Tamoxifen for adults with hepatocellular carcinoma.

RATIONALE: Hepatocellular carcinoma is the most common type of liver cancer, accounting for 70% to 85% of individuals with primary liver cancer. Tamoxifen has been evaluated in randomised clinical trials in people with hepatocellular cancer. The reported results have been inconsistent. OBJECTIVES: To evaluate the benefits and harms of tamoxifen or tamoxifen plus any other anticancer drugs compared with no intervention, placebo, any type of standard care, or alternative treatment in adults with hepatocellular carcinoma, irrespective of sex, administered dose, type of formulation, and duration of treatment. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, three other databases, and major trials registries, and handsearched reference lists up to 26 March 2024. ELIGIBILITY CRITERIA: Parallel-group randomised clinical trials including adults (aged 18 years and above) diagnosed with advanced or unresectable hepatocellular carcinoma. Had we found cross-over trials, we would have included only the first trial phase. We did not consider data from quasi-randomised trials for analysis. OUTCOMES: Our critical outcomes were all-cause mortality, serious adverse events, and health-related quality of life. Our important outcomes were disease progression, and adverse events considered non-serious. RISK OF BIAS: We assessed risk of bias using the RoB 2 tool. SYNTHESIS METHODS: We used standard Cochrane methods and Review Manager. We meta-analysed the outcome data at the longest follow-up. We presented the results of dichotomous outcomes as risk ratios (RR) and continuous data as mean difference (MD), with 95% confidence intervals (CI) using the random-effects model. We summarised the certainty of evidence using GRADE. INCLUDED STUDIES: We included 10 trials that randomised 1715 participants with advanced, unresectable, or terminal stage hepatocellular carcinoma. Six were single-centre trials conducted in Hong Kong, Italy, and Spain, while three were conducted as multicentre trials in single countries (France, Italy, and Spain), and one trial was conducted in nine countries in the Asia-Pacific region (Australia, Hong Kong, Indonesia, Malaysia, Myanmar, New Zealand, Singapore, South Korea, and Thailand). The experimental intervention was tamoxifen in all trials. The control interventions were no intervention (three trials), placebo (six trials), and symptomatic treatment (one trial). Co-interventions were best supportive care (three trials) and standard care (one trial). The remaining six trials did not provide this information. The number of participants in the trials ranged from 22 to 496 (median 99), mean age was 63.7 (standard deviation 4.18) years, and mean proportion of men was 74.7% (standard deviation 42%). Follow-up was three months to five years. SYNTHESIS OF RESULTS: Ten trials evaluated oral tamoxifen at five different dosages (ranging from 20 mg per day to 120 mg per day). All trials investigated one or more of our outcomes. We performed meta-analyses when at least two trials assessed similar types of tamoxifen versus similar control interventions. Eight trials evaluated all-cause mortality at varied follow-up points. Tamoxifen versus the control interventions (i.e. no treatment, placebo, and symptomatic treatment) results in little to no difference in mortality between one and five years (RR 0.99, 95% CI 0.92 to 1.06; 8 trials, 1364 participants; low-certainty evidence). In total, 488/682 (71.5%) participants died in the tamoxifen groups versus 487/682 (71.4%) in the control groups. The separate analysis results for one, between two and three, and five years were comparable to the analysis result for all follow-up periods taken together. The evidence is very uncertain about the effect of tamoxifen versus no treatment on serious adverse events at one-year follow-up (RR 0.44, 95% CI 0.19 to 1.06; 1 trial, 36 participants; very low-certainty evidence). A total of 5/20 (25.0%) participants in the tamoxifen group versus 9/16 (56.3%) participants in the control group experienced serious adverse events. One trial measured health-related quality of life at baseline and at nine months' follow-up, using the Spitzer Quality of Life Index. The evidence is very uncertain about the effect of tamoxifen versus no treatment on health-related quality of life (MD 0.03, 95% CI -0.45 to 0.51; 1 trial, 420 participants; very low-certainty evidence). A second trial found no appreciable difference in global health-related quality of life scores. No further data were provided. Tamoxifen versus control interventions (i.e. no treatment, placebo, or symptomatic treatment) results in little to no difference in disease progression between one and five years' follow-up (RR 1.02, 95% CI 0.91 to 1.14; 4 trials, 720 participants; low-certainty evidence). A total of 191/358 (53.3%) participants in the tamoxifen group versus 198/362 (54.7%) participants in the control group had progression of hepatocellular carcinoma. Tamoxifen versus control interventions (i.e. no treatment or placebo) may have little to no effect on adverse events considered non-serious during treatment, but the evidence is very uncertain (RR 1.17, 95% CI 0.45 to 3.06; 4 trials, 462 participants; very low-certainty evidence). A total of 10/265 (3.8%) participants in the tamoxifen group versus 6/197 (3.0%) participants in the control group had adverse events considered non-serious. We identified no trials with participants diagnosed with early stages of hepatocellular carcinoma. We identified no ongoing trials. AUTHORS' CONCLUSIONS: Based on the low- and very low-certainty evidence, the effects of tamoxifen on all-cause mortality, disease progression, serious adverse events, health-related quality of life, and adverse events considered non-serious in adults with advanced, unresectable, or terminal stage hepatocellular carcinoma when compared with no intervention, placebo, or symptomatic treatment could not be established. Our findings are mostly based on trials at high risk of bias with insufficient power (fewer than 100 participants), and a lack of trial data on clinically important outcomes. Therefore, firm conclusions cannot be drawn. Trials comparing tamoxifen administered with any other anticancer drug versus standard care, usual care, or alternative treatment as control interventions were lacking. Evidence on the benefits and harms of tamoxifen in participants at the early stages of hepatocellular carcinoma was also lacking. FUNDING: This Cochrane review had no dedicated funding. REGISTRATION: Protocol available via DOI: 10.1002/14651858.CD014869.

