Are estrogen receptor-positive breast cancers in BRCA1 mutation carriers sporadic?

There is a strong association between BRCA1 mutation carrier status and estrogen receptor-negative breast cancer. This has led to the idea that estrogen receptor-positive breast cancers in BRCA1 mutation carriers may be incidental or sporadic in nature and not as a direct result of BRCA1 dysfunction. A recent paper in Breast Cancer Research challenges this view

'People still want a face and that's where we can fill in': a qualitative study of community pharmacists' experiences of providing healthcare advice about preconception and pregnancy.

OBJECTIVES: This study aimed to explore community pharmacists' practices and attitudes towards the provision of healthcare advice regarding preconception and pregnancy. METHODS: A qualitative focus group study was conducted virtually with community pharmacists around urban areas of London in October 2021. A topic guide was utilised to cover pharmacy practice, barriers and confidence in counselling women, education and training and thoughts on how to improve preconception and pregnancy health services. Focus groups were transcribed and analysed using thematic analysis. KEY FINDINGS: Eleven community pharmacists participated. Three themes were identified: 'Community Driven Needs'; 'Needs of Community Pharmacists'; 'Shared Needs and Understanding' which were related through a central organising concept of 'Unmet Needs in Pharmacy-led Preconception and Pregnancy Care'. Community pharmacists are frequently consulted by women before and during pregnancy, however, a discord was uncovered between current pharmacy practice and the needs of the community. A clear need was identified for the incorporation of risk minimisation counselling focusing on smoking, alcohol intake and drug use. Education and organisational factors were reported as challenges to providing advice. CONCLUSIONS: Community pharmacists can play a pivotal role in providing information and support to women before and during pregnancy. Our findings suggest integration of community pharmacy-led structured counselling may be a useful public health strategy to optimise pregnancy health. Our work highlights educational and organisational barriers which hinder the ability of pharmacists to promote preconception and pregnancy health. These must be addressed, and we provide recommendations for change to both policy and practice

Things change: Women’s and men’s marital disruption dynamics in Italy during a time of social transformations, 1970-2003

We study women’s and men’s marital disruption in Italy between 1970 and 2003. By applying an event-history analysis to the 2003 Italian variant of the Generations and Gender Survey we found that the spread of marital disruption started among middle-highly educated women. Then in recent years it appears that less educated women have also been able to dissolve their unhappy unions. Overall we can see the beginning of a reversed educational gradient from positive to negative. In contrast the trend in men’s marital disruption risk appears as a change over time common to all educational groups, although with persisting educational differentials.determinants, educational differences, event history analysis, gender difference, Italy, marital disruption

The African Vaccine-Preventable Diseases Network: a vaccine advocacy initiative

Achieving high and equitable childhood immunisation coverage in Africa will not only protect children from disability and premature death, it will also boost productivity, reduce poverty and support the economic growth of the continent. Thus, Africa needs innovative and sustainable vaccine advocacy initiatives. One such initiative is the African Vaccine-Preventable Diseases Network, formed in 2009. This association of immunisation practitioners, vaccinologists, paediatricians, and infectious disease experts provides a platform to advocate for the introduction of newly available vaccines (e.g. 10-valent and 13-valent pneumococcal conjugate and rotavirus vaccines) into the Expanded Programme on Immunisation (EPI) as well as increased and equitable coverage for established EPI vaccines.Key words: Vaccine preventable diseases, vaccine, network, Africa, awareness, child healt

“There's very little that you can do other than refer them to the doctor if you think they've got postnatal depression”: Scoping the potential for perinatal mental health care by community pharmacists: Community pharmacists and perinatal mental health

Background: Twenty percent of women in the UK develop perinatal mental health (PMH) problems, which have widespread effects on maternal and child health. Community pharmacists are ideally placed to identify PMH problems and refer to other trained healthcare professionals. Objective: This study explored community pharmacists’ attitudes, current counselling practices, and barriers to providing mental health advice to perinatal women. Methods: A qualitative focus group study was performed virtually with community pharmacists (n = 11), working in urban settings across London. A topic guide was used to cover current counselling practice, barriers to and confidence in counselling women, and thoughts on potential pharmacist-led perinatal mental health services. The focus groups were recorded, transcribed, and analysed using thematic analysis. Results: Three themes were identified: Doing Mental Health Care; Willing, but Unable; and Introspection and reflection, which were related through a central organising concept of ‘Perinatal mental health care as a new frontier for community pharmacy’. It was found that while community pharmacists provide mental health advice to perinatal women and their partners, they lacked confidence, which was related to a lack of knowledge and inadequate training opportunities. Organisational barriers were identified including a lack of a formal referral pathway to existing mental health services and other trained healthcare professionals. Perceptions of opportunities and recommendations for service improvement and change were also garnered. Conclusion: This study demonstrates community pharmacists have a potential role within community mental healthcare in identification of PMH problems and providing appropriate advice and support. Upskilling community pharmacists in mental health should be considered to increase knowledge and confidence while formal referral pathways to other trained healthcare professionals and existing services should be established and made available to pharmacists

