Lorraine Shack

Risk of cancer other than breast or ovarian in individuals with BRCA1 and BRCA2 mutations

The risks of cancers other than breast and ovarian amongst BRCA1 and BRCA2 mutation carriers are based on relatively few family based studies with the risk of specific cancers tested in population based samples of cancers from founder populations. We assessed risks of “other cancers” in 268 BRCA1 families and 222 BRCA2 families using a person years at risk analysis from 1975 to 2005. Cancer confirmations were overall higher than in previous family based studies at 64%. There was no overall increase in risk for BRCA1 carriers although oesophagus had a significant increased RR of 2.9 (95% CI 1.1–6.0) and stomach at 2.4 (95% CI 1.2–4.3), these were based mainly on unconfirmed cases. For BRCA2 increased risks for cancers of the pancreas (RR 4.1, 95% CI 1.9–7.8) and prostate (RR 6.3, 95% CI 4.3–9.0) and uveal melanoma (RR 99.4, 95% CI 11.1–359.8) were confirmed. Possible new associations with oesophagus (RR 4.1, 95% CI 1.9–7.8) and stomach (RR 2.7, 95% CI 1.3–4.8) were detected but these findings should be treated with caution due to lower confirmation rates. In contrast to previous research a higher risk of prostate cancer was found in males with mutations in the BRCA2 OCCR region. The present study strengthens the known links between BRCA2 and pancreatic and prostate cancer, but throws further doubt onto any association with BRCA1. New associations with upper gastro-intestinal malignancy need to be treated with caution and confirmed by large prospective studies.

Cure by age and stage at diagnosis for colorectal cancer patients in North West England, 1997-2004: A population-based study

BACKGROUNDnStage and age at diagnosis are important prognostic factors for patients with colorectal cancer. However, the proportion cured by stage and age is unknown in England.nnnMATERIALS AND METHODSnThis population-based study includes 29,563 adult patients who were diagnosed and registered with colorectal cancer during 1997-2004 and followed till 2007 in North West England. Multiple imputation was used to provide more reliable estimates of stage at diagnosis, when these data were missing. Cure mixture models were used to estimate the proportion cured and the median survival of the uncured by age and stage.nnnRESULTSnFor both colon and rectal cancer the proportion of patients cured and median survival time of the uncured decreased with advancing stage and increasing age. Patients aged under 65 years had the highest proportion cured and longest median survival of the uncured.nnnCONCLUSIONnCure of colorectal cancer patients is dependent on stage and age at diagnosis with younger patients or those with less advanced disease having a better prognosis. Further efforts are required, in order to reduce the proportion of patients presenting with stage III and IV disease and ultimately increase the chance of cure.

Trends in the incidence of human papillomavirus–related noncervical and cervical cancers in Alberta, Canada: a population-based study

INTRODUCTIONnRecent epidemiologic studies have suggested that the incidence of noncervical cancers associated with human papillomavirus (HPV) is increasing. We assessed temporal, age-specific and sex-specific changes in the incidence of HPV-associated cancers in a population-based study.nnnMETHODSnWe used the Alberta Cancer Registry, a registry of all cancers diagnosed in the province of Alberta, Canada, to identify patients with cancers of the oropharynx, cervix, vulva, vagina, anus and penis (cancers associated with HPV) between Jan. 1, 1975, and Dec. 31, 2009. We estimated the age-standardized incidence of each cancer by sex- and age-specific group and assessed the annual percentage change using joinpoint regression.nnnRESULTSnThe age-standardized incidence of oropharyngeal cancers increased for each 5-year interval of the study period among men (annual percentage change 3.4, pxa0<xa00.001) and women (annual percentage change 1.5, pxa0=xa00.009). For anal cancers, the age-standardized rates increased among women (annual percentage change 2.2, pxa0<xa00.001) and men (annual percentage change 1.8, pxa0=xa00.008). The age-standardized incidence of cervical cancer increased with age, reaching an annual percentage change of -3.5 among women aged 75-84 years (p = 0.04). The rates of other HPV-associated cancers (vulvar, vaginal and penile) showed little change.nnnINTERPRETATIONnOur findings showed increases in the incidence of the HPV-associated cancers of the oropharynx and anus among men and women, and increases in cervical cancer among younger women. The incidence of HPV-related cancers in younger age groups should continue to be monitored. Programs to prevent HPV infection, such as vaccination, should be considered for males as well as females.

