Susan C. Harvey

An Abbreviated Protocol for High-Risk Screening Breast MRI Saves Time and Resources

PURPOSE To review the ability of an abbreviated, high-risk, screening, breast MRI protocol to detect cancer and save resources. METHODS High-risk screening breast MR images were reviewed, from both an abbreviated protocol and a full diagnostic protocol. Differences in cancer detection, scanner utilization, interpretation times, and need for additional imaging were recorded in an integrated data form, and reviewed and compared. RESULTS A total of 568 MRI cases were reviewed, with the abbreviated and full protocols. No difference was found in the number of cancers detected. Scan times were decreased by 18.8 minutes per case, for a total of 10,678 minutes (178 hours). Interpretation time, on average, was 1.55 minutes for the abbreviated protocol, compared with 6.43 minutes for the full protocol. Review of the full protocol led to a significant change in the final BI-RADS(®) assessment in 12 of 568 (2.1%) cases. CONCLUSIONS Abbreviated MRI is as effective as full-protocol MRI for demonstration of cancers in the high-risk screening setting, with only 12 (2.1%) cases recommended for additional MRI evaluation. The efficiency and resource savings of an abbreviated protocol would be significant, and would allow for opportunities to provide MRI for additional patients, as well as improved radiologist time management and workflow, with the potential to add real-time MRI interpretation or double reading.

Systematic review of 3D mammography for breast cancer screening

This review investigated the relative performance of digital breast tomosynthesis (DBT) (alone or with full field digital mammography (FFDM) or synthetic digital mammography) compared with FFDM alone for detecting breast cancer lesions in asymptomatic women. A systematic review was carried out according to systematic reviewing principles provided in the Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy. A protocol was developed a priori. The review was registered with PROSPERO (number CRD42014013949). Searches were undertaken in October 2014. Following selection, five studies were eligible. Higher cancer detection rates were observed when comparing DBT + FFDM with FFDM in two European studies: the summary difference per 1000 screens was 2.43 (95% CI: 1.8 to 3.1). Both European studies found lower false positive rates for individual readers. One found a lower recall rate based on conditional recall. The second study was not designed to compare post-arbitration recall rates between FFDM and DBT + FFDM. One European study presented data on interval cancer rates; sensitivity and specificity for DBT + FFDM were both higher compared to FFDM. One large multicentre US study showed a higher cancer detection rate for DBT + FFDM, while two smaller US studies did not find statistically significant differences. Reductions in recall and false positive rates were observed in the US studies in favour of DBT + FFDM. In comparison to FFDM, DBT, as an adjunct to FFDM, has a higher cancer detection rate, increasing the effectiveness of breast cancer screening. Additional benefits of DBT may also include reduced recalls and, consequently, reduced costs and distress caused to women who would have been recalled.

Image-guided core breast biopsy of ductal carcinoma in situ presenting as a non-calcified abnormality

OBJECTIVE Ductal carcinoma in situ (DCIS) typically presents as calcifications which are detected mammographically. Our aim was to evaluate the less common presentations of ductal carcinoma in situ diagnosed by image-guided core biopsy and correlate with histopathologic diagnoses. METHODS AND MATERIAL Imaging and histopathologic findings were retrospectively reviewed in 11 patients with ductal carcinoma in situ diagnosed at core biopsy that presented as noncalcified radiographic abnormalities. RESULTS Mammography showed non-calcified, circumscribed nodules, ill-defined nodules and architectural distortion. In two patients, no mammographic abnormality was detected. Sonography showed circumscribed, round or oval, solid masses; irregular, heterogeneous masses; and a tubular structure. Histopathologic diagnoses included multiple architectural subtypes and ranged from low to high nuclear grade. CONCLUSION Although image-guided core biopsy diagnosis of ductal carcinoma is typically made when sampling calcifications, DCIS can be diagnosed following biopsy of non-calcified masses or distortion. There is no correlation between histopathologic subtype and radiologic appearance.

