromatase inhibitor (AI) therapies have been associated with increased risk of thromboembolic and cardiovascular events, respectively, in addition to other side effects. This study analysed the risk of these events and the overall survival (OS) benefit in breast cancer patients treated with AI, compared with TAM-treated patients, in a large population-based cohort. Methods: This observational cohort study included women diagnosed with breast cancer and treated with TAM or AI. Data were extracted from primary care records in a population database (SIDIAP, System for the Development of Research in Primary Care). Incidence rates of study outcomes are reported. Survival analyses included Kaplan-Meier estimation and Cox proportional hazards models. Sensitivity analysis was carried out, using Fine and Gray models to account for competing risk of death. Confounding was minimized using propensity score adjustment and inverse probability weighting (IPW) adjustment. Results: Data from 3082 postmenopausal women treated with TAM, and 18,455 treated with AI, were available. Adjusted hazard ratios (HRs) [95% confidence interval (CI)] for AI users, compared with TAM group, were 0.93 (95%CI 0.69-1.26) for thromboembolic events (TEEs); 1.13 (95%CI 0.79-1.63) for cardiovascular events, and 0.76 (95%CI 0.70-0.82) for mortality. Additional analyses using competing risk analysis had similar results, while IPW adjustment showed a potential risk of pulmonary embolism (PE) [2.26 (95%CI 1.02-4.97)] in AI-treated patients. Conclusions: AI users had >20% lower all-cause mortality compared with TAM users, without increasing risk to experience cardiovascular and TEEs. This would locate AI therapy on the first line in clinical practice. Thus, AI might be the most preferable option in adjuvant hormonal therapy choice