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Purpose: To assess the efficacy and safety of apalutamide plus goserelin for androgen receptor (AR)-positive unresectable or recurrent/metastatic salivary gland carcinoma., Patients and Methods: This trial was an open-label, single-arm, multicenter phase II study. Patients with histologically confirmed unresectable or recurrent/metastatic salivary gland carcinoma with AR expression were included. The primary endpoint was the overall response rate (ORR) according to RECIST v1.1 by an independent central radiology review in the first 24 response-evaluable (RE) patients who had been observed at least 24 weeks from study initiation (primary RE patients). The efficacy was to be declared when at least 8 of the 24 primary RE patients responded., Results: A total of 31 patients were enrolled. In the first 24 primary RE patients with a median follow-up of 7.4 months, confirmed ORR by independent central radiology review was 25.0% [6/24 patients; 95% confidence interval, 9.8%-46.7%; P = 0.11 (one-sided)], which did not meet the predefined criteria of efficacy. Clinical benefit rate (ORR + rate of stable disease for at least 24 weeks) and median progression-free survival were 50.0% and 7.4 months, respectively. Both median duration of response and overall survival were not reached. Exploratory analyses showed a better ORR of 54.5% (6/11) in patients with AR positivity ≥70% and no history of prior systemic therapy. Grade 3 or higher treatment-emergent adverse events were reported in 35.5% (11/31), which included skin rash, anemia, leukopenia, and cancer pain., Conclusions: Although this study did not meet the predefined efficacy criteria, apalutamide plus goserelin showed clinically meaningful efficacy in a subset of patients with AR-positive salivary gland carcinoma and safety consistent with prior experience in prostate cancer., (©2024 American Association for Cancer Research.)

Purpose: This study evaluated the effectiveness of ovarian function suppression (OFS) of various gonadotropin-releasing hormone agonists (GnRHa) combined with aromatase inhibitors (AI) in premenopausal patients with hormone receptor-positive (HR-positive) breast cancer. Potential risk factors associated with insufficient OFS were analyzed., Patients and Methods: Premenopausal HR-positive breast cancer patients who had received AI with GnRHa were studied retrospectively. Patients were divided into different groups according to monthly or trimonthly GnRHa schedules they received, and the effectiveness of OFS was compared between groups. Insufficient OFS was defined as at least one instance of estradiol ≥ 30 pg/ml. Patient data was gathered from medical records for this comparison., Results: Of the 264 patients enrolled in this study, 117 were administered 3.6 mg of goserelin monthly (goserelin 1 M group), 63 received 3.75 mg of leuprorelin monthly (leuprorelin 1 M group) and 84 were given 11.25 mg of leuprorelin every three months (leuprorelin 3 M group). Overall, 7.20% experienced insufficient OFS. The incidence rates in the three GnRHa depot groups were 7.69%, 6.35%, and 7.14%, respectively, without a significant statistical difference (P = 0.900). Notably, younger patients exhibited a higher likelihood of insufficient OFS [OR = 0.900, 95%CI (0.824-0.982), P = 0.018]., Conclusion: Insufficient OFS remains a concern during GnRHa and AI treatment. The effectiveness of the three GnRHa depots commonly used in China seems comparable. Younger patients face a heightened risk of insufficient OFS., (© 2024. The Author(s).)

Objective: We carried out this study to explore the possibility of initiating goserelin therapy during the non-menstrual period in patients diagnosed with adenomyosis., Methods: 115 premenopausal adenomyosis patients were enrolled and divided into three groups based on their menstrual cycle phase during the initial outpatient visit: menstrual, follicular, and luteal. Each received a 3.6 mg subcutaneous dose of goserelin monthly for three months. The endpoints encompassed alterations in uterine volume, dysmenorrhea Numerical Rating Scale (NRS) score, CA125 level, hemoglobin (HGB) after a 12-week treatment course, and the occurrence and duration of uterine hemorrhage during the first treatment cycle., Results: Analysis revealed that the timing of goserelin therapy initiation in the menstrual cycle did not significantly impact its effectiveness in reducing uterine size, alleviating pain, lowering CA125 levels, or improving hemoglobin concentrations. However, patients starting treatment during the luteal phase experienced increased uterine bleeding (reference: menstrual period, OR = 4.33, 95% CI 1.23-15.25, p  = .023)., Conclusions: The results suggested non-inferiority of goserelin therapy initiated during the non-menstrual period, but the uterine bleeding rate was higher in the luteal phase group. Therefore, goserelin treatment for outpatient adenomyosis patients should not be limited to starting during the menstrual period; it can also be initiated outside the menstrual period, providing more convenience for patients as most consultations occur outside the menstrual period. However, the use of goserelin during the luteal phase should be avoided to reduce the risk of exacerbated bleeding, especially in anemic patients with heavy menstrual bleeding. This study highlights the importance of individualizing treatment initiation based on the patient's health profile to optimize therapeutic outcomes and minimize adverse effects., Trial Registration: ChiCTR2200059548.

Objectives: Metastatic prostate cancer is the most common malignant cancer and the second leading cause of death due to various types of cancer among men after lung cancer. This study aimed to analyze the cost-effectiveness of triptorelin, goserelin, and leuprolide in the treatment of the patients with metastatic prostate cancer from the societal perspective in Iran in 2020., Methods: This is a cost-effectiveness study in which a 20-year Markov transition modeling was applied. In this study, local cost and quality-of-life data of each health state were gathered from cohort of patients. The TreeAge pro 2020 and Microsoft Excel 2016 software were used to simulate cost-effectiveness of each treatment in the long term. The one-way and probabilistic sensitivity analyses were also performed to measure robustness of the model outputs., Results: The findings indicated that the mean costs and utility gained over a 20-year horizon for goserelin, triptorelin, and leuprolide treatments were $ 13 539.13 and 6.365 quality-adjusted life-years (QALY), $ 18 124.75 and 6.658 QALY, and $ 26 006.92 and 6.856 QALY, respectively. Goserelin was considered as a superior treatment option, given the estimated incremental cost-effectiveness ratio. The one-way and probabilistic sensitivity analyses confirmed the robustness of the study outcomes., Conclusions: According to the results of the present study, goserelin was the most effective and cost-effective strategy versus 2 other options. It could be recommended to policy makers of the Iran healthcare system to prioritize it in clinical guidelines and reimbursement policies., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section., (Copyright © 2024 International Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Background: Ribociclib has been shown to have a significant overall survival benefit in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. Whether this benefit in advanced breast cancer extends to early breast cancer is unclear., Methods: In this international, open-label, randomized, phase 3 trial, we randomly assigned patients with HR-positive, HER2-negative early breast cancer in a 1:1 ratio to receive ribociclib (at a dose of 400 mg per day for 3 weeks, followed by 1 week off, for 3 years) plus a nonsteroidal aromatase inhibitor (NSAI; letrozole at a dose of 2.5 mg per day or anastrozole at a dose of 1 mg per day for ≥5 years) or an NSAI alone. Premenopausal women and men also received goserelin every 28 days. Eligible patients had anatomical stage II or III breast cancer. Here we report the results of a prespecified interim analysis of invasive disease-free survival, the primary end point; other efficacy and safety results are also reported. Invasive disease-free survival was evaluated with the use of the Kaplan-Meier method. The statistical comparison was made with the use of a stratified log-rank test, with a protocol-specified stopping boundary of a one-sided P-value threshold of 0.0128 for superior efficacy., Results: As of the data-cutoff date for this prespecified interim analysis (January 11, 2023), a total of 426 patients had had invasive disease, recurrence, or death. A significant invasive disease-free survival benefit was seen with ribociclib plus an NSAI as compared with an NSAI alone. At 3 years, invasive disease-free survival was 90.4% with ribociclib plus an NSAI and 87.1% with an NSAI alone (hazard ratio for invasive disease, recurrence, or death, 0.75; 95% confidence interval, 0.62 to 0.91; P = 0.003). Secondary end points - distant disease-free survival and recurrence-free survival - also favored ribociclib plus an NSAI. The 3-year regimen of ribociclib at a 400-mg starting dose plus an NSAI was not associated with any new safety signals., Conclusions: Ribociclib plus an NSAI significantly improved invasive disease-free survival among patients with HR-positive, HER2-negative stage II or III early breast cancer. (Funded by Novartis; NATALEE ClinicalTrials.gov number, NCT03701334.)., (Copyright © 2024 Massachusetts Medical Society.)

Background: Pharmacobiological behavior differs between gonadotropin-releasing hormone (GnRH) antagonists and GnRH agonists. However, reliable evidence clarifying the difference between them is limited., Objectives: We aimed to elucidate the difference in recovery profile between GnRH antagonist (degarelix) and GnRH agonist (leuprorelin acetate or goserelin acetate) as short-term (12 weeks) neoadjuvant androgen deprivation therapy (ADT) prior to 125I-transperineal prostate brachytherapy (TPPB) for localized prostate cancer., Materials and Methods: This study was initially designed as a single-center, prospective, open-label, randomized controlled trial. The primary endpoint was a serum testosterone level above the castration range (>50 ng/dl) after the cessation of 12-week neoadjuvant ADT (GnRH antagonist or GnRH agonists). All patients underwent 12 weeks of neoadjuvant ADT. The recovery profiles of hormones, prostate-specific antigen, total prostate volume (TPV), bone mineral density, and quality of life scores were investigated., Results: Testosterone recovery duration after the last injection was significantly longer in the GnRH antagonist arm than in the GnRH agonist arm (median, 27.3 vs. 4.8 weeks, p < 0.001). The serum levels of luteinizing hormone and follicle-stimulating hormone in the GnRH antagonist arm also remained significantly lower than those in the GnRH agonist arm between 16 and 24 weeks (p < 0.01). Meanwhile, reduction in TPV at the time of TPPB was comparable between both arms (p = 0.128). There were also no significant between-arm differences in the International Prostate Symptom Score and the International Index of Erectile Function scores., Discussion and Conclusion: The recovery patterns of hormonal profiles after short-term (12 weeks) neoadjuvant ADT differ between GnRH antagonists and GnRH agonists. The choice between these drugs matters and may have a clinical impact depending on the primary objective of ADT., (© 2021 American Society of Andrology and European Academy of Andrology.)

