Risk of cancer treatment-related osteoporosis and fractures among women with breast cancer receiving aromatase inhibitors

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 557-557 ◽  
Author(s):  
B. Mincey ◽  
M. Duh ◽  
S. Thomas ◽  
E. Moyneur ◽  
M. Marynchencko ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Relative Risk ◽  
Bone Loss ◽  
Aromatase Inhibitors ◽  
Univariate Analysis ◽  
Estrogen Therapy ◽  
Control Group ◽  
Estrogen Production ◽  
Increased Risk ◽  
Risk Of Cancer

557 Background: Aromatase inhibitors (AIs) are a novel hormonal therapy for breast cancer. However, AIs can cause bone loss by blocking estrogen production. This study aims to assess the association between AIs and treatment-related bone loss in a large managed care population of women with breast cancer. Methods: Using medical and pharmacy claims data from over 5 million beneficiaries between 01/01/1998 and 01/31/2005, we identified 12,368 patients with ≥ 2 breast cancer claims in a 6-month period, who also had no bone metastasis and no prior osteoporosis or fracture claims. Patients who received anti-estrogen therapy were also excluded to remove the protective confounding effects. 1,354 patients receiving an AI (anastrozole, exemestane, letrozole) were compared to 11,014 controls who did not receive an AI with respect to their risk of bone loss. The observation start date for the AI and control groups was defined as the service date of the first AI claim and breast cancer claim, respectively. The bone loss endpoints analyzed were osteoporosis (including osteopenia) and clinical fractures. Results: The univariate analysis found that the prevalence of osteoporosis was 8.7% in the AI group vs. 7.1% in the control group, resulting in a statistically significant relative risk of 1.3 (95% CI=1.1–1.6, p=0.01). The prevalence of bone fracture was also statistically significantly elevated in the AI group compared to the controls (13.5% vs. 10.3%) with a relative risk of 1.4 (95% CI=1.2–1.6, p=0.001). Multivariate Cox proportional hazards regressions showed that after adjusting for age and comorbidities, the risk of bone loss remained statistically significantly higher in the AI group than the non-AI group, with 27% (95% CI=4%-55%, p=0.02) and 21% (95% CI=3%-43%, p=0.02) increase in the risk of osteoporosis and fractures, respectively. Conclusions: This retrospective longitudinal analysis of a large cohort of breast cancer patients corroborates previous findings from smaller clinical trials and demonstrates that AI therapies carry an increased risk of bone loss. Monitoring and treatment management strategies to alleviate bone loss risk are warranted in women receiving AI for breast cancer. [Table: see text]

scholarly journals Pathological Significance of GLUT-1 Expression in Breast Cancer Cells in Diabetic and Obese Patients: The French Guiana Study

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 437
Author(s):  
Valentin Suteau ◽  
John Bukasa-Kakamba ◽  
Beatrice Virjogh-Cenciu ◽  
Antoine Adenis ◽  
Nadia Sabbah ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Size ◽  
French Guiana ◽  
Proliferation Index ◽  
Control Group ◽  
Obese Patients ◽  
Glucose Transporter 1 ◽  
Glut 1 ◽  
Increased Risk ◽  
Risk Of Cancer

The prevalence of obesity and type 2 diabetes is higher in French Guiana compared to mainland France. These metabolic disorders are associated with an increased risk of cancer. One of the factors involved is hyperinsulinemia that promotes the action of glucose transporter 1 (GLUT-1). The objective of this study is to characterize the expression of GLUT-1 in breast cancers cells in diabetic and obese patients compared to those who are not and to describe the clinical and histological prognostic factors of breast cancer in this population. We conducted a monocentric study including patients with breast cancer diagnosed between 2014 and 2020. Patients were classified into three groups: diabetes, obesity, and control group. The GLUT-1 expression was assessed by immunohistochemistry. In total, 199 patients were included in this study. The median age was 53.5 years, and the median tumor size was 2.8 cm. Luminal A was the most frequent molecular type (58.1%), followed by the triple-negative type (19.9%). The breast cancer in our population was characterized by a younger age at diagnosis, more aggressive molecular types, and larger tumor size. Thus, we suggest the advancement of the age of breast cancer screening in this territory. A total of 144 patients (31 diabetes, 22 obese, and 91 control group) were included for the study of GLUT-1 expression. Overexpression of GLUT-1 was observed in 60.4% of cases and in all carcinoma in situ lesions. GLUT-1 overexpression was associated with more aggressive cancers. This overexpression is correlated with high histological grade, high proliferation index, and aggressive molecular types. Our study found no difference in GLUT-1 expression between the diabetic or obese patients and the control group. These results highlight the potential role of GLUT-1 as a tumor metabolic prognostic marker and also as an interesting target therapy, independently of patient metabolic disorder.

