Premenopausal Status Research Articles

Gender differences in the response to antipsychotic medication in patients with schizophrenia: An individual patient data meta-analysis of placebo-controlled studies

ObjectiveTo determine whether gender and menopausal status moderate the response to antipsychotic medication in patients with schizophrenia. MethodsWe analyzed data of 22 short-term placebo-controlled registration trials of antipsychotic medications, which included 5,231 patients with schizophrenia. We applied two-step individual patient data meta-regression analyses to establish the influence of gender and menopausal status on treatment response in mean difference in symptom severity and difference in response (>30% symptom reduction). Analyses were performed both with and without correction for baseline (negative) symptom severity. ResultsAntipsychotic treatment is associated with larger mean symptom reduction in women than in men with schizophrenia. The number needed to treat (NNT) for a response in women was 6.9, in men 9.4. Although, we found an age by gender effect, the gender by treatment effect was independent of premenopausal status and baseline (negative) symptom severity. ConclusionIn the treatment of schizophrenia we found evidence of a higher response to antipsychotic medication in women relative to men. We found no evidence that this effect was driven by menopausal status, or baseline (negative) symptom severity. Despite the impact of gender and age on effect size in acute antipsychotic treatment, efficacy was clinically relevant in all subgroups.

Isomer-Specific Serum Concentrations of Perfluorooctane Sulfonic Acid among U.S. Adults: Results from the National Health and Nutrition Examination Survey (NHANES) and the Study of Women's Health Across the Nation Multi-Pollutant Study (SWAN-MPS).

Electrochemical fluorination manufacture of perfluorooctane sulfonic acid (PFOS), one of the most studied per- and polyfluoroalkyl substances, produces mixtures of linear and branched isomers, but little is known about human exposure to linear or branched PFOS isomers. We examined determinants affecting isomer-specific patterns of PFOS in serum in two adult populations in the United States, the National Health and Nutrition Examination Survey (NHANES) and the Study of Women's Health Across the Nation Multi-Pollutant Study (SWAN-MPS). After adjusting for demographic variables, fish consumption (in both populations), a glomerular filtration rate above 90 mL/min/1.73 m2 (observed in NHANES; not tested in SWAN-MPS), premenopausal status (only observed in SWAN-MPS), and less consumption of processed food (observed in SWAN-MPS; not tested in NHANES) were associated with a higher proportion of linear PFOS. Non-Hispanic Black and Asian participants were likely to have a higher proportion of linear PFOS than non-Hispanic White participants in both populations. Our findings suggest that isomer-specific patterns of PFOS serum concentrations in humans vary depending on population characteristics that affect PFOS exposure and excretion. Consideration of specific PFOS isomers in future human biomonitoring and epidemiologic studies can provide useful insight to better understand PFOS exposure.

Association between nociplastic pain and premature endocrine therapy discontinuation in breast cancer patients.

At least 5years of adjuvant endocrine therapy (ET) is recommended for patients with hormone receptor-positive invasive breast cancer to reduce cancer recurrence risk. Up to half of patients prematurely discontinue ET, often due to musculoskeletal pain. Nociplastic pain is abnormal central nervous system pain processing without evidence of tissue or neuronal damage. This study aimed to evaluate the relationship between baseline nociplastic pain and ET discontinuation. This was a retrospective, single center, cohort study. Included patients were female, had stage 0-III invasive breast cancer, did not receive neoadjuvant therapy, and completed quality of life questionnaires prior to breast surgery, including Fibromyalgia Survey for nociplastic pain. Clinical data including duration of ET were abstracted from the medical record. Patient characteristics were analyzed with t-tests and Chi-squared tests, as appropriate. Univariate and multivariable regressions were performed with Cox proportional hazard models. Six hundred eighty-one patients diagnosed between 2012 and 2019 met inclusion criteria; 480 initiated ET and were included in the analysis. Of these 480 patients, 203 (42.3%) prematurely discontinued initial ET therapy. On univariate analysis, tamoxifen use (hazard ratio [HR] 0.70, p = 0.021) and premenopausal status (HR 0.73, p = 0.04) were inversely associated with ET discontinuation, while Fibromyalgia Score was positively associated (HR 1.04, p = 0.043). On multivariable analysis, baseline Fibromyalgia Score remained associated with ET discontinuation. Nociplastic pain present prior to surgery was associated with premature ET discontinuation. Fibromyalgia Score screening may be useful for evaluating ET discontinuation risk. Treatments targeting nociplastic pain may be more effective for treating ET-emergent pain.

