Plasma Aromatase Activity Index, Gonadotropins and Estrone Are Associated with Frailty Syndrome in Post-Menopausal Women with Breast Cancer

Abstract

Frailty syndrome is associated with poor outcomes, morbidity and premature mortality. We performed a cross-sectional study to evaluate the presence of frailty syndrome based on Fried’s frailty phenotype in post-menopausal women with breast cancer. We further analyzed the association between frailty syndrome with geriatric assessments and the association with the concentration of gonadotropins LH and FSH, estrogens, androgens and the aromatase activity index in the blood. We enrolled 47 post-menopausal women with localized breast cancer (mean age 66.8 ± 1.3 years (range 52–83)) prior to the starting of adjuvant endocrine therapy. Patients were identified as “non-frail” (robust) or “prefrail/frail” if they fulfilled at least one frailty criteria. In order to determine associations among variables and to control for other variables potentially affecting frailty syndrome (age, comorbidity index and previous chemotherapy treatment), we performed a logistic regression analysis. The receiver operating characteristic curve was performed to assess the sensitivity and specificity of the hormonal concentration to discriminate prefrail/frail versus non-frail individuals. Significant positive associations were observed between the severity of frailty syndrome and estrone, FSH and LH concentrations and the aromatase activity index in the blood (p < 0.05). Further research into the role of hormonal biomarkers should be evaluated in follow-up studies in order to recommend their use as suitable biomarkers of frailty syndrome in breast cancer patients.

Androstenedione and Follicle-Stimulating Hormone Concentration Predict the Progression of Frailty Syndrome at One Year Follow-Up in Patients with Localized Breast Cancer Treated with Aromatase Inhibitors

“…Notably, almost 50% of the patients showed worsened frailty at 12 months of follow-up, while approximately 25% remained stable and 25% showed improvement of their frailty status. The latter effect (i.e., improvement) is not surprising, since frailty syndrome is a reversible condition mainly in the pre-frailty phase [ 27 , 28 ], and the women in our study were mostly (63.8%) prefrail (i.e., they met one or two frailty criteria) at baseline before receiving AROi treatment [ 23 ]. A recent longitudinal study (with one year of follow-up, as our study) in community-dwelling individuals found that one third of the frail older adults regressed to pre-frailty status, and 8.7% of the pre-frail older adults regressed to non-frailty status [ 29 ].…”

“…Some of them received adjuvant chemotherapy ( n = 15; 31.9%) and radiotherapy ( n = 44; 93.6%) as per protocol of their adjuvant treatment. One month after the last radiotherapy session, all women had started adjuvant hormonal treatment with aromatase inhibitors (anastrozole or letrozole) [ 23 ]. The sociodemographic and oncology data are shown in Table 1 .…”

“…For the calculation of the minimum sample size (unicentric study) that was representative of the patients attended to in the Oncology Department of the Hospital Universitario Dr. Peset (Valencia, Spain), it was estimated that an average of 77 post-menopausal women with breast cancer started adjuvant treatment with aromatase inhibitors in the Hospital every year (with the program G*Power 3.1.9.2 (G*Power©, Dusseldorf, Germany) as described previously [ 23 ]. For the descriptive analysis, quantitative variables were presented with the mean and standard deviation (SD), and categorical variables with the absolute value and the corresponding percentage.…”

“…In addition, a study in approximately 500 older women aged 70–79 years showed decreases in free testosterone to be a risk factor for frailty [ 14 , 21 ]. However, in women there are conflicting results regarding the relationship between testosterone levels and frailty [ 22 , 23 ], and the burden of androgens in blood has been shown to be a stronger predictor of frailty status although the relationship is nonlinear [ 24 ]. In a cross-sectional study, our group has shown that in postmenopausal women with ER-positive breast cancer, frailty syndrome is positively correlated to plasma estrone, gonadotropins concentrations and to the aromatase activity index in blood [ 23 ].…”