scholarly journals The Association Between Triglyceride-Glucose Index as a Marker of Insulin Resistance and the Risk of Breast Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Sonar Soni Panigoro ◽  
Noorwati Sutandyo ◽  
Fiastuti Witjaksono ◽  
Nurjati Chairani Siregar ◽  
Ramadhan Ramli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dose Response ◽  
Univariate Analysis ◽  
Control Group ◽  
Tyg Index ◽  
Cancer Group ◽  
Triglyceride Glucose Index ◽  
Increased Risk ◽  
Referral Hospitals ◽  
Breast Cancer Group

BackgroundThis study aims to evaluate the association and dose-response between triglyceride-glucose (TyG) index and breast cancer.MethodThis is a multicenter case-control study conducted in six public referral hospitals in Indonesia. Cases are individuals aged 19 years or above who were diagnosed with breast cancer within 1 year of diagnosis, based on histopathology and immunohistochemistry. Controls were recruited from corresponding hospitals. TyG index was determined by the formula: ln (fasting TG [mg/dl] × fasting glucose [mg/dl]).ResultsThere were 212 participants in the breast cancer group and 212 participants in the control group. TyG index was higher in patients with breast cancer (median 8.65 [7.38, 10.9] vs. 8.30 [7.09, 10.84], p < 0.001). When compared with TyG quartile of Q1, Q4 was associated with an OR of 2.42 (1.77, 3.31), p < 0.001, Q3 was associated with an OR of 1.53 (1.21, 1.93), p < 0.001, Q2 was associated with an OR of 1.39 (1.12, 1.73), p = 0.002 for the risk of breast cancer. The dose-response relationship was nonlinear (p < 0.001). On univariate analysis, smoking (OR 2.15 [1.44, 3.22], p < 0.001), use of contraception (1.73 [1.15, 2.60], p = 0.008), alcohol consumption (OR 2.04 [0.96, 4.35], p = 0.064), and TyG Index >8.87 (OR 3.08 [1.93, 4.93], p < 0.001) were associated with risk of breast cancer. Independently associated with increased risk of breast cancer included smoking (OR 1.93 [1.23, 3.01], p = 0.004), use of contraception (OR 1.59 [1.02, 2.48], p = 0.039), and TyG Index >8.87 (OR 2.93 [1.72, 4.98], p < 0.001)ConclusionTyG index was associated with breast cancer in a nonlinear dose-response fashion.

Do Aromatase Inhibitors Increase Hemoglobin in Women with Breast Cancer?

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4575-4575
Author(s):  
Daniel J. Lachant ◽  
Kanu P. Sharan ◽  
Andres Ferber ◽  
Robert Somer ◽  
Generosa Grana ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Regression Analysis ◽  
Linear Regression ◽  
Postmenopausal Women ◽  
Aromatase Inhibitors ◽  
Linear Regression Analysis ◽  
Estrogen Therapy ◽  
Stage I ◽  
Control Group ◽  
The Mean

