Tumor size distribution of invasive breast cancers and the sensitivity of screening methods in the Canadian National Breast Screening Study.

INTRODUCTION: This study set out to explore if breast cancers of different sizes are detected with varying sensitivity. In addition, we attempt to determine the effect of tumor size on screening detectability. SUBJECTS AND METHODS: Data arising from the Canadian National Breast Screening Study (CNBSS) was used to perform all analyses. The CNBSS consists of two randomized controlled trials, which includes data on detection methods, age, and allocation groups. We stratified tumor size by 5 mm; age into 40-49 and 50-59 years age groups; and cancer detection or presentation methods into mammography only, physical breast examination only, both mammography and physical breast examination, interval cancers, and incident cancers. RESULTS: This study revealed that a difference in tumor size exists for age (smaller tumor sizes are found in older women) and breast cancer detection or presentation modes. More specifically, breast cancers detected by mammography screening are statistically smaller than those detected by physical breast examination or those presenting as incident or interval cancers. This study also found that tumor size affects screening detectability for women in their 50's but not in their forties. That is, a statistically significant difference between mammography screening alone and physical examination alone was observed for women between the ages of 50-59 for tumor sizes up to 20 mm, including prevalent cases, and up to 15 mm when prevalent cases were excluded. CONCLUSION: The results of this study suggest that smaller breast cancers are more likely to be detected among women in their 50s.

Predictors of competing mortality to invasive breast cancer incidence in the Canadian National Breast Screening study.

BACKGROUND: Evaluating the cost-effectiveness of breast cancer screening requires estimates of the absolute risk of breast cancer, which is modified by various risk factors. Breast cancer incidence, and thus mortality, is altered by the occurrence of competing events. More accurate estimates of competing risks should improve the estimation of absolute risk of breast cancer and benefit from breast cancer screening, leading to more effective preventive, diagnostic, and treatment policies. We have previously described the effect of breast cancer risk factors on breast cancer incidence in the presence of competing risks. In this study, we investigate the association of the same risk factors with mortality as a competing event with breast cancer incidence. METHODS: We use data from the Canadian National Breast Screening Study, consisting of two randomized controlled trials, which included data on 39 risk factors for breast cancer. The participants were followed up for the incidence of breast cancer and mortality due to breast cancer and other causes. We stratified all-cause mortality into death from other types of cancer and death from non-cancer causes. We conducted separate analyses for cause-specific mortalities. RESULTS: We found that "age at entry" is a significant factor for all-cause mortality, and cancer-specific and non-cancer mortality. "Menstruation length" and "number of live births" are significant factors for all-cause mortality, and cancer-specific mortality. "Ever noted lumps in right/left breasts" is a factor associated with all-cause mortality, and non-cancer mortality. CONCLUSIONS: For proper estimation of absolute risk of the main event of interest common risk factors associated with competing events should be identified and considered.

Incidence of invasive breast cancer in the presence of competing mortality: the Canadian National Breast Screening Study.

Mortality due to causes other than breast cancer is a potential competing risk which may alter the incidence probability of breast cancer and as such should be taken into account in predictive modelling. We used data from the Canadian National Breast Screening Study (CNBSS), which consist of two randomized controlled trials designed to evaluate the efficacy of mammography among women aged 40-59. The participants in the CNBSS were followed up for incidence of breast cancer and mortality due to breast cancer and other causes; this allowed us to construct a breast cancer risk prediction model while taking into account mortality for the same study population. In this study, we use 1980-1989 as the study period. We exclude the prevalent cancers from the CNBSS to estimate the probability of developing breast cancer, given the fact that women were cancer-free at the beginning of the follow-up. By the end of 1989, from 89,434 women, 944 (1.1 %) were diagnosed with invasive breast cancer, 922 (1.0 %) died from causes other than breast cancer, and 87,568 (97.9 %) were alive and not diagnosed with invasive breast cancer. We constructed a risk prediction model for invasive breast cancer based on 39 risk factors collected at the time of enrolment or the initial physical examination of the breasts. Age at entry (HR 1.07, 95 % CI 1.05-1.10), lumps ever found in left or right breast (HR 1.92, 95 % CI 1.19-3.10), abnormality in the left breast (HR 1.26, 95 % CI 1.07-1.48), history of other breast disease, family history of breast cancer score (HR 1.01, 95 % CI 1.00-1.01), years menstruating (HR 1.02, 95 % CI 1.01-1.03) and nulliparity (HR 1.70, 95 % CI 1.23-2.36) are the model's predictors. We investigated the effects of time-dependent factors. The model is well calibrated with a moderate discriminatory power (c-index 0.61, 95 % CI 0.59-0.63); we use it to predict the 9-year risk of developing breast cancer for women of different age groups. As an example, we estimated the probability of invasive cancer at 5 years after enrolment to be 0.00448, 0.00556, 0.00691, 0.00863, and 0.01034, respectively, for women aged 40, 45, 50, 55, and 59, all of whom had never noted lumps in their breasts, had 32 years of menstruating, 1-2 live births, no other types of breast disease and no abnormality found in their left breasts. The results of this study can be used by clinicians to identify women at high risk of breast cancer for screening intervention and to recommend a personalized intervention plan. The model can be also utilized by a woman as a breast cancer risk prediction tool.

