A prospective study of vitamin D, proinflammatory cytokines, and risk of fragility fractures in women on aromatase inhibitors for breast cancer.

BACKGROUND: Vitamin D is critical to bone health by regulating intestinal absorption of calcium, whereas proinflammatory cytokines, including IL-1, IL-6, IL-12, and TNF-α, are known to increase bone resorption. We hypothesized that vitamin D and these cytokines at the time of breast cancer diagnosis were predictive for fragility fractures in women receiving aromatase inhibitors (AIs). METHODS: In a prospective cohort of 1,709 breast cancer patients treated with AIs, we measured the levels of 25-hydroxyvitamin D (25OHD), IL-1ß, IL-6, IL-12, and TNF-α from baseline blood samples. The associations of these biomarkers were analyzed with bone turnover markers (BALP and TRACP), bone regulatory markers (OPG and RANKL), bone mineral density (BMD) close to cancer diagnosis, and risk of fragility fractures during a median of 7.5 years of follow up. RESULTS: Compared to patients with vitamin D deficiency, patients with sufficient levels had higher bone turnover, lower BMD, and higher fracture risk; the latter became non-significant after controlling for covariates including BMD and no longer existed when patients taking vitamin D supplement or bisphosphonates or with history of fracture or osteoporosis were excluded. There was a non-significant trend of higher levels of IL-1ß and TNF-α associated with higher risk of fracture (highest vs. lowest tertile, IL-1ß: adjusted HR=1.37, 95% CI=0.94-1.99; TNF-α: adjusted HR=1.38, 95% CI=0.96-1.98). CONCLUSIONS: Our results do not support proinflammatory cytokines or vitamin D levels as predictors for risk of fragility fractures in women receiving AIs for breast cancer.

Androgen receptor-mediated pharmacogenomic expression quantitative trait loci: implications for breast cancer response to AR-targeting therapy.

BACKGROUND: Endocrine therapy is the most important treatment modality of breast cancer patients whose tumors express the estrogen receptor α (ERα). The androgen receptor (AR) is also expressed in the vast majority (80-90%) of ERα-positive tumors. AR-targeting drugs are not used in clinical practice, but have been evaluated in multiple trials and preclinical studies. METHODS: We performed a genome-wide study to identify hormone/drug-induced single nucleotide polymorphism (SNP) genotype - dependent gene-expression, known as PGx-eQTL, mediated by either an AR agonist (dihydrotestosterone) or a partial antagonist (enzalutamide), utilizing a previously well characterized lymphoblastic cell line panel. The association of the identified SNPs-gene pairs with breast cancer phenotypes were then examined using three genome-wide association (GWAS) studies that we have published and other studies from the GWAS catalog. RESULTS: We identified 13 DHT-mediated PGx-eQTL loci and 23 Enz-mediated PGx-eQTL loci that were associated with breast cancer outcomes post ER antagonist or aromatase inhibitors (AI) treatment, or with pharmacodynamic (PD) effects of AIs. An additional 30 loci were found to be associated with cancer risk and sex-hormone binding globulin levels. The top loci involved the genes IDH2 and TMEM9, the expression of which were suppressed by DHT in a PGx-eQTL SNP genotype-dependent manner. Both of these genes were overexpressed in breast cancer and were associated with a poorer prognosis. Therefore, suppression of these genes by AR agonists may benefit patients with minor allele genotypes for these SNPs. CONCLUSIONS: We identified AR-related PGx-eQTL SNP-gene pairs that were associated with risks, outcomes and PD effects of endocrine therapy that may provide potential biomarkers for individualized treatment of breast cancer.

Identifying drivers of first-line HR+/HER2- metastatic breast cancer treatment choices.

Aim: Assess factors associated with first-line (1L) treatment for HR+/HER2- metastatic breast cancer. Materials & methods: A cross-sectional survey of 250 US oncologists was conducted. Correlations were calculated between treatment class and demographics, treatment perceptions and other clinical/nonclinical characteristics. Results: Efficacy and safety/tolerability were critical in oncologists' 1L decision-making. CDK4/6i use positively correlated with proportion of Medicare and postmenopausal patients (r = 0.54-0.67). Chemotherapy use demonstrated positive correlations with perimenopausal and premenopausal patients and symptom burden (r = 0.31-0.42). Aromatase inhibitor (AI) monotherapy correlated positively with anticipated treatment compliance (r = 0.42). Conclusion: Efficacy and safety/tolerability were most important to 1L decision-making. Clinical characteristics corresponded with CDK4/6i and chemotherapy use. Anticipated compliance was associated with AI monotherapy use.

