Prospective Evaluation of Immune Activation Associated with Response to Radioembolization Assessed with PET/CT in Women with Breast Cancer Liver Metastasis.

Background The impact of transarterial radioembolization (TARE) of breast cancer liver metastasis (BCLM) on antitumor immunity is unknown, which hinders the optimal selection of candidates for TARE. Purpose To determine whether response to TARE at PET/CT in participants with BCLM is associated with specific immune markers (cytokines and immune cell populations). Materials and Methods This prospective pilot study enrolled 23 women with BCLM who planned to undergo TARE (June 2018 to February 2020). Peripheral blood and liver tumor biopsies were collected at baseline and 1-2 months after TARE. Monocyte, myeloid-derived suppressor cell (MDSC), interleukin (IL), and tumor-infiltrating lymphocyte (TIL) levels were assessed with use of gene expression studies and flow cytometry, and immune checkpoint and cell surface marker levels with immunohistochemistry. Modified PET Response Criteria in Solid Tumors was used to determine complete response (CR) in treated tissue. After log-transformation, immune marker levels before and after TARE were compared using paired t tests. Association with CR was assessed with Wilcoxon rank-sum or unpaired t tests. Results Twenty women were included. After TARE, peripheral IL-6 (geometric mean, 1.0 vs 1.6 pg/mL; P = .02), IL-10 (0.2 vs 0.4 pg/mL; P = .001), and IL-15 (1.9 vs 2.4 pg/mL; P = .01) increased. In biopsy tissue, lymphocyte activation gene 3-positive CD4+ TILs (15% vs 31%; P < .001) increased. Eight of 20 participants (40% [exact 95% CI: 19, 64]) achieved CR. Participants with CR had lower baseline peripheral monocytes (10% vs 29%; P < .001) and MDSCs (1% vs 5%; P < .001) and higher programmed cell death protein (PD) 1-positive CD4+ TILs (59% vs 26%; P = .006) at flow cytometry and higher PD-1+ staining in tumor (2% vs 1%; P = .046). Conclusion Complete response to transarterial radioembolization was associated with lower baseline cytokine, monocyte, and myeloid-derived suppressor cell levels and higher programmed cell death protein 1-positive tumor-infiltrating lymphocyte levels. © RSNA, 2022 Online supplemental material is available for this article.

Malignant perivascular epithelioid cell tumor of the ileum on 18F-fluorodeoxyglucose positron emission tomography/ computed tomography with pathological correlation.

A 75-year-old woman presented with a 1-month history of abdominal pain. Contrast-enhanced computed tomography (CT) demonstrated a large solid mass in the left lower abdominal quadrant, suspicious for malignancy. Staging with 18F-fluorodeoxyglucose (FDG) positron emission tomography/CT imaging demonstrated intense FDG uptake in the mass with no evidence of metastatic disease. Complete surgical resection was performed, and histopathological analysis confirmed a malignant perivascular epithelioid cell tumor of the ileum.

Head-to-Head Evaluation of 18F-FES and 18F-FDG PET/CT in Metastatic Invasive Lobular Breast Cancer.

Invasive lobular carcinoma (ILC) demonstrates lower conspicuity on 18F-FDG PET than the more common invasive ductal carcinoma. Other molecular imaging methods may be needed for evaluation of this malignancy. As ILC is nearly always (95%) estrogen receptor (ER)-positive, ER-targeting PET tracers such as 16α-18F-fluoroestradiol (18F-FES) may have value. We reviewed prospective trials at Memorial Sloan Kettering Cancer Center using 18F-FES PET/CT to evaluate metastatic ILC patients with synchronous 18F-FDG and 18F-FES PET/CT imaging, which allowed a head-to-head comparison of these 2 PET tracers. Methods: Six prospective clinical trials using 18F-FES PET/CT in patients with metastatic breast cancer were performed at Memorial Sloan Kettering Cancer Center from 2008 to 2019. These trials included 92 patients, of whom 14 (15%) were of ILC histology. Seven of 14 patients with ILC had 18F-FDG PET/CT performed within 5 wk of the research 18F-FES PET/CT and no intervening change in management. For these 7 patients, the 18F-FES and 18F-FDG PET/CT studies were analyzed to determine the total number of tracer-avid lesions, organ systems of involvement, and SUVmax of each organ system for both tracers. Results: In the 7 comparable pairs of scans, there were a total of 254 18F-FES-avid lesions (SUVmax, 2.6-17.9) and 111 18F-FDG-avid lesions (SUVmax, 3.3-9.9) suggestive of malignancy. For 5 of 7 (71%) ILC patients, 18F-FES PET/CT detected more metastatic lesions than 18F-FDG PET/CT. In the same 5 of 7 patients, the SUVmax of 18F-FES-avid lesions was greater than the SUVmax of 18F-FDG-avid lesions. One patient had 18F-FES-avid metastases with no corresponding 18F-FDG-avid metastases. There were no patients with 18F-FDG-avid distant metastases without 18F-FES-avid distant metastases, although in one patient liver metastases were evident on 18F-FDG but not on 18F-FES PET. Conclusion:18F-FES PET/CT compared favorably with 18F-FDG PET/CT for detection of metastases in patients with metastatic ILC. Larger prospective trials of 18F-FES PET/CT in ILC should be considered to evaluate ER-targeted imaging for clinical value in patients with this histology of breast cancer.

