Joint EANM-SNMMI guideline on the role of 2-[18F]FDG PET/CT in no special type breast cancer : (endorsed by the ACR, ESSO, ESTRO, EUSOBI/ESR, and EUSOMA).

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.

Knowledge gaps in oncoplastic breast surgery.

The aims of the Oncoplastic Breast Consortium initiative were to identify important knowledge gaps in the field of oncoplastic breast-conserving surgery and nipple-sparing or skin-sparing mastectomy with immediate breast reconstruction, and to recommend appropriate research strategies to address these gaps. A total of 212 surgeons and 26 patient advocates from 55 countries prioritised the 15 most important knowledge gaps from a list of 38 in two electronic Delphi rounds. An interdisciplinary panel of the Oncoplastic Breast Consortium consisting of 63 stakeholders from 20 countries obtained consensus during an in-person meeting to select seven of these 15 knowledge gaps as research priorities. Three key recommendations emerged from the meeting. First, the effect of oncoplastic breast-conserving surgery on quality of life and the optimal type and timing of reconstruction after nipple-sparing or skin-sparing mastectomy with planned radiotherapy should be addressed by prospective cohort studies at an international level. Second, the role of adjunctive mesh and the positioning of implants during implant-based breast reconstruction should ideally be investigated by randomised controlled trials of pragmatic design. Finally, the BREAST-Q questionnaire is a suitable tool to assess primary outcomes in these studies, but other metrics to measure patient-reported outcomes should be systematically evaluated and quality indicators of surgical morbidity should be further assessed.

Real-time wireless tumor tracking during breast conserving surgery.

PURPOSE: To evaluate a novel surgical navigation system for breast conserving surgery (BCS), based on real-time tumor tracking using the Calypso[Formula: see text] 4D Localization System (Varian Medical Systems Inc., USA). Navigation-guided breast conserving surgery (Nav-BCS) was compared to conventional iodine seed-guided BCS ([Formula: see text]I-BCS). METHODS: Two breast phantom types were produced, containing spherical and complex tumors in which wireless transponders (Nav-BCS) or a iodine seed ([Formula: see text]I-BCS) were implanted. For navigation, orthogonal views and 3D volume renders of a CT of the phantom were shown, including a tumor segmentation and a predetermined resection margin. In the same views, a surgical pointer was tracked and visualized. [Formula: see text]I-BCS was performed according to standard protocol. Five surgical breast oncologists first performed a practice session with Nav-BCS, followed by two Nav-BCS and [Formula: see text]I-BCS sessions on spherical and complex tumors. Postoperative CT images of all resection specimens were registered to the preoperative CT. Main outcome measures were the minimum resection margin (in mm) and the excision times. RESULTS: The rate of incomplete tumor resections was 6.7% for Nav-BCS and 20% for [Formula: see text]I-BCS. The minimum resection margins on the spherical tumors were 3.0 ± 1.4 mm for Nav-BCS and 2.5 ± 1.6 mm for [Formula: see text]I-BCS (p = 0.63). For the complex tumors, these were 2.2 ± 1.1 mm (Nav-BCS) and 0.9 ± 2.4 mm ([Formula: see text]I-BCS) (p = 0.32). Mean excision times on spherical and complex tumors were 9.5 ±  2.7 min and 9.4 ± 2.6 min (Nav-BCS), compared to 5.8 ± 2.2  min and 4.7 ± 3.4 min ([Formula: see text]I-BCS, both (p < 0.05). CONCLUSIONS: The presented surgical navigation system improved the intra-operative awareness about tumor position and orientation, with the potential to improve surgical outcomes for non-palpable breast tumors. Results are positive, and participating surgeons were enthusiastic, but extended surgical experience on real breast tissue is required.

Diagnosis of breast cancer using diffuse optical spectroscopy from 500 to 1600 nm: comparison of classification methods.

We report on the use of diffuse optical spectroscopy analysis of breast spectra acquired in the wavelength range from 500 to 1600 nm with a fiber optic probe. A total of 102 ex vivo samples of five different breast tissue types, namely adipose, glandular, fibroadenoma, invasive carcinoma, and ductal carcinoma in situ from 52 patients were measured. A model deriving from the diffusion theory was applied to the measured spectra in order to extract clinically relevant parameters such as blood, water, lipid, and collagen volume fractions, ß-carotene concentration, average vessels radius, reduced scattering amplitude, Mie slope, and Mie-to-total scattering fraction. Based on a classification and regression tree algorithm applied to the derived parameters, a sensitivity-specificity of 98%-99%, 84%-95%, 81%-98%, 91%-95%, and 83%-99% were obtained for discrimination of adipose, glandular, fibroadenoma, invasive carcinoma, and ductal carcinoma in situ, respectively; and a multiple classes overall diagnostic performance of 94%. Sensitivity-specificity values obtained for discriminating malignant from nonmalignant tissue were compared to existing reported studies by applying the different classification methods that were used in each of these studies. Furthermore, in these reported studies, either lipid or ß-carotene was considered as adipose tissue precursors. We estimate both chromophore concentrations and demonstrate that lipid is a better discriminator for adipose tissue than ß-carotene.

On the feasibility of MRI-guided navigation to demarcate breast cancer for breast-conserving surgery.