Patients in the USA with a certain type of metastatic breast cancer (mBC, i.e., HR+/HER2−) might get chemotherapy or hormone therapy alone instead of new and potentially better medicines called cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) as their first treatment.Researchers wanted to understand how US cancer specialists decided the first treatment for this type of mBC. In a survey of 250 cancer specialists, researchers looked at different factors that might influence decision-making, including patient characteristics, doctors' opinions about the treatments and other medical and non-medical features. This study also examined the connections between these factors and the cancer specialists' choice of first treatment.Researchers found that cancer specialists care most about how well a treatment works and how safe it is when choosing the first treatment for HR+/HER2− mBC. They are more likely to use CDK4/6i if their patients have Medicare coverage or are older (i.e., women who have been through menopause). Chemotherapy is chosen if their patients are younger (i.e., women who are near and before menopause) or have more symptoms. Cancer specialists tend to choose first treatment with hormone therapy alone if they think their patients have a hard time following their treatment plan. The results showed that patient characteristics, doctors' opinions of treatments and other medical and non-medical factors play a role in choosing treatment for HR+/HER2− mBC. By understanding these factors, researchers can work toward improving treatment choices for patients with this type of mBC.

Short Adult Height After Rapid-tempo Puberty: When is it too Late to Treat?

A rarely reported phenomenon of rapid-tempo puberty in which the physical changes of puberty and testosterone levels increase very rapidly has not been reported outside apart from in two reviews. The resulting rapid advancement of skeletal age causes early completion of growth with shorter adult stature than expected. This appears to be genetic given its occurrence in the present report in two families, one with three brothers, one with two. We also describe potential treatments and found for the youngest that early initiation of standard therapy preserved or reclaimed adult height (AH) potential. The foreshortened AH in this situation involves rapidly advancing puberty resulting from high circulating testosterone levels leading to rapid advance in skeletal age. This was recognized earlier among younger brothers and treatment with gonadotropin-releasing analogues, growth hormone (GH) and/or aromatase inhibitor therapy (AIT) was tried. Two brothers in family A and family B were treated. Case 5 started treatment early enough so his AH was within target height (mid-parental height) range. Cases 2, 3, 4 were tried on GH and/or AIT with outcomes suggesting benefit. The prevalence and mechanism of rapid-tempo puberty requires further study. Furthermore, as illustrated by two of the current cases, this phenomenon may have a heightened prevalence, or at least may occur, in children previously diagnosed with constitutional delay of growth, underscoring the need to be cautious in assurance of a normal AH outcomes in this population, based on data from a single assessment.

Red Wine as an Aromatase Inhibitor: A Narrative Review.

As estrogen-dependent breast cancer is more affected by the local production of estrogen via aromatase than serum estrogen, aromatase inhibitors for treating breast carcinomas in postmenopausal women have been developed. As the aromatase enzyme converts endogenous androgen to estrogenic compounds, its blockade lowers the in situ production of estrogen, demonstrated to encourage tumor proliferation. Red wine, but not white wine, may have aromatase-inhibiting properties that are being elucidated, although the exact mechanisms of action are not known. Polyphenols, tannins, and resveratrol have all been implicated as aromatase blockers, and there may also be synergistic interplay among selected constituents. The role of red wine would be in chemoprevention, the use of natural or synthetic substances to retard, block, or reverse cancer. One gene encodes aromatase, so aromatase inhibition would stop endogenous estrogen production. The role of aromatase inhibition in breast cancer in premenopausal women is not clear. While animal studies have demonstrated that red wine contains constituents that could block aromatase in vivo, the benefits also exist with nonalcoholic grape seed extract. Further investigation is needed but there are challenges in designing appropriate clinical trials for a substance as variable as red wine. While there is insufficient evidence to advocate for red wine as an aromatase inhibitor, there is sufficient evidence to warrant further investigation.

Arthralgia and myalgia associated with aromatase inhibitors: frequency and characterization in real-life patients.

