We evaluated the diagnostic performance of fibroblast activation protein inhibitor (FAPI) PET for lesion detection at breast cancer diagnosis and response assessment after neoadjuvant chemoimmunotherapy (NAC) and compared these findings with those from [18F]FDG PET or histopathology after the completion of NAC. Methods: A systematic search across PubMed, EMBASE, Web of Science, and Cochrane Trial databases up to January 12, 2026, was conducted. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies version 2 tool. Extracted data included SUVmax, tumor-to-background ratio, and lesion detection in studies comparing FAPI PET with [18F]FDG PET. For studies comparing FAPI PET with histopathology, diagnostic performance parameters were obtained. Data on FAPI uptake, stratified by histology type, molecular subtype, and tumor grade, were extracted. Results: The literature search yielded 3662 studies, 13 of which were included in this review. Of these, 10 compared FAPI PET with [18F]FDG PET and 3 compared FAPI PET findings with those of histopathology after the completion of NAC. The reported mean SUVmax range was 6.5-17.1 versus 3.9-8.3 for primary tumors, 5.1-17.1 versus 1.2-10.3 for axillary lymph node metastases, and 4.9-21.7 versus 1.7-8.1 for distant metastases on FAPI PET versus [18F]FDG PET, respectively. FAPI PET detected more lesions compared with [18F]FDG PET in all evaluated anatomic sites. In post-NAC response assessment of the breast tumor, FAPI PET reported a sensitivity and specificity of 73%-100% and 71%-100%, respectively. Lower FAPI uptake was observed in low-grade, luminal A tumors and in those with lobular histology. Conclusion: FAPI PET demonstrated increased lesion detection compared with [18F]FDG PET at the time of breast cancer diagnosis and demonstrated considerable diagnostic performance for assessing response evaluation after NAC.

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 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. 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. 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. 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. 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.

Positron Emission Tomography (PET) has been growing in usage for patients with breast cancer, due to an increased number of FDA-approved PET radiotracers pertinent to patients with breast cancer as well as increased prospective evidence for the value of these agents. The leading PET radiotracer for patients with breast cancer is 18F-fluorodeoxyglucose (18F-FDG), which measures glucose metabolism. There is prospective evidence for the use of 18F-FDG PET in systemic staging of newly diagnosed locally advanced breast cancer (stages IIB-IIIC), monitoring breast cancer treatment response, and detecting breast cancer recurrence, particularly in no special type (NST) breast cancer. 16α-18F-fluoro-17β-Fluoroestradiol (18F-FES) is a radiolabeled estrogen which evaluates estrogen receptor (ER) accessible for estrogen binding. There is prospective evidence supporting 18F-FES PET as a predictive biomarker for selecting patients with metastatic breast cancer for endocrine therapies. 18F-FES PET has also been shown to be valuable in the evaluation of ER status of lesions which are difficult to biopsy, for evaluation of ER status in lesions that are equivocal on other imaging modalities, and for selecting optimal dosage of novel ER-targeted systemic therapies in early clinical trials. Multiple investigators have suggested 18F-FES PET will have an increasing role for patients with invasive lobular breast cancer (ILC), which is less optimally evaluated by 18F-FDG PET. Sodium 18F-Fluoride (18F-NaF) evaluates bone turnover and has been effective in evaluation of malignancies which commonly metastasize to bone. In patients with metastatic breast cancer, 18F-NaF PET/CT has demonstrated superior sensitivity for osseous metastases than 99mTc-MDP or CT. In addition to these three FDA-approved PET radiotracers, there are multiple novel radiotracers currently in clinical trials with potential to further increase PET usage for patients with breast cancer.

PET radiotracers have become indispensable in the care of patients with breast cancer. 18F-fluorodeoxyglucose has become the preferred method of many oncologists for systemic staging of breast cancer at initial diagnosis, detecting recurrent disease, and for measuring treatment response after therapy. 18F-Sodium Fluoride is valuable for detection of osseous metastases. 18F-fluoroestradiol is now FDA-approved with multiple appropriate clinical uses. There are multiple PET radiotracers in clinical trials, which may add utility of PET imaging for patients with breast cancer in the future. This article will describe the advances during the last quarter century in PET for patients with breast cancer.