Survival of breast cancer patients has improved, and treatment-related changes regarding metabolic profile deterioration after neoadjuvant systemic treatment (NST) become important issues in cancer survivors. We sought to compare metabolic profile changes and the neutrophil-to-lymphocyte ratio (NLR) between patients undergoing neoadjuvant chemotherapy (NCT) and neoadjuvant endocrine therapy (NET) 3 years after the treatment. In a prospective, randomized, phase III trial which compared 24 weeks of NCT with adriamycin and cyclophosphamide followed by docetaxel and NET with goserelin and tamoxifen (NEST), 123 patients in the Asan Medical Center were retrospectively reviewed to evaluate metabolic changes, such as body mass index (BMI), blood pressure (BP), total cholesterol (TC), fasting glucose, and the NLR. The mean age of patients was 42 years. The changes in BMI, serum glucose, and TC during NST and after 3 years were significantly different between NCT and NET. The proportion of overweight + obese group and the mean BMI were significantly increased during NCT (26.6% to 37.5%, 22.84 kg/m 2 to 23.87 kg/m 2 , p < 0.05), and these attributes found to have normalized at the 3-year follow-up. In the NET group, BMI changes were not observed (p > 0.05, all). There were no differences in changes over time among in the Hypertension group during NCT and NET (p = 0.96). The mean value of serum TC and fasting glucose significantly increased (< 0.05, both) during NCT and decreased 3 years after NCT (p < 0.05); however, no significant changes were observed in the NET group. The NLR was increased from 1.83 to 3.18 after NCT (p < 0.05) and decreased from 1.98 to 1.43 (p < 0.05) after NET. Compared with minimal metabolic effect of NET, NCT worsens metabolic profiles, which were recovered over 3 years. The NLR was increased after NCT but decreased after NET.

Background: CDK4/6 inhibitors have shown promising results for treating advanced breast cancer (ABC) and are routinely used in Singapore. In view of their high costs, it is important to assess their relative value compared to existing standards of care in the local setting., Aims: This study evaluates the cost-effectiveness of adding ribociclib to goserelin and a nonsteroidal aromatase inhibitor or tamoxifen as initial therapy for premenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) ABC in Singapore., Methods: A partitioned survival model with four health states (progression-free on first-line treatment, progression-free on second-line treatment, progressed disease, and death) was developed from a healthcare system perspective over a 10-year time horizon. Key clinical inputs were derived from the MONALEESA-7 trial, and survival curves were extrapolated beyond the trial period. Health state utilities were derived from the literature and direct medical costs were obtained from local public healthcare institutions. A discount rate of 3% was applied to both costs and outcomes. One-way deterministic and probabilistic sensitivity analyses were conducted to explore uncertainties., Results: The base-case analysis resulted in an incremental cost-effectiveness ratio (ICER) of SGD197, 667 per quality-adjusted life-year. Sensitivity analyses showed that the ICER was sensitive to the survival parametric distribution, ribociclib price, time horizon, and utility weights used. Even when these were varied, ICERs remained high and not cost-effective in the local context., Conclusion: At its current price, adding ribociclib to endocrine therapy is unlikely to be cost-effective in Singapore for HR+, HER2- ABC. Results from this study are useful to inform future funding decisions for CDK4/6 inhibitors alongside other factors including clinical effectiveness, safety, and budget impact considerations., (© 2020 The Authors. Cancer Reports published by Wiley Periodicals LLC..)

Background: Uterine fibroids can cause heavy menstrual bleeding. Medical treatments are considered to preserve fertility. It is unclear whether progestogens or progestogen-releasing intrauterine systems can reduce fibroid-related symptoms. This is the first update of a Cochrane Review published in 2013., Objectives: To determine the effectiveness of progestogens or progestogen-releasing intrauterine systems in treating premenopausal women with uterine fibroids., Search Methods: We searched the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, and PsycINFO databases to July 2020. We also searched trials registers for ongoing and registered trials, and checked references of relevant trials., Selection Criteria: All identified published or unpublished randomised controlled trials (RCTs) assessing the effect of progestogens or progestogen-releasing intrauterine systems in treating premenopausal women with uterine fibroids., Data Collection and Analysis: Two authors independently extracted data, assessed risk of bias, and assessed the quality of the evidence using the GRADE approach., Main Results: This updated review included four studies with 221 women with uterine fibroids. The evidence was very low quality, downgraded for serious risk of bias, due to poor reporting of study methods, and serious imprecision. Levonorgestrel-releasing intrauterine device (LNG-IUS) versus hysterectomy There was no information on the outcomes of interest, including adverse events. LNG-IUS versus low dose combined oral contraceptive (COC) At 12 months, we are uncertain whether LNG-IUS reduced the percentage of abnormal uterine bleeding, measured with the alkaline hematin test (mean difference (MD) 77.50%, 95% confidence interval (CI) 70.44 to 84.56; 1 RCT, 44 women; very low-quality evidence), or the pictorial blood assessment chart (PBAC; MD 34.50%, 95% CI 11.59 to 57.41; 1 RCT, 44 women; very low-quality evidence); increased haemoglobin levels (MD 1.50 g/dL, 95% CI 0.85 to 2.15; 1 RCT, 44 women; very low-quality evidence), or reduced fibroid size more than COC (MD 1.90%, 95% CI -12.24 to 16.04; 1 RCT, 44 women; very low-quality evidence). The study did not measure adverse events. LNG-IUS versus oral progestogen (norethisterone acetate (NETA)) Compared to NETA, we are uncertain whether LNG-IUS reduced abnormal uterine bleeding more from baseline to six months (visual bleeding score; MD 23.75 points, 95% CI 1.26 to 46.24; 1 RCT, 45 women; very low-quality evidence); increased the percentage of change in haemoglobin from baseline to three months (MD 4.53%, 95% CI 1.46 to 7.60; 1 RCT, 48 women; very low-quality evidence), or from baseline to six months (MD 10.14%, 95% CI 5.57 to 14.71; 1 RCT, 45 women; very low-quality evidence). The study did not measure fibroid size. Spotting (adverse event) was more likely to be reported by women with the LNG-IUS (64.3%) than by those taking NETA (30%; 1 RCT, 45 women; very low-quality evidence). Oral progestogen (dienogest, desogestrel) versus goserelin acetate Compared to goserelin acetate, we are uncertain whether abnormal uterine bleeding was reduced at 12 weeks with dienogest (PBAC; MD 216.00 points, 95% CI 149.35 to 282.65; 1 RCT, 14 women; very low-quality evidence) or desogestrel (PBAC; MD 78.00 points, 95% CI 28.94 to 127.06; 1 RCT, 16 women; very low-quality evidence). Vasomotor symptoms (adverse events, e.g. hot flashes) are only associated with goserelin acetate (55%), not with dienogest (1 RCT, 14 women; very low-quality evidence) or with desogestrel (1 RCT, 16 women; very low-quality evidence). The study did not report fibroid size., Authors' Conclusions: Because of very low-quality evidence, we are uncertain whether the LNG-IUS reduces abnormal uterine bleeding or increases haemoglobin levels in premenopausal women with uterine fibroids, compared to COC or norethisterone acetate. There was insufficient evidence to determine whether the LNG-IUS reduces the size of uterine fibroids compared to COC. We are uncertain whether oral progestogens reduce abnormal uterine bleeding as effectively as goserelin acetate, but women reported fewer adverse events, such as hot flashes., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

We report the failure to achieve castrate level of serum testosterone during luteinizing hormone-releasing hormone agonist therapy in a patient with prostate cancer. A 76-year-old man was admitted to our hospital for evaluation of an elevated serum prostate specific antigen (PSA) level (191.10 ng/ml) in August 2011. He was diagnosed with T3aN0M1b prostate adenocarcinoma. A combined androgen blockade using luteinizing hormone-releasing hormone agonist (the 1-month depot of leuprorelin acetate) and antiandrogen was administered. Due to liver dysfunction, antiandrogens, both bicalutamide and flutamide, were stopped. The 1-month depot was switched to the 3-month depot in May 2013, but the patient complained of induration and abscess at the infection site. Leuprorelin acetate was replaced by goserelin acetate. Because no adverse event appeared after injection of the 1-month depot of goserelin acetate, the 3-month depot was administered in October 2013. The PSA level increased gradually, and the testosterone level was greater than 50 ng/dl, that is, above castrate range. The 3-month depot of both leuprorelin acetate and goserelin acetate was not effective for this patient. For this reason, the 1-month depot of leuprorelin acetate was started resulting in a rapid decrease in PSA and testosterone levels. Thereafter, androgen depriving therapy could be continued. Androgen deprivation therapy is the standard treatment for patients with advanced prostate cancer and luteinizing hormone-releasing hormone aims to suppress serum testosterone to castrate range. We recommend assessing the serum testosterone levels during luteinizing hormone-releasing hormone agonist therapy for monitoring treatment efficacy and verifying progression when the PSA level increases.