Introduction: Adjuvant treatment with aromatase inhibitors (AI) in oestrogen receptor-positive and/or progesterone receptor-positive breast cancer (BC) has been shown to increase overall survival. However, arthralgias and myalgias are common adverse effects in patients treated with AI. Objective: To evaluate the frequency and characteristics of arthralgias and myalgias in patients with early BC-treated adjuvantly with AI in the Mastology Unit of the Oncology Service of the Hospital de Clínicas and the Departmental Hospital of Soriano. Materials and methods: A prospective, cross-sectional and descriptive study was performed. A questionnaire was administered to patients to assess the presence and characteristics of arthralgias and myalgias associated with AI. Statistical analysis: 'Age' was described with measures of central tendency and dispersion. Qualitative variables were presented in absolute and relative frequencies. Logistic models were used to evaluate the association between patient characteristics, tumour characteristics, treatment characteristics and the presence of pain. Results were presented by odds ratio and p-value, using R software (version 4.1.2) with a significance threshold of 5%. Results: 83 patients were included, with a median age of 69 years. 75.9% presented arthralgias and/or myalgias related to treatment, with an average intensity of 5-7. 80.9% received non-steroidal anti-inflammatory drugs (NSAIDs), achieving satisfactory analgesia. The presence of arthralgias and myalgias was significantly associated with age and time since the last menstrual period (LMP), being more frequent in patients older than 50 years and those with more than 5 years since the LMP. Conclusion: Approximately 70% of the patients presented arthralgias or myalgias. These findings suggest a possible role of oestrogen withdrawal in its mechanism of development. Multidisciplinary and translational research is crucial to evaluate the ethology and therapeutic options for patients with AI-related arthralgia.

Exploring height outcomes with adjuvant aromatase inhibition in growth hormone-deficient male survivors of childhood cancer.

BACKGROUND: Aromatase inhibitors (AI) may improve height in short stature conditions; however, the effect in childhood cancer survivors (CCS) is unknown. We assessed final adult height (FAH) in CCS treated with AI and GH compared with those treated with GH alone. METHODS: Retrospective cohort study of GH-deficient male CCS treated between 2007 and 2023. FAH was noted as the height at the fusion of growth plates or 18 years of age. Multivariable linear regression was used to examine treatment association with FAH, adjusting for other risk factors. RESULTS: Ninety-two patients were included; 70 were treated with GH and 22 with combination AI/GH. The mean age at GH initiation did not differ between groups. The mean age at AI initiation was 13.7 ± 1.9 years. A greater proportion of patients in the AI/GH group were treated with stem cell transplantation, abdominal radiation, total body irradiation, and cis-retinoic acid (p < .01). Multivariable linear regression demonstrated no significant treatment association with FAH Z-score (ß = 0.04, 95% CI: -0.9 to 0.9). History of spinal radiation (ß = -0.93, 95% CI: -1.7 to -0.2), lower starting height Z-score (ß = -0.8, 95% CI: -1.2 to -0.4), and greater difference between bone age and chronological age (ß = -0.3, 95% CI: -0.5 to -0.07) were associated with lower FAH Z-score. CONCLUSIONS: Adjuvant AI was not associated with increased FAH in male CCS compared with GH monotherapy. Future work is needed to determine the optimal adjunctive treatment to maximize FAH for this population.

Current and future advances in practice: aromatase inhibitor-induced arthralgia.

Aromatase inhibitors (AIs) have shown great success as adjuvant therapy for post-menopausal women with hormone receptor-positive breast cancers. AI-induced arthralgia (AIA) is a frequent AI toxicity contributing to non-adherence and discontinuation. This review aims to understand current knowledge of AIA. The mean incidence of AIA was 39.1% and the mean discontinuation of AI therapy due to AIA was 9.3%. Most of the AIAs were non-inflammatory. A shorter time since the last menstrual period and pre-existing joint pain were risk factors. Vitamin D3 supplementation may be a preventative measure and treatment with duloxetine, acupuncture and/or exercise is supported by large randomized controlled trials. There was consistent improvement in AIAs with switching to an alternate AI, and this could additionally allow continuation of cancer treatment with AI. Further research is needed to identify predictive biomarkers, better characterize AIA subcategories and study more reliable therapeutic options.