What is the nature and impact of cognitive difficulties following hormonal treatments for prostate cancer?: An interpretative phenomenological analysis.

OBJECTIVE: Prostate cancer hormonal treatments (e.g. androgen deprivation therapy) yield clinical benefits. However, there is increasing evidence these treatments may adversely impact cognitive functioning. This study aimed to qualitatively characterise the nature and impact of cognitive difficulties following these treatments. METHODS: Prostate cancer survivors (PCS) self-reporting cognitive difficulties following hormonal treatments (via an online survey) and their partners were invited to participate in semi-structured interviews. Telephone or videoconferencing interviews were conducted, then transcribed, double-coded and analysed using the Framework Method, following the principles of Interpretative Phenomenological Analysis. RESULTS: Eleven participants (six PCS and five partners) were interviewed. PCS reported a range of cognitive difficulties, verified by their partners, including forgetfulness, "fogginess", fatigue and slowed processing speed. For some PCS, word-finding difficulties, tangential speech and memory problems were apparent during interviews. The aetiology of the reported cognitive difficulties was unclear as it was attributed to a possible combination of cancer treatments, compounding side-effects (e.g. fatigue, sleep problems, hot flashes), exacerbation of pre-existing conditions and/or age-related changes. Cognitive difficulties were reported to have led to shifts in self-perception, interpersonal dynamics and increased emotionality. Engagement in cognitively-stimulating activities and reliance on compensatory strategies were reported to be helpful in managing some cognitive difficulties. All participants endorsed the potential benefits of neuropsychological intervention. CONCLUSIONS: There are a diverse range of cognitive difficulties following hormonal treatments for prostate cancer experienced by PCS and their partners. Understanding the impact of these difficulties is important for the development of targeted neuropsychological interventions.

Drug exposure and risk factors of maculopathy in tamoxifen users.

