Fast track — Research LettersResults of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant treatment for breast cancer
Summary
The standard adjuvant endocrine treatment for postmenopausal women with hormone-receptor-positive localised breast cancer is 5 years of tamoxifen, but recurrences and side-effects restrict its usefulness. The aromatase inhibitor anastrozole was compared with tamoxifen for 5 years in 9366 postmenopausal women with localised breast cancer. After a median follow-up of 68 months, anastrozole significantly prolonged disease-free survival (575 events with anastrozole vs 651 with tamoxifen, hazard ratio 0·87, 95% CI 0·78–0·97, p=0·01) and time-to-recurrence (402 vs 498, 0·79, 0·70–0·90, p=0·0005), and significantly reduced distant metastases (324 vs 375, 0·86, 0·74–0·99, p=0·04) and contralateral breast cancers (35 vs 59, 42% reduction, 12–62, p=0·01). Almost all patients have completed their scheduled treatment, and fewer withdrawals occurred with anastrozole than with tamoxifen. Anastrozole was also associated with fewer side-effects than tamoxifen, especially gynaecological problems and vascular events, but arthralgia and fractures were increased. Anastrozole should be the preferred initial treatment for postmenopausal women with localised hormone-receptor-positive breast cancer.
Published online December 8, 2004 http://image.thelancet.com/extras/04let11120web.pdf
References (5)
- EP Winer et al.
American Society of Clinical Oncology Technology on the use of aromatase inhibitors as adjuvant therapy for postmenopausal women with hormone-receptor-positive breast cancer: status report 2004
J Clin Oncol
(2004) Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial
Lancet
(2002)
Cited by (2102)
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2023, Fertility and SterilityTo identify patient factors associated with a clinically significant improvement in semen parameters among infertile men treated with the aromatase inhibitor anastrozole.
Multi-institutional retrospective cohort study.
Two Tertiary Academic Medical Centers.
A total of 90 infertile men treated at 2 tertiary academic medical centers who met inclusion criteria and obtained pretreatment and posttreatment semen analyses.
Prescription of anastrozole (median 3 mg/wk).
Upgrade in the World Health Organization sperm concentration category (WHO-SCC). Univariate logistic regression, multivariable logistic regression, and partitioning analyses were performed to identify statistically significant patient factors capable of predicting treatment response.
With anastrozole treatment, 46% (n = 41/90) of men responded favorably with a WHO-SCC upgrade, and 12% (n = 11/90) experienced a downgrade. Responders exhibited lower pretreatment levels of luteinizing hormone (LH, 4.7 vs. 8.3 IU/L) and follicle-stimulating hormone (4.7 vs. 6.7 IU/mL), higher pretreatment levels of testosterone (T, 356 vs. 265 ng/dL), and similar baseline level of estradiol (E2, 73% vs. 70% with detectible level). Baseline semen parameters differed, with anastrozole responders demonstrating higher baseline semen concentration (3.6 vs. 0.3 M/mL) and higher total motile sperm counts (3.7 vs. 0.1 M). Anastrozole therapy converted 29% (n = 26/90) of the cohort to normozoospermia and enabled intrauterine insemination access in 31% (n = 20/64) of previously ineligible patients. Interestingly, neither body mass index nor the baseline E2 level or E2-T ratio was associated with WHO-SCC upgrade. Multivariable logistic regression revealed the T-LH ratio (odds ratio: 1.02, 95% confidence interval: 1.00–1.03) and baseline nonazoospermia (odds ratio: 9.4, 95% confidence interval: 1.1–78.9) to be statistically significant predictors of WHO-SCC upgrade (area under receiver operating characteristic curve: 0.77). The final user-friendly partitioning model consisting of the T-LH ratio ≥100 and baseline non-azoospermia was 98% sensitive and 33% specific for WHO-SCC upgrades (area under the curve: 0.77).
Anastrozole therapy decreases serum E2 levels, increases serum gonadotropins, and clinically improves semen parameters in half of men with idiopathic infertility. Nonazoospermic infertile men with T-LH ratios ≥100 are likely to benefit from anastrozole treatment irrespective of baseline E2 level or E2-T ratio. Men with azoospermia rarely respond to anastrozole and should be counseled on alternative treatments.
La testosterona y la hormona luteinizante predicen la mejoría en los parámetros seminales en hombres infértiles tratados con anastrazol
Identificar los factores de los pacientes asociados con una mejoría clínicamente significativa en los parámetros del semen entre hombres infértiles tratados con el inhibidor de la aromatasa anastrazol.
Estudio de cohorte retrospectivo multi institucional.
Dos centros médicos académicos terciarios.
Un total de 90 hombres infértiles tratados en 2 centros médicos académicos terciarios quienes cumplieron con los criterios de inclusión y obtuvieron análisis de semen previo y post tratamiento.
Prescripción de anastrazol (mediana 3 mg/semana).
Aumento en la categoría de concentración de semen de la Organización Mundial de la Salud (OMS-SCC). Se realizaron análisis de regresión logística univariada, regresión logística multivariable y partición para identificar factores estadísticamente significativos de los pacientes capaces de predecir la respuesta al tratamiento.
Con el tratamiento con anastrazol, el 46 % (n = 41/90) de los hombres respondieron favorablemente con un aumento en OMS-SCC y el 12 % (n = 11/90) experimentó una disminución. Los que respondieron exhibieron niveles previos al tratamiento más bajos de hormona luteinizante (LH, 4,7 versus 8,3 UI/L) y hormona folículo estimulante (4,7 versus 6,7 UI/mL), niveles más altos de testosterona previo al tratamiento (T, 356 versus 265 ng/dL) y nivel basal similar de estradiol (E2, 73% vs. 70% con nivel detectable). Los parámetros basales del semen difirieron, los que respondieron al anastrazol demostraron mayor concentración inicial de semen (3,6 frente a 0,3 M/ml) y mayores recuentos totales de espermatozoides móviles (3,7 frente a 0,1 M). La terapia con anastrazol convirtió el 29% (n = 26/90) de la cohorte a normozoospermia y permitió el acceso a la inseminación intrauterina en el 31% (n = 20/64) de pacientes previamente no elegibles. De manera interesante, ni el índice de masa corporal ni el nivel inicial de E2 o la tasa E2-T se asociaron con cambios en OMS-SCC. La regresión logística multivariable reveló que la relación T-LH (odds ratio: 1,02, intervalo de confianza del 95 %: 1,00–1,03) y la no azoospermia inicial (odds ratio: 9,4; intervalo de confianza del 95%: 1,1–78,9) son predictores estadísticamente significativos de la mejora del WHOSCC (área bajo la curva característica operativa del receptor: 0,77). El modelo de partición final fácil de usar que consta de la relación T-LH R100 y la no azoospermia inicial fueron 98 % sensibles y 33 % específicas para las mejoras de WHO-SCC (área bajo la curva:0,77).
La terapia con anastrazol disminuye los niveles séricos de E2, aumenta las gonadotropinas séricas y mejora clínicamente los parámetros seminales en la mitad de los hombres con infertilidad idiopática. Los hombres infértiles no azoospérmicos con ratios T-LH R100 probablemente se beneficien del tratamiento con anastrazol independientemente del nivel inicial de E2 o la relación E2-T. Los hombres con azoospermia rara vez responden al anastrazol y se les debe aconsejar tratamientos alternativos.
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