Time to enhancement of breast lesions and normal breast parenchyma in light of menopausal status and menstrual cycle for ultrafast dynamic contrast-enhanced MRI using compressed sensing

PurposeTo assess the dependency of the Time to enhancement (TTE) of breast lesions and normal breast parenchyma from menopausal status and menstrual cycle using ultrafast compressed sensing (CS) -accelerated dynamic contrast-enhanced (DCE) MRI. MethodsThis institutional review board approved retrospective study included 89 breast cancers, 22 benign lesions and 131 normal breast parenchymal foci. A prototypical ultrafast DCE sequence obtained 30 phases with 2.9 s temporal resolution. Mean and median TTE of all breast cancers, benign lesions and normal breast parenchymal foci were assessed. we also assessed whether there were any differences in TTE regarding the menopausal status and menstrual cycle. ResultsThe TTE of breast cancer was significantly shorter than that of benign lesions and normal breast parenchymal foci in both the premenopausal status (5.8 vs. 8.7 and 8.7 s, respectively) (p = 0.0028 and < 0.0001, respectively) and postmenopausal status (5.8 vs. 11.6 and 11.6 s, respectively) (p < 0.0001 in both). The TTE of parenchymal foci in the premenopausal status was significantly shorter than that in the postmenopausal status (p = 0.0025). Although the TTE interval between cancer and parenchymal foci in premenopausal status is shorter than that in postmenopausal status, the AUCs in the pre- and postmenopausal status for differentiating breast cancer and parenchymal foci were comparable with using different cutoff TTE values. There were no differences in TTE regarding the menstrual cycle. ConclusionsThe TTE derived from ultrafast CS-accelerated DCE MRI was useful to differentiate breast cancer from benign lesions and normal breast parenchymal foci in both pre- and postmenopausal status.

Increased Fasting Plasma Glucose and Breast Cancer Risk in Sudanese Women: Association with Premenopausal Status and High Body Mass Index

Background: Female breast cancer is the most common cancer in Sudan, however little data is available about breast cancer in Sudanese. We aimed to assess whether fasting glucose and insulin levels are associated with the risk of having breast cancer in Sudanese women.Methods: This study was conducted at the National Cancer Institute – University of Gezira (NCI-UG), Sudan. A total of 174 females were enrolled, the patient group included 77 newly diagnosed untreated breast cancer women and a control group of 97 healthy women. Overnight fasting blood samples were collected to measure fasting plasma glucose and serum insulin levels. Results: The fasting plasma glucose level was significantly increased in the breast cancer patients (101.94±2.94 mg/dL) than the controls (90.75±2.02 mg/dL), p=0.002. Overweight-obese and premenopausal breast cancer patient’s subgroups revealed significant elevation of fasting glucose levels (105.35±4.06 mg/dL); (99.64±4.06 mg/dL) compared to controls (89.44±2.62 mg/dL), p=0.001; and (86.38±2.44 mg/dL), p=0.007 respectively. Only in the non-obese patients the insulin level was significantly lower (3.76±0.40 µU/ml) than in the control (6.11±1.00 µU/ml) p=0.034. The patient group was more likely to have 2.5 times higher fasting glucose level than the control (p=0.005). Moreover, the overweight-obese and premenopausal breast cancer patients subgroups were more likely to have 4.4 times and 4.5 times respectively elevated fasting blood glucose level, both with p=0.002. The non-obese breast cancer patients were tended to have 4.3 times decreased insulin level (p=0.019). Conclusion: The elevated fasting plasma glucose levels are associated with high risk of breast cancer in Sudanese women especially in the premenopausal individuals and those having BMI more than or equal to 25 kg/m2. Consequently, adjusting blood glucose level and controlling body weight by changing the lifestyle are suggested to reduce the risk of breast cancer in Sudanese women.

High-Risk pT1-2N0 Breast Cancer may Benefit from Postmastectomy Radiotherapy: A Risk Stratification Analysis Based on Nomogram

