Patterns of aggressiveness: risk of progression to invasive breast cancer by mammographic features of calcifications in screen-detected ductal carcinoma in situ.

BACKGROUND: Mammographic features of calcifications on mammograms showing invasive breast cancer are associated with survival. Less is known about mammographic features and progression to invasive breast cancer among women treated for ductal carcinoma in situ (DCIS). PURPOSE: To investigate mammographic features of calcifications in screen-detected DCIS in women who later did and did not get diagnosed with invasive breast cancer. MATERIAL AND METHODS: This registry-based nested case-control study analyzed data from women with screen-detected DCIS in BreastScreen Norway, 1995-2016. Within this cohort of women with DCIS, those who were later diagnosed with invasive breast cancer (cases) were matched (1:2) to women who were not diagnosed with invasive breast cancer (controls) after their DCIS and by the end of 2016. Information on mammographic features were collected by a national radiological review, where screening mammograms were reviewed locally at each of the 16 breast centers in Norway. We used conditional logistic regression analysis to estimate associations between mammographic features of calcifications in the DCIS mammogram and the risk of subsequent invasive breast cancer. RESULTS: We found a higher risk of invasive breast cancer associated with fine linear branching (casting) morphology (odds ratio 20.0; 95% confidence interval [CI] 2.5-158.9) compared to fine linear or fine pleomorphic morphology. Regional or diffuse distribution showed an odds ratio of 2.8 (95% CI 1.0-8.2) compared to segmental or linear distribution. CONCLUSION: Mammographic features of calcifications in screen-detected DCIS were of influence on the risk of invasive breast cancer. Unfavorable characteristics of DCIS were fine linear branching morphology, and regional or diffuse distribution.

Can breast cancer be stopped? Modifiable risk factors of breast cancer among women with a prior benign or premalignant lesion.

Physical inactivity, high postmenopausal body mass index, alcohol consumption and use of menopausal hormone therapy are established risk factors for breast cancer. Less is known about whether these factors influence the risk of progression of benign and premalignant breast lesions to invasive breast cancer. This registry-based cohort study was based on women with a precancerous lesion who were followed for breast cancer. The cohort consisted of 11 270 women with a benign lesion, 972 women with hyperplasia with atypia and 2379 women with carcinoma in situ diagnosed and treated after participation in BreastScreen Norway, 2006-2016. Information on breast cancer risk factors was collected by a questionnaire administered with the invitation letter. Cox regression analysis was used to estimate the association between breast cancer and physical activity, body mass index, alcohol consumption, tobacco smoking and menopausal hormone therapy, adjusted for age. During follow-up, 274 women with a benign lesion, 34 women with hyperplasia with atypia and 118 women with carcinoma in situ were diagnosed with invasive breast cancer. We observed an increased risk of breast cancer associated with use of menopausal hormone therapy for women with a benign or premalignant lesion. Alcohol consumption and tobacco smoking showed suggestive increased risk of breast cancer among women with a benign lesion. We were only to a limited degree able to identify associations between modifiable risk factors of breast cancer and the disease among women with a precancerous lesion, and a larger study is needed to confirm or refute associations.

Self-reported symptoms among participants in a population-based screening program.

BACKGROUND: A limited number of studies have explored the association between self-reported symptoms and the risk of breast cancer among participants of population based screening programs. METHODS: We performed descriptive statistics on recall, screen-detected and interval cancer, positive predictive value and histopathological tumour characteristics by symptom group (asymptomatic, lump, and skin or nipple changes) as reported from 785,642 women aged 50-69 when they attended BreastScreen Norway 1996-2016. Uni- and multivariable mixed effects logistic regression models were used to analyze the association between symptom group and screen-detected or interval cancer. Results were presented as odds ratios and 95% confidence intervals (CI). RESULTS: A lump or skin/nipple change was reported in 6.2% of the 3,307,697 examinations. The rate of screen-detected cancers per 1000 examinations was 45.2 among women with a self-reported lump and 5.1 among asymptomatic women. Adjusted odds ratio of screen-detected cancer was 10.1 (95% CI: 9.3-11.1) and 2.0 (95% CI: 1.6-2.5) for interval cancer among women with a self-reported lump versus asymptomatic women. Tumour diameter, histologic grade and lymph node involvement of screen-detected and interval cancer were less prognostically favourable for women with a self-reported lump versus asymptomatic women. CONCLUSION: Despite targeting asymptomatic women, 6.2% of the screening examinations in BreastScreen Norway was performed among women who reported a lump or skin/nipple change when they attended screening. The odds ratio of screen-detected cancer was higher for women with versus without symptoms. Standardized follow-up guidelines might be beneficial for screening programs in order to take care of women reporting signs or symptoms of breast cancer when they attend screening.

