Hormone Therapy Group Research Articles

Abstract P5-13-13: PIK3CA mutations co-occurring with copy number gain identify patients with adverse outcome and potentially different treatment sensitivity among hormone receptor positive and HER2 negative metastatic breast cancer

Abstract INTRODUCTION: Somatic mutations of the PIK3CA gene, encoding for the class IA PI3K p110α subunit, are the most common activating mutations in breast cancer (BC), occurring in 30-50% of early and in 28% of metastatic ER+/HER2- disease. We have previously demonstrated that PIK3CA mutations co-occurring with copy number (CN) gain (PIK3CA-mut/gain) are associated with worse outcome in patients with early hormone receptor positive and HER2 negative (HR+/HER2-) BC, including those receiving endocrine therapy (ET). Here we aim to evaluate the prognostic role of PIK3CA-mut/gain in patients with metastatic HR+/HER2- BC treated with chemotherapy, ET alone or in combination with targeted therapies (CDK4/6 inhibitors or everolimus) included in a publicly available dataset of BC. PATIENTS AND METHODS: We accessed genomic, clinical, treatment and outcome data from 1365 patients with HR+/HER2- BC included in the MSK-2018 dataset. Patients treated for distant metastases were selected. PIK3CA status, considering both protein-affecting mutations and CN alterations, was derived from pre-treatment biopsies data. Tumors were classified as: PIK3CA wt and CN neutral (-wt/neut), PIK3CA wt with CN gain (-wt/gain), PIK3CA mutant and CN neutral (-mut/neut), and PIK3CA mutant with CN gain (-mut/gain). Tumors with PIK3CA loss were excluded from the analyses. For each patient and treatment type, only progression free survival (PFS) from the first available line of treatment was analyzed, thus excluding data concerning possible retreatments with the same drug in subsequent lines. Multivariate Cox proportional hazard models were used to assess the association between PIK3CA status and PFS including treatment line and the four categories of PIK3CA as co-variates. RESULTS: The proportion of PIK3CA-mut/gain was 15.4% in the chemotherapy group (n=454), 17.3% in the ET alone group (n= 352), 13.4% in the ET plus CDK4/6 inhibitors group (n= 268) and 10.5% in the ET plus everolimus group (n= 143). As expected, in all groups treatment line was significantly and independently associated with PFS. In the ET alone group, patients whose tumors had gain in PIK3CA CN, with or without co-occurring mutations, were at significantly higher risk of progression compared with PIK3CA-wt/neut (HR 2.2 [1.53-3.2] p<0.001 for PIK3CA -mut/gain; HR 1.5 [1.03-2.2] p= 0.034 for PIK3CA-wt/gain), while PIK3CA-mut/neut status was not significantly associated with progression (HR 1.2 [0.87 − 1.6] p= 0.289). Similar observations, without reaching statistical significance, were also made in the CDK4/6 inhibitors group (HR 1.6 [0.92-2.6] p= 0.099 for PIK3CA-mut/gain; HR 1.6 [0.97-2.5] p= 0.068 for PIK3CA-wt/gain) and in the chemotherapy group (HR 1.4 [0.98-2] p= 0.063 for PIK3CA-mut/gain; 1.2 [0.89-1.6] p= 0.223 for PIK3CA-wt/gain). On the other hand, in patients treated with ET plus everolimus, while there was a borderline significant increased risk of progression for patients with PIK3CA-wt/gain tumors (HR 1.8 [1.00 − 3.3] p= 0.051) and for those with PIK3CA-mut/neut (HR 1.6 [0.98-2.5) p= 0.06), this was not observed in patients with PIK3CA-mut/gain tumors (HR 1.1 [0.5-2.2] p=0.89), potentially suggesting a treatment benefit. CONCLUSIONS: Our data suggest that patients with metastatic HR+/HER2- BC with tumors with PIK3CA-mut/gain have poor outcome. These data are in line with our previous report in patients with early BC. Further studies are warranted to understand if patients with PIK3CA-mut/gain tumors might benefit from the combination of ET and everolimus. Citation Format: Ilenia Migliaccio, Marta Paoli, Emanuela Risi, Chiara Biagioni, Laura Biganzoli, Matteo Benelli, Luca Malorni. PIK3CA mutations co-occurring with copy number gain identify patients with adverse outcome and potentially different treatment sensitivity among hormone receptor positive and HER2 negative metastatic breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-13-13.