Purpose: To assess the predictive value of molecular breast cancer subtypes in premenopausal patients with hormone receptor-positive early breast cancer who received adjuvant endocrine treatment or chemotherapy., Experimental Design: Molecular breast cancer subtypes were centrally assessed on whole tumor sections by IHC in patients of the Austrian Breast and Colorectal Cancer Study Group Trial 5 who had received either 5 years of tamoxifen/3 years of goserelin or six cycles of cyclophosphamide, methotrexate, and fluorouracil (CMF). Luminal A disease was defined as Ki67 <20% and luminal B as Ki67 ≥20%. The luminal B/HER2-positive subtype displayed 3+ HER2-IHC or amplification by ISH. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using Cox models adjusted for clinical and pathologic factors., Results: 185 (38%), 244 (50%), and 59 (12%) of 488 tumors were classified as luminal A, luminal B/HER2-negative and luminal B/HER2-positive, respectively. Luminal B subtypes were associated with poor outcome. Patients with luminal B tumors had a significantly shorter RFS [adjusted HR for recurrence: 2.22; 95% confidence interval (CI), 1.41-3.49; P = 0.001] and OS (adjusted HR for death: 3.51; 95% CI, 1.80-6.87; P < 0.001). No interaction between molecular subtypes and treatment was observed (test for interaction: P = 0.84 for RFS; P = 0.69 for OS)., Conclusions: Determination of molecular subtypes by IHC is an independent prognostic factor for recurrence and death in premenopausal women with early-stage, hormone receptor-positive breast cancer but is not predictive for outcome of adjuvant treatment with tamoxifen/goserelin or CMF. See related commentary by Hunter et al., p. 5543 ., (©2020 American Association for Cancer Research.)

Rationale: Poorly differentiated neuroendocrine carcinoma of the breast is a rare cancer with poor prognosis. There is no standard treatment for the disease. Neoadjuvant therapies and surgery are considered to be the main treatment when the tumor diameter is greater than 5.0 cm. Neoadjuvant therapies include chemotherapy and endocrine therapy. However, the effect of neoadjuvant endocrine therapy is not clear in the disease., Patient Concerns: In August 2014, a 28-year-old premenopausal woman noted a mass that was approximately 3.0 cm*2.0 cm in size on her right breast with pain. Subsequently, the mass has been always increasing significantly. In August 2015, the mass was approximately 7.0 cm*5.0 cm in size, accompanied by pain, no nipple retraction and discharge, no orange peel-like skin changes, and no dimples. In addition, she had no salient past history., Diagnoses: Histopathological examinations by a biopsy with a thick needle (hollow needle) and surgical resection confirmed poorly differentiated neuroendocrine carcinoma of the right breast., Interventions: First and remarkably, she underwent 3 months of neoadjuvant endocrine therapy (goserelin once every 28 days, and letrozole 10 mg every day). Then, she underwent surgery - stage I breast reconstruction by using prosthesis. Adjuvant endocrine therapy has been used since the operation., Outcomes: According to response evaluation criteria in solid tumors 1.1, the tumor was shrunk by 78.87% after neoadjuvant endocrine therapy. No salient complications were observed. We have followed her for 48 months, and there are no signs of recurrence and metastasis., Lessons: Poorly differentiated neuroendocrine carcinoma of the breast is rare and has a poor prognosis. Currently, there is no standard treatment for this disease. Studies show estrogen receptor and progesterone receptor of neuroendocrine carcinoma of the breast are often highly expressed. In the case, it can be observed that estrogen receptor and progesterone receptor are highly expressed. Therefore, neoadjuvant endocrine therapy may be considered in neuroendocrine carcinoma of the breast when the mass is large and the patient refuses neoadjuvant chemotherapy. We hope to provide an attractive evidence for neoadjuvant endocrine therapy of neuroendocrine carcinoma of the breast. However, more cases are still being needed for research.

Background: The OPTION trial results showed that premenopausal women with early stage breast cancer (EBC) receiving chemotherapy benefited from ovarian function protection with goserelin. The impact of treatments on patient reported Quality of Life (QoL) were also examined., Patients and Methods: 227 pre-menopausal women with EBC, were randomly assigned to chemotherapy±goserelin (C±G); 132 (58%) were ER-ve. Patients were stratified by age (≤40 years and >40 years). QoL was assessed with the Functional Assessment of Cancer Therapy - Breast, and Endocrine Symptom checklist at baseline (pre-treatment), 3, 6, 12, 18 and 24 months, then annually to 5 years. Treatment Outcome Index (TOI) score was the primary outcome., Results: 213 patients were available for QoL analysis. There was a significant decrease in TOI scores for both treatment groups at 3 and 6 months that returned to pre-treatment levels at 12 months, then continued to increase reflecting improved QoL. By 3 months there was a significant difference from baseline in both groups for menopausal symptoms, and between groups in the proportion experiencing hot flushes at any time. The C + G group experienced higher levels of vasomotor symptoms generally during the treatment phase; by 24 months, the short-term negative effect of goserelin was reversed, with hot flushes twice as frequent in the chemotherapy only group (40.9% vs 21.3%)., Conclusions: These results show that young women diagnosed with breast cancer experienced only a short-term decrease in QoL from the addition of goserelin, in order to preserve ovarian function during chemotherapy treatment., Competing Interests: Declaration of competing interest The authors have no financial relationships relevant to the submitted work. Details of Ethics Approval: The study was approved by the North West research ethics (ref MREC/03/6/90)., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Context: Most labs set the lower limit of normal for testosterone at the 2.5th percentile of values in young or age-matched men, an approach that does not consider the physiologic changes associated with various testosterone concentrations., Objective: To characterize the dose-response relationships between gonadal steroid concentrations and measures regulated by gonadal steroids in older men., Design, Participants, and Intervention: 177 men aged 60 to 80 were randomly assigned to receive goserelin acetate plus either 0 (placebo), 1.25, 2.5, 5, or 10 grams of a 1% testosterone gel daily for 16 weeks or placebos for both medications (controls)., Primary Outcomes: Changes in serum C-telopeptide (CTX), total body fat by dual energy X-ray absorptiometry, and self-reported sexual desire., Results: Clear relationships between the testosterone dosage (or the resulting testosterone levels) and a variety of outcome measures were observed. Changes in serum CTX exceeded changes in the controls in men whose testosterone levels were 0 to 99, 100 to 199, 200 to 299, or 300 to 499 ng/dL, whereas increases in total body fat, subcutaneous fat, and thigh fat exceeded controls when testosterone levels were 0 to 99 or 100 to 199 ng/dL. Sexual desire and erectile function were indistinguishable from controls until testosterone levels were <100 ng/dL., Conclusion: Changes in measures of bone resorption, body fat, and sexual function begin at a variety of testosterone concentrations with many outcome measures remaining stable until testosterone levels are well below the stated normal ranges. In light of this variation, novel approaches for establishing the normal range for testosterone are needed., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background Uterine leiomyoma is a benign tumour of the uterine smooth muscles associated with an elevated level of inflammatory cytokines. Goserelin, a synthetic gonadotropin-releasing hormone analogue, suppresses the production of sex hormones and release of inflammatory cytokines in uterine leiomyoma cells. Objective The primary objective of this study was to find out the effectiveness of subcutaneous goserelin therapy on lowering serum levels of inflammatory cytokines and improving uterine leiomyoma-related symptoms in female patients diagnosed with uterine leiomyoma. The secondary objective was to assess the tolerability to goserelin therapy used in the management of this tumour. Setting Outpatient gynaecological clinic of the medical consultation department of Baghdad Teaching Hospital, Baghdad province, Iraq. Methods A single centre, prospective, longitudinal, cohort study was carried out on female patients diagnosed with uterine leiomyoma. Goserelin 3.6 mg subcutaneous injection was given in a consecutive monthly dose for the total time duration of three months. Serum levels of inflammatory cytokines, tumour necrosis factor-α and monocyte chemotactic protein-1 were detected before and after goserelin therapy in a consecutive monthly assessment. The study also assessed the improvement in uterine leiomyoma-related symptoms, including pelvic pain alongside the incidence of goserelin-related side effects during therapy schedules. Main Outcome Measures Assessment of serum levels of tumour necrosis factor-α and monocyte chemotactic protein-1 alongside uterine leiomyoma-related symptoms, including pelvic pain and goserelin-related side effects. Results There was a significant decrease in serum levels of tumour necrosis factor-α and monocyte chemotactic protein-1 compared to the baseline level over the 3-month duration of goserelin therapy (0.11 ± 0.02 vs. 0.74 ± 0.19) pg/mL; (0.07 ± 0.00 vs. 0.44 ± 0.18) pg/mL respectively. Patients showed a clinical improvement regarding uterine leiomyoma-related symptoms following each of the consecutive monthly doses of goserelin therapy (n = 11, 55%, P < 0.0001; n = 15, 75%, P < 0.0001; n = 18, 90%, P < 0.0001) respectively. This also includes a significant decrease in the intensity of leiomyoma-related pelvic pain before and after goserelin therapy (7.2 ± 1.43 vs. 3.05 ± 1.14, P < 0.0001). The majority of patients reported vaginal dryness (60%) as the main goserelin-related side effect. Conclusion Goserelin therapy reduces serum levels of inflammatory cytokines, tumour necrosis factor- α and monocyte chemotactic protein-1, improving leiomyoma-related symptoms with good tolerability in patients with uterine leiomyoma.

