Gynecologic Cancer Research Articles

Holistic approaches to mitigating psychological distress in gynecological cancer patients

This article delves into the psychological impact of gynecological malignancies and suggests pathways to improve the quality of life (QoL) for affected patients. Building on Shang et al 's comprehensive analysis, this piece integrates insights from various studies to highlight the profound influence of psychological and physical symptoms on patients undergoing treatment for gynecological cancers. The study underscores that anxiety and depression significantly exacerbate the disease's toll. Factors such as physical exercise and digital and interactive health interventions show promise in mitigating these adverse effects. The article emphasizes the necessity for a holistic care approach that addresses both physical and emotional needs. Recommendations include enhanced training for healthcare providers, public awareness campaigns, streamlined diagnostic pathways, and improved access to specialist care. These integrated strategies aim to ensure that women facing gynecological cancers can maintain an optimal QoL through comprehensive and multidisciplinary care models.

Effect of endometriosis on prognosis of ovarian clear cell carcinoma: a 10-year retrospective study

IntroductionEndometriosis is considered as a precancerous lesion for OCCC; however its prognostic significance remains controversial. This study aims to evaluate the prognostic significance of endometriosis in patients with ovarian clear cell carcinoma (OCCC) and analyze the impact of other clinical pathological features on prognosis. Additionally, we also assess the role of laparoscopic surgery and chemotherapy in OCCC, hoping to provide evidence for improving the clinical diagnosis and treatment of OCCC.MethodsA retrospective analysis was conducted on medical records of 105 OCCC patients diagnosed and treated at the Gynecologic Cancer Center of Hubei Cancer Hospital in China from 2013 to 2022. Based on the presence or absence of endometriosis, OCCC patients were divided into two groups: a group with ovarian endometriosis consisting of 44 cases (41.9%) (EC-positive group) and a group without ovarian endometriosis consisting of 61 cases (58.1%)(EC-negative group). Clinical pathological characteristics, progression-free survival (PFS), and overall survival (OS) were compared between the two groups.ResultsThere were no statistically significant differences between the two groups in terms of age, CA125, tumor size, FIGO stage, adjuvant chemotherapy regimen, or chemotherapy efficacy (P>0.05). Residual tumor after surgery, staging, site invasion involvement, presence of ascites, positive cytology in ascitic fluid, lymph node metastasis, and chemotherapy efficacy were predictive factors for recurrence among patients with statistical significance (P<0.10); chemotherapy efficacy remained as independent predictors for recurrence (P<0.05); staging and chemotherapy efficacy remained as independent predictors for survival (P<0.05). There was no statistically significant difference observed between both groups regarding OS or PFS.ConclusionIn this study, co-existing endometriosis was not a prognostic factor for survival in patients with OCCC. The most important predictors of OS and PFS were FIGO stage and chemotherapy sensitivity. The intrinsic link between endometriosis and OCCC requires larger, better-designed prospective studies to draw more definitive conclusions.

Hormone replacement therapy in surgical menopause after gynecological malignancies

This review examines hormone replacement therapy (HRT) in cases of surgical menopause following gynecological malignancies. It aims to capture current knowledge, summarize recent findings, and provide recommendations for clinical settings. Unlike natural menopause, surgical menopause occurs abruptly, without an adjustment period, and is associated with a notably higher risk of fractures, arthritis, cognitive decline, dementia, Parkinson’s disease, and various metabolic disorders affecting glucose and lipid levels—all of which contribute to an increased risk of major cardiovascular events. In 2017, The North American Menopause Society recommended that, barring contraindications, HRT should be initiated in women who enter surgical menopause before age 45. If these women do not experience vasomotor symptoms or other issues, HRT should be maintained consistently at least until age 52. This guideline reflects contemporary knowledge and is the result of a multidisciplinary consensus, based on a review of existing literature and several randomized clinical trials focusing on women who have survived gynecological cancers and whose quality of life is significantly impacted by surgical or early menopause. Estrogen supplementation is particularly beneficial, as it is linked to marked improvements in quality of life, including delayed onset of chronic cardiovascular issues, reduced fracture risk, enhanced cognitive function, reduced inflammation, and improved self-esteem, as well as better social and work performance. Clinical implementation of HRT, however, requires a highly individualized approach. This approach must consider the type and stage of malignancy, histopathological characteristics, risk factors for recurrence (such as diet, concurrent medications, medical history, and genetic predispositions), and a thorough assessment of the potential benefits and risks of HRT, as well as the patient’s personal wishes and expectations.

