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The PHERGain trial investigated the potential of metabolic imaging to identify candidates for chemotherapy deescalation in human epidermal growth factor receptor 2 (HER2)-positive, invasive, operable breast cancer with at least 1 breast lesion evaluable by [ 18 F]FDG PET/CT. [ 18 F]FDG PET/CT responders were defined as patients with an SUV max reduction (ΔSUV max ) of at least 40% in all of their target lesions after 2 cycles of trastuzumab and pertuzumab (HP) (with or without endocrine therapy). In total, 227 of 285 patients (80%) included in the HP arm showed a predefined metabolic response and received a total of 8 cycles of HP (with or without endocrine therapy). Pathologic complete response (pCR), defined as ypT0/isN0, was achieved in 37.9% of the patients. Here, we describe the secondary preplanned analysis of the best cutoff of ΔSUV max for pCR prediction. Methods: Receiver-operating-characteristic analysis was applied to look for the most appropriate ΔSUV max cutoff in HER2-positive early breast cancer patients treated exclusively with neoadjuvant HP (with or without endocrine therapy). Results: The ΔSUV max capability of predicting pCR in terms of the area under the receiver-operating-characteristic curve was 72.1% (95% CI, 65.1-79.2%). The optimal ΔSUV max cutoff was found to be 77.0%, with a 51.2% sensitivity and a 78.7% specificity. With this cutoff, 74 of 285 patients (26%) would be classified as metabolic responders, increasing the pCR rate from 37.9% (cutoff ≥ 40%) to 59.5% (44/74 patients) ( P < 0.01). With this optimized cutoff, 44 of 285 patients (15.4%) would avoid chemotherapy in either the neoadjuvant or the adjuvant setting compared with 86 of 285 patients (30.2%) using the original cutoff ( P < 0.001). Conclusion: In the PHERGain trial, an increased SUV max cutoff (≥77%) after 2 cycles of exclusive HP (with or without endocrine therapy) achieves a pCR in the range of the control arm with chemotherapy plus HP (59.5% vs. 57.7%, respectively), further identifying a subgroup of patients with HER2-addicted tumors. However, the original cutoff (≥40%) maximizes the number of patients who could avoid chemotherapy., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: PHERGain was designed to assess the feasibility, safety, and efficacy of a chemotherapy-free treatment based on a dual human epidermal growth factor receptor 2 (HER2) blockade with trastuzumab and pertuzumab in patients with HER2-positive early breast cancer (EBC). It used an 18 fluorine-fluorodeoxyglucose-PET-based, pathological complete response (pCR)-adapted strategy., Methods: PHERGain was a randomised, open-label, phase 2 trial that took place in 45 hospitals in seven European countries. It randomly allocated patients in a 1:4 ratio with centrally confirmed, HER2-positive, stage I-IIIA invasive, operable breast cancer with at least one PET-evaluable lesion to either group A, where patients received docetaxel (75 mg/m 2 , intravenous), carboplatin (area under the curve 6 mg/mL per min, intravenous), trastuzumab (600 mg fixed dose, subcutaneous), and pertuzumab (840 mg loading dose followed by 420 mg maintenance doses, intravenous; TCHP), or group B, where patients received trastuzumab and pertuzumab with or without endocrine therapy, every 3 weeks. Random allocation was stratified by hormone receptor status. Centrally reviewed PET was conducted at baseline and after two treatment cycles. Patients in group B were treated according to on-treatment PET results. Patients in group B who were PET-responders continued with trastuzumab and pertuzumab with or without endocrine therapy for six cycles, while PET-non-responders were switched to receive six cycles of TCHP. After surgery, patients in group B who were PET-responders who did not achieve a pCR received six cycles of TCHP, and all patients completed up to 18 cycles of trastuzumab and pertuzumab. The primary endpoints were pCR in patients who were group B PET-responders after two treatment cycles (the results for which have been reported previously) and 3-year invasive disease-free survival (iDFS) in patients in group B. The study is registered with ClinicalTrials.gov (NCT03161353) and is ongoing., Findings: Between June 26, 2017, and April 24, 2019, a total of 356 patients were randomly allocated (71 patients in group A and 285 patients in group B), and 63 (89%) and 267 (94%) patients proceeded to surgery in groups A and B, respectively. At this second analysis (data cutoff: Nov 4, 2022), the median duration of follow-up was 43·3 months (range 0·0-63·0). In group B, the 3-year iDFS rate was 94·8% (95% CI 91·4-97·1; p=0·001), meeting the primary endpoint. No new safety signals were identified. Treatment-related adverse events and serious adverse events (SAEs) were numerically higher in patients allocated to group A than to group