Abstract P1-16-06: In real world, a high percentage of premenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer receive chemotherapy as first-line treatment: A study of the National Cancer Center, China

Abstract Background: In this study, we aimed to observe initial palliative treatment choices and clinical outcomes for premenopausal hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer patients (MBC) in the Chinese population in real life.Methods: The China National Cancer Center database was used to identify 2194 MBC patients diagnosed between 2004 to 2015. Premenopausal patients with HR+ HER2- MBC were included. Clinicopathological features, initial palliative treatment choices and survival information were extracted. First-line progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method and compared using the log-rank test. Prognostic factors associated with OS were analyzed using Cox regression model with 95% confidence interval (95%C.I.).Results: A total of 451 premenopausal patients meeting study criteria were identified. Median age was 44 years. The number of patients receiving chemotherapy alone, endocrine therapy and chemotherapy followed by endocrine therapy as initial palliative treatment strategy were 222(49.2%), 80 (17.7%), and 149 (33.0%), respectively. Patients receiving initial chemotherapy were more likely to be luminal B subtype, had more de novo stage IV disease than recurrent disease and had more liver metastasis, compared with patients receiving initial endocrine therapy. Both PFS and OS were significantly longer for chemotherapy-endocrine therapy group (median PFS 18.9 months and OS 75.0 months), than for endocrine therapy group (median PFS 11.7 months and OS 53.5 months). Chemotherapy alone group presented with worst survival outcomes (median PFS 7.1 months and OS 43.9 months). However, in multivariate analysis, none of the three treatment strategies were independently associated with PFS or OS.Conclusions: In real world, a high percentage of premenopausal patients with HR+ HER2- disease received chemotherapy as initial palliative treatment in China, which was not associated with worsened survival. This unexpected guideline non-adherence reflects the unmet need of establishing treatment guidelines specifically for premenopausal patients in the Chinese population. Further studies with larger sample size across China are needed to explore the relationship between this guideline non-adherence and clinical outcomes. Citation Format: Yiqun Li, Hongnan Mo, Xiuwen Guan, Shaoyan Lin, Zijing Wang, Yimeng Chen, Shanshan Chen, Qiao Li, Ruigang Cai, Jiayu Wang, Yang Luo, Ying Fan, Peng Yuan, Pin Zhang, Qing Li, Fei Ma, Binghe Xu. In real world, a high percentage of premenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer receive chemotherapy as first-line treatment: A study of the National Cancer Center, China [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-16-06.

Impacts of Neoadjuvant Hormonal Therapy Prior to Robot-Assisted Radical Prostatectomy on Postoperative Hormonal- and Sexual-Related Quality of Life - Assessment by Patient-Reported Questionnaire.

PurposeNeoadjuvant hormonal therapy (HT) before radical prostatectomy (RP) is not recommended by current guidelines in terms of oncological outcomes. Despite this, neoadjuvant HT is sometimes conducted before RP for a small proportion of patients in clinical practice. This study evaluated the impacts of neoadjuvant HT on hormonal- and sexual-related quality of life (QOL) among patients who underwent robot-assisted RP (RARP).Materials and MethodsParticipants comprised 470 patients divided into a non-neoadjuvant HT group (n = 408) and a neoadjuvant HT group (n = 62). Hormonal- and sexual-related QOL were measured using the Expanded Prostate Cancer Index Composite (EPIC) questionnaire.ResultsHormonal summary scores at 6 and 9 months, function scores before and 3, 6, and 9 months and bother score at 6 months after RARP were significantly lower in the neoadjuvant HT group than in the non-neoadjuvant HT group. Sexual function scores were decreased in the neoadjuvant HT group compared to the non-neoadjuvant HT group before and 6 months after RARP. In the neoadjuvant HT group, sexual function at 3 months after RARP was significantly worse in patients with >5 months of neoadjuvant HT than in patients with ≤5 months of neoadjuvant HT. Conversely, sexual bother at 3 months after RARP was significantly worse in patients with ≤5 months of neoadjuvant HT than in patients with >5 months of neoadjuvant HT.ConclusionVintage neoadjuvant HT prior to RARP should not be recommended due to not only oncological outcomes, but also the impacts on postoperative hormonal- and sexual-related QOL.

Safety of adjuvant CDK4/6 inhibitors during the COVID-19 pandemic.

Safety of adjuvant CDK4/6 inhibitors during the COVID-19 pandemic.

Comparison of the Efficacy between First-Line Treatment Regimens for Patients with Hormone Receptor-Positive and HER2-Negative Metastatic Breast Cancer

Purpose: Endocrine therapy is the first-line treatment recommended for patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer without visceral crisis. However, this recommendation has not been followed clinically because of efficacy issues. In this study, the survival of patients with HR-positive/HER2-negative metastatic breast cancer was evaluated based on the following first-line treatment regimens: the combination of palbociclib plus letrozole, conventional endocrine therapy, or chemotherapy.Methods: Medical records were reviewed for this retrospective analysis. Patients with HR-positive/HER2-negative metastatic breast cancer were included. Progression-free survival (PFS) and overall survival (OS) were compared based on first-line treatment regimens.Results: A total of 184 patients were included in the analysis. The first-line treatments were palbociclib plus letrozole in 46 patients (25.0%), endocrine therapy in 40 patients (21.7%), and chemotherapy in 98 patients (53.3%). The PFS of the palbociclib plus letrozole group was significantly longer than that of the endocrine therapy (hazard ratio=3.43, p<0.001) and chemotherapy (hazard ratio=2.88, p=0.001) groups. No significant difference was observed between the endocrine therapy and chemotherapy groups (p=0.430). The OS of the palbociclib plus letrozole group was significantly longer than that of the endocrine therapy (hazard ratio=5.34, p=0.009) and chemotherapy (hazard ratio 4.23, p=0.043) groups. No significant difference was observed between the endocrine therapy and chemotherapy groups (p=0.451).Conclusion: The combination regimen of palbociclib and letrozole could be recommended as the first-line treatment of choice in patients with HR-positive/HER2-negative metastatic breast cancer.

