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      Cáncer de seno y hormonoterapia: Estado actual Translated title: Breast cancer and hormone therapy: Current state of knowledge

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          Abstract

          El manejo del cáncer de seno es multidisciplinario e involucra la cirugía, la quimioterapia, la radioterapia y la hormonoterapia. La hormonoterapia es un tratamiento muy antiguo para el manejo efectivo del cáncer de seno hormono-sensible. Cerca de 75% de las pacientes expresan receptores hormonales en el tumor y el estándar de manejo ha sido con antiestrógenos como el tamoxifeno, que se viene usando desde hace más de 25 años en ensayos clínicos con buena respuesta, mejorando la supervivencia libre de enfermedad (SLE) y la supervivencia total (ST) de las pacientes, tanto en mujeres premenopáusicas como postmenopáusicas; por los efectos secundarios sobre endometrio y coagulación, se han venido desarrollando nuevas drogas llamadas inhibidores de aromatasa, que han sido comparados con el tamoxifeno en el estado metastásico y en adyuvancia, con mejores resultados de supervivencia libre de enfermedad con menos efectos secundarios sobre endometrio y menos eventos trombóticos, aunque aumentan el riesgo de osteoporosis y fracturas con su uso prolongado. El uso de inhibidores de aromatasa se restringe a pacientes posmenopáusicas. Las pacientes premenopáusicas requieren algún tipo de bloqueo ovárico para su uso. Se hace una revisión de la evolución del tratamiento en estos escenarios y en los nuevos terrenos de neoadyuvancia y quimioprevención. Se considera que toda paciente con cáncer de seno que tenga alguna expresión de receptores hormonales (más de 1% por inmunohistoquímica) se beneficia de hormonoterapia; el tamoxifeno por 5 años es una excelente droga para ser utilizada en casos de muy buen pronóstico, pero cuando está contraindicado o cuando existen factores de riesgo para recaída local o sistémica, las pacientes posmenopáusicas con tumores hormonosensibles, se benefician de un inhibidor de aromatasa en adyuvancia primaria o hacer el cambio después de 2, 3 ó 5 años de tamoxifeno. La evidencia actual muestra que el tratamiento se puede prolongar más allá de los 5 a 10 años. Este es un artículo de revisión de la hormonoterapia desde sus inicios hasta las recomendaciones actuales en los diferentes escenarios.

          Translated abstract

          The management of breast cancer is classically interdisciplinary, involving surgery, chemotherapy, and radiotherapy. Hormone therapy is a treatment modality that has been in long use for hormone-sensitive breast cancers. Around 75% of patients exhibit hormone receptors in the tumor; thus, the standard therapy has been the anti-estrogens, principally tamoxifen, an agent that has been in use for more than 25 years with solid evidence of good results; prospective clinical studies have shown good response with improvement in disease-free survival and total survival, both in premenopausal and postmenopausal women. New agents have been developed that are free of the side effects of tamoxifen over the endometrium and the coagulations mechanisms: the aromatase inhibitors, that have demonstrated superiority over tamoxifen in patients with metastatic diseases, as well as in adjuvant therapeutic schemes. The better results are manifested by longer disease-free survivals and freedom of the endometrial and thrombotic side effects. However, their prolonged use may augment the risk of osteoporosis and fractures. The use of aromatase inhibitors remains restricted to postmenopausal women. Premenopausal women require some type of concomitant ovarian blockade. In this paper the authors present a review of the current trends, including both neoajuvant therapy and chemoprevention. It is now considered that every patient with mammary cancer that exhibits any expression of hormonal receptors (more than 1% demonstrated by immunochemistry) will benefit from hormone therapy; tamoxifen given for a period of 5 years is an excellent drug to be used in cases with very good prognosis, but when contraindicated or when there exist risk factors of local or systemic recurrence, postmenopausal women with hormone-sensitive tumors will rather benefit from the use aromatase inhibitors as primary adjuvant therapy or in exchange after 2, 3, or 5 years of tamoxifen. Current evidence indicates that the treatment may be prescribed for more than 5 or 10 years. This article is a review of hormone therapy in breast cancer, from its start many years ago until the current recommendations in the different clinical scenarios.

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          Most cited references181

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          Tamoxifen for Prevention of Breast Cancer: Report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study

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            Tamoxifen for early breast cancer: an overview of the randomised trials. Early Breast Cancer Trialists' Collaborative Group.

