Christine Wilson

Pan-Canadian Study of Mammography Screening and Mortality from Breast Cancer

BACKGROUND Screening with mammography has been shown by randomized controlled trials to reduce breast cancer mortality in women aged 40 to 74 years. Estimates from observational studies following screening implementation in different countries have produced varyied findings. We report findings for seven Canadian breast screening programs. METHODS Canadian breast screening programs were invited to participate in a study aimed at comparing breast cancer mortality in participants and nonparticipants. Seven of 12 programs, representing 85% of the Canadian population, participated in the study. Data were obtained from the screening programs and corresponding cancer registries on screening mammograms and breast cancer diagnoses and deaths for the period between 1990 and 2009. Standardized mortality ratios were calculated comparing observed mortality in participants to that expected based upon nonparticipant rates. A substudy using data from British Columbia women aged 35 to 44 years was conducted to assess the potential effect of self-selection participation bias. All statistical tests were two-sided. RESULTS Data were obtained on 2796472 screening participants. The average breast cancer mortality among participants was 40% (95% confidence interval [CI] = 33% to 48%) lower than expected, with a range across provinces of 27% to 59%. Age at entry into screening did not greatly affect the magnitude of the average reduction in mortality, which varied between 35% and 44% overall. The substudy found no evidence that self-selection biased the reported mortality results, although the confidence intervals of this assessment were wide. CONCLUSION Participation in mammography screening programs in Canada was associated with substantially reduced breast cancer mortality.

Improving screening mammography return rates in overdue women: A randomized study of signed reminder letters from family physicians.

1 Background: For asymptomatic women aged 50 to 74 with an average risk for developing breast cancer, screening mammography (SM) is recommended every 2 years in British Columbia (BC). The Screening Mammography Program of BC (SMP) uses a schedule of multiple postcard reminders, which achieves an on-time (within 30 months) participation rate of 54% among those aged 50 to 69. The purpose of this study was to determine whether the SM return rate of overdue women could be improved by a reminder letter signed by their family physicians. METHODS Eligible women met the following criteria: prior normal SM, age 52 to 74, overdue by 30 to 48 months from their last SM and had agreed to being contacted for research by the SMP. All family physicians in BC were invited to participate. Consenting physicians signed the study letters, which encouraged SM, for all of the overdue women in their practice. Women were randomized to receive a postcard reminder or a postcard reminder and the signed family physician reminder letter. Six months after the mailing, the SMP database was queried to determine the SM return rate. RESULTS In BC, 822 physicians participated in the study and 5,385 women with signed letters were randomized. SMP sent a postcard to 2,689 women and a postcard and letter to 2,696 women. The age, number of prior SMs and time overdue were not statistically different between the arms. Within 6 months, 600 women (22.3%) in the postcard arm returned, while 894 women (33.2%) in the postcard and letter arm returned (odds ratio 1.7, p < 0.0001). The maximum difference between the SM return rates was observed at 4 months. On multivariable analysis, women who had >1 previous SM were more likely to return compared to those who only had 1 previous SM (odds ratio 2.2, p < 0.0001). Women who were 30 to 36 months overdue were more likely to return compared to those who were 42 to 48 months overdue (odds ratio 2.4, p < 0.0001). CONCLUSIONS A signed family physician reminder letter is a simple and effective intervention to improve screening mammography return rates in overdue women.

Flat Ductal Intraepithelial Neoplasia 1A Diagnosed at Stereotactic Core Needle Biopsy: Is Excisional Biopsy Indicated?

OBJECTIVE This study correlates ductal intraepithelial neoplasia (DIN) 1A diagnosed at stereotactic spring core needle biopsy (CNB) or vacuum-assisted biopsy (VAB) with the subsequent surgical histologic results or long-term follow-up imaging findings to predict the likelihood of upgrade to ductal carcinoma in situ (DCIS) or invasive carcinoma. MATERIALS AND METHODS Stereotactic imaging-guided CNBs and VABs were performed principally for assessment of microcalcifications seen on mammography. DIN 1A diagnoses made at CNB or VAB were correlated with subsequent excisional biopsy results or imaging follow-up. Patients were included only if there was no concomitant CNB or VAB diagnosis of DIN 1B, atypical lobular hyperplasia, lobular carcinoma in situ or DCIS, papillary lesion, or invasive carcinoma. Surgical biopsy results were obtained for 239 patients. Upgrade was defined as a diagnosis of DCIS or invasive carcinoma at surgery. Patients who did not undergo surgical excision were followed with imaging. RESULTS An upgrade rate of 4.2% (10 lesions in 239 patients) is reported. The remaining samples (229/239) had a surgical diagnosis of DIN 1A or DIN 1B, lobular carcinoma in situ, or a benign finding with no atypia. CONCLUSION The upgrade rate of DIN 1A diagnosed at CNB or VAB was 4.2%. These results indicate it may be reasonable to avert immediate surgery in favor of short-term imaging follow-up.

