Immediate and delayed effects of mammographic screening on breast cancer mortality and incidence in birth cohorts.

BACKGROUND: Trend studies investigating the impact of mammographic screening usually display age-specific mortality and incidence rates over time, resulting in an underestimate of the benefit of screening, that is, mortality reduction, and an overestimate of its major harmful effect, that is, overdiagnosis. This study proposes a more appropriate way of analysing trends. METHODS: Breast cancer mortality (1950-2009) and incidence data (1975-2009) were obtained from Statistics Netherlands, 'Stg. Medische registratie' and the National Cancer Registry in the Netherlands for women aged 25-85 years. Data were visualised in age-birth cohort and age-period figures. RESULTS: Birth cohorts invited to participate in the mammographic screening programme showed a deflection in the breast cancer mortality rates within the first 5 years after invitation. Thereafter, the mortality rate increased, although less rapidly than in uninvited birth cohorts. Furthermore, invited birth cohorts showed a sharp increase in invasive breast cancer incidence rate during the first 5 years of invitation, followed by a moderate increase during the following screening years and a decline after passing the upper age limit. CONCLUSION: When applying a trend study to estimate the impact of mammographic screening, we recommend using a birth cohort approach.

Likelihood of early detection of breast cancer in relation to false-positive risk in life-time mammographic screening: population-based cohort study.

BACKGROUND: Women require balanced, high-quality information when making an informed decision on screening benefits and harms before attending biennial mammographic screening. PATIENTS AND METHODS: The cumulative risk of a false-positive recall and/or (small) screen-detected or interval cancer over 13 consecutive screening examinations for women aged 50 from the start of screening were estimated using data from the Nijmegen programme, the Netherlands. RESULTS: Women who underwent 13 successive screens in the period 1975-1976 had a 5.3% cumulative chance of a screen-detected cancer, with a 4.2% risk of at least one false-positive recall. The risk of being diagnosed with interval cancer was 3.7%. Two decades later, these estimates were 6.9%, 7.3% and 2.9%, respectively. The chance of detection of a small, favourable invasive breast cancer, anticipating a normal life-expectancy, rose from 2.3% to 3.7%. Extrapolation to digital screening mammography indicates that the proportion of false-positive results will rise to 16%. CONCLUSION: Dutch women about to participate in the screening programme can be reassured that the chance of false-positive recall in the Netherlands is relatively low. A new screening policy and improved mammography have increased the detection of an early screening carcinoma and lowering the risk of interval carcinoma.

[Effects of the population screening into breast cancer]. / Effecten van het bevolkingsonderzoek naar borstkanker.

Annually, in the Netherlands around 900,000 women between the ages of 50-75 years undergo mammography as part of a population screening into breast cancer. In this way more than 5000 cases of breast cancer are detected (0.6% of women screened); 70% of these malignancies are < stage II, which is prognostically favourable. Due to the early detection and treatment of breast cancer, the breast cancer death risk in those women who participate in the population screening is half that of women who choose not to be screened. The downside of the population screening is that participants are relatively often referred to a hospital for a diagnostic work-up (around 2%), and 70% of them are ultimately found not to have cancer. The positive predictive value of the population screening is 30%. Early discovery also leads to over-diagnosis in patients with breast cancer that without screening would never have manifested itself. Based on computer simulations it has been estimated that in the Netherlands over-diagnosis occurs in 9% of patients in whom breast cancer is detected during a population screening.

Less mammographic density after nasal versus oral administration of postmenopausal hormone therapy.

OBJECTIVE: Nasal administration gives a more acute but shorter rise in serum hormone levels than oral administration and may therefore have less effect on the fibroglandular tissue in the breasts. We studied the change in mammographic breast density after nasal vs. oral administration of postmenopausal hormone therapy (PHT). METHODS: We studied participants in a randomized, controlled trial on the impact of nasal vs. oral administration of PHT (combined 17ß-estradiol plus norethisterone) for 1 year. Two radiologists classified mammographic density at baseline and after 1 year into four categories. Also, the percentage density was calculated by a computer-based method. The main outcome measure was the difference in the proportion of women with an increase in mammographic density category after 1 year between the nasal and oral groups. Also, the change in the percentage density was calculated. RESULTS: The study group comprised 112 healthy postmenopausal women (mean age 56 years), of whom 53 received oral and 59 intranasal PHT. An increase in mammographic density category after 1 year was seen in 20% of the women in the nasal group and in 34% of the oral group. This resulted in a non-significant difference in the proportion of women in whom mammographic breast density had increased by 214% (95% confidence interval (CI) 230% to 2.7%). The mean change in percentage density was 21.2% in the nasal group and + 1.2% in the oral group, yielding a 22.4% differential effect (95% CI 27.3% to 2.5%). CONCLUSIONS: One year of nasal PHT gave a smaller, although not statistically significant, increase in mammographic density than oral PHT. Remaining issues are the relation between the route of administration of PHT and breast complaints and breast cancer risk.

Increasingly strong reduction in breast cancer mortality due to screening.

