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Breast cancer prognosis is steadily improving due to early detection of primary cancer in screening programs and revolutionizing treatment development. In the metastatic setting, therapy improvements render breast cancer a chronic disease. Although FDG-PET/CT has emerged as a highly accurate method for staging metastatic breast cancer, there has been no change in response evaluation methods for decades. FDG-PET/CT has proven high prognostic values in patients with metastatic breast cancer when using quantitative PET methods. It has also shown a higher predictive value than conventional CT when applying the respective response evaluation criteria, RECIST and PERCIST. Response categorization using FDG-PET/CT is more sensitive in detecting progressive and regressive disease, while conventional imaging such as CT and bone scintigraphy deem stable disease more often. These findings reflect the higher accuracy of FDG-PET/CT for response evaluation in this patient group. But does the higher accuracy of FDG-PET/CT translate into a patient benefit when implementing it for monitoring response to palliative treatment? We have evidence of survival benefit from a retrospective study indicating the superiority of using FDG-PET/CT compared with conventional imaging for response evaluation in metastatic breast cancer patients. The survival benefit seems to result from earlier detection of progression with FDG-PET/CT than conventional imaging, leading to an earlier change in treatment with potentially better efficacy of the subsequent treatment line. FDG-PET/CT can be used semiquantitatively as suggested in PERCIST. However, we still need to improve clinically applicable methods based on neural network modeling to better integrate the quantitative information in a smart and standardized way, enabling relevant comparability between scans, patients, and institutions. Such innovation is warranted to support imaging specialists in diagnostic response assessment. Prospective multicenter studies analyzing patients' survival, quality of life, societal and patient costs of replacing conventional imaging with FDG-PET/CT are needed before firm conclusions can be drawn on which type of scan to recommend in future clinical guidelines.

This study aimed to compare CE-CT and 2-[18F]FDG-PET/CT for response monitoring metastatic breast cancer (MBC). The primary objective was to predict progression-free and disease-specific survival for responders vs. non-responders on CE-CT and 2-[18F]FDG-PET/CT. The secondary objective was to assess agreement between response categorization for the two modalities. Treatment response in women with MBC was monitored prospectively by simultaneous CE-CT and 2-[18F]FDG-PET/CT, allowing participants to serve as their own controls. The standardized response evaluation criteria in solid tumors (RECIST 1.1) and PET response criteria in solid tumors (PERCIST) were used for response categorization. For prediction of progression-free and disease-specific survival, treatment response was dichotomized into responders (partial and complete response) and non-responders (stable and progressive disease) at the first follow-up scan. Progression-free survival was defined as the time from baseline until disease progression or death from any cause. Disease-specific survival was defined as the time from baseline until breast cancer-specific death. Agreement between response categorization for both modalities was analyzed for all response categories and responders vs. non-responders. At the first follow-up, tumor response was reported more often by 2-[18F]FDG-PET/CT than CE-CT, with only fair agreement on response categorization between the two modalities (weighted Kappa 0.28). Two-year progression-free survival for responders vs. non-responders by CE-CT was 54.2% vs. 46.0%, compared with 59.1% vs. 14.3% by 2-[18F]FDG-PET/CT. Correspondingly, 2-year disease-specific survival were 83.3% vs. 77.8% for CE-CT and 84.6% vs. 61.9% for 2-[18F]FDG-PET/CT. Tumor response on 2-[18F]FDG-PET/CT was significantly associated with progression-free (HR: 3.49, P 18F]FDG-PET/CT appears a better predictor of progression-free and disease-specific survival than CE-CT when used to monitor metastatic breast cancer. In addition, we found low concordance between response categorization between the two modalities.Trial registration: Clinical.Trials.gov. NCT03358589. Registered 30/11/2017-Retrospectively registered, http://www.ClinicalTrials.gov.

This study examined treatment and survival among women with locally advanced breast cancer (LABC) through comparative analyses of women ≥70 years and those70 years. The primary endpoint was surgery with curative intention following neoadjuvant therapy. Secondary endpoints were 3-year disease free survival (DFS), overall survival (OS), response rates, and adherence to treatment guidelines.Patients diagnosed and treated for LABC between 2010 and 2019 at Odense University Hospital, Denmark, were eligible. Surgical information was dichotomized into surgery and no surgery for patients ≥70 years and70 years, and treatment response was extracted from scan and pathology reports. Adherence to treatment guidelines was registered for the initiated neoadjuvant treatment, and 3-year OS and DFS were estimated using Kaplan-Meier and Log-rank-test.Of 210 women, 57/102 (55.9%) of those ≥70 years received surgery with curative intent compared with 103/108 (95.4%) of those70 years. The main reason for omitting surgery was the patient's request. Fewer women ≥70 years received neoadjuvant therapy according to guidelines compared with their younger counterparts (63.7%Among women with LABC, women ≥70 years were less likely to receive neoadjuvant therapy according to guidelines. Only half of the patients ≥70 years reached the goal of surgery with curative intent, with no difference in 3-year OS and DFS between age groups.

