Digital versus screen-film mammography: impact of mammographic density and hormone therapy on breast cancer detection.

Most studies that have examined the effects of mammographic density and hormone therapy use on breast cancer detection have included screen-film mammography. This study further examines this association in post-menopausal women screened by digital mammography. Approved by the University of Toronto Research Ethics Board, this study identified 688,418 women of age 50-74 years screened with digital or screen-film mammography from 2008 to 2009 within the Ontario Breast Screening Program. Of 2993 eligible women with invasive breast cancer, 2450 were contacted and 1421 participated (847 screen-film mammography, 574 digital direct radiography). Mammographic density was measured by study radiologists using the standard BI-RADS classification system and by a computer-assisted method. Information on hormone therapy use was collected by a telephone-administered questionnaire. Logistic regression and two-tailed tests for significance evaluated associations between factors and detection method by mammography type. Women with >75 % radiologist-measured mammographic density compared to those with <25 % were more likely to be diagnosed with an interval than screen-detected cancer, with the difference being greater for those screened with screen-film (OR = 6.40, 95 % CI 2.30-17.85) than digital mammography (OR = 2.41, 95 % CI 0.67-8.58) and aged 50-64 years screened with screen-film mammography (OR = 10.86, 95 % CI 2.96-39.57). Recent former hormone therapy users were also at an increased risk of having an interval cancer with the association being significant for women screened with digital mammography (OR = 2.08, 95 % CI 1.17-3.71). Breast screening using digital mammography lowers the risk of having an interval cancer for post-menopausal women aged 50-64 with greater mammographic density.

Digital compared to screen-film mammography: breast cancer prognostic features in an organized screening program.

Our previous study found cancer detection rates were equivalent for direct radiography compared to screen-film mammography, while rates for computed radiography were significantly lower. This study compares prognostic features of invasive breast cancers by type of mammography. Approved by the University of Toronto Research Ethics Board, this study identified invasive breast cancers diagnosed among concurrent cohorts of women aged 50-74 screened by direct radiography, computed radiography, or screen-film mammography from January 1, 2008 to December 31, 2009. During the study period, 816,232 mammograms were performed on 668,418 women, and 3,323 invasive breast cancers were diagnosed. Of 2,642 eligible women contacted, 2,041 participated (77.3 %). The final sample size for analysis included 1,405 screen-detected and 418 interval cancers (diagnosed within 24 months of a negative screening mammogram). Polytomous logistic regression was performed to evaluate the association between tumour characteristics and type of mammography, and between tumour characteristics and detection method. Odds ratios (OR) and 95 % confidence intervals (CI) were recorded. Cancers detected by computed radiography compared to screen-film mammography were significantly more likely to be lymph node positive (OR 1.94, 95 %CI 1.01-3.73) and have higher stage (II:I, OR 2.14, 95 %CI 1.11-4.13 and III/IV:I, OR 2.97, 95 %CI 1.02-8.59). Compared to screen-film mammography, significantly more cancers detected by direct radiography (OR 1.64, 95 %CI 1.12-2.38) were lymph node positive. Interval cancers had worse prognostic features compared to screen-detected cancers, irrespective of mammography type. Screening with computed radiography may lead to the detection of cancers with a less favourable stage distribution compared to screen-film mammography that may reflect a delayed diagnosis. Screening programs should re-evaluate their use of computed radiography for breast screening.

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.

Clinical and prognostic factors associated with diagnostic wait times by breast cancer detection method.

INTRODUCTION: Although prognostic differences between screen-detected, interval and symptomatic breast cancers are known, factors associated with wait times to diagnosis among these three groups have not been studied. METHODS: Of the 16,373 invasive breast cancers diagnosed between January 1, 1995 and December 31, 2003 in a cohort of Ontario women aged 50 to 69, a random sample (N = 2,615) were selected for chart abstraction. Eligible women were classified according to detection method; screen-detected (n = 1181), interval (n = 319) or symptomatic (n = 406). Diagnostic wait time was calculated from the initial imaging or biopsy to breast cancer diagnosis. Logistic regression analysis examined associations between diagnostic wait times dichotomized as greater or less than the median and demographic, clinical and prognostic factors separately for each detection cohort. RESULTS: Women who underwent an open biopsy had significantly longer than median wait times to diagnosis, compared to women who underwent a fine needle aspiration or core biopsy; (screen-detected OR = 2.76, 95% CI = 2.14-3.56; interval OR = 2.56, 95% CI = 1.50-4.35; symptomatic OR = 5.56, 95% CI = 3.33-9.30). Additionally, screen-detected breast cancers diagnosed with stage II and symptomatic cancers diagnosed at stage III or IV had significantly shorter diagnostic wait times compared to those diagnosed at stage 1 (OR = 0.66 95% CI = 0.50-0.87 and OR = 0.46, 95% CI = 0.25-0.85 respectively). CONCLUSIONS: Our study is consistent with expedited diagnostic work-up for breast cancers with more advanced prognostic features. Furthermore, women who had an open surgical biopsy had a greater than the median diagnostic wait time, irrespective of detection method.

Factors associated with wait times across the breast cancer treatment pathway in Ontario.

