Randomized Trial of Letrozole Following Tamoxifen as Extended Adjuvant Therapy in Receptor-Positive Breast Cancer: Updated Findings from NCIC CTG MA.17

Goss, Paul E.; Ingle, James N.; Martino, Silvana; Robert, Nicholas J.; Muss, Hyman B.; Piccart, Martine; Castiglione, M.; Tu, Dongsheng; Shepherd, Lois E.; Pritchard, Kathleen I.; Livingston, Robert B.; Davidson, Nancy E.; Norton, Larry; Perez, Edith A.; Abrams, Jeffrey S.; Cameron, David; Palmer, Michael; Pater, Joseph L.

doi:10.1093/jnci/dji250

Cited by 1,042 publications

(722 citation statements)

References 41 publications

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“…[25][26][27][28][41][42][43][44][45][46] Several large studies (Arimidex, Tamoxifen 26,[47][48][49][50] and such therapy has been recommended as part of the standard of care in this patient group. 49,51 Neoadjuvant endocrine therapy also has a role in the treatment of breast cancer, particularly in postmenopausal women with hormone-responsive disease who are unable to tolerate toxicities associated with chemotherapy or who may be ineligible for immediate surgery. 1,17 In these patients, neoadjuvant therapy offers the promise of improving survival or enabling subsequent breast-conserving surgery.…”

Section: Discussionmentioning

confidence: 99%

Phase 2 randomized trial of primary endocrine therapy versus chemotherapy in postmenopausal patients with estrogen receptor‐positive breast cancer

Семиглазов

Semiglazov

Dashyan

et al. 2007

Cancer

288

153

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BACKGROUND.Few studies have compared primary neoadjuvant endocrine therapy with neoadjuvant chemotherapy in breast cancer patients. The need for preoperative chemotherapy with doxorubicin or taxanes may be reduced in postmenopausal patients with estrogen receptor (ER)‐positive and/or progesterone receptor (PgR)‐positive tumors. This randomized, controlled, phase 2 study evaluated the efficacy of neoadjuvant chemotherapy compared with endocrine treatment with aromatase inhibitors in postmenopausal women with ER‐positive and/or PgR‐positive breast cancer.METHODS.Eligible patients were randomly assigned to receive neoadjuvant anastrozole 1 mg/day (n = 61) or exemestane 25 mg/day (n = 60) for 3 months or doxorubicin 60 mg/m2 with paclitaxel 200 mg/m2 (four 3‐week cycles). Study end points included overall objective response determined by palpation, mammography, and ultrasound, and the number of patients who qualified for breast‐conserving surgery and radiotherapy.RESULTS.Clinical objective response was 64% in the endocrine therapy and chemotherapy treatment groups. Median time to clinical response was 57 and 51 days with aromatase inhibitors and chemotherapy, respectively (P > .05). Rates of pathological complete response (3% vs 6%) and disease progression (9% vs 9%) did not differ significantly in the endocrine therapy or chemotherapy group, respectively (P > .05). Rates of breast‐conserving surgery were slightly higher in the endocrine group (33% vs 24%; P = .058). The most frequent toxicities from chemotherapy were alopecia (79%), grade 3/4 neutropenia (33%), and grade 2 neuropathy (30%). Endocrine treatment was well tolerated. No deaths occurred during the preoperative treatment.CONCLUSIONS.Preoperative neoadjuvant endocrine therapy with aromatase inhibitors was well tolerated and resulted in rates similar to chemotherapy in overall objective response and breast‐conserving surgery in postmenopausal women with ER‐positive and/or PgR‐positive tumors. Cancer 2007. © 2007 American Cancer Society.

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Section: Discussionmentioning

confidence: 99%

Phase 2 randomized trial of primary endocrine therapy versus chemotherapy in postmenopausal patients with estrogen receptor‐positive breast cancer

Семиглазов

Semiglazov

Dashyan

et al. 2007

Cancer

288

153

View full text Add to dashboard Cite

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“…Tamoxifen, a selective estrogen receptor modulator, was the standard of care for such patients for nearly 20 years; it can significantly reduce recurrence and breast cancer-related death in patients prescribed about 5 years of adjuvant treatment [1]. However, the third-generation aromatase inhibitors (AIs) anastrozole, letrozole, and exemestane have proven more effective than tamoxifen at improving disease-free survival (DFS), whether given as upfront (initial) adjuvant therapy, as sequential or switch therapy following approximately 2-3 years of prior tamoxifen, or as extended adjuvant therapy following 5 years of tamoxifen treatment [2][3][4][5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Patterns and predictors of early recurrence in postmenopausal women with estrogen receptor-positive early breast cancer