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 [F-18]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, [F-18]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, [F-18]FDG PET/CT is instead recommended as complementary to conventional imaging to solve inconclusive findings, although ESMO and ABC also suggest [F-18]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 [F-18]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 [F-18]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 [F-18]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 [F-18]FDG PET/CT in the management of patients with NST BC supported by extensive evidence of its utility in several clinical scenarios.

PET radiotracers have become indispensable in the care of patients with breast cancer. 18F-fluorodeoxyglucose has become the preferred method of many oncologists for systemic staging of breast cancer at initial diagnosis, detecting recurrent disease, and for measuring treatment response after therapy. 18F-Sodium Fluoride is valuable for detection of osseous metastases. 18F-fluoroestradiol is now FDA-approved with multiple appropriate clinical uses. There are multiple PET radiotracers in clinical trials, which may add utility of PET imaging for patients with breast cancer in the future. This article will describe the advances during the last quarter century in PET for patients with breast cancer.

The estrogen receptor (ER), a steroid hormone receptor important in female physiology, is a significant contributor to breast carcinogenesis and progression and, as such, is an important therapeutic target. Approximately 70% of breast cancers will express ER at presentation, and the determination of ER expression by tissue assay, usually by immunohistochemistry, is part of the standard of care for newly diagnosed breast cancer. ER expression is important in guiding the approach to treatment, especially with the increase in relevant systemic therapies. The ER-targeting imaging agent 16α-[18F]fluoro-17β-estradiol ([18F]FES) is approved for clinical use by regulatory agencies in France and the United States. Multiple studies suggest the advantages of [18F]FES PET in assessing tumor ER expression, the ability of both qualitative and quantitative [18F]FES PET measures to predict response to ER-targeted therapy, and the ability of [18F]FES PET to clarify equivocal staging and restaging results in patients with ER-expressing cancers. [18F]FES PET/CT may also be helpful in staging invasive lobular breast cancer and low-grade ER-expressing invasive ductal cancers and, in some cases, may be a substitute for biopsy. The Society of Nuclear Medicine and Molecular Imaging and the European Association of Nuclear Medicine in June 2023 released a procedure standard/practice guideline for [18F]FES PET ER imaging of patients with breast cancer. The goal of the standard/guideline is to assist physicians in recommending, performing, interpreting, and reporting the results of [18F]FES PET studies for patients with breast cancer and to provide clinicians with the best available evidence, inform them about areas where robust evidence is lacking, and help them deliver the best possible diagnostic efficacy and study quality for their patients. Also reviewed are standardized quality control, quality assurance, and imaging procedures for [18F]FES PET. The authors emphasize the importance of precision, accuracy, repeatability, and reproducibility for both clinical management of patients and for use of [18F]FES PET in multicenter trials. A standardized imaging procedure, in combination with already published appropriate-use criteria, will help promote the use of [18F]FES PET and enhance subsequent research. This brief summary article reviews the content of the joint standard/guideline, which is available in its entirety at https://www.snmmi.org/ClinicalPractice/content.aspx?ItemNumber=6414&navItemNumbe=10790.

Segmentation of lymphoma lesions on [F-18]FDG PET/CT images is being increasingly used in clinical practice for more objective disease quantification, especially for the computation of the total metabolic tumor volume. Efforts in the development of fully automatic segmentation through the use of deep learning (DL) have been employed and published. Yet, proper external validation causes a decrease in performance, limiting the translation into multicentric and multi-scanner clinical settings. This study proposes a DL model based on a 3D U-Net network trained and tested with multi-scanner-based images and multi-ground truth generation segmentations. A two-channel 3D U-Net having as input PET and low-dose CT was used. This allows the use of anatomical and metabolic information of the patient in the DL model. Evaluation performance with voxel overlap metrics, lesion detection metrics, and quantification of patients' tumor burden was performed. The developed model proved to be robust across scanners and reproduces physician-based manual and semiautomatic segmentations. Plus, good or excellent agreement with the different ground truth generation segmentations in quantifying lymphoma patients' tumor burden was observed. This brings trustworthiness to the application of the proposed DL-based model in multi-scanner/multicenter clinical settings. In addition, we made the network publicly available to be tested in other clinical settings.

