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.

Screening Patients With Metastatic Breast Cancer for Psychiatric Disease: a Cross Sectional Study

Objective: To evaluate the prevalence of psychiatric disorders in a sample of Portuguese patients with metastatic breast cancer and assess the relationship between these disorders and the characteristics of the oncological disease.Methods: Cross-sectional, single-center study with female patients diagnosed with metastatic breast carcinoma and under palliative treatment between November 2020 and May 2021. Psychiatric disorders were screened by applying and filling-out the MMSE, HADS, BSI, and WHOQoL-Bref instruments at the outpatient daycare unit when patients were present for treatmen. Results: A total of 91 female patients were included, median age 59.79 years. None of the patients had cognitive impairment (MMSE). HADS scale: 18.7% of the patients scored for anxiety and 17.6% for depression. The anxiety subscale score of > 8 (HADS) was related to ovarian function suppression (p<0.001), neoadjuvant therapy (p<0.001), and type of second-line of palliative treatment (p=0.024). The depression subscale score >8 (HADS) was related to the type of surgery performed (p= 0.022), molecular subtype of the tumor (p=0.020), and occurrence of grade 3-4 toxicities in the first (p=0.018), and third-line treatments (p=0.031).Conclusion: The screening of psychiatric disorders through the application of these scales by the medical oncology team may be able to aid in diagnosis and potentially lead to psychiatric referral and intervention at an earlier stage.

Optimal Endocrine Therapy in Premenopausal Women: A Pragmatic Approach to Unanswered Questions

Recent epidemiologic data show an increasing incidence of breast cancer among premenopausal women in many higher-income countries. Among premenopausal women, those diagnosed under age 40 years experience inferior long-term outcomes, particularly in the setting of hormone receptor–positive, human epidermal growth factor receptor 2–negative disease. In addition to more advanced disease presentation and/or less favorable disease biology, suboptimal adjuvant endocrine therapy (ET) has emerged as an important driver of this age-related disparity. Historically, young women have been excluded from treatment with aromatase inhibitors (AIs), attained low rates of chemotherapy-related amenorrhea, and exhibited low adherence to ET. Recently, several studies have demonstrated treatment with ovarian function suppression (OFS) during the first 5 years postdiagnosis to be associated with improvements in breast cancer recurrence and mortality, with additional benefits achieved from pairing OFS with an AI. As the first 5 years of ET for premenopausal women has been transformed, extended ET, administered in years 5-10 postdiagnosis, has also become more common. However, the only studies of extending ET in premenopausal women have tested an additional 5 years of tamoxifen following an initial 5 years of tamoxifen and studies of AIs in the second 5 years have been limited to postmenopausal women. Herein, we review available data concerning potential benefits and risks to be considered when counseling premenopausal women on extended ET, including the continuation of OFS. We offer a pragmatic framework to support decision making given the current body of knowledge and call out the need for additional research into this issue.

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.

Ovarian function suppression in premenopausal patients with concurrent endocrine therapy use.

6574 Background: The addition of ovarian function suppression (OFS) to endocrine therapy (ET) for premenopausal women with high risk, hormone receptor-positive breast cancer improves disease outcomes. However, in the SOFT-EST study, up to 17% of patients receiving gonadotropin-releasing hormone agonists (GnRHa) did not have appropriate ovarian suppression within the first year of treatment. Few studies have explored the long-term effectiveness of OFS to maintain estrogen suppression. Guidelines for estradiol monitoring during OFS therapy are not clearly defined. Methods: We performed a retrospective, single institution review of all patients who received concurrent GnRHa injections and ET since 2010. Only estradiol concentrations that were assessed during OFS treatment were abstracted from the medical record and included in the analysis. The primary endpoint was the percentage of patients with a non-suppressed estradiol concentration (defined as standard estradiol or high-sensitivity estradiol ≥ 10 pg/ml) identified during OFS cycle 2 ( > 35 days after OFS initiation) and/or later cycles. The secondary endpoint, which included only those patients with estradiol assessment within 35 days of OFS initiation, was the percentage of patients with a non-suppressed estradiol level when measured within the first 35 days after OFS initiation. For both cohorts, differences in age, body mass index (BMI), and previous chemotherapy use were summarized via multivariable logistic regression. Results: 148 patients received concurrent OFS and ET. Patients were excluded because of lack of estradiol assessment during OFS therapy (n = 13) and non-compliance with GnRHa injections (n = 4). The average age and BMI were 43.1 years and 29.1 kg/m2, respectively. 35 of 131 patients (26.7%) had at least one non-suppressed estradiol level during OFS cycle 2 and/or later cycles. The median time to detection of non-suppression was 250 days (range: 53 – 2573 days). Patients whose estradiol concentration remained suppressed throughout treatment with OFS and ET were more likely to be older (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). For the secondary endpoint, 20 of 83 patients (24.1%) had a non-suppressed estradiol level within 35 days of OFS initiation. Lower BMI was associated with achieving ovarian suppression by 35 days (OR 0.85 [95% CI 0.77-0.93], p <.001); no association was noted for age or chemotherapy. Conclusions: More than one-fourth of patients in this “real world” population had at least one non-suppressed estradiol level during treatment, both the month after the initial OFS dose and at later time points. Patients on OFS, especially those on aromatase inhibitor therapy and those at increased risk of non-suppression, may require frequent and long-term estradiol monitoring during treatment.

Distribution of dyslipidemia in Chinese early breast cancer patients at diagnosis and comparison of dyslipidemia incidence following different endocrine therapies: a population-based cohort study

Background Dyslipidemia increases the risk of cardiovascular disease death in breast cancer (BC). Based on the large West China Hospital (WCH) BC cohort, we aimed to clarify dyslipidemia prevalence at diagnosis and compare the risk of dyslipidemia induced by different endocrine and menopause status. Methods 5917 EBC female patients recorded in WCH BC cohort, diagnosed between 2008.10 and 2017.04, were included for baseline analysis. 1883 patients receiving endocrine therapy (selective estrogen receptor modulator (SERM) or aromatase inhibitor (AI), with or without ovarian function suppression) with initial normal blood lipids were included for comparison study. Dyslipidemia was defined as abnormality of cholesterol/LDL/ HDL/triglyceride. Risk accumulation function was used to calculate the incidence of dyslipidemia to assess absolute risk, and the multivariate COX regression model was used to calculate the relative risk of dyslipidemia between groups. Results 16.5% of EBC patients had dyslipidemia at diagnosis. Among EBC patients receiving endocrine therapy, the accumulated incidence of dyslipidemia within 5 years in menopausal patients was higher than that in premenopausal patients (Adjusted HR [95%CI], 1.29 [1.04–1.59], 42.6 % vs 32.6%, P = 0.0186). In premenopausal patients, the risk of abnormal TC in OFS + AI group was significantly higher than SERM group (adjusted HR, 3.50 [ 1.74–7.02], P < 0.001, 5-year abnormal rate 22.0% vs 3.5%), and that of abnormal LDL-C was also increased(adjusted HR, 6.71 [ 3.16–14.26], P < 0.001, 5-year abnormal rate 12.2% vs 1.4%). In menopausal patients, the risk of abnormal TC or LDL-C showed the similar trend in AI group compared to SERM group. Conclusions Dyslipidemia is common concomitant disease in Chinese BC patients and needs to be closely monitored. Irrespective of menopause, AIs treatment causes higher risk of TC/LDL-C dyslipidemia than SERM.