Follow-up Routines Matter for Adherence to Endocrine Therapy in the Adjuvant Setting of Breast Cancer.

Background: Endocrine therapy (ET) adherence leads to increased survival in breast cancer (BC). How follow-up should be done to maximize adherence is not known. Objectives: To assess adherence to ET, factors favouring adherence to ET and effects on survival in a population-based cohort of BC patients in western Sweden. Design: This is a retrospective study. Methods: We included 358 patients operated for oestrogen receptor-positive BC and recommended 5 years of ET, in Region Halland, Sweden, year 2015 to 2016. Demographical, clinical and pathological data and use of ET were retrieved from the electronic medical records. Patients were considered adherent if taking ET for 5 years or during the full extent of the follow-up, until termination of ET due to BC relapse or death and where renewals of prescriptions of ET covered ⩾80% of the ordinated dose. Two follow-up routines were employed, ie, routine A where patients were contacted annually by nurses and a more passive follow-up routine B where patients were only contacted by nurses at 2 years and 5 years following start of ET. Results: Medication persistence for 4 years and more was good and similar between patients initiating aromatase inhibitor (AI) and tamoxifen (75.7% and 72.0%, respectively, P = .43). More patients initiating AIs changed ET due to side effects compared with patients initiating tamoxifen (24.3% vs 9.9%, respectively, P < .0001). Endocrine therapy adherence was better for follow-up routine B than for follow-up routine A (hazard ratio [HR] = 2.71 [1.44-5.09], P = .0027). Conclusions: Adherence to ET in BC is high in Western Sweden. Less regular nurse-initiated contacts between BC patients and nursesled surprisingly to a better adherence than a more regular nurse-initiated contact.

Follow-up routines are important for adherence to anti-hormonal therapy after breast cancer surgery In this study conducted in western Sweden, researchers looked at how well breast cancer (BC) patients followed their prescribed endocrine therapy (ET) for 5 years, which is crucial for their survival. They studied 358 patients diagnosed with oestrogen receptor-positive BC between 2015 and 2016. The study compared two follow-up routines: one where patients were contacted annually by nurses (routine A) and another where patients were contacted only at 2 years and 5 years after starting ET (routine B). Surprisingly, patients in routine B, with less frequent nurse contacts, were more likely to adhere with their ET compared with those in routine A. The study also found that patients taking aromatase inhibitors (AIs) were more likely to switch their ET due to side effects compared with those taking tamoxifen, but overall, adherence rates were similar between the 2 groups. In summary, the study showed that BC patients in western Sweden generally followed their prescribed ET well. In addition, having less frequent nurse-initiated contacts surprisingly improved patient adherence with their treatment.

Long-term effects of aromatase inhibitor withdrawal on bone mineral density in early breast cancer patients: 10-year follow-up results of the BREX study.

PURPOSE: We aimed to provide long-term bone mineral density (BMD) data on early breast cancer patients of the BREX (Breast Cancer and Exercise) study. The effects of exercise and adjuvant endocrine treatment 10 years after randomization were analyzed, with special emphasis on aromatase inhibitor (AI) therapy discontinuation at 5 years. METHODS: The BREX study randomized 573 pre- and postmenopausal breast cancer patients into a 1-year supervised exercise program or a control group. 372 patients were included into the current follow-up analysis. BMD (g/cm2) was measured by dual-energy X-ray absorptiometry at lumbar spine (LS), left femoral neck (FN), and the total hip. Separate groups were displayed according to baseline menopausal status, and whether the patient had discontinued AI therapy at 5 years or not. RESULTS: The BMD change from 5 to 10 years did not significantly differ between the two randomized arms. AI discontinuation at 5 years had statistically significant BMD effects. The FN BMD continued to decrease in patients who discontinued AI therapy during the first 5-year off-treatment, but the decrease was three-fold less than in patients without AI withdrawal (- 1.4% v. - 3.8%). The LS BMD increased (+ 2.6%) in patients with AI withdrawal during the first 5 years following treatment discontinuation, while a BMD decrease (-1.3%) was seen in patients without AI withdrawal. CONCLUSION: This study is to our knowledge the first to quantify the long-term impact of AI withdrawal on BMD. Bone loss associated with AI therapy seems partially reversible after stopping treatment. TRIAL REGISTRATION: http://www. CLINICALTRIALS: gov/ (Identifier Number NCT00639210).