Regional Lymph Node Involvement Among Patients With De Novo Metastatic Breast Cancer.

Importance: Regional nodal irradiation (RNI) for node-positive breast cancer reduces distant metastases and improves survival, albeit with limited reduction in regional nodal recurrences. The mechanism by which RNI robustly reduces distant metastases while modestly influencing nodal recurrences (ie, the presumed target of RNI) remains unclear. Objective: To determine whether some distant metastases putatively arise from occult regional nodal disease and whether regional recurrences otherwise remain largely undetected until an advanced cancer presentation. Design, Setting, and Participants: This cohort study examined patients presenting with de novo stage IV breast cancer to the Memorial Sloan Kettering Cancer Center in New York, New York, from 2006 to 2018. Medical records were reviewed to ascertain clinicopathological parameters, including estrogen receptor status and survival. Pretreatment positron emission tomography-computed tomography (PET-CT) imaging was reviewed to ascertain the extent of regional nodal involvement at metastatic diagnosis using standard nodal assessment criteria. A subset underwent regional lymph node biopsy for diagnostic confirmation and served to validate the radiographic nodal assessment. Data analysis was performed from October 2019 to February 2020. Exposures: Untreated metastatic breast cancer. Main Outcome and Measures: The primary outcome was the likelihood of regional nodal involvement at the time of metastatic breast cancer presentation and was determined by reviewing pretreatment PET-CT imaging and lymph node biopsy findings. Results: Among 597 women (median [interquartile range] age, 53 [44-65] years) with untreated metastatic breast cancer, 512 (85.8%) exhibited regional lymph node involvement by PET-CT or nodal biopsy, 509 (85%) had involvement of axillary level I, 328 (55%) had involvement in axillary level II, 136 (23%) had involvement in axillary level III, 101 (17%) had involvement in the supraclavicular fossa, and 96 (16%) had involvement in the internal mammary chain. Lymph node involvement was more prevalent among estrogen receptor-negative tumors (92.4%) than estrogen receptor-positive tumors (83.6%). Nodal involvement at the time of metastatic diagnosis was not associated with overall survival. Conclusions and Relevance: These findings suggest that a majority of patients with de novo metastatic breast cancer harbor regional lymph node disease at presentation, consistent with the hypothesis that regional involvement may precede metastatic dissemination. This is in alignment with the findings of landmark trials suggesting that RNI reduces distant recurrences. It is possible that this distant effect of RNI may act via eradication of occult regional disease prior to systemic seeding. The challenges inherent in detecting isolated nodal disease (which is typically asymptomatic) may account for the more modest observed benefit of RNI on regional recurrences. Alternative explanations of nodal involvement that arises concurrently or after metastatic dissemination remain possible, but do not otherwise explain the association of RNI with distant recurrence.

18F-FDG PET/CT Helps Differentiate Peripheral Nerve Myeloid Sarcoma From a Presumed Benign Nerve Sheath Tumor.

A 21-year-old man with NF1 (neurofibromatosis type 1) mutation and in remission from acute myeloid leukemia presented with a painless mass in the left upper limb. MRI showed a soft-tissue mass involving the ulnar nerve presumed to be a nerve sheath tumor. F-FDG PET/CT was performed demonstrating high FDG avidity in the mass, prompting a biopsy. Histopathology and immunohistochemistry of the biopsy sample demonstrated myeloid sarcoma of the ulnar nerve. This case highlights the role of F-FDG PET/CT in raising the suspicion of malignancy in otherwise presumably benign lesions of the nerve.