Tamoxifen, a pivotal therapy for hormone receptor-positive breast cancer, is known for its efficacy in reducing breast cancer recurrence and mortality. However, concerns about potential ocular complications, particularly maculopathy, have emerged. This study aims to investigate the risk and associated factors of diverse macular conditions in tamoxifen users, considering drug exposure, demographics, and systemic diseases. A nationwide cohort of tamoxifen users, comprised of 14,267 tamoxifen users, was analyzed using the health insurance review and assessment database in South Korea. Demographic and clinical characteristics were examined, and the cumulative incidence of macular diseases was stratified by age and cumulative tamoxifen dosage. We conducted logistic regression analysis to identify potential risk factors among clinical variables such as age, sex, indications for tamoxifen use, and systemic diseases associated with various macular conditions. Additionally, Cox proportional hazard models were used to determine the baseline clinical characteristics predictive of these macular conditions, with subsequent calculation of hazard ratios. Cumulative incidences of overall macular diseases, other maculopathy excluding common macular diseases, and macular edema were 26.4, 11.4, and 6.5%, respectively. The incidence of various macular conditions increased with age and the cumulative tamoxifen dose. Age, cumulative dose group, and liver diseases demonstrated significant associations with overall macular diseases and maculopathy excluding common macular diseases in multivariate logistic regression analyses (all P < 0.05). Furthermore, age emerged as significant predictive factors of maculopathy in Cox proportional hazard models. Tamoxifen-induced maculopathy poses a concern for prescribing physicians and ophthalmologists, and this study provides valuable insights into its risk and risk factors. This study may contribute to evidence-based guidelines for tamoxifen maculopathy screening, emphasizing the importance of considering age, cumulative dose, and liver diseases for recommendation on screening timing and frequency.

Precocious puberty and other endocrine disorders during mitotane treatment for paediatric adrenocortical carcinoma - case series and literature review.

INTRODUCTION: Adrenocortical carcinoma (ACC) is rare and an aggressive tumour. Mitotane is the mainstay adjuvant drug in treating ACC. The study aimed to describe patients diagnosed with precocious puberty (PP) and other endocrinological complications during mitotane therapy. MATERIAL AND METHODS: This retrospective study enrolled 4 patients with ACC treated with mitotane therapy complicated by PP. We analysed clinical manifestations, radiological, histopathological findings, and hormonal results. RESULTS: The median age at the diagnosis of ACC was 1.5 years. All patients were treated with surgery and mitotane, accompanied by chemotherapy regimens in 2 cases. The median time from surgery to the initiation of mitotane therapy was 26 days. During mitotane treatment, PP was confirmed based on symptoms, and hormonal and imaging tests. In one patient, incomplete peripheral PP was followed by central PP. The median time from the therapy initiation to the first manifestations of PP was 4 months. Additionally, due to mitotane-induced adrenal insufficiency, patients required a supraphysiological dose of hydrocortisone (HC), and in one patient, mineralocorticoid (MC) replacement with fludrocortisone was necessary. In 2 patients, hypothyroidism was diagnosed. All patients presented neurological symptoms of varying expression, which were more severe in younger children. CONCLUSIONS: The side effects of using mitotane should be recognized quickly and adequately treated. In prepubertal children, PP could be a complication of therapy. The need to use supraphysiological doses of HC, sometimes with MC, should be highlighted. Some patients require levothyroxine replacement therapy. The neurotoxicity of mitotane is a significant clinical problem.

Development of a Novel Patient-Reported Outcome Measure to Assess Symptoms and Impacts of Androgen Deprivation Therapy for Advanced Prostate Cancer.

