Hormone Therapy Research Articles

Premature ovarian insufficiency in pediatric cancer patients: a 10 year Rady Children's hospital experience.

To highlight the occurrence of premature ovarian insufficiency in pediatric cancer patients and determine which patient characteristics or treatment modalities are associated with ovarian failure and recovery. Between August 2011-August 2021, 36 of 2,661 patients with cancer were identified to have subsequent ovarian failure. Data collected included cancer type, diagnosis age, types of chemotherapy, bone marrow transplant or radiation treatment, peak FSH, peak AMH, GnRHa treatment, type of hormone replacement therapy, and if ovarian function recovery occurred. The most common cancer type identified was ALL. The mean age of diagnosis was 8.5±4.3 years and mean age of peak FSH value was 12.6±2.8 years. Most patients (97.2 %) were treated with alkylating agents and 72.2 % received radiation. Most patients (72.2 %) received hormone therapy, and 15.8 % of patients received GnRHa Lupron. Ten patients (27.8 %) had ovarian function recovery. Diagnosis age and treatment type were recovery predictors in multivariate regression modeling. Each year older in age was associated with a 30 % decrease in odds of recovery (OR: 0.7, CI: 0.5-0.95, p=0.035), and alkylating agent treatment without transplant was associated with a 3-fold increase in odds of recovery (OR: 3, CI: 2.7-564, p=0.007). This retrospective review demonstrates that POI can occur in pediatric cancer survivors, emphasizing the importance of educating patients on potential long-term effects of cancer treatment and importance of routine surveillance. This study confirmed that recovery of ovarian function is possible, especially when diagnosed at a younger age, making continued monitoring essential.

Effectiveness of combined targeted and hormonal therapies for post-menopausal women with hormone receptor-positive and HER2-negative advanced breast cancer: A systematic review and meta-analysis of RCTs.

we aim to synthesize available evidence on the effectiveness of hormonal plus targeted therapies for post-menopausal women with hormone receptor-positive and HER2-negative advanced breast cancer. We searched the following databases: Medline, PubMed, Cochrane Library, CINAHL, Web of Science, Scopus, and African Journal. Only studies that investigated the effectiveness of hormonal therapy combined with targeted therapy for HR+/HER2- advanced breast cancer treatment were included. The outcomes were progression-free survival (PFS), overall survival (OS) and objective response rate (ORR). A random-effect meta-analysis model was employed. Statistical analysis was performed using Comprehensive Meta-analysis version 3. 24 studies were included in the meta-analysis with an overall sample size of 7635. Median PFS, OS and ORR were found to be significantly increased in the combination group compared to hormonal monotherapy [SMD = 6.072 (95% CI = 3.785-8.360), p < 0.001], [SMD = 1.614 (95% CI = 0.139-3.089), p = 0.032] and [OR = 1.584 (CI 1.134-2.213), p = 0.007] respectively. Subgroup analysis showed a significant difference in PFS and ORR between patients who received "hormonal therapy + CDK4/6 inhibitors" vs hormonal therapy only [SMD = 6.015 (CI 3.069-8.960), p < 0.001], (OR = 1.828 (CI 1.030-3.243), p = 0.039] respectively. Compared with hormonal monotherapy, targeted plus hormonal therapy significantly improves PFS, OS and ORR in postmenopausal women with HR+/HER2- advanced breast cancer.

Use of Telemedicine Services Is Associated with Longer ime to TInitiation of Hormone Therapy in Transgender Teens and Young Adults.

Purpose: This is a retrospective chart review examining factors, which may contribute to timing of receipt of prescription for testosterone or estrogen-based interventions for transgender adolescents and young adults who do not receive such a prescription at their first medical appointment. Methods: A total of 176 patient records were available; of this a minority received a prescription for hormone therapy at first medical appointment. Of the remaining 108 unique individuals, 49 received a prescription at a subsequent medical. Results: Participants seen through virtual health care had a significantly longer time in care prior to receipt of estrogen or testosterone prescription (331 days vs. 220 days, p = 0.046). No other significant relationships were found. Conclusion: Patients who utilize telemedicine services for gender-related health care purposes and who did not receive a prescription for estrogen or testosterone at their initial medical encounter have a longer lead time to receipt of hormone therapy.