Cost-effectiveness comparison of dalpiciclib and abemaciclib combined with an aromatase inhibitor as first-line treatment for HR+/HER2- advanced breast cancer.

OBJECTIVES: CDK4/6 inhibitors dalpiciclib and abemaciclib have been approved by the Chinese National Medical Products Administration as first-line treatment for postmenopausal females with hormone receptor-positive (HR+) and human epidermal growth factor receptor-2 negative (HER2-) advanced breast cancer (ABC). We aimed to assess the cost-effectiveness of dalpiciclib plus letrozole/anastrozole (non-steroidal aromatase inhibitor [NSAI]) compared with abemaciclib plus NSAI as a first-line treatment for HR+/HER2- ABC in China. METHODS: We constructed a Markov model with three health states to evaluate health and economic outcomes of first-line treatment with dalpiciclib plus NSAI and abemaciclib plus NSAI for HR+/HER2- ABC. Efficacy data was obtained from MONARCH3 and DAWNA-2 trials. Quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) were calculated. RESULTS: Compared with abemaciclib plus NSAI, dalpiciclib plus NSAI resulted in 4.27 additional QALYs, with an ICER of $14827.4/QALY. At a willingness-to-pay threshold of 3 times gross domestic product per capita in China for 2023 ($37721.5/QALY), the cost-effectiveness probability of dalpiciclib plus NSAI was 77.42%. CONCLUSIONS: From the perspective of Chinese payers, dalpiciclib plus NSAI appears to be a cost-effective strategy compared with abemaciclib plus NSAI for the first-line treatment of patients with HR+/HER2- ABC in China. CLINICAL TRIAL REGISTRATION: MONARCH3, www.clinicaltrials.gov, identifier is NCT02246621 and DAWNA-2, www.clinicaltrials.gov, identifier is NCT03966898.

Treatment outcomes in older patients with metastatic breast cancer receiving palbociclib plus an aromatase inhibitor: a plain language summary.

WHAT IS THIS SUMMARY ABOUT?: This summary describes an article published in the medical journal Frontiers in Oncology in September 2023. The article reports results from a study that looked at breast cancer treatments for older patients aged 75 years or older. The study focused on a type of cancer called HR+/HER2- metastatic breast cancer. HR+/HER2- stands for hormone receptorpositive/human epidermal growth factor receptor 2-negative. This study evaluated whether older patients with this type of cancer benefited from the combination of two medicines - palbociclib and an aromatase inhibitor - compared with taking an aromatase inhibitor alone. HOW WAS THE STUDY IN THIS SUMMARY CARRIED OUT?: The Flatiron database contains medical records for people with cancer in the US. This study used deidentified health care information from this database. 'Deidentified' means that all information that could identify an individual was removed to protect individuals' privacy. People in this study received treatment in routine care and not in a clinical trial. WHAT DO THE RESULTS MEAN?: Older patients who took palbociclib plus an aromatase inhibitor lived longer than those who took an aromatase inhibitor alone. Older patients who took palbociclib plus an aromatase inhibitor also lived longer without their cancer getting worse and started chemotherapy later than those who took an aromatase inhibitor alone. These results support using palbociclib plus an aromatase inhibitor as the first treatment for patients aged 75 years or older with HR+/HER2- metastatic breast cancer.

This study evaluated outcomes in elderly patients with metastatic breast cancer treated in routine care. Overall, patients who took palbociclib plus an aromatase inhibitor (AI) lived longer, and lived longer without their cancer getting worse, than those who took an AI alone.

Letrozole delays acquisition of water maze task in female BALB/c mice: Possible involvement of anxiety.