Metastatic Disease to the Breast From Extramammary Malignancies: A Multimodality Pictorial Review

This pictorial review demonstrates imaging features of extramammary malignancies metastatic to the breast seen with multiple modalities, including mammography, ultrasound, computed tomography (CT), positron emission tomography, and magnetic resonance imaging. Although rare, metastases to the breast may have a distinct imaging appearance from the appearance of primary breast cancers. They are important to identify because they can mimic benign breast disease and their treatment differs from that of primary breast cancer. Metastatic disease to the breast most commonly appears as a single round or oval mass with circumscribed margins. Sonographically it is usually hypoechoic, and with CT or magnetic resonance imaging it usually enhances. In contrast with primary breast cancer, breast metastases do not demonstrate spiculated margins and rarely have associated calcifications. A variety of clinical presentations of breast metastases are reviewed, including presentation with a palpable mass, detection at screening mammography, and detection with CT or positron emission tomography.

An Abbreviated Protocol for High-risk Screening Breast Magnetic Resonance Imaging: Impact on Performance Metrics and BI-RADS Assessment

RATIONALE AND OBJECTIVES Annual breast magnetic resonance imaging (MRI) is recommended to screen high-risk populations for breast cancer, although costs are significant. This study assesses the performance of an abbreviated MRI protocol as a resource-efficient approach for screening patients at high-risk of breast cancer, and assesses whether the abbreviated protocol alters the assigned Breast Imaging Reporting and Data System (BI-RADS) category. MATERIALS AND METHODS This is a prospective paired cohort study performed in an academic ambulatory setting. MRI images of women at high risk of breast cancer were reviewed using an abbreviated MRI protocol, followed by an immediate review of additional sequences included in a full diagnostic protocol. BI-RADS assessments, including all changes and interpretation times, were recorded for both the abbreviated and full protocol reviews. Cancer detection rate, positive predictive value 3 (PPV3), sensitivity, and specificity were calculated. RESULTS A total of 1052 MRI cases were reviewed. The cancer detection rate was 13.3 per 1000 with a PPV3 of 30.4% based on the full protocol. Review of sequences included in the full protocol resulted in a change in the final BI-RADS assessments in 3.4% of the cases, the majority of which did not change clinical management with respect to biopsy. The sensitivity and specificity of the abbreviated and full protocols were not significantly different. CONCLUSIONS This pilot study of an abbreviated MRI protocol demonstrates effective performance in cancer detection. BI-RADS assessments were rarely altered with the additional information afforded by the full protocol. The abbreviated protocol holds promise for resource-efficient breast cancer screening in high-risk women.

Does a Picture Make a Difference? Ultrasound Guidance in the Management of the Axilla After Neoadjuvant Chemotherapy