Cyclooxygenase-2 Inhibition for the Prophylaxis and Treatment of Preinvasive Breast Cancer in a Her-2/Neu Mouse Model

Ductal carcinoma in situ (DCIS) is the most common form of preinvasive breast cancer. Several molecular alterations have been identified in DCIS. Among them, cyclooxygenase 2 (COX-2) overexpression has been shown in 60% to 80% of DCIS cases. Celecoxib is a nonsteroidal anti-inflammatory drug that selectively inhibits COX-2. In this study, we evaluated whether COX-2 inhibition by celecoxib can reduce the incidence of preinvasive breast cancer and its progression to invasive breast cancer in a mouse model exhibiting a similar phenotype to human solid-pattern DCIS. We have used the mouse model mouse mammary tumor virus (MMTV)-Neu to investigate this possibility. These mice carry a rat Her-2/Neu transgene and are known to develop DCIS-like lesions. Our results showed that celecoxib (500 ppm) given as prophylaxis was neither able to prevent tumor development nor delay tumor appearance compared with untreated mice. Furthermore, when the drug was given early in tumorigenesis, it did not reduce the progression of preinvasive to invasive tumors nor prevent lung metastasis. Reduction of prostaglandin levels was, however, achieved in mammary tumors of treated mice. In addition, celecoxib treatment caused an increase in apoptosis and decreased vascular endothelial growth factor expression in treated animals. Our results contrast with some previously published studies and highlight the complexity of the relationship between COX-2 and breast cancer. Cancer Prev Res; 3(2); 202–11

Assessing the Breast Cancer Risk Distribution for Women Undergoing Screening in British Columbia

Breast cancer risk estimations are both informative and useful at the population level, with many screening programs relying on these assessments to allocate resources such as breast MRI. This cross-sectional multicenter study attempts to quantify the breast cancer risk distribution for women between the ages of 40 to 79 years undergoing screening mammography in British Columbia (BC), Canada. The proportion of women at high breast cancer risk was estimated by surveying women enrolled in the Screening Mammography Program of British Columbia (SMPBC) for known breast cancer risk factors. Each respondents 10-year risk was computed with both the Tyrer–Cuzick and Gail risk assessment models. The resulting risk distributions were evaluated using the guidelines from the National Institute for Health and Care Excellence (United Kingdom). Of the 4,266 women surveyed, 3.5% of women between the ages of 40 to 79 years were found to have a high 10-year risk of developing breast cancer using the Tyrer–Cuzick model (1.1% using the Gail model). When extrapolated to the screening population, it was estimated that 19,414 women in the SMPBC are considered to be at high breast cancer risk. These women may benefit from additional MRI screening; preliminary analysis suggests that 4 to 5 additional MRI machines would be required to screen these high-risk women. However, the use of different models and guidelines will modify the number of women qualifying for additional screening interventions, thus impacting the MRI resources required. The results of this project can now be used to inform decision-making groups about resource allocation for breast cancer screening in BC. Cancer Prev Res; 6(10); 1084–92. ©2013 AACR.

Mammographic non-dense area and breast cancer risk in postmenopausal women: a causal inference approach in a case–control study

PurposeThe association between high mammographic density (MD) and elevated breast cancer risk is well established. However, the role of absolute non-dense area remains unclear. We estimated the effect of the mammographic non-dense area and other density parameters on the risk of breast cancer.MethodsThis study utilizes data from a population-based case–control study conducted in Greater Vancouver, British Columbia, with 477 female postmenopausal breast cancer cases and 588 female postmenopausal controls. MD measures were determined from digitized screening mammograms using computer-assisted software (Cumulus). Marginal odds ratios were estimated by inverse-probability weighting using a causal diagram for confounder selection. Akaike information criteria and receiver operating characteristic curves were used to assess the goodness of fit and predictive power of unconditional logistic models containing MD parameters.ResultsThe risk of breast cancer is 60% lower for the highest quartile compared to the lowest quartile of mammographic non-dense area (marginal OR 0.40, 95% CI 0.26–0.61, p-trend < 0.001). The cancer risk almost doubles for the highest quartile compared to the lowest quartile of dense area (marginal OR 1.81, 95% CI 1.19–2.43, p-trend < 0.001). For the highest quartile of percent density, breast cancer risk was more than three times higher than for the lowest quartile (marginal OR 3.15, 95% CI 1.90–4.40, p-trend < 0.001). No difference was seen in predictive accuracy between models using percent density alone, dense area alone, or non-dense area plus dense area.ConclusionsIn this study, non-dense area is an independent risk factor after adjustment for dense area and other covariates, inversely related with the risk of breast cancer. However, non-dense area does not improve prediction over that offered by percent density or dense area alone.