This study elucidated the degree of adenomyosis recurrence following gonadotropin-releasing hormone agonist (GnRHa) discontinuation and dienogest efficiency for recurrent adenomyosis. This retrospective cohort study included 30 patients, divided into a group of patients whose progress was observed without providing additional therapy following GnRHa administration for six months (Group G) and a group of patients administered dienogest for six months following six months of GnRHa administration (Group D). Menorrhagia, dysmenorrhea, chronic pelvic pain, abdominal fullness, and uterine volume were recorded prior to treatment, six months after the start of therapy (6 M), and 12 months after the start of therapy (12 M). In Group G ( n  = 15), although all subjective symptoms disappeared at 6 M, nearly all symptoms recurred at 12 M. Uterine volume significantly decreased from 341.0 cm 3 to 156.0 cm 3 at 6 M ( p  = .001) and significantly increased again to 282.3 cm 3 at 12 M ( p  = .003). In Group D ( n  = 15), all subjective symptoms disappeared at 6 M, and only abdominal fullness returned in a significant number of patients (5 of 5; p  = .021) at 12 M. Uterine volume decreased significantly at 6 M ( p  = .003) and significantly increased again from 162.5 cm 3 to 205.6 cm 3 at 12 M ( p  = .006). Subjective symptoms, except for abdominal fullness, did not recur when dienogest was administered after GnRHa.

In this study, we aimed to compare changes in cavernosal tissues in rats with antiandrogen treatment and orchiectomy. A total of 42 Wistar albino rats were divided into four groups. Group I, control group, Group II, LH-RH was given for 1 month, Group III-LH-RH + Bicalutamide was given for 1 month, and Group IV was defined as orchiectomy and followed up for 1 month. Measurements of intracavernosal pressure with different electrical stimuli and pathological findings of smooth muscle collagen in cavernosal tissues were examined. While the cavernosal pressure response in all the different electrical stimuli given in the control group and in all other groups was significantly lower than that in the other groups, it was statistically significant at 7.5 and 10 V (p = .005, p < 0001). According to the pathologic evaluation, the density of tissue collagen increased significantly in the other groups according to the control group. In groups 3 and 4, the density of 4+ collagen was found to be increased according to Groups 1 and 2. In the LH-RH alone group, it appears that there are no 4+ colloid density and less damage. According to these findings, the negative effect of LH-RH treatment on cavernosal tissues appears to be less., (© 2020 Blackwell Verlag GmbH.)

Introduction: Neoadjuvant endocrine therapy (NET) has demonstrated efficacy in post-menopausal patients with hormone-responsive breast cancer. This trial was designed to compare the efficacy of neoadjuvant chemotherapy (NCT) with NET in pre-menopausal breast cancer., Patients and Methods: In this prospective, randomised, phase III study, oestrogen receptor (ER)-positive, HER2-negative, and lymph node-positive pre-menopausal breast cancer patients were recruited from 7 hospitals in South Korea. Enrolled patients were randomly assigned (1:1) to receive 24 weeks of either NCT or NET with goserelin and tamoxifen. The primary purpose was to evaluate the non-inferiority of NET compared to NCT using clinical response, assessed by MRI. Besides, pathological complete response rate (pCR), changes in Ki-67 expression, breast conservation surgery (BCS) rate, and quality of life were included as secondary endpoints., Results: A total of 187 patients were assigned to receive NCT (n = 95) or NET (n = 92), and 87 patients in each group completed treatments. More NCT patients had complete response or partial response than NET patients using MRI (NCT 83.7% vs. NET 52.9%, 95% CI 17.6-44.0, p < 0.001) and callipers (NCT 83.9% vs. NET 71.3%, 95% CI 0.4-24.9, p = 0.046). Three NCT patients (3.4%) and one NET patient (1.2%) showed pCR (p < 0.005). No difference existed in the conversion rate of BCS (13.8% for NCT vs. 11.5% for NET, p = 0.531) and Ki-67 change (p = 0.114) between the two groups. Nineteen NCT patients had treatment-related grade 3 or worse events compared with none in the NET group., Conclusions: Better clinical responses were observed in pre-menopausal patients after 24 weeks of NCT compared to those observed after NET., Trial Registration: Clinicaltrials.gov, NCT01622361. Registration June 19, 2012.

Background: Immunosuppressive cytokines have the potential to promote prostate cancer progression. Assessing their longitudinal changes may implicate mechanisms of progression, treatment resistance, and suggest new therapeutic targets., Methods: Thirty-seven men with biochemically recurrent (BCR) prostate cancer who received 6 months of androgen deprivation therapy (ADT) and were monitored until the time to prostate-specific antigen progression (TTPP) were identified from a completed phase III trial (NCT00020085). Serum samples were archived at baseline, 3 months after ADT, and at TTPP. Cytokine concentrations were quantified using a 36-parameter electrochemiluminescence assay. The Wilcoxon signed-rank sum test was used to compare observations between time points. Kaplan-Meier analysis was used to calculate TTPP dichotomized by cytokine values above or below the median. Pearson's rank correlation coefficient was used to compare continuous variables., Results: Median TTPP was 399 days (range, 114-1641). Median prostate-specific antigen (PSA) at baseline and progression were 8.5 and 5.3 ng/mL, respectively. Twenty-three patients (62%) achieved undetectable PSA with ADT. Castrate levels of testosterone (<50 ng/dL) after 3 months of ADT occurred in 35 patients (95%). TNF-α (P = .002), IL-23 (P = .002), and CXCL10 (P = .001) significantly increased from baseline to post ADT. Certain cytokines correlated longitudinally: TNF-α correlated with IL-23 (r = .72; P < .001) and IL-8 (r = .59; P < .001) from baseline to post ADT and to PSA progression. Neutrophil-to-lymphocyte ratio correlated with IL-27 (r = .57; P < .001) and MIP-3α (r = .56; P < .001). Patients with a detectable PSA after ADT had elevated levels of IL-6 (P = .049) and IL-8 (P = .013) at PSA progression as compared with those with an undetectable PSA. There was a trend toward shorter TTPP in patients with TNF-α levels above the median (P = .042)., Conclusions: Several innate cytokines were associated with biochemically recurrent prostate cancer., (© 2019 Wiley Periodicals, Inc.)

Aim: This study evaluated the patient experience of receiving subcutaneous chemotherapy at home via a unique 'Cancer Treatment at Home' outreach service adapted by the UK Clatterbridge Cancer Centre NHS Foundation Trust. Patients & methods: The service involved using highly trained nurses to deliver cancer treatments to patients in their own homes. Patient outcomes were monitored over 12 months via the Systemic Anti-Cancer Therapy at Home (SACT) survey using handheld electronic devices. Results: Of the 56 participating cancer patients, 53 provided responses. Patients received subcutaneous trastuzumab, denosumab, pembrolizumab, fulvestrant and goserelin. Overall, 96% of respondents were 'very satisfied' and 4% 'satisfied' with the service. All respondents would recommend the service to others. Conclusion: The 'Cancer Treatment at Home' service has improved the patient experience for cancer care and has been recognized nationally for its achievements.

This study aimed to prepare and optimize goserelin acetate (GOS) loaded hydrogel poly(d,l-lactic acid- co -glycolic acid) (PLGA) microsphere that is suitable for long-acting clinical treatment, investigate its structure, and regulate the initial release manner. Here, the PLGA microsphere containing Poloxamer hydrogel loaded with ∼15% (w/w) GOS was prepared by double-emulsion-solvent evaporation method and evaluated in terms of microscopic structure, physicochemical properties, and release manner in vitro and in vivo. Raman volume imaging and scanning electron microscopy studies revealed a core-shell Di-Depot structure of the microsphere, in which multi-GOS-loaded hydrogel depots were distributed in the core region. Under the interaction of hydrogel and PLGA depots, high encapsulation efficiency (94.16%) and low burst release (less than 2%) were achieved, along with the accompanying prolonged administration interval (49 days); an enhanced relative bioavailability 9.36-fold higher than that of Zoladex implant was also observed. Also, by addition of 1-5% acetic acid, the lag time was shortened to 6 days. The strategy for regulating the initial release provides new insights for manipulating the release behavior of the PLGA microspheres. The desirable property of the Poloxamer hydrogel PLGA microsphere indicated its promising application in controlled release drug delivery system.

Background: Testosterone suppression is the standard treatment for advanced prostate cancer, and it is associated with side-effects that impair patients' quality of life, like sexual dysfunction, osteoporosis, weight gain, and increased cardiovascular risk. We hypothesized that abiraterone acetate with prednisone (AAP) and apalutamide, alone or in combination, can be an effective hormonal therapy also possibly decreasing castration-associated side effects., Methods: Phase II, open-label, randomized, efficacy trial of abiraterone acetate plus prednisone (AAP) and Androgen Deprivation Therapy (ADT) versus apalutamide versus the combination of AAP (without ADT) and apalutamide. Key eligibility criteria are confirmed prostate adenocarcinoma; biochemical relapse after definitive treatment (PSA ≥ 4 ng/ml and doubling time less than 10 months, or PSA ≥ 20 ng/ml); newly diagnosed locally advanced or metastatic prostate cancer; asymptomatic to moderately symptomatic regarding bone symptoms. Patients with other histology besides adenocarcinoma or previous use of hormonal therapy or chemotherapy were excluded., Discussion: There is an urgent need to study and validate regimens such as new hormonal agents that may add benefit to castration with an acceptable safety profile. We aim to evaluate if apalutamide in monotherapy or in combination with AAP is an effective and safety hormonal treatment that can spare patients of androgen deprivation therapy., Trial Registration: This trial was registered in ClinicalTrials.gov on October 16, 2017, under Identifier: NCT02867020.