Tumor heterogeneity in breast cancer tumors is widely recognized but evolution of the breast cancer genome is complex and not yet understood. Characterizing the evolutionary landscape of breast tumors can provide biological understanding of tumor progression and metastasis may be important for directing effective treatments. We performed copy number profiling and mutation detection based on whole exome sequencing of primary tumors, lymph node and distant metastasis as well as on plasma circulating tumor DNA from twelve metastatic breast cancer patients. Preliminary data shows diverse patterns of tumor evolution. Although linear evolution with late dissemination of metastatic cells was common, parallel evolution with early dissemination from primary tumor to distant sites was evident in some cases. Comparing tissue biopsies with plasma samples, we could detect variants mirroring primary tumor and/or metastasis, depending on the time span between the progression steps. The genomic discordance between the different stages of tumor evolution in these patients not only emphasizes the importance of molecular profiling of metastatic tissue but also the possibilities of liquid biopsies for real-time tracking of tumor clonal evolution. Citation Format: Stephanie Kavan, Torben A Kruse, Lars Andersen, Martin Larsen, Malene G Hildebrandt, Anne-Marie Bak Jylling, Marianne Ewertz, Marianne Vogsen, Mads Thomassen. Mapping clonal evolution and tumor heterogeneity by whole exome sequencing of tissue and plasma circulating tumor DNA in metastatic breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-07-07.

We compared the image quality and quantification parameters through bayesian penalized likelihood reconstruction algorithm (Q.Clear) and ordered subset expectation maximization (OSEM) algorithm for 2-[18F]FDG-PET/CT scans performed for response monitoring in patients with metastatic breast cancer in prospective setting. We included 37 metastatic breast cancer patients diagnosed and monitored with 2-[18F]FDG-PET/CT at Odense University Hospital (Denmark). A total of 100 scans were analyzed blinded toward Q.Clear and OSEM reconstruction algorithms regarding image quality parameters (noise, sharpness, contrast, diagnostic confidence, artefacts, and blotchy appearance) using a five-point scale. The hottest lesion was selected in scans with measurable disease, considering the same volume of interest in both reconstruction methods. SULpeak (g/mL) and SUVmax (g/mL) were compared for the same hottest lesion. There was no significant difference regarding noise, diagnostic confidence, and artefacts within reconstruction methods; Q.Clear had significantly better sharpness (p < 0.001) and contrast (p = 0.001) than the OSEM reconstruction, while the OSEM reconstruction had significantly less blotchy appearance compared with Q.Clear reconstruction (p < 0.001). Quantitative analysis on 75/100 scans indicated that Q.Clear reconstruction had significantly higher SULpeak (5.33 ± 2.8 vs. 4.85 ± 2.5, p < 0.001) and SUVmax (8.27 ± 4.8 vs. 6.90 ± 3.8, p < 0.001) compared with OSEM reconstruction. In conclusion, Q.Clear reconstruction revealed better sharpness, better contrast, higher SUVmax, and higher SULpeak, while OSEM reconstruction had less blotchy appearance.

Breast cancer is a spatially and temporally dynamic disease in which differently evolving genetic clones are responsible for progression and clinical outcome. We review tumor heterogeneity and clonal evolution from studies comparing primary tumors and metastasis and discuss plasma circulating tumor DNA as a powerful real-time approach for monitoring the clonal landscape of breast cancer during treatment and recurrence. We found only a few early studies exploring clonal evolution and heterogeneity through analysis of multiregional tissue biopsies of different progression steps in comparison with circulating tumor DNA (ctDNA) from blood plasma. The model of linear progression seemed to be more often reported than the model of parallel progression. The results show complex routes to metastasis, however, and plasma most often reflected metastasis more than primary tumor. The described patterns of evolution and the polyclonal nature of breast cancer have clinical consequences and should be considered during patient diagnosis and treatment selection. Current studies focusing on the relevance of clonal evolution in the clinical setting illustrate the role of liquid biopsy as a noninvasive biomarker for monitoring clonal progression and response to treatment. In the clinical setting, circulating tumor DNA may be an ideal support for tumor biopsies to characterize the genetic landscape of the metastatic disease and to improve longitudinal monitoring of disease dynamics and treatment effectiveness through detection of residual tumor after resection, relapse, or metastasis within a particular patient.

