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Background: Reproductive factors and hormone use in postmenopausal women have been hypothesised to affect the risk of developing lung cancer, but the epidemiological evidence is inconsistent., Methods: Using the Korean National Health Insurance System database, we identified 4,775,398 postmenopausal women older than 40 years who had undergone both cardiovascular health- and cancer screening between 1 January 2009 and 31 December 2014. Information about reproductive factors was obtained from a self-administered questionnaire. The risk of lung cancer was estimated using Cox proportional hazard regression models., Results: During a median follow-up of 4.4 years, 16,556 women (15,223 non-smokers) were diagnosed with lung cancer. The risk of lung cancer was not significantly influenced by early menarche age (adjusted hazard ratio [aHR] 1.03 for menarche ≥18 vs. ≤14; 95% confidence interval [CI], 0.98-1.09) or late age at menopause (aHR 1.02 for menopause ≥55 vs. <40; 95% CI, 0.91-1.14). Furthermore, the number of children, duration of breastfeeding and use of hormone replacement therapy were not associated with the risk of lung cancer., Conclusions: No statistically significant association was found between reproductive factors and the risk of lung cancer in postmenopausal Korean women.

The differences in bladder cancer outcomes between the sexes has again been highlighted. Uncommon among cancers, bladder cancer outcomes are notably worse for women than for men. Furthermore, bladder cancer is three to four times more common among men than among women. Factors that might explain these sex differences include understanding the importance of haematuria as a symptom of bladder cancer by both clinicians and patients, the resultant delays in diagnosis and referral of women with haematuria, and health-care access. Notably, these factors seem to have geographical variation and are not consistent across all health-care systems. Likewise, data relating to sex-specific treatment responses for patients with non-muscle-invasive or muscle-invasive bladder cancer are inconsistent. The influence of differences in the microbiome, bladder wall thickness and urine dwell times remain to be elucidated. The interplay of hormone signalling, gene expression, immunology and the tumour microenvironment remains complex but probably underpins the sexual dimorphism in disease incidence and stage and histology at presentation. The contribution of these biological phenomena to sex-specific outcome differences is probable, albeit potentially treatment-specific, and further understanding is required. Notwithstanding these aspects, we identify opportunities to harness biological differences to improve treatment outcomes, as well as areas of fundamental and translational research to pursue. At the level of policy and health-care delivery, improvements can be made across the domains of patient awareness, clinician education, referral pathways and guideline-based care. Together, we aim to highlight opportunities to close the sex gap in bladder cancer outcomes., (© 2023. Springer Nature Limited.)

Individuals that have gynecologic reproductive organs with pathogenic variants in BRCA1 or BRCA2 ("BRCA-positive") have an increased risk of developing high-grade serous ovarian cancer (HGSOC). The majority of HGSOC develops in the fallopian tubes and later spreads to the ovaries and peritoneal cavity. Therefore, risk-reducing salpingo-oophorectomy (RRSO) is recommended for those who are BRCA-positive to preventatively remove their ovaries and fallopian tubes. The Hereditary Gynecology Clinic (HGC) is a provincial program in Winnipeg, Canada, that specifically targets care to the unique needs of such individuals through an interdisciplinary team of gynecological oncologists, menopause specialists, and registered nurses. A mixed-methods study design was used to explore the decision-making processes of these BRCA-positive individuals who have been recommended (or who completed) RRSO and experiences with healthcare providers at the HGC influenced this decision. Individuals who are BRCA-positive without a previous diagnosis of HGSOC and who had previously received genetic counselling were recruited from the HGC and the provincial cancer genetics program (Shared Health Program of Genetics & Metabolism). Forty-three people completed a survey and 15 participated in an in-depth interview about their experiences and decisions surrounding RRSO. Surveys were analyzed to compare scores on validated scales related to decision-making and cancer-related worry. Qualitative interviews were transcribed, coded, and analyzed using interpretive description. Participants described the complex decisions faced by those who are BRCA-positive, which are intertwined with life experiences and circumstances including age, marital status, and family disease history. Participants interpreted their HGSOC risk through a personalized "lens" of contextual factors that impacted perceptions about the practical and emotional implications of RRSO and the need for surgery. Mean scores on validated scales evaluating the HGC's impact on decisional outcomes and preparedness for decision-making about RRSO were not significant, indicating that the HGC played a supportive role, rather than helping with decision-making itself. Therefore, we present a novel framework that consolidates the various influences on decision-making and connects them to the psychological and practical implications of RRSO in the context of the HGC. Strategies for improving support, decisional outcomes, and the overall experiences of individuals who are BRCA-positive attending the HGC are also described., (© 2023 The Authors. Journal of Genetic Counseling published by Wiley Periodicals LLC on behalf of National Society of Genetic Counselors.)

