A última palavra em terapia adjuvante para câncer de mama

Adjuvant systemic therapy has been shown to reduce relapses in treated women and to prolong their survival. This is true for all studied subpopulations. Multidrug chemotherapy for the duration of 6 months with the addition of tamoxifen for patients with hormone receptorpositive tumors and for the premenopausal patients, and tamoxifen or short-term chemotherapy with long-term tamoxifen for the postmenopausal patients represent the treatments of choice to reduce the risk of relapse. In general, patients should be treated with a much more individualized adjuvant therapy program than is currently being prescribed. Current practice is based largely on estimates of average chemotherapy effects obtained from patients with heterogeneous disease and menopausal status characteristics. Some of the open questions relate to i) the definition of the populations for which risk of relapse justifies therapy, and ii) the optimal way of using available therapies might find answer from ongoing research in the next future. The modest but real improvement of the prognosis in operable breast cancer was exclusively obtained by means of clinical trials, and it is mandatory that participation in programs of clinical research become medically and socially the treatment of choice for patients and for their doctors.Estudos têm demonstrado que a terapia sistêmica adjuvante diminui os relapsos em mulheres submetidas a tratamento e melhora a sua sobrevida. Isto se verifica para todas as sub-populações estudadas. A quimioterapia com múltiplas drogas, com duração de 6  meses e adição de tamoxifeno para pacientes com tumores positivos para receptores de hormônios e para pacientes pré-menopausa, e de tamoxifeno ou quimioterapia de curto prazo com tamoxifeno a longo prazo para pacientes pós-menopausa representam os tratamentos de escolha para reduzir os riscos de relapso. Em geral, os pacientes devem ser tratados com programas de terapias adjuvantes mais individualizados do que o que está sendo feito na prática atual. A prática atual é largamente baseada em estimativas de efeitos médios de quimioterapia obtidos com pacientes com doenças heterogêneas e características de quadro de menopausa. Algumas das questões que precisam ser respondidas são: i) a definição das populações de risco para relapso justifica a terapia e ii) a maneira mais otimizada de utilizar as terapias disponíveis poderá ser encontrada nas pesquisas que estarão sendo desenvolvidas em um futuro próximo. A melhora modesta, mas real, no prognóstico de câncer operável foi obtida exclusivamente através de testes clínicos. É necessário, ainda, que a participação em programas de pesquisas clínicas seja o tratamento de escolha em termos médicos e sociais para pacientes e seus médicos.

Re-evaluating Adjuvant Breast Cancer Trials: Assessing Hormone Receptor Status by Immunohistochemical Versus Extraction Assays

Background: Tumor levels of steroid hormone receptors, a factor used to select adjuvant treatment for early-stage breast cancer, are currently determined with immunohistochemical assays. These assays have a discordance of 10%-30% with previously used extraction assays. We assessed the concordance and predictive value of hormone receptor status as determined by immunohistochemical and extraction assays on specimens from International Breast Cancer Study Group Trials VIII and IX. These trials predominantly used extraction assays and compared adjuvant chemoendocrine therapy with endocrine therapy alone among pre- and postmenopausal patients with lymph node-negative breast cancer. Trial conclusions were that combination therapy provided a benefit to pre- and postmenopausal patients with estrogen receptor (ER)-negative tumors but not to ER-positive postmenopausal patients. ER-positive premenopausal patients required further study. Methods: Tumor specimens from 571 premenopausal and 976 postmenopausal patients on which extraction assays had determined ER and progesterone receptor (PgR) levels before randomization from October 1, 1988, through October 1, 1999, were re-evaluated with an immunohistochemical assay in a central pathology laboratory. The endpoint was disease-free survival. Hazard ratios of recurrence or death for treatment comparisons were estimated with Cox proportional hazards regression models, and discriminatory ability was evaluated with the c index. All statistical tests were two-sided. Results: Concordance of hormone receptor status determined by both assays ranged from 74% (κ = 0.48) for PgR among postmenopausal patients to 88% (κ = 0.66) for ER in postmenopausal patients. Hazard ratio estimates were similar for the association between disease-free survival and ER status (among all patients) or PgR status (among postmenopausal patients) as determined by the two methods. However, among premenopausal patients treated with endocrine therapy alone, the discriminatory ability of PgR status as determined by immunohistochemical assay was statistically significantly better (c index = 0.60 versus 0.51; P = .003) than that determined by extraction assay, and so immunohistochemically determined PgR status could predict disease-free survival. Conclusions: Trial conclusions in which ER status (for all patients) or PgR status (for postmenopausal patients) was determined by immunohistochemical assay supported those determined by extraction assays. However, among premenopausal patients, trial conclusions drawn from PgR status differed—immunohistochemically determined PgR status could predict response to endocrine therapy, unlike that determined by the extraction assa

Predictive Value of Tumor Ki-67 Expression in Two Randomized Trials of Adjuvant Chemoendocrine Therapy for Node-Negative Breast Cancer

Several small studies have reported that having a high percentage of breast tumor cells that express the proliferation antigen Ki-67 (ie, a high Ki-67 labeling index) predicts better response to neoadjuvant chemotherapy. However, the predictive value of a high Ki-67 labeling index for response to adjuvant chemotherapy is unclear. To investigate whether Ki-67 labeling index predicts response to adjuvant chemoendocrine therapy, we assessed Ki-67 expression in tumor tissue from 1924 (70%) of 2732 patients who were enrolled in two randomized International Breast Cancer Study Group trials of adjuvant chemoendocrine therapy vs endocrine therapy alone for node-negative breast cancer. A high Ki-67 labeling index was associated with other factors that predict poor prognosis. Among the 1521 patients with endocrine-responsive tumors, a high Ki-67 labeling index was associated with worse disease-free survival but the Ki-67 labeling index did not predict the relative efficacy of chemoendocrine therapy compared with endocrine therapy alone. Thus, Ki-67 labeling index was an independent prognostic factor but was not predictive of better response to adjuvant chemotherapy in these studie

Controversies of adjuvant endocrine treatment for breast cancer and recommendations of the 2007 St Gallen conference

Endocrine treatment for breast cancer was introduced more than a century ago. The discovery of hormone receptors has allowed targeting of endocrine treatment to patients whose primary tumours express these receptors. In the adjuvant setting, different approaches are used in premenopausal or postmenopausal women. In premenopausal patients, suppression of ovarian function and the use of tamoxifen are the most important therapeutic options, even though questions on timing, duration, and combination of these compounds remain unanswered. The use of aromatase inhibitors in combination with ovarian-function suppression is currently under investigation in the premenopausal setting. In postmenopausal patients, aromatase inhibitors given after 2-3 years or 5 years of tamoxifen have shown a significant benefit over tamoxifen alone. However, questions on this treatment also remain unanswered. For example, whether all patients should receive an aromatase inhibitor or whether some subgroups of patients might be optimally treated by tamoxifen alone is yet to be established. In this paper we review the published work on adjuvant endocrine treatment in breast cancer and provide recommendations from the 2007 St Gallen International Conference on Primary Therapy of Early Breast Cancer