Antibody–Drug Conjugates: A Start of a New Era in Gynecological Cancers

Antibody–drug conjugates (ADCs) are a new class of therapeutic agents designed to target specific antigens on tumor cells, combining the specificity of monoclonal antibodies with the cytotoxicity of chemotherapy agents. ADCs have been available for over a decade, but in gynecological cancers, these agents are relatively new with great promise ahead. More than 80% of ongoing trials in gynecological cancers are evaluating ADCs’ safety and efficacy, of which 40% are early-phase trials. Around twenty ADCs are currently under investigation, either alone or in combination with chemotherapies or immune checkpoint inhibitors. Among them, mirvetuximab soravtansine has been recently approved by the Food and Drug Administration (FDA) in platinum-resistant ovarian cancer with high folate-α receptor expression, as a single agent or in combination. Tisotumab vedotin and trastuzumab deruxtecan are also now approved by the FDA in patients with pre-treated cervical and uterine cancers and further investigation is ongoing. Overall, the toxicity profiles of ADCs are acceptable. Ocular toxicity is one of the specific side effects of some ADCs, but most of the cases are manageable with the use of prophylactic steroids and dose adjustments. This review aims to provide an overview of the fundamental and operational features of ADCs and examine the latest and most promising data, with a particular focus on the Canadian viewpoint.

Transforming Pain into a Purpose: Post-Traumatic Growth and Life Meaning in Gynaecological Cancer

Transforming Pain into a Purpose: Post-Traumatic Growth and Life Meaning in Gynaecological Cancer

Assessing the impact of contraceptive use on reproductive cancer risk among women of reproductive age—a systematic review

BackgroundContraceptives play a crucial role in women's reproductive health, their hormonal components may be linked to cancer risks, specifically breast, and gynecological cancers. Given the high usage rates of hormonal contraceptives, it is vital to systematically evaluate their potential impact on cancer outcomes, especially among women with a family history of gynecological cancers.ObjectivesThis study aims to evaluate the evidence on the association between modern contraceptive use and the risk of breast and reproductive cancers (ovarian, endometrial, and cervical cancer) among women of reproductive age, to inform healthcare providers, women, and program managers about cancer outcomes related to contraceptive use.MethodsA systematic review was conducted according to PRISMA guidelines. Searches were performed in databases such as CINAHL, OVID Medline, EMBASE, and more from inception to February 2022. Eligible studies included randomized controlled trials, cohort studies, and case-control studies that compared cancer outcomes between contraceptive users and non-users. Data extraction, quality assessment, and meta-analyses were conducted following predefined protocols. Subgroup and sensitivity analyses examined variations in contraceptive methods, doses, and duration.ResultsA total of 51 studies were included, comprising 2 RCTs and 49 observational studies. The review identified a significant reduction in ovarian and endometrial cancer incidence among contraceptive users. Hormonal contraceptive users had a 36% lower risk of ovarian cancer (RR 0.64, 95% CI 0.60–0.68), with specific reductions seen in combined oral contraceptive users (RR 0.62, 95% CI 0.57–0.68) and hormonal IUD users (RR 0.68, 95% CI 0.48–0.96). The rate ratio of cervical cancer was higher among non- users compared to hormonal contraceptive users when we pooled the results (1.28, 95% CI 1.21, 1.35). No significant association was found between contraceptive use and breast cancer risk among healthy women (RR 1.00, 95% CI 0.94–1.06). However, BRCA1/2 mutation carriers using oral contraceptives showed a heightened risk of breast cancer (HR 1.39, 95% CI 1.15–1.67).ConclusionThis systematic review highlights the protective effects of modern contraceptives against ovarian and endometrial cancers while identifying an increased risk of cervical. No significant breast cancer risk was found for healthy women, but BRCA1/2 mutation carriers faced increased risks. These findings underscore the need for personalized contraceptive counselling that considers cancer risk factors. Further research is needed to explore contraceptive impacts across different genetic profiles and dosing regimens.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, Prospero (CRD42022332647).

