Search

Udgivelsesdato: 2008-May-28 AIM: To examine the extent of use of specific therapies in clinical practice, and their relationship to therapies validated in clinical trials. METHODS: The US National Cancer Institutes' Patterns of Care study was used to examine therapies and survival of patients diagnosed in 2001 with histologically-confirmed gastroesophageal adenocarcinoma (n = 1356). The study re-abstracted data and verified therapy with treating physicians for a population-based stratified random sample. RESULTS: Approximately 62% of patients had stomach adenocarcinoma (SAC), while 22% had gastric-cardia adenocarcinoma (GCA), and 16% lower esophageal adenocarcinoma (EAC). Stage IV/unstaged esophageal cancer patients were most likely and stage I-III stomach cancer patients least likely to receive chemotherapy as all or part of their therapy; gastric-cardia patients received chemotherapy at a rate between these two. In multivariable analysis by anatomic site, patients 70 years and older were significantly less likely than younger patients to receive chemotherapy alone or chemoradiation for all three anatomic sites. Among esophageal and stomach cancer patients, receipt of chemotherapy was associated with lower mortality; but no association was found among gastric-cardia patients. CONCLUSION: This study highlights the relatively low use of clinical trials-validated anti-cancer therapies in community practice. Use of chemotherapy-based treatment was associated with lower mortality, dependent on anatomic site. Findings suggest that physicians treat lower esophageal and SAC as two distinct entities, while gastric-cardia patients receive a mix of the treatment strategies employed for the two other sites.

TO THEEDITOR:InarecentJournalofClinicalOncologyeditorial, Desta and Flockhart 1 asked a yes-no question about the germline pharmacogeneticsoftamoxifenresponse:“Havewelearnedenough?” They ultimately answer by writing that recommendations regarding genetic testing for CYP2D6 variants must await further data, but the list of open questions preceding this answer did not include the question of whether there is a main effect. We therefore raise this question about the main effect: “Has it been established that tamoxifen is a less effectiveadjuvanttherapyforestrogenreceptor‐positivebreastcancer patients with functionally variant CYP2D6 allele(s) than for those without functionally variant alleles?” Figure 1 depicts the results of the five epidemiologic studies of thisquestion. 2-6 Toexaminethedepartureofthedistributionofthese results from the null (ie, relative risk of 1.0), we first ranked the five relative risks of recurrence from lowest to highest (citations 2 to 6 in ascending order). We then plotted each study’s relative risk and its 95%CIagainsttheinversenormalofitsrankpercentile. 7 Thestippled lineshowstheregressionofinverse-varianceweightedlog-relativerisk against the inverse normal of rank percentile. If the accumulated evidenceisarandomsamplefromalognormaldistributionofrelative risks centered on the null, then the relative risks should fall along this line and the line should intersect the x-axis at zero. The results of the accumulated studies fit just such a pattern. Indeed, the inversevariance weighted geometric mean of the relative risks equals 1.04 (95%CI,0.77,1.41).Eachstudyhascertainstrengthsandlimitations, some of which were pointed out by Desta and Flockhart, and consideration of them against one another is of value. Nonetheless, the simplest explanation for the results to date is that they are sampled from an underlying null association. The integer above each interval in Fig 1 shows the number of women in the study (as best we can determine) with a recurrence and with the variant allele(s). Because both recurrence and the variant allele are rare, this number is the primary determinant of the study’s precision. Summed over all of the studies, there are only approximately sixty women with both a recurrence and the variant allele(s), about half from studies reporting a protective association and half fromstudiesreportingacausalassociation.Inourview,sixtywomen, evenlydistributedaboutthenull,istoosmallanumbertoconsiderthe association between CYP2D6-variant alleles and tamoxifen effective

Epidemiologic studies investigating the effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on breast cancer have yielded conflicting results. We examined the association between use of aspirin and nonaspirin NSAIDs and breast cancer risk among 28 695 women in the Danish Diet, Cancer and Health cohort. Information on NSAID and paracetamol use was obtained from a self-administered questionnaire completed at baseline (1993-1997) and updated through 2003 using a nationwide prescription database. Detailed information on breast cancer incidence and tumour characteristics was obtained from nationwide health registers. Cox proportional hazards regression was used to compute incidence rate ratios (RRs) and 95% confidence intervals (CIs). We identified 847 breast cancer cases over an average follow-up period of 7.5 years. Any NSAID use at baseline was associated with an increased incidence of breast cancer compared with nonuse (RR, 1.27; 95% CI, 1.10-1.45). A similar result was observed for any NSAID use in a combined analysis of baseline and prescription data (1.34; 95% CI, 1.15-1.56). Aspirin-only users experienced a slightly higher breast cancer incidence (RR, 1.38; 95% CI, 1.12-1.69) than exclusive users of nonaspirin NSAIDs (RR, 1.25; 95% CI, 1.04-1.49). Introduction of a lag time of 1 year provided similar results. We found no clear differences in risk estimates with frequency, recency or duration of NSAID use, or by hormone receptor status of the breast tumours. Paracetamol use was unrelated to breast cancer incidence. The increased breast cancer incidence among NSAID users may reflect a noncausal association, but our study provides no evidence of a chemopreventive effect of NSAIDs against breast cancer over the durations studied. Udgivelsesdato: 2008-Apr

