Purpose: Nipple discharge is the third most common breast-related complaint. It is recommended to exclude malignancy in pathologic nipple discharge (PND). Mammography and ultrasound are the first-line conventional diagnostic (CD) imaging. Although magnetic resonance is often used as a complementary modality, molecular breast imaging (MBI) with Tc-99m sestamibi may be a suitable alternative. Considering the lack of information on this subject and its clinical importance, this study aimed to evaluate the role of MBI in ruling out malignancy in patients with PND and negative/indeterminate CD. Patients and Methods: Retrospective cohort single-center study including all patients with PND evaluated by CD and MBI between 2012 and 2020. Pathology was considered the gold standard. Follow-up was used when pathology was not available. Results: Of the 96 cases of PND included, 78 were benign, and 18 (20%) corresponded to breast cancer (BC). Although CD and MBI were concordant in the BIRADS classification in 81% (78/96), half of BC were detected by MBI only. BC was located directly behind the nipple in a minority of patients (11%), meaning that MBI could significantly prevent futile central ductal excision. MBI presented higher sensitivity (83% vs. 33%) and negative predictive value (96% vs. 86%) than CD alone, with similar specificity (89% vs. 92%) and positive predictive value (63% vs. 50%). The area under the curve of MBI and CD was 0,86 (P-value<0.001 [95% CI: 0.75-0.97]) and 0.63 (P-value=0.091 [95% CI: 0.47-0.79]), respectively. Conclusions: MBI showed good diagnostic accuracy for detecting BC in patients with PND with negative/indeterminate findings on CD imaging.

The appropriate use criteria (AUC) documents are intended to aid medical practitioners in the appropriate use of imaging technology in specific clinical scenarios based on rigorous appraisal of the available published evidence. The purpose of this document is to summarize the appropriate use of PET/CT with ¹⁸F-FDG in the initial staging of malignant disease. A multidisciplinary expert panel convened to appraise an independently performed systematic review and develop the AUC for initial staging of head and neck cancer, lung cancer, breast cancer, esophageal cancer, colorectal cancer, pancreatic cancer, melanoma, lymphoma, myeloma, and sarcoma with an appropriateness score for each clinical scenario established by using a modified Delphi process (Table 1). The full document including the methodology details, discussion of evidence, appendices, and the supplemental material can be accessed at https://snmmi.org/Web/Clinical-Practice/Appropriate-Use-Criteria/Articles/Appropriate_Use_Criteria_for_18F-FDG_PET_CT_for_Initial_Staging_of_Malignant_Disease.

Background
The second most common breast cancer subtype is invasive lobular cancer (ILC). Its locoregional staging is challenging, even when using breast MRI. Different non-[18F]FDG PET tracers have been explored in these patients, and promising results were reported with [18F]FACBC. Nevertheless, no publications directly comparing breast MRI and [18F]FACBC PET are available.

Aim
To compare the performance of prone [18F]FACBC PET/CT and breast MRI for assessing disease extent in the breast and for depicting lymph node metastases in patients with locally advanced ILC.

Methods
Retrospective selection of case series of patients with proven locally advanced luminal-like ILC, who underwent both breast MRI and prone [18F]FACBC PET/CT, according to the local clinical standards.

Results
Eight patients were included. [18F]FACBC PET/CT performed similarly to MRI in T-staging and outperformed MRI in N-staging, especially outside axillary level I/II. [18F]FACBC uptake in the index breast lesion was on average 9 times higher than the breast background. Among the 6 patients submitted to surgery, [18F]FACBC provided the correct T&N staging in 5 patients, confirmed by pathology.

Conclusion
This initial descriptive case series suggests that prone [18F]FACBC PET/CT could be a valuable imaging tool for both local and regional staging of low-grade luminal-like ILC. A larger prospective clinical trial is needed to further evaluate this potential application.

To plan optimal management in a patient with breast cancer (BC), accurate baseline staging and early detection and staging of recurrence are necessary.1-3 Representatives from the European Association of Nuclear Medicine (EANM) and the Society of Nuclear Medicine and Molecular Imaging (SNMMI) recently published the joint European-American guidelines on the role of 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography ([18F]FDG-PET/CT) in no special type (NST) BC, endorsed by several other imaging and clinical societies: the American College of Radiology (ACR), European Society of Surgical Oncology, European Society for Radiotherapy and Oncology (ESTRO), European Society of Breast Imaging, European Society of Radiology, and European Society of Breast Cancer Specialists (EUSOMA).1 Considering the low [18F]FDG-avidity in invasive lobular carcinoma (ILC), the EANM-SNMMI guidelines focused on NST BC. Guidelines from clinical societies such as the American National Comprehensive Cancer Network (NCCN),4 European Society for Medical Oncology (ESMO),5-7 and Advanced Breast Cancer (ABC) international consensus guidelines8 also evaluate imaging techniques, but they include all histological subtypes of BC. There is a lack of consistency in the optimal utilization of [18F]FDG-PET/CT among published guidelines. This manuscript summarizes available evidence, emphasizes the value of [18F]FDG-PET/CT for staging and restaging of patients with BC, and highlights agreements and discrepancies among international guidelines.

