An Overview of Long-Acting GnRH Agonists in Premenopausal Breast Cancer Patients: Survivorship Challenges and Management.

Managing breast cancer in premenopausal women poses unique challenges due to its considerable effect on both morbidity and mortality. Goserelin, a gonadotropin-releasing hormone agonist, has emerged among the various modalities as a preferred option for ovarian function suppression, owing to its efficacy in reducing ovarian estrogen production in premenopausal women with hormone receptor-positive breast cancer. Recent studies have affirmed the efficacy and safety of long-acting (LA) goserelin 10.8 mg every 12 weeks, offering comparable outcomes to monthly injections. This flexibility enables personalized treatment approaches, potentially enhancing patient satisfaction. Off-label utilization of goserelin LA surged during the coronavirus disease pandemic, prompting initiatives to broaden its use for breast cancer treatment. Switching to goserelin LA can streamline treatment, boost adherence, and optimize resource utilization. With the recent approval of goserelin 10.8 mg LA by Health Canada on 6 May 2024, for use in breast cancer, Canada is the latest to join over 60 countries worldwide to expand the accepted indications for goserelin LA and ensure its availability to potentially enhance healthcare delivery, patient care, and breast cancer outcomes. Goserelin LA offers premenopausal patients a means to more effectively manage the constraints imposed by breast cancer treatment and its impact on survivorship.

Monitoring of estradiol levels in premenopausal women receiving adjuvant abemaciclib and ovarian function suppression.

PURPOSE: Approximately 15% of women who receive ovarian function suppression (OFS) as adjuvant treatment for high-risk, localized hormone receptor-positive (HR+) breast cancer may have inadequate estradiol suppression which can require therapeutic modification when used in combination with an aromatase inhibitor (AI). We previously reported that abemaciclib may interfere with the estradiol Abbott Alinity chemiluminescent microparticle immunoassay (CMIA) commonly used to monitor estradiol levels and suggested liquid chromatography-mass spectrometry (LC-MS/MS) is preferred in this setting. The aim of this study was to determine discrepancies in estradiol levels using CMIA compared to LC-MS/MS and subsequent treatment changes in a larger patient population. METHODS: We conducted a retrospective review of premenopausal women with early-stage HR+ breast cancer at our institution who received adjuvant OFS and abemaciclib with at least 1 CMIA estradiol level drawn during abemaciclib therapy from October 2021 to April 2023. RESULTS: Of the 22 women who met criteria for review, 20 (90.9%) had CMIA estradiol levels in the premenopausal range, of whom 9 also had estradiol measured by LC-MS/MS. All 9 women receiving OFS and abemaciclib with estradiol measurements by both methods had premenopausal range CMIA estradiol levels and postmenopausal range LC-MS/MS estradiol levels. Of the 20 patients with premenopausal estradiol levels by CMIA estradiol, treatment changes included increased OFS dosage or preparation (n = 7), change from AI to tamoxifen (n = 3), and surgical oophorectomy (n = 7). CONCLUSION: Our findings suggest the likely interference of abemaciclib with the Abbott Alinity immunoassay which may lead to unnecessary treatment changes. It is recommended that the LC-MS/MS assay be used when monitoring estradiol levels in patients receiving abemaciclib concurrently with OFS.

Adjuvant endocrine therapy choices in premenopausal patients with hormone receptor-positive early breast cancer: Insights from the prospective GIM23-POSTER study.