Spiritual Care Experiences of Nurses Caring for Gynecologic Cancer Patients in Türkiye: A Qualitative Research.

The study aimed to examine the spiritual care experiences of nurses caring for gynecologic cancer patients. The study was conducted using a phenomenological design, one of the qualitative research methods. Nurses caring for gynecologic cancer patients were included in the study. In sample selection, the criterion sampling method, one of the purposeful sampling methods, was used, and the sample size was ten nurses. A semi-structured interview guide was used to collect the data. Content analysis was performed using the MAXQDA package program. The study was written based on the COREQ checklist. The nurses' statements determined themes, sub-themes, and codes in line with the research findings. Accordingly, four themes were identified as "spiritual care practices," "emotional effects of spiritual care," "factors affecting spiritual care," and "recommendations to improve spiritual care".In line with the findings obtained, it is recommended that in-service training should be provided to nurses caring for gynecologic cancer patients to provide spiritual care at a professional level. Moreover, the excessive workload caused by working conditions should be reduced, and regulations and institutional policies should be established to increase the number of nurses.

Lymphaticovenular Anastomosis as a Treatment for Neurogenic Bladder in Patients With Lower Extremity Lymphedema After Gynecologic Cancer Treatment.

Neurogenic bladder (NB), a complication of gynecological cancer treatment, entails significant symptoms such as loss of urinary urgency, incontinence, and renal dysfunction. To investigate whether lymphatic fluid stagnation at the pelvis causes NB, we investigated the effectiveness of lymphaticovenular anastomosis (LVA) for NB. In this retrospective study between 2014 and April 2024, LVA was performed on 52 patients complaining of preoperative urinary dysfunction with lower extremity lymphedema following pelvic lymphadenectomy in gynecologic cancer treatment. Pre- and postoperative assessments evaluated NB symptoms and volume reduction of lower extremities. With an average follow-up period of 35.0 months, the volume of the affected limbs was reduced in all patients. Symptoms of urinary function were improved in 44 out of 52 patients, as improved urinary urgency, disappearance of incontinence, and independence from self-catheterization. Among 15 patients who underwent pre- and postoperative questionnaire assessment of NB, the mean score of NB severity decreased significantly from 16.9 ± 7.1 points preoperatively to 4.3 ± 3.6 points postoperatively (p < 0.01). The specific reason for NB following gynecologic cancer treatment remains unclear. Our study results suggest that lymphatic fluid stagnation itself might be a reason for NB and LVA could reduce these symptoms.

Comparison of Treatment Outcomes Between First-Line Chemotherapy With or Without Bevacizumab for Advanced Ovarian Clear Cell Carcinoma (Tohoku Gynecologic Cancer Unit: TGCU-RS001A Study)