Background [18F]-fluorodeoxyglucose-positron emission tomography / computed tomography ([18F]FDG-PET/CT) has been implemented sporadically in hospital settings as the standard of care examination for recurrent breast cancer. We aimed to explore the clinical impact of implementing [18F]FDG-PET/CT for patients with clinically suspected recurrent breast cancer and validate the diagnostic accuracy. Methods Women with suspected distant recurrent breast cancer were prospectively enrolled in the study between September 2017 and August 2019. [18F]FDG-PET/CT was performed, and the appearance of incidental benign and malignant findings was registered. Additional examinations, complications, and the final diagnosis were registered to reflect the clinical consequence of such findings. The diagnostic accuracy of [18F]FDG-PET/CT as a stand-alone examination was analyzed. Biopsy and follow-up were used as a reference standard. Results [18F]FDG-PET/CT reported breast cancer metastases in 72 of 225 women (32.0%), and metastases were verified by biopsy in 52 (52/225, 23.1%). Prior probability and posterior probability of a positive test for suspected metastatic cancer and incidental malignancies were 27%/85% and 4%/20%, respectively. Suspected malignant incidental findings were reported in 46 patients (46/225, 20.4%), leading to further examinations and final detection of nine synchronous cancers (9/225, 4.0%). These cancers originated from the lung, thyroid, skin, pancreas, peritoneum, breast, kidney, one was malignant melanoma, and one was hematological cancer. False-positive incidental malignant findings were examined in 37/225 patients (16.4%), mainly in the colon (n = 12) and thyroid gland (n = 12). Ten incidental findings suspicious for benign disease were suggested by [18F]FDG-PET/CT, and further examinations resulted in the detection of three benign conditions requiring treatment. Sensitivity, specificity, and AUC-ROC for diagnosing distant metastases were 1.00 (0.93-1.0), 0.88 (0.82-0.92), and 0.98 (95% CI 0.97-0.99), respectively.Conclusion [18F]FDG-PET/CT provided a high posterior probability of positive test, and a negative test was able to rule out distant metastases in women with clinically suspected recurrent breast cancer. One-fifth of patients examined for incidental findings detected on [18F]FDG-PET/CT were diagnosed with clinically relevant conditions. Further examinations of false-positive incidental findings in one of six women should be weighed against the high accuracy for diagnosing metastatic breast cancer.Trial registration: Clinical.Trials.gov. NCT03358589. Registered 30 November 2017 - Retrospectively registered, http://www.ClinicalTrials.gov

Purpose: To investigate the clinical impact of FDG-PET/CT for staging and treatment planning in high-risk primary breast cancer. Methods: Women with high-risk primary breast cancer were enrolled between September 2017 and August 2019 at Odense University Hospital, Denmark. Conventional mammography with/without MRI was performed before staging by FDG-PET/CT. We studied the accuracy of FDG-PET/CT for the detection of distant metastases, the effect on the change of treatment, and the prevalence of incidental findings. Biopsy and follow-up were used as a reference standard for the accuracy analysis. Results: Of 103 women, 24 (23%) were diagnosed with distant metastases by FDG-PET/CT. Among these, breast surgery was omitted in 18 and could have been spared in six. Another sixteen (16%) patients were upstaged to more advanced loco-regional disease, leading to more extensive radiotherapy. Sensitivity and specificity for diagnosing distant metastases were 1.00 (95% confidence interval: 0.86–1.00) and 0.95 (0.88–0.99), respectively. Twenty-nine incidental findings were detected in 24 women (23%), leading to further examinations in 22 and diagnosis of eight (8/22, 36%) synchronous diseases: cancer (n = 4), thyroiditis (n = 2), aorta aneurysm (n = 1), and meningioma (n = 1). Conclusions: FDG-PET/CT had a substantial impact on staging and change of treatment in women with high-risk primary breast cancer, and further examination of incidental findings was considered clinically relevant. Our findings suggest that FDG-PET/CT should be considered for primary staging in high-risk primary breast cancer to improve treatment planning.

Aim: The F+10 method in supine position, which has been implemented at our Nuclear Medicine department since 2015, involves a 30- minute long dynamic acquisition. The diuretic is only administered ...

While current international guidelines include imaging of the target lesion for response monitoring in metastatic breast cancer, they do not provide specific recommendations for choice of imaging modality or response criteria. This is important as clinical decisions may vary depending on which imaging modality is used for monitoring metastatic breast cancer. FDG-PET/CT has shown high accuracy in diagnosing metastatic breast cancer, and the Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) have shown higher predictive values than the CT-based Response Evaluation Criteria in Solid Tumors (RECIST) for prediction of progression-free survival. No studies have yet addressed the clinical impact of using different imaging modalities or response evaluation criteria for longitudinal response monitoring in metastatic breast cancer. We present a case study of a patient with metastatic breast cancer who was monitored first with conventional CT and then with FDG-PET/CT. We retrospectively applied PERCIST to evaluate the longitudinal response to treatment. We used the one-lesion PERCIST model measuring SULpeak in the hottest metastatic lesion on consecutive scans. This model provides a continuous variable that allows graphical illustration of disease fluctuation along with response categories. The one-lesion PERCIST approach seems able to reflect molecular changes and has the potential to support clinical decision-making. Prospective clinical studies addressing the clinical impact of PERCIST in metastatic breast cancer are needed to establish evidence-based recommendations for response monitoring in this disease.