Application of autologous platelet-rich gel formed by calcium gluconate combined with hormone therapy for endometrial repair after hysteroscopic transcervical resection of adhesion surgery and successful pregnancy: case report and literature review

IntroductionIntrauterine adhesion (IUA), a common gynecological disease, is mainly caused by traumatic or infectious factors that lead to basal endometrial layer physiological repair disorders. IUA is mostly treated via hysteroscopic transcervical resection of adhesion and although it can restore uterine cavity shape, its endometrial repair effectiveness is limited. The figures showed that after surgery, patients with IUA have a high recurrence rate. Therefore, quick endometrial damage repair is key to successful treatment.Case presentationA 34-year-old patient visited our hospital after experiencing amenorrhea for 4 months following an induced abortion and had a fertility requirement. Based on the American Fertility Society intrauterine scores, the patient was diagnosed with moderate IUA. She underwent transcervical resection of adhesion, followed by autologous platelet-rich gel intrauterine perfusion and periodic estrogen–progesterone treatment for three menstrual cycles. No complications developed during treatment and the patient’s endometrium was significantly repaired, with successful pregnancy being achieved.ConclusionAutologous platelet-rich gel promoted endometrial repair and acted as a mechanical barrier to prevent intrauterine adhesion. This approach May offer new insights into IUA treatment.

Absolute lymphocyte count predicts efficacy of palbociclib in patients with metastatic luminal breast cancer

BackgroundAbsolute lymphocyte count (ALC) is a predictive and prognostic factor for various tumor types, including breast cancer. Palbociclib is a CDK4/6 inhibitor widely used for the treatment of metastatic estrogen receptor (ER)-positive, HER2-negative breast cancer. However, predictive biomarkers of the efficacy of palbociclib remain unelucidated. We conducted a retrospective study to examine the predictive value of the baseline ALC in patients treated with palbociclib.MethodsThe medical records of patients with ER-positive, HER2-negative breast cancer treated with palbociclib plus hormonal therapy between December 2017 and December 2021 were analyzed retrospectively. The cutoff value of ALC was set at 1800 cells/μL at the initiation of palbociclib treatment. The clinical benefit rate (CBR) was defined as the rate of complete or partial response or stable disease for at least 6 months. Progression-free survival (PFS) rates were estimated using the Kaplan–Meier method and compared using the log-rank test. Univariate and multivariate analyses were performed using Cox proportional hazards regression.ResultsAll of the 202 patients were women, with a median age of 59 years and a performance status (PS) of ≤ 2. The median numbers of lines of chemotherapy and endocrine therapy before palbociclib treatment were 0 (range, 0–9) and 1 (range, 0–7), respectively. Fifty-one patients had liver metastases. Forty-six patients tested negative for progesterone receptor (PgR) expression. The median follow-up time was 9.1 months. The CBR was significantly higher in the ALC-high group than in the ALC-low group (79% vs. 60%; P = 0.018). The median PFS was significantly longer in the ALC-high group than in the ALC-low group (26.8 months vs. 8.4 moths, respectively; P = 0.000013). ALC, age, PS, PgR status, prior chemotherapy, prior endocrine therapy, and liver metastasis were entered into the multivariate analysis. ALC was identified as an independent factor for PFS (P = 0.00085), along with liver metastasis (P = 0.0020), PS (P = 0.026), and prior endocrine therapy (P = 0.019).ConclusionALC can serve as a predictor of palbociclib efficacy in patients with metastatic ER-positive, HER2-negative breast cancer.

Effect of hormone therapy on personality traits: preliminary evidence in older men and women.