Objective: The usefulness of bevacizumab (BEV) as first-line chemotherapy for advanced ovarian clear cell carcinoma (CCC) was retrospectively evaluated at Tohoku Gynecologic Cancer Unit institutions. Patients and Methods: A total of 81 patients (52 patients without BEV and 29 with BEV) with advanced ovarian CCC who received initial platinum-based chemotherapy were enrolled. We selected 26 patients each without and with BEV according to propensity score matching methods, and compared the platinum-resistant recurrence rate, response rate, progression-free survival (PFS), overall survival (OS), and adverse events between the two groups. Results: The objective response rates for the patients with measurable disease in the non-BEV and BEV groups were 60.0% and 95.5%, respectively (p = 0.007). The recurrence of platinum-resistant patients was observed in 50.0% of the non-BEV group and 23.1% of the BEV group (p = 0.117). The median PFS was 12 and 22 months, respectively (p = 0.034), and the median OS was 32 and 47 months, respectively (p = 0.223). In the BEV group, grade 3 hypertension and proteinuria occurred in two patients, and thrombosis and carboplatin hypersensitivity occurred in one patient. Grade 4 gastrointestinal perforation occurred in one patient. Conclusions: First-line chemotherapy with BEV in advanced CCC showed the potential for high response rates and improved PFS.

Venous thromboembolism among gynecologic cancer patients in Zaria

Cancer is one of the most important acquired risk factors for Venous Thromboembolism (VTE) including Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE). Patients with active malignancy have up to six-fold increased risk of symptomatic VTE than the general population. The risk of VTE in patients with gynecologic malignancy is especially high because of the nature of the tumor, its pelvic location, associated comorbidities, and systemic chemotherapy. The objective of this study was to determine other risk factors, incidence, clinical presentation, and immediate outcome of treatment of thromboembolism in patients with gynecologic cancers in Ahmadu Bello University Teaching Hospital (ABUTH), Zaria, Nigeria. It was a retrospective cross-sectional descriptive study of gynecologic cancer cases that were diagnosed with VTE while on admission from 2007-2016 in ABUTH. The overall prevalence of clinical VTE was 2.8% in gynaecologic malignancy. All were DVT. Most cases of DVT were present in ovarian cancers with left-sided preponderance. There is a need for the provision of modern imaging equipment to facilitate timely and highly sensitive diagnosis of VTE in low-resource settings. The main limitation of this study was the inability to find any confirmed case of PE.

A Comprehensive Evaluation of a Coumarin Derivative and Its Corresponding Palladium Complex as Potential Therapeutic Agents in the Treatment of Gynecological Cancers: Synthesis, Characterization, and Cytotoxicity

Background: The aim of this research is the synthesis and characterization of coumarin-palladium complex and the investigation of the cytotoxicity of both the ligand and the complex. Methods: The palladium( II) complex (CC) was obtained in the reaction between (E)-3-(1-((4-hydroxy-3-methoxyphenyl)amino)ethylidene)-2,4-dioxochroman-7-yl-acetate (CL) and potassium-tetrachloropalladate(II) and characterized using IR and NMR spectra, experimentally and theoretically. Cytotoxicity of CL and CC were determined for human cervical carcinoma HeLa, ovarian cancer A2780, hormone dependent breast cancer MCF7, and colorectal cancer HCT116 lines. The interaction of investigated compounds with HSA was followed by spectrofluorimetric method. The binding mechanism in the active pocket was assessed via molecular docking simulations. Results: A low mean absolute error between experimental and theoretical data proved that the optimized structure corresponded to the experimental one. Both compounds showed a satisfactory selectivity index towards neoplastic cells. The binding affinity of tested compounds to the HSA were confirmed. The molecular docking showed a much lower change in the Gibbs free energy of binding for CC compared to CL. Conclusions: The obtained results revealed that CL and CC exhibit significant effects on several cancer cell lines and good binding properties to HSA, while molecular docking discovered that CC has the most pronounced activity against alpha-fetoprotein.

Lymphadenectomy and chemotherapy are effective treatments for patients with 2023 international federation of gynecology and obstetrics stage IIC-high risk endometrial cancer in Japan.