PURPOSE: The aim of this study was to investigate the feasibility of image-guided navigation approaches to demarcate breast cancer on the basis of preacquired magnetic resonance (MR) imaging in supine patient orientation. METHODS: Strategies were examined to minimize the uncertainty in the instrument-tip position, based on the hypothesis that the release of instrument pressure returns the breast tissue to its predeformed state. For this purpose, four sources of uncertainty were taken into account: (1) U(ligaments): Uncertainty in the reproducibility of the internal mammary gland geometry during repeat patient setup in supine orientation; (2) U(r_breathing): Residual uncertainty in registration of the breast after compensation for breathing motion using an external marker; (3) U(reconstruction): Uncertainty in the reconstructed location of the tip of the needle using an optical image-navigation system (phantom experiments, n = 50); and (4) U(deformation): Uncertainty in displacement of breast tumors due to needle-induced tissue deformations (patients, n = 21). A Monte Carlo study was performed to establish the 95% confidence interval (CI) of the combined uncertainties. This region of uncertainty was subsequently visualized around the reconstructed needle tip as an additional navigational aid in the preacquired MR images. Validation of the system was performed in five healthy volunteers (localization of skin markers only) and in two patients. In the patients, the navigation system was used to monitor ultrasound-guided radioactive seed localization of breast cancer. Nearest distances between the needle tip and the tumor boundary in the ultrasound images were compared to those in the concurrently reconstructed MR images. RESULTS: Both U(reconstruction) and U(deformation) were normally distributed with 0.1 +/- 1.2 mm (mean +/- 1 SD) and 0.1 +/- 0.8 mm, respectively. Taking prior estimates for U(ligaments) (0.0 +/- 1.5 mm) and U(r_breathing) (-0.1 +/- 0.6 mm) into account, the combined impact resulted in 3.9 mm uncertainty in the position of the needle tip (95% CI) after release of pressure. The volunteer study showed a targeting accuracy comparable to that in the phantom experiments: 2.9 +/- 1.3 versus 2.7 +/- 1.1 mm, respectively. In the patient feasibility study, the deviations were within the 3.9 mm CI. CONCLUSIONS: Image-guided navigation to demarcate breast cancer on the basis of preacquired MR images in supine orientation appears feasible if patient breathing is tracked during the navigation procedure, positional uncertainty is visualized and pressure on the localization instrument is released prior to verification of its position.

Prophylactic mastectomy in BRCA1 and BRCA2 mutation carriers: very low risk for subsequent breast cancer.

AIM: To examine the outcome of prophylactic mastectomy in a hospital-based series of BRCA1/2 gene mutation carriers with and without a history of breast cancer. PATIENTS AND METHODS: A center-based consecutive series of 254 BRCA1/2 gene mutation carriers that had prophylactic mastectomy after a normal surveillance round including breast-magnetic resonance imaging were identified. One hundred forty-seven asymptomatic carriers underwent bilateral mastectomy and 107 symptomatic women had contralateral mastectomy after a mean cancer free interval of 3.6 years. All removed breasts were histopathologically examined. RESULTS: In one asymptomatic BRCA2 carrier (0.7%) an occult small invasive breast cancer was diagnosed, while in 6 asymptomatic carriers (4.0% BRCA1 and 4.3% BRCA2) and in 5 symptomatic carriers (2.5% BRCA1 and 10.7% BRCA2) DCIS was detected at prophylactic mastectomy. No breast cancer occurred in the asymptomatic group after a postprophylactic follow-up period of 778 women-years. In the symptomatic carriers 1 invasive breast cancer was detected after 580 follow-up years. From age-, cohort-, and gene-specific reference data we calculated that 15 invasive first cancers in the asymptomatic carriers were prevented during follow-up. CONCLUSION: One invasive breast cancer in 147 bilateral prophylactic mastectomies (0.7%) was detected, this makes a sentinel node procedure redundant and preoperative imaging vital. The prophylactic procedure is highly effective in preventing invasive breast cancer in BRCA1/2 mutation carriers. Since the remaining risk is less than 0.2%/woman-year, continued surveillance of the asymptomatic carriers is not warranted.

Dynamic contrast-enhanced MRI for prediction of breast cancer response to neoadjuvant chemotherapy: initial results.

OBJECTIVE: The aim of this study was to establish changes in contrast-enhanced MRI of breast cancer during neoadjuvant chemotherapy that are indicative of pathology outcome. MATERIALS AND METHODS: In 54 patients with breast cancer, dynamic contrast-enhanced MRI was performed before chemotherapy and after two chemotherapy cycles. Imaging was correlated with final histopathology. Multivariate analysis with cross-validation was performed on MRI features describing kinetics and morphology of contrast uptake in the early and late phases of enhancement. Receiver operating characteristic (ROC) analysis was used to develop a guideline that switches patients at high risk for incomplete remission to a different chemotherapy regimen while maintaining first-line therapy in 95% of patients who are not at risk (i.e., high specificity). RESULTS: Change in largest diameter of late enhancement during chemotherapy was the single most predictive MRI characteristic for tumor response in multivariate analysis (A(z) [area under the ROC curve] = 0.73, p < 0.00001). Insufficient (< 25%) decrease in largest diameter of late enhancement during chemotherapy was most indicative of residual tumor at final pathology. Using this criterion, the fraction of unfavorable responders indicated by MRI was 41% (22/54). Approximately half (44%, 14/32) of the patients who showed favorable response at MRI achieved complete remission at pathology. Conversely, 95% (21/22) of patients who showed unfavorable response at MRI had residual tumor at pathology. CONCLUSION: Reduction of less than 25% in largest diameter of late enhancement during neoadjuvant chemotherapy shows the potential to predict residual tumor after therapy with high specificity.