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. 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). 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. 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. 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.

The objective is to assess the performance of seven semiautomatic and two fully automatic segmentation methods on [ 18 F]FDG PET/CT lymphoma images and evaluate their influence on tumor quantification. All lymphoma lesions identified in 65 whole-body [ 18 F]FDG PET/CT staging images were segmented by two experienced observers using manual and semiautomatic methods. Semiautomatic segmentation using absolute and relative thresholds, k -means and Bayesian clustering, and a self-adaptive configuration (SAC) of k -means and Bayesian was applied. Three state-of-the-art deep learning–based segmentations methods using a 3D U-Net architecture were also applied. One was semiautomatic and two were fully automatic, of which one is publicly available. Dice coefficient (DC) measured segmentation overlap, considering manual segmentation the ground truth. Lymphoma lesions were characterized by 31 features. Intraclass correlation coefficient (ICC) assessed features agreement between different segmentation methods. Nine hundred twenty [ 18 F]FDG-avid lesions were identified. The SAC Bayesian method achieved the highest median intra-observer DC (0.87). Inter-observers’ DC was higher for SAC Bayesian than manual segmentation (0.94 vs 0.84, p < 0.001). Semiautomatic deep learning–based median DC was promising (0.83 (Obs1), 0.79 (Obs2)). Threshold-based methods and publicly available 3D U-Net gave poorer results (0.56 ≤ DC ≤ 0.68). Maximum, mean, and peak standardized uptake values, metabolic tumor volume, and total lesion glycolysis showed excellent agreement (ICC ≥ 0.92) between manual and SAC Bayesian segmentation methods. The SAC Bayesian classifier is more reproducible and produces similar lesion features compared to manual segmentation, giving the best concordant results of all other methods. Deep learning–based segmentation can achieve overall good segmentation results but failed in few patients impacting patients’ clinical evaluation.

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.

Significant advances in breast cancer (BC) treatment have been made in the last decade, including the use of immunotherapy and, in particular, immune checkpoint inhibitors that have been shown to improve the survival of patients with triple negative BC. This narrative review summarizes the studies supporting the use of immunotherapy in BC. Furthermore, the usefulness of 2-deoxy-2-[18F]fluoro-D-glucose (2-[18F]FDG) positron emission/computerized tomography (PET/CT) to image the tumor heterogeneity and to assess treatment response is explored, including the different criteria to interpret 2-[18F]FDG PET/CT imaging. The concept of immuno-PET is also described, by explaining the advantages of mapping treatment targets with a non-invasive and whole-body tool. Several radiopharmaceuticals in the preclinical phase are referred too, and, considering their promising results, translation to human studies is needed to support their use in clinical practice. Overall, this is an evolving field in BC treatment, despite PET imaging developments, the future trends also include expanding immunotherapy to early-stage BC and using other biomarkers.

Complete pathological response to neoadjuvant systemic treatment (NAST) in some subtypes of breast cancer (BC) has been used as a surrogate of long-term outcome. The possibility of predicting BC pathological response to NAST based on the baseline 18F-Fluorodeoxyglucose positron emission tomography (FDG PET), without the need of an interim study, is a focus of recent discussion. This review summarises the characteristics and results of the available studies regarding the potential impact of heterogeneity features of the primary tumour burden on baseline FDG PET in predicting pathological response to NAST in BC patients. Literature search was conducted on PubMed database and relevant data from each selected study were collected. A total of 13 studies were eligible for inclusion, all of them published over the last 5 years. Eight out of 13 analysed studies indicated an association between FDG PET-based tumour uptake heterogeneity features and prediction of response to NAST. When features associated with predicting response to NAST were derived, these varied between studies. Therefore, definitive reproducible findings across series were difficult to establish. This lack of consensus may reflect the heterogeneity and low number of included series. The clinical relevance of this topic justifies further investigation about the predictive role of baseline FDG PET.