Myocardial infarction risk and tamoxifen therapy for breast cancer

Tamoxifen prevents recurrence after breast cancer and breast cancer among high-risk women, and may prevent myocardial infarction (MI). To assess the impact of tamoxifen on MI risk, we conducted a case–control study of first MI after breast cancer nested among women diagnosed with breast cancer, while enrolled in a health maintenance organisation from 1980 to 2000. We obtained information on breast cancer treatment and MI risk factors through medical record reviews and interviews. Data were analysed using conditional logistic regression. Of 11 045 women with breast cancer, 134 met MI criteria and were matched to two MI-free control subjects on year of birth and breast cancer diagnosis. After adjusting for smoking, hypertension and diabetes, tamoxifen was unassociated with MI (odds ratio (OR)=1.2, 95% confidence interval (CI)=0.7–1.9). Duration, cumulative dose and recency of use were not associated with MI. Radiation therapy was associated with MI (OR=2.0, 95% CI=1.1–3.5), an association that varied slightly but not statistically significantly by tamoxifen use (radiation with tamoxifen, OR=2.0, 95% CI=0.9–4.4; radiation without tamoxifen, OR=2.9, 95% CI=1.2–7.5). Tamoxifen treatment for breast cancer does not appear to increase or decrease MI risk, although radiation therapy appears to increase MI risk

Residence, income and cancer hospitalizations in British Columbia during a decade of policy change

BACKGROUND: Through the 1990s, governments across Canada shifted health care funding allocation and organizational foci toward a community-based population health model. Major concerns of reform based on this model include ensuring equitable access to health and health care, and enhancing preventive and community-based resources for care. Reforms may act differentially relative to specific conditions and services, including those geared to chronic versus acute conditions. The present study therefore focuses on health service utilization, specifically cancer hospitalizations, in British Columbia during a decade of health system reform. METHODS: Data were drawn from the British Columbia Linked Health Data resource; income measures were derived from Statistics Canada 1996 Census public use enumeration area income files. Records with a discharge (separation) date between 1 January 1991 and 31 December 1998 were selected. All hospitalizations with ICD-9 codes 140 through 208 (except skin cancer, code 173) as principal diagnosis were included. Specific cancers analyzed include lung; colorectal; female breast; and prostate. Hospitalizations were examined in total (all separations), and as divided into first and all other hospitalizations attributed to any given individual. Annual trends in age-sex adjusted rates were analyzed by joinpoint regression; longitudinal multivariate analyses assessing association of residence and income with hospitalizations utilized generalised estimating equations. Results are evaluated in relation to cancer incidence trends, health policy reform and access to care. RESULTS: Age-sex adjusted hospitalization rates for all separations for all cancers, and lung, breast and prostate cancers, decreased significantly over the study period; colorectal cancer separations did not change significantly. Rates for first and other hospitalizations remained stationary or gradually declined over the study period. Area of residence and income were not significantly associated with first hospitalizations; effects were less consistent for all and other hospitalizations. No interactions were observed for any category of separations. CONCLUSIONS: No discontinuities were observed with respect to total hospitalizations that could be associated temporally with health policy reform; observed changes were primarily gradual. These results do not indicate whether equity was present prior to health care reform. However, findings concur with previous reports indicating no change in access to health care across income or residence consequent on health care reform

Tangential beam IMRT versus tangential beam 3D-CRT of the chest wall in postmastectomy breast cancer patients: A dosimetric comparison

<p>Abstract</p> <p>Background</p> <p>This study evaluates the dose distribution of reversed planned tangential beam intensity modulated radiotherapy (IMRT) compared to standard wedged tangential beam three-dimensionally planned conformal radiotherapy (3D-CRT) of the chest wall in unselected postmastectomy breast cancer patients</p> <p>Methods</p> <p>For 20 unselected subsequent postmastectomy breast cancer patients tangential beam IMRT and tangential beam 3D-CRT plans were generated for the radiotherapy of the chest wall. The prescribed dose was 50 Gy in 25 fractions. Dose-volume histograms were evaluated for the PTV and organs at risk. Parameters of the dose distribution were compared using the Wilcoxon matched pairs test.</p> <p>Results</p> <p>Tangential beam IMRT statistically significantly reduced the ipsilateral mean lung dose by an average of 21% (1129 cGy versus 1437 cGy). In all patients treated on the left side, the heart volume encompassed by the 70% isodose line (V70%; 35 Gy) was reduced by an average of 43% (5.7% versus 10.6%), and the mean heart dose by an average of 20% (704 cGy versus 877 cGy). The PTV showed a significantly better conformity index with IMRT; the homogeneity index was not significantly different.</p> <p>Conclusions</p> <p>Tangential beam IMRT significantly reduced the dose-volume of the ipsilateral lung and heart in unselected postmastectomy breast cancer patients.</p

