Unaffected Women Research Articles

Expression of Reversion-Inducing Cysteine-Rich Protein with Kazal Motifs (RECK) Gene and Its Regulation by miR200b in Ovarian Endometriosis.

Endometriosis is a common chronic disorder characterized by the growth of endometrium-like tissue outside the uterine cavity. The disease is associated with chronic inflammation and pelvic pain and may have an impact on the patient's fertility. The causative factors and pathophysiology of the disease are still poorly recognized. The dysregulation of the immune system, aberrant tissue remodeling, and angiogenesis contribute to the disease progression. In endometriosis patients, the proteins regulating the breakdown and reorganization of the connective tissue, e.g., collagenases, and other proteases, as well as their inhibitors, show an incorrect pattern of expression. Here, we report that the expression of reversion-inducing cysteine-rich protein with Kazal motifs (RECK), one of the inhibitors of connective tissue proteases, is elevated in endometrioma cysts as compared to normal endometrium from unaffected women. We also demonstrate a reduced level of miR200b in endometriotic tissue that correlates with RECK mRNA levels. Furthermore, we employ the 12Z cell line, derived from a peritoneal endometriotic lesion, and the Ishikawa cell line, originating from endometrial adenocarcinoma to identify RECK as a direct target of miR200b. The described effect of miR200b on RECK, together with the aberrant expression of both genes in endometrioma, may help to understand the role played by the tissue remodeling system in the pathogenesis of endometriosis.

Hybrid segmentation and 3D Imaging: Comprehensive framework for breast cancer patient segmentation and classification based on digital breast tomosynthesis

Breast cancer is among the deadliest conditions and the second-leading reason for cancer mortality in women. Breast cells begin to develop into malignant, cancerous tumors, which is how breast cancer develops. Self-tests and routine professional examinations aid in early diagnosis, which increases the likelihood of surviving. A major difficulty for researchers is the categorization of breast cancer as a medical procedure. The prevailing aim of this research is the earlier recognition of breast cancer using 3D images and AI monitors. Initially, the mammogram images are collected and preprocessed to enhance the image quality. Noise removal is done using a Multistage Selective Convolution Filter (MSCF), contrast enhancement is done using an Enhanced Contrast Limited Adaptive Histogram (ECLAH), and an Improved Canny Operator (ICO) is employed for edge detection. Segmentation is done using the DENSE Squeeze Excitation Network (DENSE SE- Net). The preprocessed images are converted to 3D images using Digital Breast Tomosynthesis (DBT). From the hybrid segmented and 3D images, the objects are identified utilizing the You Only Look Once v7 (YOLO v7), and the images are classified into mild, medium, severe, and unaffected women using semi-supervised CNN (SS CNN). Finally, an AI monitor is used to monitor the patients. The simulation findings reveal that the suggested technique yields higher accuracy, precision, recall, and F1 score and better ROC characteristics than the existing approaches.

Cohort profile: a nationwide study in Dutch CHEK2 c.1100delC families using the infrastructure of the HEreditary Breast and Ovarian cancer study Netherlands – Hebon-CHEK2

PurposeCHEK2 c.1100delC is associated with an increased breast cancer risk in women. While this variant is prevalent in the Netherlands (1% in the general population), knowledge of aetiology and prognosis...

Blood molybdenum level as a marker of cancer risk on BRCA1 carriers

ObjectiveTo investigate whether Molybdenum blood level is a marker of cancer risk on BRCA1 carriers.MethodsA prospective cohort study was conducted among 989 initially unaffected women with a BRCA1 mutation. Blood samples were collected to measure molybdenum levels, and participants were followed for an average of 7.5 years. Cox proportional hazards models were used to assess the association between blood molybdenum levels and cancer incidence, adjusting for potential confounders.ResultsHigh blood molybdenum levels (> 0.70 µg/L) were significantly associated with an increased risk of developing ovarian cancer (HR = 5.55; 95%CI: 1.59–19.4; p = 0.007) and any cancer (HR = 1.74; 95%CI: 1.17–2.61; p = 0.007) but not breast cancer (HR = 1.46, CI = 0.91–2.33; p = 0.12). The cumulative incidence of ovarian cancer at ten years was 1.2% for the lowest molybdenum tertile, 4.2% for the middle tertile, and 8.7% for the highest tertile.ConclusionElevated blood molybdenum levels are associated with an increased risk of ovarian cancer on BRCA1 mutation carriers. Lowering molybdenum levels may potentially reduce cancer risk in this population, and high molybdenum levels could serve as a marker for considering preventive oophorectomy in BRCA1 carriers. Further research is warranted to confirm these findings and explore interventions targeting molybdenum levels as a preventive measure for ovarian cancer in BRCA1 mutation carriers.

