Risks of second primary cancers among 584,965 female and male breast cancer survivors in England: a 25-year retrospective cohort study

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

Mitochondrial dysfunction and mitophagy defects in LRRK2-R1441C Parkinson's disease models

Mutations in the Leucine-Rich Repeat Kinase 2 (LRRK2) gene have been identified as one of the most common genetic causes of Parkinson’s disease (PD). The LRRK2 PD-associated mutations LRRK2G2019S and LRRK2R1441C, located in the kinase domain and in the ROC-COR domain, respectively, have been demonstrated to impair mitochondrial function. Here, we sought to further our understanding of mitochondrial health and mitophagy by integrating data from LRRK2R1441C rat primary cortical and human induced pluripotent stem cell-derived dopamine (iPSC-DA) neuronal cultures as models of PD. We found that LRRK2R1441C neurons exhibit decreased mitochondrial membrane potential, impaired mitochondrial function and decreased basal mitophagy levels. Mitochondrial morphology was altered in LRRK2R1441C iPSC-DA but not in cortical neuronal cultures or aged striatal tissue, indicating a cell-type-specific phenotype. Additionally, LRRK2R1441C but not LRRK2G2019S neurons demonstrated decreased levels of the mitophagy marker pS65Ub in response to mitochondrial damage, which could disrupt degradation of damaged mitochondria. This impaired mitophagy activation and mitochondrial function were not corrected by the LRRK2 inhibitor MLi-2 in LRRK2R1441C iPSC-DA neuronal cultures. Furthermore, we demonstrate LRRK2 interaction with MIRO1, a protein necessary to stabilize and to anchor mitochondria for transport, occurs at mitochondria, in a genotype-independent manner. Despite this, we found that degradation of MIRO1 was impaired in LRRK2R1441C cultures upon induced mitochondrial damage, suggesting a divergent mechanism from the LRRK2G2019S mutation

Older breast cancer survivors' views and preferences for physical activity

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, holis-tic, involving other older breast cancer survivors, and with an instructor who was knowledgeable about both breast cancer and aging

Article announcing Malcolm Muggeridge's resignation from the judging panel: Part 17

Cuttings referring to Malcolm Muggeridge's withdrawal from the Booker judging pane

Why are older women not having surgery for breast cancer? A qualitative study

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 PETmost 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. © 2015 The Authors. Psycho-Oncology published by John Wiley &amp; Sons Ltd