Dynamics of fluorescence depolarisation in star-shaped oligofluorene-truxene molecules.

Star-shaped molecules are of growing interest as organic optoelectronic materials. Here a detailed study of their photophysics using fluorescence depolarisation is reported. Fluorescence depolarisation dynamics are studied in branched oligofluorene-truxene molecules with a truxene core and well-defined three-fold symmetry, and are compared with linear fluorene oligomers. An initial anisotropy value of 0.4 is observed which shows a two-exponential decay with time constants of 500 fs and 3-8 ps in addition to a long-lived component. The femtosecond component is attributed to exciton localisation on one branch of the molecule and its amplitude reduces when the excitation is tuned to the low energy tail of the absorption spectrum. The picosecond component shows a weak dependence on the excitation wavelength and is similar to the calculated rate of the resonant energy transfer of the localised exciton between the branches. These assignments are supported by density-functional theory calculations which show a disorder-induced splitting of the two degenerate excited states. Exciton localisation is much slower than previously reported in other branched molecules which suggests that efficient light-harvesting systems can be designed using oligofluorenes and truxenes as building blocks.

Optimizing Canadian breast cancer screening strategies: a perspective for action.

While controversies regarding optimal breast cancer screening modalities, screening start and end ages, and screening frequencies continue to exist, additional population-based randomized trials are unlikely to be initiated to examine these concerns. Simulation models have been used to evaluate the efficacy and effectiveness of various breast cancer screening strategies, however these models were all developed using US data. Currently, there is a need to examine the optimal screening and treatment policies in the Canadian context. In this commentary, we discuss the current controversies pertaining to breast cancer screening, and describe the fundamental components of a simulation model, which can be used to inform breast cancer screening and treatment policies.

Optical excitations in star-shaped fluorene molecules.

A detailed study of the low-energy optical transitions in two families of star-shaped molecules is presented. Both families have 3-fold rotational symmetry with oligofluorene arms attached to a central core. In one family, the core of the molecule is a rigid meta-linked truxene, while the other is a meta-linked benzene moiety. The low-energy transitions were studied both experimentally and using time-dependent density functional theory (TD-DFT). The optical transitions of these new star-shaped molecules were compared with corresponding linear oligofluorenes. Both families of star-shaped molecules showed higher absorption and fluorescence dipoles and photoluminescence quantum yields than straight chain oligofluorenes. TD-DFT calculations show that absorption takes place across the entire molecule, and after excited state relaxation, the emission results from a single arm. In both theory and experiment the transition dipole moments show an approximate n(0.5) dependence on the number of fluorene units in each arm.

Semiconducting polymer waveguides for end-fired ultra-fast optical amplifiers.

A method to fabricate conjugated polymer waveguides with well defined edge facets is demonstrated. The utility of the approach is explored for application as end-fired ultrafast optical amplifiers based on poly(9,9'-dioctylfluorene-co-benzothiadiazole). An internal gain of 19 dB was achieved on a 760 microm long waveguide at 565 nm wavelength. This fabrication procedure may be applied to a wide range of conjugated polymers and organic light-emitting devices, providing an important step towards future applications of organic integrated photonics.

Effect of exciton self-trapping and molecular conformation on photophysical properties of oligofluorenes.

Electronic absorption and fluorescence transitions in fluorene oligomers of differing lengths are studied experimentally and using density functional theory (DFT) and time-dependent DFT. Experimental values are determined in two ways: from the measured molar absorption coefficient and from the radiative rate deduced from a combination of fluorescence quantum yield and lifetime measurements. Good agreement between the calculated and measured transition dipoles is achieved. In both theory and experiment a gradual increase in transition dipoles with increasing oligomer length is found. In absorption the transition dipole follows an approximately n(0.5) dependence on the number of fluorene units n for the range of 2 < or = n < or = 12, whereas a clear saturation of the transition dipole with oligomer length is found in fluorescence. This behavior is attributed to structural relaxation of the molecules in the excited state leading to localization of the excitation (exciton self-trapping) in the middle of the oligomer for both twisted and planar backbone conformations. Twisted oligofluorene chains were found to adopt straight or bent geometries depending on alternation of the dihedral angle between adjacent fluorene units. These different molecular conformations show the same values for the transition energies and the magnitude of the transition dipole.