Premature menopause is a serious long-term side effect of chemotherapy. We evaluated long-term pregnancy and disease-related outcomes for patients in S0230/POEMS, a study in premenopausal women with stage I-IIIA estrogen receptor-negative, progesterone receptor-negative breast cancer to be treated with cyclophosphamide-containing chemotherapy. Women were randomly assigned to standard chemotherapy with or without goserelin, a gonadotropin-releasing hormone agonist, and were stratified by age and chemotherapy regimen. All statistical tests were two-sided. Of 257 patients, 218 were eligible and evaluable (105 in the chemotherapy + goserelin arm and 113 in the chemotherapy arm). More patients in the chemotherapy + goserelin arm reported at least one pregnancy vs the chemotherapy arm (5-year cumulative incidence = 23.1%, 95% confidence interval [CI] = 15.3% to 31.9%; and 12.2%, 95% CI = 6.8% to 19.2%, respectively; odds ratio = 2.34; 95% CI = 1.07 to 5.11; P = .03). Randomization to goserelin + chemotherapy was associated with a nonstatistically significant improvement in disease-free survival (hazard ratio [HR] = 0.55; 95% CI = 0.27 to 1.10; P = .09) and overall survival (HR = 0.45; 95% CI = 0.19 to 1.04; P = .06). In this long-term analysis of POEMS/S0230, we found continued evidence that patients randomly assigned to receive goserelin + chemotherapy were not only more likely to avoid premature menopause, but were also more likely to become pregnant without adverse effect on disease-related outcomes., (© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The NRG/RTOG 9413 study showed that whole pelvic radiotherapy (WPRT) plus neoadjuvant hormonal therapy (NHT) improved progression-free survival in patients with intermediate-risk or high-risk localised prostate cancer compared with prostate only radiotherapy (PORT) plus NHT, WPRT plus adjuvant hormonal therapy (AHT), and PORT plus AHT. We provide a long-term update after 10 years of follow-up of the primary endpoint (progression-free survival) and report on the late toxicities of treatment., Methods: The trial was designed as a 2 × 2 factorial study with hormonal sequencing as one stratification factor and radiation field as the other factor and tested whether NHT improved progression-free survival versus AHT, and NHT plus WPRT versus NHT plus PORT. Eligible patients had histologically confirmed, clinically localised adenocarcinoma of the prostate, an estimated risk of lymph node involvement of more than 15% and a Karnofsky performance status of more than 70, with no age limitations. Patients were randomly assigned (1:1:1:1) by permuted block randomisation to receive either NHT 2 months before and during WPRT followed by a prostate boost to 70 Gy (NHT plus WPRT group), NHT 2 months before and during PORT to 70 Gy (NHT plus PORT group), WPRT followed by 4 months of AHT (WPRT plus AHT group), or PORT followed by 4 months of AHT (PORT plus AHT group). Hormonal therapy was combined androgen suppression, consisting of goserelin acetate 3·6 mg once a month subcutaneously or leuprolide acetate 7·5 mg once a month intramuscularly, and flutamide 250 mg twice a day orally for 4 months. Randomisation was stratified by T stage, Gleason Score, and prostate-specific antigen concentration. NHT was given 2 months before radiotherapy and was continued until radiotherapy completion; AHT was given at the completion of radiotherapy for 4 months. The primary endpoint progression-free survival was analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00769548. The trial has been terminated to additional follow-up collection and this is the final analysis for this trial., Findings: Between April 1, 1995, and June 1, 1999, 1322 patients were enrolled from 53 centres and randomly assigned to the four treatment groups. With a median follow-up of 8·8 years (IQR 5·07-13·84) for all patients and 14·8 years (7·18-17·4) for living patients (n=346), progression-free survival across all timepoints continued to differ significantly across the four treatment groups (p=0·002). The 10-year estimates of progression-free survival were 28·4% (95% CI 23·3-33·6) in the NHT plus WPRT group, 23·5% (18·7-28·3) in the NHT plus PORT group, 19·4% (14·9-24·0) in the WPRT plus AHT group, and 30·2% (25·0-35·4) in the PORT plus AHT group. Bladder toxicity was the most common grade 3 or worse late toxicity, affecting 18 (6%) of 316 patients in the NHT plus WPRT group, 17 (5%) of 313 in the NHT plus PORT group, 22 (7%) of 317 in the WPRT plus AHT group, and 14 (4%) of 315 in the PORT plus AHT group. Late grade 3 or worse gastrointestinal adverse events occurred in 22 (7%) of 316 patients in the NHT plus WPRT group, five (2%) of 313 in the NHT plus PORT group, ten (3%) of 317 in the WPRT plus AHT group, and seven (2%) of 315 in the PORT plus AHT group., Interpretation: In this cohort of patients with intermediate-risk and high-risk localised prostate cancer, NHT plus WPRT improved progression-free survival compared with NHT plus PORT and WPRT plus AHT at long-term follow-up albeit increased risk of grade 3 or worse intestinal toxicity. Interactions between radiotherapy and hormonal therapy suggests that WPRT should be avoided without NHT., Funding: National Cancer Institute., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Aim: of this study is to determine the temporal resolution of therapy-induced pneumonitis, and to assess promoting factors in adjuvant treated patients with unilateral mammacarcinoma., Patients and Methods: A total of 100 post-surgery patients were recruited. The cohort was treated by 2 field radiotherapy (2FRT; breast and chest wall, N = 75), 3 field radiotherapy (3FRT; + supraclavicular lymphatic region, N = 8), or with 4 field radiotherapy (4FRT; + parasternal lymphatic region, N = 17). Ninety-one patients received various systemic treatments prior to irradiation. Following an initial screening visit post-RT, two additional visits after 12 and 25 weeks were conducted including radiographic examination. In addition, general anamnesis and the co-medication were recorded. The endpoint was reached as soon as a pneumonitis was developed or at maximum of six months post-treatment., Results: A pneumonitis incidence of 13% was determined. Of 91 patients with prior systemic therapy, 11 patients developed pneumonitis. Smoking history and chronic obstructive pulmonary disease (COPD) appeared to be positive predictors, whereas past pneumonia clearly promoted pneumonitis. Further pneumonitis-promoting predictors are represented by the applied field extensions (2 field radiotherapy [2FRT] < 3 field radiotherapy [3FRT] < 4 field radiotherapy [4FRT]) and the type of combined initial systemic therapies. As a consequence, all of the three patients in the study cohort treated with 4FRT and initial chemotherapy combined with anti-hormone and antibody protocols developed pneumonitis. A combination of the hormone antagonists tamoxifen and goserelin might enhance the risk for pneumonitis. Remarkably, none of the 11 patients co-medicated with statins suffered from pneumonitis., Conclusions: The rapidly increasing use of novel systemic therapy schedules combined with radiotherapy (RT) needs more prospective studies with larger cohorts. Our results indicate that contribution to pneumonitis occurrence of various (neo)adjuvant therapy approaches followed by RT is of minor relevance, whereas mean total lung doses of >10 Gy escalate the risk of lung tissue complications. The validity of potential inhibitors of therapy-induced pneumonitis as observed for statin co-medication should further be investigated in future trials.

Non-inferiority in the cumulative castration rate of the 3-month formulation of degarelix compared with the 3-month formulation of goserelin was evaluated in subjects with prostate cancer. A phase III, open-label, parallel-arm study was carried out. An initial dose of 240 mg degarelix or 3.6 mg goserelin was given s.c.; after day 28, a maintenance dose of 480 mg degarelix or 10.8 mg goserelin was given once every 84 days. Non-inferiority in castration rate and safety of degarelix to goserelin were evaluated. The primary end-point was the cumulative castration rate from day 28 to day 364 and the non-inferiority margin was set to be 10%. A total of 234 subjects with prostate cancer were randomized to the degarelix group (n = 117) and the goserelin group (n = 117). The cumulative castration rate was 95.1% in the degarelix group and 100.0% in the goserelin group. As there were no events in the goserelin group, an additional analysis was carried out using 95% confidence intervals of the difference in the proportion of subjects with castration. Analyses indicated the non-inferiority of the 3-month formulation of degarelix to goserelin. Degarelix showed more rapid decreases in testosterone, luteinizing hormone, follicle stimulating hormone, and prostate-specific antigen levels compared with goserelin. The most common adverse events in the degarelix group were injection site reactions. Non-inferiority of the 3-month formulation of degarelix to goserelin was shown for testosterone suppression. The 3-month formulation of degarelix was also found to be tolerated as an androgen deprivation therapy for patients with prostate cancer. This trial was registered with ClinicalTrials.gov (identifier NCT01964170)., (© 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Purpose: Among harmful effects of chemotherapy is the reduction of ovarian function. The aim was to determine the serum levels of FSH, LH, estradiol and AMH after chemotherapy followed by endocrine therapy in breast cancer patients., Methods: The study included 40 premenopausal hormone receptor-positive breast cancer patients aged 33-50 years. Anthracycline-based chemotherapy received 14/40 while anthracycline-taxane combination received 26/40 of patients, followed by tamoxifen (30/40) or tamoxifen plus goserelin (10/40). All of them experienced chemotherapy-induced secondary amenorrhea. Hormone levels were determined by ELISA. Statistics included Spearman's test, Mann-Whitney test and multiple linear regression analysis., Results: Undetectable AMH levels were observed in 62.5 and 33.3% of patients with time period < 2 and ≥ 2 years from completion of chemotherapy to sample collection. Median levels of hormones for patients treated with anthracycline-based compared to anthracycline-taxane therapy were: 15.5 vs. 22.3 IU/L for FSH; 10.9 vs. 13.6 IU/L for LH; 55.5 vs. 39.5 pg/mL for estradiol; 0.11 vs. 0.11 ng/mL for AMH. The multiple linear regression showed that: women who received goserelin had significantly lower FSH; those with shorter time from completion of chemotherapy to sample collection had significantly higher LH and lower estradiol; younger women had higher AMH levels., Conclusions: The ovarian function was recovered from chemotherapy-induced secondary amenorrhea with time elapsed since the completion of adjuvant chemotherapy. It may be less disrupted in patients who received anthracycline-based chemotherapy and goserelin plus tamoxifen, as well.