Conditional relative survival: a different perspective to measuring cancer outcomes.

Lorraine Shack *, Heather Bryant , Gina Lockwood , Larry F. Ellison d a Population and Public Health, Alberta Health Services, Calgary, Canada Divisions of Oncology and Community Health Sciences, University of Calgary, Calgary, Canada Canadian Partnership Against Cancer, 1 University Ave., Suite 300, Toronto, ON M5J 2P1, Canada Health Statistics Division, Statistics Canada, Ottawa, ON, Canada

Determining the need and utilization of radiotherapy in cancers of the breast, cervix, lung, prostate and rectum: A population level study

PURPOSEnDetermining the appropriate rate of radiotherapy (RT) utilization is important for health care planning and resource allocation. The difference between the observed and the appropriate RT rate is influenced by the choice of a criterion based benchmarking (CBB) or evidence-based estimates (EBEST) measure. Our primary objective was to determine the utilization of radiotherapy for cancers of the breast (B), cervix (C), lung (L), prostate (P) and rectum (R) in Alberta (AB) Canada and to compare the observed RT rates to estimates of need derived from the criterion based benchmarking (CBB) and evidence-based estimates (EBEST).nnnMATERIALS AND METHODSnAll incident cases of B,C,L,P and R cancers diagnosed in AB during 2004-8 (prior to the decentralization of provincial RT capacity) were identified from the Alberta Cancer Registry. Patients receiving RT within one year (RT-1y) of diagnosis were identified and the proportion receiving RT-1y was then calculated. Factors associated with RT utilization were analysed by region. Estimates of the need for RT were derived from CBB and EBEST methods in the literature.nnnRESULTSnA total of n=68,164 cancer cases were identified from the ACR. RT-1y rates (95% C.I.) were B: 51.5% (50.1-52.9), C: 48.9% (43.8-54.0), L: 37.1% (35.4-38.8), P: 26.9% (25.1-28.7) and R: 39.3% (36.5-42.1). Observed rates of RT in AB were lower than estimates derived using the CBB and EBEST estimates. Shortfalls varied across cancer sites according to whether a CBB or EBEST estimate was used ranging from a low of -0.3% in cancer of the cervix to a high of 30.3% in rectal cancer.nnnCONCLUSIONSnRT shortfalls exist in the utilization of RT in AB, Canada despite centralized cancer care and a publically funded health care system. Decisions to address shortfalls need to be mindful of how model selection can impact on findings.

Premature Mortality Due to Malignancies of the Central Nervous System in Canada, 1980–2010

Background: In this study, we investigated whether there has been an improvement in premature mortality due to central nervous system (CNS) cancers among the Canadian population from 1980 through 2010. Methods: Mortality data for CNS cancers were obtained from World Health Organization mortality database. Years of life lost (YLL) was estimated using Canadian life tables. Average lifespan shortened (ALSS) was calculated and defined as the ratio of YLL relative to the expected lifespan. Results: Over this study period, we observed decreases in age standardized rates to the World Standard Population for mortality due to CNS cancers from 5.3 to 4.1 per 100,000 men, and from 3.6 to 2.9 per 100,000 women. Average YLL decreased from 23.6 to 21.5 years of life among men, and from 27.0 to 23.1 years among women in 1980 and 2010, respectively. The ALSS showed that men with CNS cancers lost 30.1% of their life span and women lost 32.5% in 1980, whereas they lost 25.8 and 26.6% in 2010, respectively. Conclusion: Our study shows that Canadian people with CNS cancers have had their lives prolonged at the end of the study period.