Real world initial palliative treatment patterns and clinical outcomes in premenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer: A study of the National Cancer Center, China

BackgroundTo observe whether guideline non-adherence in initial palliative treatment choices for premenopausal hormone receptor-positive (HR+), HER2-negative metastatic breast cancer (MBC) patients result in worse clinical outcomes in the Chinese population. MethodsThe China National Cancer Center database was used to identify 2194 patients diagnosed between 2004 and 2015. A total of 451 premenopausal patients with HR + HER2- MBC were included. Clinicopathological features and survival information were extracted. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method and compared using log-rank test. ResultsThe number of patients receiving initial chemotherapy, endocrine therapy and chemo-endocrine therapy were 222 (49.2%), 80 (17.7%), and 149 (33.0%), respectively. Patients receiving initial chemotherapy were more likely to be luminal B subtype, had more de novo stage IV disease and more liver metastasis, compared with patients receiving initial endocrine therapy. Both PFS and OS were significantly longer for chemo-endocrine therapy group (median PFS 18.9 months and OS 75.0 months), than for endocrine therapy group (median PFS 11.7 months and OS 53.5 months), and chemotherapy group (median PFS 7.1 months and OS 43.9 months). In multivariate analysis, none of the three treatment strategies were independently associated with PFS or OS. ConclusionIn real world, a high percentage of premenopausal patients with HR + HER2- disease received chemotherapy as initial palliative treatment in China, which was not associated with worsened survival. Further studies with larger sample size across China are needed to explore the relationship between this guideline non-adherence and clinical outcomes.

Association of Second-generation Antiandrogens With Depression Among Patients With Prostate Cancer

Previous studies have shown a consistent association between hormone therapy (HT), such as androgen deprivation therapy, to treat prostate cancer and depression risk. However, the association between second-generation antiandrogens (AAs) and depression is unknown. To test the a priori hypothesis that second-generation AAs are associated with an increased risk of depression, including compared with traditional forms of HT. This retrospective cohort study analyzed patients aged 66 years and older who were diagnosed with prostate cancer without a second cancer in 12 months from January 2011 to December 2015. Patients with continuous Medicare Parts A, B, and D coverage were included. Individuals who received any form of HT prior to prostate cancer diagnosis and those previously diagnosed with depression were excluded. Data were collected from the Surveillance, Epidemiology, and End Results-Medicare and Texas Cancer Registry-Medicare linked databases. Data were analyzed from February to May 2021. The following treatment groups were compared: (1) no HT group, (2) traditional HT group (HT without second-generation AA exposure), and (3) second-generation AA group. Risk of depression in the second-generation AA group compared with the no HT and traditional HT groups, determined prior to data collection, stratified by diagnosis stage. Of 210 804 patients diagnosed with prostate cancer during the study window, 30 069 men (11 484 [38%] aged 66-70 years; 22 594 [75%] White) who met inclusion criteria were identified. Overall, 17 710 (59%) received no HT, 11 311 (38%) received traditional HT only, and 1048 (3%) received a second-generation AA. Those receiving a second-generation AA were more likely to be older (aged ≥81 years: second-generation AA group, 246 [24%]; traditional HT group, 1997 [18%]; no HT group, 1173 [7%]) and present with advanced disease (eg, distant disease: second-generation AA group, 562 [24%]; traditional HT group, 876 [8%]; no HT group, 129 [0.7%]). Multivariable Cox proportional hazards analysis showed that the second-generation AA group had an increased risk of depression compared with the no HT group (hazard ratio [HR], 2.15; 95% CI, 1.79-2.59; P < .001) and the traditional HT group (HR, 2.26; 95% CI, 1.88-2.73; P < .001), including specifically among those with metastatic disease at diagnosis (HR, 2.40; 95% CI, 1.38-4.15; P = .002). In this cohort study, patients with prostate cancer who received a second-generation AA had a large and clinically significant increased risk of depression compared with patients who received traditional HT alone or no HT, including when limiting our analysis to individuals with metastatic disease at diagnosis.

