Dense Breast Notification and Supplemental Screening: A Survey of Current Strategies and Sentiments.

Dense breast parenchyma obscures breast lesions and has been shown to be an independent risk factor for development of breast cancer. An ever-increasing number of states have approved laws requiring patient notification of dense breast tissue. Reviews of supplemental screening imaging modalities are available, but there is no consensus and little discussion regarding what radiologists are specifically doing to manage patients with dense breasts. Our goal was to survey breast imagers facing these issues in an effort to simplify dense breast management. A survey was administered via email to the Society of Breast Imaging member directory, designed to collect information regarding current practices in dense breast notification and supplemental screening. There were 223 surveys completed to entirety, including 38% from respondents in states without mandatory breast density reporting laws and 62% from states with reporting laws. A majority of respondents from both groups, 60% and 51% in those without and with laws, respectively, felt they lacked adequate resources to offer or sustain supplemental screening. In those offering supplemental imaging, the modalities offered varied widely as did the manner of offering a supplemental exam. Levels of satisfaction, concerns, and standard practices of respondents were also queried. Strategizing optimal imaging approaches and algorithms to handle dense breast management issues is important to maintain efficiency in breast imaging departments. Sharing current ideas and practices may facilitate a smoother workflow in mandatory dense breast reporting and supplemental imaging, allowing breast imagers to correct or prevent systems-based flaws.

Exome sequencing reveals frequent deleterious germline variants in cancer susceptibility genes in women with invasive breast cancer undergoing neoadjuvant chemotherapy.

When sequencing blood and tumor samples to identify targetable somatic variants for cancer therapy, clinically relevant germline variants may be uncovered. We evaluated the prevalence of deleterious germline variants in cancer susceptibility genes in women with breast cancer referred for neoadjuvant chemotherapy and returned clinically actionable results to patients. Exome sequencing was performed on blood samples from women with invasive breast cancer referred for neoadjuvant chemotherapy. Germline variants within 142 hereditary cancer susceptibility genes were filtered and reviewed for pathogenicity. Return of results was offered to patients with deleterious variants in actionable genes if they were not aware of their result through clinical testing. 124 patients were enrolled (median age 51) with the following subtypes: triple negative (n = 43, 34.7%), HER2+ (n = 37, 29.8%), luminal B (n = 31, 25%), and luminal A (n = 13, 10.5%). Twenty-eight deleterious variants were identified in 26/124 (21.0%) patients in the following genes: ATM (n = 3), BLM (n = 1), BRCA1 (n = 4), BRCA2 (n = 8), CHEK2 (n = 2), FANCA (n = 1), FANCI (n = 1), FANCL (n = 1), FANCM (n = 1), FH (n = 1), MLH3 (n = 1), MUTYH (n = 2), PALB2 (n = 1), and WRN (n = 1). 121/124 (97.6%) patients consented to return of research results. Thirteen (10.5%) had actionable variants, including four that were returned to patients and led to changes in medical management. Deleterious variants in cancer susceptibility genes are highly prevalent in patients with invasive breast cancer referred for neoadjuvant chemotherapy undergoing exome sequencing. Detection of these variants impacts medical management.

Malignancy rates of non-masslike enhancement on breast magnetic resonance imaging using American College of Radiology Breast Imaging Reporting and Data System descriptors.

The purpose of this study was to evaluate the malignancy rates for non-masslike enhancement on breast magnetic resonance imaging by American College of Radiology Breast Imaging Reporting and Data System descriptors. We retrospectively reviewed breast magnetic resonance imaging reports with non-masslike enhancement performed at Mayo Clinic Florida from April 1, 2003, through March 14, 2007. Each descriptor of non-masslike enhancement as per the American College of Radiology Breast Imaging Reporting and Data System magnetic resonance lexicon was correlated with percutaneous biopsy pathologic results and/or surgical pathologic results and follow-up imaging. Positive predictive values were obtained for each Breast Imaging Reporting and Data System descriptor. We identified 578 incidents of non-masslike enhancement in 378 patients. Of 343 non-masslike enhancements that could be correlated with pathology results, 141 (41.1%) were malignant. Of the malignant lesions, 53% were found to be ductal carcinoma in situ at percutaneous biopsy. Clumped pattern of enhancement and segmental distribution of non-masslike enhancement had the highest sensitivities of 40.5% and 23.5%, respectively. Asymmetric pattern and segmental distribution had the highest positive predictive values of 75.0% and 57.4%, respectively. We concluded that the moderate positive predictive values make it difficult to establish guidelines for management of non-masslike enhancement and reveal the current limitations of breast magnetic resonance imaging.