Safety of aromatase inhibitors in the adjuvant setting

The third-generation aromatase inhibitors (AIs) letrozole, anastrozole, and exemestane are replacing tamoxifen as adjuvant therapy in most postmenopausal women with early breast cancer. Although AIs have demonstrated superior efficacy and better overall safety compared with tamoxifen in randomized controlled trials, they may not provide the cardioprotective effects of tamoxifen, and bone loss may be a concern with their long-term adjuvant use. Patients require regular bone mineral density monitoring, and prophylactic bisphosphonates are being evaluated to determine whether they may protect long-term bone health. AIs decrease the risks of thromboembolic and cerebrovascular events compared with tamoxifen, and the overall rate of cardiovascular events in patients treated with AIs is within the range seen in age-matched, non-breast-cancer populations. AIs are also associated with a lower incidence of endometrial cancer and fewer vaginal bleeding/discharge events than tamoxifen. Compared with tamoxifen, the incidence of hot flashes is lower with anastrozole and letrozole but may be higher with exemestane. Generally, adverse events with AIs are predictable and manageable, whereas tamoxifen may be associated with life-threatening events in a minority of patients. Overall, the benefits of AIs over tamoxifen are achieved without compromising overall quality of life

Using physician-linked mailed invitations in an organised colorectal cancer screening programme: effectiveness and factors associated with response

OBJECTIVES: A central tenet of organised cancer screening is that all persons in a target population are invited. The aims of this study were to identify participant and physician factors associated with response to mailed physician-linked invitations (study 1) and to evaluate their effectiveness in an organised colorectal cancer (CRC) screening programme (study 2). DESIGN AND SETTING: 2 studies (study 1-cohort design and study 2-matched cohort design, comprising study 1 participants and a matched control group) were conducted in the context of Ontario's organised province-wide CRC screening programme. PARTICIPANTS: 102 family physicians and 11 302 associated eligible patients from a technical evaluation ('the Pilot') of large-scale mailed invitations for CRC screening were included. Matched controls were randomly selected using propensity scores from among eligible patients associated with family physicians in similar practice types as the Pilot physicians. INTERVENTION: Physician-linked mailed invitation to have CRC screening. OUTCOMES: Uptake of faecal occult blood test (FOBT) within 6 months of mailed invitation (primary) and uptake of FOBT or colonoscopy within 6 months of mailed invitation (secondary). RESULTS: Factors significantly associated with uptake of FOBT included prior FOBT use, older participant age, greater participant comorbidity and having a female physician. In the matched analysis, Pilot participants were more likely to complete an FOBT (22% vs 8%, p<0.0001) or an FOBT or colonoscopy (25% vs 11%, p<0.0001) within 6 months of mailed invitation than matched controls. The number needed to invite to screen one additional person was 7. CONCLUSIONS: Centralised large-scale mailing of physician-linked invitations is feasible and effective in the context of organised CRC screening

Morbidity and mortality after major large bowel resection of non-malignant polyp among participants in a population-based screening program

