Long-term renal safety profile of ibandronate 6 mg infused over 15 minutes

In an earlier study, intravenous (i.v.) ibandronate 6 mg administered every 3-4 weeks had a similarly good renal safety profile whether infused over 15 or 60 min in women with breast cancer and bone metastases. This current study focuses on the renal safety of the extended use of ibandronate

Adjuvant therapy after excision and radiation of isolated postmastectomy locoregional breast cancer recurrence: definitive results of a phase III randomized trial (SAKK 23/82) comparing tamoxifen with observation

Background: Adjuvant systemic treatment for patients with isolated locoregional recurrence (ILRR) of breast cancer is based on a single reported randomized trial. The trial, conducted by the Swiss Group for Clinical Cancer Research, compared tamoxifen (TAM) with observation after complete excision of the ILRR and proper radiotherapy. We performed a definitive analysis of treatment outcome at >11 years of follow-up, after the majority of the patients had a subsequent event of interest. Patient and methods One hundred and sixty-seven patients with ‘good-risk' characteristics of disease were randomized. ‘Good-risk' was defined as estrogen receptor expression in the ILRR, or having a disease-free interval of >12 months and a recurrence consisting of three or less tumor nodules, each ≤3 cm in diameter. Seventy-nine percent of the patients were postmenopausal at randomization. Results: The median follow-up time of the surviving patients was 11.6 years. The median post ILRR disease-free survival (DFS) was 6.5 years with TAM and 2.7 years with observation (P = 0.053). The difference was mainly due to reduction of further local relapses (P = 0.011). In postmenopausal patients, TAM led to an increase of DFS from 33% to 61% (P = 0.006). In premenopausal women, 5-year DFS was 60%, independent of TAM medication. For the whole study population, the median post-recurrence overall survival (OS) was 11.2 and 11.5 years in the observation and the TAM group, respectively; premenopausal patients experienced a 5-year OS of 90% for observation compared with 67% for TAM (P = 0.175), while the respective figures for postmenopausal patients were both 75%. Conclusions: These definitive results confirmed that TAM significantly improves the post-recurrence DFS of patients after local treatment for ILRR. This beneficial effect does not translate into a detectable OS advantag

Regional differences and trends in breast cancer surgical procedures and their relation to socioeconomic disparities and screening patterns

Background Important regional disparities in patterns of care in breast cancer have recently been described. In Switzerland, nationwide data on hospitalisations have been collected since 1998. They have not been used up to now to explore space–time patterns and trends of breast cancer healthcare-related procedures for control and health planning purposes. We aimed to assess geographical and temporal variation of mastectomy rates. Methods Bayesian negative-binomial spatio-temporal models have been applied. Covariates included patient characteristics as provided in the hospital data, data on mammography screening programme duration, and surgeon and gynaecologist density. Results We analyzed more than 70,000 patients. Mastectomy rates declined from 43% to 30% in Switzerland between 2000 and 2012 for patients aged 50–69 and from 61% to 43% for those 70+, and remained stable for those under 50. Important geographical differences in rates were present. Rates were significantly influenced by age [relative rate ratio (RR) 50–69: 0.92, RR 70+: 1.25], differences in co-morbidity (RR one co-morbidity: 1.17, RR more than one: 1.35), higher surgeon or gynaecologist density (RR surgeons: 1.01, RR gynaecologists: 1.06). Regions in the French-speaking part (RR: 0.72) and/or with mammography screening programmes showed significantly lower rates (RR: 0.87). No difference was found for patients in different socio-economic groups or with different insurance types. Conclusion This research unveiled important differences in mastectomy rates in Switzerland. The results play an essential role in the identification of regions where special attention is required, and indications for extensive surgery in breast cancer should be revisited

Predictors of state-of-the-art management of early breast cancer in Switzerland

Background: The aim of this study was to investigate predictors of state-of-the-art management of early breast cancer in Switzerland. Patients and methods: The study included 3499 women aged 25-79 years diagnosed with invasive breast cancer stages I-IIIA in 2003-2005. Patients were identified through population-based cancer registries and treated in all kinds of settings. Concordance with national and international recommendations was assessed for 10 items covering surgery, radiotherapy, systemic adjuvant therapy and histopathology reporting. We used multivariate logistic regression to identify independent predictors of high (10 points) and low (≤7 points) concordance. Results: In one-third of the patients, management met guidelines in all items, whereas in about one-fifth, three or more items did not comply. Treatment by a surgeon with caseload in the upper tercile and team involved in clinical research were independent predictors of a high score, whereas treatment by a surgeon with a caseload in the lower tercile was associated with a low score. Socioeconomic characteristics such as income and education were not independent predictors, but patient's place of residence and age independently predicted management according to recommendations. Conclusion: Specialization and involvement in clinical research seem to be key elements for enhancing the quality of early breast cancer management at population leve

First-line fadrozole HCI (CGS 16949A) versus tamoxifen in postmenopausal women with advanced breast cancer: Prospective randomised trial of the Swiss Group for Clinical Cancer Research SAKK 20/88