INTRODUCTION: This qualitative research study was conducted to develop a novel, comprehensive, patient-reported outcome measure (PRO), the "Symptoms and Impacts of Androgen Deprivation Therapy (ADT) for Prostate Cancer" (SIADT-PC), assessing hormonal therapy-related symptoms and their impacts on men with advanced prostate cancer. METHODS: Concept elicitation (CE) interviews were conducted among adult men with prostate cancer to evaluate their experiences with ADT. Based on key symptom and impact concepts mentioned, an initial PRO measure was developed. The draft measure was further assessed in cognitive debriefing (CD) interviews with men with prostate cancer, in which participants reviewed items, response options, and recall periods. Initial item-based psychometric analyses were conducted using interview data. The draft questionnaire was revised on the basis of participant feedback, quantitative psychometric results, and consultation with clinical experts. RESULTS: A total of 21 participants were interviewed (CE concept elicitation, n = 12; CD cognitive debriefing, n = 17; n = 8 completed both). Mean participant age (SD) was 59.7 (8.7) years and 76.2% were white. The de novo SIADT-PC measure consists of 27 items: 11 symptoms (e.g., fatigue, hot flashes, and erectile dysfunction), 2 long-term symptoms (e.g., weight gain), 10 impacts (e.g., impacts on physical activities and relationships), and 4 related to mode of administration (i.e., injection-site reactions). Items were assessed with a 5-point verbal rating scale, with answer choices that capture frequency or severity. CONCLUSIONS: Once fully validated, this de novo measure may be used in clinical studies and clinical practice to assess hormone therapy-related symptoms and impacts, enabling physicians to identify timely and appropriate interventions.

Oral octreotide capsules for acromegaly treatment: application of clinical trial insights to real-world use.

INTRODUCTION: Acromegaly is a rare endocrine disorder usually caused by a benign growth hormone‒secreting pituitary adenoma. Surgical adenoma resection is typically the first line of treatment, and medical therapy is used for patients with persistent disease following surgery, for adenoma recurrence, or for patients ineligible for, or declining, surgery. Approved somatostatin receptor ligands (SRLs) have been limited to injectable options, until recently. Oral octreotide capsules (OOC) are the first approved oral SRL for patients with acromegaly. AREAS COVERED: We review published reports and provide case study examples demonstrating practical considerations on the use of OOC. Using two hypothetical case scenarios, we discuss current treatment patterns, breakthrough symptoms and quality of life (QoL), efficacy of SRLs, OOC dose titration, evaluation of OOC treatment response, and incidence and management of adverse events. EXPERT OPINION: OOC are an option for patients with acromegaly including those who experience breakthrough symptoms, who have preference for oral therapies, or other reasons for declining injectable SRLs. OOC have been associated with improved patient-reported QoL measures compared with those reported for lanreotide and octreotide. Continued real-world experience will determine whether OOC, alone or in combination with other therapies, provides further advantages over current injectable acromegaly treatments.

Drug-induced liver injury secondary to tamoxifen.

Tamoxifen is a non-steroidal selective oestrogen receptor modulator commonly used in the treatment of breast cancer. It is associated with the development of fatty liver and steatohepatitis however drug-induced liver injury is rare. We report a woman in her 50s who developed malaise with an acute moderate aminotransferase elevation without jaundice 6 months after starting tamoxifen. She was not commenced on any other recent drugs and extensive investigation including infective and autoimmune liver screen, cross-sectional imaging and FibroScan were unremarkable. Liver biopsy revealed moderate lobular hepatitis with hepatocyte drop-out. Tamoxifen was ceased and the liver enzymes showed resolution over the following 3 months and improvement of her symptoms.

Quantitative evaluation of the efficacy and safety profiles of two types of targeted inhibitors combined with endocrine therapy in ER+/HER2- metastatic breast cancer.

PURPOSE: The aim of this study was to quantitatively compare the efficacy and safety of CDK4/6 inhibitors and PI3K/AKT/mTOR inhibitors for ER+/HER2- metastatic breast cancer. METHODS: A parametric survival function was used to analyze the time course of overall survival (OS) and progression-free survival (PFS). The objective response rate (ORR) and the incidence of any grade and grade 3-4 adverse events were summarized using the random-effects model of a single-arm meta-analysis. RESULTS: This study included 44 arms from 48 publications, with a total sample size of 7881 patients. Our study revealed that CDK4/6 inhibitors had a median OS of 40.7 months, a median PFS of 14.8 months, and an ORR of 40%, whereas PI3K/AKT/mTOR inhibitors had a median OS of 29.8 months, a median PFS of 8.3 months, and an ORR of 20%. Additionally, this study also found that the proportion of patients with visceral metastases and specific endocrine therapy used in combination significantly impact OS and PFS. In terms of adverse events, CDK4/6 inhibitors exhibited a relatively high incidence of hematological adverse events. CONCLUSION: Our study provides solid quantitative evidence for the first-line recommendation of CDK4/6 inhibitors combined with endocrine therapy for ER+/HER2- metastatic breast cancer in clinical guidelines.

