Rene Shumak

Influence of delay to diagnosis on prognostic indicators of screen‐detected breast carcinoma

Although delay to diagnosis after a breast screening abnormality causes anxiety, its effect on prognosis is unknown.

Tumor Characteristics Associated With Mammographic Detection of Breast Cancer in the Ontario Breast Screening Program

BACKGROUND Few studies have compared the prognostic value of tumor characteristics by type of breast cancer diagnosed in the interval between mammographic screenings with screen-detected breast cancers. METHODS We conducted a case-case study within the cohort of women (n = 431 480) in the Ontario Breast Screening Program who were aged 50 years and older and were screened between January 1, 1994, and December 31, 2002. Interval cancers, defined as breast cancers diagnosed within 24 months after a negative screening mammogram, were designated as true interval cancers (n = 288) or missed interval cancers (n = 87) if they were not identified at the time of screening but were identified in retrospect. Screen-detected breast cancers (n = 450) were selected to match interval cancers. Tumors were evaluated for stage, grade, mitotic index, histology, and expression of hormone receptors and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by conditional logistic regression. RESULTS Both true and missed interval cancers were of higher stage and grade than matched screen-detected breast cancers. However, true interval cancers had a higher mitotic index (OR = 3.13, 95% CI = 1.81 to 5.42), a higher percentage of nonductal histology (OR = 1.94, 95% CI = 1.05 to 3.59), and were more likely to be both estrogen receptor-negative (OR = 2.09, 95% CI = 1.32 to 3.30) and progesterone receptor-negative (OR = 2.49, 95% CI = 1.68 to 3.70) compared with matched screen-detected tumors. CONCLUSIONS In this study, interval cancers were of higher stage and grade compared with screen-detected cancers. True interval cancers were more likely to have additional adverse prognostic features of estrogen and progesterone receptor negativity and nonductal morphology. The findings suggest a need for more sensitive screening modalities to detect true interval breast cancers and different approaches for early detection of fast-growing tumors.

Effectiveness of Screening With Annual Magnetic Resonance Imaging and Mammography: Results of the Initial Screen From the Ontario High Risk Breast Screening Program

PURPOSE The Ontario Breast Screening Program expanded in July 2011 to screen women age 30 to 69 years at high risk for breast cancer with annual magnetic resonance imaging (MRI) and digital mammography. To the best of our knowledge, this is the first organized screening program for women at high risk for breast cancer. PATIENTS AND METHODS Performance measures after assessment were compared with screening results for 2,207 women with initial screening examinations. The following criteria were used to determine eligibility: known mutation in BRCA1, BRCA2, or other gene predisposing to a markedly increased risk of breast cancer, untested first-degree relative of a gene mutation carrier, family history consistent with hereditary breast cancer syndrome and estimated personal lifetime breast cancer risk ≥ 25%, or radiation therapy to the chest (before age 30 years and at least 8 years previously). RESULTS The recall rate was significantly higher among women who had abnormal MRI alone (15.1%; 95% CI, 13.8% to 16.4%) compared with mammogram alone (6.4%; 95% CI, 5.5% to 7.3%). Of the 35 breast cancers detected (16.3 per 1,000; 95% CI, 11.2 to 22.2), none were detected by mammogram alone, 23 (65.7%) were detected by MRI alone (10.7 per 1,000; 95% CI, 6.7 to 15.8), and 25 (71%) were detected among women who were known gene mutation carriers (30.8 per 1,000, 95% CI, 19.4 to 43.7). The positive predictive value was highest for detection based on mammogram and MRI (12.4%; 95% CI, 7.3% to 19.3%). CONCLUSION Screening with annual MRI combined with mammography has the potential to be effectively implemented into an organized breast screening program for women at high risk for breast cancer. This could be considered an important management option for known BRCA gene mutation carriers.

The Contribution of Clinical Breast Examination to the Accuracy of Breast Screening

BACKGROUND There is controversy about whether adding clinical breast examination (CBE) to mammography improves the accuracy of breast screening. We compared the accuracy of screening among centers that offered CBE in addition to mammography with that among centers that offered only mammography. METHODS The cohort included 290 230 women aged 50-69 years who were screened at regional cancer centers or affiliated centers within the Ontario Breast Screening Program between January 1, 2002, and December 31, 2003, and were followed up for 12 months. The regional cancer centers offer screening mammography and CBE performed by a nurse. All affiliated centers provide mammography but not all provide CBE. Performance measures for 232 515 women who were screened by mammography and CBE at the nine regional cancer centers or 59 affiliated centers that provided CBE were compared with those for 57 715 women who were screened by mammography alone at 34 affiliated centers that did not provide CBE. RESULTS Sensitivity of referrals was higher for women who were screened at regional cancer centers or affiliated centers that offered CBE in addition to mammography than for women screened at affiliated centers that did not offer CBE (initial screen: 94.9% and 94.6%, respectively, vs 88.6%; subsequent screen: 94.9% and 91.7%, respectively, vs 85.3%). Mammography sensitivity was similar between centers that offered CBE and those that did not. However, women without cancer who were screened at regional cancer centers or affiliated centers that offered CBE had a higher false-positive rate than women screened at affiliated centers that offered only mammography (initial screen: 12.5% and 12.4%, respectively, vs 7.4%; subsequent screen: 6.3% and 8.3%, respectively, vs 5.4%). CONCLUSIONS Women should be informed of the benefits and risks of having a CBE in addition to mammography for breast screening.