BACKGROUND: Most premenopausal patients with early breast cancer (eBC) are diagnosed with hormone receptor-positive disease and therefore candidate for adjuvant endocrine therapy (ET). PATIENTS AND METHODS: The Gruppo Italiano Mammella (GIM) 23-POSTER (GIM23) is a multicenter, prospective, observational study conducted in 26 Italian institutions, aiming to evaluate ET choices for premenopausal patients affected by hormone receptor-positive eBC in a real-world setting. Here we report also the results in terms of type of ET prescribed according to the definition of high-risk patients by monarchE and NATALEE trials. RESULTS: Between October 2019 and June 2022, 600 premenopausal patients were included, with a median age of 46 years. Almost half (271, 45.2 %) of the patients had stage I disease, while 254 (42.3 %) and 60 (10.0 %) patients had stage II and III, respectively. Overall, 149 (25.1 %) patients received tamoxifen alone, 83 (14.0 %) tamoxifen with ovarian function suppression (OFS), while 361 (60.9 %) received aromatase inhibitor (AI) with OFS. Patients treated with AI and OFS had higher number of metastatic axillary nodes, higher grade and more often received chemotherapy (all p < 0.001). According to the inclusion criteria of the monarchE and NATALEE trials, 81 patients (15.6 %) were considered high-risk for the monarchE and received AI with OFS in 88.9 % of the cases, while 231 patients (44.4 %) were considered high-risk for the NATALEE trial and received AI with OFS in 74.5 % of cases. CONCLUSIONS: AI with OFS is the most prescribed adjuvant ET among premenopausal patients, especially in the presence of high-risk features.

Effectiveness of gonadotropin-releasing hormone agonists for ovarian function suppression in premenopausal patients with hormone receptor-positive breast cancer: a retrospective single-center real-world study.

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.

Empowerment-Led Guided Self-Help Intervention for Symptom Burden in Breast Cancer Women Treated With Ovarian Function Suppression: A Randomized Trial Protocol.

Background: Ovarian function suppression (OFS) treatment causes breast cancer patients' estrogens to fall rapidly to postmenopausal levels, and the 5-year treatment duration and 28-day treatment cycles place a heavy physical and psychological symptom burden on them, which in turn directly or indirectly affects the survival benefit. Managing symptom burden early in treatment is critical, but OFS-related studies have yet to be seen. Self-management is essential for patients' symptom burden. However, self-help management is hampered by patients' lack of knowledge, skills, motivation, etc. Guided self-help intervention (GSH) provides a feasible approach. Empowerment theory is a promising theoretical framework to guide self-management. Methods: A prospective two-arm parallel randomized controlled single-blind clinical trial will be conducted to investigate the effect of symptom burden GSH based on empowerment theory in breast cancer patients in the early stages of OFS treatment. A block randomization method is used to allocate 144 patients to either the control or intervention group. The program is conducted according to the OFS return-to-hospital treatment cycle. The intervention group will receive a total of two rounds and five sessions of empowering GSH, lasting at least 15 weeks in total; the control group will receive only usual nursing care. Symptom burden and related metrics will be assessed at baseline and 1, 3, and 6 months after OFS treatment, and changes between and within groups will be explored. This paper adhered to the SPIRIT and CONSORT guidelines. Conclusion: These results will help to validate the GSH in symptom burden management for breast cancer patients in OFS treatment early stages. It enriches its symptom burden management research and may provide implications for the whole cycle of OFS treatment patients.

Ovarian Suppression: Early Menopause, Late Effects.

PURPOSE OF REVIEW: Pre-menopausal women diagnosed with hormone receptor (HR) breast cancer are candidates for prolonged hypoestrogenism to improve cancer outcomes. However, the disease benefit eclipses the toxicities associated with ovarian function suppression (OFS), which are often under-reported. RECENT FINDINGS: Increased risk of mortality from cardiovascular disease, bone disorders, and metabolic disorders is well reported in women with no history of cancer, after surgical oophorectomy or premature ovarian failure. Vasomotor symptoms, urogenital atrophy, weight gain, sexual dysfunction, cognitive decline, and sleep disturbances contribute to the increased non-compliance associated with OFS, especially in younger women. Balancing the toxicities of prolonged OFS with its benefits should be critically analyzed by providers when making recommendations for their patients. Supportive care to manage multi-system toxicities and to counteract the long-term impact on all-cause mortality should be emphasized by every cancer program. Future studies with OFS should incorporate patient outcomes and strategies for symptom management in addition to focusing on improving disease outcomes.