Introduction: There is much literature about the role of 2-[¹⁸F]FDG PET/CT in patients with breast cancer (BC). However, there exists no international guideline with involvement of the nuclear medicine societies about this subject. Purpose: To provide an organized, international, state-of-the-art, and multidisciplinary guideline, led by experts of two nuclear medicine societies (EANM and SNMMI) and representation of important societies in the field of BC (ACR, ESSO, ESTRO, EUSOBI/ESR, and EUSOMA). Methods: Literature review and expert discussion were performed with the aim of collecting updated information regarding the role of 2-[¹⁸F]FDG PET/CT in patients with no special type (NST) BC and summarizing its indications according to scientific evidence. Recommendations were scored according to the National Institute for Health and Care Excellence (NICE) criteria. Results: Quantitative PET features (SUV, MTV, TLG) are valuable prognostic parameters. In baseline staging, 2-[¹⁸F]FDG PET/CT plays a role from stage IIB through stage IV. When assessing response to therapy, 2-[¹⁸F]FDG PET/CT should be performed on certified scanners, and reported either according to PERCIST, EORTC PET, or EANM immunotherapy response criteria, as appropriate. 2-[¹⁸F]FDG PET/CT may be useful to assess early metabolic response, particularly in non-metastatic triple-negative and HER2+ tumours. 2-[¹⁸F]FDG PET/CT is useful to detect the site and extent of recurrence when conventional imaging methods are equivocal and when there is clinical and/or laboratorial suspicion of relapse. Recent developments are promising. Conclusion: 2-[¹⁸F]FDG PET/CT is extremely useful in BC management, as supported by extensive evidence of its utility compared to other imaging modalities in several clinical scenarios.

Purpose
The recently released EANM/SNMMI guideline, endorsed by several important clinical and imaging societies in the field of breast cancer (BC) care (ACR, ESSO, ESTRO, EUSOBI/ESR, EUSOMA), emphasized the role of [18F]FDG PET/CT in management of patients with no special type (NST) BC. This review identifies and summarizes similarities, discrepancies and novelties of the EANM/SNMMI guideline compared to NCCN, ESMO and ABC recommendations.

Methods
The EANM/SNMMI guideline was based on a systematic literature search and the AGREE tool. The level of evidence was determined according to NICE criteria, and 85 % agreement or higher was reached regarding each statement. Comparisons with NCCN, ESMO and ABC guidelines were examined for specific clinical scenarios in patients with early stage through advanced and metastatic BC.

Results
Regarding initial staging of patients with NST BC, [18F]FDG PET/CT is the preferred modality in the EANM-SNMMI guideline, showing superiority as a single modality to a combination of contrast-enhanced CT of thorax-abdomen-pelvis plus bone scan in head-to-head comparisons and a randomized study. Its use is recommended in patients with clinical stage IIB or higher and may be useful in certain stage IIA cases of NST BC. In NCCN, ESMO, and ABC guidelines, [18F]FDG PET/CT is instead recommended as complementary to conventional imaging to solve inconclusive findings, although ESMO and ABC also suggest [18F]FDG PET/CT can replace conventional imaging for staging patients with high-risk and metastatic NST BC. During follow up, NCCN and ESMO only recommend diagnostic imaging if there is suspicion of recurrence. Similarly, EANM-SNMMI states that [18F]FDG PET/CT is useful to detect the site and extent of recurrence only when there is clinical or laboratory suspicion of recurrence, or when conventional imaging methods are equivocal. The EANM-SNMMI guideline is the first to emphasize a role of [18F]FDG PET/CT for assessing early metabolic response to primary systemic therapy, particularly for HER2+ BC and TNBC. In the metastatic setting, EANM-SNMMI state that [18F]FDG PET/CT may help evaluate bone metastases and determine early response to treatment, in agreement with guidelines from ESMO.

Conclusions
The recently released EANM/SNMMI guideline reinforces the role of [18F]FDG PET/CT in the management of patients with NST BC supported by extensive evidence of its utility in several clinical scenarios.

Breast cancer is the most common cancer in females worldwide. Nuclear medicine plays an important role in patient management, not only in initial staging, but also during follow-up. Radiopharmaceuticals to study breast cancer have been used for over 50 years, and several of these are still used in clinical practice, according to the most recent guideline recommendations.In this critical review, an overview of nuclear medicine procedures used during the last decades is presented. Current clinical indications of each of the conventional nuclear medicine and PET/CT examinations are the focus of this review, and are objectively provided. Radionuclide therapies are also referred, mainly summarising the methods to palliate metastatic bone pain. Finally, recent developments and future perspectives in the field of nuclear medicine are discussed. In this context, the promising potential of new radiopharmaceuticals not only for diagnosis, but also for therapy, and the use of quantitative imaging features as potential biomarkers, are addressed.Despite the long way nuclear medicine has gone through, it looks like it will continue to benefit clinical practice, paving the way to improve healthcare provided to patients with breast cancer.