Influence of Patterns of hormone replacement therapy use and mammographic density on breast cancer detection

Background: There is evidence that factors such as current hormone replacement therapy (HRT) use and mammographic density may each lower the sensitivity of mammography and are associated with a greater risk of developing an interval cancer. This study explores this relationship further by examining the influence of patterns of HRT use and the percentage of mammographic density on the detection of breast cancer by classification of interval cancer. Methods: This study uses a case-case design nested within a cohort of women screened by the Ontario Breast Screening Program between 1994 and 2002. Interval cancers, both those missed at screening but seen on retrospective review (n = 87) or true intervals without visible tumor signs at screening (n = 288) were matched to 450 screen-detected cancers. The association between the percentage of mammographic density, measured by radiologists and a computer-assisted method, and HRT use, ascertained from a mailed questionnaire, and the risk of being diagnosed with an interval cancer was estimated using conditional logistic regression. Results: A monotonic gradient of increasing risk for interval cancers was found for each 25% increase in mammographic density [odds ratio (OR), 1.77; 95% confidence intervals (95% CI), 1.07-2.95 for missed intervals and OR, 2.16; 95% CI, 1.59-2.94 for true intervals]. After adjusting for mammographic density, a significantly increased risk for true-interval cancers remained for women taking estrogen alone (OR, 1.75; 95% CI, 1.11-2.83) as well as for missed- (OR, 2.84; 95% CI, 1.32-6.13) and true-interval cancers (OR, 1.79; 95% CI, 1.10-2.90) for women taking combined HRT. Conclusions: Information on mammographic density and HRT use should routinely be collected at the time of screening. Women at risk should be made aware of the lower sensitivity of mammography and offered alternative procedures for screening. (Cancer Epidemiol Biomarkers Prev 2006;15(10):1856–63)

A hybrid breast biopsy system combining ultrasound and MRI

System design and initial phantom accuracy results for a novel biopsy system integrating both magnetic resonance (MR) and ultrasound (US) imaging modalities are presented. A phantom experiment was performed to investigate the efficacy of this hybrid guidance biopsy technique in a breast tissue mimicking phantom. A comparison between MR-guided core biopsy verses MR/US-guided core biopsy of phantom targets was realized using a scoring system based on the consistency of the acquired core samples (14 gauge). It was determined that the addition of US to guide needle placement improved the accuracy from an average score of 7.4 out of 10 (MRI guidance alone), to 9.6 (MRI/US guidance) over 21 trials. The average amount of needle tip correction resulting from the additional US information was determined to be 3.7 mm. This correction value is substantial, equal to approximately one radius of the intended targets. Hybrid US/MRI guided biopsy appears to offer a simple means to ensure accurate breast tissue sampling without the need for repeat MRI scans for verification or the need for real-time imaging in open MRI geometries.

Digital compared with screen-film mammography: performance measures in concurrent cohorts within an organized breast screening program.

PURPOSE To evaluate the performance of digital direct radiography (DR) and computed radiography (CR) compared with that of screen-film mammography (SFM) in large concurrent cohorts. MATERIALS AND METHODS This study was approved by the University of Toronto Research Ethics Board and did not require informed consent. Concurrent cohorts of women aged 50-74 years screened with DR (n = 220 520), CR (n = 64 210), or SFM (n = 403 688) between 2008 and 2009 were identified and followed for 12 months. Performance was compared between cohorts, with SFM as the referent cohort. Associations were examined by using mixed-effect logistic regression. RESULTS The cancer detection rate was similar for DR (4.9 per 1000; 95% confidence interval [CI]: 4.7, 5.2) and SFM (4.8 per 1000; 95% CI: 4.7, 5.0); however, the rate was significantly lower for CR (3.4 per 1000; 95% CI: 3.0, 3.9) (odds ratio, 0.79; 95% CI: 0.68, 0.93). Recall rates were higher for DR (7.7%; 95% CI: 7.6%, 7.8%) and lower for CR (6.6%; 95% CI: 6.5%, 6.7%) than for SFM (7.4%; 95% CI: 7.3%, 7.5%). Positive predictive value was lower for CR (5.2%; 95% CI: 4.7%, 5.8%) than for SFM (6.6%; 95% CI: 6.4%, 6.8%); however, the adjusted odds were not significant. CONCLUSION Although DR is equivalent to SFM for breast screening among women aged 50-74 years, the cancer detection rate was lower for CR. Screening programs should monitor the performance of CR separately and may consider informing women of the potentially lower cancer detection rates.

Favourable prognostic factors of subsequent screen-detected breast cancers among women aged 50-69.