Self‐reported history of estrogen hormone therapy differentiates rates of amyloid accumulation (PiB‐PET) relative to males: Findings from the Harvard Aging Brain Study

AbstractBackgroundWomen’s Health Initiative Memory Study (WHIMS) findings suggest that hormone therapy increases risk of dementia. Conversely, evidence from the Kronos Early Estrogen Prevention Study (KEEPS) implicates estrogen hormone therapy (HT) as protective against ß‐amyloid (Aß) burden. We sought to explore if self‐reported HT use is associated with rates of Aß accumulation in an observational sample of clinically‐unimpaired older adults.Method134 participants (Age=73yrs±5.8) underwent at least three timepoints of Pittsburgh compound‐B (PiB)‐PET scans over an average of 9.7 years. Longitudinal PiB‐PET was examined as aggregate neocortical DVR (composite reference region: whole cerebellum + eroded white matter). Concurrent with baseline PiB‐PET, female participants self‐reported if they ever took HT. Participants were thus identified as: females who never used HT (HT‐:n=36), females who have ever taken HT to any extent (HT+:n=42), and males (M:n=56). We examined the relationship between these three groups and longitudinal PiB‐PET using linear mixed models, adjusting for baseline age, and with random slopes and intercepts. Post‐hoc analyses adjusted for APOEε4 status and examined interactions between HT and baseline PiB‐PET on change in PiB‐PET from baseline.ResultWhile we found no significant sex (male/female) difference in PiB‐PET accumulation (t=1.5,p&gt;0.05,Fig 1A), we observed significant HT group differences with HT‐ exhibiting approximately half the PiB‐PET rate of change than M (t=2.3,p=0.02) and HT+ (t=1.8,p=0.07; Fig 1B). There was no significant slope difference between M and HT+ (t=0.32,p=0.75). These differences survived after covarying for APOEε4. A three‐way interaction with baseline PiB‐PET revealed a greater slope difference between HT‐ and M (t=2.1,p=0.04) in those with higher baseline PiB‐PET relative to lower baseline PiB‐PET (Fig 2).ConclusionHT‐ showed significantly slower rates of Aß accumulation than males and a trend‐level slower rate compared to HT+; these differences appear heightened with greater baseline Aß burden. With similar ages across HT groups (p=0.20), these differences did not appear to be a function of chronological age. It remains unclear whether the introduction of estrogen, a mediating commonality, or collider bias is driving these results. Our findings, in conjunction with other studies, suggest the relationship between HT and Aß is complicated and necessitates examination of HT type and duration.

Kuntai capsules in treatment of premature ovarian failure: A systematic review and meta-analysis

ObjectiveTo assess the effectiveness and safety of Kuntai capsules (KTC) in treatment of premature ovarian failure (POF). MethodA systematic review and meta-analysis of randomized controlled trials studied KTC alone or combined with hormone therapy (HT) used for treating POF. PubMed, Cochrane Library, China National Knowledge Infrastructure, China Biology Medicine, Chinese Scientific Journal and Wanfang database were searched until July 2019. The Cochrane risk of bias method was used to assess the quality of the included studies, a meta-analysis was conducted with Review Manager 5.3 software and the level of evidence was rated by using GRAEDpro 3.6 software. ResultsA total of 14 RCTs (1257 participants) were included. Meta-analysis indicated that KTC can significantly improve the total clinical effective rate (P < 0.00001) and the serum hormone levels (P < 0.00001), with no statistically significant report of adverse reactions (P = 0.07) compared with HT. By the subgroup meta-analysis, the results of KTC combined with HT group were similar compared with the original analysis in the serum hormone level (P < 0.00001), and the KTC alone group were better in FSH and LH level (P < 0.00001) but not in E2 level (P = 0.22). Based on the GRADE system for grading, the qualities of the evidence were not high. ConclusionKTC may be effective for POF treatment, and lower risk of side effects. More high-quality articles are needed to provide more reliable sources and data to evaluate the clinical efficacy of KTC in the future.

Real-World Data of Palbociclib in Combination With Endocrine Therapy for the Treatment of Metastatic Breast Cancer in Men.

This report examined the benefits and risks of palbociclib plus endocrine therapy (ET) in men with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC). Palbociclib was evaluated using three independent data sources: real-world data from pharmacy and medical claims, a de-identified real-world data source derived from electronic health records (EHRs), and a global safety database. From medical and pharmacy records, 1,139 men with MBC were identified; in the first-line setting, median duration of treatment was longer with palbociclib plus ET (n=37, 8.5months, 95% confidence interval (CI), 4.4-13.0) than ET alone (n=214, 4.3months, 95% CI, 3.0-5.7) and specifically, was longer with palbociclib plus letrozole (n=26, 9.4months, 95% CI, 4.4-14.0) than letrozole alone (n=63, 3.0months, 95% CI, 1.8-4.8). In the EHR-derived database, 59 men received treatment for MBC; real-world response across all lines of therapy in the metastatic setting was reported in 4 of 12 patients (33.3%) in the palbociclib plus ET group vs. 1 of 8 (12.5%) patients in the ET group. Review of the global safety database did not identify any new safety signals in palbociclib-treated men. Real-world data indicated that men with MBC benefit from palbociclib plus ET, with a safety profile consistent with previous observations in women with MBC. Collective data on palbociclib in women and men in this report, including clinical trial data, real-world data, and a well-established risk/benefit profile, led to US approval of an expansion of the palbociclib indication to include men with MBC.

Electroacupuncture for the treatment of perimenopausal syndrome: a systematic review and meta-analysis of randomized controlled trials.