Identification of HER2-Positive Metastases in Patients with HER2-Negative Primary Breast Cancer by Using HER2-targeted 89Zr-Pertuzumab PET/CT.

Background Human epidermal growth factor receptor 2 (HER2)-targeted therapies are successful in patients with HER2-positive malignancies; however, spatial and temporal heterogeneity of HER2 expression may prevent identification of optimal patients for these therapies. Purpose To determine whether imaging with the HER2-targeted PET tracer zirconium 89 (89Zr)-pertuzumab can depict HER2-positive metastases in women with HER2-negative primary breast cancer. Materials and Methods From January to June 2019, women with biopsy-proven HER2-negative primary breast cancer and biopsy-proven metastatic disease were enrolled in a prospective clinical trial (ClinicalTrials.gov NCT02286843) and underwent 89Zr-pertuzumab PET/CT for noninvasive whole-biopsy evaluation of potential HER2-positive metastases. 89Zr-pertuzumab-avid foci that were suspicious for HER2-positive metastases were tissue sampled and examined by pathologic analysis to document HER2 status. Results Twenty-four women (mean age, 55 years ± 11 [standard deviation]) with HER2-negative primary breast cancer were enrolled. Six women demonstrated foci at 89Zr-pertuzumab PET/CT that were suspicious for HER2-positive disease. Of these six women, three had biopsy-proven HER2-positive metastases, two had pathologic findings that demonstrated HER2-negative disease, and one had a fine-needle aspirate with inconclusive results. Conclusion Human epidermal growth factor receptor 2 (HER2)-targeted imaging with zirconium 89-pertuzumab PET/CT was successful in detecting HER2-positive metastases in women with HER2-negative primary breast cancer. This demonstrates the ability of targeted imaging to identify patients for targeted therapies that might not otherwise be considered. © RSNA, 2020 Online supplemental material is available for this article. See the editorial by Mankoff and Pantel in this issue.

[18F]FDG-PET/CT Radiomics for Prediction of Bone Marrow Involvement in Mantle Cell Lymphoma: A Retrospective Study in 97 Patients.

Biopsy is the standard for assessment of bone marrow involvement in mantle cell lymphoma (MCL). We investigated whether [18F]FDG-PET radiomic texture features can improve prediction of bone marrow involvement in MCL, compared to standardized uptake values (SUV), and whether combination with laboratory data improves results. Ninety-seven MCL patients were retrospectively included. SUVmax, SUVmean, SUVpeak and 16 co-occurrence matrix texture features were extracted from pelvic bones on [18F]FDG-PET/CT. A multi-layer perceptron neural network was used to compare three combinations for prediction of bone marrow involvement-the SUVs, a radiomic signature based on SUVs and texture features, and the radiomic signature combined with laboratory parameters. This step was repeated using two cut-off values for relative bone marrow involvement: REL > 5% (>5% of red/cellular bone marrow); and REL > 10%. Biopsy demonstrated bone marrow involvement in 67/97 patients (69.1%). SUVs, the radiomic signature, and the radiomic signature with laboratory data showed AUCs of up to 0.66, 0.73, and 0.81 for involved vs. uninvolved bone marrow; 0.68, 0.84, and 0.84 for REL ≤ 5% vs. REL > 5%; and 0.69, 0.85, and 0.87 for REL ≤ 10% vs. REL > 10%. In conclusion, [18F]FDG-PET texture features improve SUV-based prediction of bone marrow involvement in MCL. The results may be further improved by combination with laboratory parameters.

CD38-targeted Immuno-PET of Multiple Myeloma: From Xenograft Models to First-in-Human Imaging.