As geographical location can impact the gut microbiome, it is important to study region-specific microbiome signatures of various diseases. Therefore, we profiled the gut microbiome of breast cancer (BC) patients of the Midwestern region of the United States. The bacterial component of the gut microbiome was profiled utilizing 16S ribosomal RNA sequencing. Additionally, a gene pathway analysis was performed to assess the functional capabilities of the bacterial microbiome. Alpha diversity was not significantly different between BC and healthy controls (HC), however beta diversity revealed distinct clustering between the two groups at the species and genera level. Wilcoxon Rank Sum test revealed modulation of several gut bacteria in BC specifically reduced abundance of those linked with beneficial effects such as Faecalibacterium prausnitzii. Machine learning analysis confirmed the significance of several of the modulated bacteria found by the univariate analysis. The functional analysis showed a decreased abundance of SCFA (propionate) production in BC compared to HC. In conclusion, we observed gut dysbiosis in BC with the depletion of SCFA-producing gut bacteria suggesting their role in the pathobiology of breast cancer. Mechanistic understanding of gut bacterial dysbiosis in breast cancer could lead to refined prevention and treatment., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Excess body weight has been established as a risk factor for at least twelve cancer sites, though questions remain as to the timing of associations for adiposity and cancer risk throughout the life course. We conducted a narrative review summarizing existing evidence to provide insights into the complex timing relationship between adiposity and risk of seven common obesity-related cancers. We considered five types of studies, including traditional epidemiologic studies examining adiposity at different time points, studies examining weight gain in specific life phases, studies examining weight loss over a period including from bariatric surgery, life course trajectory analysis, and Mendelian randomization studies. The results showed that lifetime excess body weight is associated with increased risk of cancers of endometrium, colorectum, liver, kidney, and pancreas. Early life obesity is one of the strongest risk factors for pancreatic cancer but less directly important than adult obesity for endometrial and kidney cancer. Interestingly, heavy weight during childhood, adolescence, and early adulthood is protective against pre- and postmenopausal breast cancer and possibly advanced prostate cancer. It is apparent that preventing weight gain later in adulthood would likely reduce risk of many cancers, including postmenopausal breast cancer, endometrial cancer, colorectal cancer (especially in men), liver cancer, kidney cancer, and probably advanced prostate cancer. Furthermore, weight loss even late in life may confer benefits for cancers of breast, endometrium, colorectum, and liver among patients with obesity, as mostly demonstrated by studies of bariatric surgery. Overall, maintaining a healthy weight throughout the life course will help prevent a large number of cancers., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: We describe temporal trends in breast cancer incidence by molecular subtypes in Scotland because public health prevention programmes, diagnostic and therapeutic services are shaped by differences in tumour biology., Methods: Population-based cancer registry data on 72,217 women diagnosed with incident primary breast cancer from 1997 to 2016 were analysed. Age-standardised rates (ASR) and age-specific incidence were estimated by tumour subtype after imputing the 8% of missing oestrogen receptor (ER) status. Joinpoint regression and age-period-cohort models were used to assess whether significant differences were observed in incidence trends by ER status., Results: Overall, ER-positive tumour incidence increased by 0.4%/year (95% confidence interval (CI): -0.1, 1.0). Among routinely screened women aged 50-69 years, we observed an increase in ASR from 1997 to 2011 (1.6%/year, 95% CI: 1.2-2.1). ER-negative tumour incidence decreased among all ages by 2.5%/year (95% CI: -3.9 to -1.1%) over the study period. Compared with the 1941-1959 birth cohort, women born in 1912-1940 had lower incidence rate ratios (IRR) for ER+ tumours and women born in 1960-1986 had lower IRR for ER- tumours., Conclusions: Future incidence and survival reporting should be monitored by molecular subtypes to inform clinical planning and cancer control programmes.

Background: We tested the hypothesis that body mass index (BMI) aged 20 years modifies the association of adult weight gain and breast cancer risk., Methods: We recruited women (aged 47-73 years) into the PROCAS (Predicting Risk Of Cancer At Screening; Manchester, UK: 2009-2013) Study. In 47,042 women, we determined BMI at baseline and (by recall) at age 20 years, and derived weight changes. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for new breast cancer using Cox models and explored relationships between BMI aged 20 years, subsequent weight changes and breast cancer risk., Results: With median follow-up of 5.6 years, 1142 breast cancers (post-menopausal at entry: 829) occurred. Among post-menopausal women at entry, BMI aged 20 years was inversely associated [HR per SD: 0.87 (95% CI: 0.79-0.95)], while absolute weight gain was associated with breast cancer [HR per SD:1.23 (95% CI: 1.14-1.32)]. For post-menopausal women who had a recall BMI aged 20 years <23.4 kg/m 2 (75th percentile), absolute weight gain was associated with breast cancer [HR per SD: 1.31 (95% CIs: 1.21-1.42)], but there were no associations for women with a recall BMI aged 20 years of >23.4 kg/m 2 (P interaction values <0.05)., Conclusions: Adult weight gain increased post-menopausal breast cancer risk only among women who were <23.4 kg/m 2 aged 20 years.