<h3>Purpose/Objective(s)</h3> Postmastectomy radiation therapy (PMRT) had heterogeneous effects on clinical outcome of patients with pT1-2N0 breast cancer. We aimed to develop nomograms for predicting locoregional recurrence-free survival (LRRFS) and disease-free survival (DFS), and to explore the potential effect of PMRT in pT1-2N0 breast cancer. <h3>Materials/Methods</h3> Clinical data were collected from 840 patients with newly diagnosed pT1-2N0 breast cancer between January 2015 and December 2018. Nomograms predicting the LRRFS and DFS rates were developed based on the risk factors identified by Cox regression analysis in patients treated with mastectomy alone (n =671). Furthermore, the effect of PMRT was indirectly investigated by comparing patients treated with mastectomy alone with those treated with breast-conserving surgery (BCS) plus radiotherapy (n =169) in different risk subgroups stratified by the nomogram scores. The optimal cut-off points were identified by X-tile software. LRRFS and DFS were evaluated using the Kaplan-Meier method, and the differences were compared using the log-rank test. Propensity score matching analysis (PSM) was performed to balance the backgrounds of patients between the mastectomy alone and BCS plus radiotherapy sets. <h3>Results</h3> After a median follow-up duration of 62 months (range, 9–79 months) and 50 months (range, 10–79 months) in the mastectomy alone and BCS plus radiotherapy sets, respectively. The 5-year LRRFS rates (97.0% vs. 97.3%, P = 0.516) and the 5-year DFS rates (92.0% vs. 92.7%, P = 0.339) were similar between the mastectomy alone and BCS plus radiotherapy sets, respectively. Multivariate Cox regression showed that larger tumor size, high grade, and hormone receptor (HR)-negative status were independent poor prognostic factors for both LRRFS and DFS (P<0.05 for all), while premenopausal status was independently associated with worse LRRFS (P=0.019). Incorporation of these factors into the constructed nomograms showed high accuracy when predicting the 5-year LRRFS and DFS rates, with concordance indexes of 0.794 (95%CI: 0.704-0.884) and 0.726 (95%CI: 0.659-0.793), respectively, after internal validation. Based on nomogram scores, patients were classified into different risk groups. After PSM in subgroups, compared with mastectomy alone, BCS plus radiotherapy significantly improved the LRRFS (84.9% vs. 96.6%, p = 0.026) and DFS (71.8% vs. 100%, p = 0.033) in the high-risk group, but not in the low-risk or intermediate-risk group (P>0.05 for all). <h3>Conclusion</h3> The constructed nomograms can not only estimate the individualized 5-year LRRFS and DFS rates among patients with pT1-2N0 breast cancer after mastectomy but can also stratify patients into different risk subgroups, and thus, they can help identify high-risk patients who are more likely to benefit from PMRT.

Can MRI Be Used as a Sole Diagnostic Modality in Determining Clinical Stage in Cervical Cancer?

The objective of this study was to compare staging by MRI to clinical staging in patients with cervical cancer and to determine the histological accuracy of staging by MRI and examination under anesthesia (EUA) in early stage disease. This was a retrospective cohort study of patients diagnosed with cervical cancer between 2010 and 2020 at the Radboud University Medical Centre, the Netherlands. Pretreatment stage (FIGO 2009) by MRI was compared with staging by EUA. Diagnostic accuracy in terms of sensitivity, specificity, positive, and negative predictive value was calculated for MRI and EUA in patients undergoing surgery (early stage disease) with histological results as a reference standard. A total of 358 patients were included in the study and MRI-based stage differed from EUA stage in 30.7%. In 12.3% this meant a discrepancy in treatment assignment between MRI and EUA. Diagnostic accuracy of MRI in terms of sensitivity and specificity for detecting early stage disease was comparable to EUA in surgical patients. Further analyses showed that premenopausal status, early stage disease and a tumor diameter of <2 cm were associated with improved comparability of MRI and EUA (98%). There is still a large discrepancy between MRI and EUA. In patients with suspected early stage disease, diagnostic accuracy of MRI is similar to EUA, especially for premenopausal women with early stage disease and a tumor diameter of <2 cm.

Breast Tissue Chemistry Measured In Vivo In Healthy Women Correlate with Breast Density and Breast Cancer Risk

Representative two-dimensional correlated spectroscopy (2D COSY) spectra of the region F2/F1: 0.00 ppm to 6.00 ppm in participants at low risk. (a) low dense tissue and premenopausal status (30 years old), (b) low dense tissue and postmenopausal (54 years old), (c) high dense tissue and premenopausal (36 years old), and (d) high dense tissue and postmenopausal (66 years old). Note the increase in intensity for cross peaks F, D, G, and G′ across categories. By Gorane Santamaría et al. (1355–1369)

Impact of margin width on local recurrence after breast conservative surgery following neoadjuvant chemotherapy

Background: The main goal of BCS after NAC is complete excision of the tumor with clear margin, however, no clear definition of what constitutes a clear margin has been proposed. An additional challenge for surgeons is the extent of resection especially in good responders to NAC. The aim of this study was to determine the impact of margin width on local recurrence after breast conservative surgery for patients who responded to neoadjuvant chemotherapy. Patients and Methods: This study is a prospective observational cohort study conducted at the National Cancer Institute, Cairo university, Egypt. The study included 75 Egyptian female breast cancer patients who responded to NAC and then assigned to BCS in the period from October 2019 till October 2020. Patients were assessed with regular appointments at the outpatient clinics up to 2 years follow up after surgery.Results: The mean age was 43.8±9.5 years and 65.3 % of patients were in the premenopausal status. All patients (75 cases) had either cT2 or cT3 disease. Clinical nodal disease (cN1-3) was found in 68 patients (90.7%). Radiologic complete response was seen in 31 patients (41.3%). Most patients (85.3%) had a least circumferential margin of more than 2 mm. Positive nodal involvement was confirmed in 22 patients (29.3%). Over 70% of patients had ypT stage 1c or 2 and over 60 % of patients had ypN stage 0. By the end of follow up, four patients developed local recurrence. The unadjusted local recurrence rate was 5.3% and cumulative local recurrence free survival of the whole studied group at 36 months was 94.6%. The least circumferential resection margin (2mm) had no impact on local recurrence free survival.Conclusion: Margin after NAC and BCS is safe according to ‘‘no ink on tumor’’ guideline and we emphasize the resection of the clipped area in cases of cCR and/or rCR, however, further studies with larger sample size and longer duration of follow up are required to mitigate the local recurrence after BCS following NAC.