Relationship between endometriosis and uterine cervical elasticity assessed using ultrasound strain elastography.

Internal cervical os (ICO) stiffness is related to menstrual pain, a key symptom of endometriosis. The study evaluated whether women with endometriosis have a stiffer ICO than unaffected women. A retrospective cross-sectional analysis was conducted using prospectively collected data from women with and without endometriosis, spanning from June 2020 to September 2022. Endometriosis was diagnosed through clinical and ultrasound evaluations, with histological confirmation in a subset of participants. Strain elastography (SE) was employed to measure tissue elasticity in four cervical regions of interest: the ICO and the anterior, posterior, and middle cervical compartments (ACC, PCC, and MCC, respectively). Tissue elasticity was quantified using a color-based scoring system ranging from 0.1 (blue, indicating less elasticity) to 3.0 (red, indicating greater elasticity). Overall, 287 women were included, with 157 diagnosed with endometriosis and 130 controls. On SE, women with endometriosis exhibited a lower color score (mean±standard deviation), indicating lower elasticity, for the ICO (0.56±0.28 vs. 0.70±0.26, P=0.001) and PCC (0.69±0.30 vs. 0.80±0.27, P=0.002). Additionally, they had a lower ICO/MCC ratio (0.45±0.28 vs. 0.60±0.32, P=0.001) and ICO/ACC ratio (0.68±0.42 vs. 0.85±0.39, P=0.001). Multiple logistic regression analysis revealed that endometriosis was associated with the ICO color score (odds ratio, 0.053; 95% confidence interval, 0.014 to 0.202; R2=0.358; P=0.001), even after adjusting for confounding factors like the presence of myomas (P=0.040) and the use of hormonal therapy (P=0.001). The results were corroborated in women with histologically confirmed endometriosis (n=71). The findings suggest a potential relationship between a stiffer ICO and endometriosis.

Barriers and facilitators to breast cancer screening among high-risk women: a qualitative study.

Women with greater than 20-25% lifetime breast cancer risk are recommended to have breast cancer screening with annual mammogram and supplemental breast MRI. However, few women follow these screening recommendations. The objective of this study was to identify barriers and facilitators of screening among women at high risk for breast cancer, guided by the Health Services Utilization Model (HSUM). Unaffected high-risk women (N=63) completed semi-structured qualitative interviews exploring their experiences with breast cancer screening. Interviews were audio recorded, transcribed verbatim, and analyzed using a combined deductive and inductive approach. Most participants (84%) had received a screening mammogram; fewer (33%) had received a screening breast MRI. Only 14% had received neither screening. In line with the HSUM, qualitative analysis identified predisposing factors, enabling factors, and need factors associated with receipt of breast cancer screening. Enabling factors - including financial burden, logistic barriers, social support, and care coordination - were most frequently discussed. Predisposing factors included knowledge, health beliefs, and self-advocacy. Need factors included healthcare provider recommendation, family history of breast cancer, and personal medical history. Although HSUM themes were consistent for both mammography and breast MRI, participants did highlight several important differences in barriers and facilitators between the two screening modalities. Barriers and enabling factors associated with supplemental screening for high-risk women represent possible intervention targets. Future research is needed to develop and test multilevel interventions targeting these factors, with the ultimate goal of increasing access to supplemental screening for high-risk women.

Antioxidant Properties of Zinc and Copper-Blood Zinc-to Copper-Ratio as a Marker of Cancer Risk BRCA1 Mutation Carriers.

Pathogenic mutations in BRCA1 (BReast CAncer gene 1) confer high risks of both breast (up to 70%) and ovarian (up to 40%) cancers. Zinc (Zn) and copper (Cu) are essential for various physiological functions, including antioxidant reactions. Their balance, reflected in the Zn/Cu ratio, plays a crucial role in maintaining redox homeostasis, which is vital for cancer prevention. This study examines the antioxidant properties of Zn and Cu, specifically focusing on the blood Zn/Cu ratio as a potential marker for cancer risk among BRCA1 mutation carriers. The study cohort consisted of 989 initially unaffected women, followed up for 7.5 years. Blood samples were analyzed using inductively coupled plasma mass spectrometry. Although individual Zn and Cu levels did not significantly correlate with overall cancer risk, those women with a Zn/Cu ratio above 6.38 experienced a significantly lower cancer risk than women with a ratio below this cut-off point. This suggests that the Zn/Cu ratio may be a valuable biomarker for cancer prevention in this high-risk group. Given the increased cancer risk in BRCA1 mutation carriers, optimizing Zn and Cu levels through dietary and active interventions could provide a preventive strategy.