In early-stage endometrial cancer (EC), the treatment of aggressive histological subtypes (endometrioid carcinoma grade 3, serous carcinoma, clear-cell carcinoma, undifferentiated carcinoma, mixed carcinoma, and carcinosarcoma) is controversial. We aimed to investigate the treatment of patients with International Federation of Gynecology and Obstetrics (FIGO) stage IC and stage IIC EC according to the 2023 classification. We retrospectively identified patients with FIGO 2023 stage IC, IIC-intermediate risk (IIC-I), and IIC-high risk (IIC-H) EC who underwent adjuvant therapy or observation after surgery at eight medical institutions from 2004 to 2023. Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan-Meier estimates and univariate and multivariate analyses. The PFS and OS were significantly worse in patients with FIGO 2023 stage IIC-H EC than in those with FIGO 2023 stage IIC-I EC (PFS: p = 0.008 and OS: p = 0.006). According to the FIGO 2023 stage IIC-H classification, lymphadenectomy and chemotherapy resulted in better prognoses regarding both PFS and OS (p < 0.001 for both) than other treatments. Our findings suggest that lymphadenectomy and chemotherapy effectively reduced vaginal stump and lymph node metastases in FIGO 2023 stage IIC-H EC (p < 0.001 and p = 0.008, respectively). Furthermore, in the multivariate analysis, not undergoing lymphadenectomy or chemotherapy were independent predictors of recurrence and poor prognoses in patients with FIGO 2023 stage IIC-H EC (p < 0.001 and p = 0.031, respectively). Lymphadenectomy and chemotherapy resulted in better prognoses regarding both recurrence and survival in patients with FIGO 2023 stage IIC high-risk EC.

Sensitive Detection of Gynecological Cancer Recurrence Using Circulating Tumor DNA and Digital PCR: A Comparative Study with Serum Biochemical Markers

Early detection of recurrences in gynecological cancers is crucial for women’s health. Circulating tumor DNA (ctDNA) analysis through liquid biopsy offers a promising approach for monitoring disease progression and identifying relapses. This study investigated the utility of digital Polymerase Chain Reaction (dPCR) for ctDNA detection in three gynecological cancer patients with clinically confirmed relapses during a two-year post-surgical follow-up. Patient-specific tumor mutations were identified through whole-exome sequencing (WES) and confirmed via Sanger sequencing. dPCR probes targeting these mutations were used to quantify the ctDNA levels in plasma samples collected throughout the follow-up period, and the findings were compared with standard serum biochemical markers. In two patients, persistent positive dPCR signals for the selected mutations were detected after tumor removal, with ctDNA levels progressively increasing even after post-surgical chemotherapy. Notably, dPCR identified elevated ctDNA levels before an increase in the cancer antigen 125 (CA125) biochemical marker was observed. In the third patient, no ctDNA signals from the two selected mutations were detected despite clinical evidence of recurrence, suggesting the emergence of new mutations. While this study highlights the promise of dPCR for early recurrence detection in gynecological cancers, it also underscores the critical need for comprehensive mutation panels to overcome the inherent challenges posed by tumor heterogeneity and the emergence of new mutations during disease progression.

Ultrasound assessment of lymph nodes for staging of gynecological cancer: consensus opinion on terminology and examination technique.

The lymphatic pathway is an important route of metastasis in gynecological malignancy. Therefore, the examination of lymph nodes is an essential part of the ultrasound evaluation in patients with known or suspected gynecological malignancy. The lymph nodes most frequently involved in gynecological malignancy (apart from vulvar cancer) are parietal (retroperitoneal) and visceral abdominopelvic lymph nodes. In advanced disease, more distant lymph-node regions, such as the inguinal, axillary and supraclavicular lymph nodes, can also be involved. The standardized description of lymph nodes has been published previously by the Vulvar International Tumor Analysis (VITA) collaborative group. Herein, a collaborative group of gynecologists and gynecological oncologists with extensive ultrasound experience presents a systematic methodology for ultrasonographic lymph-node assessment performed as part of the locoregional and distant work-up to assess the extent of gynecological malignancy. The aim of this consensus opinion is also to describe the anatomical classification and drainage pathways of the lymphatic system as relevant to the gynecological organs. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Cervicovaginal lavages uncover growth factors as key biomarkers for early diagnosis and prognosis of endometrial cancer