BACKGROUND AND AIMS: Colonoscopy following positive fecal occult blood screening may detect non-malignant polyps deemed to require major large bowel resection. We aimed to estimate the major inpatient morbidity and mortality associated with major resection of non-malignant polyps detected at colonoscopy following positive guaiac fecal occult blood screening in Ontario's population-based colorectal screening program. METHODS: We identified those without a diagnosis of colorectal cancer in the Ontario Cancer Registry ≤24 months following the date of colonoscopy prompted by positive fecal occult blood screening between 2008 and 2017, who underwent a major large bowel resection ≤24 months after the colonoscopy, with a diagnosis code for non-malignant polyp, in the absence of a code for any other large bowel diagnosis. We extracted records of major inpatient complications and readmissions ≤30 days following resection. We computed mortality within 90 days following resection. RESULTS: For those undergoing colonoscopy ≤6 months following positive guaiac fecal occult blood screening, 420/127,872 (0.03%) underwent major large bowel resection for a non-malignant polyp. In 50/420 (11.9%), the resection included one or more rectosigmoid or rectal polyps, with or without a colonic polyp. There were one or more major inpatient complications or readmissions within 30 days in 117/420 (27.9%). Death occurred within 90 days in 6/420 (1.4%). CONCLUSIONS: Serious inpatient complications and readmissions following major large bowel resection for non-malignant colorectal polyps are common, but mortality ≤90 days following resection is low. These outcomes should be considered as unintended adverse consequences of population-based colorectal screening programs

A population-based case-cohort study of the risk of myocardial infarction following radiation therapy for breast cancer.

OBJECTIVE: To describe the risk of acute myocardial infarction (AMI) after radiation therapy (RT) for breast cancer (BrCa) in an exposed population. METHODS: We identified and validated cases of AMI (vAMI), by electrocardiographic or enzyme criteria, among all 6680 women who received post-operative RT following lumpectomy or mastectomy, within 12 months following diagnosis of BrCa between 1982 and 1988 in Ontario, Canada. We identified women without vAMI whose death certification was ascribed to AMI (dAMI). We abstracted risk factors and treatment exposures for a random sample of women from the 6680, and for all with vAMI or dAMI. The hazards of vAMI and of dAMI were estimated using multivariate Cox proportional hazards models, corrected for study design. RESULTS: We validated 121 cases of vAMI and identified 92 cases of dAMI. The risk of vAMI associated with RT to the left breast HR=1.96 (1.09,3.54) among women at age &gt;/= 60 at time of RT, adjusted for history of smoking and prior MI. The adjusted HR dAMI=1.90 (1.08,3.35) for exposure to anterior internal mammary node (IMC) RT. Among women who received anterior left breast boost RT, increasing area of the boost is associated with adjusted HR vAMI=1.02 (1.00,1.03)/cm(2), and adjusted HR dAMI=1.02 (1.01,1.03)/cm(2). CONCLUSION: The risks of vAMI and dAMI following RT for BrCa are related to anatomic sites of RT (left breast, area of anterior left breast boost field, and anterior IMC field)

Evaluating the impact of public health initiatives on trends in fecal occult blood test participation in Ontario

BACKGROUND: Since the publication of two randomized controlled trials (RCT) in 1996 demonstrating the effectiveness of fecal occult blood test (FOBT) in reducing colorectal cancer (CRC) mortality, several public health initiatives have been introduced in Ontario to promote FOBT participation. We examined the effect of these initiatives on FOBT participation and evaluated temporal trends in participation between 1994 and 2012. METHOD: Using administrative databases, we identified 18 annual cohorts of individuals age 50 to 74 years eligible for CRC screening and identified those who received FOBT in each quarter of a year. We used negative binomial segmented regression to examine the effect of initiatives on trends and Joinpoint regression to evaluate temporal trends in FOBT participation. RESULTS: Quarterly FOBT participation increased from 6.5 per 1000 in quarter 1 to 41.6 per 1000 in quarter 72 (January-March 2012). Segmented regression indicated increases following the publication of the RCTs in 1996 (Δ slope = 6%, 95% CI = 4.3-7.9), the primary care physician financial incentives announcement in 2005 (Δ slope = 2.2%, 95% CI = 0.68-3.7), the launch of the ColonCancerCheck (CCC) Program (Δ intercept = 35.4%, 95% CI = 18.3 -54.9), and the CCC Program 2-year anniversary (Δ slope = 7.2%, 95% CI = 3.9 - 10.5). Joinpoint validated these findings and identified the specific points when changes occurred. CONCLUSION: Although observed increases in FOBT participation cannot be definitively attributed to the various initiatives, the results of the two statistical approaches suggest a causal association between the observed increases in FOBT participation and most of these initiatives