Therapeutic Options in the Management of Aromatase Inhibitor-Associated Bone Loss.

2021 ◽  
Vol 21 ◽  
Author(s):  
Agostino Gaudio ◽  
Anastasia Xourafa ◽  
Rosario Rapisarda ◽  
Pietro Castellino
Keyword(s):  
Breast Cancer ◽  
Side Effects ◽  
Bone Loss ◽  
Postmenopausal Women ◽  
Early Breast Cancer ◽  
Disease Free Survival ◽  
Therapeutic Options ◽  
Free Survival ◽  
Hormone Receptor Positive ◽  
Disease Free

Background: Breast cancer is the most commonly occurring cancer in women worldwide. Early breast cancer is a kind of invasive neoplasm that has not proliferated beyond the breast or the axillary lymph nodes. Current therapeutic strategies for breast cancer mainly include local therapies such as surgery or radiotherapy and systemic therapies like chemotherapy, endocrine, and targeted therapy.Nowadays, the adjuvant treatment for hormone receptor-positive early breast cancer in postmenopausal women remains the main effective systemic therapy which can improve disease-free survival and overall survival; it involves several endocrine treatment regimens including selective estrogen receptor modulators (SERMs), aromatase inhibitors (AIs), or a combination of them. AIs have been shown to be more effective in preventing recurrence in postmenopausal women with early breast cancer when compared with tamoxifen, thus representing the standard of care for adjuvant endocrine therapy. Although AIs are usually well-tolerated, they can have some side effects. Apart from the appearance of arthralgias or myalgias and cardiovascular events, AI therapies, reducing already low endogenous postmenopausal estradiol levels, cause increased bone loss and increase fracture risk in postmenopausal women. Objectives: To evaluate the therapeutic options in the management of aromatase inhibitor-associated bone loss (AIBL). Methods: We reviewed the current literature dealing with different therapeutic options in the treatment of AIBL. Results : Clinical practice guidelines recommend a careful evaluation of skeletal health in all women with breast cancer before AI therapy initiation. Adequate calcium and vitamin D intake have also been suggested. Pharmacological attempts to minimize AI-related bone loss have focused on the use of antiresorptive agents, such as bisphosphonates and denosumab, to protect bone integrity and reduce the risk of fractures. Furthermore, clinical trials have shown that by making the bone microenvironment less susceptible to breast cancer metastasis, these drugs are able to increase disease-free survival. Conclusions: AI, thatare the pillar of the systemic treatment for patients with hormone receptor-positive breast cancer, are associated with different side effects, and in particular osteoporosis and fractures. Both bisphosphonates and denosumab are able to prevent this negative effect.

Cost-effectiveness of zoledronic acid (ZOL) in postmenopausal women with early breast cancer receiving adjuvant letrozole.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 553-553
Author(s):  
Mei Xue ◽  
Peter Fishman ◽  
Marc Botteman
Keyword(s):  
Breast Cancer ◽  
Cost Effectiveness ◽  
Postmenopausal Women ◽  
Early Breast Cancer ◽  
Disease Free Survival ◽  
Mineral Density ◽  
Free Survival ◽  
T Score ◽  
Life Years ◽  
Disease Free

553 Background: In the ZO-FAST trial, postmenopausal women with early breast cancer and a bone mineral density (BMD) T-score ≥ –2 and receiving adjuvant letrozole (2.5 mg/day) were randomized to either immediate ZOL (4 mg/6 months) treatment (upfront ZOL) or to the same therapy but only when BMD T-score decreased to < –2 or fracture occurrence (delayed ZOL). After 60 months, upfront ZOL increased both BMD and disease-free survival (P < .05) relative to delayed ZOL. The present analysis assessed, from a US payer perspective, the cost effectiveness of upfront ZOL vs delayed ZOL in this population. Methods: A Markov state-transition model was developed to estimate the lifetime costs and quality-adjusted life-years (QALYs) for a hypothetical cohort of postmenopausal women with early breast cancer receiving letrozole with upfront or delayed ZOL. Consistent with ZO-FAST, patients were 57 years of age and breast cancer recurrence-free at baseline. Patients could progress over time to Local Recurrence, Contra-lateral Tumor, Distant Recurrence, or Death. Transition probabilities were derived from ZO-FAST, supplemented with literature. Costs and utilities were literature based. All outcomes were discounted 3% per year. Results: Compared to delayed ZOL, upfront ZOL resulted in better overall survival, disease-free survival, and QALYs, but at a higher cost (Table). In the base case, the incremental cost/QALY gained with upfront vs delayed ZOL was $7,967. In > 95% of 1,000 probabilistic sensitivity analysis runs, upfront ZOL costs less than $38,376/QALY gained. Conclusions: Upfront ZOL may increase survival and QALY and, at a cost per QALY well under the $50,000/QALY threshold, is very cost-effective in this population. [Table: see text]

Optimizing Adjuvant Endocrine Therapy in Postmenopausal Women With Early-Stage Breast Cancer: A Decision Analysis

2005 ◽  
Vol 23 (22) ◽  
pp. 5178-5187 ◽  
Author(s):  
Rinaa S. Punglia ◽  
Karen M. Kuntz ◽  
Eric P. Winer ◽  
Jane C. Weeks ◽  
Harold J. Burstein
Keyword(s):  
Breast Cancer ◽  
Aromatase Inhibitor ◽  
Postmenopausal Women ◽  
Treatment Strategies ◽  
Disease Free Survival ◽  
Sequential Therapy ◽  
Sequential Treatment ◽  
Modest Improvement ◽  
Free Survival ◽  
Disease Free