Abstract Aromatase inhibitors (AI) block the conversion of testosterone and androstenedione to the estrogen estrone by inhibiting the aromatase enzyme complex. AI are used to treat estrogen receptor positive (ER+) breast cancer in postmenopausal women. With AI therapy, estrogen levels decrease to 85–95% of baseline. In women with metastatic disease, androstenedione levels do not increase. We have evaluated 2 women for polycythemia during AI therapy. Case 1 is 52 years old with stage II breast cancer treated with lumpectomy, TAC × 6 and radiation. Tamoxifen was started 4 months later. The mean hemoglobin during 6 months of tamoxifen was 14.0±0.1 gm/dl. When switched to exemestane, the mean hemoglobin over the next 24 months was 16.1±0.5 gm/dl (Mann-Whitney, p<0.003). Case 2 is an 80 year old with stage I breast cancer treated with lumpectomy followed by radiation. Her baseline hemoglobin was 13.8 gm/dl. 26 months after starting exemestane, her hemoglobin reached 18.0 gm/dl. After extensive evaluation, neither patient met the criteria for polycythemia vera and no etiology for secondary polycythemia was found. The presumption was that the temporal increase in hemoglobin may be due to AI therapy. Previous clinical trials have not reported an increase in hemoglobin in women receiving AI therapy for breast cancer. However, given the dramatic increase in hemoglobin in our 2 patients, we wished to test the hypothesis that inhibition of aromatase may lead to an increase in hemoglobin in postmenopausal women receiving AI therapy for breast cancer. The Cooper University Hospital Tumor Registry was used as a source of potential subjects. Women over the age of 50 years, diagnosed with ER+ nonmetastatic breast cancer between 2002 and 2006 were identified. Women included for study were postmenopausal, and treated with breast surgery +/− local radiation. Women receiving chemotherapy were excluded because of the potential effect of chemotherapy or therapeutic erythropoietin on the hemoglobin level. In order to be included for study, women needed to have a hemoglobin prior to surgery or prior to starting anti-estrogen therapy and at least 3 hemoglobin measurements over a minimum of 12 months after starting anti-estrogen therapy. AI included anastrozole and exemestane. Of 123 charts available for review, 82 had inadequate data for analysis. 27 evaluable women received only an AI. The mean age was 67±8 years and 67% were stage I. The mean hemoglobin before and during AI therapy was 13.7±0.4 and 13.2±1.1 gm/dl, respectively (Mann Whitney, p<0.09). 3/27 had an increase in hemoglobin after starting AI therapy by linear regression analysis (r ≥ 0.60). The increase in hemoglobin ranged from 0.9 to 1.1 gm/dl. As a control group, 11 women received tamoxifen rather than an AI. Mean age was 59±8 years and 54% were stage I. The mean hemoglobin before and during tamoxifen therapy was 13.0±1.0 and 12.8±0.8 gm/dl, respectively (Mann Whitney, p=0.53). 0/11 had an increase in hemoglobin by linear regression analysis (r > 0.60). 2 additional women received tamoxifen which was subsequently changed to an AI, 1 of whom had a mean hemoglobin of 12.9±0.3 gm/dl on tamoxifen which increased to 14.9±0.4 gm/dl on exemestane (Mann Whitney, p<0.05). 1 additional woman had a rise in hemoglobin of > 1 gm/dl while on AI therapy which decreased back to baseline when switched to tamoxifen. In conclusion, although the numbers are small and the data retrospective, these data suggest that AI therapy may be associated with an increase in hemoglobin in a subgroup of women treated with AI therapy for localized breast cancer. Given that AI have not been shown to significantly increase the systemic androgen level, the mechanism for the increase in hemoglobin remains unclear. A well designed, prospective study is needed to determine if AI have an effect on hemoglobin in women being treated for breast cancer.

The effect of aromatase inhibitors use on endothelial function among postmenopausal women with breast cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12064-e12064
Author(s):  
Ronny Maor ◽  
Elad Maor ◽  
Amanda Wanous ◽  
Sandhya Pruthi ◽  
Amir Lerman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Endothelial Function ◽  
Postmenopausal Women ◽  
Aromatase Inhibitors ◽  
Vascular Injury ◽  
Statistical Difference ◽  
Control Group ◽  
Increased Risk