To assess the efficacy, comparative effectiveness and safety of electroacupuncture (EA) in the treatment of perimenopausal syndrome (PMS). Nine databases were searched until June 2019. Only relevant randomized controlled trials (RCTs) of EA for PMS were included. Twelve trials involving 746 women were included. EA and hormone therapy (HT) did not significantly differ in terms of effective rate (risk ratio (RR) = 0.98, 95% confidence interval (CI) = 0.93 to 1.04), Kupperman index (KI) (mean difference (MD) = -0.25, 95% CI = -0.76 to 0.26) and serum levels of follicle-stimulating hormone (FSH) (MD = -3.80, 95% CI = -11.59 to 3.98) or luteinizing hormone (LH) (MD = -2.51, 95% CI = -10.72 to 5.70). Serum estradiol (E2) levels were significantly lower in EA versus HT groups (MD = -60.58, 95% CI = -71.93 to -49.23). Compared with sham EA, EA had a significantly greater effect on reductions in KI (MD = -4.71, 95% CI = -6.57 to -2.86) and hot flushes score/24 h (MD = -2.43, 95% CI = -2.93 to -1.93). There were no significant differences between EA and manual acupuncture (MA) in terms of effective rate (RR = 1.14, 95% CI = 0.98 to 1.33) or serum FSH (MD = -2.87, 95% CI = -29.65 to 23.91), LH (MD = 2.73, 95% CI = -9.65 to 15.11) or E2 (MD = 26.80, 95% CI = -12.06 to 65.65). However, it seemed that EA had a better effect than MA on KI (MD = -2.44, 95% CI = -4.80 to -0.08). Subgroup analyses indicated that EA may have more of a benefit in the pre-menopausal state (hot flushes score/24 h: MD = -1.66, 95% CI = -3.49 to 0.17) compared to post-menopause (p > 0.05). The effect of EA appeared broadly similar to HT and MA in the treatment of PMS, although EA-associated reductions in KI were superior to MA and sham EA, suggesting effects beyond placebo. The evidence base is limited by a small number of eligible studies, risk of bias and clinical/statistical heterogeneity, limiting our ability to draw firm conclusions. As such, additional larger scale, high-quality RCTs are needed.

Delays in operative management of early-stage, estrogen receptor–positive breast cancer during the COVID-19 pandemic: A multi-institutional matched historical cohort study

BackgroundDuring the COVID-19 pandemic, guidelines recommended that breast cancer centers delay estrogen receptor–positive breast cancer surgeries with neoadjuvant endocrine therapy. We aimed to evaluate pathologic upstaging of breast cancer patients affected by these guidelines. MethodsFemale patients with stage I/II breast cancer receiving neoadjuvant endocrine therapy were prospectively identified and were matched to a historical cohort of stage I/II estrogen receptor–positive breast cancer patients treated with upfront surgery ≤35 days. Primary outcomes were pathologic T and N upstaging versus clinical staging. ResultsAfter matching, 28 neoadjuvant endocrine therapy and 48 control patients remained. Median age in each group was 65 (P = .68). Most patients (78.6% and 79.2%) had invasive ductal carcinoma with a clinical tumor size of 0.9 cm vs 1.7 cm (P = .056). Time to surgery was 68 days in the neoadjuvant endocrine therapy group and 26.5 days in the control (P < .001). A total of 23 neoadjuvant endocrine therapy patients (82.1%) had the same or lower pT-stage compared with 31 (64.5%) control patients (P = .115). Only 3 (10.7%) neoadjuvant endocrine therapy patients had increased pN-stage vs 14 (29.2%) control patients (P = .063). ConclusionDespite 2.5-times longer delays, patients with early-stage estrogen receptor–positive breast cancer receiving neoadjuvant endocrine therapy did not experience pathologic upstaging during the COVID-19 pandemic. These findings may support the use of neoadjuvant endocrine therapy in similar patients if delays to surgery are projected.

Deep Learning Algorithms-Based CT Images in Glucocorticoid Therapy in Asthma Children with Small Airway Obstruction.