            There have been many randomised trials of adjuvant tamoxifen among women with early breast cancer, and an updated overview of their results is presented. In 1995, information was sought on each woman in any randomised trial that began before 1990 of adjuvant tamoxifen versus no tamoxifen before recurrence. Information was obtained and analysed centrally on each of 37000 women in 55 such trials, comprising about 87% of the worldwide evidence. Compared with the previous such overview, this approximately doubles the amount of evidence from trials of about 5 years of tamoxifen and, taking all trials together, on events occurring more than 5 years after randomisation. Nearly 8000 of the women had a low, or zero, level of the oestrogen-receptor protein (ER) measured in their primary tumour. Among them, the overall effects of tamoxifen appeared to be small, and subsequent analyses of recurrence and total mortality are restricted to the remaining women (18000 with ER-positive tumours, plus nearly 12000 more with untested tumours, of which an estimated 8000 would have been ER-positive). For trials of 1 year, 2 years, and about 5 years of adjuvant tamoxifen, the proportional recurrence reductions produced among these 30000 women during about 10 years of follow-up were 21% (SD 3), 29% (SD 2), and 47% (SD 3), respectively, with a highly significant trend towards greater effect with longer treatment (chi2(1)=52.0, 2p<0.00001). The corresponding proportional mortality reductions were 12% (SD 3), 17% (SD 3), and 26% (SD 4), respectively, and again the test for trend was significant (chi2(1) = 8.8, 2p=0.003). The absolute improvement in recurrence was greater during the first 5 years, whereas the improvement in survival grew steadily larger throughout the first 10 years. The proportional mortality reductions were similar for women with node-positive and node-negative disease, but the absolute mortality reductions were greater in node-positive women. In the trials of about 5 years of adjuvant tamoxifen the absolute improvements in 10-year survival were 10.9% (SD 2.5) for node-positive (61.4% vs 50.5% survival, 2p<0.00001) and 5.6% (SD 1.3) for node-negative (78.9% vs 73.3% survival, 2p<0.00001). These benefits appeared to be largely irrespective of age, menopausal status, daily tamoxifen dose (which was generally 20 mg), and of whether chemotherapy had been given to both groups. In terms of other outcomes among all women studied (ie, including those with "ER-poor" tumours), the proportional reductions in contralateral breast cancer were 13% (SD 13), 26% (SD 9), and 47% (SD 9) in the trials of 1, 2, or about 5 years of adjuvant tamoxifen. The incidence of endometrial cancer was approximately doubled in trials of 1 or 2 years of tamoxifen and approximately quadrupled in trials of 5 years of tamoxifen (although the number of cases was small and these ratios were not significantly different from each other). The absolute decrease in contralateral breast cancer was about twice as large as the absolute increase in the incidence of endometrial cancer. Tamoxifen had no apparent effect on the incidence of colorectal cancer or, after exclusion of deaths from breast or endometrial cancer, on any of the other main categories of cause of death (total nearly 2000 such deaths; overall relative risk 0.99 [SD 0.05]). For women with tumours that have been reliably shown to be ER-negative, adjuvant tamoxifen remains a matter for research. However, some years of adjuvant tamoxifen treatment substantially improves the 10-year survival of women with ER-positive tumours and of women whose tumours are of unknown ER status, with the proportional reductions in breast cancer recurrence and in mortality appearing to be largely unaffected by other patient characteristics or treatments.
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              Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial.

              Tamoxifen is approved for the reduction of breast cancer risk, and raloxifene has demonstrated a reduced risk of breast cancer in trials of older women with osteoporosis. To compare the relative effects and safety of raloxifene and tamoxifen on the risk of developing invasive breast cancer and other disease outcomes. The National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene trial, a prospective, double-blind, randomized clinical trial conducted beginning July 1, 1999, in nearly 200 clinical centers throughout North America, with final analysis initiated after at least 327 incident invasive breast cancers were diagnosed. Patients were 19,747 postmenopausal women of mean age 58.5 years with increased 5-year breast cancer risk (mean risk, 4.03% [SD, 2.17%]). Data reported are based on a cutoff date of December 31, 2005. Oral tamoxifen (20 mg/d) or raloxifene (60 mg/d) over 5 years. Incidence of invasive breast cancer, uterine cancer, noninvasive breast cancer, bone fractures, thromboembolic events. There were 163 cases of invasive breast cancer in women assigned to tamoxifen and 168 in those assigned to raloxifene (incidence, 4.30 per 1000 vs 4.41 per 1000; risk ratio [RR], 1.02; 95% confidence interval [CI], 0.82-1.28). There were fewer cases of noninvasive breast cancer in the tamoxifen group (57 cases) than in the raloxifene group (80 cases) (incidence, 1.51 vs 2.11 per 1000; RR, 1.40; 95% CI, 0.98-2.00). There were 36 cases of uterine cancer with tamoxifen and 23 with raloxifene (RR, 0.62; 95% CI, 0.35-1.08). No differences were found for other invasive cancer sites, for ischemic heart disease events, or for stroke. Thromboembolic events occurred less often in the raloxifene group (RR, 0.70; 95% CI, 0.54-0.91). The number of osteoporotic fractures in the groups was similar. There were fewer cataracts (RR, 0.79; 95% CI, 0.68-0.92) and cataract surgeries (RR, 0.82; 95% CI, 0.68-0.99) in the women taking raloxifene. There was no difference in the total number of deaths (101 vs 96 for tamoxifen vs raloxifene) or in causes of death. Raloxifene is as effective as tamoxifen in reducing the risk of invasive breast cancer and has a lower risk of thromboembolic events and cataracts but a nonstatistically significant higher risk of noninvasive breast cancer. The risk of other cancers, fractures, ischemic heart disease, and stroke is similar for both drugs. clinicaltrials.gov Identifier: NCT00003906.
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                Author and article information

                Contributors
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                Journal
                rcci
                Revista Colombiana de Cirugía
                rev. colomb. cir.
                Asociación Colombiana de Cirugía (Bogotá )
                2011-7582
                March 2007
                : 22
                : 1
                : 47-71
                Affiliations
                [1 ] Clínica del Country Colombia
                [2 ] Instituto Nacional de Cancerología Mexico
                [3 ] Hospital Universitario Fundación Santafé
                [4 ] Clínica de seno
                Article
                S2011-75822007000100008
                9a8a8b15-1ae8-482e-9122-9e8bbb1923fb

                http://creativecommons.org/licenses/by/4.0/

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                SciELO Colombia

                Self URI (journal page): http://www.scielo.org.co/scielo.php?script=sci_serial&pid=2011-7582&lng=en
                Categories
                SURGERY

                Surgery
                hormonal antineoplastic agents,breast neoplasms,estrogen receptor,adjuvant therapy,agentes antineoplásicos hormonales,cáncer de seno,receptores estrogénicos,quimioterapia adyuvante

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