Prognostic factors and benefit populations of ovarian function suppression in premenopausal HR+/HER2+ early-stage breast cancer patients who received trastuzumab: Evidence from a real-world study with long-term follow-up.

BACKGROUND: Hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-positive (HER2+) breast cancer exhibits considerable heterogeneity, and it is of great interest whether patients with premenopausal HR+/HER2+ breast cancer treated with trastuzumab can benefit from ovarian function suppression (OFS) therapy similarly to HR+/HER2- breast cancer. Here, we conducted a real-world study in this population to identify both who would derive substantial benefits from the addition of OFS and clinicopathological factors with potential prognostic value. METHODS: Multicenter data from 253 premenopausal patients with HR+/HER2+ early-stage breast cancer who received trastuzumab from October 2009 to October 2018 were retrospectively included. The Kaplan-Meier method was used for survival analysis, while the log-rank test was used to compare the survival rates. Univariate and multifactor Cox regression analyses were performed to analyze the independent risk factors affecting invasive disease-free survival (IDFS). RESULTS: After a median follow-up of 98.50 months, compared with tamoxifen/toremifene alone, tamoxifen/toremifene/aromatase inhibitors plus OFS demonstrated significant benefits in the overall study population (HR = 0.289, 95% CI: 0.100-0.835, p = 0.022, 8-year IDFS rate: 90.78% vs. 95.54%), especially in the lymph node-positive subgroup and age ≤40 years subgroup. Age ≤40 years, histological grade >2, lymph node involvement, PR ≤50%, and tamoxifen alone were independent prognostic factors. CONCLUSIONS: For premenopausal HR+ breast cancer patients, HER2 positivity alone is an indication for the addition of OFS in adjuvant endocrine therapy. Age, histological grade, lymph node status, the expression of PR, and OFS treatment were independent prognostic factors in this population.

Cost-Effectiveness Analysis of Adjuvant Endocrine Therapy With Ovarian Suppression in Premenopausal Patients With Hormone Receptor-Positive Early Breast Cancer in China.

PURPOSE: Endocrine therapy combined with ovarian function suppression (OFS) is recommended in intermediate- or high-risk patients among premenopausal women with hormone receptor-positive early breast cancer. However, in China, the cost-effectiveness of this strategy compared with endocrine therapy alone is unclear. This study aimed to evaluate the long-term cost-effectiveness of tamoxifen (TAM), TAM+OFS, and exemestane plus OFS (EXE+OFS). METHODS: On the basis of prognostic data from the Suppression of Ovarian Function Trial (SOFT), cost data from the Hospital Information System of the West China Hospital of Sichuan University, and health utility values from the published literature, a Markov model was established. The incremental cost-effectiveness ratio (ICER) was used to compare the treatment strategies. RESULTS: In a 25-year simulation of adjuvant therapy in Chinese women with early breast cancer, the total costs of TAM, TAM+OFS, and EXE+OFS were $7821, $9318, and $9445, respectively. The quality-adjusted life-years (QALYs) were 11.615, 11.896, and 11.734 years, respectively. Compared with TAM, the ICERs of TAM+OFS and EXE+OFS were $5,327.4021/QALY and $13,647.0588/QALY, respectively. The ICERs of TAM+OFS and EXE+OFS were below the threshold of $32,517/QALY. The reliability and stability of the simulation results were verified using Monte Carlo simulation and sensitivity analysis. CONCLUSION: In the context of limited resources in China, TAM+OFS and EXE+OFS are cost-effective options compared with TAM.

Adjuvant Endocrine Therapy in Premenopausal Women With Hormone Receptor-Positive Early-Stage Breast Cancer: Risk Stratification in a Real-World Setting.

