Triple negative breast cancer is typically an aggressive and difficult to treat subtype. It is often associated with loss of function of the BRCA1 gene, either through mutation, loss of heterozygosity or methylation. This study aimed to measure methylation of the BRCA1 gene promoter at individual CpG sites in blood, tumour and normal breast tissue, to assess whether levels were correlated between different tissues, and with triple negative receptor status, histopathological scoring for BRCA-like features and BRCA1 protein expression. Blood DNA methylation levels were significantly correlated with tumour methylation at 9 of 11 CpG sites examined (p<0.0007). The levels of tumour DNA methylation were significantly higher in triple negative tumours, and in tumours with high BRCA-like histopathological scores (10 of 11 CpG sites; p<0.01 and p<0.007 respectively). Similar results were observed in blood DNA (6 of 11 CpG sites; p<0.03 and 7 of 11 CpG sites; p<0.02 respectively). This study provides insight into the pattern of CpG methylation across the BRCA1 promoter, and supports previous studies suggesting that tumours with BRCA1 promoter methylation have similar features to those with BRCA1 mutations, and therefore may be suitable for the same targeted therapies.

BACKGROUND Reproductive health conditions such as endometriosis, uterine fibroids and polycystic ovary syndrome affect a large proportion of women and people who menstruate worldwide. Prevalence estimates for these conditions range from 5-40% of women of reproductive age. Long diagnostic delays, up to 12 years, are common and contribute to health complications and increased healthcare costs. Symptom checker apps provide users with information and tools to better understand their symptoms and thus have the potential to reduce the time to diagnosis for reproductive health conditions. OBJECTIVE This study aims to evaluate the accuracy of three symptom checkers developed by Flo Health assessing symptoms of endometriosis, uterine fibroids and polycystic ovary syndrome (PCOS) against current medical guidelines. METHODS Independent general practitioners were recruited to create clinical case vignettes of simulated users with and without the conditions of interest. Vignettes were reviewed, modified and approved by separate general practitioners. A further independent panel of general practitioners reviewed the cases and designated a final classification. Vignettes were entered into the symptom checkers and the outcomes were compared with the final classification from the panel using accuracy metrics including percent agreement, sensitivity and specificity. RESULTS A total of 24 cases were created per condition. Overall, exact matches between the vignette classification and the symptom checker outcome was 83.3% for endometriosis and uterine fibroids, and 87.5% for PCOS. While sensitivity was high for all conditions (>81%) and very high (100%) for PCOS, specificity was >81% for endometriosis and uterine fibroids and 75% for PCOS. CONCLUSIONS The single condition symptom checkers have high levels of accuracy for endometriosis, uterine fibroids and PCOS. Given long delays in diagnosis for many reproductive health conditions, which lead to increased medical costs and potential health complications for individuals and healthcare providers, innovative health apps and symptom checkers hold the potential to improve care pathways.

Background Reproductive health conditions such as endometriosis, uterine fibroids and polycystic ovary syndrome affect a large proportion of women and people who menstruate worldwide. Prevalence estimates for these conditions range from 5-40% of women of reproductive age. Long diagnostic delays, up to 12 years, are common and contribute to health complications and increased healthcare costs. Symptom checker apps provide users with information and tools to better understand their symptoms and thus have the potential to reduce the time to diagnosis for reproductive health conditions. Objective This study aims to evaluate the accuracy of three symptom checkers developed by Flo Health assessing symptoms of endometriosis, uterine fibroids and polycystic ovary syndrome (PCOS) against current medical guidelines. Methods Independent general practitioners were recruited to create clinical case vignettes of simulated users with and without the conditions of interest. Vignettes were reviewed, modified and approved by separate general practitioners. A further independent panel of general practitioners reviewed the cases and designated a final classification. Vignettes were entered into the symptom checkers and the outcomes were compared with the final classification from the panel using accuracy metrics including percent agreement, sensitivity and specificity. Results A total of 24 cases were created per condition. Overall, exact matches between the vignette classification and the symptom checker outcome was 83.3% for endometriosis and uterine fibroids, and 87.5% for PCOS. While sensitivity was high for all conditions (>81%) and very high (100%) for PCOS, specificity was >81% for endometriosis and uterine fibroids and 75% for PCOS. Conclusion The single condition symptom checkers have high levels of accuracy for endometriosis, uterine fibroids and PCOS. Given long delays in diagnosis for many reproductive health conditions, which lead to increased medical costs and potential health complications for individuals and healthcare providers, innovative health apps and symptom checkers hold the potential to improve care pathways.