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Background: Second primary cancers (SPCs) after breast cancer (BC) present an increasing public health burden, with little existing research on socio-demographic, tumour, and treatment effects. We addressed this in the largest BC survivor cohort to date, using a novel linkage of National Disease Registration Service datasets. Methods: The cohort included 581,403 female and 3562 male BC survivors diagnosed between 1995 and 2019. We estimated standardized incidence ratios (SIRs) for combined and site-specific SPCs using incidences for England, overall and by age at BC and socioeconomic status. We estimated incidences and Kaplan-Meier cumulative risks stratified by age at BC, and assessed risk variation by socio-demographic, tumour, and treatment characteristics using Cox regression. Findings: Both genders were at elevated contralateral breast (SIR: 2.02 (95% CI: 1.99-2.06) females; 55.4 (35.5-82.4) males) and non-breast (1.10 (1.09-1.11) females, 1.10 (1.00-1.20) males) SPC risks. Non-breast SPC risks were higher for females younger at BC diagnosis (SIR: 1.34 (1.31-1.38) <50 y, 1.07 (1.06-1.09) ≥50 y) and more socioeconomically deprived (SIR: 1.00 (0.98-1.02) least deprived quintile, 1.34 (1.30-1.37) most). Interpretation: Enhanced SPC surveillance may benefit BC survivors, although specific recommendations require more detailed multifactorial risk and cost-benefit analyses. The associations between deprivation and SPC risks could provide clinical management insights. Funding: CRUK Catalyst Award CanGene-CanVar (C61296/A27223). Cancer Research UK grant: PPRPGM-Nov 20∖100,002. This work was supported by core funding from the NIHR Cambridge Biomedical Research Centre (NIHR203312)]. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.
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BACKGROUND: Sebaceous carcinomas (SC) may be associated with the cancer predisposition syndrome Muir-Torre/Lynch syndrome (MTS/LS), identifiable by SC mismatch repair (MMR) screening; however, there is limited data on MMR status of SC. OBJECTIVE: To describe the epidemiology of SC, copresentation of other cancers, and population level frequency of MMR screening in SC. METHODS: A population-based retrospective cohort study of SC patients in the National Cancer Registration and Analysis Service in England. RESULTS: This study included 1077 SC cases (739 extraocular, 338 periocular). Age-standardized incidence rates (ASIR) were higher in men compared with women, 2.74 (95% CI, 2.52-9.69) per 1,000,000 person-years for men versus 1.47 person-years (95% CI, 1.4-1.62) for women. Of the patients, 19% (210/1077) developed at least one MTS/LS-associated malignancy. MMR immunohistochemical screening was performed in only 20% (220/1077) of SC tumors; of these, 32% (70/219) of tumors were MMR deficient. LIMITATIONS: Retrospective design. CONCLUSIONS: Incorporation of MMR screening into clinical practice guidelines for the management of SC will increase the opportunity for MTS/LS diagnoses, with implications for cancer surveillance, chemoprevention with aspirin, and immunotherapy treatment targeted to MTS/LS cancers.
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Adenocarcinoma Sebáceo , Carcinoma Basocelular , Neoplasias Colorrectales , Síndrome de Muir-Torre , Neoplasias de Anexos y Apéndices de Piel , Neoplasias de las Glándulas Sebáceas , Masculino , Humanos , Femenino , Síndrome de Muir-Torre/diagnóstico , Síndrome de Muir-Torre/epidemiología , Síndrome de Muir-Torre/metabolismo , Estudios Retrospectivos , Neoplasias de las Glándulas Sebáceas/diagnóstico , Neoplasias de las Glándulas Sebáceas/epidemiologíaRESUMEN
A complete understanding of how exposure to environmental substances promotes cancer formation is lacking. More than 70 years ago, tumorigenesis was proposed to occur in a two-step process: an initiating step that induces mutations in healthy cells, followed by a promoter step that triggers cancer development1. Here we propose that environmental particulate matter measuring ≤2.5 µm (PM2.5), known to be associated with lung cancer risk, promotes lung cancer by acting on cells that harbour pre-existing oncogenic mutations in healthy lung tissue. Focusing on EGFR-driven lung cancer, which is more common in never-smokers or light smokers, we found a significant association between PM2.5 levels and the incidence of lung cancer for 32,957 EGFR-driven lung cancer cases in four within-country cohorts. Functional mouse models revealed that air pollutants cause an influx of macrophages into the lung and release of interleukin-1ß. This process results in a progenitor-like cell state within EGFR mutant lung alveolar type II epithelial cells that fuels tumorigenesis. Ultradeep mutational profiling of histologically normal lung tissue from 295 individuals across 3 clinical cohorts revealed oncogenic EGFR and KRAS driver mutations in 18% and 53% of healthy tissue samples, respectively. These findings collectively support a tumour-promoting role for PM2.5 air pollutants and provide impetus for public health policy initiatives to address air pollution to reduce disease burden.