BACKGROUND: Ovarian function suppression (OFS) and hormone therapy (HT) represent an adjuvant option in premenopausal hormone receptor-positive early breast cancer (HR+EBC). The SOFT-TEXT trials showed improved outcomes upon receiving aromatase inhibitors (AIs)/OFS. METHODS: In order to estimate the magnitude of absolute improvements, we conducted a retrospective study applying composite risk (CR) to 237 premenopausal HR+EBC patients. RESULTS: Overall, 119 of these received tamoxifen (T)/OFS and 118 received AIs/OFS. The median age was 45 years (ys). After a median follow up of 65 months, recurrence was 6.7% in T patients and 10.2% in AI ones. CR (cutoff: 2.67) and ET duration (five-year cutoff) was found to have a significant impact on DFS. Invasive disease-free survival (IDFS) at 5 ys amounted to 82.9% for a CR>2.67 and 95% with CR

Ovarian Function Suppression in Premenopausal Women With Concurrent Endocrine Therapy Use.

INTRODUCTION: Almost 20% of patients receiving ovarian function suppression (OFS) and endocrine therapy (ET) for breast cancer treatment had inadequate OFS within the first year of treatment. Few studies have explored the long-term effectiveness of OFS to maintain estrogen suppression. PATIENTS AND METHODS: This retrospective, single institution study examined premenopausal women with early-stage breast cancer undergoing treatment with OFS and ET. The primary endpoint was the percentage of patients with inadequate ovarian suppression (estradiol ≥10 pg/mL) during OFS cycle 2 or later. The secondary endpoint was the percentage of patients with inadequate ovarian suppression within the first cycle after OFS initiation. Differences in age, body mass index (BMI), and previous chemotherapy use were summarized via multivariable logistic regression. RESULTS: Of the 131 patients included in the analysis, 35 (26.7%) lacked adequate suppression during OFS cycle 2 or later cycles. Patients with adequate suppression throughout treatment were more likely to be older (odds ratio [OR] 1.12 [95% CI, 1.05-1.22], P = .02), have a lower BMI (OR 0.88 [95% CI, 0.82-0.94], P < .001), and have received chemotherapy (OR 6.30 [95% CI, 2.06-20.8], P = .002). A total of 20 of 83 patients (24.1%) had an inadequately suppressed estradiol level within 35 days of OFS initiation. CONCLUSION: This "real world" cohort demonstrates that estradiol concentrations above the postmenopausal range of the assay are frequently detected, including more than 1 year after the start of OFS. Additional research is needed to establish estradiol monitoring guidelines and optimal degree of ovarian suppression.

The impact of obesity and endocrine therapy on the prognosis of premenopausal women with hormone receptor-positive breast cancer: A single-institute retrospective study.

BACKGROUND: Higher body mass index (BMI) is associated with worse prognosis in pre- and postmenopausal patients with breast cancer (BC). However, there is insufficient evidence regarding the optimal adjuvant endocrine therapy for obese premenopausal women with hormone receptor (HR)-positive BC. AIM: To evaluate the impact of obesity and adjuvant endocrine therapy on prognosis in premenopausal patients with BC. METHODS AND RESULTS: We retrospectively reviewed the medical record of premenopausal women who received curative surgery for clinical stage I-III HR-positive BC from 2007 to 2017. Patients were classified into five groups according to BMI: underweight (UW), normal weight (NW), obese 1 degree (OB1), obese 2 degree (OB2), and obese 3 degree (OB3) categories. The primary analysis was a comparison of BC-specific survival (BCSS) according to BMI (UW/NW vs. OB1-3) and adjuvant endocrine therapy (with or without ovarian function suppression [OFS]). Of 13 021 patients, the data of 3380 patients were analyzed. BCSS in OB1-3 patients was significantly worse than that in patients with UW/NW (hazard ratio [HR] 2.37; 95% confidence interval [CI], 1.40-4.02: p = .0009). In OB1-3 patients who received tamoxifen (TAM), BCSS was significantly worse than that in UW/NW patients (p = .0086); however, a significant difference was not shown in patients who received TAM and OFS (p = .0921). CONCLUSION: High BMI was associated with worse prognosis in premenopausal patients with HR-positive BC who received adjuvant TAM. The role of OFS as adjuvant endocrine therapy remains unclear, and further studies are required to explore the adequate management of obese premenopausal patients.