Mildly elevated diastolic blood pressure increases subsequent risk of breast cancer in postmenopausal women in the Health Examinees-Gem study.

Epidemiological evidence suggests that hypertension is associated with breast cancer risk. However, previous studies disregard blood pressure components in the healthy population. We aimed to examine the relationship between systolic and diastolic blood pressure and breast cancer risk in a Korean population-based prospective cohort. A total of 73,031 women from the Health Examinees Gem Study were followed from baseline (2004 to 2013) through 2018. Systolic and diastolic blood pressure were measured by trainee physicians at baseline recruitment and then categorized based on the international guidelines for clinical hypertension. Associations between systolic and diastolic blood pressure with overall breast cancer and stratified by premenopausal and postmenopausal status were evaluated using adjusted multivariable Cox proportional hazard regression. A total of 858 breast cancer cases were recorded for a median follow-up period of 9 years. Compared with the normal DBP category (< 85 mmHg), the normal-high category was positively associated with breast cancer risk in postmenopausal women (85–89 mmHg, HR 1.73 95% CI 1.28–2.33), but not in premenopausal women (85–89 mmHg, HR 0.87 95% CI 0.56–1.35). Similar results were found when all cases of self-reported hypertension were excluded. Results for SBP did not show a significant association with breast cancer risk. The association between DBP and breast cancer suggests DBP could be an important factor in cancer prevention, especially for women after menopause. Our study provides a first detailed approach to understanding the importance of diastolic blood pressure for breast cancer prevention and warrants further investigation.

Clinical characteristics and a 2-year follow-up of unsatisfactory conventional Pap smears: a retrospective case–control study

The objective of this study was to conduct a 2-year follow-up of individuals having unsatisfactory reports of Pap smears and to analyze the contributing factors. This was a retrospective study at a medical center that performed about 5000–6000 Pap smears annually in Eastern Taiwan. Women who had unsatisfactory results due to scant cellularity between January 1, 2015–December 31, 2016, were included in this study. The control group comprised age-matched women with normal Pap smears at a 1:4 ratio, during the same period. The clinical characteristics and the 2-year outcomes were followed. Patients who were unavailable for follow-up assessments or who had insufficient clinical information were excluded. Student’s t-test and chi-square test were used for continuous and categorical variables, respectively. Statistical significance was defined as a p-value < 0.05. A total of 887 Pap smears were included. A total of 717 and 170 women had normal Pap and unsatisfactory Pap tests, respectively. After excluding women who were unavailable for follow-up, the final analysis included 248 and 67 women with normal and unsatisfactory Pap tests, respectively. The mean age was not significantly different between the two groups (49.97 ± 10.69 and 51.61 ± 11.28 years in the unsatisfactory Pap and control groups, respectively [p > 0.05]). The percentage of menopause and vaginal discharge were significantly different between the two groups. Multivariate analysis revealed that premenopausal status, increased discharge were associated with the risk of unsatisfactory Pap tests. Of the 67 women with unsatisfactory Pap tests, all tested negative for any malignancies at a 2-year follow-up assessment. Women with increased vaginal discharge and without menopause were at an increased risk of having an unsatisfactory Pap test. Our results indicate that an unsatisfactory Pap smear due to scant cellularity might not increase the risk of intraepithelial neoplasia or cancer after 2 years. Further, large-scale studies with longer follow-up periods are required.

Comprehensive characterization of immune landscape of Indian and Western triple negative breast cancers