Bilateral Myeloid Sarcoma of the Breast: A Case Report With Radiological and Pathological Correlation.

Myeloid sarcoma is a solid extramedullary mass of immature myeloid cells, often in patients with myeloid leukemia. Myeloid sarcoma of the breast is extremely uncommon, and bilateral involvement is even rarer. Myeloid sarcoma of the breast can mimic primary breast cancer, lymphoma, and other neoplasms. Differentiation between myeloid sarcoma and primary breast malignancy is imperative, as management and treatment are drastically different. We present a case of myeloid sarcoma of both breasts in a 63-year-old female with relapsed acute myelogenous leukemia (AML), a personal history of ovarian cancer, and a family history of both leukemia and breast cancer. This report highlights the need for high clinical, radiological, and pathological suspicion to diagnose myeloid sarcoma of the breast.

Value of Axillary Ultrasound after Negative Axillary MRI for Evaluating Nodal Status in High-Risk Breast Cancer.

BACKGROUND: It is assumed that axillary ultrasound (AxUS) is the best method for axillary nodal evaluation in newly diagnosed breast cancer patients. However, few have evaluated the efficacy of preoperative axillary MRI. We compared the statistical accuracy of AxUS and MRI in detecting nodal metastases among breast cancer patients who were selected for neoadjuvant chemotherapy. STUDY DESIGN: We retrospectively analyzed 219 breast cancer patients undergoing neoadjuvant chemotherapy from 2007 to 2015, all of whom had AxUS and breast MRI before chemotherapy. Two breast radiologists, blinded to clinical, pathologic, and AxUS findings, re-reviewed all breast MRIs, specifically focusing on axillary nodal characteristics. We correlated clinico-pathologic characteristics, AxUS, and MRI findings, and quantified predictive values of both imaging modalities. RESULTS: Overall, 101 of 219 (47%) patients had T2 tumors. The most common abnormal nodal finding was size >10 mm. Axillary ultrasound and MRI agreed on nodal status in 192 of 219 patients (87.6%). When correlated with pre-chemotherapy needle biopsy in 129 patients, AxUS and axillary MRI performed similarly (sensitivity of 99.1% vs 97.4% and specificity 15.4% vs 15.4%, respectively). Only 4 of 129 (3.1%) patients had a negative MRI and positive AxUS; 3 of 4 of these patients (75%) had a positive biopsy and 2 of 3 had positive lymph nodes on final pathology, therefore suggesting MRI missed clinically significant disease in only 2 of 129 (1.5%) patients. CONCLUSIONS: In a high-risk patient population, AxUS and MRI have similar statistical profiles in evaluating axillary nodal status. Routine use of AxUS after a normal axillary MRI is not warranted.

Breast Density Reporting Laws and Supplemental Screening-A Survey of Referring Providers' Experiences and Understanding.

Dense breast parenchyma obscures breast lesions on mammography and is an independent risk factor for development of breast cancer. Many states have approved laws requiring patient notification of dense breast tissue. Supplemental screening modalities are available however their utilization and efficacy are quite variable. Our aim was to survey primary care providers in an effort to gauge awareness of and familiarity with dense breast legislation and supplemental screening. A multisite survey was administered via e-mail to all Mayo Clinic staff physicians, residents and fellows, as well as nurse practitioners and physician assistants in the departments of Internal Medicine, Family Medicine, and Obstetrics and Gynecology. 362 responses were collected. 68% of respondents were aware of breast density notification laws; 32% had no knowledge of these laws. Implementation of supplemental imaging was variable. Of eligible respondents, 26% offered a supplemental examination to every patient with dense breasts, 47% offered it only to certain patients based upon unique patient or risk factors, 15% did not offer supplemental examinations, and 11% offered an examination based on other criteria. When assessing comfort level in answering questions regarding breast density, 32% were "slightly comfortable" and 18% were "not comfortable." When estimating the percentage of patients with adequate insurance coverage for supplemental imaging, 62% were unsure while 11% did not inquire. Despite public and legislative support, there is a lack of familiarity and considerable practice variation among primary care providers when managing patients with mammographically dense breast tissue. Further research and advances in patient and provider education on this topic are needed to improve management. Radiologists can assist by educating referring providers and consolidating imaging strategies to help circumvent systems-based flaws.

