Paula B. Gordon

Ultrasound for breast cancer screening and staging

The question then arises whether and for whom BWBS should be recommended. As yet there are no scientific criteria on which to base an answer, and the examination should not be considered the standard of care until its benefits can be established prospectively. We know that mass screening mammography will detect occult cancers in two to seven of every 1000 women screened, depending on patient age and whether the screens are prevalence or incidence examinations. Should we expect a similar yield for survey US? Kopans commented that Kolbs cancer detection rate was lower than would be expected from a mammographic prevalence screen. This was not a reasonable comparison. These women all had negative findings on screening mammography and would normally be told to have repeat screening mammography 1 year later. Kolbs cancer detection rate using US was comparable to a mammographic incidence screen, so the cancer diagnoses of these fortunate women were advanced by 1 year. To maximize the yield, it is obvious that US has little to offer over mammography in women with fatty breasts because mammography is less likely to be falsely negative. The group of patients in whom incidental cancers would be expected to be found more commonly are those with dense breasts who also are at higher-than-average risk either because of a previous personal history of breast cancer (Fig. 2) or a significant family history. Because it would be impractical to consider BWBS for all women with radiographically dense breasts, it would be useful to know what its potential yield would be in the relatively smaller group of high-risk patients. Annual mammography remains the standard of care for breast cancer screening. However, in our practice in Vancouver, I suggest that high-risk women undergo mammography and US annually, recognizing that this goes beyond the standard of care. Instead of having both examinations simultaneously, I recommend that they alternate the two modalities at 6-month intervals. Theoretically, this could increase lead-time in the detection of occult cancers. The usefulness of this approach remains to be determined. BWBS for staging in women known to have breast cancer has tremendous promise and should be considered for any breast cancer patient with dense breast tissue in whom the finding of additional unsuspected foci would change the planned management. The cost of implementation would be substantial but considerably less than staging MRI. A large-scale study comparing these two modalities is needed, including assessment of the impact of identifying additional mammographically occult lesions on breast cancer mortality.

Early Hydronephrosis following Aortic Bifurcation Graft Surgery: A Prospective Study

The true incidence and natural history of ureteral obstruction following reconstructive vascular surgery have not been determined previously. A series of 101 patients undergoing aortofemoral and aortoiliac reconstructive surgery were studied prospectively to determine the frequency of hydronephrosis in the first postoperative year. Serial real-time ultrasound examinations were performed preoperatively as well as at 1 week, 3 months and 1 year postoperatively. Ninety-three patients completed the study, with a total of 181 kidneys at risk. Hydronephrosis of mild to moderate degree developed in 15 kidneys (8 per cent) in 11 patients (12 per cent). All patients were asymptomatic, and the obstruction resolved spontaneously in 10 of 11 patients, including 9 within 3 months of onset. Only a single case persisted at 1 year. This study confirms that the hydronephrosis that occurs within the first year after aortic bifurcation graft surgery is not uncommon but it is rarely of clinical significance in the asymptomatic patient.

Ultrasound RF Time Series for Classification of Breast Lesions

This work reports the use of ultrasound radio frequency (RF) time series analysis as a method for ultrasound-based classification of malignant breast lesions. The RF time series method is versatile and requires only a few seconds of raw ultrasound data with no need for additional instrumentation. Using the RF time series features, and a machine learning framework, we have generated malignancy maps, from the estimated cancer likelihood, for decision support in biopsy recommendation. These maps depict the likelihood of malignancy for regions of size 1 mm2 within the suspicious lesions. We report an area under receiver operating characteristics curve of 0.86 (95% confidence interval [CI]: 0.84%-0.90%) using support vector machines and 0.81 (95% CI: 0.78-0.85) using Random Forests classification algorithms, on 22 subjects with leave-one-subject-out cross-validation. Changing the classification method yielded consistent results which indicates the robustness of this tissue typing method. The findings of this report suggest that ultrasound RF time series, along with the developed machine learning framework, can help in differentiating malignant from benign breast lesions, subsequently reducing the number of unnecessary biopsies after mammography screening.

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.

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.

The negative predictive value of ultrasound-guided 14-gauge core needle biopsy of breast masses: a validation study of 339 cases.

Abstract Purpose: To determine the negative predictive value of sonographically guided 14-gauge core needle biopsy of breast masses, with detailed analysis of any false-negative cases. Materials and methods: We reviewed 669 cases of sonographically guided 14-gauge core needle biopsies that had benign pathologic findings. Given a benign pathology on core biopsy, true-negatives had either benign pathology on surgical excision or at least 2 years of stable imaging and/or clinical follow-up; false-negatives had malignant histology on surgical excision. Results: Follow-up was available for 339 breast lesions; 117 were confirmed to be benign via surgical excision, and 220 were stable after 2 years or more of imaging or clinical follow-up (mean follow-up time 33.1 months, range 24–64 months). The negative predictive value was determined to be 99.4%. There were 2 false-negative cases, giving a false-negative rate of 0.1%. There was no delay in diagnosis in either case because the radiologist noted discordance between imaging and core biopsy pathology, and recommended surgical excision despite the benign core biopsy pathology. Conclusions: Sonographically guided 14-gauge core needle biopsy provides a high negative predictive value in assessing breast lesions. Radiologic/pathologic correlation should be performed to avoid delay in the diagnosis of carcinoma.