Background: In a phase III randomized trial, we compared the effectiveness and tolerability of fadrozole (CGS 16949A), a non-steroidal aromatase inhibitor, to tamoxifen as first-line endocrine therapy in postmenopausal women with advanced breast cancer. Patients and methods: Two hundred twelve eligible patients were randomized to receive tamoxifen 20 mg daily, or fadrozole 1 mg twice daily orally until disease progression or the advent of undue toxicity. The treatments were to be discontinued upon disease progression. Results: Prognostic factors were well balanced between the treatment groups, except for sites of metastatic disease. Fadrozole-treated patients had significantly more visceral, especially liver, involvement and less bone-dominant disease. Response rates for fadrozole and tamoxifen were similar, 20% and 27% (95% Confidence Limits (CL): 13%-29% and 21%-35%), respectively. Time to treatment failure was longer in patients randomized to tamoxifen (8.5 months for tamoxifen vs. 6.1 months for fadrozole), but did not reach statistical significance after adjustment for prognostic factors (P=0.09). Fadrozole, for which a significantly lower percentage of clinically relevant toxic effects (WHO toxicity gradeij2) was recorded (27% vs. 13% respectively; P=0.009), was better tolerated than tamoxifen. Severe cardiovascular events including 3 fatalities were seen only in patients treated with tamoxifen. Eighty-two patients crossed over to tamoxifen and 66 patients to fadrozole. Crossover endocrine therapy led to response or stable disease in 64% of the patients. The overall survival times of the two treatment groups were similar. Conclusions: Fadrozole and tamoxifen showed similar efficacy as first-line treatments in postmenopausal patients with advanced breast cancer. Fadrozole was significantly better tolerated and may therefore be an appropriate alternative to tamoxifen, especially for patients predisposed to thromboembolic event

Clinical benefit of fulvestrant in postmenopausal women with advanced breast cancer and primary or acquired resistance to aromatase inhibitors: final results of phase II Swiss Group for Clinical Cancer Research Trial (SAKK 21/00)

Background: The aim of this study was to evaluate the efficacy and tolerability of fulvestrant, an estrogen receptor antagonist, in postmenopausal women with hormone-responsive tumors progressing after aromatase inhibitor (AI) treatment. Patients and methods: This is a phase II, open, multicenter, noncomparative study. Two patient groups were prospectively considered: group A (n = 70) with AI-responsive disease and group B (n = 20) with AI-resistant disease. Fulvestrant 250 mg was administered as intramuscular injection every 28 (±3) days. Results: All patients were pretreated with AI and 84% also with tamoxifen or toremifene; 67% had bone metastases and 45% liver metastases. Fulvestrant administration was well tolerated and yielded a clinical benefit (CB; defined as objective response or stable disease [SD] for ≥24 weeks) in 28% (90% confidence interval [CI] 19% to 39%) of patients in group A and 37% (90% CI 19% to 58%) of patients in group B. Median time to progression (TTP) was 3.6 (95% CI 3.0 to 4.8) months in group A and 3.4 (95% CI 2.5 to 6.7) months in group B. Conclusions: Overall, 30% of patients who had progressed following prior AI treatment gained CB with fulvestrant, thereby delaying indication to start chemotherapy. Prior response to an AI did not appear to be predictive for benefit with fulvestran

Early stopping of clinical trials

Early stopping of clinical trials in favour of a new treatment creates ethical and scientific difficulties, which are different from those associated with early stopping due to toxicity or futility. Two major breast cancer trials have recently taken such a decision, and the problem is relevant for several ongoing trials. Here we argue that such a decision should be taken with the utmost gravity and should be based on a clear overall clinical benefit for the new treatment, and not as an automatic response to crossing a predefined threshold. Predefined rules can be used to trigger a debate within the Independent Data Monitoring and Safety Committee (IDMC) about early stopping, but the IDMC should retain the responsibility of assessing overall clinical benefit in making its recommendation

Bone mineral density in breast cancer patients treated with adjuvant letrozole, tamoxifen, or sequences of letrozole and tamoxifen in the BIG 1-98 study (SAKK 21/07)

Background: The risk of osteoporosis and fracture influences the selection of adjuvant endocrine therapy. We analyzed bone mineral density (BMD) in Swiss patients of the Breast International Group (BIG) 1-98 trial [treatment arms: A, tamoxifen (T) for 5 years; B, letrozole (L) for 5 years; C, 2 years of T followed by 3 years of L; D, 2 years of L followed by 3 years of T]. Patients and methods: Dual-energy X-ray absorptiometry (DXA) results were retrospectively collected. Patients without DXA served as control group. Repeated measures models using covariance structures allowing for different times between DXA were used to estimate changes in BMD. Prospectively defined covariates were considered as fixed effects in the multivariable models. Results: Two hundred and sixty-one of 546 patients had one or more DXA with 577 lumbar and 550 hip measurements. Weight, height, prior hormone replacement therapy, and hysterectomy were positively correlated with BMD; the correlation was negative for letrozole arms (B/C/D versus A), known osteoporosis, time on trial, age, chemotherapy, and smoking. Treatment did not influence the occurrence of osteoporosis (T score < −2.5 standard deviation). Conclusions: All aromatase inhibitor regimens reduced BMD. The sequential schedules were as detrimental for bone density as L monotherap

Patterns and risk factors for locoregional failures after mastectomy for breast cancer: an International Breast Cancer Study Group report

Background Rates and risk factors of local, axillary and supraclavicular recurrences can guide patient selection and target for postmastectomy radiotherapy (PMRT). Patients and methods Local, axillary and supraclavicular recurrences were evaluated in 8106 patients enrolled in 13 randomized trials. Patients received chemotherapy and/or endocrine therapy and mastectomy without radiotherapy. Median follow-up was 15.2 years. Results Ten-year cumulative incidence for chest wall recurrence of >15% was seen in patients aged 10%: ≥4 positive nodes (10.2%); for axillary failures of >5%: aged 15% were age <40, peritumoral vessel invasion or 0-7 uninvolved nodes. Age, number of positive nodes and number of uninvolved nodes were significant parameters for each locoregional relapse site. Conclusion PMRT to the chest wall and supraclavicular fossa is supported in patients with ≥4 positive nodes. With 1-3 positive nodes, chest wall PMRT may be considered in patients aged <40 years, with 0-7 uninvolved nodes or with vascular invasion. The findings do not support PMRT to the dissected axill