Findings concerning the effects of hormone therapy (HT) on cognition and dementia are mixed, with some trials suggesting increased harm at older ages. Personality, like cognition, changes with dementia, but no clinical trials to date have examined the effects of HT on personality traits. This study aimed to determine the effects of HT on personality traits in older men and women. Secondary data analysis was performed from randomized, double-blind, placebo-controlled cross-over studies of menopausal HT in women and testosterone therapy (TT) in men. Participants were community-dwelling cognitively normal adults (mean age = 75.2 years), including 29 men and 22 women. Three months of hormone intervention (for women, 0.625 mg/day conjugated equine estrogen with or without 2.5 mg/day medroxyprogesterone acetate; for men, 200 mg intramuscular testosterone enanthate every 2 weeks) were crossed over with 3 months of identical placebo with a 3-month washout between intervention phases. The main outcome measure was neuroticism and conscientiousness personality domains and facets assessed with the Revised NEO Personality Inventory (NEO-PI-R) after the active and placebo intervention phases. In linear mixed-effect models, HT in women decreased conscientiousness (p < 0.01) and the conscientiousness facet of achievement striving (p < 0.01), and increased vulnerability, a facet of neuroticism (p < 0.05). Testosterone in men decreased conscientiousness (p < 0.05) and the conscientiousness facet of dutifulness (p < 0.05), and increased vulnerability (p < 0.05). In a preliminary study of healthy older adults, HT and TT formulations produced adverse changes in vulnerability and conscientiousness facets that parallel personality changes in dementia.

A plain language summary of the CAPItello-291 study: Capivasertib in hormone receptor-positive advanced breast cancer.

This is a summary of the article discussing the results of the CAPItello-291 study. In the study, participants had advanced breast cancer that could not be completely removed with surgery, and that was diagnosed as a type of breast cancer where tumor cells had hormone receptors (HR-positive) but did not have HER2 receptors (HER2-negative). All participants were also required to have previously received treatment with a type of therapy called an aromatase inhibitor (with or without a CDK4/6 inhibitor), but over time their cancer cells had still grown or spread. The CAPItello-291 study researchers wanted to find out if a treatment combination of the medications capivasertib plus fulvestrant worked better than placebo plus fulvestrant. Capivasertib is a drug that blocks the activity of a protein called AKT, which is found inside breast cancer cells. The main finding was that participants who took capivasertib plus fulvestrant lived longer without their disease getting worse (progressing) compared with those treated with placebo plus fulvestrant. This is called progression-free survival. This result was seen across all participants (median progression-free survival of 7.2months with capivasertib plus fulvestrant vs 3.6months with placebo plus fulvestrant). It was also seen in participants whose tumors had detectable genetic alterations in genes called PIK3CA, AKT1, and/ or PTEN (median progression-free survival of 7.3months with capivasertib plus fulvestrant vs 3.1months with placebo plus fulvestrant). The most common side effects experienced by participants included diarrhea and different types of rash. These were as expected (given how capivasertib works). The CAPItello-291 study is still ongoing, and more results are expected to be released in the future. Results from the CAPItello-291 study showed that capivasertib plus fulvestrant compared with placebo plus fulvestrant improved progression-free survival in participants with HR-positive/ HER2-negative advanced breast cancer whose cancer had grown or spread despite hormone therapy (with/without a CDK4/6 inhibitor).Clinical Trial Registration: NCT04305496 (CAPItello-291) (ClinicalTrials.gov).

Insights on estetrol, the native estrogen: from contraception to hormone replacement therapy.

Estetrol (E4) is a natural estrogen that has recently emerged as new option for contraception and hormone replacement therapy (HRT). Unlike other estrogens, E4 primarily stimulates nuclear estrogen receptor alpha (ERα) and does not activate membrane ERα. For this reason, this novel estrogen has tissue-specific effects across various organs such as liver, vascular endothelium, mammary glands, brain, vagina, and uterus. The selective activation of the nuclear ERα results in distinct pharmacological properties that contribute to its unique therapeutic profile. Moreover, E4 shows minimal interaction with the hepatic cytochrome P450 enzyme system, leading to a favorable pharmacokinetic profile and a reduced potential for drug-drug interactions. Currently, E4 is commercially available in combination with drospirenone as a combined oral contraceptive and its application in HRT is undergoing late-stage clinical development. Many studies have demonstrated that E4 has a lower impact on hemostatic and metabolic parameters compared to other estrogens, potentially reducing the risk of adverse effects commonly associated with hormonal therapies such as thromboembolic events or dyslipidemia. Beyond its role in contraception and HRT, E4 shows promising therapeutic potential in other medical fields, including neuroprotection in neonatal hypoxic-ischemic encephalopathy, enhancement of hematopoietic stem cell transplantation outcomes and prostate cancer management. This review synthesizes the latest evidence on E4 primarily focusing on its pharmacological characteristics and clinical applications. The findings suggest that E4 versatility and peculiar mechanism of action may represent an important therapeutic option for a broad spectrum of medical conditions.