O-146 Serum Progesterone levels do not differ between patients with endometriosis and unaffected patients who conceive after Hormone Replacement Therapy-Frozen Embryo Transfer (HRT-FET) cycles

Abstract Study question Do endometriosis women who achieve a live birth (LB) after Hormone Replacement Therapy-Frozen Embryo Transfer (HRT-FET) have different transfer-day progesterone levels than controls? Summary answer In women achieving a LB after HRT-FET, serum progesterone levels on the day of the transfer did not differ between endometriosis and unaffected patients. What is known already In HRT-FET, several studies have highlighted the correlation between serum progesterone levels at the time of frozen embryo transfer and LB rates. In the pathophysiology of endometriosis, progesterone resistance is typically described in the eutopic endometrium. This has led to the hypothesis that women with endometriosis may require higher progesterone levels to achieve a LB, especially in HRT-FET cycles without a corpus luteum. Study design, size, duration We conducted an observational cohort study at the university-based reproductive medicine center of our institution, focusing on women who underwent a single autologous frozen blastocyst transfer after HRT using exogenous estradiol and micronized vaginal progesterone for endometrial preparation between January 2019 and December 2021. Women were included only once during the study period. Serum progesterone levels were measured on the morning of the FET by a single laboratory. Participants/materials, setting, methods Patients were divided into groups based on whether they had endometriosis or not and whether they achieved a LB. The diagnosis of endometriosis was based on published imaging criteria (transvaginal sonography/magnetic resonance imaging) and/or confirmed histology. The primary outcome was progesterone levels on the day of the HRT-FET leading to a LB in patients with endometriosis compared to unaffected women. Subgroup analyses were performed based on the presence of deep infiltrating endometriosis or adenomyosis. Main results and the role of chance A total of 1784 patients were included. The mean age of the women was 35.1 ± 4.1 years. Five hundred and sixty women had endometriosis, while 1224 did not. 179/560 (32.0%) with endometriosis and 381/1224 (31.2%) without endometriosis achieved a LB. Among women who achieved a LB after HRT-FET, there was no significant difference in the mean progesterone level on the day of the HRT-FET between those with endometriosis and those without (13.6 ± 4.3 ng/mL versus 13.2 ± 4.4 ng/mL, respectively; p = 0.302). In the subgroup of women with deep infiltrating endometriosis (n = 142) and adenomyosis (n = 100), the mean progesterone level was 13.1 ± 4.1 ng/mL and 12.6 ± 3.7 ng/mL, respectively, with no significant difference compared to endometriosis-free patients. After adjustment for BMI, parity, duration of infertility, and tobacco use, neither the presence of endometriosis (coefficient 0.38; 95% CI -0.63 to 1.40; p = 0.457) nor the presence of adenomyosis (coefficient 0.97; 95%CI -0.24 to 2.19; p = 0.114) was associated with the progesterone level on the day of HRT-FET. Among women who did not conceive, there was no significant difference in the mean progesterone level on the day of the HRT-FET between those with endometriosis and those without (p = 0.709). Limitations, reasons for caution The primary limitation of our study is associated with its observational design. Extrapolating our results to other laboratories or different routes and/or dosages of administering progesterone also requires validation. Wider implications of the findings This study shows that patients diagnosed with endometriosis do not require higher progesterone levels on the day of a frozen blastocyst transfer to achieve a LB in hormonal replacement therapy cycles. Trial registration number NA

Perinatal depression and risk of maternal cardiovascular disease: a Swedish nationwide study.