Letrozole, an aromatase inhibitor preventing estrogen synthesis from testosterone, is used as an adjuvant therapy in estrogen receptor-positive breast cancer patients. However, like other aromatase inhibitors, it induces many side effects, including impaired cognition. Despite its negative effect in humans, results from animal models are inconsistent and suggest that letrozole can either impair or improve cognition. Here, we studied the effects of chronic letrozole treatment on cognitive behavior of adult female BALB/c mice, a relevant animal model for breast cancer studies, to develop an appropriate animal model aimed at testing therapies to mitigate side effects of letrozole. In Morris water maze, letrozole 0.1 mg/kg impaired reference learning and memory. Interestingly, most of the letrozole 0.1 mg/kg-treated mice were able to learn the new platform position in reversal training and performed similar to control mice in a reversal probe test. Results of the reversal test suggest that letrozole did not completely disrupt spatial navigation, but rather delayed acquisition of spatial information. The delay might be related to increased anxiety as suggested by increased thigmotactic behavior during the reference memory training. The learning impairment was water maze-specific since we did not observe impairment in other spatial tasks such as in Y-maze or object location test. In contrast, the dose of 0.3 mg/kg did not have effect on water maze learning and facilitated locomotor habituation and recognition in novel object recognition test. The current study shows that letrozole dose-dependently modulates behavioral response and that its effects are task-dependent.

[Pharmacological therapies for height improvement in pubertal children with short stature]. / 青春期矮身材儿童身高改善的药物治疗.

Short stature in puberty significantly affects the physical and mental health of adolescents. The continuous acceleration of skeletal maturation, caused by sex hormones during puberty, limits the time available for growth and poses a considerable challenge for the treatment of short stature. To date, there is still no standardized treatment protocol for this disorder. However, puberty is the last period to improve the final adult height. Currently, commonly used pharmacological treatments in clinical settings include recombinant human growth hormone, gonadotropin-releasing hormone analogs, and third-generation aromatase inhibitors. In recent years, personalized treatment aiming to improve the final adult height has become a key focus in clinical practice. This article provides a comprehensive summary of research on pharmacological therapies for height improvement in pubertal children with short stature, offering valuable insights for healthcare professionals.

Aromatase Inhibitor Therapy Increases the Risk of New-Onset Atrial Fibrillation in Patients With Breast Cancer.

Background: Previous studies suggest that aromatase inhibitors (AIs) increase the risk of adverse cardiovascular events and cardiac arrhythmias in patients with breast cancer, but it is unclear whether AIs also increase the risk of new-onset atrial fibrillation (AF). Objectives: The purpose of this study was to investigate whether the use of AIs was associated with an increased risk of new-onset AF in patients with breast cancer. Methods: We performed a retrospective analysis involving 5,707 patients with breast cancer (mean age 63.9 ± 11.2 years and 99.9% women) who received adjunctive hormone therapy with an AI (AI group, n = 4,878) or tamoxifen (tamoxifen group, n = 829) in Hong Kong between January 1, 1999, and December 31, 2020. After propensity score matching, there were 1,658 and 829 patients with balanced characteristics in the AI group and tamoxifen group, respectively. Results: After 8,863 patient-years of follow-up, patients who were prescribed AI had a trend toward more new-onset arrhythmias compared with those prescribed tamoxifen (0.62 vs 0.30 per 100 patient-years; crude HR: 2.05; P = 0.053). The difference in arrhythmic risk was mainly driven by a higher incidence rate of new-onset AF in the AI group (0.59 vs 0.27 per 100 patient-years; crude HR: 2.18; P = 0.046). The use of AIs was confirmed to be an independent risk factor for new-onset AF on multivariate analysis (adjusted HR: 2.75; P = 0.01). Conclusions: Among breast cancer patients prescribed adjunctive hormonal therapy, AI was associated with an increased risk of new-onset AF. Regular surveillance for new-onset AF should be considered in breast cancer patients treated with an AI.

Aromatase inhibitor-induced arthralgia ameliorated by Mediterranean diet and active lifestyle guided by continuous glucose monitoring: a case report and review of the literature.

Aromatase inhibitors (AIs) are a cornerstone adjuvant treatment of many hormone receptor-positive breast cancers, and nearly half of women taking aromatase inhibitors suffer from AI-induced arthralgia (AIA), also known as AI-associated musculoskeletal syndrome (AIMSS), for which there are limited evidence-based treatments. Pharmacologic management and complementary methods including supplements, exercise, physical therapy, yoga, acupuncture, and massage have all shown mixed results. Comprehensive diet and lifestyle strategies are understudied in AIA/AIMSS despite their disease-modifying effects across many chronic conditions. Here we report a case of a woman with stage 2 estrogen and progesterone receptor-positive invasive ductal carcinoma on adjuvant anastrozole whose AI-induced arthralgia was durably controlled through a Mediterranean plant-forward diet and daily physical activity guided by continuous glucose monitoring. We posit that diet and a lifestyle inclusive of daily physical activity constitute a low-cost, low-risk, and potentially high-reward strategy for controlling common AI-induced musculoskeletal symptoms and that more investigation in this arena, including well-designed randomized trials, is warranted.