Cryoablation Without Excision for Early-Stage Breast Cancer: ICE3 Trial 5-Year Follow-Up on Ipsilateral Breast Tumor Recurrence.

The ICE3 trial evaluated the safety and efficacy of cryoablation in women aged ≥60years with low-risk, early-stage breast cancers, aiming to provide a non-operative treatment option and avoid potential surgical risks. This study presents 5-year follow-up trial results. The ICE3 trial is an Institutional Review Board-approved, prospective, multicentered, non-randomized trial including women ≥ 60 years of age with unifocal, ultrasound visible, invasive ductal carcinoma ≤ 1.5cm in size, histologic grade 1-2, hormone receptor (HR)-positive, and human epidermal growth factor receptor 2 (HER2)-negative. The primary study endpoint of 5-year ipsilateral breast tumor recurrence (IBTR) was evaluated based on Kaplan-Meier estimates. Overall, 194 patients meeting eligibility received successful cryoablation treatment per protocol and were included for analysis. The mean age was 74.9years (55-94) with a mean tumor size of 7.4mm transverse (2.8-14.0mm) and 8.1mm sagittal (2.5-14.9mm). With a mean follow-up period of 54.16 months, the IBTR rate at 5 years was 4.3% and breast cancer survival was 96.7%. Of the 124 patients who received endocrine therapy only, the IBTR was 3.7%. No serious device-related adverse events were reported. Minor (88.2%) and moderate (9.6%) adverse events were mild in severity and resolved without residual effects. Quality-of-life score demonstrated statistically significant improvement (p<0.001) in distress at 6 months as compared with baseline. Breast cryoablation presents a promising alternative to surgery in selected patients, offering the benefits of a minimally invasive procedure with minimal risks. Further studies are encouraged to confirm cryoablation as a viable alternative to surgical excision low-risk patients.

Trastuzumab Deruxtecan after Endocrine Therapy in Metastatic Breast Cancer.

Outcomes in patients with hormone receptor-positive metastatic breast cancer worsen after one or more lines of endocrine-based therapy. Trastuzumab deruxtecan has shown efficacy in patients with metastatic breast cancer with low expression of human epidermal growth factor receptor 2 (HER2) after previous chemotherapy. We conducted a phase 3, multicenter, open-label trial involving patients with hormone receptor-positive metastatic breast cancer with low HER2 expression (a score of 1+ or 2+ on immunohistochemical [IHC] analysis and negative results on in situ hybridization) or ultralow HER2 expression (IHC 0 with membrane staining) who had received one or more lines of endocrine-based therapy and no previous chemotherapy for metastatic breast cancer. Patients were randomly assigned in a 1:1 ratio to receive trastuzumab deruxtecan or the physician's choice of chemotherapy. The primary end point was progression-free survival (according to blinded independent central review) among the patients with HER2-low disease. Secondary end points included progression-free survival among all the patients who had undergone randomization, overall survival, and safety. Of the 866 patients who underwent randomization, 713 had HER2-low disease, and 153 had HER2-ultralow disease. Among the patients with HER2-low disease, the median progression-free survival was 13.2 months (95% confidence interval [CI], 11.4 to 15.2) in the trastuzumab deruxtecan group and 8.1 months (95% CI, 7.0 to 9.0) in the chemotherapy group (hazard ratio for disease progression or death, 0.62; 95% CI, 0.51 to 0.74; P<0.001); the results were consistent in the exploratory HER2-ultralow population. Data for overall survival were immature. Adverse events of grade 3 or higher occurred in 52.8% of the patients in the trastuzumab deruxtecan group and in 44.4% of those in the chemotherapy group. Adjudicated interstitial lung disease or pneumonitis occurred in 49 patients (11.3%; three events were grade 5 in severity) and in 1 patient (0.2%; grade 2), respectively. Among patients with hormone receptor-positive, HER2-low or HER2-ultralow metastatic breast cancer who had received one or more lines of endocrine-based therapy, treatment with trastuzumab deruxtecan resulted in longer progression-free survival than chemotherapy. No new safety signals were identified. (Funded by AstraZeneca and Daiichi Sankyo; DESTINY-Breast06 ClinicalTrials.gov number, NCT04494425.).