Tumor size and axillary nodal status are important prognostic indicators and guide management in early-stage breast cancer. Surgery in the form of a sentinel lymph node (SLN) biopsy (SLN surgery) or full axillary lymph node dissection (ALND) remains the standard approach, with SLN surgery now established as the standard initial procedure in patients with a clinically negative axilla in view of its lower morbidity. Consequently, there is interest in expanding the use of SLN surgery alone for some patients with low volume of axillary involvement. Recent findings from the American College of Surgeons Oncology Group (ACOSOG) Trial Z0011 showed that SLN surgery without follow-up ALND could be safely offered to patients with T1-2 tumors and low axillary burden (one or two SLNs involved) when their treatment included lumpectomy and radiation therapy for completion of breast conservation. While this study enrolled fewer patients and had fewer events than originally planned, SLN surgery demonstrated noninferiority for the overall survival end point based on a one-sided hazard ratio margin of 1.3. Despite these limitations, SLN surgery alone has been embraced in the United States as a standard for patients who meet Z0011 eligibility criteria. Of interest, and contrary to protocol requirements, a nontrivial number (in both arms) of trial Z0011 patients received direct nodal irradiation through a third field (high tangents), especially among patients with more nodes involved. The impact of this is, and will remain, unknown. ACOSOG also conducted trial Z1071, where the role of SLN surgery was compared with standard ALND after neoadjuvant chemotherapy in 756 patients with operable breast cancer and pre treatment biopsy proven axillary nodal involvement (cT0-T4 cN1-N2). While feasible, the observed 12.6% false negative rate (FNR) of SLN surgery after neoadjuvant chemotherapy was higher than the clinically accepted cutoff of 10%. Consequently, the Z1071 authors concluded that strategies were needed to optimally identify patients with biopsy proven node-positive disease treated with neoadjuvant therapy whom could then be offered SLN surgery alone as an alternative to ALND. In the article that accompanies this editorial, ACOSOG investigators report on a secondary analysis of trial Z1071. This analysis assessed axillary ultrasound (AUS) as a selection criterion to stratify women for risk of residual axillary involvement following neoadjuvant chemotherapy with the goal of identifying those who could be safely spared a full ALND in the setting of negative SLN surgery. In this report, Z1071 investigators observed that the use of AUS to assess the axilla following neoadjuvant chemotherapy and before surgery reduced the FNR of SLN surgery to 9.8%, below the cutoff of 10%. This new analysis of Z1071 describes a subset of 611 patients who underwent an AUS after neoadjuvant chemotherapy, and whom had similar characteristics (based on age, clinical node status at presentation, completion of chemotherapy, and numbers of nodes removed by ALND, but not race) of patients included in the primary analysis of in trial Z1071. Central review of all images was done by a single radiologist, though no standard imaging protocol or equipment was mandated, and the FNR with and without AUS was reviewed. Four hundred and thirty patients of them (70.4%) had normal nodal anatomy by AUS based on imaging criteria of nodal cortex smaller than 3 mm and a preserved fatty hilum. Among these 430 patients with normal AUS, 342 (56.5% of them) were ultimately found to have node involvement by ALND, while 130 of the 181 patients with abnormal AUS (71.8% of them) had node involvement. These results were statically significant showing that AUS does improve predictions of nodal status. An abnormal AUS after neoadjuvant chemotherapy was also associated with more positive nodes (75.4%) compared with patients with a normal AUS (63.9%). Lower FNR was seen in the group with suspicious nodes at AUS, but this did not reach statistical significance. However, a key point is that if combined, normal AUS and SLN had a FRN of 9.8%, under the 10% threshold for clinical care. Nonetheless, in the setting of normal AUS, only 39.0% of women had complete pathologic response. This high percentage, 61%, without complete pathologic response indicates that at this time, surgical staging remains critical to appropriate care. AUS has been used extensively and is now an established imaging tool to assess the axilla as part of the diagnostic evaluation of a suspicious breast mass and in patients with newly diagnosed breast cancer. Although the performance of AUS is operator dependent, historically it has outperformed other imaging modalities like magnetic resonance imaging or positron imaging. Data on the reported sensitivity (27% to 94%) and specificity (53% to 98%) of AUS varies widely, and the evaluation of its accuracy is JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 33 NUMBER 30 OCTOBER 2

Invasive Breast Cancer Preferably and Predominantly Occurs at the Interface Between Fibroglandular and Adipose Tissue.

Micro‐Abstract The position of invasive breast tumor in relation to fibroglandular and adipose tissue was assessed in this retrospective dynamic contrast‐enhanced magnetic resonance imaging investigation of 294 patients. These tumors were found to occur predominantly at the interface between fibroglandular and adipose tissue. Background: Increasing evidence suggests adipocyte involvement in malignant breast tumor invasive front or margin. The aim of this study was to evaluate the location of invasive breast tumors in relation to fibroglandular and adipose tissue by dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI). Patients and Methods: Pretreatment breast DCE‐MRI images of 294 patients with biopsy‐proven invasive breast cancer from 2008 to 2014 were studied. Invasive breast tumors were visualized as enhanced lesions in the postcontrast subtraction images. Positive identification of biopsy‐confirmed invasive breast tumors on DCE‐MRI images was achieved by correlation of findings from breast MRI and pathology reports. Tumor location in relation to fibroglandular and adipose tissue was investigated using precontrast T1‐weighted MRI images. Results: Of 294 patients, 291 had DCE‐MRI discernable invasive breast tumors located at the interface between fibroglandular and adipose tissues, regardless of the tumor size, type, receptor status, or breast composition. Conclusion: Invasive breast cancer preferably and predominantly occurs adjacent to breast adipose tissue.