Tumor Sequencing and Patient-Derived Xenografts in the Neoadjuvant Treatment of Breast Cancer.

Background: Breast cancer patients with residual disease after neoadjuvant chemotherapy (NAC) have increased recurrence risk. Molecular characterization, knowledge of NAC response, and simultaneous generation of patient-derived xenografts (PDXs) may accelerate drug development. However, the feasibility of this approach is unknown. Methods: We conducted a prospective study of 140 breast cancer patients treated with NAC and performed tumor and germline sequencing and generated patient-derived xenografts (PDXs) using core needle biopsies. Chemotherapy response was assessed at surgery. Results: Recurrent "targetable" alterations were not enriched in patients without pathologic complete response (pCR); however, upregulation of steroid receptor signaling and lower pCR rates (16.7%, 1/6) were observed in triple-negative breast cancer (TNBC) patients with luminal androgen receptor (LAR) vs basal subtypes (60.0%, 21/35). Within TNBC, TP53 mutation frequency (75.6%, 31/41) did not differ comparing basal (74.3%, 26/35) and LAR (83.3%, 5/6); however, TP53 stop-gain mutations were more common in basal (22.9%, 8/35) vs LAR (0.0%, 0/6), which was confirmed in The Cancer Genome Atlas and British Columbia data sets. In luminal B tumors, Ki-67 responses were observed in tumors that harbored mutations conferring endocrine resistance ( p53, AKT, and IKBKE ). PDX take rate (27.4%, 31/113) varied according to tumor subtype, and in a patient with progression on NAC, sequencing data informed drug selection (olaparib) with in vivo antitumor activity observed in the primary and resistant (postchemotherapy) PDXs. Conclusions: In this study, we demonstrate the feasibility of tumor sequencing and PDX generation in the NAC setting. "Targetable" alterations were not enriched in chemotherapy-resistant tumors; however, prioritization of drug testing based on sequence data may accelerate drug development.

Classification system for identifying women at risk for altered partial breast irradiation recommendations after breast magnetic resonance imaging.

PURPOSE: To study the utility of preoperative breast MRI for partial breast irradiation (PBI) patient selection, using multivariable analysis of significant risk factors to create a classification rule. METHODS AND MATERIALS: Between 2002 and 2009, 712 women with newly diagnosed breast cancer underwent preoperative bilateral breast MRI at Mayo Clinic Florida. Of this cohort, 566 were retrospectively deemed eligible for PBI according to the National Surgical Adjuvant Breast and Bowel Project Protocol B-39 inclusion criteria using physical examination, mammogram, and/or ultrasound. Magnetic resonance images were then reviewed to determine their impact on patient eligibility. The patient and tumor characteristics were evaluated to determine risk factors for altered PBI eligibility after MRI and to create a classification rule. RESULTS: Of the 566 patients initially eligible for PBI, 141 (25%) were found ineligible because of pathologically proven MRI findings. Magnetic resonance imaging detected additional ipsilateral breast cancer in 118 (21%). Of these, 62 (11%) had more extensive disease than originally noted before MRI, and 64 (11%) had multicentric disease. Contralateral breast cancer was detected in 28 (5%). Four characteristics were found to be significantly associated with PBI ineligibility after MRI on multivariable analysis: premenopausal status (P=.021), detection by palpation (P<.001), first-degree relative with a history of breast cancer (P=.033), and lobular histology (P=.002). Risk factors were assigned a score of 0-2. The risk of altered PBI eligibility from MRI based on number of risk factors was 0:18%; 1:22%; 2:42%; 3:65%. CONCLUSIONS: Preoperative bilateral breast MRI altered the PBI recommendations for 25% of women. Women who may undergo PBI should be considered for breast MRI, especially those with lobular histology or with 2 or more of the following risk factors: premenopausal, detection by palpation, and first-degree relative with a history of breast cancer.