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Adenocarcinoma del Pulmón , Contaminantes Atmosféricos , Contaminación del Aire , Transformación Celular Neoplásica , Neoplasias Pulmonares , Animales , Ratones , Adenocarcinoma del Pulmón/inducido químicamente , Adenocarcinoma del Pulmón/genética , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/análisis , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Transformación Celular Neoplásica/inducido químicamente , Transformación Celular Neoplásica/efectos de los fármacos , Transformación Celular Neoplásica/genética , Exposición a Riesgos Ambientales , Receptores ErbB/genética , Neoplasias Pulmonares/inducido químicamente , Neoplasias Pulmonares/genética , Material Particulado/efectos adversos , Material Particulado/análisis , Tamaño de la Partícula , Estudios de Cohortes , Macrófagos Alveolares/efectos de los fármacos , Células Epiteliales Alveolares/efectos de los fármacos , Células Epiteliales Alveolares/patologíaRESUMEN
OBJECTIVE: Surgery is the mainstay of treatment for breast cancer. However, there is evidence that older women are not receiving this treatment. This study explores reasons why older women are not having surgery. METHODS: Twenty eight in-depth interviews were conducted with women over 70 years old with operable breast cancer receiving primary endocrine therapy (PET) as their primary treatment. The interviews focused on their perceptions of why they were being treated with PET rather than surgery. Transcripts were analysed using the Framework method. RESULTS: Based on reasons for PET, patients were divided into three groups: 'Patient Declined', 'Patient Considered' or 'Surgeon Decided'. The first group 'Patient Declined' absolutely ruled out surgery to treat their breast cancer. These patients were not interested in maximising their survival and rejected surgery citing their age or concerns about impact of treatment on their level of functioning. The second group 'Patient Considered' considered surgery but chose to have PET most specifying if PET failed then they could have the operation. Patients viewed this as offering them two options of treatment. The third group 'Surgeon Decided' was started by the surgeon on PET. These patients had comorbidities and in most cases the surgeon asserted that the comorbidities were incompatible with surgery. CONCLUSIONS: Older women represent a diverse group and have multifaceted reasons for foregoing surgery. Discussions about breast cancer treatment should be patient centred and adapted to differing patient priorities.
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Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Mama/terapia , Toma de Decisiones , Factores de Edad , Anciano , Toma de Decisiones Clínicas , Comorbilidad , Femenino , Humanos , Atención Dirigida al Paciente/métodos , Atención Dirigida al Paciente/tendencias , Investigación CualitativaRESUMEN
Evidence suggests that physical activity improves quality of life and physical functioning among breast cancer patients and survivors. However, previous studies have tended to focus on younger patients, despite higher incidence and lower survival among older breast cancer survivors. In this study we explored physical activity preferences of older breast cancer survivors to inform the development of future targeted interventions. Twenty-nine female breast cancer survivors (1 to 5 years postdiagnosis) aged 59 to 86 (mean 66.54, SD 6.50) took part in either a semistructured interview or a focus group exploring physical activity patterns, motivators, facilitators, barriers, and preferences. The main factors influencing physical activity were body image, weight issues, vitality, mood, and the desire to carry on as normal. Preference was expressed for activities that were gentle, tailored to age and cancer-related abilities, holistic, involving other older breast cancer survivors, and with an instructor who was knowledgeable about both breast cancer and aging.
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Actitud Frente a la Salud , Neoplasias de la Mama/psicología , Ejercicio Físico/psicología , Sobrevivientes/psicología , Anciano , Anciano de 80 o más Años , Imagen Corporal , Femenino , Grupos Focales , Humanos , Entrevistas como Asunto , Persona de Mediana Edad , Motivación , Reino UnidoRESUMEN
BACKGROUND: Studies largely from the market research field suggest that the inclusion of a stamped addressed envelope, rather than a pre-paid business reply, increases the response rate to mail surveys. The evidence that this is also the case regarding patient mail surveys is limited. METHODS: The aim of this study is to investigate whether stamped addressed envelopes increase response rates to patient mail surveys compared to pre-paid business reply envelopes and compare the relative costs. A sample of 477 initial non-responders to a mail survey of patients attending breast clinics in Greater Manchester between 1/10/2002 - 31/7/2003 were entered into the trial: 239 were randomly allocated to receive a stamped envelope and 238 to receive a pre-paid envelope in with their reminder surveys. Overall cost and per item returned were calculated. RESULTS: The response to the stamped envelope group was 31.8% (95% CI: 25.9% - 37.7%) compared to 26.9% (21.3% - 32.5%) for the pre-paid group. The difference (4.9% 95% CI: -3.3% - 13.1%) is not significant at alpha = 0.05 (chi2 = 1.39; 2 tailed test, d.f. = 1; P = 0.239). The stamped envelopes were cheaper in terms of cost per returned item (1.20 pounds) than the pre-paid envelopes (1.67 pounds). However if the set up cost for the licence to use the pre-paid service is excluded, the cost of the stamped envelopes is more expensive than pre-paid returns (1.20 pounds versus 0.73 pounds). CONCLUSION: Compared with pre-paid business replies, stamped envelopes did not produce a statistically significant increase in response rate to this patient survey. However, the response gain of the stamped strategy (4.9%) is similar to that demonstrated in a Cochrane review (5.3%) of strategies to increase response to general mail surveys. Further studies and meta analyses of patient responses to mail surveys via stamped versus pre-paid envelopes are needed with sufficient power to detect response gains of this magnitude in a patient population.