Endometrial cancer (EC) rates are continuing to rise and it remains the most common gynecologic cancer in the US. Existing diagnostic methods are invasive and can cause pain and anxiety. Hence, there is a need for less invasive diagnostics for early EC detection. The study objective was to evaluate the utility of growth factors collected through minimally invasive cervicovaginal lavage (CVL) sampling as diagnostic and prognostic biomarkers for EC. CVL samples from 192 individuals undergoing hysterectomy for benign or malignant conditions were collected and used to quantify the concentrations of 19 growth and angiogenic factors using multiplex immunoassays. Patients were categorized based on disease groups: benign conditions (n = 108), endometrial hyperplasia (n = 18), and EC (n = 66). EC group was stratified into grade 1/2 endometrial endometrioid cancer (n = 53) and other EC subtypes (n = 13). Statistical associations were assessed using receiver operating characteristics, Spearman correlations and hierarchical clustering. Growth and angiogenic factors: angiopoietin-2, endoglin, fibroblast activation protein (FAP), melanoma inhibitory activity, and vascular endothelial growth factor-A (VEGF-A) were significantly (p < 0.0001) elevated in EC patients. A multivariate model combining 11 proteins with patient age and body mass index exhibited excellent discriminatory potential (area under curve = 0.918) for EC, with a specificity of 90.7% and a sensitivity of 87.8%. Moreover, angiopoietin-2, FAP and VEGF-A significantly (p < 0.05–0.001) associated with tumor grade, size, myometrial invasion, and mismatch repair status. Our results highlight the innovative use of growth and angiogenic factors collected through CVL sampling for the detecting endometrial cancer, showcasing not only their diagnostic potential but also their prognostic value.

Trends in hospitalization for female breast and gynecological cancer in China from 2004 to 2020

Breast and gynecological cancers are common cancers with high mortality and have profound effects on the various physical functions of women. This study assessed trends in the number of hospitalizations, in-hospital mortality, length of stay (LOS), and hospital charges for female breast and gynecological cancer from 2004 to 2020. The data for this study come from the China Health Statistics Yearbook. Time trends of categorical variables were assessed with the Cochran-Armitage Test. The linear model was used to test for the trend of continuous variables. The hospitalizations for breast cancer increased from 15,204 to 276,387 (P for trend < 0.001) and gynecological cancer increased from 12,418 to 214,956 (P for trend < 0.001). The in-hospital mortality rate due to breast cancer decreased from 1.70 to 1.07% (P for trend < 0.001). Hospitalizations for both breast and gynecological cancer increased clearly, whether in urban or rural. The gap between urban and rural has narrowed. The average cost per hospitalization for breast cancer significantly increased. However, the average LOS for breast cancer gradually decreased (from 17.0 to 10.7 days, P for trend < 0.001). The average cost per hospitalization for gynecological cancer increased significantly. However, this steady downward trend was observed in the average LOS for gynecological cancer (from 10.34 to 6.69 days, P for trend = 0.003). The increase in hospitalizations and medical expenses for breast and gynecological cancer should encourage healthcare policymakers and healthcare system stakeholders to develop more cost-effective approaches to women’s cancer management.

Gynaecologic oncology referrals to specialist palliative care in a tertiary referral centre: population, characteristics and outcomes

BackgroundThe early integration of a specialist palliative care team is demonstrated to have numerous benefits for patients. These extend beyond end-of-life care to include reducing depressive symptoms, improving quality of...