CT image information data under deep learning algorithms was adopted to evaluate small airway function and analyze the clinical efficacy of different glucocorticoid administration ways in asthmatic children with small airway obstruction. The Res-NET in the deep learning algorithm was used to perform feature extraction, summary classification, and other reconstruction of CT images. A deep learning network model Mask-R-CNN was constructed to enhance the ability of image reconstruction. A total of 118 children hospitalized with acute exacerbation of asthma in the hospital were recruited. After acute exacerbation treatment, 96 children with asthma were screened out for small airway obstruction, which were divided into glucocorticoid aerosol inhalation group (group A, 32 cases), glucocorticoid combined with bronchodilator aerosol inhalation group (group B, 32 cases), and oral hormone therapy group (group C, 32 cases). Asthmatic children with small airway obstruction were screened after acute exacerbation treatment and were rolled into glucocorticoid aerosol inhalation group (group A), glucocorticoid combined with bronchodilators aerosol inhalation group (group B), and oral hormone therapy group (group C). Lung function indicators (maximal mid-expiratory flow (MMEF75 and 25), 50% forced expiratory flow (FEF50), and 75% forced expiratory flow (FEF75)), FeNO level, and airway inflammation indicators (IL-6, IL-35, and eosinophilic (EOS)) were compared before and one month after treatment. The ratio of airway wall thickness to outer diameter (T/D) and the percentage of airway wall area to total airway area (WA%) were measured by e-Health high-resolution CT (HRCT). The constructed network model was used to measure the patient's coronary artery plaque and blood vessel volume, and the image was reconstructed on the Res-Net network. It was found that the MSE value of the Res-Net network was the lowest, and the efficiency was very high during the training process. T/D and WA (%) of asthmatic children with small airway obstruction after treatment were significantly lower than those before treatment (P < 0.01). After treatment, MMEF75/25 and FEF75 were significantly higher than those before treatment (P < 0.05). Lung function-related indicator FEF50 was significantly higher than that before treatment (P < 0.01). FeNO level after treatment was remarkably lower than that before treatment (P < 0.01). In addition, lung function-related indicators, airway inflammation indicators, and FeNO level improved the most in group C, followed by group B, and those improvements in group A were the least obvious, with great differences among groups (P < 0.05). In summary, the Res-Net model proposed was of certain feasibility and effectiveness for CT image segmentation and can effectively improve the clinical evaluation of patient CT image information. Glucocorticoids could improve small airway function and airway inflammation in asthmatic children with small airway obstruction, and oral corticosteroids were more effective than aerosol inhalation therapy.

Overview of systematic reviews on Kuntai Capsules in treatment of perimenopausal syndrome

To evaluate the efficacy and safety of Kuntai Capsules in the treatment of perimenopausal syndrome. Systematic reviews on Kuntai Capsules in the treatment of perimenopausal syndrome were retrieved from Chinese and English databases from database establishment to August 31, 2020. AMSTER-2 scale, GRADE scale and ROBIS tools were used respectively to evaluate the methodological quality, evidence quality level and bias risk of the finally included systematic reviews. A total of 6 systematic reviews with 28 outcome indicators were included. The results of AMSTER-2 methodological quality assessment showed that one of the six systematic reviews was of low quality, and the other five were of extremely low quality. GRADE scale showed that 28 clinical outcome indicators were evaluated, three of which were intermediate-level ones, and the rest were low-level or very low-level ones. Two evidences of the three intermediate evidences were total efficiency, and the other intermediate evidence was Kupperman score. ROBIS bias risk assessment showed all the included studies were of high risk. The results showed that, Kuntai Capsules were effective in the treatment of perimenopausal symptoms, such as hot flashes and sweating. The improvement of E_2 level was not as good as that in the menopause hormone therapy group, but the incidence of adverse reactions was lower than that in the menopause hormone therapy group. However, the quality of evidence needs to be improved due to the low quality of methodology and high risk of bias. It is suggested that systematic review and reasonable design should be carried out in the future, and attention should be paid to the registration of research schemes. In addition, the research reports shall be prepared according to PRISMA statement.

Characteristics and progression-free survival of Afro-Caribbean men with metastatic hormone-sensitive prostate cancerat the time of diagnosis.

Metastatic hormone-sensitive prostate cancer (mHSPC) accounts for 12% of prostate cancers diagnosed in Guadeloupe according to the Guadeloupean cancer registry. Most published studies have been conducted on the Caucasian population, whereas data concerning mHSPC in the Afro-Caribbean population are lacking. We aimed to describe the patient characteristics and estimate the progression-free survival of men with mHSPC in an Afro-Caribbean population according to the available treatment. This was a monocentric retrospective study that consecutively included 133 men with mHSPC between January 1, 2015 and December 31, 2019 at the University Hospital of Guadeloupe. The primary endpoint was a description of the patients' characteristics with a description of complications at diagnosis. The secondary endpoint was progression-free survival. Kaplan-Meier survival and Cox proportional hazard analyses were performed. The median age at diagnosis was 71 years. The median prostate-specific antigen (PSA) was 147 ng/ml and 37% of patients presented with a disease-related complication at diagnosis. The survival analysis according to treatment showed median survival of 15 months for the androgen deprivation therapy (ADT) + chemotherapy group, 20 months for the ADT + new hormone therapy group, and 21.5 months for the ADT alone group, with no significant difference between the three therapeutic options (log-rank test: 0.27). In univariate analysis, none of the patient characteristics at diagnosis (i.e., age, PSA, bone lesions, visceral lesions) were significantly associated with the risk of progression, regardless of the treatment. There was no significant difference in terms of progression-free survival between currently validated treatments administered in the first line, regardless of the tumor volume or risk group. Future studies with larger numbers of patients and involving molecular factors are required to confirm or invalidate these results and understand the evolution of prostate cancer in our population and thus better prevent complications related to the disease.