PurposeTriple-negative breast cancer (TNBC) is a heterogeneous disease with a significant challenge to effectively manage in the clinic worldwide. Immunotherapy may be beneficial to TNBC patients if responders can be effectively identified. Here we sought to elucidate the immune landscape of TNBCs by stratifying patients into immune-specific subtypes (immunotypes) to decipher the molecular and cellular presentations and signaling events of this heterogeneous disease and associating them with their clinical outcomes and potential treatment options. Experimental DesignWe profiled 730 immune genes in 88 retrospective Indian TNBC samples using the NanoString platform, established immunotypes using non-negative matrix factorization-based machine learning approach, and validated them using Western TNBCs (n=422; public datasets). Immunotype-specific gene signatures were associated with clinicopathological features, immune cell types, biological pathways, acute/chronic inflammatory responses, and immunogenic cell death processes. Responses to different immunotherapies associated with TNBC immunotypes were assessed using cross-cancer comparison to melanoma (n=504). Tumor-infiltrating lymphocytes (TILs) and pan-macrophage spatial marker expression were evaluated. ResultsWe identified three robust transcriptome-based immunotypes in both Indian and Western TNBCs in similar proportions. Immunotype-1 tumors, mainly representing well-known claudin-low and immunomodulatory subgroups, harbored dense TIL infiltrates and T-helper-1 (Th1) response profiles associated with smaller tumors, pre-menopausal status, and a better prognosis. They displayed a cascade of events, including acute inflammation, damage-associated molecular patterns, T-cell receptor-related and chemokine-specific signaling, antigen presentation, and viral-mimicry pathways. On the other hand, immunotype-2 was enriched for Th2/Th17 responses, CD4+ regulatory cells, basal-like/mesenchymal immunotypes, and an intermediate prognosis. In contrast to the two T-cell enriched immunotypes, immunotype-3 patients expressed innate immune genes/proteins, including those representing myeloid infiltrations (validated by spatial immunohistochemistry), and had poor survival. Remarkably, a cross-cancer comparison analysis revealed the association of immunotype-1 with responses to anti-PD-L1 and MAGEA3 immunotherapies. ConclusionOverall, the TNBC immunotypes identified in TNBCs reveal different prognoses, immune infiltrations, signaling, acute/chronic inflammation leading to immunogenic cell death of cancer cells, and potentially distinct responses to immunotherapies. The overlap in immune characteristics in Indian and Western TNBCs suggests similar efficiency of immunotherapy in both populations if strategies to select patients according to immunotypes can be further optimized and implemented.

Sexual Pain Symptoms in Premenopausal Women with Vulvar Lichen Sclerosus

ABSTRACT Introduction Lichen sclerosus (LS) is a chronic, inflammatory skin condition that primarily affects the anogenital epithelium in women. Vulvar LS has historically been regarded as a condition of premenarchal girls and postmenopausal women, overlooking women of reproductive age. Although vulvar LS characteristically presents with pruritis, specialists in LS have clinically observed that premenopausal women often present with dyspareunia related to introital tearing and vulvar skin changes. Objective This study aims to characterize the clinical presentation of vulvar LS among premenopausal women related to sexual pain. Methods A cross-sectional web-based study was conducted in premenopausal women with biopsy-confirmed vulvar LS between the ages of 18-50 years. Participants completed a 28-question survey evaluating characteristics of symptoms, as well as timing and accuracy of diagnosis. Numerical data were expressed as mean +/- standard deviation. Bivariate Pearson correlation was used to determine the relationship between age of symptom onset and time interval to diagnosis. Results Of the 956 responses received, 503 met inclusion criteria of biopsy confirmed LS and premenopausal status. Self-reported ethnicity of the study population was 87% White, 4% Latina or Hispanic, 2% Asian, and 1% Black. The mean age of the population was 37 years, ranging from 19-50 years. There was a 4-year delay in diagnosis, with an average age of symptom onset of 27 years and average age of diagnosis of 32 years. There was an inverse correlation between the age at which symptoms began and the time interval to diagnosis with a Pearson correlation coefficient of -0.487 (t(455)=14.184, p&amp;lt;.0001). Most prevalent symptoms were dyspareunia (68%), tearing with intercourse or vaginal insertion (63%), and decreased clitoral sensation (35%). Symptoms reported as most affecting the individual were dyspareunia (44%), tearing with intercourse or vaginal insertion (39%) and pruritis (25%), followed by decreased clitoral sensation (13%). Symptoms that most frequently prompted patients to seek medical attention were dyspareunia (35%), pruritus (31%), and tearing with intercourse or vaginal insertion (26%). Only 4% of respondents reported that decreased clitoral sensation prompted medical attention. Most prevalent skin changes included hypopigmentation (81%), vulvar fissures (72%), labial resorption (60%), clitoral phimosis (39%), and vaginal stenosis (37%), with vulvar fissures affecting the individual the most (48%) and prompting medical attention (39%). Sixty-six percent of respondents initially received an alternative diagnosis, most commonly vulvovaginal yeast infection (49%). Conclusions Vulvar LS affects premenopausal women and often causes skin changes related to sexual function. This condition is often misdiagnosed as vulvovaginal candidiasis, leading to a delay in diagnosis of 4 years, which is consistent with existing literature. LS symptoms in premenopausal women related to sexual function and pain include dyspareunia, tearing with intercourse or vaginal insertion, and decreased clitoral sensation. These symptoms may be more concerning to premenopausal women, who are more likely to be sexually active, than the classic symptoms of vulvar pruritis found predominantly in postmenopausal women. Vulvar LS should be considered and evaluated in women of all ages presenting with vulvar symptoms and sexual pain. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Consultant for Good Clean Love and Mahana Therapeutics; Part-time employee of Dare Bioscience, has received research funding from Dare Science, SST, Endoceutics, The Cellular Medicine Association, and Ipsen for other projects, and is a consultant for Ipsen, SST, and AMAG

Edmonton Symptom Assessment Scale may reduce medical visits in patients undergoing chemotherapy for breast cancer.