The vaginal microbiome of transgender men receiving gender-affirming hormonal therapy in comparison to that of cisgender women

The vaginal microbiome of trans men and menopausal women is suspected to be similar due to a lack of estrogen leading to the absence of lactobacilli. However, data are scarce. We performed an analysis of the vaginal microbiome of trans men (n = 25) in comparison to that of menopausal (n = 25) and premenopausal women (n = 25). The vaginal microbiome of trans men and menopausal women showed a higher alpha diversity than that of premenopausal women. Various beta diversity indices (e.g., Bray‒Curtis (Un-)Weigthed Unifrac), showed significant differences in community composition between trans men and premenopausal (p < 0.001) and menopausal women (p < 0.001). The vaginal microbiome of trans men is characterized by a loss of Lactobacillus and an increase in bacteria associated with the intestinal flora (e.g., Campylobacter, Anaerococcus, Dialister, Prevotella). The abundance of Dialister and Prevotella decreased with the length of hormonal therapy in trans men. The Nugent score, Pap smear and HPV status did not differ between the study groups. The vaginal microbiome of trans men differs from that of premenopausal women but shows similarities to that of menopausal women. The duration of hormonal therapy in trans men may have important impacts on the vaginal microbiome and thus possibly on the risk for STIs.

Impact of HDAC6-mediated progesterone receptor expression on the response of breast cancer cells to hormonal therapy

Modulation of estrogen receptor (ER) and progesterone receptor (PR) expression, as well as their emerging functional crosstalk, remains a potential approach for enhancing the response to hormonal therapy in breast cancer. Aberrant epigenetic alterations induced by histone deacetylases (HDACs) were massively implicated in dysregulating the function of hormone receptors in breast cancer. Although much is known about the regulation of ER signaling by HDAC, the precise role of HDAC in modulating the expression of PR and its impact on the outcomes of hormonal therapy is poorly defined. Here, we demonstrate the involvement of HDAC6 in regulating PR expression in breast cancer cells. The correlation between HDAC6 and hormone receptors was investigated in patients’ tissues by immunohistochemistry (n = 80) and publicly available data (n = 3260) from breast cancer patients. We explored the effect of modulating the expression of HDAC6 as well as its catalytic inhibition on the level of hormone receptors by a variety of molecular analyses, including western blot, immunofluorescence, Real-time PCR, RNA-seq analysis and chromatin immunoprecipitation. Based on our in-silico and immunohistochemistry analyses, HDAC6 levels were negatively correlated with PR status in breast cancer tissues. The downregulation of HDAC6 enhanced the expression of PR-B in hormone receptor-positive and triple-negative breast cancer (TNBC) cells. The selective targeting of HDAC6 by tubacin resulted in the enrichment of the H3K9 acetylation mark at the PGR-B gene promoter region and enhanced the expression of PR-B. Additionally, transcriptomic analysis of tubacin-treated cells revealed enhanced activity of acetyltransferase and growth factor signaling pathways, along with the enrichment of transcription factors involved in the transcriptional activity of ER, underscoring the crucial role of HDAC6 in regulating hormone receptors. Notably, the addition of HDAC6 inhibitor potentiated the effects of anti-ER and anti-PR drugs mainly in TNBC cells. Together, these data highlight the role of HDAC6 in regulating PR expression and provide a promising therapeutic approach for boosting breast cancer sensitivity to hormonal therapy.

Menopausal symptoms and utilization of menopausal hormone therapy among women aged 40–60 years in Addis Ababa, Ethiopia: a cross-sectional study