Multicenter Study on the Frequency of Low Bone Mineral Density in Young Women With Breast Cancer and Associated Factors.

INTRODUCTION: Young women with breast cancer (BC) may experience bone mineral density (BMD) loss secondary to cancer treatment effects on estrogen levels. Studies assessing BMD in BC patients have had a limited representation of young women. This multicenter retrospective study analyzed the frequency of low BMD and associated factors in this age group. METHODS: Women diagnosed with stage 0-III BC at ≤40 years, treated with chemotherapy and/or endocrine therapy between 2010 and 2020 at 5 Mexican BC referral centers were eligible. Demographic, clinical and treatment data were collected, as well as bone dual-energy X-ray absorptiometry (DEXA) results. Low BMD was defined as lumbar or femoral neck T-score < -1.0 or Z-score ≤ -2.0. RESULTS: A total of 1259 patients were included; median age at diagnosis was 36 years (21-40). Overall, 93% received chemotherapy and 65% endocrine therapy (tamoxifen was received at some point by 61%, aromatase inhibitors by 17%, and GnRH agonists/bilateral oophorectomy by 21%). DEXA scans were documented in 254 (20%), of which 163 (64%; 95% confidence interval [CI] 58%-70%) had a low BMD report. Low BMD was associated with receiving aromatase inhibitors (Odds ratio [OR] 1.92; 95% CI 1.13-3.24), and GnRH agonists/bilateral oophorectomy (OR 2.25; 95% CI 1.21-4.21). CONCLUSION: The suboptimal frequency of BMD monitoring observed displays an alarming disregard for bone health in young patients. Thus, a high proportion of women with low BMD are potentially being missed and precluded from the opportunity to receive timely interventions. Particular focus should be put on BMD monitoring among patients treated with aromatase inhibitors, GnRH agonists or bilateral oophorectomy.

Tooth loss in breast cancer patients: A comparison between tamoxifen-treated and non-treated patients.

BACKGROUND: Tooth loss (TL) affects quality of life and general health. The literature suggesting that tamoxifen treatment in patients with breast cancer (BC) could be associated with alterations in oral health, increasing the risk of TL, is still scarce. This work aimed to determine the relationship between TL and tamoxifen consumption in patients with BC. MATERIAL AND METHODS: This cross-sectional observational study was carried out from July to September 2023 in the medical oncology services of the "Virgen de la Puerta" - ESSALUD High Complexity Hospital and "Dr. Luis Pinillos Ganoza" - IREN Norte - Regional Institute of Neoplastic Diseases, in Trujillo - Peru. Overall, 200 adult patients diagnosed with BC were evaluated, of which 100 consumed tamoxifen and 100 did not. Inter- and intra-rater reliability was determined with respect to TL, resulting in intra-class correlation values RHO = 0.971 and interclass RHO = 0.938. The oncologist of the corresponding service performed BC diagnosis and stage. Poisson regression was used to analyze results with a significance level of p<0.05. RESULTS: No relationship was found between TL and tamoxifen consumption in patients with breast cancer (p= 0.221); however, greater TL was observed in women who consumed tamoxifen for more than one year compared to those who did not use it (p=0.025) and in older adult women compared to young women (p=0.030). CONCLUSIONS: There is a relationship between TL and time of use of tamoxifen in patients with BC, concluding that patients who consumed tamoxifen for more than one year had greater TL than those who did not. Furthermore, no relationship was found between TL and cancer stages, but there was greater TL in older adult patients and also in those who consumed tamoxifen and did not receive chemotherapy or radiotherapy.