Background Current measurements of multiple myeloma disease burden are suboptimal. Daratumumab is a monoclonal antibody that targets CD38, an antigen expressed on nearly all myeloma cells. Purpose To demonstrate preclinical and first-in-human application of an antibody composed of the native daratumumab labeled with the positron-emitting radionuclide zirconium 89 (89Zr) through the chelator deferoxamine (DFO), or 89Zr-DFO-daratumumab, for immunologic PET imaging of multiple myeloma. Materials and Methods 89Zr-DFO-daratumumab was synthesized by conjugating 89Zr to daratumumab with DFO. A murine xenograft model using CD38-positive OPM2 multiple myeloma cells was used to evaluate CD38-specificity of 89Zr-DFO-daratumumab. Following successful preclinical imaging, a prospective phase I study of 10 patients with multiple myeloma was performed. Study participants received 74 MBq (2 mCi) of intravenous 89Zr-DFO-daratumumab. Each participant underwent four PET/CT scans over the next 8 days, as well as blood chemistry and whole-body counts, to determine safety, tracer biodistribution, pharmacokinetics, and radiation dosimetry. Because 89Zr has a half-life of 78 hours, only a single administration of tracer was needed to obtain all four PET/CT scans. Results 89Zr-DFO-daratumumab was synthesized with radiochemical purity greater than 99%. In the murine model, substantial bone marrow uptake was seen in OPM2 mice but not in healthy mice, consistent with CD38-targeted imaging of OPM2 multiple myeloma cells. In humans, 89Zr-DFO-daratumumab was safe and demonstrated acceptable dosimetry. 89Zr-DFO-daratumumab uptake was visualized at PET in sites of osseous myeloma. Conclusion These data demonstrate successful CD38-targeted immunologic PET imaging of multiple myeloma in a murine model and in humans. © RSNA, 2020 Online supplemental material is available for this article.

Lymph Node Imaging in Patients with Primary Breast Cancer: Concurrent Diagnostic Tools.

The detection of lymph node metastasis affects the management of patients with primary breast cancer significantly in terms of staging, treatment, and prognosis. The main goal for the radiologist is to determine and detect the presence of metastatic disease in nonpalpable axillary lymph nodes with a positive predictive value that is high enough to initially select patients for upfront axillary lymph node dissection. Features that are suggestive of axillary adenopathy may be seen with different imaging modalities, but ultrasound is the method of choice for evaluating axillary lymph nodes and for performing image-guided lymph node interventions. This review aims to provide a comprehensive overview of the available imaging modalities for lymph node assessment in patients diagnosed with primary breast cancer. IMPLICATIONS FOR PRACTICE: The detection of lymph node metastasis affects the management of patients with primary breast cancer. The main goal for the radiologist is to detect lymph node metastasis in patients to allow for the selection of patients who should undergo upfront axillary lymph node dissection. Features that are suggestive of axillary adenopathy may be seen with mammography, computed tomography, and magnetic resonance imaging, but ultrasonography is the imaging modality of choice for evaluating axillary lymph nodes. A normal axillary lymph node is characterized by a reniform shape, a maximal cortical thickness of 3 mm without focal bulging, smooth margins, and, depending on size, a discernable central fatty hilum.

Preclinical and first-in-human-brain-cancer applications of [18F]poly (ADP-ribose) polymerase inhibitor PET/MR.

BACKGROUND: We report preclinical and first-in-human-brain-cancer data using a targeted poly (ADP-ribose) polymerase 1 (PARP1) binding PET tracer, [18F]PARPi, as a diagnostic tool to differentiate between brain cancers and treatment-related changes. METHODS: We applied a glioma model in p53-deficient nestin/tv-a mice, which were injected with [18F]PARPi and then sacrificed 1 h post-injection for brain examination. We also prospectively enrolled patients with brain cancers to undergo dynamic [18F]PARPi acquisition on a dedicated positron emission tomography/magnetic resonance (PET/MR) scanner. Lesion diagnosis was established by pathology when available or by Response Assessment in Neuro-Oncology (RANO) or RANO-BM response criteria. Resected tissue also underwent PARPi-FL staining and PARP1 immunohistochemistry. RESULTS: In a preclinical mouse model, we illustrated that [18F]PARPi crossed the blood-brain barrier and specifically bound to PARP1 overexpressed in cancer cell nuclei. In humans, we demonstrated high [18F]PARPi uptake on PET/MR in active brain cancers and low uptake in treatment-related changes independent of blood-brain barrier disruption. Immunohistochemistry results confirmed higher PARP1 expression in cancerous than in noncancerous tissue. Specificity was also corroborated by blocking fluorescent tracer uptake with an excess unlabeled PARP inhibitor in patient cancer biospecimen. CONCLUSIONS: Although larger studies are necessary to confirm and further explore this tracer, we describe the promising performance of [18F]PARPi as a diagnostic tool to evaluate patients with brain cancers and possible treatment-related changes.