e12064 Background: Data on long-term cardiovascular effects and safety of aromatase inhibitors (AI) are limited and conflicting. The purpose of the current study was to evaluate the effect of AI on vascular injury as assessed by peripheral endothelial function among women with breast cancer. Methods: This is an observational, prospective study of 96 postmenopausal women with breast cancer at initiation of treatment, with or without AI. All participants underwent baseline and 6-12 months follow up non-invasive peripheral endothelial function measurement. Reactive hyperemia index (RHI) was measured using the EndoPAT test. The primary endpoint was endothelial function deterioration of at least 20% between baseline and follow-up. Results: Mean age of the study population was 66±7 years. There was no statistical difference in demographic data between the groups. Compared with the control group, more women in the treatment group demonstrated worsening of RHI (53% vs. 42%, p = 0.207) between baseline and 6-12 month follow up measurement. There was no statistical difference between the groups at baseline. When RHI deterioration was evaluated as a dichotomous variable, with a 20% cutoff, women in the AI group demonstrated higher rates of RHI deterioration (28% vs. 8%, p=0.020). The risk of AIs for endothelial dysfunction was correlated with burden of cardiovascular (CV) risk, such that in women with >3 CV risk factors, AIs were associated with increased risk of RHI deterioration (42% vs. 10%, p=0.016), whereas in women with <2 CV risk factors, rates of RHI deterioration were similar in AI and control groups (20% vs. 7%, p = 0.232). Conclusions: This study suggests that AI therapy may be associated with vascular injury as detected by deterioration in endothelial function. The effect is more pronounced among women with higher baseline CV risk factor burden. The results of this study have potentially important implications for patients with breast cancer being treated with AI and for women at increased lifetime risk of breast cancer who may use AI for breast cancer risk reduction. Clinical trial information: NCT00719966.

Does Long-Term Exposure to Gel-Filled Silicone Implants Increase the Risk of Relapse after Breast Cancer?

1998 ◽  
Vol 84 (5) ◽  
pp. 525-528 ◽  
Author(s):  
Jean-Yves Petit ◽  
Monique Lê ◽  
Mario Rietjens ◽  
Geneviève Contesso ◽  
Andrée Lehmann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Reconstruction ◽  
Proportional Hazards Model ◽  
Silicone Implants ◽  
Control Group ◽  
Second Primary ◽  
Increased Risk ◽  
Risk Of Cancer

Background An increased risk of cancer and autoimmune diseases associated with gel-filled silicone implants, debated by FDA experts since 1991, has given rise to a profusion of literature on the subject. However, such effects have not been adequately investigated in patients with breast cancer. In a previous report we compared 146 breast cancer patients with gel-filled silicone implants for breast reconstruction to 146 control patients in whom no reconstruction had been performed. The observed results were reassuring, as the evolution of the disease after 10 years was better in the reconstruction group than in the control group. We now report the end results of this study with a median follow-up of 13 years after the breast reconstruction (range, 10-20 years). Method The relative risks of detrimental events were estimated with Cox's Proportional Hazards Model, with stratification according to age at diagnosis. Results The risks of locoregional recurrences and distant metastasis were significantly lower in the BR group than in the control group. The risks of death, of a second breast cancer and of a second primary cancer at a site other than the breast were not significantly different between the two groups of patients. Conclusion Long-term follow-up of patients exposed to gel-filled silicone implants confirms the absence of detrimental effects after breast cancer. The power of our study is, however, below that required to detect a very slight increase in the risks studied.

Effect of zoledronic acid on bone loss in postmenopausal women with early breast cancer treated with sequential tamoxifen and letrozole

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 599-599
Author(s):  
T. Safra ◽  
R. Bernstein Molho ◽  
I. Stephansky ◽  
N. Yaal-Hahoshen ◽  
M. Inbar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Zoledronic Acid ◽  
Bone Loss ◽  
Postmenopausal Women ◽  
Adjuvant Treatment ◽  
Control Group ◽  
T Score ◽  
Increased Risk ◽  
To Receive