Polypharmacy, over-the-counter medications, and aromatase inhibitor adherence in early-stage breast cancer.

PURPOSE: Polypharmacy is associated with negative health outcomes and decreased medication adherence. Polypharmacy is common in cancer populations, but few studies have evaluated the relationship between polypharmacy and aromatase inhibitor (AI) adherence. No studies have evaluated the relationship between over-the-counter (OTC) supplements and AI adherence. Our primary hypothesis was that polypharmacy would be associated with increased risk of premature AI discontinuation. METHODS: This exploratory analysis used data from the Exemestane and Letrozole Pharmacogenetics (ELPh) trial, a prospective, multicenter, randomized controlled trial that enrolled participants from 2005 to 2009. Included patients were female, postmenopausal, with stage 0-III breast cancer, who had completed indicated chemotherapy, surgery, and radiation. Participants were randomized to adjuvant exemestane or letrozole and completed serial clinical examinations and questionnaires for two years. Concomitant medication data were collected prospectively. Cox proportion models were used for statistical analysis of the relationship between polypharmacy, OTCs, medication class, and AI adherence. RESULTS: In the 490 analyzed participants, use of any prescription medications at baseline was associated with decreased risk of premature AI discontinuation (HR 0.56, p = 0.02). Use of selective serotonin reuptake inhibitors (SSRIs) or selective serotonin and norepinephrine reuptake inhibitors (SNRIs) at baseline was associated with decreased risk of premature AI discontinuation (HR 0.67, p = 0.04). Use of any OTCs was not associated with AI discontinuation. CONCLUSION: Baseline use of prescription medications but not OTCs was associated with increased AI persistence. Future research is needed to understand how this can be utilized to promote AI adherence.

Real-world comparative effectiveness of palbociclib plus aromatase inhibitor in HR+/HER2- metastatic breast cancer.

Aim: Provide real-world data on palbociclib as evidence of effectiveness in patient populations from routine clinical practice. Methods: This was a retrospective, observational cohort study of patients with HR+/HER2- metastatic breast cancer treated with palbociclib plus aromatase inhibitor (AI) or AI alone as first-line therapy within the US Oncology Network. Results: Patients treated with palbociclib plus AI (n = 838) versus AI alone (n = 450) had a numerically longer median overall survival (42.1 vs 35.7 months; hazard ratio [HR] = 0.90 [95% CI: 0.75-1.07]; p = 0.117) and a significantly extended real-world progression-free survival (21.0 vs 15.7 months; HR = 0.75 [95% CI: 0.64-0.88]; p = 0.0002) after normalized inverse probability treatment weighting. Conclusion: These real-world results support the use of palbociclib plus AI as first-line treatment in routine clinical practice for patients with HR+/HER2- metastatic breast cancer.

What is this summary about? This summary describes how well palbociclib works when used with an aromatase inhibitor in the real-world setting for people with a certain type of breast cancer that has spread to other areas of the body. Palbociclib stops cancer cells from growing and dividing. An aromatase inhibitor prevents the body from making the hormone estrogen, which is needed for certain types of breast cancer cells to grow. Palbociclib with an aromatase inhibitor is a standard first treatment used for people with this type of breast cancer that needs estrogen to grow and has spread to other areas of the body. In clinics, doctors may not always prescribe the two treatments together. The study wanted to find out if using the two treatments together worked better than using an aromatase inhibitor alone in the real-world setting. What were the results? The results suggest that in this population of patients treated in a real-world setting, people with breast cancer that needs estrogen to grow and has spread to other areas of the body who were treated with palbociclib plus an aromatase inhibitor lived longer without their cancer getting worse than those treated with an aromatase inhibitor alone. What do the results of the study mean? The results support the use of palbociclib with an aromatase inhibitor as a first treatment for breast cancer that has spread to other areas of the body, rather than an aromatase inhibitor only.