PET/CT Imaging Characteristics After Radioembolization of Hepatic Metastasis from Breast Cancer.

PURPOSE: To define positron emission tomography/computed tomography (PET/CT) imaging characteristics during follow-up of patients with metastatic breast cancer (MBC) treated with yttrium-90 (Y90) radioembolization (RE). MATERIALS AND METHODS: From January 2011 to October 2017, 30 MBC patients underwent 38 Y90 glass or resin RE treatments. Pre-RE PET/CT was performed on average 51 days before RE. There were 68 PET/CTs performed after treatment. Response was assessed using modified PERCIST criteria focusing on the hepatic territory treated with RE, normalizing SUVpeak to the mean SUV of liver uninvolved by tumor. An objective response (OR) was defined as a decrease in SUVpeak by at least 30%. RESULTS: Of the 68 post-RE scans, 6 were performed at 0-30 days, 15 at 31-60 days, 9 at 61-90 days, 13 at 91-120 days, 14 scans at 121-180 days, and 11 scans at > 180 days after RE. Of the 30 patients, 25 (83%) achieved OR on at least one follow-up. Median survival was 15 months after the first RE administration. Highest response rates occurred at 30-90 days, with over 75% of cases demonstrating OR at that time. After 180 days, OR was seen in only 25%. There was a median TTP of 169 days among responders. CONCLUSION: In MBC, follow-up PET/CT after RE demonstrates optimal response rates at 30-90 days, with progression noted after 180 days. These results help to guide the timing of imaging and also to inform patients of expected outcomes after RE.

Patient Repositioning Reveals a Malignant Pleura Effusion Initially Mistaken as a Bone Metastasis on 18FDG PET/CT.

A 70-year-old woman with breast cancer underwent F-FDG PET/CT for restaging. An FDG-avid focus corresponding to a rib on CT images was identified and interpreted as suggestive of an osseous metastasis. A PET/CT-guided biopsy was planned with the patient in prone position. Prone images demonstrated the FDG focus "moved" to the anterior chest and corresponding to pleural fluid. The diagnosis was altered from osseous metastases to pleural malignancy, and the bone biopsy was not performed. This case not only emphasizes the sensitivity of PET in the detection of malignancy, but also highlights the difficulty localizing small, mobile, FDG-avid foci.

Radiomic features of glucose metabolism enable prediction of outcome in mantle cell lymphoma.

PURPOSE: To determine whether [18F]FDG PET/CT-derived radiomic features alone or in combination with clinical, laboratory and biological parameters are predictive of 2-year progression-free survival (PFS) in patients with mantle cell lymphoma (MCL), and whether they enable outcome prognostication. METHODS: Included in this retrospective study were 107 treatment-naive MCL patients scheduled to receive CD20 antibody-based immuno(chemo)therapy. Standardized uptake values (SUV), total lesion glycolysis, and 16 co-occurrence matrix radiomic features were extracted from metabolic tumour volumes on pretherapy [18F]FDG PET/CT scans. A multilayer perceptron neural network in combination with logistic regression analyses for feature selection was used for prediction of 2-year PFS. International prognostic indices for MCL (MIPI and MIPI-b) were calculated and combined with the radiomic data. Kaplan-Meier estimates with log-rank tests were used for PFS prognostication. RESULTS: SUVmean (OR 1.272, P = 0.013) and Entropy (heterogeneity of glucose metabolism; OR 1.131, P = 0.027) were significantly predictive of 2-year PFS: median areas under the curve were 0.72 based on the two radiomic features alone, and 0.82 with the addition of clinical/laboratory/biological data. Higher SUVmean in combination with higher Entropy (SUVmean >3.55 and entropy >3.5), reflecting high "metabolic risk", was associated with a poorer prognosis (median PFS 20.3 vs. 39.4 months, HR 2.285, P = 0.005). The best PFS prognostication was achieved using the MIPI-bm (MIPI-b and metabolic risk combined): median PFS 43.2, 38.2 and 20.3 months in the low-risk, intermediate-risk and high-risk groups respectively (P = 0.005). CONCLUSION: In MCL, the [18F]FDG PET/CT-derived radiomic features SUVmean and Entropy may improve prediction of 2-year PFS and PFS prognostication. The best results may be achieved using a combination of metabolic, clinical, laboratory and biological parameters.

18F-FDG PET/CT for Systemic Staging of Newly Diagnosed Breast Cancer in Men.

