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Breast cancer (BC) is the most prevalent malignancy among women worldwide, with a rising incidence in young, premenopausal patients. For those diagnosed with hormone receptor-positive (HR+) BC, tamoxifen is a cornerstone of adjuvant endocrine therapy, significantly reducing recurrence risk and improving long-term survival. However, its prolonged use poses challenges for women desiring pregnancy, prompting interest in temporary treatment interruption as a strategy to achieve reproductive goals while maintaining oncological safety. This systematic review evaluates the impact of tamoxifen on fertility, the feasibility of treatment interruption, and associated reproductive and oncological outcomes. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a comprehensive search across major databases, identifying three relevant studies, including one randomized controlled trial (RCT) and two observational cohort studies. The findings suggest that temporary tamoxifen interruption allows for successful pregnancies without significantly increasing short-term recurrence rates. Notably, the POSITIVE trial demonstrated a pregnancy achievement rate of 74% and a live birth rate of 63.8%, with comparable three-year disease-free survival between patients who interrupted tamoxifen and those who continued therapy. However, concerns remain regarding tamoxifen’s teratogenic risks, emphasizing the need for strict contraceptive measures and preconception counseling. Despite emerging evidence supporting this approach, long-term safety data are limited. Further research is warranted to refine clinical recommendations and optimize reproductive counseling for young BC survivors.

At 8 years of follow-up, premenopausal women with breast cancer had higher rates of disease-free and overall survival with the addition of ovarian suppression to antiestrogen therapy and a higher rate of hormonal side effects than with tamoxifen alone.

Tamoxifen is essential in treating estrogen receptor-positive (ER+) breast cancer, primarily through its active metabolite, endoxifen. Emerging research suggests potential interactions between tamoxifen and gut microbiota. This study investigates the effects of tamoxifen on gut microbiota composition in postmenopausal ER+ and human epidermal growth factor receptor 2 negative (HER2−) breast cancer patients and explores correlations between gut microbiota and endoxifen plasma levels. This prospective observational study included postmenopausal ER+/HER2− breast cancer patients. Fecal and blood samples were collected before and during 6–12 weeks of tamoxifen therapy. Gut microbiota composition was analyzed using 16S rRNA amplicon sequencing of the hypervariable V4 gene region, and plasma endoxifen levels were measured using liquid chromatography-mass spectrometry. Changes in microbial diversity and composition were assessed, with correlations to endoxifen levels. A total of 62 patients were included. Tamoxifen significantly increased microbial richness ( p  = 0.019), although overall community structure remained consistent between pre- and during-treatment samples. Notable changes were observed in specific microbial taxa, with significant increases in genera such as Blautia ( p adjusted  = 0.003) and Streptococcus ( p adjusted  = 0.010), and decreases in Prevotella_9 ( p adjusted  = 0.006). No significant correlations between gut microbiota and endoxifen levels were identified after multiple comparisons. Tamoxifen therapy increases gut microbial diversity in postmenopausal ER+/HER2− breast cancer patients, though overall microbial community structure remains stable. The absence of significant correlations with endoxifen levels suggests that while tamoxifen affects the gut microbiota, its role in endoxifen metabolism requires further study. More comprehensive research is needed to understand the relationship between tamoxifen, gut microbiota, and therapeutic outcomes.

AbstractObjectiveTo investigate the effect of endocrine therapies on a wide range of specific clinical cardiovascular disease outcomes in women with a history of non-metastatic breast cancer.DesignSystematic review and meta-analysis of randomised controlled trials and observational studies.Data sourcesMedline and Embase up until June 2018.Eligibility criteria for selecting studiesStudies were included if they investigated the risk of a specific cardiovascular disease outcome associated with use of either tamoxifen or an aromatase inhibitor, or compared the two treatments, in women with a history of non-metastatic breast cancer.Appraisal and data extractionRelevant studies were originally identified and results extracted by one researcher, with a full replication of the study identification process by a combination of two other researchers. The Cochrane Collaboration’s tool for assessing risk of bias was used to assess risk of bias in randomised controlled trials, and this tool was adapted to assess risk of bias in observational studies.Results26 studies were identified, with results for seven specific cardiovascular disease outcomes (venous thromboembolism, myocardial infarction, stroke, angina, heart failure, arrhythmia, and peripheral vascular disease). Results suggested an increased risk of venous thromboembolism in tamoxifen users compared with both non-users and aromatase inhibitor users. Results were also consistent with a higher risk of the vascular diseases myocardial infarction and angina in aromatase inhibitor users compared with tamoxifen users, but there was also a suggestion that this may be partly driven by a protective effect of tamoxifen on these outcomes. Data were limited, and evidence was generally inconsistent for all other cardiovascular disease outcomes.ConclusionThis review has collated substantial randomised controlled trial and observational evidence on the effect of endocrine therapies on several specific cardiovascular disease outcomes including venous thromboembolism and myocardial infarction, progressing knowledge. Although the choice of aromatase inhibitor or tamoxifen will primarily be based on the effectiveness against the recurrence of breast cancer, this review shows that the individual patient’s risk of venous or arterial vascular disease should be an important secondary consideration.Systematic review registrationProspero CRD42017065944.