Impact of medicare shared savings program accountable care organizations at screening mammography: A retrospective cohort study

Purpose To evaluate the impact of accountable care organizations (ACOs) on use of screening mammography in the Medicare Shared Savings Program (MSSP), the largest value-based reimbursement program in U.S. HISTORY Materials and Methods Institutional review board approval was waived, as the study used publicly available unidentifiable data. Medicare data were retrospectively obtained for participating ACOs from 2012 to 2014. Baseline information and the ACO-20 measure (percentage of women aged 40-69 years who underwent screening mammography within 24 months) were obtained. Negative binomial regression models were used to evaluate baseline and longitudinal mammography use, with stratified analyses performed for year of entry into the ACO, number of beneficiaries, and geographic region. Results A total of 333 ACOs with 5 329 831 Medicare beneficiaries (mean size, 16 006 beneficiaries) participated in the MSSP. Screening use varied across ACOs (median, 63.0%; range, 8.8%-90.3%), with differences found across regions (use was highest in the Midwest [66.6%] and lowest in the South [58.2%], P = .038). A total of 208 ACOs reported longitudinal outcomes, with mean change in screening mammography use of +2.6% (range, -33.2% to +42.2%), with 128 (61.6%) ACOs reporting improvements (incidence rate ratio, 1.04; 95% confidence interval: 1.02, 1.07) (P = .002). No longitudinal differences in use were seen across regions (P = .078), year of entry (P = .902), number of beneficiaries (P = .814), or total composite quality score (P = .324), nor was there a difference between ACOs that saved money and those that did not (P = .391). Conclusion ACOs in the MSSP have produced small significant improvements in screening mammography use.

Strategies for Decreasing Screening Mammography Recall Rates While Maintaining Performance Metrics

RATIONALE AND OBJECTIVE This study aimed to determine the impact of interventions designed to reduce screening mammography recall rates on screening performance metrics. MATERIALS AND METHODS We assessed baseline performance for full-field digital mammography (FFDM) and digital breast tomosynthesis mammography (DBT) for a 3-year period before intervention. The first intervention sought to increase awareness of recalls from screening mammography. Breast imagers discussed their perceptions regarding screening recalls and were required to review their own recalled cases, including outcomes of diagnostic evaluation and biopsy. The second intervention implemented consensus double reading of all recalls, requiring two radiologists to agree if recall was necessary. Recall rates, cancer detection rates, and positive predictive value 1 (PPV1) were compared before and after each intervention. RESULTS The baseline recall rate, cancer detection rate, and PPV1 were 11.1%, 3.8/1000, and 3.4%, respectively, for FFDM, and 7.6%, 4.8/1000, and 6.0%, respectively, for DBT. Recall rates decreased significantly to 9.2% for FFDM and to 6.6% for DBT after the first intervention promoting awareness, as well as to 9.9% for FFDM after the second intervention implementing group consensus. PPV1 increased significantly to 5.7% for FFDM and to 9.0% for DBT after the second intervention. Cancer detection rate did not significantly change with the implementation of these interventions. An average of 2.3 minutes was spent consulting for each recall. CONCLUSION Reduction in recall rates is desirable, provided performance metrics remain favorable. Our interventions improved performance and could be implemented in other breast imaging settings.

Imaging of Nonprostate Cancers Using PSMA-Targeted Radiotracers: Rationale, Current State of the Field, and a Call to Arms

Prostate-specific membrane antigen (PSMA) is a type II transmembrane glycoprotein that is highly overexpressed on prostate cancer epithelial cells and for which there is a growing body of literature examining the role of small-molecule and antibody radiotracers targeted against this protein for prostate cancer detection and therapy. Despite its name, PSMA is also expressed, to varying degrees, in the neovasculature of a wide variety of nonprostate cancers; indeed, the pathology literature is replete with promising immunohistochemistry findings. Several groups have begun to correlate those pathology-level results with in vivo imaging and therapy in nonprostate cancers using the same PSMA-targeted agents that have been so successful in prostate cancer. The potential to leverage radiotracers targeted to PSMA beyond prostate cancer is a promising approach for many cancers, and PSMA-targeted agents may be able to supplement or fill gaps left by other agents. However, to date, most of the reported findings with PSMA-targeted radiotracers in nonprostate malignancies have been in case reports and small case series, and the field must adopt a more thorough approach to the design and execution of larger prospective trials to realize the potential of these promising agents outside prostate cancer.