Number of prior negative screening outcomes does not influence future risk of breast cancer.

We questioned whether a history of negative screening outcomes could be used to predict breast cancer risk, and thus be used as a potential factor for stratification of mammographic screening. Data from the Norwegian population based breast cancer screening program, BreastScreen Norway, was used to estimate cumulative hazard rates for breast cancer by number of prior negative screening outcomes among participants from 1995 through 2016. We followed three age cohorts of women, who started screening at age 50-54, 55-59, and 60-64 years. Further, we estimated the absolute and relative risk of breast cancer by number of prior negative screening outcomes. The cumulative hazard curves were parallel for all numbers of negative screening outcomes for all age cohorts. The absolute risk of breast cancer increased with number of negative screening outcomes for the youngest age cohort. For the oldest age cohorts, the absolute risk was stable during the screening period and decreased thereafter. The number of negative screening outcomes was not associated with risk of breast cancer, adjusted for age, percent screening attendance and calendar years (HR 1.00, 95% CI 0.98-1.02). Our results suggest that the number of negative screening outcomes does not predict breast cancer risk among participants in BreastScreen Norway.

Risk of breast cancer by prior screening results among women participating in BreastScreen Norway.

BACKGROUND: A premalignant lesion in the breast is associated with an increased risk of breast cancer. The aim of this article was to identify women with an increased risk of breast cancer based on prior screening results (PSRs). METHODS: This registry-based cohort study followed women who participated in the organized breast cancer screening program in Norway, BreastScreen Norway, in 1995-2016. Incidence rates and incidence rate ratios were used to estimate absolute and relative risks of breast cancer associated with PSRs. Histopathological characteristics of subsequent breast cancers were presented by PSRs. RESULTS: This study included 762,643 women with up to 21 years of follow-up. In comparison with negatively screened women, increased incidence rate ratios of 1.8, 2.0, 2.9, and 3.8 were observed after negative additional imaging, for benign biopsy, for hyperplasia with atypia, and for carcinoma in situ, respectively. Subsequent breast cancers did not differ in tumor diameter or histological grade, whereas the proportion of lymph node-positive breast cancers decreased as the presumed malignancy potential of PSRs increased. CONCLUSIONS: The risk of subsequent breast cancer increased with the presumed malignancy potential of PSRs, whereas the tumor characteristics of subsequent cancers did not differ except for the lymph node status. Women with screen-detected benign lesions or hyperplasia with atypia might benefit from more frequent screening.

Optimizing performance of BreastScreen Norway using value of information in graphical models.

This study proposes a method to optimize the performance of BreastScreen Norway through a stratified recommendation of tests including independent double or single reading of the screening mammograms and additional imaging with or without core needle biopsy. This is carefully evaluated by a value of information analysis. An estimated graphical probabilistic model describing the relationship between a set of risk factors and the corresponding risk of breast cancer is used for this analysis, together with a Bayesian network modeling screening test results conditional on the true (but unknown) breast cancer status of a woman. This study contributes towards evaluating a possibility of improving the efficiency of the screening program, where all women aged 50 to 69 are invited every second year, regardless of individual risk factors. Our stratified recommendation of tests is dependent on the probability that an asymptomatic woman has developed breast cancer at the time she is invited to a screening.