BackgroundThe onset of menopause leads to diminished estrogen exposure, resulting in a high morbidity burden related to menopausal symptoms. Menopausal hormonal therapy is an effective therapy that offers more advantages than disadvantages for women aged less than 60 years or who have had menopause for less than 10 years.ObjectiveThis study aimed to assess the prevalence of menopausal symptoms, identify factors associated with menopausal symptoms, and assess the use of menopausal hormone therapy among women aged 40–60 who visited the gynecological clinics of three hospitals in Addis Ababa, Ethiopia.MethodsA facility-based cross-sectional study was conducted from January 2022 to June 2022 at Gandhi Memorial Hospital, Tikur Anbessa Hospital, and Zewditu Memorial Hospital on 296 middle-aged women. Data were collected using an interviewer-administered structured questionnaire and analyzed for sociodemographic factors, utilization of menopausal hormone therapy, and prevalence of menopausal symptoms using the menopause rating scale. Data were analyzed using SPSS version 25. Bivariate and multivariate logistic regression analyses were performed to identify independent predictors of each subscale of menopausal symptoms. The strength of the association was measured using odds ratios with 95% confidence intervals, and statistical significance was set at a value of P < 0.05.ResultThe prevalence of menopausal symptoms was 89.9%. According to the menopausal rating scale, the frequency of reported symptoms was hot flushes (54.7%), muscle and joint pain (32.1%) on the somatic subscale; physical and mental exhaustion (55.1%), irritability (48.6%) on psychological subscale; and sexual problems (41.3%), bladder problems (39.2%) on urogenital subscale. This study also showed that the age of women [aOR: 0.317, 95%CI (0.102, 0.990)], and monthly family income [aOR = 0.182, 95% CI (0.041, 0.912)] were significantly associated with somatic menopausal symptoms. There was no utilization of menopausal hormonal therapy to treat menopausal symptoms and to prevent complications.ConclusionThe prevalence of menopausal symptoms is high; however, the utilization of individualized administration of menopausal hormone therapy according to symptoms is negligible. It appears essential for these institutions to work on service availability and delivery of menopausal hormone therapy for those in need of wider benefits for their clients.

Dual HER2 inhibition: mechanisms of synergy, patient selection, and resistance.

HER2-targeted therapies for patients with HER2+ breast cancer are rapidly evolving, offering a range of more complex and personalized treatment options. Currently, an array of anti-HER2 monoclonal antibodies, tyrosine kinase inhibitors and antibody-drug conjugates are administered, sometimes alongside chemotherapy or endocrine therapy, both in curative and palliative contexts. However, the heterogeneous nature of HER2+ breast cancer demands a deeper understanding of disease biology and its role in responsiveness to novel HER2-targeted agents, as well as non-HER2-targeted therapies, in order to optimize patient outcomes. In this Review, we revisit the mechanisms of action of HER2-targeted agents, examine the evidence supporting the use of dual HER2 blockade in patients with HER2-amplified tumours, and explore the role of biomarkers in guiding future treatment strategies. We also discuss potential implications for the future treatment of patients with HER2+ breast cancer.

Risk factors and severity of melasma in patients attending dermatology outpatient department of a tertiary care hospital: A cross-sectional study.

Melasma is a chronic acquired dysfunction of melanogenesis characterized by dark brown irregular macules on skin. Genetic predisposition, pregnancy, sun exposure, and hormonal therapy are common risk factors. Prevalence of melasma is variable, ranging from 5% to 46%. This study aimed to assess the severity and potential risk factors of melasma in a tertiary care setting. An analytical cross-sectional study was conducted on patients with melasma visiting dermatology department of a tertiary care center in Nepal. Nonprobability consecutive sampling was adopted. Severity of melasma was assessed using the Modified Melasma Area and Severity Index score. Data analysis was performed using the Statistical Package for the Social Sciences, version-23. Bivariate analysis was done by using Student t test/Mann-Whitney U test, or Chi-square/Fischer exact test for continuous and categorical variables, respectively. The overall median Modified Melasma Area and Severity Index score was 5.40 (3.60-6.75). Most patients (168, 88.42%) had mild melasma. The severity score was significantly higher in older age (P = .024), women having parity more than 3 (P = .014), centrofacial pattern (P = .024), and patients having dermatological comorbidities (P = .014). Severity was significantly lower in those who used cosmetics at home. Moreover, the use of digital screens was not associated with an increase in melasma severity. Most of the cases had mild melasma. Severity was significantly associated with age, parity, pattern, practice of cosmetic use, and presence of dermatological comorbidities.

Trajectory patterns and factors associated with acceptance of disability in young and middle-aged breast cancer patients: a longitudinal study.