Purpose The optimal adjuvant endocrine strategy for postmenopausal breast cancer is unknown. Options include the antiestrogen tamoxifen, estrogen deprivation with aromatase inhibitors, and sequential therapy with tamoxifen and then an aromatase inhibitor. Methods We developed Markov models to simulate 10-year disease-free survival among postmenopausal women with hormone receptor–positive breast cancer. The treatment strategies analyzed were 5 years of tamoxifen alone, 5 years of an aromatase inhibitor alone, and sequential treatment consisting of tamoxifen with cross over to an aromatase inhibitor at 2.5 or 5 years. Risk estimates were derived from reported randomized clinical trials. Results Sequential therapy with tamoxifen followed by cross over to an aromatase inhibitor at 2.5 years yielded a modest improvement in disease-free survival compared with planned aromatase inhibitor monotherapy. At 10 years, the cross-over strategy yielded absolute disease-free survival rates of 83.7% and 67.6% for node-negative and node-positive patients, respectively, compared with 82.6% and 65.5%, respectively, for aromatase inhibitor monotherapy, which is a 6% relative risk reduction. Sequential therapy improved disease-free survival estimates by year 6 after treatment initiation. Later cross over from tamoxifen to an aromatase inhibitor at 5 years did not further improve 10-year disease-free survival estimates. Sensitivity analyses suggest that sequential treatment strategies optimized 10-year disease-free and distant disease–free survival independent of the degree of the beneficial carryover effect after aromatase inhibitor therapy or the ratio of local to distant tumor recurrence. Conclusion Modeling estimates suggest that sequential adjuvant therapy with tamoxifen followed by an aromatase inhibitor after 2.5 years yields improved outcomes compared with either drug alone or cross-over treatment after 5 years of tamoxifen.

scholarly journals Adding pertuzumab to adjuvant therapy for high-risk HER2-positive early breast cancer in APHINITY: a GRADE analysis

2020 ◽  
Vol 9 (6) ◽  
pp. 423-430 ◽  
Author(s):  
Alberto Zambelli ◽  
Giovanni Pappagallo ◽  
Paolo Marchetti
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Adjuvant Therapy ◽  
Early Breast Cancer ◽  
Disease Free Survival ◽  
Invasive Disease ◽  
Her2 Positive ◽  
Free Survival ◽  
Distant Relapse ◽  
Disease Free

Aim: Adding pertuzumab to standard trastuzumab-based adjuvant therapy significantly improved invasive disease-free survival (IDFS) in the APHINITY trial. However, the magnitude of benefit was marginal in the overall population. Methods: We used GRADE (Grading of Recommendations Assessment, Development and Evaluation) analysis on data from APHINITY to build summary-of-findings tables to evaluate the efficacy, safety and quality of evidence of predefined clinical outcomes for the addition of pertuzumab to trastuzumab-based adjuvant therapy in patients with high-risk HER2-positive early breast cancer. Results: Pertuzumab significantly improved 3-year, event-free, absolute benefit in disease-free survival, IDFS and distant relapse-free interval (DFRI) in patients with node-positive or hormone receptor-negative disease. The analysis provides strength of evidence supporting the addition of pertuzumab in this patient population.

Vitamin D status and survival in patients with triple negative breast cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e18210-e18210
Author(s):  
John Khoury ◽  
Sruthi Jinna ◽  
Ali Sahlieh ◽  
Rebecca Chacko ◽  
David Macari ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Vitamin D ◽  
Postmenopausal Women ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Disease Free Survival ◽  
Premenopausal Women ◽  
Stage I ◽  
Free Survival ◽  
Disease Free

e18210 Background: Although many studies have investigated the association of blood 25OH-vitamin D (vit-D) levels with breast cancer prognosis, the results have been mixed. It has been suggested that low vit-D concentrations were associated with advanced tumor stage and triple-negative (TNBC) subtype. We retrospectively investigated associations of serum vit-D levels with triple negative breast cancer outcome. Methods: Out of 797 cases of TNBC diagnosed at William Beaumont Hospital between 2006-2017, 163 patients had vit-D level available within 1 year prior to diagnosis. Analyses of vit-D levels was classified by 3 cut points (deficient, < 20.0 ng/mL; insufficient, 20.0-29.9 ng/mL; sufficient, ≥30.0 ng/mL). Primary outcomes are disease free survival (DFS) and overall survival (OS). SPSS statistics 25 software was used to analyze the data. Results: Median age of diagnosis of TNBC was 60. Of these patients 43.6% were diagnosed with stage I, 37.4% at stage II, 4.9% at stage III and 4.9% at stage IV. 47.2% of the patients had sufficient vit-D level prior to diagnosis, 28.2% with insufficient vit-D level and 24.5% with deficient vit-D. Vit-D deficiency was more prevalent in premenopausal than in postmenopausal women (33.3%, 41% and 25.6% in premenopausal women for deficient, insufficient and sufficient levels respectively vs 21.8%, 24.2% and 54% in postmenopausal women). Rates of Vit-D deficiency were not different between early disease and advanced disease (24.3% of patient with stage I-II vs 25% in patients with stage III-IV). Median OS and disease-free survival were not statistically different among the 3 different categories. 5-year OS was 91%, 91% and 85% for deficient, insufficient and sufficient levels respectively. 5-year DFS was 93%, 95% and 95% for deficient, insufficient and sufficient levels respectively. Multivariate COX regression analysis demonstrated that age and stage were associated with mortality, whereas vit-D level was not. Conclusions: The results from this study show that adequate vit-D level do not have an impact on OS and DFS in patients with triple negative breast cancer. Premenopausal women are more likely to have inadequate vit-D level. Identification and treatment of vitamin D deficiency is still important for musculoskeletal health and possibly extraskeletal health in general population and breast cancer survivors specifically.

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