Udgivelsesdato: 2008-null Using hospital discharge data from the counties in Northern Denmark and the Danish Cancer Registry, we examined the trend in the prevalence of breast-conserving surgery (BCS) to treat primary breast cancer from 1982 through 2002, with an emphasis on publications that may have influenced surgical practice in Denmark. Overall, the prevalence of BCS increased from less than 1% of breast cancer operations in 1982 to approximately 25% by 2002. The rise in prevalence was most pronounced for the treatment of young women and women with early-stage breast cancer. Of three pivotal clinical trials, the most significant trigger of the upward trend appeared to be a study conducted by the Danish Breast Cancer Cooperative Group, published in 1988. After 1988, there was a steep rise in the prevalence of BCS. By 2002, BCS prevalence appeared to reach a threshold at 25% of breast cancer operations, seemingly defined by the proportion of new breast cancer cases who are good candidates for BCS.

Background: Incidences of inflammatory bowel disease (IBD) and of breast cancer have increased over the last decades. The influence of IBD on breast cancer prognosis, however, is unknown. We therefore examined the impact of IBD on treatment receipt and survival in breast cancer patients.Methods: Information on breast cancer patients (stage and treatment) diagnosed between 1980 and 2004 was sourced from the Danish Cancer Registry. Data on IBD and potential confounders were extracted from the Danish National Registry of Patients covering all Danish hospitals. Cox regression was used to compute mortality rate ratios (MRRs) among breast cancer patients with IBD, compared to their non-IBD counterparts, adjusting for age, stage, comorbidity measured by the Charlson Index, and calendar year.Results: We identified 71,148 breast cancer cases; 67 also had Crohn's disease (CD) and 216 had ulcerative colitis (UC). Patients with CD had more advanced stage and received radiotherapy less, and chemotherapy more, frequently than patients without IBD. In the adjusted analyses there was no substantial survival difference in breast cancer patients with and without IBD (MRR(CD) = 1.22; 95% confidence interval [CI] = 0.85-1.75; MRR(UC) = 1.09; 95% CI = 0.86-1.38). In a stratified analysis, chemotherapy was associated with poorer survival in patients with CD (MRR(CD) = 1.93; 95% CI = 1.00-3.72).Conclusions: Breast cancer patients with UC receive the same treatment and have similar survival to breast cancer without IBD. In contrast, breast cancer patients with CD are treated with radiotherapy less often. Survival of breast cancer in patients with CD treated with chemotherapy is poorer compared to survival in patients without IBD.(Inflamm Bowel Dis 2007). Udgivelsesdato: 2007-Dec-10

Background Persistent human papillomavirus (HPV) infection may promote carcinogenesis by hyperactivation of the immune system. We therefore explored the associations between HPV infection and risk of Hodgkin’s and non-Hodgkin lymphoma in a nationwide cohort study using conisation as a surrogate marker. Methods We identified all Danish women who underwent conisation between 1978 and 2011. We computed standardised incidence ratios and 95% confidence interval (CI) for Hodgkin’s and non-Hodgkin lymphomas based on rates of national cancer incidence. Findings Of 87,435 women who underwent conisation (1978–2011), we noted an increased incidence of Hodgkin’s lymphomas (standardised incidence ratio [SIR] 1.48, 95% CI 1.05–2.02), but only a slight increase in incidence for non-Hodgkin lymphoma (SIR 1.10, 95% CI 0.97–1.25). Interpretation HPV infection, as measured by conisation, is associated with an increased risk of lymphoma. This association may be attributable to a chronic immune activation induced by persistent HPV infection or poor clearance of HPV.