Increasing evidence suggests that some reproductive factors/hazards are associated with a future risk of cardiovascular disease (CVD) in women. While major (non-perinatal) depression has consistently been associated with CVD, the long-term risk of CVD after perinatal depression (PND) is largely unknown. A nationwide population-based matched cohort study involving 55 539 women diagnosed with PND during 2001-14 in Sweden and 545 567 unaffected women individually matched on age and year of conception/delivery was conducted. All women were followed up to 2020. Perinatal depression and CVD were identified from Swedish national health registers. Using multivariable Cox models, hazard ratios (HR) of any and type-specific CVD according to PND were estimated. The mean age at the PND diagnosis was 30.8 [standard deviation (SD) 5.6] years. During the follow-up of up to 20 years (mean 10.4, SD 3.6), 3533 (6.4%) women with PND (expected number 2077) and 20 202 (3.7%) unaffected women developed CVD. Compared with matched unaffected women, women with PND had a 36% higher risk of developing CVD [adjusted HR = 1.36, 95% confidence interval (CI): 1.31-1.42], while compared with their sisters, women with PND had a 20% higher risk of CVD (adjusted HR = 1.20, 95% CI 1.07-1.34). The results were most pronounced in women without a history of psychiatric disorder (P for interaction < .001). The association was observed for all CVD subtypes, with the highest HR in the case of hypertensive disease (HR = 1.50, 95% CI: 1.41-1.60), ischaemic heart disease (HR = 1.37, 95% CI: 1.13-1.65), and heart failure (HR 1.36, 95% CI: 1.06-1.74). Women with PND are at higher risk of CVD in middle adulthood. Reproductive history, including PND, should be considered in CVD risk assessments of women.

Progesterone levels do not differ between patients with or without endometriosis/adenomyosis both in those who conceive after hormone replacement therapy-frozen embryo transfer cycles and those who do not.

Do women with endometriosis who achieve a live birth (LB) after HRT-frozen embryo transfer (HRT-FET) have different progesterone levels on the day of transfer compared to unaffected women? In women achieving a LB after HRT-FET, serum progesterone levels on the day of the transfer did not differ between patients with endometriosis and unaffected patients. In HRT-FET, several studies have highlighted the correlation between serum progesterone levels at the time of FET and LB rates. In the pathophysiology of endometriosis, progesterone resistance is typically described in the eutopic endometrium. This has led to the hypothesis that women with endometriosis may require higher progesterone levels to achieve a LB, especially in HRT-FET cycles without a corpus luteum. We conducted an observational cohort study at the university-based reproductive medicine center of our institution, focusing on women who underwent a single autologous frozen blastocyst transfer after HRT using exogenous estradiol and micronized vaginal progesterone for endometrial preparation between January 2019 and December 2021. Women were included only once during the study period. Serum progesterone levels were measured on the morning of the FET by a single laboratory. Patients were divided into groups based on whether they had endometriosis or not and whether they achieved a LB. The diagnosis of endometriosis was based on published imaging criteria (transvaginal sonography/magnetic resonance imaging) and/or confirmed histology. The primary outcome was progesterone levels on the day of the HRT-FET leading to a LB in patients with endometriosis compared to unaffected women. Subgroup analyses were performed based on the presence of deep infiltrating endometriosis or adenomyosis. A total of 1784 patients were included. The mean age of the women was 35.1 ± 4.1 (SD) years. Five hundred and sixty women had endometriosis, while 1224 did not. About 179/560 (32.0%) with endometriosis and 381/1224 (31.2%) without endometriosis achieved a LB. Among women who achieved a LB after HRT-FET, there was no significant difference in the mean progesterone level on the day of the HRT-FET between those with endometriosis and those without (13.6 ± 4.3 ng/ml vs 13.2 ± 4.4 ng/ml, respectively; P = 0.302). In the subgroup of women with deep infiltrating endometriosis (n = 142) and adenomyosis (n = 100), the mean progesterone level was 13.1 ± 4.1 ng/ml and 12.6 ± 3.7 ng/ml, respectively, with no significant difference compared to endometriosis-free patients. After adjusting for BMI, parity, duration of infertility, tobacco use, and geographic origin, neither the presence of endometriosis (coefficient 0.38; 95% CI: -0.63 to 1.40; P = 0.457) nor the presence of adenomyosis (coefficient 0.97; 95% CI: -0.24 to 2.19; P = 0.114) was associated with the progesterone level on the day of HRT-FET. Among women who did not conceive, there was no significant difference in the mean progesterone level on the day of the HRT-FET between those with endometriosis and those without (P = 0.709). The primary limitation of our study is associated with its observational design. Extrapolating our results to other laboratories or different routes and/or dosages of administering progesterone also requires validation. This study shows that patients diagnosed with endometriosis do not require higher progesterone levels on the day of a frozen blastocyst transfer to achieve a LB in hormonal replacement therapy cycles. None declared. N/A.

