Interval Cancers In Screening Research Articles

A review of the influence of mammographic density on breast cancer clinical and pathological phenotype.

It is well established that high mammographic density (MD), when adjusted for age and body mass index, is one of the strongest known risk factors for breast cancer (BC), and also associates with higher incidence of interval cancers in screening due to the masking of early mammographic abnormalities. Increasing research is being undertaken to determine the underlying histological and biochemical determinants of MD and their consequences for BC pathogenesis, anticipating that improved mechanistic insights may lead to novel preventative or treatment interventions. At the same time, technological advances in digital and contrast mammography are such that the validity of well-established relationships needs to be re-examined in this context. With attention to old versus new technologies, we conducted a literature review to summarise the relationships between clinicopathologic features of BC and the density of the surrounding breast tissue on mammography, including the associations with BC biological features inclusive of subtype, and implications for the clinical disease course encompassing relapse, progression, treatment response and survival. There is reasonable evidence to support positive relationships between high MD (HMD) and tumour size, lymph node positivity and local relapse in the absence of radiotherapy, but not between HMD and LVI, regional relapse or distant metastasis. Conflicting data exist for associations of HMD with tumour location, grade, intrinsic subtype, receptor status, second primary incidence and survival, which need further confirmatory studies. We did not identify any relationships that did not hold up when data involving newer imaging techniques were employed in analysis.

A retrospective observational study examining the characteristics and outcomes of tumours diagnosed within and without of the English NHS Bowel Cancer Screening Programme

Background:Colorectal cancer is common in England and, with long-term survival relatively poor, improving outcomes is a priority. A major initiative to reduce mortality from the disease has been the introduction of the National Health Service (NHS) Bowel Cancer Screening Programme (BCSP). Combining data from the BCSP with that in the National Cancer Data Repository (NCDR) allows all tumours diagnosed in England to be categorised according to their involvement with the BCSP. This study sought to quantify the characteristics of the tumours diagnosed within and outside the BCSP and investigate its impact on outcomes.Methods:Linkage of the NCDR and BCSP data allowed all tumours diagnosed between July 2006 and December 2008 to be categorised into four groups; screen-detected tumours, screening-interval tumours, tumours diagnosed in non-participating invitees and tumours diagnosed in those never invited to participate. The characteristics, management and outcome of tumours in each category were compared.Results:In all, 76 943 individuals were diagnosed with their first primary colorectal cancer during the study period. Of these 2213 (2.9%) were screen-detected, 623 (0.8%) were screening-interval cancers, 1760 (2.3%) were diagnosed in individuals in non-participating invitees and 72 437 (94.1%) were diagnosed in individuals not invited to participate in the programme due to its ongoing roll-out over the time period studied. Screen-detected tumours were identified at earlier Dukes’ stages, were more likely to be managed with curative intent and had significantly better outcomes than tumours in other categories.Conclusion:Screen-detected cancers had a significantly better prognosis than other tumours and this would suggest that the BCSP should reduce mortality from colorectal cancer in England.

Evidence of the effect of adjunct ultrasound screening in women with mammography-negative dense breasts: Interval breast cancers at 1 year follow-up

Surveillance of interval cancers (IC) provides a measure of breast screening efficacy. Increased breast density is a predictor of breast cancer risk and of the risk of IC in screening. Improving screening sensitivity in women with dense breasts, through adjunct ultrasound (US), may potentially reduce IC; however this has not been proven. We report on first-year IC in a retrospective cohort of 8865 women who had 19,728 screening examinations (2001–2006): women with non-dense (D1–D2) breasts received mammography (M) screening, and women with dense (D3–D4) breasts also received ultrasound. Data linkage with both hospital discharge records and cancer registry databases was used to identify IC. Underlying cancer rates (cancers observed within 1-year from screening) were 6.3/1000 screens in the D1–D2 group and 8.3/1000 screens in the D3–D4 group. Cancer detection rate (CDR) was 5.98/1000 in all screening examinations; in D3–D4 breasts ultrasound had an additional CDR of 4.4/1000 screens. There were 21 first-year IC, an overall interval cancer rate (ICR) of 1.07/1000 negative screens: 0.95/1000 in women <50 years and 1.16/1000 screens in women ⩾50 years. ICR by breast density were 1.0/1000 negative screens in D1–D2, and 1.1/1000 negative screens in D3-D4. Interval cancers were early stage (in situ or small invasive) cancers, almost all were node-negative. Screening sensitivity was 83.5% for mammography alone in D1–D2 breasts relative to 86.7% for mammography with ultrasound in D3–D4 breasts. Our study shows that including ultrasound as adjunct screening in women with D3–D4 breasts brings the IC rate to similar levels as IC in non-dense breasts – this suggests that additional cancer detection by ultrasound is likely to improve screening benefit in dense breasts, and supports the implementation of a randomised trial of adjunct ultrasound in women with increased breast tissue density.

13 The mammographic and pathological features of 1521 breast screening interval cancers

13 The mammographic and pathological features of 1521 breast screening interval cancers

Interval cancers in screening with fecal occult blood test for colorectal cancer.

Interval cancers, which are cancers diagnosed in spite of one or more negative screening tests, were studied in a randomized population with Hemoccult-II for colorectal cancer in 61,938 persons between 45 and 74 years old. Three biannual screenings were performed from 1985 to 1991, and 52% of all the cancers detected after doing at least one Hemoccult-II test were interval cancers (81 persons). These were more advanced than cancers diagnosed after a positive Hemoccult-II test, of larger size, less frequently of Dukes stage A, more often invading neighboring organs, and less often resectable for cure. They were located in the rectum more often than cancers diagnosed by screening and cancers in controls. Otherwise, interval cancers did not differ from cancers in controls or cancers in non-responders, and all characteristics suggested that no delay in diagnosis resulted from one or more negative Hemoccult-II tests, compared with controls. However, even if screening with Hemoccult-II demonstrates a reduction in mortality from colorectal cancer, the present high number of interval cancers makes it necessary to look for other methods of screening populations for colorectal cancer.

The biology and natural history of breast cancer from the screening perspective.

A review of the tumor biology of breast cancer from the screening perspective reveals important research issues. It is not known if the induction phase includes any detectable preneoplastic lesions. Evidence for the existence of preneoplasias is conflicting. The effect of removal of such lesions on the incidence of breast cancer has not yet been studied. The mechanisms that govern progression of in situ lesions--or even small preclinical invasive cancers--are not fully understood. It is not clear to what extent progression into cancers with metastatic behavior occurs. Current predictors for progression are weak. One major benefit of the scientific evaluation of the screening programs is that we can learn more about the natural history of the disease. Mammographic screening detects tumors that are smaller in size than those detected by clinical examination only. There is an inverse relationship between tumor size and the probability that the patient has acquired axillary metastases. These facts, taken together, indicate that the mortality reduction seen in screening is a result of a real impact on the natural history. Calculations of the lead time gained in randomized screening projects give empirical proof that a third of the cancers progress from a localized stage to a disseminated disease relatively late in the preclinical phase of the tumor. Analyses of interval cancers in screening have pointed to the conclusion that the net growth rate of the primary tumor does not directly parallel metastatic ability, and that the tumors grow faster in younger women.