18F-FDG PET/CT has demonstrated substantial value in systemic staging of newly diagnosed breast cancer in women. However, it is not known whether breast cancer in male patients benefits similarly. This study assesses 18F-FDG PET/CT systemic staging in patients with newly diagnosed male breast cancer and determines detection rates for unsuspected distant metastases stratified by pre-PET/CT stage. Methods: In this Institutional Review Board-approved retrospective study, our Health Care Information System was screened for stage I-III male patients with breast cancer who underwent 18F-FDG PET/CT before systemic or radiation therapy from 2004 to 2017. Initial stage was determined by mammography, ultrasound, or surgery. 18F-FDG PET/CT was evaluated to identify unsuspected extraaxillary regional nodal and distant metastases, and a post-PET/CT stage was determined. Rates of upstaging to stage IV were determined for each initial stage. Results: During the 14-y period, 10,124 unique patients underwent 18F-FDG PET/CT for breast cancer at our institution. Of these, 106 patients were men, and 39 of these patients were imaged at initial staging and met the inclusion criteria. Median age was 62 y (range, 31-90 y), most had ductal carcinoma (95%), and most were estrogen receptor-positive (97%). In 7 of 39 patients (18%), 18F-FDG PET/CT identified previously unsuspected distant metastases, which increased patient stage to IV. This included 3 of 19 (16%) initial stage IIB patients and 4 of 12 (33%) initial stage III patients. 18F-FDG PET/CT also detected an unsuspected synchronous lymphoma in 1 patient. Conclusion:18F-FDG PET/CT revealed previously unsuspected distant metastases in 16% of male patients with pre-PET/CT stage IIB breast cancer and 33% of those with stage III breast cancer. These rates are comparable to previously published upstaging rates in female patients. 18F-FDG PET/CT demonstrates value for systemic staging of male patients with breast cancer and should be considered for use in newly diagnosed patients, particularly those with stage IIB and III disease.

Association of PI3K Pathway Mutations with Early Positron-Emission Tomography/CT Imaging Response after Radioembolization for Breast Cancer Liver Metastases: Results of a Single-Center Retrospective Pilot Study.

PURPOSE: To describe imaging response and survival after radioembolization for metastatic breast cancer and to delineate genetic predictors of imaging responses and outcomes. MATERIALS AND METHODS: This retrospective study included 31 women (average age, 52 y) with liver metastasis from invasive ductal carcinoma who underwent resin and glass radioembolization (average cumulative dose, 2.0 GBq ± 1.8) between January 2011 and September 2017 after receiving ≥ 3 lines of chemotherapy. Twenty-four underwent genetic profiling with MSK-IMPACT or Sequenom; 26 had positron-emission tomography (PET)/CT imaging before and after treatment. Survival after the first radioembolization and 2-4-month PET/CT imaging response were assessed. Laboratory and imaging features were assessed to determine variables predictive of outcomes. Unpaired Student t tests and Fisher exact tests were used to compare responders and nonresponders categorized by changes in fluorodeoxyglucose avidity. Kaplan-Meier survival analysis was used to determine the impact of predictors on survival after radioembolization. RESULTS: Median survival after radioembolization was 11 months (range, 1-49 mo). Most patients (18 of 26; 69%) had complete or partial response based on changes in fluorodeoxyglucose avidity. Imaging response was associated with longer survival (P = .005). Whereas 100% of patients with PI3K pathway mutations showed an imaging response, only 45% of wild-type patients showed a response (P = .01). Median survival did not differ between PI3K pathway wild-type (10.9 mo) and mutant (undefined) patients (P = .50). CONCLUSIONS: These preliminary data suggest that genomic profiling may predict which patients with metastatic breast cancer benefit most from radioembolization. PI3K pathway mutations are associated with improved imaging response, which is associated with longer survival.

Imaging Phenotypes in Women at High Risk for Breast Cancer on Mammography, Ultrasound, and Magnetic Resonance Imaging Using the Fifth Edition of the Breast Imaging Reporting and Data System.