Fertility Preservation and Assisted Reproduction in Patients With Breast Cancer Interrupting Adjuvant Endocrine Therapy to Attempt Pregnancy.

PURPOSE: We investigated time to pregnancy, efficacy and safety of fertility preservation, and assisted reproductive technologies (ARTs) in women with early hormone receptor-positive breast cancer (BC) desiring future pregnancy. PATIENTS AND METHODS: POSITIVE is an international, single-arm, prospective trial, in which 518 women temporarily interrupted adjuvant endocrine therapy to attempt pregnancy. We evaluated menstruation recovery and factors associated with time to pregnancy and investigated if ART use was associated with achieving pregnancy. The cumulative incidence of BC-free interval (BCFI) events was estimated according to the use of ovarian stimulation at diagnosis. The median follow-up was 41 months. RESULTS: Two hundred seventy-three patients (53%) reported amenorrhea at enrollment, of whom 94% resumed menses within 12 months. Among 497 patients evaluable for pregnancy, 368 (74%) reported at least one pregnancy. Young age was the main factor associated with shorter time to pregnancy with cumulative incidences of pregnancy by 1 year of 63.5%, 54.3%, and 37.7% for patients age <35, 35-39, and 40-42 years, respectively. One hundred and seventy-nine patients (36%) had embryo/oocyte cryopreservation at diagnosis, of whom 68 reported embryo transfer after enrollment. Cryopreserved embryo transfer was the only ART associated with higher chance of pregnancy (odds ratio, 2.41 [95% CI, 1.75 to 4.95]). The cumulative incidence of BCFI events at 3 years was similar for women who underwent ovarian stimulation for cryopreservation at diagnosis, 9.7% (95% CI, 6.0 to 15.4), compared with those who did not, 8.7% (95% CI, 6.0 to 12.5). CONCLUSION: In POSITIVE, fertility preservation using ovarian stimulation was not associated with short-term detrimental impact on cancer prognosis. Pregnancy rates were highest among those who underwent embryo/oocyte cryopreservation followed by embryo transfer.

Adverse event signal mining and serious adverse event influencing factor analysis of fulvestrant based on FAERS database.

Fulvestrant, as the first selective estrogen receptor degrader, is widely used in the endocrine treatment of breast cancer. However, in the real world, there is a lack of relevant reports on adverse reaction data mining for fulvestrant. To perform data mining on adverse events (AEs) associated with fulvestrant and explore the risk factors contributing to severe AEs, providing a reference for the rational use of fulvestrant in clinical practice. Retrieved adverse event report information associated with fulvestrant from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database, covering the period from market introduction to September 30, 2023. Suspicious AEs were screened using the reporting odds ratio (ROR) and proportional reporting ratio methods based on disproportionality analysis. Univariate and multivariate logistic regression analyses were conducted on severe AEs to explore the risk factors associated with fulvestrant-induced severe AEs. A total of 6947 reports related to AEs associated with fulvestrant were obtained, including 5924 reports of severe AEs and 1023 reports of non-severe AEs. Using the disproportionality analysis method, a total of 210 valid AEs were identified for fulvestrant, with 45 AEs (21.43%) not listed in the product labeling, involving 11 systems and organs. The AEs associated with fulvestrant were sorted by frequency of occurrence, with neutropenia (325 cases) having the highest number of reports. By signal strength, injection site pruritus showed the strongest signal (ROR = 658.43). The results of the logistic regression analysis showed that concurrent use of medications with extremely high protein binding (≥ 98%) is an independent risk factor for severe AEs associated with fulvestrant. Age served as a protective factor for fulvestrant-related AEs. The co-administration of fulvestrant with CYP3A4 enzyme inhibitors did not show statistically significant correlation with the occurrence of severe AEs. Co-administration of drugs with extremely high protein binding (≥ 98%) may increase the risk of severe adverse reactions of fulvestrant. Meanwhile, age (60-74 years) may reduce the risk of severe AEs of fulvestrant. However, further clinical research is still needed to explore and verify whether there is interaction between fulvestrant and drugs with high protein binding through more clinical studies.