Most studies reporting more favourable biological features of screen-detected breast cancers compared with symptomatic or interval cancers include initial or prevalent screens and therefore may not indicate the real benefit of screening on breast cancer mortality. We conducted case–case comparisons within a cohort of eligible women (N=771 715) who were aged 50–69 between 1 January 1995 and 31 December 2003. A randomly selected sample of breast cancers (N=1848) diagnosed among these women were compared by detection method. Tumour characteristics of interval cancers (N=362) diagnosed after 6–24 months of a negative screen or symptomatic breast cancers (N=491) were compared with subsequent screen-detected breast cancers diagnosed within 6 months of a positive screen (N=995) using polytomous logistic regression. Tumours were evaluated for clinical presentation, histology and expression of hormone receptors. Women with symptomatic detected [odds ratio (OR)=7.48, 95% confidence interval (CI)=5.38–10.38] and interval cancers (OR=2.20, 95% CI=1.56–3.10) were more often diagnosed at stage III–IV versus I than women with rescreen-detected cancers. After adjusting for tumour size, women with symptomatic cancers had tumours of higher grade (OR=1.50, 95% CI=1.05–2.15) and mitotic score (OR=1.69, 95% CI=1.15–2.49) and women with interval cancers had tumours of higher mitotic score (OR=1.52, 95% CI=1.01–2.28) compared with women diagnosed at screening. Subsequent screen-detected cancers are not only detected at an earlier stage but are also less aggressive, leading to a better prognosis. As long-term mortality reduction for breast screening may depend on subsequent screens, our study indicates that mammography screening can be effective in women aged 50–69.

Digital Compared with Screen-Film Mammography: Measures of Diagnostic Accuracy among Women Screened in the Ontario Breast Screening Program

PURPOSE To compare measures of diagnostic accuracy between large concurrent cohorts of women screened with digital computed radiography (CR), direct radiography (DR), and screen-film mammography (SFM). MATERIALS AND METHODS This study was approved by the University of Toronto Research Ethics Board; informed consent was not required. Three concurrent cohorts of women aged 50-74 years who were screened from 2008-2009 in the Ontario Breast Screening Program with SFM (487,334 screening examinations, 403,688 women), DR (254,758 screening examinations, 220,520 women), or CR (74,140 screening examinations, 64,210 women) were followed for 2 years or until breast cancer diagnosis. Breast cancers were classified as screening-detected or interval on the basis of the womans final screening and assessment results. Interval cancer rate (per 10 000 negative screening examinations), sensitivity, and specificity were compared across the cohorts by using mixed-effects logistic regression analysis. RESULTS Interval cancer rates were higher, although not significantly so, for CR (15.2 per 10,000; 95% confidence interval [CI]: 12.8, 17.8) and were similar for DR (13.7 per 10,000; 95% CI: 12.4, 15.0) compared with SFM (13.0 per 10,000; 95% CI: 12.1, 13.9). For CR versus SFM, specificity was similar while sensitivity was significantly lower (odds ratio [OR] = 0.62; 95% CI: 0.47, 0.83; P = .001), particularly for invasive cancers detected at a rescreening examination, for women with breast density of less than 75%, for women with no family history, and for postmenopausal women. For DR versus SFM, sensitivity was similar while specificity was lower (OR = 0.92; 95% CI: 0.87, 0.98; P = .01), particularly for rescreening examinations, for women aged 60-74 years, for women with breast density of less than 75%, for women with a family history, and for women who were postmenopausal. CONCLUSION Given the 38% lower sensitivity of CR imaging systems compared with SFM, programs should assess the continued use of this technology for breast screening.

Influence of Nurses on Compliance with Breast Screening Recommendations in an Organized Breast Screening Program

Background: Evidence from breast screening trials has shown that a significant reduction in breast cancer mortality from screening can be achieved by regular attendance. Few studies have evaluated the influence of nurses on compliance with breast screening recommendations. Methods: The cohort included 157,788 women ages 50 to 69 years who were screened at 1 of 9 regional cancer centers or 57 affiliated centers with nurses or 26 affiliated centers without nurses between January 1, 2002, and December 31, 2002, within the Ontario Breast Screening Program. These women were followed up prospectively for at least 30 months to compare compliance for annual and biennial screening recommendations among women who attended centers with and without nurses. The associations between type of screening center and the odds of compliance were modeled using mixed-effect logistic regression models. All P values are two-sided. Results: Women attending a regional cancer center [odds ratios (OR), 1.96; 95% confidence interval (95% CI), 1.07-3.58] or affiliated center with nurses (OR, 1.75; 95% CI, 1.38-2.22) were significantly more likely to return within 18 months of their annual screening recommendation than women attending affiliated centers without nurses. In addition, women attending regional cancer centers (OR, 2.28; 95% CI, 1.34-3.89) or affiliated centers with nurses (OR, 2.30; 95% CI, 1.86-2.83) were significantly more likely to make a timely return within the recommended biennial screening interval of between 18 and 30 months. Conclusions: Breast screening programs should consider methods of integrating educational activities as provided by the nurses to improve compliance with screening. Cancer Epidemiol Biomarkers Prev; 19(3); 697–706