Premature mortality due to breast cancer among Canadian women: an analysis of a 30-year period from 1980 through 2010

BackgroundnBreast cancer is the most commonly diagnosed cancer and the second most common cause of cancer deaths for women. In the present study, we examined the trend of premature mortality due to breast cancer among Canadian women from 1980 through 2010 and proposed a new measure of lifespan shortening.nnnMethodsnMortality data for female breast cancer was obtained from the World Health Organization mortality database. Years of life lost (YLL) was estimated using Canadian life tables. Average lifespan shortened (ALSS) that is calculated and expressed by a ratio of YLL relative to expected lifespan.nnnResultsnOver this study period, age-standardized rates of breast cancer mortality adjusted to World Standard Population decreased by 40% from 23.2 to 14.2 per 100 000 women. The adjusted YLL rates fell from 5.3 years per 1000 women to 3.3 years. On average women with breast cancer died 20.8 years prior to expected death in 1980 and 18.3 years early in 2010. A novel measure of lifespan shortening, the ALSS decreased from one-fourth of the lifespan in 1980 to one-fifth in 2010.nnnConclusionsnOur study reports that among Canadian women with breast cancer, a smaller proportion of life was lost on average at the end of the study period. The life lost measures presented in this study would be useful tools to monitor the pattern of premature mortality for chronic conditions. These measures gauge the effectiveness of the health system with respect to early detection and treatment.

Determining the need and utilization of radiotherapy in cancers of the breast, cervix, lung, prostate, and rectum in Alberta, Canada.

116 Background: Determining the appropriate rate of RT is important for health care planning and resource allocation. Establishing RT shortfalls (difference between observed and estimates of RT need) could provide an estimate of the capacity expansion that would be required to address them. Our primary objective was to determine the utilization of RT for cancers of the breast, cervix, lung, prostate and rectum in Alberta (AB), Canada. To determine the burden of RT shortfalls in AB, the secondary objective was to compare the observed AB RT rates to estimates of need derived from criterion-based benchmarking (CBB) and evidence-based estimates (EBEST).nnnMETHODSnAll incident cases of breast (B), cervix (C), lung (L), prostate (P) and rectal (R) cancers diagnosed in 2004-8 in AB were identified from the provincial cancer registry (ACR). Ethics board approval was obtained. Patients receiving RT within one year (RT-1y) of diagnosis were identified and grouped by cancer site. The proportion of cases receiving RT-1y was then calculated. Rates were compared using a Z statistic of the normal approximation for a difference in proportions. Estimates of the appropriate RT rate were derived from CBB and EBEST methods described in the literature.nnnRESULTSnA total of 68,164 cancer cases of interest were identified from the ACR. RT-1y rates for AB (95%CI) were: B: 50.5%(49.5-51.4), C: 45.7%(42.2-49.3), L: 36.5%(35.5-37.3), P:26.4%(25.6-27.3) and R:38.8%(37.1-40.6). Observed rates of RT in AB were lower than estimates derived using CBB and EBEST of RT-1y for B: 60.7%(59.3-62.1) and 57.1%(52.6-62.0), C: 48.6%(39.1-58.1) and 63.4%(61.1-65.7), L: 41.3%(39.9-42.7) and 44.6%(41.0-48.2), P: 37.2%(35.8-38.7) and 32.0%(28.4-36.0), and R: 43.4%(39.1-47.6) and 69.6%(68.7-70.5). Shortfalls varied across cancer sites according to whether CBB or EBEST estimates were referenced, ranging from 4.8% in lung cancer to 30.8% in rectal cancer.nnnCONCLUSIONSnImportant shortfalls exist in the utilization of RT in Alberta, Canada despite centralized cancer care and a publically funded health care system. The magnitude of the shortfall varied according to whether a CBB or EBEST estimate of RT was applied.