Search

Background Clinical trial data have shown that among breast cancer patients who were disease free after 5 years of adjuvant treatment with tamoxifen, further extended treatment with the nonsteroidal aromatase inhibitor letrozole reduces breast cancer recurrence. We examined the efficacy and tolerability of extended adjuvant therapy with another aromatase inhibitor, anastrozole, for 3 years among women who had completed 5 years of adjuvant therapy. Methods Austrian Breast and Colorectal Cancer Study Group (ABCSG) Trial 6a is an extension of ABCSG Trial 6, in which hormone receptor-positive postmenopausal patients received 5 years of adjuvant tamoxifen, with or without the aromatase inhibitor aminoglutethimide, for the first 2 years of therapy. For ABCSG Trial 6a, patients who were disease free at the end of Trial 6 were randomly assigned to receive either 3 years of anastrozole or no further treatment. Efficacy data were analyzed with the use of a Cox proportional hazards regression model with two-sided P values and Kaplan-Meier curves, and tolerability data were estimated using logistic regression analysis with odds ratios and 95% confidence intervals (CIs). Results ABCSG Trial 6a included 856 patients. At a median follow-up of 62.3 months, women who received anastrozole (n = 387) had a statistically significantly reduced risk of recurrence (locoregional recurrence, contralateral breast cancer, or distant metastasis) compared with women who received no further treatment (n = 469; hazard ratio = 0.62; 95% CI = 0.40 to 0.96, P = .031). Anastrozole was well tolerated, and no unexpected adverse events were reported. Conclusions These data confirm the benefit of extending adjuvant tamoxifen therapy beyond 5 years with anastrozole compared with no further treatment. Further research is required to define the optimum length of extended adjuvant therapy and to investigate the possibility of tailoring this period to suit different disease types. [ABSTRACT FROM AUTHOR]

Objective: Recombinant granulocyte colony-stimulating factors (G-CSF) have been shown to be effective in reducing the risk of infections associated with antitumour chemotherapy. This report describes a single-centre experience of the efficacy of pegfilgrastim compared with filgrastim or lenograstim in reducing the incidence of febrile neutropenia in patients receiving combination chemotherapy with taxane and epirubicin in a neoadjuvant and adjuvant setting. Methods: A total of 118 patients with breast cancer were treated with either epirubicin 75 mg/m2 and docetaxel 75 mg/m2 or epirubicin 90 mg/m2 and paclitaxel 200 mg/m2 every 3 weeks; 88 received G-CSF support with daily filgrastim or lenograstim and 30 with pegfilgrastim once per cycle. Results: Eight patients (9.1%) with prophylactic filgrastim or lenograstim support developed febrile neutropenia, as well as 1 patient (3.3%) in the pegfilgrastim group (p = 0.445). Febrile neutropenia occurred in 13 (2.7%) of 476 filgrastim or lenograstim supported chemotherapy cycles and in 2 (1.2%) of 172 cycles with pegfilgrastim support (p = 0.376). The frequency of chemotherapy delays and dose reductions was not significantly different between the two G-CSF treatment groups. Conclusion: These data show a trend towards superiority of pegfilgrastim over filgrastim or lenograstim in reducing the frequency of febrile neutropenia in patients treated with taxane and epirubicin chemotherapy regimens for breast cancer. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Summary: Background: The Austrian Breast and Colorectal Cancer Study Group trial-12 (ABCSG-12) bone substudy assesses zoledronic acid for preventing bone loss associated with adjuvant endocrine therapy and reports on long-term findings of bone-mineral density (BMD) during 3 years of treatment and 2 years after completing adjuvant treatment with or without zoledronic acid. The aim of this substudy is to gain insight into bone health in this setting. Methods: ABCSG-12 is a randomised, open-label, phase III, 4-arm trial comparing tamoxifen (20 mg/day orally) and goserelin (3·6 mg subcutaneously every 28 days) versus anastrozole (1 mg/day orally) and goserelin (3·6 mg subcutaneously every 28 days), both with or without zoledronic acid (4 mg intravenously every 6 months) for 3 years in premenopausal women with endocrine-responsive breast cancer. This prospective bone subprotocol measured BMD at 0, 6, 12, 36, and 60 months. The primary endpoint of the bone substudy (secondary endpoint in the main trial) was change in BMD at 12 months, assessed by dual-energy X-ray absorptiometry in assessable patients. Analyses were intention to treat. Statistical significance was assessed by t tests. The ABCSG-12 trial is registered on the ClinicalTrials.gov website, number NCT00295646. Findings: 404 patients were prospectively included in the bone substudy and randomly assigned to endocrine therapy alone (goserelin and anastrozole or goserelin and tamoxifen; n=199) or endocrine therapy concurrent with zoledronic acid (goserelin, anastrozole, and zoledronic acid or goserelin, tamoxifen, and zoledronic acid; n=205). After 3 years of treatment, endocrine therapy alone caused significant loss of BMD at the lumbar spine (−11·3%, mean difference −0·119 g/cm2 [95% CI −0·146 to −0·091], p<0·0001) and trochanter (−7·3%, mean difference −0·053 g/cm2 [−0·076 to −0·030], p<0·0001). In patients who did not receive zoledronic acid, anastrozole caused greater BMD loss than tamoxifen at 36 months at the lumbar spine (−13·6%, mean difference −0·141 g/cm2 [−0·179 to −0·102] vs −9·0%, mean difference −0·095 g/cm2 [−0·134 to −0·057], p<0·0001 for both). 2 years after the completion of treatment (median follow-up 60 months [range 15·5–96·6]), patients not receiving zoledronic acid still had decreased BMD at both sites compared with baseline (lumbar spine −6·3%, mean difference −0·067 g/cm2 [−0·106 to −0·027], p=0·001; trochanter −4·1%, mean difference −0·03 g/cm2 [−0·062 to 0·001], p=0·058). Patients who received zoledronic acid had stable BMD at 36 months (lumbar spine +0·4%, mean difference 0·004 g/cm2 [−0·024 to 0·032]; trochanter +0·8%, mean difference 0·006 g/cm2 [−0·018 to 0·028]) and increased BMD at 60 months at both sites (lumbar spine +4·0%, mean difference 0·039 g/cm2 [0·005–0·075], p=0·02; trochanter +3·9%, mean difference 0·028 g/cm2 [0·003–0·058], p=0·07) compared with baseline. Interpretation: Goserelin plus tamoxifen or anastrozole for 3 years without concomitant zoledronic acid caused significant bone loss. Although there was partial recovery 2 years after completing treatment, patients receiving endocrine therapy alone did not recover their baseline BMD levels. Concomitant zoledronic acid prevented bone loss during therapy and improved BMD at 5 years. Funding: AstraZeneca (London, UK) and Novartis (Basel, Switzerland). [Copyright &y& Elsevier]