The role of stress in modulating AIPB expression and estradiol synthesis in triple-negative breast tumors.

e13146 Background: In the United States, invasive breast cancer affects 1 in 8 women during their lifetime, with over 3.8 million individuals living as survivors. Breast cancers vary, with some being hormone-responsive and categorized on the presence or absence of estrogen (ER), progesterone (PR), and HER2 receptors. While targeted therapies exist for Estrogen Receptor positive (Er+) and Progesterone Receptor positive (PR+) cancers, triple-negative breast cancer (TNBC), which lacks all three receptors, affects about 15% of patients and is unresponsive to effective molecular treatments. Only a fraction of the cases respond to chemotherapy which emphasizes a need for new prognostic markers and treatments. Aromatase is the key enzyme in converting testosterone to estradiol which plays a crucial role in tumor growth, especially after menopause. Our research lab has identified the “Aromatase Interacting Partner in Breast or AIPB, whose overexpression inhibits aromatase, leading to a reduction in estradiol levels. However, in triple-negative breast cancer, there is an increase in AIPB expression when compared to ER+/PR+/Her2- breast tumors or unaffected women. This devastating prognosis and low survival rates can contribute to a considerable amount of stress in the diagnosed patients, in turn leading to an increase in cortisol production. Our hypothesis suggests that this stress or increase in cortisol could alter AIPB production in the tumorigenic cells which could potentially lead to a decrease in estradiol synthesis. Methods: Stress stimulation was achieved in a lab setting by subjecting engineered triple-negative breast cancer cells, capable of conditional AIPB overexpression upon tetracycline addition, to a 42 °C heat shock for various durations (0,15, 30, 45 minutes). Results: Following the 45 minutes of stress, MDA-MMD-231 cells exhibited a significant reduction in estradiol levels, decreasing from 160ng/ml to 100ng/ml. MDA-MD-231 cells engineered to overexpress AIPB produced only 62ng/ml of estradiol, marking an 18.75% decrease. The introduction of doxycycline led to a further reduction in estradiol levels to 47ng/ml, which is approximately a 29.4% drop. Western blot analysis using a CT antibody revealed heightened AIPB expression in MDA-MD-231-AIPB cells when stress and doxycycline treatments were combined. Conclusions: Given the absence of aromatase in triple-negative breast cancer, our findings suggest that AIPB’s role in estradiol production is independent of aromatase, highlighting its significance in these cancer cells. The data supports the hypothesis that enhancing AIPB expression could potentially improve patient outcomes by reducing estradiol synthesis.

Mortality Risk Among Women With Premenstrual Disorders in Sweden

Premenstrual disorders (PMDs) adversely affect the quality of life of millions of women worldwide, yet research on the long-term consequences of PMDs is limited, and the risk of mortality has not been explored. To estimate the associations of PMDs with overall and cause-specific mortality. This nationwide, population-based, matched cohort study used data from population and health registers in Sweden. Participants included women of reproductive age with a first diagnosis of PMDs between January 1, 2001, and December 31, 2018. Data analysis was performed from September 2022 to April 2023. PMDs were identified through inpatient and outpatient diagnoses and drug dispensing. Dates of death and underlying causes were ascertained from the National Cause of Death Register. Conditional Cox regression was used to estimate the hazard ratios (HRs) of overall and cause-specific death (eg, death due to natural or nonnatural cause, suicide, or cardiovascular events), adjusting for age, socioeconomic status, and somatic and psychiatric comorbidities; in a separate sibling comparison, models were also adjusted for all factors that sisters share. A total of 67 748 women with clinically diagnosed PMDs and 338 740 matched unaffected women were included, for a total of 406 488 women. Women with PMDs received a diagnosis at a mean (SD) age of 35.8 (8.2) years. During a mean (SD) follow-up of 6.2 (4.6) years (range, 1-18 years), 367 deaths were observed among women with PMDs (rate, 8.4 deaths per 10 000 person-years; 95% CI, 7.6-9.3 deaths per 10 000 person-years), and 1958 deaths were observed among women without PMDs (rate, 9.1 deaths per 10 000 person-years; 95% CI, 8.7-9.6 deaths per 10 000 person-years). Compared with unaffected women, women with PMDs had increased risk of death due to nonnatural causes (HR, 1.59; 95% CI, 1.25-2.04), particularly suicide (HR, 1.92; 95% CI, 1.43-2.60), but they did not have increased risk of overall mortality (adjusted HR, 0.91; 95% CI, 0.82-1.02). Notably, women who received a diagnosis before the age of 25 years experienced higher all-cause mortality (HR, 2.51; 95% CI, 1.42-4.42) and death from both suicide (HR, 3.84; 95% CI, 1.18-12.45) and natural causes (HR, 2.59; 95% CI, 1.21-5.54). The findings of this matched cohort study suggest that women with PMDs are not at increased risk of early death overall. However, the risk was elevated among young women and for death by suicide. This supports the importance of careful follow-up for young patients and highlights the need to develop suicide prevention strategies for all women with PMDs.