599 Background: Adjuvant treatment with aromatase inhibitors (AIs) in postmenopausal women (PMW) with early breast cancer (EBC) can be associated with decreased bone mineral density (BMD) and increased risk of osteoporosis and fractures. Tamoxifen (TAM) has bone protective effect. BIG 1–98 recent, 71 months update suggests that sequential therapy of TAM and letrozole (LET) in either order, have similar efficacy to 5 years of LET. This study is designed to evaluate the efficacy and safety of zoledronic acid (ZA) in preventing AIs bone loss after 2.5 years of TAM. Methods: This is an open-label, randomized phase II study of PMW with hormone receptor positive EBC previously treated with TAM for the last 2.5 years (with BMD T score ≥ -2.5). Patients are randomly assigned to receive LET (2.5mg/ daily) ± ZA. Patients on treatment arm receive 4 mg IV ZA every 6 months for 2 years. All patients are being evaluated every 6 (0–36) months with blood chemistry and BMD test. All patients receive vitamin D and calcium supplement. A comparison between groups and between time points is performed by one-way ANOVA with repeated measures using the Mixed model. Results: Seventy four patients were screened. Median age was 58.9 years (46.5–83.6). All patients are alive, one had an ipsilateral recurrence. Seventy two patients were evaluable (2 were screening failure), 33 randomized to receive ZA and 39 to the control group. Median follow-up (FU) was 18.2 months (1–47). At this point in time a significant interaction between groups and time trend was found, in favor of ZA treated group in lumbar T score (p = 0.0055). While in the control group a significant decline in lumbar BMD was noticed (p = 0.008), in the treatment group BMD did not change over time (p = 0.2971). Adverse events with ZA were mild with some flue like syndrome. No serious renal adverse event or ONJ (osteonecrosis of jaw) cases were reported. ZA was safe and well tolerated. Conclusions: Sequential adjuvant treatment with TAM and AIs in PMW with EBC can be associated with decreased BMD and increased risk of osteoporosis. In our study, LET-induced bone loss increases with time. A significant benefit in BMD was seen when ZA was added to LET. A longer follow up is needed to evaluate the real magnitude of ZA protective effects. [Table: see text]

scholarly journals Revisiting Estrogen: Efficacy and Safety for Postmenopausal Bone Health

2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Sandra M. Sacco ◽  
Wendy E. Ward
Keyword(s):  
Breast Cancer ◽  
Bone Loss ◽  
Bone Health ◽  
Effective Means ◽  
Rapid Decline ◽  
Efficacy And Safety ◽  
Estrogen Production ◽  
Increased Risk ◽  
Endogenous Estrogen ◽  
Future Fracture

The rapid decline in endogenous estrogen production that occurs during menopause is associated with significant bone loss and increased risk for fragility fracture. While hormone therapy (HT) is an effective means to re-establish endogenous estrogen levels and reduce the risk of future fracture, its use can be accompanied by undesirable side effects such as stroke and breast cancer. In this paper, we revisit the issue of whether HT can be both safe and effective for the prevention of postmenopausal bone loss by examining standard and alternative doses and formulations of HT. The aim of this paper is to continue the dialogue regarding the benefits and controversies of HT with the goal of encouraging the dissemination of-up-to date evidence that may influence how HT is viewed and prescribed.

Risk of Cancer Treatment—Associated Bone Loss and Fractures Among Women with Breast Cancer Receiving Aromatase Inhibitors

2006 ◽  
Vol 7 (2) ◽  
pp. 127-132 ◽  
Author(s):  
Betty A. Mincey ◽  
Mei Sheng Duh ◽  
Simu K. Thomas ◽  
Erick Moyneur ◽  
Maryna Marynchencko ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Loss ◽  
Cancer Treatment ◽  
Aromatase Inhibitors ◽  
Risk Of Cancer

scholarly journals Protective Effect of Aerobic Physical Activity on Sleep Behavior in Breast Cancer Survivors

2016 ◽  
Vol 16 (1) ◽  
pp. 21-31 ◽  
Author(s):  
Eliana Roveda ◽  
Jacopo A. Vitale ◽  
Eleonora Bruno ◽  
Angela Montaruli ◽  
Patrizia Pasanisi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Physical Activity ◽  
Circadian Rhythm ◽  
Activity Level ◽  
Control Group ◽  
Sleep Study ◽  
Wake Time ◽  
Increased Risk ◽  
Immobility Time ◽  
Risk Of Cancer