OBJECTIVE: To assess imaging phenotypes of familial breast cancer on mammography (MG), ultrasound (US), and magnetic resonance imaging (MRI) using the fifth edition of the BI-RADS; to investigate inter-observer agreement and to correlate imaging phenotypes with risk status, histopathology, and molecular subtypes derived by immunohistochemical surrogate. MATERIALS AND METHODS: Forty-nine women (BRCA-1/2 mutation carriers and women with >20% lifetime risk) were diagnosed with breast cancer within our high-risk screening program. BI-RADS MG, US, and MRI imaging descriptors were correlated with risk status, histopathology, and molecular subtypes derived by immunohistochemical surrogate. Inter-rater agreement for BI-RADS MG, US, and MRI categories was assessed. RESULTS: Fifty-two breast cancers were diagnosed and 98% were detectable in at least one modality. MRI detected more cancers (P < 0.001). No lesion had benign morphology on BI-RADS. BRCA-1 had triple-negative and high-grade tumors in the posterior part and in the upper-outer quadrant (P ≤ 0.01); positive-family-history patients had intermediate-grade neoplasms (P < 0.01) in the middle part (P = 0.04) and in the upper-outer quadrants (P = 0.05). There was moderate inter-rater agreement for the assigned BI-RADS assessment for MG (k = 0.554) and MRI (k = 0.512) and substantial inter-rater agreement for US (k = 0.741). CONCLUSIONS: Imaging phenotypes of familial breast cancers with BI-RADS are malignant in all imaging modalities. Risk status seems to influence cancer location.

Accuracy of screening women at familial risk of breast cancer without a known gene mutation: Individual patient data meta-analysis.

INTRODUCTION: Women with a strong family history of breast cancer (BC) and without a known gene mutation have an increased risk of developing BC. We aimed to investigate the accuracy of screening using annual mammography with or without magnetic resonance imaging (MRI) for these women outside the general population screening program. METHODS: An individual patient data (IPD) meta-analysis was conducted using IPD from six prospective screening trials that had included women at increased risk for BC: only women with a strong familial risk for BC and without a known gene mutation were included in this analysis. A generalised linear mixed model was applied to estimate and compare screening accuracy (sensitivity, specificity and predictive values) for annual mammography with or without MRI. RESULTS: There were 2226 women (median age: 41 years, interquartile range 35-47) with 7478 woman-years of follow-up, with a BC rate of 12 (95% confidence interval 9.3-14) in 1000 woman-years. Mammography screening had a sensitivity of 55% (standard error of mean [SE] 7.0) and a specificity of 94% (SE 1.3). Screening with MRI alone had a sensitivity of 89% (SE 4.6) and a specificity of 83% (SE 2.8). Adding MRI to mammography increased sensitivity to 98% (SE 1.8, P < 0.01 compared to mammography alone) but lowered specificity to 79% (SE 2.7, P < 0.01 compared with mammography alone). CONCLUSION: In this population of women with strong familial BC risk but without a known gene mutation, in whom BC incidence was high both before and after age 50, adding MRI to mammography substantially increased screening sensitivity but also decreased its specificity.

Comparison of FDG-PET/CT and contrast-enhanced CT for monitoring therapy response in patients with metastatic breast cancer.

PURPOSE: The aim of this study was to compare fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) and contrast-enhanced computed tomography (CE-CT) for the prediction of progression-free survival (PFS) and disease-specific survival (DSS) in patients with stage IV breast cancer undergoing systemic therapy. METHODS: Sixty-five patients with metastatic breast cancer treated with first- or second-line systemic therapy in prospective clinical trials were included. Response to treatment was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for CE-CT and by PET Response Criteria in Solid Tumors (PERCIST), respectively. RESULTS: All responders by RECIST (n = 22) were also responders by PERCIST, but 40% (17/43) of non-responders by RECIST were responders by PERCIST. Responses according to RECIST and PERCIST both correlated with PFS, but PERCIST showed a significantly higher predictive accuracy (concordance index for PFS: 0.70 vs. 0.60). One-year PFS for responders vs. non-responders by RECIST was 59% vs. 27%, compared to 63% vs. 0% by PERCIST. Four-year DSS of responders and non-responders by RECIST was 50% and 38%, respectively (p = 0.2, concordance index: 0.55) as compared to 58% vs. 18% for PERCIST (p < 0.001, concordance index: 0.65). Response on PET/CT was also a significantly better predictor for DSS than disease control on CE-CT. CONCLUSIONS: In patients with metastatic breast cancer, tumor response on PET/CT appears to be a superior predictor of PFS and DSS than response on CE-CT. Monitoring tumor response by PET/CT may increase the power of clinical trials using tumor response as an endpoint, and may improve patient management in clinical routine.