Extended adjuvant endocrine treatment for premenopausal women: A Delphi approach to guide clinical practice.

The use of an aromatase inhibitor (AI) in combination with ovarian function suppression (OFS) has become the mainstay of adjuvant endocrine therapy in high-risk premenopausal patients with hormone receptor-positive breast cancer. Although five years of such therapy effectively reduces recurrence rates, a substantial risk of late recurrence remains in this setting. Multiple trials have shown that extending AI treatment beyond five years could offer further protection. However, as these studies comprised only postmenopausal patients, no direct evidence currently exists to inform about the potential benefits and/or side effects of extended AI + OFS therapies in premenopausal women. Given these grey areas, we conducted a Delphi survey to report on the opinion of experts in breast cancer treatment and summarize a consensus on the discussed topics. A total of 44 items were identified, all centred around two main themes: 1) defining reliable prognostic factors to pinpoint premenopausal patients eligible for endocrine therapy extension; 2) designing how such therapy should optimally be administered in terms of treatment combinations and duration based on patients' menopausal status. Each item was separately discussed and anonymously voted by 12 experts representing oncological institutes spread across Italy. The consensus threshold was reached in 36 out of 44 items (82%). Herein, we discuss the levels of agreement/disagreement achieved by each item in relation to the current body of literature. In the absence of randomized trials to guide the tailoring of extended AI treatment in premenopausal women, conclusions from our study provide a framework to assist routine clinical practice.

Ovarian Function Suppression: A Deeper Consideration of the Role in Early Breast Cancer and its Potential Impact on Patient Outcomes: A Consensus Statement from an International Expert Panel.

It has been suggested that the benefit of adjuvant chemotherapy (CT) in premenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) early breast cancer may be related, at least in part, to CT-induced ovarian function suppression (OFS) in this subgroup of patients. Although this hypothesis has not been directly tested in large randomized clinical trials, the observations from prospective studies have been remarkably consistent in showing a late benefit of CT among the subgroup of patients who benefit (ie, women who were close to menopause). The hypothesis has important clinical implications, as it may be possible to spare the associated adverse effects of adjuvant CT in a select group of women with early breast cancer, in favor of optimizing OFS and endocrine therapy (ET), without compromising clinical outcomes. Such an approach has the added benefit of preserving the key quality of life outcomes in premenopausal women, particularly by preventing the irreversible loss of ovarian function that may result from CT use. For this reason, we convened an international panel of clinical experts in breast cancer treatment to discuss the key aspects of the available data in this area, as well as the potential clinical implications for patients. This article summarizes the results of these discussions and presents the consensus opinion of the panel regarding optimizing the use of OFS for premenopausal women with HR+, HER2- early breast cancer.

The Effects of Endocrine Therapies on Lipid Profiles in Chinese Young Women With Early Breast Cancer.

This study aimed to evaluate and compare the effects of various endocrine therapies on lipid profiles in young patients with breast cancer. A retrospective, single-center study was performed to investigate the effects of tamoxifen (TAM), tamoxifen plus ovarian function suppression (TAM+OFS), and aromatase inhibitors plus ovarian function suppression (AI+OFS) on lipid profiles during the 60 months of endocrine therapy in hormone receptor-positive patients aged <40 with early breast cancer. The primary endpoint was the cumulative incidence of lipid events, and the secondary endpoints were the changes in lipid profiles. A total of 230 young patients were included with the mean age of 35.7 years old. The patients in TAM group had significantly lower incidence of 5-year lipid events than those in TAM+OFS group (7.4% versus 21.3%; P=0.016) and AI+OFS group (7.4% versus 21.6%; P=0.009). The incidence of fatty liver was significantly higher in TAM+OFS group than TAM group (52.5%versus 30.9%; P=0.043). Lipid events were associated with younger age (odds ratio (OR)=0.865, 95% confidence interval (CI): 0.780-0960; P=0.006), higher baseline LDL-C (OR=14.959, 95% CI: 4.379-51.105; P<0.001), and use of OFS (OR=3.557, 95% CI: 1.151-10.989; P=0.027). Therefore, application of OFS, with younger age and higher baseline LDL-C, may increase the incidence of lipid events in premenopausal breast cancer. More care should be taken for lipid profiles during the endocrine therapy for young breast cancer patients.