Background: Ovarian suppression in premenopausal women is known to reduce breast cancer risk. This study aimed to assess uptake and compliance with ovarian suppression using the luteinizing hormone releasing hormone (LHRH) analogue, goserelin, with add-back raloxifene, as a potential regimen for breast cancer prevention. Methods: Women at ≥30% lifetime risk breast cancer were approached and randomized to mammographic screening alone (C-Control) or screening in addition to monthly subcutaneous injections of 3.6 mg goserelin and continuous 60 mg raloxifene daily orally (T-Treated) for 2 years. The primary endpoint was therapy adherence. Secondary endpoints were toxicity/quality of life, change in bone density, and mammographic density. Results: A total of 75/950 (7.9%) women approached agreed to randomization. In the T-arm, 20 of 38 (52%) of women completed the 2-year period of study compared with the C-arm (27/37, 73.0%). Dropouts were related to toxicity but also the wish to have established risk-reducing procedures and proven chemoprevention. As relatively few women completed the study, data are limited, but those in the T-arm reported significant increases in toxicity and sexual problems, no change in anxiety, and less cancer worry. Lumbar spine bone density declined by 7.0% and visually assessed mammographic density by 4.7% over the 2-year treatment period. Conclusions: Uptake is somewhat lower than comparable studies with tamoxifen for prevention with higher dropout rates. Raloxifene may preserve bone density, but reduction in mammographic density reversed after treatment was completed. Impact: This study indicates that breast cancer risk reduction may be possible using LHRH agonists, but reducing toxicity and preventing bone changes would make this a more attractive option. Cancer Epidemiol Biomarkers Prev; 27(1); 58-66. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Background: The optimal treatment for high-risk prostate cancer (PCa) remains to be established. We previously reported favorable, biochemical recurrence-free survival in high-risk PCa patients treated with a neoadjuvant gonadotropin-releasing hormone agonist or antagonist and estramustine phosphate (EMP) (chemohormonal therapy; CHT) followed by radical prostatectomy (RP). We conducted a retrospective study to elucidate the clinical benefit of neoadjuvant CHT for high-risk PCa patients., Methods: We reviewed the clinical and pathological records of 1254 PCa patients who underwent RP and bilateral pelvic lymphadenectomy between July 1996 and April 2016 at Hirosaki University. According to the D'Amico risk classification, we focused on 613 patients in the high-risk group. The high-risk PCa patients were further divided into two groups based on whether the patients received neoadjuvant CHT before RP (EMP group) or not (non-EMP group). The endpoint was overall survival (OS) after surgery., Results: The 5- and 10-year OS rates were 98.5 and 92.6%, respectively. The 10-year OS rate in the EMP group was significantly higher compared to the non-EMP group (P = 0.021). In multivariate analysis, administration of neoadjuvant CHT, lymph node involvement, and castration-resistant PCa status were significantly associated with OS., Conclusions: RP with neoadjuvant CHT using EMP for high-risk PCa patients provided excellent long-term OS.

Long-term administration of luteinizing hormone-releasing hormone analogs (LHRHa) is the main type of androgen-deprivation therapy (ADT) for lethal prostate cancer. A fully insertable microneedle system, composed of embeddable chitosan microneedles and a dissolvable polyvinyl alcohol/polyvinyl pyrrolidone supporting array, was developed for sustained delivery of LHRHa to the skin. A porcine cadaver skin test showed that chitosan microneedles can be fully embedded within the skin and microneedle-created micropores reseal within 7 days. The measured LHRHa loading amount was 73.3±2.8 μg per microneedle patch. After applying goserelin-containing microneedles to mice, serum LH levels increased initially and then declined below baseline at day 7. In contrast, serum testosterone levels increased to reach a peak at day 14 and then declined to a castration level at day 21. Additionally, such a castration level was maintained for 2 weeks. Therefore, transdermal delivery of goserelin with embeddable chitosan microneedles can produce a castrated state in mice. Such a system is a promising, feasible means of delivering ADT., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Aggressive angiomyxoma is a rare, locally infiltrative tumor, frequently occurring in female patients. Although wide local excision is considered standard therapy, radical surgery may be needed., Case: A 49-year-old woman presented with an aggressive angiomyxoma involving the vulva and bladder. Given the hormone receptor status and size of the tumor, the patient was initially treated with fulvestrant and goserelin acetate in an attempt to reduce the size of the mass. She was followed up at 1- to 3-month intervals; after 6 months of treatment, owing to increasing size of the mass and worsening symptoms, the decision was made to proceed with radical surgery., Conclusion: Although a less radical surgical approach is preferred, radical surgery is possible for treatment of aggressive angiomyxoma when needed.

Objective: To investigate the clinical effects of integrated traditional Chinese and Western medicine in the treatment of castration-resistant prostate cancer (CRPC)., Methods: A total of 54 CRPC patients were randomly divided into a control and a trial group, all treated by endocrine therapy (oral Bicalutamide at 50 mg per d plus subcutaneous injection of Goserelin at 3.6 mg once every 4 wk) and chemotherapy (intravenous injection of Docetaxel at 75 mg/m2 once every 3 wk plus oral Prednisone at 5 mg bid), while the latter group by Fuyang Huayu Prescription (a Traditional Chinese Medicine ［TCM］ prescription for tonifying yang and dispersing blood stasis) in addition, for a course of 24 weeks. Comparisons were made between the two groups of patients in the level of serum prostate-specific antigen (PSA), Karnofsky physical condition scores, function assessment of cancer therapy-prostate (FACT-P) scores, and TCM symptoms scores before and after 12 or 24 weeks of treatment., Results: Compared with the baseline, the serum PSA level was significantly decreased after 12 weeks of treatment both in the control (［25.9 ± 39.3］ vs ［20.0 ± 21.1］ μg/L, P <0.05) and in the trial group (［22.1 ± 33.9］ vs ［17.9 ± 19.1］ μg/L, P <0.05), with no statistically significant differences between the two groups (P >0.05). At 24 weeks, however, the PSA levels in the control and trial groups were slightly increased to (23.1 ± 28.4) and (19.6 ± 23.5) μg/L, respectively, with no statistically significant differences in between (P >0.05). Karnofsky, FACT-P and TCM symptoms scores were all markedly improved in the trial group after 12 weeks of treatment (P <0.05) and remained stable at 24 weeks, but not in the control group either at 12 or at 24 weeks (P >0.05)., Conclusions: TCM Fuyang Huayu Prescription combined with endocrine therapy and chemotherapy is effective for CRPC.