BACKGROUNDAdjuvant chemotherapy is recommended in high-risk breast cancer. However, no universally accepted guidelines exist on pre-chemotherapy assessment. In particular, the number and frequency of medical visits vary according to each institution’s policy. We hypothesised that the Edmonton Symptom Assessment Scale (ESAS) may have a favourable impact on the pre-treatment assessment in candidates for adjuvant chemotherapy.AIMTo investigate whether the ESAS can be used to safely reduce the number of medical visits in women with breast cancer undergoing adjuvant chemotherapy.METHODSIn a retrospectively prospective matched-pair analysis, 100 patients who completed the ESAS questionnaire before administration of adjuvant chemotherapy (ESAS Group) were compared with 100 patients who underwent chemotherapy according to the traditional modality, without ESAS (no-ESAS Group). Patients of the ESAS Group received additional visits before treatment if their ESAS score was > 3. The primary endpoint was the total number of medical visits during the entire duration of the chemotherapy period. The secondary endpoints were the occurrence of severe complications (grade 3-4) and the number of unplanned visits during the chemotherapy period.RESULTSThe study variables did not statistically differ between patients of the ESAS Group and no-ESAS Group (age P = 0.880; breast cancer stage P = 0.56; cancer histology P = 0.415; tumour size P = 0.258; lymph node status P = 0.883; immunohistochemical classification P = 0.754; type of surgery P = 0.157), except for premenopausal status (P = 0.015). The study variables did not statistically differ between patients of the ESAS Group and no-ESAS Group regarding age, cancer stage, histology, tumour size, lymph node status, immunohistochemical classification, and type of surgery. Unplanned visits during the entire duration of chemotherapy were 8 in the ESAS Group and 18 in the no-ESAS Group visits (P = 0.035). Grade 3-4 toxicity did not differ between the study groups (P = 0.652). Forty-eight patients of the ESAS Group received additional visits due to an ESAS score > 3. The mean number of medical visits was 4.38 ± 0.51 in the ESAS Group and 16.18 ± 1.82 in the no-ESAS group (P < 0.001). With multivariate analysis, women of the ESAS group were more likely to undergo additional visits for an ESAS score > 3 if they were aged 60 or older, received a mastectomy, or had tumour stage II/III.CONCLUSIONThe ESAS score may safely reduce the number of medical visits in candidates for adjuvant chemotherapy for early breast cancer. Our results suggest that the ESAS score may be used for selecting a group of breast cancer patients for whom it is safe to reduce the number of medical visits in the setting of adjuvant chemotherapy. This may translate into several advantages, such as a more rational utilization of human resources and a possible reduction of coronavirus pandemic infection risk in oncologic patients.

A Study to Evaluate Risk of Ovarian Malignancy Algorithm (ROMA) in Patients with Ovarian Masses

Abstract Objective The aim of this study was to evaluate risk of ovarian malignancy algorithm (ROMA) in premenopausal patients with ovarian masses. Materials and Methods A mixed observational study was conducted in the Department of Obstetrics and Gynecology at Lilavati Hospital and Research Centre, Mumbai, from the month of June 2017 to March 2018. In this study, premenopausal females with ovarian masses, satisfying the inclusion criteria, were evaluated for the purpose of preoperative analysis. Results In premenopausal females, ROMA less than 11.4% is normal and more than or equal to 1.4% is increased. Considering histopathology reports as the gold standard, significant association was present between ROMA score and premenopausal status. Conclusion ROMA includes two recognized markers that are being used in the current scenario for the purpose of preoperative risk assessment of ovarian cancer, cancer antigen 125 (CA125), and human epididymis protein 4 (HE4). CA125 has been shown to be elevated in most ovarian cancer cells but has a low specificity for ovarian malignancies. HE4 is a recently developed biomarker that is elevated in ovarian cancers, as well as few other cancers, and has been shown to have higher specificity than CA125. Combining CA125 and HE4 provides a relatively more accurate prediction of malignancy than either test alone. ROMA culminates the benefits of the combined CA125 and HE4 biomarkers along with menopausal status to help assign a numeric risk stratification of malignancy in cases of ovarian tumors.