Major depressive symptoms in breast cancer patients with ovarian function suppression: a cross-sectional study comparing ovarian ablation and gonadotropin-releasing hormone agonists.

BACKGROUND: Ovarian function suppression (OFS) is indicated in premenopausal women with early or metastasis breast cancer, which may be achieved with similar effect by gonadotropin-releasing hormone agonists (GnRHa) or ovarian ablation (OA). We examined whether there were differences in major depressive symptoms outcomes and its associated factors between gonadotropin-releasing hormone agonists (GnRHa) and ovarian ablation (OA) in premenopausal breast cancer patients. METHODS: Premenopausal breast cancer patients from seven hospitals who received OFS participated in the study between June 2019 and June 2020. The correlated variable was the type of ovarian suppression, categorized as either OA (n = 174) or GnRHa (n = 389). Major depressive symptoms was evaluated using the Patient Health Questionnaire (PHQ-9), and the Female Sexual Function Index questionnaire was used to assess sexual function. RESULTS: A total of 563 patients completed the surveys. The mean PHQ-9 sum score was slightly lower in the GnRHa cohort than in the OA cohort (11.4 ± 5.7 vs. 12.8 ± 5.8, P = 0.079). There were significantly fewer patients with major depressive symptoms (PHQ-9 ≥ 15) in the GnRHa cohort (31.1% vs. 40.2%, Exp (B)=1.805, P=0.004). Further, breast-conserving surgery and sexual dysfunction were negatively correlated with major depressive symptoms [mastectomy vs. breast-conserving: Exp (B) = 0.461, P <0.001;[sexual dysfunction vs. normal: Exp (B) = 0.512, P = 0.001]. CONCLUSIONS: This is the first study to demonstrate that GnRHa results in more favorable depressive symptoms outcomes than OA. Moreover, most patients preferred alternatives to their OFS treatment. These findings can contribute to improving and alleviating the adverse effects of OFS.

Ovarian Function Suppression With Luteinizing Hormone-Releasing Hormone Agonists for the Treatment of Hormone Receptor-Positive Early Breast Cancer in Premenopausal Women.

Chemotherapy and endocrine therapies are mainstays of treatment for early and advanced hormone receptor-positive (HR+) breast cancer. In premenopausal women with HR+ tumors, the benefits of adding ovarian function suppression (OFS) to endocrine therapy have been debated. Consequently, for many years, tamoxifen monotherapy has been the standard of care for endocrine treatment in the adjuvant setting. Recent studies have, however, provided new evidence that, in some premenopausal patients, OFS in combination with tamoxifen or aromatase inhibitors (AIs) can significantly increase survival versus tamoxifen alone. Luteinizing hormone-releasing hormone agonists (LHRHa), including goserelin, triptorelin, and leuprorelin, achieve OFS through sustained suppression of the release of follicle-stimulating hormone and luteinizing hormone from the pituitary. In turn, this suppresses production and secretion of estradiol, an ovarian hormone that supports cancer cell growth, survival, and proliferation. In this review, we discuss the clinical evidence supporting the addition of LHRHa to adjuvant endocrine therapies, including tamoxifen and AIs, for premenopausal women with breast cancer. We also discuss the role of LHRHa use in combination with adjuvant chemotherapy to preserve ovarian function and fertility in young patients with breast cancer. Finally, we discuss important practical aspects of the use of LHRHa in breast cancer treatment, including side-effects, patient adherence to treatment, and the use of slow-release, long-acting drug formulations.