Background We investigated temporal trends in treatment, and factors influencing treatment receipt and survival, for upper gastrointestinal cancers in routine community-based clinical practice. Patients and methods Oesophageal and gastric-cardia cancers, diagnosed during the period 1994–2001, were sourced from the National Cancer Registry (Ireland). Analysis was by Joinpoint regression and multivariate logistic and Cox models. Results Thirty-five percent of patients received surgery, 35% radiotherapy and 24% chemotherapy. Over time chemo- and radiotherapy receipt increased significantly, whilst surgery decreased. Treatment patterns varied by tumour site, histology and stage. Older and/or unmarried patients were significantly less likely to receive treatment. Among surgically treated patients, those aged 70+ had higher mortality. Among both surgical and non-surgical patients, those receiving chemotherapy or radiotherapy had a modest, short-term, survival benefit. Conclusions The use of adjuvant therapies is increasing in routine practice. After adjusting for clinical factors, patient-related factors predicted treatment and mortality. Improving equity in gastrointestinal cancer treatment may help improve survival.

Statins may affect non-cardiovascular endpoints, including cancer incidence and survival. These effects may depend on the solubility of the specific medicine. Our objective was to measure the association between post-diagnosis lipophilic and hydrophilic statin use and recurrence among non-metastatic breast cancer patients. We ascertained incident cases of stage I-III invasive breast cancer diagnosed in Denmark between 1996 and 2006 from the Danish Breast Cancer Cooperative Group registry, and linked these records to the Register of Medicinal Products (RMP), which automatically logs pharmacy transactions in Denmark. We determined statin prescriptions filled by cohort members by searching the RMP for appropriate ATC codes. Statins were classified by solubility (Table 1) and exposure status was updated yearly. Follow-up began upon completion of primary therapy and continued until the first of breast cancer recurrence, death from any cause, emigration from Denmark, or the end of 2006. Associations were estimated with time-dependent crude and multivariate Cox regression models. We enrolled 18,769 breast cancer patients, with a median follow-up of 6.2 years. Of the 3,282 women ever prescribed a statin after diagnosis, 2,518 were exclusively prescribed lipophilic statins and 210 were exclusively prescribed hydrophilic statins. Crude and multivariate models yielded similar estimates. Lipophilic (but not hydrophilic) statin use was associated with a reduced rate of breast cancer recurrence (compared with no statin use: multivariate HR for lipophilic statin use = 0.65, 95% CI: 0.55, 0.76; multivariate HR for hydrophilic statin use = 0.89, 95% CI: 0.61, 1.3). Associations were similar when estimated in the subset of women with no pre-diagnosis statin exposure. In this population-based prospective cohort study with complete information on prognostic and treatment variables, breast cancer patients who took lipophilic statins had a reduced rate of breast cancer recurrence. (a) Hazard ratios adjusted for age, menopausal status, tumor stage, ER status, adjuvant hormonal therapy, type of surgery, comorbidity, and co-prescription of aspirin. Estimates were similar in models further adjusted for chemotherapy, type of surgery, receipt of radiotherapy, and co-prescription of hormone replacement therapy, NSAIDs, anticoagulants and ACE inhibitors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4678. doi:10.1158/1538-7445.AM2011-4678

9604 Background: Although venous thromboembolism (VTE) is recognized as a serious complication of malignancy, population-based data on the incidence of VTE in cancer, particularly by site and stage...

Udgivelsesdato: 2010-Mar-1 ABSTRACT: INTRODUCTION: Non-steroidal anti-inflammatory drugs (NSAIDs) prevent the growth of mammary tumours in animal models. Two population-based case-control studies suggest a reduced risk of breast cancer associated with selective cyclooxygenase-2 (sCox-2) inhibitor use, but data regarding the association between breast cancer occurrence and use of non-selective NSAIDs are conflicting. METHODS: We conducted a population-based case-control study using Danish healthcare databases to examine if use of NSAIDs, including sCox-2 inhibitors, was associated with a reduced risk of breast cancer. We included 8,195 incident breast cancer cases diagnosed in 1991 through 2006 and 81,950 population controls. RESULTS: Overall, we found no reduced breast cancer risk in ever users (>2 prescriptions) of sCox-2 inhibitors (odds ratio (OR) = 1.08, 95% confidence interval (95% CI) = 0.99, 1.18), aspirin (OR = 0.98, 95% CI = 0.90-1.07), or non-selective NSAIDs OR = 1.04, (95% CI = 0.98, 1.10)). Recent use (>2 prescriptions within two years of index date) of sCox-2 inhibitors, aspirin, or non-selective NSAIDs was likewise not associated with breast cancer risk (Ors = 1.06 (95% CI = 0.96, 1.18), 0.96 (95% CI = 0.87, 1.06) and 0.99 (95% CI = 0.85, 1.16), respectively). Risk estimates by duration (