Abstract PO3-08-01: Decision curve analysis to compare breast cancer risk predictions for a polygenic integrated clinical risk model with those of a gold standard

Abstract Risk-based guidelines have been developed to provide advice on options that are available to women who are at increased risk of breast cancer. We and others are focused on improving risk prediction models for general population use. For breast cancer, polygenic risk has been identified as important for risk prediction, especially when combined with clinical risk factors such as family history, anthropometric measures, breast imaging measures, and hormonal and reproductive risk factors. When comparing the performance of risk prediction models, the AUC is most often used but it focuses on performance in terms of distinguishing between affected and unaffected individuals and does not take into account differences in the specificity (true negative rate) and sensitivity (true positive rate) of the models being compared. In contrast, decision curve analysis takes sensitivity and specificity into account and enables the comparison of the net benefit of risk prediction tools at the clinical risk thresholds that are used to guide clinical management decisions. Herein, we use decision curve analysis to compare breast cancer risk prediction guidelines for BRISK and the Breast Cancer Risk Assessment Tool (BCRAT) in the UK Biobank, and for BRISK and IBIS version 7 in the Nurses’ Health Study. We evaluated the net benefit at the 5-year risk thresholds (1.67% and 3%) that are used to guide clinical management decisions around risk-reducing medication and at the remaining lifetime risk of 20% that is used to guide supplemental MRI surveillance. In the UK Biobank, BRISK showed a net benefit over BCRAT at the 5-year risk thresholds of 1.67% and 3.0%. The AUCs were 0.649 (95% CI = 0.640, 0.695) for BRISK and 0.567 (95% CI = 0.556, 0.577) for BCRAT and showed that, overall, BRISK discriminated between affected and unaffected women better than BCRAT (P &amp;lt; 0.001). In the Nurses’ Health Study, BRISK showed a net benefit over IBIS at the remaining lifetime risk threshold of 20%. The AUCs were 0.647; 95% CI = 0.627, 0.668 for BRISK and 0.571; 95% CI = 0.546, 0.595 for IBIS, a statistically significant improvement for BRISK over IBIS (P &amp;lt; 0.0001). We also looked at sensitivity, specificity, positive predictive value and negative predictive value even though these risk models are one-step removed from breast cancer diagnosis by screening/risk-reduction options. The positive predictive values are higher for the BRISK (27.1%) model compared to BCRAT (5.5%) in the UK Biobank dataset and higher for BRISK (15.4%) compared to IBISv7 (14.0%) in the Nurses’ dataset. We have shown the application of a statistical tool that can be used to directly compare risk models at clinically relevant thresholds. We have shown that BRISK, which comprises polygenic risk and clinical risk factors, shows higher net benefit at both 1.67% and 3% thresholds compared to BCRAT and at 20% remaining lifetime risk for IBIS version 7. In breast cancer risk prediction, a tool with high specificity (and therefore a necessary trade-off for low sensitivity) is preferred because we do not want to incorrectly classify women as not being at high risk and deny them the opportunity for intervention in the form of more frequent screening, alternative modes of screening or risk-reducing medication. This improvement in general population risk stratification that BRISK can provide has the potential to have a clinically significant effect on women’s health. Citation Format: Erika Spaeth, Bernard A Rosner, Gill Dite. Decision curve analysis to compare breast cancer risk predictions for a polygenic integrated clinical risk model with those of a gold standard [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-08-01.

Erratum to ‘The benefit of adding polygenic risk scores, lifestyle factors, and breast density to family history and genetic status for breast cancer risk and surveillance classification of unaffected women from germline CHEK2 c.1100delC families’ [The Breast 73 (2024) 103611]

Erratum to ‘The benefit of adding polygenic risk scores, lifestyle factors, and breast density to family history and genetic status for breast cancer risk and surveillance classification of unaffected women from germline CHEK2 c.1100delC families’ [The Breast 73 (2024) 103611]

Genital arousal and responsive desire among women with and without sexual interest/arousal disorder symptoms.