P16-3 Maintenance therapy in HER2 and hormone receptor-positive breast cancer

After the standard first-line treatment for HER2 and hormone receptor-positive breast cancer, maintenance therapies are still controversial. Here, we report the real-world data of trastuzumab plus endocrine therapy compared with trastuzumab plus chemotherapy in HER2 and hormone receptor-positive metastatic breast cancer. This retrospective, multicenter, observational cohort study enrolled women aged 18 years or older with measurable or evaluable HER2 and hormone receptor-positive metastatic breast cancer who received chemotherapy and trastuzumab as first-line treatment between January 2009 and October 2019. We evaluated the efficacy and safety of trastuzumab plus endocrine therapy and trastuzumab plus chemotherapy. 102 patients were selected: 67 (65.7%) patients received trastuzumab plus endocrine therapy including aromatase inhibitors, fulvestrant, tamoxifen, or toremifene. While 35 (34.3%) patients received trastuzumab plus chemotherapy including capecitabine or vinorelbine as maintenance therapy. Maintenance endocrine therapy significantly improved progression-free survival (PFS) compared with chemotherapy (median progression-free survival 10.6 months [95% CI 8.609-12.658] vs 6.7 months [5.276-8.058], respectively; adjusted hazard ratio [HR] 0.648 [95% CI 0.428-0.981], p=0.040). The median PFS in patients without brain metastasis was 10.8 months (95% CI 9.380-12.154) in the endocrine therapy group versus 6.7 months (5.202-8.132) in the chemotherapy group (HR 0.485 [95% CI 0.303-0.777]), p=0.003). The most common adverse event was arthralgia (8,12%) in the endocrine therapy group, while hand-foot syndrome (25,71%) occurred in the chemotherapy group. Maintenance endocrine therapy could improve the survival of HER2 and hormone receptor-positive metastatic breast cancer patients.

Venous thrombosis with oral postmenopausal hormone therapy: Roles of activated protein C resistance and tissue factor pathway inhibitor

BackgroundOral postmenopausal hormone therapy (HT) increases the risk of venous thrombosis (VT). We postulated that activated protein C (APC) resistance induced by HT is one of the mechanisms causing VT, and also assessed the role of one of the main determinants of APC resistance (i.e., tissue factor pathway inhibitor [TFPI]). MethodsWe performed a nested case‐control study embedded within two Women's Health Initiative hormone trials. Women were randomized to hormone therapy or placebo. Biomarkers were measured at baseline and after 1 year in 217 cases and 817 controls. ResultsIncreased APC resistance and decreased TFPI at baseline were associated with VT (odds ratio 1.20–2.06). However, women with such prothrombotic profile at baseline did not have further increased risk of VT when randomized to HT compared with placebo. Although there was no change in APC resistance or TFPI in placebo group after 1 year, HT group showed prothrombotic changes in the biomarkers (i.e., an increase in APC resistance) (mean [standard deviation] 0.39 [0.54]) and decrease in TFPI (−0.21 [0.50]: free TFPI, −0.24 [0.22]: TFPI activity −0.22 [0.20]: total TFPI). However, HT induced prothrombotic change in biomarkers did not increase risk of VT. ConclusionWomen with prothrombotic levels of APC resistance and TFPI at baseline were not at increased risk of VT when randomized to HT compared with placebo. This suggests that testing for these biomarkers before starting HT is not required. HT led to prothrombotic change in these biomarkers after one year, but this did not relate to increased risk of VT.

Immunogenicity of SARS-CoV-2 messenger RNA vaccines in patients with cancer.

Patients with cancer experience a higher burden of SARS-CoV-2 infection, disease severity, complications, and mortality, than the general population. SARS-CoV-2 mRNA vaccines are highly effective in the general population; however, few data are available on their efficacy in patients with cancer. Using a prospective cohort, we assessed the seroconversion rates and anti-SARS-CoV-2 spike protein antibody titers following the first and second dose of BNT162b2 and mRNA-1273 SARS-CoV-2 vaccines in patients with cancer in US and Europe from January to April 2021. Among 131 patients, most (94%) achieved seroconversion after receipt of two vaccine doses. Seroconversion rates and antibody titers in patients with hematological malignancy were significantly lower than those with solid tumors. None of the patients with history of anti-CD-20 antibody in the 6 months before vaccination developed antibody response. Antibody titers were highest for clinical surveillance or endocrine therapy groups and lowest for cytotoxic chemotherapy or monoclonal antibody groups.