The 825C>T polymorphism in the gene for the G-protein β3 subunit (GNB3) has been linked to the occurrence of a splice variant of GNB3 and distinct cellular and metabolic features and may be associated with malignant disease. 500 patients with histologically confirmed breast cancer and 500 female age-matched healthy control subjects were genotyped for the GNB3 polymorphism to analyze its role for breast cancer. Prevalences of GNB3 CC, CT and TT genotypes were similar among patients (49.7, 39.8, 10.5%) and controls (50.1, 42.4, 7.5%, P=0.25). The GNB3 genotype was furthermore not linked to tumor size, histological grading, estrogen or progesterone receptor status and age at diagnosis. In an exploratory analysis, carriage of a 825-T allele was associated with a longer metastasis-free period in patients with primary low-grade breast cancer, but not in those with primary high-grade breast cancer (Cox regression, P=0.025). We conclude that the GNB3 825C>T polymorphism does not appear to be associated with breast cancer risk, but may influence development of metastasis in low-grade tumors. [Copyright &y& Elsevier]

Transforming growth factor-beta 1 (TGF-β1) is a potent inhibitor of proliferation of epithelial, endothelial and hematopoietic cells and acts as a tumor suppressor. The gene for TGF-β1, TGFB1, carries a common T/C variation of nucleotide 29, resulting in a leucine (L) to proline (P) polymorphism at codon 10 (TGFB1 L10P). The less common 10P allele has repeatedly been linked to higher TGF-β1 levels and in at least one study to a lower incidence of breast cancer. To further analyze the role of this polymorphism for breast cancer risk, 500 patients with histologically confirmed breast cancer and 500 sex-and age-matched healthy control subjects were genotyped for the TGFB1 L10P polymorphism by an allele-specific polymerase chain reaction assay. TGFB1 LL, LP and PP genotype frequencies were not significantly different for patients (39.6, 44.2, 16.2%) and controls (36.5, 45.9, 17.6%). We conclude that the TGFB1 L10P polymorphism is not associated with breast cancer risk. [Copyright &y& Elsevier]