Mansell

Monypenny

Skene

et al. 2008

Breast Cancer Res Treat

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Previous studies suggest that disease recurrence peaks at around 2 years in patients with early stage breast cancer (EBC), but provide no data regarding recurrence type. This retrospective analysis aimed to identify early recurrence types and risk factors in estrogen receptor-positive (ER?) EBC patients treated with adjuvant tamoxifen following breast cancer surgery. Postmenopausal women diagnosed with ER? EBC from 1995 to 2004 were evaluated. Annual hazard ratios (HR) for recurrence at different sites were calculated. Time-dependent Cox regression analysis was used to identify predictors of recurrence within 2.5 years of diagnosis, including factors that were more strongly predictive of early than later recurrence. Of 3,614 patients evaluated, 476 developed recurrence during the 5-year median follow-up. Cumulative recurrence rates at 2.5 years (95% confidence interval) were: overall 6.3% (5.5-7.1), locoregional 1.1% (0.7-1.5), contralateral 0.5% (0.3-0.7), and distant 4.8% (4.0-5.6). The annual HR of overall recurrence peaked at 2 years (4.3% per annum).The majority of this peak represented distant recurrence (3.4% per annum). In Cox regression analysis, tumor size and grade, lymph node involvement, lymphovascular invasion, and symptomatic presentation were significant independent predictors of early recurrence. Age at diagnosis was independently predictive of recurrence within 2.5 years of diagnosis but not later recurrence. This study identified an early recurrence peak at 2 years, most of which were distant recurrences. Implementing an aromatase inhibitor after an initial 2-3 years of tamoxifen fails to address this early peak of distant recurrence and the potential breast cancer-associated mortality.

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“…Therefore, there is a need for alternative treatments. Treatment with aromatase inhibitors is now proving to be an effective strategy for sequential therapy after 5 years of tamoxifen [21][22][23][24]. More significantly, ATAC and BIG trials have demonstrated superior efficacy of aromatase inhibitors compared to tamoxifen [13,21,25,26].…”

Section: Discussionmentioning

confidence: 99%

Toremifene–atamestane; alone or in combination: Predictions from the preclinical intratumoral aromatase model

Sabnis

Macedo

Goloubeva

et al. 2008

The Journal of Steroid Biochemistry and Molecular Biology

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Since most breast cancers occur in post-menopausal women and are hormone dependent, we developed a model system that mimics this situation. In this model, tumors of human estrogen receptor ER positive breast cancer cells stably transfected with aromatase (Ac-1) are grown in immune compromised mice. Using this model we have explored a number of therapeutic strategies to maximize the antitumor efficacy of antiestrogens (AEs) and aromatase inhibitors (AIs). This intratumoral aromatase xenograft model has proved accurate in predicting the outcome of several clinical trials. In this current study we compared the effect of an AE toremifene and steroidal AI atamestane, alone or in combination, on growth of hormone dependent human breast cancer. We have also compared toremifene plus atamestane combination with tamoxifen in this study.The growth of Ac-1 cells was inhibited by tamoxifen, toremifene and atamestane in vitro with IC 50 values of 1.8±1.3μM, 1±0.3μM and 60.4±17.2μM, respectively. The combination of toremifene plus atamestane was found to be better than toremifene or atamestane alone in vitro. The effect of this combination was then studied in vivo using Ac-1 xenografts grown in ovariectomized female SCID mice. The mice were injected with toremifene (1000μg/day), atamestane (1000μg/day), tamoxifen (100μg/day), or the combination of toremifene plus atamestane. In this study, our results indicate that the combination of toremifene plus atamestane was as effective as toremifene or tamoxifen alone but may not provide any additional benefit over toremifene alone or tamoxifen alone.

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Randomized Trial of Letrozole Following Tamoxifen as Extended Adjuvant Therapy in Receptor-Positive Breast Cancer: Updated Findings from NCIC CTG MA.17

Abstract: Letrozole after tamoxifen is well-tolerated and improves both disease-free and distant disease-free survival but not overall survival, except in node-positive patients.

Cited by 1,042 publications

References 41 publications

Phase 2 randomized trial of primary endocrine therapy versus chemotherapy in postmenopausal patients with estrogen receptor‐positive breast cancer

Phase 2 randomized trial of primary endocrine therapy versus chemotherapy in postmenopausal patients with estrogen receptor‐positive breast cancer

Patterns and predictors of early recurrence in postmenopausal women with estrogen receptor-positive early breast cancer

Toremifene–atamestane; alone or in combination: Predictions from the preclinical intratumoral aromatase model

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