Hypotheses. Sleep disorders are associated with an increased risk of cancer, including breast cancer (BC). Physical activity (PA) can produce beneficial effects on sleep. Study design. We designed a randomized controlled trial to test the effect of 3 months of physical activity on sleep and circadian rhythm activity level evaluated by actigraphy. Methods. 40 BC women, aged 35-70 years, were randomized into an intervention (IG) and a control group (CG). IG performed a 3 month of aerobic exercise. At baseline and after 3 months, the following parameters were evaluated both for IG and CG: anthropometric and body composition measurements, energy expenditure and motion level; sleep parameters (Actual Sleep Time-AST, Actual Wake Time-AWT, Sleep Efficiency-SE, Sleep Latency-SL, Mean Activity Score-MAS, Movement and Fragmentation Index-MFI and Immobility Time-IT) and activity level circadian rhythm using the Actigraph Actiwatch. Results. The CG showed a deterioration of sleep, whereas the IG showed a stable pattern. In the CG the SE, AST and IT decreased and the AWT, SL, MAS and MFI increased. In the IG, the SE, IT, AWT, SL, and MAS showed no changes and AST and MFI showed a less pronounced change in the IG than in the CG. The rhythmometric analysis revealed a significant circadian rhythm in two groups. After 3 months of PA, IG showed reduced fat mass %, while CG had improved weight and BMI. Conclusion. Physical activity may be beneficial against sleep disruption. Indeed, PA prevented sleep worsening in IG. PA can represent an integrative intervention therapy able to modify sleep behaviour.

scholarly journals Cancer Treatment–Induced Bone Loss (CTIBL): State of the Art and Proper Management in Breast Cancer Patients on Endocrine Therapy

2021 ◽  
Vol 22 (5) ◽  
Author(s):  
Anna Diana ◽  
Francesca Carlino ◽  
Emilio Francesco Giunta ◽  
Elisena Franzese ◽  
Luigi Pio Guerrera ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Loss ◽  
Cancer Treatment ◽  
Endocrine Therapy ◽  
Aromatase Inhibitors ◽  
Bone Health ◽  
Optimal Time ◽  
Breast Cancer Patients ◽  
Antiresorptive Agents

Opinion statementAbout 70–80% of early breast cancer (BC) patients receive adjuvant endocrine therapy (ET) for at least 5 years. ET includes in the majority of cases the use of aromatase inhibitors, as upfront or switch strategy, that lead to impaired bone health. Given the high incidence and also the high prevalence of BC, cancer treatment–induced bone loss (CTIBL) represents the most common long-term adverse event experimented by patients with hormone receptor positive tumours. CTIBL is responsible for osteoporosis occurrence and, as a consequence, fragility fractures that may negatively affect quality of life and survival expectancy. As recommended by main international guidelines, BC women on aromatase inhibitors should be carefully assessed for their fracture risk at baseline and periodically reassessed during adjuvant ET in order to early detect significant worsening in terms of bone health. Antiresorptive agents, together with adequate intake of calcium and vitamin D, should be administered in BC patients during all course of ET, especially in those at high risk of osteoporotic fractures, as calculated by tools available for clinicians. Bisphosphonates, such as zoledronate or pamidronate, and anti-RANKL antibody, denosumab, are the two classes of antiresorptive drugs used in clinical practice with similar efficacy in preventing bone loss induced by aromatase inhibitor therapy. The choice between them, in the absence of direct comparison, should be based on patients’ preference and compliance; the different safety profile is mainly related to the route of administration, although both types of drugs are manageable with due care, since most of the adverse events are predictable and preventable. Despite advances in management of CTIBL, several issues such as the optimal time of starting antiresorptive agents and the duration of treatment remain unanswered. Future clinical trials as well as increased awareness of bone health are needed to improve prevention, assessment and treatment of CTIBL in these long-term survivor patients.

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