To explore the trajectories of acceptance of disability in young and middle-aged breast cancer patients based on a latent class growth analysis, investigate factors associated with each trajectory, and identify whether return to normal living differs in different trajectories. Young and middle-aged patients newly diagnosed with breast cancer who underwent surgery were followed up at baseline, and 1, 3, and 6months in China. Participants completed sociodemographic information questionnaires, the Adaptation of Disability Scale Revised, and the Reintegration to Normal Living Index. A latent class growth analysis was used to explore the trajectories of acceptance of disability. Among 212 patients newly diagnosed with breast cancer, the mean age of patients was 45.44years. The majority of participants were with invasive carcinoma (77.8%). Three classes were identified: high acceptance of disability increasing group (high-increasing, 13.7%), moderate acceptance of disability stable group (moderate-stable, 67.9%), and moderate acceptance of disability decreasing group (moderate-decreasing, 18.3%). Being unemployed or retired and receiving endocrine therapy are risk factors associated with acceptance of disability. Carcinoma in situ is a protective factor associated with acceptance of disability. Participants diagnosed with carcinoma in situ and who not receive endocrine therapy were more likely to be in high-increasing group. Unemployed participants before surgery were more likely to be in moderate-decreasing group. Moreover, the Reintegration to Normal Living Index scores had significant differences from baseline to 6months of follow-up. The high-increasing group had the highest average Reintegration to Normal Living Index scores than the moderate-stable group and the moderate-decreasing group, showing similar patterns at four timepoints. We identified three trajectories of acceptance of disability. Dynamic and individualized intervention should be continuously provided to ensure patients acquire adequate medical resources to comprehensively increase acceptance of disability.

Salvage therapies for biochemical recurrence after definitive local treatment: a systematic review, meta-analysis, and network meta-analysis.

Recent advancements in the management of biochemical recurrence (BCR) following local treatment for prostate cancer (PCa), including the use of androgen receptor signaling inhibitors (ARSIs), have broadened the spectrum of therapeutic options. We aimed to compare salvage therapies in patients with BCR after definitive local treatment for clinically non-metastatic PCa with curative intent. In October 2023, we queried PubMed, Scopus, and Web of Science databases to identify randomized controlled trials (RCTs) and prospective studies reporting data on the efficacy of salvage therapies in PCa patients with BCR after radical prostatectomy (RP) or radiation therapy (RT). The primary endpoint was metastatic-free survival (MFS), and secondary endpoints included progression-free survival (PFS) and overall survival (OS). We included 19 studies (n = 9117); six trials analyzed RT-based strategies following RP, ten trials analyzed hormone-based strategies following RP ± RT or RT alone, and three trials analyzed other agents. In a pairwise meta-analysis, adding hormone therapy to salvage RT significantly improved MFS (HR: 0.69, 95% CI: 0.57-0.84, p < 0.001) compared to RT alone. Based on treatment ranking analysis, among RT-based strategies, the addition of elective nodal RT and androgen deprivation therapy (ADT) was found to be the most effective in terms of MFS. On the other hand, among hormone-based strategies, enzalutamide + ADT showed the greatest benefit for both MFS and OS. The combination of prostate bed RT, elective pelvic irradiation, and ADT is the preferred treatment for eligible patients with post-RP BCR based on our analysis. In remaining patients, or in case of post-RT recurrence, especially for those with high-risk BCR, the combination of ADT and ARSI should be considered.

Real-world outcomes following biochemical recurrence after definitive therapy with a short prostate-specific antigen doubling time: potential role of early secondary treatment.

The natural history of biochemical recurrence (BCR) managed with delayed hormonal therapy is well documented by data from Johns Hopkins. However, as many patients receive treatment prior to metastasis, we evaluated the natural history and role of prostate-specific antigen doubling time (PSADT) in a more contemporary cohort of BCR patients with nonmetastatic castration-sensitive prostate cancer (nmCSPC). Patients in the Veterans Health Administration (VHA; 01/01/06 to 06/22/20) with nmCSPC and BCR were divided into rapid ( ≤9 months) and less rapid ( >9 to ≤15 months) PSADT cohorts. Patients with PSADT >15 months were excluded as outcomes, even with delayed treatment, are excellent. Outcomes included time to first antineoplastic therapy after BCR, metastasis, metastasis-free survival (MFS), and overall survival (OS). Cox models adjusted for baseline demographics and clinical characteristics. Overall, 781 patients with BCR were identified (502 rapid; 279 less rapid PSADT). Rapid PSADT was associated with shorter time to first systemic antineoplastic therapy (median 11.4 vs. 28.3 months, adjusted hazard ratio [95% confidence interval] 2.17 [1.83-2.57]), metastasis (102.4 months vs. not reached, 1.79 [1.33-2.40]), MFS (76.1 vs. 106.3 months, 1.73 [1.33-2.24]), and OS (120.5 vs. 140.5 months, 1.76 [1.22-2.54]) versus less rapid PSADT. Most patients with rapid PSADT underwent secondary treatment within 1 year after BCR. More contemporary patients treated with early secondary treatment had better outcomes than historical data from patients who had delayed treatment. Whether these results reflect the benefits of early secondary treatment or overall improvements in prostate cancer outcomes over time requires further study.