Patient, disease and surgeon predictors of successful bilateral sentinel lymph node mapping for endometrial cancer: A retrospective, multicenter analysis

Objective: Sentinel lymph node mapping is an acceptable standard for lymph node evaluation in patients with endometrial cancer. The purpose of this study was to evaluate the adoption of this technique at two academic institutions, including which patient and disease features are associated with rates of successfully identifying sentinel lymph nodes with fluorescent mapping. In addition, we sought to characterize if and how surgeons experience the technique related to successful bilateral sentinel lymph node mapping. Methods: A retrospective chart review was performed of patients at two academic institutions who underwent sentinel lymph node mapping prior to a minimally invasive hysterectomy for endometrial cancer over the first 30 months during which the technique was adopted at each institution. A modified Poisson regression model was used to determine the relationships between patient, disease, and surgeon factors on outcomes of sentinel lymph node mapping. Results: A total of 460 charts were reviewed. The mean age was 64 and the median body mass index was 34.2. The most disease was stage I (83%), endometrioid (89%), and Grade I (64%). The bilateral sentinel lymph node mapping success rate was 65%, while unilateral or bilateral success occurred in 91% of cases. Sentinel lymph node mapping was significantly more likely to be successful in premenopausal women (RR 1.25; 95% CI 1.07 - 1.46; p = 0.005) and Asian women (RR 1.48; 95% CI 1.3-1.68; p &lt; 0.001). BMI was not significantly predictive of mapping success (RR 1.03; 95% CI 1.00 - 1.07; p = 0.05). Increasing surgeon experience with the technique did predict successful bilateral sentinel lymph node mapping (RR 1.02; 95% CI 1.00 - 1.03; p = 0.02). Conclusion: Premenopausal status and surgeon experience with the technique increases the likelihood of bilateral sentinel lymph node detection for endometrial cancer.

Increased morbidity evaluated on hospital contacts and prescriptions among 100,834 Danish breast cancer survivors.

Cardiovascular disease competes with breast cancer (BC) as the leading cause of death for females diagnosed with breast cancer. Not much is known concerning morbidity and medicine use in the short and long term after a BC diagnosis. The aim of this study was to determine acute and long-term morbidity in Danish women treated for BC. A nationwide registry-based cohort study of 100,834 BC patients identified in the clinical database of Danish Breast Cancer Cooperative Group (DBCG) and 1,100,320 (10 per patient) age-matched Danish women without BC, serving as controls. Morbidity was studied using complete data on hospital contacts and medicinal use. The risk of hospital contacts was significantly increased in BC survivors compared with controls evaluated both by means of Cox regression and negative binomial regression analysis both during and after cessation of breast cancer treatment. Young age at breast cancer diagnosis was associated with the most pronounced increase in risk of hospital contacts, both during and after cessation of BC treatment. Medicinal use was significantly increased among BC patients compared to controls, both during (HR 1.27 (1.26-1.28), p < 0.0001) and after BC treatment (HR 1.18 (1.17-1.19), p < 0.0001, and present for all subgroups of medicine. Overall, BC survivors have a pronounced increase in hospital contacts and medicinal use compared to women without BC. Premenopausal status at BC diagnosis was associated with an overall higher excess morbidity and a higher burden both during and after treatment.

Per- and polyfluoroalkyl substances exposure and bone mineral density in the U.S. population from NHANES 2005-2014.

Environmental exposures such as perfluoroalkyl substances (PFASs) were considered potential risks for bone mineral density (BMD). To examine the associations between PFASs and BMD among the U.S. population. This study included a total of 6416 participants from the National Health and Nutrition Examination Survey (NHANES 2005-2014). Multiple linear regression models were used to analyze the associations between serum PFASs and BMD and the coefficient β with 95% confidence intervals (95% CI) was calculated as the effect estimate. Covariates such as age, race, BMI, smoking, alcohol intake, milk intake, and physical activity were adjusted in these models. Additionally, gender and menopausal period were considered in further subgroup analyses. Based on the combined data of NHANES 2005-2014, the effects from exposure to PFASs on BMD were found with gender and menopausal status differences. Positive associations were found in PFOA (β = 0.010; 95% CI: 0.003, 0.016), PFHxS (β = 0.007; 95% CI: 0.003, 0.012), and PFNA (β = 0.001; 95% CI: 0.001, 0.017) in total population. Negative associations for PFOA (β = -0.020; 95% CI: -0.029, -0.012), PFOS (β = -0.011; 95% CI: -0.028, -0.011), PFHxS (β = -0.019; 95% CI: -0.025, -0.013), PFDE (β = -0.010; 95% CI: -0.016, -0.005), and PFNA (β = -0.011; 95% CI: -0.021, -0.002) were found in women, while no significant association was found in men. In further subgroup analyses, women in pre-menopause status showed consistent negative associations. PFASs exposure may be associated with BMD and gender and menopausal status confound the associations.

Female reproductive status and exogenous sex hormone use in rheumatoid arthritis patients treated with tocilizumab and csDMARDs.