Background: Chemotherapy-induced premature ovarian insufficiency (POI) impacts fertility and other aspects of women's health. The OPTION trial tested whether administration of a gonadotropin-releasing hormone agonist during chemotherapy for early breast cancer reduced the risk of POI., Patients and Methods: This was a prospective, randomized, parallel group study of the gonadotropin-releasing hormone agonist goserelin administered before and during chemotherapy for breast cancer with stage I-IIIB disease. The primary outcome was amenorrhoea between 12 and 24 months after randomization, supported by elevated follicle stimulating hormone concentrations to give an additional analysis as rate of POI., Results: A total of 227 patients were randomized and the primary analysis was conducted on 202 patients. Goserelin reduced the prevalence of amenorrhoea between 12 and 24 months to 22% versus 38% in the control group (P = 0.015) and the prevalence of POI to 18.5% versus 34.8% in the control group (P = 0.048). Follicle stimulating hormone concentrations were also lower in all women treated with goserelin at both 12 and 24 months (P = 0.027, P = 0.001, respectively). The effect of goserelin was not statistically significant in women >40 years. Assessment of the ovarian reserve using anti-Müllerian hormone showed a marked fall in both groups during treatment to median values of 5% of pretreatment levels in the control group and 7% in the goserelin group, which were not significantly different between groups., Conclusion: This study shows that goserelin reduced the risk of POI in women treated with chemotherapy for early breast cancer, with particular efficacy in women aged ≤40 years old. The degree of ovarian protection also seems limited and the clinical significance for fertility and longer term prevention of estrogen deficiency-related outcomes needs to be determined., (© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: The effect of ovarian ablation or suppression (OAS) in premenopausal women with breast cancer is controversial. The overall survival (OS), disease-free survival (DFS) and adverse event of OAS versus no OAS were compared., Methods: A literature review of EMBASE, Web of Science, PUBMED, and Cochrane Library was conducted. The hazard ratio (HR) and 95% confidence interval (CI) for OS and DFS, as well as risk ratio (RR) and 95% CI for adverse events were evaluated. I-squared statistic (I 2 ) represents heterogeneity., Results: Twenty-nine studies with a total of 21,249 women were included. In premenopausal women aged 40 years or younger, there were significant differences in OS (HR 0.78, 95% CI: 0.66-0.94, P=0.008, I 2  = 0%) and DFS (HR 0.84, 95% CI: 0.73-0.97, P=0.02, I 2  = 0%) between OAS and no OAS. In advanced stage breast cancer, a significant difference was found in OS (HR 0.76, 95% CI: 0.60-0.96, P=0.02, I 2  = 0%). Patients treated with OAS had more chances to have hot flushes (RR 1.91, 95% CI: 1.62-2.26, P < 0.01, I 2  = 0%) and vaginal dryness (RR 1.19, 95% CI: 1.08-1.31, P=0.0003, I 2  = 0%). No significant difference in depression (RR 1.28, 95% CI: 0.94-1.74, P=0.12, I 2  = 0%)., Conclusions: The study shows that OAS plays a beneficial role in premenopausal women aged 40 years or younger and advanced stage breast cancer. However, OAS is associated with increase in hot flushes and vaginal dryness., (Copyright © 2016 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Purpose: To assess the effectiveness and safety of tamsulosin combined with androgen deprivation therapy (ADT) for lower urinary tract symptoms (LUTS) in advanced prostate cancer (PC) patients., Methods: Ninety PC patients with moderate-to-severe LUTS randomized into two groups of 45 each. One group received ADT (group 1), and the other received ADT plus tamsulosin (group 2) for 24 weeks. The outcome measures were changes in the International Prostate Symptom Score (IPSS), IPSS obstructive and irritative subscores, quality of life (QoL), maximum urinary flow rate (Q max ), post-voiding residual (PVR) and prostate-specific antigen (PSA) from baseline. The treatment response was monitored at 8, 16 and 24 weeks., Results: Both ADT monotherapy and ADT plus tamsulosin significantly improved IPSS,QoL score, Q max and PVR at the end of the treatment period. ADT plus tamsulosin had a greater impact on total IPSS, IPSS obstructive subscore, QoL and PVR at week 8 and week 16 than ADT monotherapy. Tamsulosin group showed greater improvement in Q max than ADT group. Significant improvements of IPSS, IPSS obstructive subscore and QoL were achieved at early treatment stage (week 8) in group 2, whereas similar improvements were achieved at week 16 in group 1. There were no significant differences in IPSS, IPSS subscores, QoL and PVR between the two groups at week 24., Conclusions: Additional administration of tamsulosin showed significantly greater and sooner relief in LUTS than ADT monotherapy, with good acceptability. It is feasible that ADT is used alone after 16-24 weeks of combination therapy.

Purpose: Trial RTOG 9202 was a phase 3 randomized trial designed to determine the optimal duration of androgen deprivation therapy (ADT) when combined with definitive radiation therapy (RT) in the treatment of locally advanced nonmetastatic adenocarcinoma of the prostate. Long-term follow-up results of this study now available are relevant to the management of this disease., Methods and Materials: Men (N=1554) with adenocarcinoma of the prostate (cT2c-T4, N0-Nx) with a prostate-specific antigen (PSA) <150 ng/mL and no evidence of distant metastasis were randomized (June 1992 to April 1995) to short-term ADT (STAD: 4 months of flutamide 250 mg 3 times per day and goserelin 3.6 mg per month) and definitive RT versus long-term ADT (LTAD: STAD with definitive RT plus an additional 24 months of monthly goserelin)., Results: Among 1520 protocol-eligible and evaluable patients, the median follow-up time for this analysis was 19.6 years. In analysis adjusted for prognostic covariates, LTAD improved disease-free survival (29% relative reduction in failure rate, P<.0001), local progression (46% relative reduction, P=.02), distant metastases (36% relative reduction, P<.0001), disease-specific survival (30% relative reduction, P=.003), and overall survival (12% relative reduction, P=.03). Other-cause mortality (non-prostate cancer) did not differ (5% relative reduction, P=.48)., Conclusions: LTAD and RT is superior to STAD and RT for the treatment of locally advanced nonmetastatic adenocarcinoma of the prostate and should be considered the standard of care., (Published by Elsevier Inc.)

Objective: In patients with prostate cancer (PCa), prostate enlargement may give rise to lower urinary tract symptoms (LUTS); many patients suffer from moderate-to-severe symptoms. We compare the efficacy of degarelix and goserelin plus bicalutamide in improving LUTS in PCa patients., Methods: Data were pooled from three Phase 3, randomized clinical trials of once-monthly treatment for 12 weeks with degarelix (240/80 mg; n = 289) or goserelin (3.6 mg) plus bicalutamide (50 mg; n = 174) for initial flare protection. LUTS at weeks 4, 8, and 12 were compared to baseline. Clinically relevant LUTS relief was a ≥3-point International Prostate Symptom Score (IPSS) decrease. Adverse events were assessed throughout the trials., Results: Patients receiving degarelix had significantly greater decreases in IPSS vs. goserelin at week 12 (adjusted difference: -1.24; 95% CI -2.33 to -0.14, P = 0.03). Clinically relevant LUTS relief with degarelix was especially pronounced in patients with moderate-to-severe LUTS (baseline IPSS ≥13) (odds ratio; OR 2.31; 95% CI 1.19-4.47, P = 0.01) and advanced PCa (OR 2.36; 95% CI 1.10-5.04, P = 0.03). A twofold higher OR for early (week 4) LUTS relief was seen with degarelix vs. goserelin (OR 2.03; 95% CI 1.14-3.60, P = 0.02). No difference in total prostate volume or urinary tract infection-related adverse events (2%) was seen between treatment groups., Conclusion: An early, significant and clinically more pronounced improvement of LUTS, especially in patients with moderate-to-severe LUTS or advanced PCa, was seen with degarelix vs. goserelin plus bicalutamide., (© 2015 Wiley Publishing Asia Pty Ltd.)

Purpose: Degarelix, a new gonadotropin-releasing hormone (GnRH) receptor antagonist with demonstrated efficacy as first-line treatment in the management of high-risk prostate cancer, possesses some theoretical advantages over luteinizing hormone-releasing hormone (LHRH) analogues in terms of avoiding "testosterone flare" and lower follicle-stimulating hormone (FSH) levels. We set out to determine whether preoperative degarelix influenced surrogates of disease control in a randomized phase II study. Experimental Design: Thirty-nine patients were randomly assigned to one of three different neoadjuvant arms: degarelix only, degarelix/bicalutamide, or LHRH agonist/bicalutamide. Treatments were given for 3 months before prostatectomy. Patients had localized prostate cancer and had chosen radical prostatectomy as primary treatment. The primary end point was treatment effect on intratumoral dihydrotestosterone levels. Results: Intratumoral DHT levels were higher in the degarelix arm than both the degarelix/bicalutamide and LHRH agonist/bicalutamide arms (0.87 ng/g vs. 0.26 ng/g and 0.23 ng/g, P < 0.01). No significant differences existed for other intratumoral androgens, such as testosterone and dehydroepiandrosterone. Patients in the degarelix-only arm had higher AMACR levels on immunohistochemical analysis ( P = 0.01). Serum FSH levels were lower after 12 weeks of therapy in both degarelix arms than the LHRH agonist/bicalutamide arm (0.55 and 0.65 vs. 3.65, P < 0.01), and inhibin B levels were lower in the degarelix/bicalutamide arm than the LHRH agonist/bicalutamide arm (82.14 vs. 126.67, P = 0.02). Conclusions: Neoadjuvant degarelix alone, compared with use of LHRH agonist and bicalutamide, is associated with higher levels of intratumoral dihydrotestosterone, despite similar testosterone levels. Further studies that evaluate the mechanisms behind these results are needed. Clin Cancer Res; 23(8); 1974-80. ©2016 AACR ., (©2016 American Association for Cancer Research.)