Models depicting sexual desire as responsive to sexual arousal may be particularly apt for women experiencing arousal or desire difficulties, and the degree to which arousal triggers desire may depend on the relationship context and desire target and timing-yet, these associations have not been directly tested among women with and without sexual interest/arousal disorder (SIAD). To assess the role of SIAD status and relationship satisfaction in the associations between genital arousal and 4 types of responsive desire. One hundred women (n = 27 meeting diagnostic criteria for SIAD) in romantic relationships with men viewed a sexual film (pleasurable intimate depiction of oral sex and penile-vaginal intercourse) while their genital arousal was recorded via vaginal photoplethysmography (n = 63) or thermal imaging of the labia (n = 37). Partner and solitary desire was assessed immediately before and after the film (immediate desire) and 3days later (delayed desire). Outcomes consisted of genital response (z scored by method) and associations between genital response and responsive sexual desire. The key difference between women with and without SIAD was not in their ability to experience genital arousal but in how their genital responses translated to responsive sexual desire. Women with SIAD actually exhibited greater genital arousal than unaffected women. Associations between genital arousal and desire were significant only for women with SIAD and depended on relationship satisfaction and desire type. For women with SIAD with low relationship satisfaction, higher arousal predicted lower immediate desire for a partner; for those with high relationship satisfaction, arousal was either positively related (vaginal photoplethysmography) or unrelated (thermal imaging of the labia) to immediate desire for a partner. Associations with other desire types were not significant. Patterns of genital arousal and partner-specific responsive desire among women affected with SIAD were indicative of an avoidance model in response to heightened genital arousal, unless relationship satisfaction was high; attending to genital arousal sensations could be a means of triggering sexual desire for women with SIAD who are satisfied in their relationships. This is one of the first sexual psychophysiologic studies to connect relationship factors to patterns of sexual response. The differing arousal assessment procedures and lack of official diagnosis may have attenuated results. The homogeneous sample and in-person session requirement limit generalizability. When compared with unaffected women, women affected by SIAD may exhibit stronger arousal responses with sufficiently incentivized sexual stimuli, and the connection between their genital arousal and responsive desire for their partners may be stronger and more dependent on relationship context.

Oral Microbiota of Infants in Maternal Gestational Diabetes: A Systematic Review.

Gestational diabetes mellitus (GDM) affects approximately 5-20% of pregnant women and is associated with adverse pregnancy outcomes. This review aimed to assess whether the oral microbiota of infants and their mothers with GDM had a different composition from that found in unaffected women and offspring. PubMed, Embase, Scopus, and Google Scholar were searched in December 2023 after protocol registration in the International Prospective Register of Systematic Reviews (CRD42023406505). Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal tools. Overall, 1113 articles were identified; after evaluating the full texts, 12 papers were included in the qualitative analysis. In six studies of the eight included, significant differences in microbiota between M-GDM and M-nGDM were found. In four studies, a depletion of Firmicutes and an enrichment of Proteobacteria was found in the microbiota of infants. Since all included studies were judged to have high risk of bias, a quantitative synthesis of the results was not carried out. In conclusion, although the oral microbiota of infants from mothers with GDM could be different from that of infants from mothers without GDM, there is insufficient evidence to clarify this aspect so far.

Abstract 769: Incorporating a cross-ancestry polygenic risk score into a clinical model improved breast cancer risk prediction in women with pathogenic variants

Abstract Introduction. We previously developed and validated a cross-ancestry polygenic risk score (caPRS) to predict risk of developing breast cancer (BC) in women who do not carry pathogenic variants (PVs) in BC susceptibility genes. Here we aimed to expand upon that study by integrating the caPRS with the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) model to combine the effects of genetic and clinical factors in carriers of PVs in BRCA1, BRCA2, PALB2, CHEK2 and ATM. Methods. We explored the association of caPRS among 12,525 women from the UK Biobank and the Consortium of Investigators of Modifiers of BRCA1/2. The effect size of the caPRS was evaluated separately for individuals carrying PVs in BRCA1, BRCA2, CHEK2, ATM and PALB2. We used a logistic regression model adjusted for age, first-degree BC family history (FHx) and cohort for BRCA1 and BRCA2 to examine the association of the caPRS with BC. The effect sizes were expressed as standardized odds ratios (ORs) with 95% confidence intervals (CIs). The estimated absolute risks to age 80 of developing BC were calculated for unaffected women by combining the caPRS-based risk with gene-specific clinical risk estimates from the BOADICEA model based on U.S. incidences. Results. The caPRS was significantly associated with BC risk across all PV carrier groups. Using BOADICEA alone, the estimated absolute BC risk by age 80 for an average unaffected 20-year-old female in the U.S. with an unknown FHx ranged from 23.8% for CHEK2 carriers to 79.4% for BRCA2 carriers. Integration of caPRS into BOADICEA, yielded the distribution of risk for each gene. (Table) Gene N OR per SD (95% CI) Absolute risk by BOADICEA Median absolute risk by BOADICEA + caPRS (Range) ATM 2,037 1.46 (1.25 - 1.71) 24.9% 27.1% (0.1 - 70.5) BRCA1 5,794 1.24 (1.18 - 1.31) 76.1% 75.6% (55.6 - 87.7) BRCA2 4,018 1.40 (1.31 - 1.49) 79.4% 78.7% (45.2 - 92.1) CHEK2 372 1.88 (1.41 - 2.55) 23.8% 28.2% (0.0 - 78.4) PALB2 304 1.81 (1.37 - 2.43) 53.9% 56.3% (2.9 - 90.9) Conclusions. The caPRS significantly modified BC risk for carriers of PVs and could help tailor guidelines for women with PVs, particularly in moderate penetrance genes. More data is needed to increase the precision and reach of risk assessment in diverse populations. Citation Format: Placede Tshiaba, Monika Sun, Dariusz Ratman, Jeffrey N. Weitzel, Premal Shah, Matthew Rabinowitz, Akash Kumar, Kate Im. Incorporating a cross-ancestry polygenic risk score into a clinical model improved breast cancer risk prediction in women with pathogenic variants [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 769.