Sex is well known to influence risk, severity and treatment outcomes of RA, although the underlying causes are uncertain. The aim of this research was to examine whether factors influencing female sex hormones (reproductive status and exogenous sex hormone use) are associated with the efficacy of DMARDs. Individual participant data were pooled from five phase 3 clinical trials where RA patients were treated with tocilizumab and/or conventional synthetic DMARDs. The primary outcome was the time to first remission according to the Simplified Disease Activity Index. The relationship between menopausal status or use of exogenous sex hormones and the time of first remission was assessed via Cox proportional analysis. Analysed data included sex, baseline menopausal status (premenopausal, perimenopausal, early postmenopausal and postmenopausal), participant age, body mass index, race, number of previous DMARDs and baseline disease activity. Analysis included 4474 female patients, of whom 2817 (62.9%) were postmenopausal, 202 (4.5%) were early postmenopausal, 1021 (22.8%) were premenopausal and 414 (9.2%) were perimenopausal. Of these, 221 (7.8%), 13 (6.4%), 255 (25%) and 47 (11.4%), respectively, were taking exogenous sex hormones. In the pooled analysis, perimenopausal status was associated with reduced remission compared with premenopausal status [adjusted HR 0.78 (95% CI 0.61, 0.99)]. Sex hormone use was associated with significantly higher remission [adjusted HR 1.20 (95% CI 1.01, 1.43)]. Perimenopausal women were less likely to achieve remission compared with premenopausal RA patients. The use of exogenous sex hormones appeared to be associated with more frequent remission in female RA patients, particularly those who were perimenopausal and early postmenopausal, although further research is required to confirm and identify the drivers for this observation and how it interacts with menopausal status.

Abstract 2696: Catechol estrogen profiles of patients with EGFR- and ALK-positive non-small cell lung cancer (NSCLC)

Abstract Prior research from this group indicates that the human lung extensively metabolizes parent estrogens to reactive catechols. Estrone (E1) and estradiol (E2) are converted to the putative carcinogens, 4-hydroxyestrone (4-OHE1) and 4-hydroxyestradiol (4-OHE2), by cytochrome P450 1B1 (CYP1B1). In contrast, CYP1A1 metabolizes parent estrogens to 2-OHE1 and 2-OHE2, which may ultimately be converted to anti-proliferative derivatives. Our previous data strongly indicate that 4-OHEs contribute to lung tumorigenesis. However, their role in oncogene-driven NSCLC has not been investigated. The goal of this study was to compare the urinary profile of catechol estrogens in patients with EGFR- and ALK-positive NSCLC with those of cancer-free controls. The resulting levels of estrogen derivatives were correlated with genotypic variants in the estrogen metabolizing enzymes CYP1B1 and COMT. Patients with EGFR- and ALK-mutated NSCLC were recruited from the recently established Never-Smokers Lung Cancer Clinic at our institution. Study participants were 50 years of age or older to circumvent any confounding impact of pre-menopausal status on estrogen profiles. Mutation status was determined from tumor tissue biopsies. Cancer-free control subjects were Caucasian post-menopausal women with no prior smoking history. To date, 34 patients with tumors possessing EGFR mutations, 10 patients with ALK mutations, and 17 cancer-free control subjects have been enrolled. Urine specimens were collected from all participants and urinary estrogen species (E1, E2, E3, 4-OHE1, 4-OHE2, 2-OHE1, 2-OHE2, 16α-OHE1, 2-OME1, 4-OME1, OME2) were quantified using a newly established UPLC-MS/MS method. Blood lymphocytes, collected from NSCLC subjects, were genotyped for SNPs in CYP1B1 (L432V/rs1056836, R48G/rs10012, N453S/rs1800440) and COMT (V158M/rs4680) by real-time PCR. Preliminary investigation of the E1 metabolic pathway suggests a trend of higher ratios of 4-OHE1 to 2-OHE1 in patients with EGFR- and ALK-positive NSCLC as compared to cancer-free controls. Among NSCLC subjects, those possessing the high activity Leu432 variant of CYP1B1 (Leu/Leu + Leu/Val) tended to have higher ratios of 4-OHE1 to 2-OHE1 as compared to patients with the low activity Val/Val genotype. Early findings suggest enhanced production of C4 estrogen derivates may contribute to the development of oncogene-driven lung tumors. Targeting CYP1B1 may be of preventive and therapeutic interest. Recruitment of study participants is ongoing to validate these early findings in a larger cohort. (Supported by an In Vino Vita Award from Fox Chase Cancer Center) Citation Format: J. Nicholas Bodor, Joseph Treat, Daniel D. Krzizike, Carolyn L. Zawislak, Lisa Vanderveer, Sarah Eidbo, Eric A. Ross, Martin J. Edelman, Andrew J. Andrews, Margie L. Clapper. Catechol estrogen profiles of patients with EGFR- and ALK-positive non-small cell lung cancer (NSCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2696.