BACKGROUND: Longer times from diagnosis to breast cancer treatment are associated with poorer prognosis. This study examined factors associated with wait times by phase in the breast cancer treatment pathway. METHODS: There were 1760 women eligible for the study, aged 50-69 diagnosed in Ontario with invasive breast cancer from 1995-2003. Multivariate logistic regression examined factors associated with greater than median wait times for each phase of the treatment pathway; from diagnosis to definitive surgery; from final surgery to radiotherapy without chemotherapy and from final surgery to chemotherapy. RESULTS: The median wait times were 17 days (Inter Quartile Range (IQR) = 0-31) from diagnosis to definitive surgery, 44 days (IQR = 34-56) from final surgery to postoperative chemotherapy and 75 days (IQR = 57-97) from final surgery to postoperative radiotherapy. Diagnosis during 2000-2003 compared to 1995-1999 was associated with significantly longer wait times for each phase of the treatment pathway. Higher income quintile was associated with longer wait time from diagnosis to surgery (OR = 1.47, 95% CI = 1.05-2.06) and shorter wait times from final surgery to radiotherapy (OR = 0.60, 95% CI = 0.37-0.96). Greater stage at diagnosis was associated with shorter wait times from diagnosis to definitive surgery (stage III vs I: OR = 0.49, 95% CI = 0.34-0.71). CONCLUSIONS: While diagnosis during the latter part of the study period was associated with significantly longer wait times for all phases of the treatment pathway, there were variations in the associations of stage and income quintile with wait times by treatment phase. Continued assessment of factors associated with wait times across the breast cancer treatment pathway is important, as they indicate areas to be targeted for quality improvement with the ultimate goal of improving prognosis.

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.

Improving work-up of the abnormal mammogram through organized assessment: results from the ontario breast screening program.

PURPOSE: Women with an abnormal screening mammogram should ideally undergo an organized assessment to attain a timely diagnosis. This study evaluated outcomes of women undergoing work-up after abnormal mammogram through a formal breast assessment affiliate (BAA) program with explicit care pathways compared with usual care (UC) using developed quality indicators for screening mammography programs. METHODS: Between January 1 and December 31, 2007, a total of 320,635 women underwent a screening mammogram through the Ontario Breast Screening Program (OBSP), of whom 25,543 had an abnormal result requiring further assessment. Established indicators assessing timeliness, appropriateness of follow-up, and biopsy rates were compared between women who were assessed through either a BAA or UC using χ(2) analysis. RESULTS: Work-up of the abnormal mammogram for patients screened through a BAA resulted in a greater proportion of women attaining a definitive diagnosis within the recommended time interval when a histologic diagnosis was required. In addition, use of other quality measures including specimen radiography for both core biopsies and surgical specimens and preoperative core needle biopsy was greater in BAA facilities. CONCLUSION: These findings support future efforts to increase the number of BAAs within the OBSP, because the pathways and reporting methods associated with them result in improvements in our ability to provide timely and appropriate care for women requiring work-up of an abnormal mammogram.

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.

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.

Effect of screening result on waiting times to assessment and breast cancer diagnosis: results from the Ontario Breast Screening Program.

BACKGROUND: The effect of severity of screening result on delays to diagnosis has primarily been examined for mammographic abnormalities. This study will examine delays to assessment and diagnosis for women with an abnormal mammogram compared to women with an abnormal clinical breast examination (CBE) or abnormal CBE and mammogram. METHODS: Using data routinely collected by Ontario Breast Screening Program (OBSP), 12,675 women aged 50 to 69 with an abnormal screening result between January 1, 2000 and December 31, 2000 were followed prospectively to the completion of their assessment process. Median waiting times from abnormal screen to first assessment procedure and diagnosis were compared by modality of referral and among women with a breast cancer diagnosis by prognostic features. RESULTS: The median waiting time to first assessment and to diagnosis was significantly longer for women with only a clinical abnormality compared to women with a mammographic abnormality. In addition, women diagnosed with cancers of larger size had longer delays when the abnormality was detected only clinically. However, women referred by both modalities had significantly shorter waiting times to first assessment procedure and to diagnosis of poor prognosis cancers compared to women referred by mammography alone. INTERPRETATION: Women with an abnormal CBE and mammogram are assessed more promptly and have shorter diagnostic times. However, women with only a CBE abnormality had delays to diagnosis as a result of longer waiting times to first assessment procedure. Integration of the OBSP with assessment centres should improve times to diagnosis irrespective of modality of referral.

Contrast-enhanced digital mammography: initial clinical experience.

PURPOSE: To investigate the potential of using intravenous contrast material with full-field digital mammography to facilitate the detection and characterization of lesions in the breast. MATERIALS AND METHODS: Twenty-two women scheduled for biopsy because they were suspected of having abnormalities at breast imaging underwent imaging with contrast material-enhanced digital mammography. Six sequential images of the affected breast were obtained, with a contrast agent injected intravenously between the time the first and second images were obtained. Image processing included registration and logarithmic subtraction. Lesions were evaluated for the presence, morphology, and kinetics of enhancement. Lesion type, size, and pathologic findings were correlated with the findings at contrast-enhanced digital mammography. RESULTS: At contrast-enhanced digital mammography, enhancement was observed in eight of 10 patients with biopsy-proved cancers. In one case of ductal carcinoma in situ and one case of invasive ductal carcinoma, enhancement was not observed. No enhancement was seen in seven of 12 cases in which lesions were suspected of being malignant at initial imaging but were benign. Morphology generally correlated with the pathologic diagnosis. The kinetics of lesion enhancement showed similarity to that seen with gadolinium-enhanced magnetic resonance imaging but was not consistent. CONCLUSION: The results of this preliminary study suggest that contrast-enhanced digital mammography potentially may be useful in identification of lesions in the mammographically dense breast. Further investigation of contrast-enhanced digital mammography as a diagnostic tool for breast cancer is warranted.