Balancing Hormone Therapy: Mitigating Adverse Effects of Androgen-Deprivation Therapy and Exploring Alternatives in Prostate Cancer Management.

Androgen-deprivation therapy (ADT) is well established as the standard of care in metastatic prostate cancer (PCa) management; however, ADT has significant adverse effects (AEs) that must be addressed. This review aims to highlight opportunities to mitigate AEs of ADT and explore alternatives in PCa management. Specifically, we discuss behavioral and pharmacologic strategies for mitigating ADT AEs as well as ADT-sparing approaches for hormone-sensitive and castration-resistant PCa. Equipped with effective mitigation strategies and possible alternatives, clinicians and researchers can optimize health-related quality of life for patients currently receiving ADT for PCa and consider treatments that spare patients from AEs of ADT.

Anastrozole Dose Escalation for Optimal Estrogen Suppression in Postmenopausal Early-Stage Breast Cancer: A Prospective Trial.

PURPOSE: We previously reported that postmenopausal women with estrogen receptor-α-positive breast cancer receiving adjuvant anastrozole 1 mg/day (ANA1) with estrone (E1) ≥1.3 pg/mL and estradiol (E2) ≥0.5 pg/mL [inadequate estrogen suppression (IES)] had a threefold increased risk of a breast cancer event. The objective of this study was to determine if increasing anastrozole to 10 mg/day (ANA10) could result in adequate estrogen suppression (AES: E1 <1.3 pg/mL and/or E2 <0.5 pg/mL) among those with IES on ANA1. PATIENTS AND METHODS: Postmenopausal women with estrogen receptor-α-positive breast cancer planning to receive adjuvant ANA1 were eligible. E1 and E2 were assessed pre- and post-8 to 10 weeks of ANA1. Those with IES were switched to 8- to 10-week cycles of ANA10 followed by letrozole 2.5 mg/day. E1 and E2 were assessed after each cycle. Anastrozole concentrations were measured post-ANA1 and post-ANA10. Primary analyses included patients who documented taking at least 80% of the planned treatment (adherent cohort). RESULTS: In total, 132 (84.6%) of 156 eligible patients were ANA1 adherent. IES occurred in 40 (30.3%) adherent patients. Twenty-five (78.1%) of 32 patients who began ANA10 were adherent, and AES was achieved in 19 (76.0%; 90% confidence interval, 58.1%-89.0%) patients. Anastrozole concentrations post-ANA1 and post-ANA10 did not differ by estrogen suppression status among adherent patients. AES was maintained/attained in 21 (91.3%) of 23 letrozole-adherent patients. CONCLUSIONS: Approximately 30% of ANA1-adherent patients had IES. Among those who switched to ANA10 and were adherent, 76% had AES. Further studies are required to validate emerging data that ANA1 results in IES for some patients and to determine the clinical benefit of switching to ANA10 or an alternative aromatase inhibitor.

Adverse effects of tamoxifen treatment on bone mineral density in premenopausal patients with breast cancer: a systematic review and meta-analysis.

