Letrozole improved disease-free survival in postmenopausal women after tamoxifen treatment for breast cancer

2004 ◽  
Vol 6 (2) ◽  
pp. 91-92
Keyword(s):  
Breast Cancer ◽  
Postmenopausal Women ◽  
Disease Free Survival ◽  
Tamoxifen Treatment ◽  
Free Survival ◽  
Disease Free

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.

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]

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.

A randomized trial (MA.17R) of extending adjuvant letrozole for 5 years after completing an initial 5 years of aromatase inhibitor therapy alone or preceded by tamoxifen in postmenopausal women with early-stage breast cancer.

2016 ◽  
Vol 34 (18_suppl) ◽  
pp. LBA1-LBA1 ◽  
Author(s):  
Paul E. Goss ◽  
James N. Ingle ◽  
Kathleen I. Pritchard ◽  
Nicholas J. Robert ◽  
Hyman Muss ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Aromatase Inhibitor ◽  
Postmenopausal Women ◽  
Early Stage ◽  
Controlled Trial ◽  
Disease Free Survival ◽  
Early Stage Breast Cancer ◽  
Rank Test ◽  
Free Survival ◽  
Disease Free

LBA1 Background: Five years of aromatase inhibitor (AI) therapy either as up-front treatment or after 2-5 years of tamoxifen has become the standard of care for postmenopausal women with hormone receptor positive early breast cancer. Extending treatment with an AI to 10 years may further reduce the risk of breast cancer recurrence. Methods: We conducted a double-blind, placebo-controlled trial (Canadian Cancer Trials Group MA.17R) to test the efficacy of extending AI treatment for an additional five years using letrozole. The primary endpoint was disease-free survival. Results: A total of 1,918 women with early stage breast cancer were enrolled (median follow-up 75 months, 6.3 years). A total of 165 disease-free survival (DFS) events (67 on letrozole and 98 on placebo) occurred, of which 42 versus 53 were distant recurrences on letrozole and placebo, respectively. There were 200 deaths (100 in each treatment group). The 5 year DFS was respectively 95% for patients receiving letrozole versus 91% for those on placebo (HR 0.66; P = 0.01) from a two-sided log-rank test stratified by nodal status, prior adjuvant chemotherapy, interval between last dose of AI therapy and randomization, and duration of prior tamoxifen at randomization. The 5 year overall survival was respectively 93% for subjects on letrozole and 94% on placebo with a HR of 0.97 (P = 0.83). The annual incidence rate of contralateral breast cancer was 0.21% for subjects on letrozole versus 0.49% on placebo (P = 0.007). Conclusions: Compared to 5 years of AI treatment as initial therapy or preceded by 2-5 years of tamoxifen, extending AI treatment to 10 years significantly improves disease-free survival. Further analyses will provide a comprehensive picture of toxicities and QOL. Clinical trial information: NCT00754845.

scholarly journals Expression of ER-α36, a Novel Variant of Estrogen Receptor α, and Resistance to Tamoxifen Treatment in Breast Cancer

2009 ◽  
Vol 27 (21) ◽  
pp. 3423-3429 ◽  
Author(s):  
Liang Shi ◽  
Bin Dong ◽  
Zhongwu Li ◽  
Yunwei Lu ◽  
Tao Ouyang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Tamoxifen Resistance ◽  
Disease Free Survival ◽  
Estrogen Receptor Α ◽  
Tamoxifen Treatment ◽  
Free Survival ◽  
Novel Variant ◽  
Disease Free ◽  
Disease Specific

Purpose Recently, a 36-kDa variant of estrogen receptor α (ER-α66), ER-α36, has been identified and cloned. ER-α36 predominantly localizes on the plasma membrane and in the cytoplasm and mediates a membrane-initiated “nongenomic” signaling pathway. Here, we investigate the association between ER-α36 expression and tamoxifen resistance in patients with breast cancer. Patients and Methods ER-α36 protein expression in tumors from 896 women (two independent cohorts, 1 and 2) with operable primary breast cancer was assessed using an immunohistochemistry assay. Results In the first cohort of 710 consecutive patients, overexpression of ER-α36 was associated with poorer disease-free survival (DFS) and disease-specific survival (DSS) in patients with ER-α66–positive tumors who received tamoxifen treatment (chemotherapy plus tamoxifen or tamoxifen alone, n = 307). In contrast, ER-α36 was not associated with survival in patients with ER-α66–positive tumors who did not receive tamoxifen (chemotherapy alone, n = 129) and in patients with ER-α66–negative tumors whether they received tamoxifen (n = 73) or not (n = 149). In the second cohort of 186 patients who only received tamoxifen as adjuvant therapy, overexpression of ER-α36 was significantly associated with poorer DFS and DSS in 156 ER-α66–positive patients from this cohort, and ER-α36 remained an independent unfavorable factor for both DFS and DSS in these 156 patients by a multivariate analysis (DFS: hazard ratio [HR] = 5.47; 95% CI, 1.81 to 16.51; P =. 003; DSS: HR = 13.97; 95% CI, 1.58 to 123.53; P = .018). Conclusion Women with ER-α66–positive tumors that also express high levels of ER-α36 are less likely to benefit from tamoxifen treatment.

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