Trends in Mammogram Image Quality, Dose and Screen-Detected Cancer Rates in an Organized Screening Mammography Program

BACKGROUND: The Screening Mammography Program of British Columbia (SMPBC), Canada is a population based program that regularly performs quality assurance testing and outcomes analysis.

Abstract B114: Core biopsy in breast cancer diagnosis: The provincial evaluation of utilization and relationship with treatment outcomes

Purpose:To determine: 1) The proportion of women in British Columbia (BC) who have a pre-operative diagnosis of breast cancer by image-guided core biopsy; 2) Whether women who have a pre-operative radiological diagnosis of breast cancer with core biopsy have fewer breast surgeries as part of their initial therapy; 3) Whether local/ locoregional relapse is lower in women who have had a pre-operative diagnosis of breast cancer with a core biopsy versus an open biopsy; 4) Whether there is regional variation in the use of pre-operative core biopsies versus open biopsies in the diagnosis of breast cancer in B.C. 5) Whether the risk of pN0i+ on sentinel node biopsy (SNB) is reduced when the initial diagnosis of breast cancer is made on core biopsy versus open biopsy. Methods: All B.C residents diagnosed with breast cancer in 2006 were reviewed. The women were divided into groups according to the method of diagnosis- pre-operative core needle biopsy, operative biopsy (open biopsy or other surgery), versus other diagnosis. Core biopsies were further divided into image-guided versus clinically-directed core. Women with denovo metastatic disease, locally advanced disease, prior or synchronous invasive or insitu breast cancer, Paget9s, alone or with insitu disease, patients with surgical procedures performed out of province, patients diagnosed on death certificate/ autopsy only, and cases without pathology were all excluded. Results: 3130 patients diagnosed in 2006 were identified in the BC Cancer Agency Registry. After exclusions, 2589 patients were included in the study cohort. 32% of patients had diagnosis made on an open surgical procedure, and 68% were diagnosed on a non-open biopsy, of which, 80% were image-guided core biopsies. Seventy-five percent of women with an image-guided core had one or less surgical procedure compared to only 26% of women whose diagnosis was made by surgery, despite the image-guided core biopsy group having larger, more invasive tumors and increased nodal positivity. The type of biopsy did not impact the prevalence of pN0i+ on SNB, or local and locoregional relapse rate. Regionally, Vancouver Coastal and Vancouver Island Health Authority, which are more densely populated urban centres, had the highest proportion of patients diagnosed by core biopsy, 70.3% and 75.4% respectively, and the sparsely populated Northern Health Authority had the lowest proportion at 46.7%. Conclusions: Core biopsies for breast cancer diagnosis are under-utilized in British Columbia and show significant regional variation. Although core biopsy diagnosis does not impact rate of pN0i+ on nodal biopsy or locoregional relapse rates, it is associated with substantially fewer breast/nodal surgeries. More resources are required to promote the use of CNB to providers and patients. Citation Format: Kristy KM Cho, Christine Wilson, Scott Tyldesley, Caroline Speers. Core biopsy in breast cancer diagnosis: The provincial evaluation of utilization and relationship with treatment outcomes. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research: Genetics, Biology, and Clinical Applications; Oct 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2013;11(10 Suppl):Abstract nr B114.

Stratification of 5-year cancer detection rate in an organized breast screening program based on Gail model risk factors.

7 Background: The Gail model has been validated in the United States and several European countries, but to our knowledge, it has not been validated in organized breast screening programs in Canada. The Screening Mammography Program of British Columbia (SMPBC) records participant data from a questionnaire based on Gail model parameters (which include family and personal medical history). This study investigates whether the Gail model is a valid tool to predict the breast cancer risk for the population undergoing screening mammography in the province of BC. METHODS Client information of the 223,349 British Columbian women who participated in the year 2000, along with their tumor status from 2000-2004, was extracted from the provincial database. A software program was developed to rapidly calculate the absolute 5-year Gail score from questionnaire data. Participant data was separated into .5% risk intervals and also into quintiles based on increasing Gail scores, and the mean absolute risks were compared to the actual five year rate of cancer as detected by the SMPBC. RESULTS Overall, goodness of fit between Gail score and SMPBC detection (E/O) across the categories can be rejected (χ2=247.9, df=9, p value < .001). The Gail model significantly underpredicts the cancer detection for risk categories up to 2%, however it provides a sufficient fit for categories 2%-4% as the E/O ratio is not significantly different from 1.0 in these intervals. For the highest risk interval, categorized as greater than 4% risk, the model significantly overpredicts cancer detection. Additionally, when presented in quintiles, the Gail model under-predicts risk in all but the highest quintile (1.77-11.43% risk range). CONCLUSIONS Our results, based on participants of SMPBC, suggest that the Gail model significantly under-predicts cancer detection. Although this model provides a sufficient fit for women with a Gail score between 1.51-4%, it does not predict breast cancer risk accurately for low and high risk women in the Screening Mammography Program of BC.