Letrozole as upfront endocrine therapy for postmenopausal women with hormone-sensitive breast cancer: BIG 1-98

The BIG 1-98 trial is a large, randomized, independently conducted clinical trial designed to compare the efficacy of upfront letrozole versus tamoxifen monotherapy and to compare sequential or up-front use of letrozole and/or tamoxifen as an early adjuvant therapy for patients with early breast cancer. We report on the results from the primary core analysis of the BIG 1-98 trial of 8,010 patients, which compares monotherapy with letrozole versus tamoxifen. This pre-planned core analysis allowed the use of patient data from the monotherapy arms of letrozole and tamoxifen and from the sequential arms prior to the drug switch point. Patients randomized to letrozole had a 19% improved disease-free survival (hazard ratio [HR] = 0.81; P = 0.003), due especially to reduced distant metastases (HR = 0.73; P = 0.001). A 14% risk reduction of fatal events in favor of letrozole was also observed (P = NS). The results from the monotherapy arms alone confirmed the findings from the primary core analysis. Based on the results from this trial, the aromatase inhibitor letrozole (Femara®) is currently recommended as a part of standard adjuvant therapy for postmenopausal women with endocrine-responsive breast cancer and has recently been approved in the early adjuvant setting in both Europe and the United States. A subsequent analysis after additional follow-up will address the question of monotherapy versus sequential therapy

Prevention of docetaxel- or paclitaxel-associated taste alterations in cancer patients with oral glutamine : a randomized, placebo-controlled, double-blind study

Taste alteration (dysgeusia), an underrecognized toxicity associated with taxane-based chemotherapy (TaxCh), lacks standard treatment. We investigated prevention of dysgeusia with oral glutamine in patients undergoing first-time TaxCh. Adult patients were randomized to receive either 30 g/day glutamine or placebo (maltodextrin) from day 1 of TaxCh. Dysgeusia was measured daily with a visual analogue scale (VAS). On each chemotherapy cycle, objective (sour, sweet, salty, bitter) and subjective (four-category scale) taste and toxicity (National Cancer Institute Common Toxicity Criteria, v.3) were assessed. Stomatitis and zinc deficiency were treated. For primary outcomes, repeated dysgeusia scores were analyzed with a linear mixed model. Repeated data on each objective or subjective taste item were analyzed with a generalized estimating equation. Of 52 patients randomized, 41 completed treatment (median study duration, 74 days). At baseline, the glutamine (n = 21) and placebo (n = 20) groups were comparable for age (64 years), gender (32% men), tumor types, chemotherapy (docetaxel, 44%; paclitaxel, 56%), schedule (weekly, 78%; 3-weekly, 22%), treatment intention (15% adjuvant), dysgeusia (VAS, 11/100), and taste recognition (88%). Twenty-four patients had peripheral neuropathy grades 1-2; none had grade 3. Glutamine and placebo were not different for maximal dysgeusia and increase from baseline, with an insignificant linear time effect. Separate subgroup analyses for patients with baseline dysgeusia > or =11 or <11 did not alter the results. Objective or subjective taste tests were not different, neither were adverse events. Compared with placebo, oral glutamine did not prevent or decrease subjective taste disturbances or altered taste perception associated with TaxCh. The role of glutamine in supportive care of taxane-associated dysgeusia seems limited

Ki-67 assessment in early breast cancer: SAKK28/12 validation study on the IBCSG VIII and IBCSG IX cohort

The assessment of Ki-67 in early-stage breast cancer has become an important diagnostic tool in planning adjuvant therapy, particularly for the administration of additional chemotherapy to hormone-responsive patients. An accurate determination of the Ki-67 index is of the utmost importance; however, the reproducibility is currently unsatisfactory. In this study, we addressed the predictive/prognostic value of Ki-67 index assessed by using the most reproducible methods, which were identified in the pilot phase. Paraffin blocks obtained from patients with moderately differentiated, estrogen receptor (ER)-positive early-stage breast cancer in Switzerland, who were originally randomized to the treatment arms with and without chemotherapy in the IBCSG VIII-IX trials, were retrieved. Of these 344 randomized patients, we identified 158 patients (82 treated with and 76 treated without chemotherapy) for whom sufficient tumour tissue was available. The presence of Ki-67 was assessed visually by counting 2000 cells at the periphery (A) and estimating the number of positive cells in five different peripheral regions (C), which was determined to be the most reproducible method identified the pilot phase. The prognostic and predictive value was assessed by calculating the breast cancer-free interval (BCFI) and overall survival (OS) rate. Ki-67 was considered a numerical and categorical variable when different cut-off values were used (10%, 14%, 20% and 30%). An mRNA-based subtyping by using the MammaTyper kit with the application of a 20% Ki-67 immunohistochemistry (IHC) cut-off equivalent was also performed. 158 of 344 randomized patients could be included in the Ki-67 analysis. The mean Ki-67 values obtained by using the two methods differed (A: 21.32% and C: 16.07%). Ki-67 assessed by using method A with a cut-off of 10% was a predictive marker for OS, as the hazard ratio (>10% vs. <=10%) in patients with chemotherapy was 0.48 with a 95% confidence interval of [0.19-1.19]. Further, the HR of patients treated without chemotherapy was 3.72 with a 95% confidence interval of [1.16-11.96] (pinteraction=0.007). Higher Ki-67 index was not associated with outcome and using the 10% Ki-67 cut-off there was an opposite association for patients with and without chemotherapy. Ki-67 assessments with IHC significantly correlated with MammaTyper results (p=0.002). The exact counting method (A) performed via a light-microscope revealed the predictive value of Ki-67 assessment with a 10% cut-off value. Further analyses employing image analyses and/or mRNA-based-assessments in larger populations are warranted