Datopotamab Deruxtecan Versus Chemotherapy in Previously Treated Inoperable/Metastatic Hormone Receptor-Positive Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer: Primary Results From TROPION-Breast01.

The global, phase 3, open-label, randomized TROPION-Breast01 study assessed the trophoblast cell surface antigen 2-directed antibody-drug conjugate datopotamab deruxtecan (Dato-DXd) versus investigator's choice of chemotherapy (ICC) in hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer. Adult patients with inoperable/metastatic HR+/HER2‒ breast cancer, who had disease progression on endocrine therapy, for whom endocrine therapy was unsuitable, and had received one to two previous lines of chemotherapy in the inoperable/metastatic setting, were randomly assigned 1:1 to Dato-DXd (6 mg/kg once every 3 weeks) or ICC (eribulin/vinorelbine/capecitabine/gemcitabine). Dual primary end points were progression-free survival (PFS) by blinded independent central review (BICR) and overall survival (OS). Patients were randomly assigned to Dato-DXd (n = 365) or ICC (n = 367). Dato-DXd significantly reduced the risk of progression or death versus ICC (PFS by BICR hazard ratio [HR], 0.63 [95% CI, 0.52 to 0.76]; P < .0001). Consistent PFS benefit was observed across subgroups. Although OS data were not mature, a trend favoring Dato-DXd was observed (HR, 0.84 [95% CI, 0.62 to 1.14]). The rate of grade ≥3 treatment-related adverse events (TRAEs) with Dato-DXd was lower than ICC (20.8% v 44.7%). The most common TRAEs (any grade; grade ≥3) were nausea (51.1%; 1.4%) and stomatitis (50%; 6.4%) with Dato-DXd and neutropenia (grouped term, 42.5%; 30.8%) with ICC. Patients receiving Dato-DXd had statistically significant and clinically meaningful improvement in PFS and a favorable and manageable safety profile, compared with ICC. Results support Dato-DXd as a novel treatment option for patients with inoperable/metastatic HR+/HER2‒ breast cancer who have received one to two previous lines of chemotherapy in this setting.

Systematic review and recommendations for re-irradiation for intraprostatic radiorecurrent prostate cancer after definitive radiation therapy.

Intraprostatic recurrence (IRR) of prostate cancer after radiation therapy is increasingly identified. Our objective was to review the literature to determine the optimal workup for identifying IRR, the management options, and practical considerations for the delivery of re-irradiation as salvage local therapy. We performed a systematic review of available publications and ongoing studies on the topics of IRR, with a focus on salvage re-irradiation. Work up of biochemically recurrent prostate cancer includes PSMA PET/CT and multiparametric MRI, followed by biopsy to confirm IRR. Management options include continued surveillance, palliative hormonal therapy, and salvage local therapy. Salvage local therapy can be delivered using re-irradiation with low dose rate brachytherapy, high dose rate (HDR) brachytherapy, and stereotactic body radiotherapy (SBRT), as well as non-radiation modalities, such as cryotherapy, high-intensity focused ultrasound, irreversible electroporation and radical prostatectomy. Data demonstrate that HDR brachytherapy and SBRT have similar efficacy compared to the other salvage local therapy modalities, while having more favorable side effect profiles. Recommendations for radiation therapy planning and delivery using HDR and SBRT based on the available literature are discussed. Salvage re-irradiation is safe and effective and should be considered in patients with IRR.