Alopecia areata (AA), a complex autoimmune hair loss condition, affects approximately 2.1% of the population. Individuals with AA have increased susceptibility to diseases such as atopy and autoimmune disorders, but little is known about first-degree relatives' risk to develop AA and associated conditions. Genetic counseling for multifactorial conditions, including autoimmune disease is complex, but potentially valuable. Anecdotally we know patients with AA ask medical providers about recurrence risk for family members as well as question whether they and their relatives are at risk for other conditions. Data on AA recurrence risks and comorbid conditions among relatives of affected individuals comprise valuable information that may guide clinical management by genetic counselors. This study investigated the recurrence risk of AA and compared the prevalence of associated conditions among first-degree relatives to the general population. The study also assessed the validity of self-reported conditions for a subset of participants. Relatives of individuals with AA (N = 155), recruited from the National Alopecia Areata Foundation Registry, completed telephone surveys about their personal medical history for 70 medical conditions associated with AA. Medical records for 60 participants were compared to self-reported responses. One-sided proportional tests, in which it is assumed the disease prevalence in first-degree relatives is higher than for those in the general population, yielded a 7.8% estimated risk of AA versus the general population prevalence of 2.1%. Furthermore, there are increased risks of 33 associated conditions, including atopy and other autoimmune conditions. Comparison of medical reports to self-reported conditions indicated only 12% was incongruent. The findings may help genetic counselors better serve patients and their families by informing them of lifetime risk estimates of developing AA and comorbid conditions, resulting in early diagnosis of autoimmune diseases in AA families. Findings also provide evidence supporting the validity of self-report data in AA families., (© 2019 National Society of Genetic Counselors.)

Background: Breast cancer risk and reconstructive options after massive weight loss are undefined. Use of the resulting pannus for autologous reconstruction is possible, with one option being the superficial inferior epigastric artery (SIEA) flap. Large superficial inferior epigastric vessels have been observed in massive weight loss patients during abdominal contouring procedures, but their anatomical features have not been assessed., Methods: Thirty-two consecutive massive weight loss patients undergoing abdominal contouring had their superficial inferior epigastric vessels measured intraoperatively to assess correlation with body mass indices and pannus weight using appropriate statistical analyses., Results: Sixty-four hemiabdomens were assessed. Mean age was 46 +/- 9.8 years. Mean maximum body mass index was 49.5 +/- 8.3, current body mass index was 29.6 +/- 6.0, change in body mass index was 19.9 +/- 5.6, and mean pannus weight was 3338.4 g. Mean artery size was 1.7 mm and mean vein size was 2.9 mm. Thirty-two of 62 hemiabdomens (52 percent) had a usable vessel (>or=1.5 mm). Maximum body mass index was related to the overall presence of a SIEA (p = 0.009) or usable artery (p = 0.04), whereas both current body mass index and maximum body mass index were related to superficial inferior epigastric vein size (p < 0.001). Pannus weight was correlated to superficial inferior epigastric vein and SIEA size (p < 0.001) and strongly correlated to current body mass index (r = 0.78) and maximum body mass index (r = 0.46)., Conclusions: The superficial inferior epigastric vessel system is commonly present in massive weight loss patients. Body mass index before weight loss is the strongest predictor of SIEA presence and usability. When massive weight loss patients present for breast reconstruction, careful patient selection along with weight loss history and assessment of pannus size may aid in determining the likelihood of using the SIEA flap.

Background: In 2005, convincing safety and efficacy data were presented, resulting in the approval of Mentor MemoryGel Implants, with conditions., Methods: The 1007 women enrolled in the 10-year, multicenter, Mentor Core MemoryGel Study were distributed into four cohorts: 551 primary augmentation patients, 146 revision-augmentation patients, 251 primary reconstruction patients, and 59 revision-reconstruction patients. Preoperatively and postoperatively, study instruments and physical examinations were administered to assess medical history, patient satisfaction, quality of life and body image, connective tissue disease diagnosis, rheumatology symptoms, and chest size change to determine the efficacy of surgery., Results: Safety assessments included complication rates and rates of reoperation. Results at 3 years were reported at the U.S. Food and Drug Administration panel. Results indicate that the risk of any complication (including reoperation) at some point through 3 years after implant surgery is 36.6 percent for primary patients, 50.1 percent for revision-augmentation patients, 49.4 percent for primary reconstruction patients, and 47.5 percent for revision-reconstruction patients. Suspected rupture rates reported from the magnetic resonance imaging cohort were 0.5 percent for primary augmentation, 7.7 percent for revision-augmentation, 0.9 percent for primary reconstruction, and 0 percent for revision-reconstruction. Only two implants, in a single patient, were found surgically to be ruptured. There were 4.7 percent primary and 12.3 percent revision-augmentation patients who had their implants removed, with patient choice and severe capsular contracture being the most common reasons., Conclusion: The data demonstrated safety and efficacy of the devices, but also indicate that a focus must be placed on better education and technique to improve clinical outcomes in the future.