Comparison of The Effects of Epidural Analgesia and Conventional Analgesia on Survival in Patients Undergoing Gynecological Oncological Surgery: A retrospective analysis

Purpose: We aimed to determine whether mortality due to gynecologic cancer differs in patients who received epidural analgesia versus conventional analgesia. Additionally, we aimed to investigate which analgesia approach results in a better prognosis for gynecologic cancer. Materials and Methods: Patients who underwent surgery for a gynecologic malignancy were divided into two study groups based on the type of analgesia used: the Epidural Analgesia Group (n=120) and the Conventional Analgesia Group (n=88). All data were retrospectively collected from patient case charts. Variables recorded included patients’ age, body mass index (BMI), presence of comorbid diseases, duration of anesthesia, amount of blood transfusion. During surgery, duration of hospital stay, duration of intensive care unit stay, presence of postoperative infection, and type of postoperative treatment. Results: Survival after surgery tended to be higher in patients who received conventional analgesia (81 out of 88 patients) compared to those who received epidural analgesia (102 out of 120 patients), although this difference was not statistically significant (p=0.123). After controlling for all other factors, the coefficient for blood transfusion was -0.192 with a p- value of 0.007, indicating that a lower amount of blood transfusion was associated with increased survival. Similarly, the coefficient for the presence of comorbid diseases was -0.163 with a p-value of 0.022, suggesting that fewer comorbidities contributed to better survival post-surgery. Conventional analgesia showed higher survival rates (coefficient=0.163,p=0.022) compared to epidural analgesia. None of the other variables showed a significant correlation with survival. Conclusion: This study is among the pioneering research efforts to explore the impact of analgesia methods on the prognosis of patients with non-metastatic gynecologic cancer. A lower amount of blood transfusion during surgery and fewer comorbid diseases contribute to improved survival rates.

Systemic hormone therapy after breast and gynecological cancers: an Italian expert group consensus opinion.

The specific Italian Group of Study of the Menopause formulated a consensus opinion on the use of estrogen therapy (ET) or combined estro-progestin hormone therapy (HT) after breast and gynecological cancers. This consensus is based on the risk of recurrence of the specific cancer during ET/HT, the presence of steroid receptors in cancer cells, the use of adjuvant hormone therapies and data on the use of ET/HT after cancer. The following positions were reached. ET/HT can be used after vulvar cancers and melanoma, but with great caution after the rare adenocarcinomas. ET/HT can be used after cervical cancer, but ET should be used with caution after adenocarcinomas. ET/HT can be used after International Federation of Obstetrics and Gynecology (FIGO) stage I-II estrogen-dependent endometrial cancers, except in Black women, and can probably be used after estrogen-independent endometrial cancers. ET/HT cannot be administered or should be used with great caution after most uterine sarcomas. ET/HT can probably be used after ovarian neoplasms except for granulosa cell tumors, and with great caution after low-grade serous ovarian carcinoma and serous borderline ovarian tumors. ET/HT can be used with great caution in women after estrogen receptor (ER)/progesterone receptor (PR)-positive breast cancer and is probably allowed after ER/PR-negative breast cancer.

Spatio-temporal localization of P21-activated kinase in endometrial cancer.

Endometrial cancer is the sixth most common gynecologic cancer, and has been reported as a malignancy arising due to the idiopathic effects of certain anticancer agents. Tamoxifen is the drug of choice in ER-positive breast cancer, and several studies have shown better disease-free survival in these patients. However, the long-term usage of tamoxifen has been associated with resistance and risk for endometrial malignancy. A direct mechanistic basis for tamoxifen-induced endometrial tumorigenesis is still unclear. Hyperactivation of PAK1 in endometrial cancer correlates with poor overall survival. The present study demonstrates that tamoxifen treatment induces nuclear localization of PAK1 in endometrial carcinoma cells. This nuclear transit is mediated through JAK2 phosphorylation of PAK1 and binding of β-PIX. In addition, a computational approach involving molecular modeling and simulation of phosphorylated and unphosphorylated forms of PAK1 was used to elucidate the dynamics of nuclear localization. Thus, PAK1 phosphorylation by JAK2 is a prerequisite for its nuclear localization and its tumorigenic effects on endometrial cancer cells.