Managing Menopausal Symptoms in Young Women With Breast Cancer: When Medicine Is Not All. The Take Care Project.

In the last decade, endocrine therapy strategies in perimenopausal women with hormone-responsive early breast cancer (BC) have changed and now ovarian function suppression (OFS) is recommended for the majority of patients. Side effects of OFS mimic menopausal symptoms, including hot flushes, sweats, weight gain, and sexual dysfunction, which may negatively impact quality of life (QoL). Aims of the Take Care Project are the education of physicians and patients to have all the information (medical and nonmedical) they need to manage menopausal symptoms by distributing educational materials useful to face menopause. Four different areas have been identified by surveys conducted among physicians and young patients: for each area, interventions and tools have been elaborated by a doctor and nonphysician professionals of these identified areas, to offer the widest information available. Clinical and practical suggestions have been provided. Based on the evidence given, we strongly suggest setting up a multidisciplinary team for the treatment planning of young patients with BC, which could help patients to face and manage their new menopause condition. The reduction of side effects and the improvement in QoL should be the best ally to treat young patients with BC.

A follow-up study of a randomized controlled study evaluating safety and efficacy of leuprorelin acetate every-3-month depot for 2 versus 3 or more years with tamoxifen for 5 years as adjuvant treatment in premenopausal patients with endocrine-responsive breast cancer.

BACKGROUND: Previously, we conducted the 5-year open-label, randomized controlled trial (RCT) of leuprorelin adjuvant therapy in post-operative premenopausal patients with endocrine-responsive breast cancer, which was a pilot study to investigate the optimal duration of leuprorelin treatment. Since, however, long-term outcomes became required for the adjuvant endocrine therapy, we performed this follow-up observation study. METHODS: Follow-up observation study was performed up to 10th year after randomization, continuing RCT to evaluate the efficacy and safety of leuprorelin every 3 months for ≥ 3 versus 2 years, with daily tamoxifen for 5 years. Primary endpoints were disease-free survival (DFS) and 2-year landmark DFS. RESULTS: Eligible patients (N = 222) were randomly assigned to receive leuprorelin for either 2 years (N = 112) or ≥ 3 years (N = 110) with tamoxifen. Leuprorelin treatment for ≥ 3 years versus 2 years provided no significant difference in DFS (HR 0.944, 95% CI 0.486-1.8392) or 2-year landmark DFS (N = 99 and 102 in 2-year and ≥ 3-year groups, HR 0.834, 0.397-1.753). In small, higher-risk subgroup (n = 17); however, 2-year landmark DFS in ≥ 3-year group was significantly longer (HR 0.095, 0.011-0.850) than that in 2-year group. The incidence of bone-related adverse events was around 5% in both groups. CONCLUSIONS: Adjuvant leuprorelin treatment for ≥ 3 years with tamoxifen only showed similar efficacy and safety profiles to those for 2 years in analyses among all patients but suggested greater benefit in higher-risk patients. No new safety signal was identified for long-term leuprorelin treatment. TRIAL REGISTRATION NUMBER: Not applicable. This was an observational study.

Endocrine Therapy in Early Breast Cancer.

BACKGROUND: Endocrine therapy with a standard duration of 5 years is well known as an effective treatment for endocrine-sensitive breast cancer. SUMMARY: In the adjuvant setting this treatment reduces the 15-year mortality rates by about 30 and 40% with tamoxifen and aromatase inhibitor, respectively. The well-known long-term recurrence risk of luminal cancers led to multiple trials examining the benefit of extended endocrine treatment for up to 15 years. Additional benefit with extended therapy was seen for patients with high recurrence risk. Also, additional ovarian suppression for premenopausal women exhibited a significant benefit for patients at higher risk. KEY MESSAGES: The data of the last years will be summarized and discussed, also considering the side effects of the different treatment options.