BACKGROUND: It is well known that adjuvant tamoxifen treatment for breast cancer in postmenopausal women decreased bone loss. However, the effects of adjuvant tamoxifen therapy on bone mineral density (BMD) in premenopausal patients with breast cancer remains uncertain. Tamoxifen would have a potential impact of premenopausal BMD on health. The aim of this meta-analysis was to assess this in premenopausal women with primary breast cancer. METHODS: Through April 2020, studies reporting BMD changes of lumbar spine or hip in premenopausal women with primary breast cancer treated with adjuvant tamoxifen and tamoxifen plus chemotherapy or ovarian function suppression (OFS) were collected from EMBASE and PubMed. The meta-analysis was performed using random effects model of the standardized mean difference (SMD) of BMD in patients. RESULTS: A total of 1432 premenopausal patients were enrolled in eight studies, involving 198 patients treated with tamoxifen alone in three studies. After a 3-year median follow-up, adjuvant tamoxifen decreased the lumbar spinal and hip BMD by as much as an SMD of -1.17 [95% confidence interval (CI); -1.58 to -0.76)] and -0.66 (95% CI, -1.55 to 0.23), respectively. In subgroup analysis in patients treated adjuvant tamoxifen and tamoxifen plus chemotherapy or OFS according to follow-up duration, the bone change of < 3 years follow-up group was -0.03 SMD (95% CI, -0.47 to 0.41) and that of ≥ 3 years follow-up group was -1.06 SMD (95% CI, -1.48 to -0.64). Compared with patients who received tamoxifen alone, patients who received combination therapy with chemotherapy or OFS showed lesser bone loss at the lumbar spine. CONCLUSIONS: Our meta-analysis demonstrated that adjuvant tamoxifen therapy in premenopausal patients caused bone loss after 3 years of follow-up, especially at the lumbar spines. For a definite evaluation of the adverse effects of tamoxifen on bone, it is necessary to accumulate more relevant studies.

The impact of symptom clusters on endocrine therapy adherence in patients with breast cancer.

BACKGROUND: When taken as prescribed, endocrine therapy is effective in reducing risk of recurrence and mortality in the treatment of patients with breast cancer. However, treatment side effects can act as a barrier to medication adherence. Existing research has not identified any specific side effects as consistent predictors of nonadherence. Our aim was to explore the influence of symptom clusters on self-reported adherence in patients with breast cancer. METHODS: A cross-sectional online survey was conducted, including patients with breast cancer currently or previously prescribed endocrine therapy (N = 1051). This included measures of self-reported endocrine therapy adherence and common symptoms among this population (insomnia, depression, anxiety, fatigue, musculoskeletal, and vasomotor symptoms). RESULTS: Unintentional nonadherence was higher than intentional nonadherence (50.8 % vs 31.01 %). The most troublesome symptom was insomnia (73.83 % displayed probable insomnia disorder). K-means cluster analysis identified 2 symptom clusters: overall High symptoms, and overall Low symptoms. Participants in the Low symptoms cluster were significantly more likely to be classed as adherent based on unintentional and intentional items. CONCLUSIONS: Nonadherence was high in the current sample, and significantly more likely in participants reporting overall severe symptoms. Clinicians should be aware of the scale of common side effects and facilitate open conversation about potential barriers to adherence. Follow-up care should include assessment of common symptoms and signpost patients to appropriate support or treatment when required. Future research should explore potential for a central symptom to act as a target for intervention, to relieve overall side effect burden and facilitate better medication adherence.

Osteoporotic fracture risk in women with breast cancer treated with aromatase inhibitors: a health insurance claims database study in Japan.

BACKGROUND: Hormone therapy with aromatase inhibitors (AIs) for estrogen receptor-dependent breast cancer may expose patients to an increased osteoporosis risk. This study was performed to estimate fracture risk in women with breast cancer to whom AIs were prescribed in Japan. METHODS: This retrospective study used data from the Japanese Medical Data Vision database. Women with breast cancer prescribed AIs over a 12-month period were identified and matched to women not prescribed AIs using a propensity score. Fracture rates were estimated by a cumulative incidence function and compared using a cause-specific Cox hazard model. The proportion of women undergoing bone density tests was retrieved. RESULTS: For all fractures sites combined, cumulative fracture incidence at 10 years was 0.19 [95%CI: 0.16-0.22] in women prescribed AIs and 0.18 [95%CI: 0.15-0.21] without AIs. AI prescription was not associated with any changes in risk (adjusted hazard ratio: 1.08 [95%CI: 0.99-1.17] p = 0.08). Women prescribed AI more frequently underwent bone density testing (31.9% [95% CI: 31.2%; 32.6%] versus 2.2% [95% CI: 2.0%; 2.4%]). CONCLUSIONS: The anticipated association between AI exposure and osteoporotic fracture risk in Japanese women with breast cancer was not seen clearly.