A common missense variant in BRCA2 predisposes to early onset breast cancer

INTRODUCTION: Mutations in the BRCA2 gene are one of the two major causes of hereditary breast cancer. Protein-truncating mutations of BRCA2 are usually deleterious and increase the risk of breast cancer up to 80% over a lifetime. A few missense mutations in BRCA2 are believed to have a similarly high penetrance, apart from more common neutral polymorphisms. It is often difficult to classify a particular sequence variant as a mutation or a polymorphism. For a deleterious variant, one would expect a greater allele frequency in breast cancer cases than in ethnic-matched controls. In contrast, neutral polymorphic variants should be equally frequent in the two groups. METHODS: We genotyped 3,241 cases of breast cancer diagnosed at under 51 years of age, unselected for family history, from 18 hospitals throughout Poland and 2,791 ethnic-matched controls for a single BRCA2 C5972T variant. RESULTS: The variant was present in approximately 6% of the Polish population. In the study, 13 women (11 cases and two controls (OR = 4.7; p = 0.02)) were homozygous for the variant allele. The overall odds ratio for breast cancer in women with a single copy of the BRCA2 C5972T variant was 1.1 (p = 0.7); however, the effect was significant for patients diagnosed at or before age 40 (OR = 1.4; p = 0.04). We reviewed the association between the BRCA2 variant in different histologic subgroups and found the effect most pronounced in women who had ductal carcinoma in situ (DCIS) with micro-invasion (OR = 2.8; p < 0.0001). CONCLUSION: The BRCA2 C5972T allele is a common variant in Poland that increases the risk of DCIS with micro-invasion. The homozygous state is rare but increases the risk of breast cancer five-fold

Clinical and pathological features of BRCA1 associated carcinomas in a hospital-based sample of Dutch breast cancer patients

Thus far, studies investigating the differences in tumour characteristics between breast cancer in BRCA1-carriers and other patients, have focused on highly selected groups of patients, potentially limiting the conclusions that can be drawn. Previously, we had identified 10 patients with BRCA1 germline mutations in a hospital-based series of 642 breast cancer patients not selected for age or family history. The aim of this analysis is to investigate the clinical and pathological features of these BRCA1 associated carcinomas as compared to other breast cancers in this representative sample. Tumours from patients with BRCA1 germline mutations (n= 10) were compared to an age-matched sample of other patients (n= 50) from the same cohort. The following characteristics were considered: axillary nodal status and tumour size, histologic parameters (tumour type, histologic grade, mitotic rate, tubule formation, nuclear grade, CIS and lymphangio invasion) and expression of several proteins (oestrogen and progesterone receptors, cyclin D1, p53, HER2/neu, E-cadherin). In BRCA1associated tumours receptors for oestrogen and progesterone were expressed less frequently (respectively P= 0.001 and P= 0.002) than in controls, which is in line with findings from other studies. Other differences were also in accordance with findings from other studies, although not statistically significant. We conclude that the features of BRCA1 associated tumours detected in a hospital-based series of breast cancer patients not selected for family history of age at diagnosis are similar to tumours in cases selected for family history or age at diagnosis. © 2001 Cancer Research Campaign  http://www.bjcancer.co

Immunophenotypic predictive profiling of BRCA1-associated breast cancer

The immunophenotypic predictive profile of BRCA1-associated cancers including major predictive markers, i.e., PARP-1, EGFR, c-kit, HER-2, and steroid hormones (ER/PR) that may have therapeutic relevance has not yet been reported in a comprehensive study. Using immunohistochemistry, we examined the expression of these proteins in a large cohort of BRCA1-associated breast cancers. PARP-1 immunoreactivity was found in 81.9%, EGFR in 43.6%, ER/PR in 17.9%, c-kit in 14.7%, and overexpression of HER-2 in 3.6% of cancers. For all markers studied, 8.2% of tumors were negative. Expression of only one predictive marker was found in 29.7% of cancers, and most frequently, it was PARP-1 (20.8%). In 62.1% of tumors, more than one predictive marker was expressed: PARP-1 and EGFR in 30.4%, PARP-1, and hormone receptors in 13.3% and PARP-1 with c-kit in 7.5% of all tumors. Coexpression of two or more other predictive markers was rare. There were significant differences in the median age at diagnosis of BRCA1-associated cancer between patients with ER+ vs. ER− and grades 1–2 vs. grade 3 tumors. These results demonstrate that BRCA1-associated cancers differ with respect to expression of proteins that are regarded as targets for specific therapies and that 92% of patients with BRCA1-associated cancers may benefit from one or several options for specific therapy (in addition to DNA damaging agents, e.g., cisplatin). About 8% of cancers which do not express therapeutic target proteins may not respond to such therapies. Knowledge of the immunophenotypic predictive profile may help with the recruitment of patients for trials of targeted therapies

Novel truncating mutations in CTNND1 cause a dominant craniofacial and cardiac syndrome.

CTNND1 encodes the p120-catenin (p120) protein, which has a wide range of functions, including the maintenance of cell-cell junctions, regulation of the epithelial-mesenchymal transition and transcriptional signalling. Due to advances in next-generation sequencing, CTNND1 has been implicated in human diseases including cleft palate and blepharocheilodontic (BCD) syndrome albeit only recently. In this study, we identify eight novel protein-truncating variants, six de novo, in 13 participants from nine families presenting with craniofacial dysmorphisms including cleft palate and hypodontia, as well as congenital cardiac anomalies, limb dysmorphologies and neurodevelopmental disorders. Using conditional deletions in mice as well as CRISPR/Cas9 approaches to target CTNND1 in Xenopus, we identified a subset of phenotypes that can be linked to p120-catenin in epithelial integrity and turnover, and additional phenotypes that suggest mesenchymal roles of CTNND1. We propose that CTNND1 variants have a wider developmental role than previously described and that variations in this gene underlie not only cleft palate and BCD but may be expanded to a broader velocardiofacial-like syndrome