Impact of changing from annual to biennial mammographic screening on breast cancer outcomes in women aged 50-79 in British Columbia

Objectives The objective of this study was to compare breast cancer outcomes among women subject to different policies on mammography screening frequency. Setting Data were obtained for women participating in the Screening Mammography Programme of British Columbia (SMPBC) for 1988–2005. The SMPBC changed its policy for women aged 50–79 years from annual to biennial mammography in 1997, but retained an annual recommendation for women aged 40–49 years. Methods Breast cancer outcomes were compared for women participating in the programme before and after 1997 for two groups: ages 40–49 and 50–79 years. Results There were data on 658,151 women. Comparing pre-1997 and post-1997, the median interscreen interval increased by 11.1 months in women 50–79 but by only 0.3 months in women aged 40–49. Excluding those detected at initial screen, 6291 breast cancers were identified. Comparing pre-1997 and post-1997: the relative rates (RR) of screen detected cancer increased in women aged 40–49 (RR = 1.32) and the rate of invasive cancers ≥20 mm at diagnosis decreased (RR = 0.83); the rate of cancers with axillary node involvement increased in women aged 50–79 (RR = 1.23). Cancer survival improved after 1997 for women diagnosed at ages 40–49 (hazard ratio = 0.62), but was unchanged for women aged 50–79. Breast cancer mortality rates did not change between the periods in either age group. Conclusion The proximal cancer outcomes considered (staging and survival) improved in women aged 40–49 but this was offset in women aged 50–79 associated with the change in screen frequency. These changes did not result in alterations in breast cancer mortality rates in either age group.

Clarifying the debate on population-based screening for breast cancer with mammography: A systematic review of randomized controlled trials on mammography with Bayesian meta-analysis and causal model

Background: The recent controversy about using mammography to screen for breast cancer based on randomized controlled trials over 3 decades in Western countries has not only eclipsed the paradigm of evidence-based medicine, but also puts health decision-makers in countries where breast cancer screening is still being considered in a dilemma to adopt or abandon such a well-established screening modality. Methods: We reanalyzed the empirical data from the Health Insurance Plan trial in 1963 to the UK age trial in 1991 and their follow-up data published until 2015. We first performed Bayesian conjugated meta-analyses on the heterogeneity of attendance rate, sensitivity, and over-detection and their impacts on advanced stage breast cancer and death from breast cancer across trials using Bayesian Poisson fixed- and random-effect regression model. Bayesian meta-analysis of causal model was then developed to assess a cascade of causal relationships regarding the impact of both attendance and sensitivity on 2 main outcomes. Results: The causes of heterogeneity responsible for the disparities across the trials were clearly manifested in 3 components. The attendance rate ranged from 61.3% to 90.4%. The sensitivity estimates show substantial variation from 57.26% to 87.97% but improved with time from 64% in 1963 to 82% in 1980 when Bayesian conjugated meta-analysis was conducted in chronological order. The percentage of over-detection shows a wide range from 0% to 28%, adjusting for long lead-time. The impacts of the attendance rate and sensitivity on the 2 main outcomes were statistically significant. Causal inference made by linking these causal relationships with emphasis on the heterogeneity of the attendance rate and sensitivity accounted for the variation in the reduction of advanced breast cancer (none-30%) and of mortality (none-31%). We estimated a 33% (95% CI: 24–42%) and 13% (95% CI: 6–20%) breast cancer mortality reduction for the best scenario (90% attendance rate and 95% sensitivity) and the poor scenario (30% attendance rate and 55% sensitivity), respectively. Conclusion: Elucidating the scenarios from high to low performance and learning from the experiences of these trials helps screening policy-makers contemplate on how to avoid errors made in ineffective studies and emulate the effective studies to save women lives.

Identifying malignant and benign breast lesions using vibroelastography

Vibroelastography is a technique to measure tissue elasticity using a multi-frequency shear wave approach. The method uses ultrasound to image dynamic deformation of soft tissue while an actuator applies surface vibrations. In this paper we evaluate vibroelastography for the first time in differentiating between malignant and benign breast lesions. A dataset of 20 lesions, including fibroadenoma and invasive ductal carcinoma (IDC) lesions was analysed. Ultrasound radio-frequency data were captured while the breast tissue was vibrated with a snap-on actuator at multiple frequencies at an amplitude of less than 100 microns. After the VE exam, the subjects underwent core-needle biopsy. The pathology report was used as the ground truth to validate the VE result. The VE results indicate that both benign fibroadenoma and IDC result in hardening of the tissue; however, IDC lesions exhibits higher values of elasticity compared to benign masses which can be captured using absolute and relative elasticity maps provided by VE.

A new approach to ultrasonic detection of malignant breast tumors

In this work, we report the use of ultrasound RF time series analysis for separating benign and malignant breast lesions with similar B-mode appearance. The RF time series method is versatile and requires only a few seconds of imaging. We have employed the spectral and fractal features of ultrasound RF time series and used support vector machines with leave-one-patient-out cross validation of the classification. We have also produced cancer probability maps, by estimating the posterior malignancy probability of regions of size 1 mm2 in the suspicious lesions. The first 12 patient cases of our ongoing study are reported here. Pathologic analysis of the cores using ultrasound guided needle biopsy confirmed the tissue type. We report an area under receiver operating characteristic curve of 0.82. We were able to successfully classify 6 out of 7 patients with malignant breast lesions and 4 out of 5 patients with benign lesions, with success defined as correct classification of at least 75% of the 1 mm2 regions in the area of the lesion. The above findings suggest that ultrasound time series along with support vector machines can help in differentiating malignant from benign breast lesions.