The role of preoperative bilateral breast magnetic resonance imaging in patient selection for partial breast irradiation in ductal carcinoma in situ.

Purpose. Women with ductal carcinoma in situ (DCIS) are often candidates for breast-conserving therapy, and one option for radiation treatment is partial breast irradiation (PBI). This study evaluates the use of preoperative breast magnetic resonance imaging (MRI) for PBI selection in DCIS patients. Methods. Between 2002 and 2009, 136 women with newly diagnosed DCIS underwent a preoperative bilateral breast MRI at Mayo Clinic in Florida. One hundred seventeen women were deemed eligible for PBI by the NSABP B-39 (National Surgical Adjuvant Breast and Bowel Project, Protocol B-39) inclusion criteria using physical examination, mammogram, and/or ultrasound. MRIs were reviewed for their impact on patient eligibility, and findings were pathologically confirmed. Results. Of the 117 patients, 23 (20%) were found ineligible because of pathologically proven MRI findings. MRI detected additional ipsilateral breast cancer in 21 (18%) patients. Of these women, 15 (13%) had more extensive disease than originally noted before MRI, and 6 (5%) had multicentric disease in the ipsilateral breast. In addition, contralateral breast cancer was detected in 4 (4%). Conclusions. Preoperative breast MRI altered the PBI recommendations for 20% of women. Bilateral breast MRI should be an integral part of the preoperative evaluation of all patients with DCIS being considered for PBI.

Clinical experience with MRI-guided vacuum-assisted breast biopsy.

OBJECTIVE: The objective of our study was to evaluate a new commercially available method of MRI-guided vacuum-assisted breast biopsy using an open coil and a closed 1.5-T scanner. MATERIALS AND METHODS: Consecutive MRI-guided vacuum-assisted breast biopsies of 38 lesions in 28 women performed between May and September 2003 at two practice sites in the United States were retrospectively reviewed. Lesion characteristics including size, morphology, and enhancement were recorded. Times to perform each procedure, defined as the time from the start of the first localizing scan to the final scan after biopsy, were recorded. Histologic results for all lesions were obtained, and surgical, imaging, or clinical follow-up was performed. RESULTS: Enhancing masses and foci ranged from 2.5 to 19 mm. Nonmasslike enhancements ranged from 6 to 70 mm. All 38 biopsies (100%) were technically successful, and no complications were associated with any of the biopsy procedures. The average time to perform the 19 single-site MRI-guided procedures was 38 min (range, 23-57 min). The 11 multiple-site biopsies performed in a single breast averaged 59 min (range, 51-68 min), and eight bilateral biopsies averaged 64 min (range, 46-80 min). Histologic results from vacuum-assisted breast biopsy revealed malignancy in 14 lesions (37%), atypical ductal hyperplasia in two lesions (5%), and benign findings in 22 lesions (58%). One of two lesions with atypical ductal hyperplasia was upgraded to ductal carcinoma in situ after surgery, for an overall cancer yield of 40% (15/38). CONCLUSION: This new method of MRI-guided vacuum-assisted breast biopsy is a safe, effective, and time-efficient means of MRI-guided tissue sampling.

The role of positron emission tomographic imaging in breast cancer.

Studies have shown that deoxy-2-fluorodeoxyglucose ((18)FDG) positron emission tomography (PET) has limited value in detecting primary tumors and axillary lymph node involvement in breast cancer. PET is most successful when it is used to evaluate locally advanced breast tumors. Identification of smaller, earlier-stage tumors and noninvasive or lobular tumors has been suboptimal. Because of several factors, PET should not replace standard techniques for evaluation of breast cancer, especially for micrometastasis. However, PET can provide invaluable information about disease extent, recurrent disease, and distant metastases, and this information can affect treatment decisions. (18)FDG PET can also facilitate the differentiation of therapy responders from nonresponders, allowing treatment regimen changes at an earlier stage.