Breast cancer (BC) is one of the leading causes of death from cancer in women; second only to lung cancer. Tamoxifen (TAM) is a hydrophobic anticancer agent and a selective estrogen modulator (SERM), approved by the FDA for hormone therapy of BC. Despite having striking efficacy in BC therapy, concerns regarding the dose-dependent carcinogenicity of TAM still persist, restricting its therapeutic applications. Nanotechnology has emerged as one of the most important strategies to solve the issue of TAM toxicity, owing to the ability of nano-enabled-formulations to deliver smaller concentrations of TAM to cancer cells, over a longer period of time. Various TAM-containing-nanosystems have been successfully fabricated to selectively deliver TAM to specific molecular targets found on tumour membranes, reducing unwanted toxic effects. This review begins with an outline of breast cancer, the current treatment options and a history of how TAM has been used as a combatant of BC. A detailed discussion of various nanoformulation strategies used to deliver lower doses of TAM selectively to breast tumours will then follow. Finally, a commentary on future perspectives of TAM being employed as a targeting vector, to guide the delivery of other therapeutic and diagnostic agents selectively to breast tumours will be presented.

Background: Although the use of complementary and alternative medicines is widespread in cancer patients, clinical evidence of their benefits is sparse. Furthermore, while they are often assumed to be safe with regard to concurrent use of anticancer therapies, few studies have been carried out to investigate possible interactions. Fucoidans are a group of sulfated carbohydrates, derived from marine brown algae, which have long been used as dietary supplements due to their reported medicinal properties, including anticancer activity. The aim of this study was to investigate the effect of co-administration of fucoidan, derived from Undaria pinnatifida, on the pharmacokinetics of 2 commonly used hormonal therapies, letrozole and tamoxifen, in patients with breast cancer. Methods: This was an open label non-crossover study in patients with active malignancy taking letrozole or tamoxifen (n = 10 for each group). Patients took oral fucoidan, given in the form of Maritech extract, for a 3-week period (500 mg twice daily). Trough plasma concentrations of letrozole, tamoxifen, 4-hydroxytamoxifen, and endoxifen were measured using HPLC-CAD (high-performance liquid chromatography charged aerosol detector), at baseline and after concomitant administration with fucoidan. Results: No significant changes in steady-state plasma concentrations of letrozole, tamoxifen, or tamoxifen metabolites were detected after co-administration with fucoidan. In addition, no adverse effects of fucoidan were reported, and toxicity monitoring showed no significant differences in all parameters measured over the study period. Conclusions: Administration of Undaria pinnatifida fucoidan had no significant effect on the steady-state trough concentrations of letrozole or tamoxifen and was well tolerated. These results suggest that fucoidan in the studied form and dosage could be taken concomitantly with letrozole and tamoxifen without the risk of clinically significant interactions.

Background: Low adherence to adjuvant tamoxifen is associated with worse health outcomes but little is known about the cost-effectiveness of high adherence. Methods: We conducted an economic evaluation using data for all women with incident breast cancer between 1993 and 2000 who were subsequently prescribed tamoxifen in the Tayside region of Scotland. Patient-level, lifetime Markov models evaluated the impact of high vs low adherence to tamoxifen using linked prescribing, cancer registry, clinical cancer audit, hospital discharge and death records. Direct medical costs were estimated for each patient and quality-of-life weights were assigned. Recurrence information was collected by case note review and adherence calculated from prescribing records with low adherence classed below 80%. Results: A total of 354 (28%) patients had a recorded recurrence and 504 (39%) died. Four hundred and seventy-five (38%) patients had low adherence over the treatment period, which was associated with reduced time to recurrence of 52% ( P <0.001). Time to other cause mortality was also reduced by 23% ( P =0.055) but this was not statistically significant. For an average patient over her lifetime, low adherence was associated with a loss of 1.43 (95% CI: 1.15–1.71) discounted life years or 1.12 (95% CI: 0.91–1.34) discounted quality-adjusted life years (QALYs) and increased discounted medical costs of £5970 (95% CI: £4644–£7372). Assuming a willingness to pay threshold of £25 000 per QALY, the expected value of changing a patient from low to high adherence is £33 897 (95% CI: £28 322–£39 652). Conclusion: Patients with low adherence have shorter time to recurrence, increased medical costs and worse quality of life. Interventions that encourage patients to continue taking their treatment on a daily basis for the recommended 5-year period may be highly cost-effective.

This trial did not support routine use of ovarian suppression in premenopausal breast cancer. Nevertheless, there may be some benefit from ovarian suppression in the subgroup of younger patients whose menses return after adjuvant chemotherapy, but also more symptoms. Adjuvant endocrine therapy with tamoxifen has been recommended for premenopausal women with hormone-receptor–positive breast cancer (positive for estrogen receptor, progesterone receptor, or both) during the past 15 years. 1 , 2 The value of therapeutic suppression of ovarian estrogen production in premenopausal women who receive tamoxifen is uncertain. 3 The American Society of Clinical Oncology endorsed guidelines recommending that ovarian ablation or suppression (hereafter, ovarian suppression) not be added routinely to adjuvant therapy in premenopausal women. 4 Chemotherapy-induced ovarian suppression (amenorrhea) is correlated with a reduced risk of relapse 5 – 7 but is less likely to be achieved in very young women. International consensus guidelines . . .