Menstrual Blood Donation for Endometriosis Research: A Cross-Sectional Survey on Women’s Willingness and Potential Barriers

An anonymous online survey in French was used to assess if endometriosis patients would be as ready as unaffected women to donate their menstrual blood for biological research on endometriosis and evaluate potential barriers to such donation. It was distributed in September 2022 by social media and two mailing lists, including a French patient organization. The questionnaire assessed participant age and brief medical history (hormonal contraception, endometriosis diagnosis, type of endometriosis), menstrual experience (menstrual blood abundance, dysmenorrhea), and whether participants would donate menstrual blood. Women who self-declared with an established endometriosis diagnosis versus no endometriosis were compared. Seven hundred seventy-eight women answered the survey. Among women with menstruation (n = 568), 78% are willing to donate menstrual blood for research. Importantly, this proportion was higher in women who declared having an established endometriosis diagnosis (83%, n = 299) compared to self-declared unaffected women (68%, n = 134, p < 0.001). The previous use of a menstrual cup and dysmenorrhea were significantly associated with the willingness to donate menstrual blood, while the use of hormonal contraception was significantly associated with an unwillingness to donate. Only the previous use of the menstrual cup had a predictive value for menstrual blood donation. No significant relationship was observed between menstrual blood donation and age, heavy menstrual bleeding and in endometriosis patients, endometriosis subtypes. In conclusion, women affected or not by endometriosis are largely willing to donate their menstrual blood for research on endometriosis, dysmenorrhea is not a barrier for donation, and women who use a menstrual cup are the more likely to donate.

Body Composition and Metabolism in Adults With Molecularly Confirmed Silver-Russell Syndrome.

Low birth weight, as seen in Silver-Russell syndrome (SRS), is associated with later cardiometabolic disease. Data on long-term outcomes and adult body composition in SRS are limited. To evaluate body composition and metabolic health in adults with SRS. This was an observational study of 25 individuals with molecularly confirmed SRS, aged ≥ 18 years, from research facilities across the UK. Body composition and metabolic health were assessed at a single appointment. Individuals with SRS were compared with unaffected men and women (from the Southampton Women's Survey [SWS]). Fat mass, lean mass, bone mineral density (BMD), blood pressure, lipids, and blood glucose were measured. Twenty-five adults with SRS were included (52% female). The median age was 32.9 years (range, 22.0 to 69.7). Fat percentage was greater in the SRS group than the SWS cohort (44.1% vs 30.3%, P < .001). Fat mass index was similar (9.6 vs 7.8, P = .3). Lean mass percentage (51.8% vs 66.2%, P < .001) and lean mass index (13.5 kg/m2 vs 17.3 kg/m2, P < .001) were lower in the SRS group than the SWS cohort. BMD was lower in the SRS group than the SWS cohort (1.08 vs 1.24, P < .001; all median values). Total cholesterol was ≥ 5 mmol/L in 52.0%. Triglyceride levels were ≥ 1.7 mmol/L in 20.8%. Fasting blood glucose levels were ≥ 6.1 mmol/L in 25.0%. Hypertension was present in 33.3%. Adults with SRS have an unfavorable body composition and predisposition to cardiometabolic disease. These results support the need for a health surveillance strategy to mitigate adverse outcomes.

Perinatal depression and risk of mortality: nationwide, register based study in Sweden

ObjectiveTo determine whether women with perinatal depression are at an increased risk of death compared with women who did not develop the disorder, and compared with full sisters.DesignNationwide, register based...