BACKGROUND: Favourable outcomes of breast cancer screening trials in the 1970s and 1980s resulted in the launch of population-based service screening programmes in many Western countries. We investigated whether improvements in mammography and treatment modalities have had an influence on the effectiveness of breast cancer screening from 1975 to 2008. METHODS: In Nijmegen, the Netherlands, 55,529 women received an invitation for screening between 1975 and 2008. We designed a case-referent study to evaluate the impact of mammographic screening on breast cancer mortality over time from 1975 to 2008. A total number of 282 breast cancer deaths were identified, and 1410 referents aged 50-69 were sampled from the population invited for screening. We estimated the effectiveness by calculating the odds ratio (OR) indicating the breast cancer death rate for screened vs unscreened women. RESULTS: The breast cancer death rate in the screened group over the complete period was 35% lower than in the unscreened group (OR=0.65; 95% CI=0.49-0.87). Analysis by calendar year showed an increasing effectiveness from a 28% reduction in breast cancer mortality in the period 1975-1991 (OR=0.72; 95% CI=0.47-1.09) to 65% in the period 1992-2008 (OR=0.35; 95% CI=0.19-0.64). CONCLUSION: Our results show an increasingly strong reduction in breast cancer mortality over time because of mammographic screening.

A novel and automatic mammographic texture resemblance marker is an independent risk factor for breast cancer.

OBJECTIVE: We investigated whether breast cancer is predicted by a breast cancer risk mammographic texture resemblance (MTR) marker. METHODS: A previously published case-control study included 495 women of which 245 were diagnosed with breast cancer. In baseline mammograms, 2-4 years prior to diagnosis, the following mammographic parameters were analysed for relation to breast cancer risk: (C) categorical parenchymal pattern scores; (R) radiologist's percentage density, (P) computer-based percentage density; (H) computer-based breast cancer risk MTR marker; (E) computer-based hormone replacement treatment MTR marker; and (A) an aggregate of P and H. RESULTS: Density scores, C, R, and P correlated (tau=0.3-0.6); no other pair of scores showed large (tau>0.2) correlation. For the parameters, the odds ratios of future incidence of breast cancer comparing highest to lowest categories (146 and 106 subject respectively) were C: 2.4(1.4-4.2), R: 2.4(1.4-4.1), P: 2.5(1.5-4.2), E: non-significant, H: 4.2(2.4-7.2), and A: 5.6(3.2-9.8). The AUC analysis showed a similarly increasing pattern (C: 0.58±0.02, R: 0.57±0.03, P: 0.60±0.03, H: 0.63±0.02, A: 0.66±0.02). The AUC of the aggregate marker (A) surpasses others significantly except H. HRT-MTR (E) did not significantly identify future cancers or correlate with any other marker. CONCLUSIONS: Breast cancer risk MTR marker was independent of density scores and more predictive of risk. The hormone replacement treatment MTR marker did not identify patients at risk.

Large increase in a Dutch woman's lifetime risk of developing breast cancer.

A large increase in the incidence of breast cancer has been observed in many countries over the last two decades. On the other hand, however, breast cancer mortality has decreased. The prominent burden of breast cancer in the female population induces a lot of discussion about incidence and mortality rates, whereas lifetime risks are less mentioned. This study provides information on the changes in risks for Dutch women with regards to being diagnosed with breast cancer (both invasive and in situ) or dying from this disease during the screening era. We used the life table method to calculate lifetime risks for the period 1989-2003. The lifetime risk for developing breast cancer increased from 1 in 10 in 1989 to 1 in 7 in 2003; the risk of dying from breast cancer decreased respectively from 1 in 22 to 1 in 26. The increasing incidence is alarming but has to be seen in perspective; the decreasing mortality is promising and shows that, at most, one third of the breast cancer cases are fatal.

Cost-effectiveness of different reading and referral strategies in mammography screening in the Netherlands.

In mammography screening with double reading, different strategies can be used when the readers give discordant recommendations for referral. We investigated whether the results of the Dutch breast cancer screening programme can be optimised by replacing the standard referral strategy by consensus. Twenty-six screening radiologists independently and blinded to outcome read a test set consisting of previous screening mammograms of 250 cases (screen-detected and interval cancers) and 250 controls. Their referral recommendations were paired and, in case of discrepancy, re-read according to three referral strategies: (1) decision by one of the readers; (2) arbitration by a third reader; (3) referral if both readers agree (consensus). Data allowed studying other referral strategies, including referral if any reader suggests, as well. Double reading with referral if any reader suggests resulted in a 1.03 times higher sensitivity (76.6%) and a 1.31 times higher referral rate (1.26%) than double reading with consensus. To estimate the cost-effectiveness, the outcomes were used in a microsimulation model. Even if double reading with referral if any reader suggests results in four times as high referral rates and an accompanying increase of biopsies or other invasive procedures, the cost-effectiveness of 4,190 Euros per life-year gained may well be in the range of acceptable cost-effectiveness for Dutch health care programmes.

Computer aided detection of masses in mammograms as decision support.

Performance of a computer aided detection (CAD) system for masses in mammograms was investigated. Using data collected in an observer study, in which experienced screening radiologists read a series of 500 screening mammograms without CAD, performance of radiologists was compared to the standalone performance of the CAD system. Due to a larger number of FPs (false positives), the performance of CAD was lower than that of the readers. However, when analysis was restricted to mammographic regions identified by the radiologists, it was found that the CAD system was comparable to the readers in discriminating these regions in cancer and non-cancer. In a retrospective analysis, the effect of independent combination of reader scores with CAD was compared to independent combination of scores of two radiologists. No significant difference was found between the results of these two methods. Both methods improved single reading results significantly.