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Parameter estimates for invasive breast cancer progression in the Canadian National Breast Screening Study.

ABSTRACT: The aim of screening is to detect a cancer in the preclinical state. However, a false-positive or a false-negative test result is a real possibility.We describe invasive breast cancer progression in the Canadian National Breast Screening Study and construct progression models with and without covariates. The effect of risk factors on transition intensities and false-negative probability is investigated. We estimate the transition rates, the sojourn time and sensitivity of diagnostic tests for women aged 40-49 and 50-59.Although younger women have a slower transition rate from healthy state to preclinical, their screen-detected tumour becomes evident sooner. Women aged 50-59 have a higher mortality rate compared with younger women. The mean sojourn times for women aged 40-49 and 50-59 are 2.5 years (95% CI: 1.7, 3.8) and 3.0 years (95% CI: 2.1, 4.3), respectively. Sensitivity of diagnostic procedures for older women is estimated to be 0.75 (95% CI: 0.55, 0.88), while women aged 40-49 have a lower sensitivity (0.61, 95% CI: 0.42, 0.77). Age is the only factor that affects the false-negative probability. For women aged 40-49, 'age at entry', 'history of breast disease' and 'families with breast cancer' are found to be significant for some of the transition rates. For the age-group 50-59, 'age at entry', 'history of breast disease', 'menstruation length' and 'number of live births' are found to affect the transition rates.Modelling and estimating the parameters of cancer progression are essential steps towards evaluating the effectiveness of screening policies. The parameters include the transition rates, the preclinical sojourn time, the sensitivity, and the effect of different risk factors on cancer progression.

SUBMITTER: Taghipour S

PROVIDER: S-EPMC3593551 | biostudies-other | 2013 Feb

REPOSITORIES: biostudies-other

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Project description:BackgroundTBX3 is a T-box transcription factor repressor that is elevated in metastatic breast cancer and is believed to promote malignancy of tumor cells, possibly by promoting cell survival and epithelial-mesenchymal transition.MethodsThe relative expression of TBX3 was assessed in the 21T cell lines which were derived from an individual patient and represent three distinct stages of breast cancer progression: 21PT, atypical ductal hyperplasia; 21NT, ductal carcinoma in situ; and 21MT-1, invasive mammary carcinoma. Two different isoforms of TBX3 (TBX3iso1 and TBX3iso2) were overexpressed to evaluate cell survival/colony forming ability, growth, and invasion in the ductal carcinoma in situ-like 21NT cell line using an in vitro Matrigel model of cancer progression. In addition, TBX3 expression was knocked down to evaluate the effects of downregulating TBX3 on the invasive mammary carcinoma-like 21MT-1 cell line. Finally, PCR array profiling was used to assess alterations in gene expression due to TBX3 overexpression in the 21NT cells.ResultsTBX3 is abundant in the invasive 21MT-1 cell line, while being minimally expressed in the non-invasive 21NT and 21PT cell lines. Overexpression of either TBX3iso1 or TBX3iso2 in 21NT cells resulted in increased cell survival/colony forming ability, growth vs. apoptosis and invasion in Matrigel. In contrast, short hairpin RNA-mediated knockdown of TBX3 in the 21MT-1 cells resulted in smaller colonies, with a more regular, less dispersed (less infiltrative) morphology. Array profiling of the 21NT TBX3 iso1 and iso2 transfectants showed that there are common alterations in expression of several genes involved in signal transduction, cell cycle control/cell survival, epithelial-mesenchymal transition and invasiveness.ConclusionsOverall, these results indicate that TBX3 (isoform 1 or 2) expression can promote progression in a model of early breast cancer by altering cell properties involved in cell survival/colony formation and invasiveness, as well as key regulatory and EMT/invasiveness-related gene expressions.

Project description:BackgroundCancer screening guidelines reflect the costs and benefits of population-based screening based on evidence from clinical trials. While most of the existing literature on compliance with cancer screening guidelines only measures raw screening rates in the target age groups, we used a novel approach to estimate degree of guideline compliance across Canadian provinces for breast, colorectal and prostate cancer screening. Measuring compliance as the change in age-specific screening rates at the guideline-recommended initiation age (50), we generally found screening patterns across Canadian provinces that were not consistent with guideline compliance.MethodsWe calculated age-cancer-specific screening rates for ages 40-60 using the Canadian Community Health Survey (2003 and 2005), a cross-sectional, nationally representative survey of health status, health care utilization and health determinants in the Canadian population. We estimated the degree of compliance using logistic regression to measure the change in adjusted screening rates at the guideline-recommended initiation age for each province in the sample.ResultsFor breast cancer, after adjusting for age trends and other covariates, being above age 50 in Quebec increased the probability of being screened by 19 percentage points, from an average screening rate of 24% among 40-49 year olds. None of the other regions exhibited a statistically significant change in screening rates at age 50. Additional analyses indicated that these patterns reflect asymptomatic screening and that Quebec's breast cancer screening program enhanced the degree of guideline compliance in that province. Colorectal cancer screening practice was consistent with guidelines only in Saskatchewan, as screening rates increased at age 50 by 12 percentage points, from an average rate of 6% among 40-49 year olds. For prostate cancer, the regions examined here are not compliant with Canadian guidelines since screening rates were quite high, and there was not a discrete increase at any particular age.ConclusionsScreening practice for breast, colorectal and prostate cancer was generally not consistent with Canadian clinical guidelines. Quebec (breast) and Saskatchewan (colorectal) were exceptions to this, and the impact of Quebec's breast cancer screening program suggests a role for policy in improving screening guideline compliance.

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Parameter estimates for invasive breast cancer progression in the Canadian National Breast Screening Study.

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