Objectives: To study the outcomes of adjuvant goserelin combined with tamoxifen (GosTam) compared to chemotherapy followed by tamoxifen (ChemTam) in premenopausal patients with early stage, luminal A breast cancer., Methods: From 2008 until 2013, data were retrospectively collected for premenopausal patients who underwent surgery for invasive tumors that were ≤2.0 cm, node-negative, strongly positive for estrogen and progesterone receptors, HER-2-negative, and Ki-67 < 25%. The patients were divided into two groups according to adjuvant regimen, either GosTam or ChemTam. All patients who underwent different adjuvant regimens were excluded., Results: In total, 235 patients underwent GosTam and 171 patients underwent ChemTam. There were significantly more patients younger than 40 years in the GosTam group (32% GosTam vs. 22% ChemTam, p = 0.031). Mean tumor size was significantly smaller (1.19 cm vs. 1.48 cm, p < 0.001), Ki-67 significantly lower (p = 0.049), and nuclear grade was low in a significant number of patients in the GosTam group (2% vs. 13%, p < 0.001). After a median follow-up of 51.3 months, there was no mortality in either group. There was no significant difference in 5-year disease-free survival (DFS) between the two groups even after univariate analysis considering age, tumor size, nuclear grade, and P53% (GosTam = 98.9% vs. ChemTam = 95.7%, HR = 0.404, 95% CI = [0.073, 2.222], p = 0.248)., Conclusion: There was no difference between treatment groups, and neither chemotherapy nor ovarian suppression seemed to improve the outcome. Thus, tamoxifen alone might be a sufficient option for this low-risk patient population., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Monthly goserelin 3.6 mg dosing suppresses estradiol (E2) production and has proven efficacy in pre-menopausal women with estrogen receptor (ER)-positive breast cancer. This non-inferiority study evaluated the efficacy and safety of 3-monthly goserelin 10.8 mg compared with monthly goserelin 3.6 mg., Methods: This was a Phase 3, open-label, multicenter trial. Pre-menopausal women with ER-positive advanced breast cancer were randomized to 3-monthly goserelin 10.8 mg or monthly goserelin 3.6 mg; all patients received concomitant tamoxifen (20 mg daily). The primary endpoint was progression-free survival (PFS) rate at 24 weeks; non-inferiority was to be confirmed if the entire 95 % confidence interval (CI) for the treatment difference was above -17.5 %. Secondary endpoints included objective response rate (ORR), serum E2 levels, safety, and tolerability., Results: In total, 222 patients were randomized (goserelin 10.8 mg, n = 109; goserelin 3.6 mg, n = 113). PFS rate at week 24 was 61.5 % (goserelin 10.8 mg) and 60.2 % (goserelin 3.6 mg); treatment difference (95 % CI) was 1.3 % (-11.4, 13.9), confirming non-inferiority of goserelin 10.8 mg compared with goserelin 3.6 mg. ORR was 23.9 % (goserelin 10.8 mg) and 26.9 % (goserelin 3.6 mg); treatment difference (95 % CI) was -3.0 % (-15.5, 9.7). At week 24, mean serum E2 concentrations were similar in the goserelin 10.8 mg and goserelin 3.6 mg groups (20.3 pg/mL and 24.8 pg/mL, respectively)., Conclusion: A regimen of 3-monthly goserelin 10.8 mg demonstrated non-inferiority compared with monthly goserelin 3.6 mg for PFS rate at 24 weeks, with similar pharmacodynamic and safety profiles, in pre-menopausal women with ER-positive breast cancer., Competing Interests: Compliance with ethical standards Conflicts of interest Y. Itoh and E. Shin are employees of, and hold stock in, AstraZeneca. S. Noguchi has received honoraria from AstraZeneca and funding for research from AstraZeneca and Takeda. The remaining authors have no conflicts of interest to declare.

Background: Neoadjuvant androgen deprivation therapy (ADT) has been suggested to confer several clinical benefits in patients with prostate cancer (PCa) undergoing transperineal prostate brachytherapy (TPPB). Unlike gonadotropin-releasing hormone (GnRH) receptor agonists, a GnRH antagonist such as degarelix can achieve castrate levels of testosterone without testosterone flare. However, normalization of serum testosterone levels following completion of neoadjuvant ADT in either form of treatment has never been compared in clinical trials., Methods/design: This is a single-center, open-label, randomized controlled study that will compare the efficacy and safety of degarelix with those of existing GnRH agonists combined with (125)I-TPPB. A total of 56 patients with low/intermediate-risk clinically localized PCa will be enrolled and randomized to one of two treatment groups: the GnRH agonist group and the degarelix group. Patients in the GnRH agonist group will receive leuprorelin acetate or goserelin acetate, and those in the degarelix group will receive the initial dose of 240 mg as 2 subcutaneous injections of 120 mg each, and then 80 mg of maintenance doses every 4 weeks for 12 weeks. Those randomly assigned to the 12-week intervention period will subsequently undergo 48-weeks of follow-up after (125)I-TPPB. The primary endpoint is defined as normalization of serum testosterone levels (>50 ng/dL) following completion of neoadjuvant ADT. All patients will be assessed every 4 weeks for the first 24 weeks, then every 12 weeks for the next 36 weeks after administrations of these drugs. Secondary endpoints are the proportion of normalized serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH), the percent reduction in prostate specific antigen (PSA) compared with pretreatment levels, the percent reduction in total prostate volume (TPV) during neoadjuvant ADT, the percent increase in TPV after (125)I-TPPB, the percent reduction in hemoglobin, serum alkaline phosphatase (ALP), changes in free testosterone and bone mineral content measurement, the proportion of patients who have serum testosterone levels over 50 ng/dL at 12 weeks following completion of neoadjuvant ADT, and the improvement of quality of life (QOL)., Discussion: The present study will provide additional insight regarding the benefit and potency of degarelix and will examine its potential as a new option for administration in neoadjuvant ADT., Trial Registration: Identification number: UMIN000015519 . Registration date: October 24, 2014.

Study Objective: To describe the rates of use and effectiveness of gonadotropin-releasing hormone (GnRH) agonists and other forms of hormonal menstrual suppression in prevention of vaginal bleeding among young women who underwent hematopoietic stem cell transplantation (HCT)., Design: Retrospective descriptive study., Setting: University-based pediatric HCT practice., Participants: Fifty-five postmenarchal women who underwent HCT between 2004 and 2011., Interventions: Administration of GnRH agonists or other forms of hormonal menstrual suppression., Main Outcome Measures: Rates of use of GnRH agonists and other forms of hormonal menstrual suppression, and rates and descriptions of vaginal bleeding., Results: Forty-six of the 55 patients had experienced regular or irregular vaginal bleeding before HCT and were considered to be at risk for thrombocytopenia-associated menorrhagia. Forty of the 46 (87%) received hormonal menstrual suppression. Thirty-three patients were treated with a GnRH agonist, 4 with combined hormonal contraceptive pills, 1 with a combined hormonal contraceptive patch, 1 with depot medroxyprogesterone, and 1 with oral norethindrone. Twenty-nine of the 33 patients (88%) who received a GnRH agonist had complete amenorrhea during HCT and 4 of 33 (12%) experienced some degree of vaginal bleeding., Conclusion: GnRH agonists appear effective in prevention of vaginal bleeding complications in most postmenarchal women who underwent HCT. Some patients who might benefit do not receive a GnRH agonist and multiple barriers exist in identification and treatment of them., (Copyright © 2015 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.)

The aim of our study was to investigate the relationship between cancer-related fatigue and clinical parameters, and the effect factors of fatigue for the prostate cancer patients. Long-term follow-up is performed using the Fatigue Symptom Inventory before treatment (A), at the end of intensity-modulated radiotherapy (B), and 3 months (C), 12 months (D), 24 months (E), 36 months (F), and 48 months (G) after the end of intensity-modulated radiotherapy. Three dimensions of fatigue are assessed during follow-up: severity, perceived interference with quality of life, and duration in the past week. In all, 97 patients with locally advanced prostate cancer were enrolled in the study. Median follow-up time was 43.9 months. The fatigue index was significantly higher in the prostate-specific antigen >20 ng/mL, Gleason score >8, the Eastern Cooperative Oncology Group scores, and the higher education. The most severe fatigue occurred at time points B and C. The score for duration of fatigue fluctuated across the time points, with significantly increased scores at time points D, E, and F.In conclusion, we show that cancer-related fatigue is the important symptom which affects the quality of life for the prostate cancer patients. For patients with locally advanced prostate cancer with a high Eastern Cooperative Oncology Group score, a Gleason score of >8 points, prostate-specific antigen levels of >20 ng/mL, and high education, attention should be paid to the interference of fatigue with quality of life, especially general level of activity, ability to concentrate, and mood, after radiotherapy combined with hormonal therapy., Competing Interests: The authors report no conflicts of interest.

Background: Ovarian function suppression (OFS) has been shown to be effective as adjuvant endocrine therapy in premenopausal women with hormone receptor-positive breast cancer. However, it is currently unclear if addition of OFS to standard tamoxifen therapy after completion of adjuvant chemotherapy results in a survival benefit. In 2008, the Korean Breast Cancer Society Study Group initiated the ASTRRA randomized phase III trial to evaluate the efficacy of OFS in addition to standard tamoxifen treatment in hormone receptor-positive breast cancer patients who remain or regain premenopausal status after chemotherapy., Methods: Premenopausal women with estrogen receptor-positive breast cancer treated with definitive surgery were enrolled after completion of neoadjuvant or adjuvant chemotherapy. Ovarian function was assessed at the time of enrollment and every 6 months for 2 years by follicular-stimulating hormone levels and bleeding history. If ovarian function was confirmed as premenopausal status, the patient was randomized to receive 2 years of goserelin plus 5 years of tamoxifen treatment or 5 years of tamoxifen alone. The primary end point will be the comparison of the 5-year disease-free survival rates between the OFS and tamoxifen alone groups. Patient recruitment was finished on March 2014 with the inclusion of a total of 1483 patients. The interim analysis will be performed at the time of the observation of the 187th event., Discussion: This study will provide evidence of the benefit of OFS plus tamoxifen compared with tamoxifen only in premenopausal patients with estrogen receptor-positive breast cancer treated with chemotherapy., Trial Registration: ClinicalTrials.gov Identifier NCT00912548 . Registered May 31 2009. Korean Breast Cancer Society Study Group Register KBCSG005 . Registered October 26 2009.