Effects of menopausal hormone therapy on erythrocyte n–3 and n–6 PUFA concentrations in the Women’s Health Initiative randomized trial

The factors other than dietary intake that determine tissue concentrations of EPA and DHA remain obscure. Prior studies suggested that, in women, endogenous estrogen may accelerate synthesis of DHA from ɑ-linolenic acid (ALA), but the effects of exogenous estrogen on RBC n-3 (ɷ-3) PUFA concentrations are unknown. We tested the hypothesis that menopausal hormone therapy (HT) would increase RBC n-3 PUFA concentrations. Postmenopausal women (ages 50-79 y) were assigned to HT or placebo in the Women's Health Initiative (WHI) randomized trial. The present analyses included a subset of 1170 women (ages 65-79 y) who had RBC PUFA concentrations measured at baseline and at 1 y as participants in the WHI Memory Study. HT included conjugated equine estrogens (E) alone for women without a uterus (n=560) and E plus medroxyprogesterone acetate (P) for those with an intact uterus (n=610). RBC n-3 and n-6 (ɷ-6) PUFAs were quantified. Effects of E alone and E+P on PUFA profiles were similar and were thus combined in the analyses. Relative to the changes in the placebo group after 1 y of HT, docosapentaenoic acid (DPA; n-3) concentrations decreased by 10% (95% CI: 7.3%, 12.5%), whereas DHA increased by 11% (95% CI: 7.4%, 13.9%) in the HT group. Like DHA, DPA n-6 increased by 13% from baseline (95% CI: 10.0%, 20.3%), whereas linoleic acid decreased by 2.0% (95% CI: 1.0%, 4.1%; P values at least <0.01 for all). EPA and arachidonic acid concentrations were unchanged. HT increased RBC concentrations of the terminal n-3 and n-6 PUFAs (DHA and DPA n-6). These findings are consistent with an estrogen-induced increase in DHA and DPA n-6 synthesis, which is consistent with an upregulation of fatty acid elongases and/or desaturases in the PUFA synthetic pathway. The clinical implications of these changes require further study. The Women's Health Initiative Memory Study is registered at clinicaltrials.gov as NCT00685009. Note that the data presented here were not planned as part of the original trial, and therefore are to be considered exploratory.

The effect of everolimus on body composition (BC) in patients with metastatic breast cancer (MBC).

e13026 Background: BC measurement can distinguish adipose tissue distribution, as well as the quantity and quality of muscle. Dysregulation in the mammalian target of rapamycin (mTOR) signaling pathway is associated with obesity and its related diseases. Everolimus (Eve), an mTOR inhibitor, is used in combination with endocrine therapy (ET) in hormone positive, HER2 negative (HR+/HER2-) MBC. However, there is limited data on the effect of Eve on BC. We aim to assess the effect of Eve on BC in patients (pts) with HR+/HER2- MBC. Methods: Pts with HR+/HER2- MBC who received Eve and ET between 2012 and 2019 at our institution were identified. We collected information about breast cancer diagnosis and treatment, weight (wt), body mass index (BMI), and computed tomography (CT). BC measurements; including skeletal muscle area (SMA), skeletal muscle density (SMD), subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and muscle adiposity (MA); were analyzed at the L3 region on CT scans using Tomovision’s SliceOmatic Version 5.0. Total adipose tissue (TAT) was defined as SAT+VAT+MA. To isolate the effect of Eve on BC we also identified a cohort of pts who received ET only. We compared change in wt, BMI, and BC before and after 3 and 6 months of therapy. Wilcoxon signed rank test was used to compare BC parameters. Results: Our study included 42 pts who received Eve plus ET; 43% were Hispanic and 33% were Black. The median number of prior ET and chemotherapy lines were 1 and 0, respectively. The cohort who received ET alone included 63 patients. Median age was 68 years (interquartile range [IQR] 56-74) for the Eve and ET group and 67 years (IQR 55-74) for the ET only group (p = 0.74). Median baseline BMI was 25.8 kg/m2 (IQR 23.1-28.2) for the Eve and ET group and 28.5kg/m2 (IQR 24.2-30.8) for ET only (p = 0.08). Visceral disease was present in 24 (57%) pts on Eve and ET and 41 (65%) pts on ET only (p = 0.54). At month 3 of treatment with Eve and ET, there was a significant decrease in wt (-2.75kg, IQR -4.53-0.40, p &lt; 0.005), BMI (-1.15kg/m2, IQR -1.71-0.14, p &lt; 0.01), SAT (-21.93cm2, IQR -50.13-5.08, p &lt; 0.01), and TAT (-22.34cm2, IQR -69.89-11.98, p = 0.02), which remained statistically significant at month 6 (wt: -5.70kg, IQR –7.75-1.83, p &lt; 0.01; BMI: -2.3kg/m2, IQR -2.83-0.72, p &lt; 0.01; SAT: -43.00cm2, IQR -73.81-10.69, p &lt; 0.01; TAT: -32.56cm2, IQR –92.18-9.61, p = 0.03). These findings were not seen in pts who received ET only at 3 months (wt: 0.00kg, IQR –2.65-2.38, p = 0.99; BMI: 0.00kg/m2, IQR –1.07-0.91, p = 0.94; SAT: -1.82cm2, IQR -26.10-25.15, p = 0.59; TAT: 0.71cm2, IQR -44.39-27.43, p = 0.35), with similar results at 6 months. There were no statistically significant changes in VAT, SMA, SMD, or MA in both groups at 3 or 6 months. Conclusions: Everolimus is associated with decrease in SAT, with no significant change in VAT, SMA, or SMD. Further investigation is required to determine if these changes are associated with disease outcomes or everolimus toxicities.