B (grade ≥3 62% vs 33%; SAEs 28% vs 14%). Group B PET-responders with pCR presented the lowest incidence of treatment-related grade 3 or higher adverse events (1%) without any SAEs., Interpretation: Among HER2-positive EBC patients, a PET-based, pCR-adapted strategy was associated with an excellent 3-year iDFS. This strategy identified about a third of patients who had HER2-positive EBC who could safely omit chemotherapy., Funding: F Hoffmann-La Roche., Competing Interests: Declaration of interests JMP-G reports consulting roles for Roche, Lilly, Eisai, Daiichi Sankyo, AstraZeneca, Gilead, MSD, and Seattle Genetics and travel expenses from Roche. JC reports consulting roles for Roche, Celgene, Cellestia, AstraZeneca, Biothera Phgroupaceutical, Merus, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Servier, MSD, GSK, Leuko, Bioasis, and Clovis Oncology; honoraria from Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, MSD, and Daiichi Sankyo; research funding to their institution from Roche, Ariad pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, F Hoffman-La Roche, Guardanth health, MSD, Pfizer, Piqur Therapeutics, Puma C, and Queen Mary University of London; and intellectual property for Medica Scientia Innovation Research (MEDSIR). MR-B reports membership of a speaker bureau and advisory board for Novartis. MC reports a research grant to their institution from Roche and the role of co-chair of the scientific committee of the International Breast Cancer Study Group. AS reports consulting roles for Roche, AstraZeneca, Seagen, Novartis, and Boehringer Ingelheim; to be part of a speaker bureau for Daiichi Sankyo, Roche, and Novartis; and travel expenses from Pfizer, Novartis, and Eisai. BB reports receiving fees for medical education in a consulting or advisory role with MSD, Roche, Pierre Fabre, Novartis, AstraZeneca, and Seagen; participating in a speakers bureau for Pfizer, Roche, MSD, Palex, Eisai, Daichii Sankyo, AstraZeneca, and Seagen. SE-d-R reports consulting roles for Daiichi Sankyo/AstraZeneca, Seagen, and Pierre Fabre; to be part of a speaker bureau for Daiichi Sankyo/AstraZeneca, Pfizer, Novartis, Seagen; to have received research funding from Roche, Synthon, Byondis, MEDSIR, SOLTI, Zymeworks, and Daiichi Sankyo/AstraZeneca; and travel, accommodation, or expenses from Pfizer, Kern Pharma, and Daiichi Sankyo/AstraZeneca. NR reports research funding from Pfizer; and to be part of speaker bureau for Novartis, Pfizer, Gilead, and Daiichi Sankyo/AstraZeneca. FM reports grants from Roche, Novartis, AstraZeneca, GSK, MSD, Clovis, Vaccibody, Gilead Sciences, and Esai; consulting fees from AstraZeneca, GSK, and Roche; honoraria from AstraZeneca, MSD, Lilly, Pfizer, Novartis, GSK, Clovis, Myriad, Daiichi Sankyo, Seagen, Pierre Fabre, and Agendia; travel support from AstraZeneca, GSK, Pfizer, and Roche; and participation in advisory boards for Palleos and Amgen. AC reports consulting or advisory roles for Daiichi Sankyo/AstraZeneca, Seagen, and Pierre Fabre; being part of a speakers bureau for Daiichi Sankyo/AstraZeneca, Pfizer, Novartis, and Seagen; institutional research funding from Roche, Synthon, Byondis, MEDSIR, SOLTI, Zymeworks, and Daiichi Sankyo/AstraZeneca; and expert testimony and travel or accommodations expenses from Pfizer, Kern Pharma, and Daiichi Sankyo/AstraZeneca. AP reports honoraria from Pfizer, Novartis, Roche, MSD Oncology, Lilly, Daiichi Sankyo, and Amgen; to have consulting roles for Roche, AstraZeneca, Peptomyc, Novartis, and Daiichi Sankyo; research funding to their institution from Roche, AstraZeneca, Novartis, and Reveal Genomics; to have intellectual property (ERBB2 and HER2DX patents); travel expenses from Daiichi Sankyo; and a share in ownership at Reveal Genomics. PS reports honoraria from Pfizer, AstraZeneca, Novartis, Roche, Merck, and Boehringer Ingelheim; a consulting role in Pfizer, AstraZeneca, Novartis, Roche, Merck, Boehringer Ingelheim, Bayer, Eisai, Celgene, and Puma; and grants to their institution from Roche, Genentech, Oncogenex, and Novartis. SB reports a consulting or advisory board role at Daiichi Sankyo, AstraZeneca, Novartis, and Roche; speaker or conference fees from Daiichi Sankyo, AstraZeneca, Novartis, and Roche; and travel fees from Daiichi Sankyo, AstraZeneca, Novartis, and Roche. SDC reports receiving fees for medical education from Novartis, Pierre Fabre, and IQVIA; institutional grant IG 20774 of Fondazione AIRC per la Ricerca sul Cancro; Cancer Can.Heal European EU4 Health Programme 101080009–European Commission; and serving as an ad hoc medical advisor for MEDSIR. MG reports honoraria from Roche, Novartis, Gilead, and AstraZeneca; travel grants and accommodation from Roche, Pfizer, and AstraZeneca; and an advisory role at Gilead. GA reports honoraria from MEDSIR. AL-C reports leadership roles at Eisai, Celgene, Lilly, Pfizer, Roche, Novartis, and MSD; intellectual property for MEDSIR and Initia Research; to have consulting roles for Lilly, Roche, Pfizer, Novartis, Pierre Fabre, GenomicHealth, and GSK; to be part of a speakers bureau for Lilly, AstraZeneca, and MSD; research funding from Roche, Foundation Medicine, Pierre Fabre, and Agendia; and travel expenses from Roche, Lilly, Novartis, Pfizer, and AstraZeneca. CP, ES, DA-L, PG, JR-M, LM, and MS-C are employees of MEDSIR. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Several de-escalation approaches are under investigation in patients with HER2-positive, early-stage breast cancer. We assessed early metabolic responses to neoadjuvant trastuzumab and pertuzumab using 18 F-fluorodeoxyglucose ( 18 F-FDG)-PET ( 18 F-FDG-PET) and the possibility of chemotherapy de-escalation using a pathological response-adapted strategy., Methods: We did a multicentre, randomised, open-label, non-comparative, phase 2 trial in 45 hospitals in Spain, France, Belgium, Germany, the UK, Italy, and Portugal. Eligible participants were women aged 18 years or older with centrally confirmed, HER2-positive, stage I-IIIA, invasive, operable breast cancer (≥1·5 cm tumour size) with at least one breast lesion evaluable by 18 F-FDG-PET, an Eastern Cooperative Oncology Group performance status of 0 or 1, and a baseline left ventricular ejection fraction of at least 55%. We randomly assigned participants (1:4), via an interactive response system using central block randomisation with block sizes of five, stratified by hormone receptor status, to either docetaxel (75 mg/m 2 intravenous), carboplatin (area under the concentration-time curve 6 mg/mL  per  min intravenous), trastuzumab (subcutaneous 600 mg fixed dose), and pertuzumab (intravenous 840 mg loading dose, 420 mg maintenance doses; group A); or trastuzumab and pertuzumab (group B). Hormone receptor-positive patients allocated to group B were additionally given letrozole if postmenopausal (2·5 mg/day orally) or tamoxifen if premenopausal (20 mg/day orally). Centrally reviewed 18 F-FDG-PET scans were done before randomisation and after two treatment cycles. Patients assigned to group A completed six cycles of treatment (every 3 weeks) regardless of 18 F-FDG-PET results. All patients assigned to group B initially received two cycles of trastuzumab and pertuzumab. 18 F-FDG-PET responders in group B continued this treatment for six further cycles; 18 F-FDG-PET non-responders in this group were switched to six cycles of docetaxel, carboplatin, trastuzumab, and pertuzumab. Surgery was done 2-6 weeks after the last dose of study treatment. Adjuvant treatment was selected according to the neoadjuvant treatment administered, pathological response, hormone receptor status, and clinical stage at diagnosis. The coprimary endpoints were the proportion of 18 F-FDG-PET responders in group B with a pathological complete response in the breast and axilla (ypT0/is ypN0) as determined by a local pathologist after surgery after eight cycles of treatment, and 3-year invasive disease-free survival of patients in group B, both assessed by intention to treat. The definitive assessment of pathological complete response was done at this primary analysis; follow-up to assess invasive disease-free survival is continuing, hence these data are not included in this Article. Safety was assessed in all participants who received at least one dose of study drug. Health-related quality-of-life was assessed with EORTC QLQ-C30 and QLQ-BR23 questionnaires at baseline, after two cycles of treatment, and before surgery. This trial is registered with EudraCT (2016-002676-27) and ClinicalTrials.gov (NCT03161353), and is ongoing., Findings: Between June 26, 2017, and April 24, 2019, we randomly assigned 71 patients to group A and 285 to group B. Median follow-up was 5·7 months (IQR 5·3-6·0). 227 (80%) of 285 patients in group B were 18 F-FDG-PET responders, of whom 86 (37·9%, 95% CI 31·6-44·5; p<0·0001 compared with the historical rate) of 227 had a pathological complete response. The most common haematological grade 3-4 adverse events were anaemia (six [9%] of 68 patients in group A vs four [1%] of 283 patients in group B), neutropenia (16 [24%] vs ten [4%]), and febrile neutropenia (14 [21%] vs 11 [4%]). Serious adverse events occurred in 20 (29%) of 68 patients in group A versus 13 (5%) of 283 patients in group B. No deaths were reported during neoadjuvant treatment. Global health status declined by at least 10% in 65·0% (95% CI 46·5-72·4) and 35·5% (29·7-41·7) of patients in groups A and B, respectively INTERPRETATION: 18 F-FDG-PET identified patients with HER2-positive, early-stage breast cancer who were likely to benefit from chemotherapy-free dual HER2 blockade with trastuzumab and pertuzumab, and a reduced impact on global health status. Depending on the forthcoming results for the 3-year invasive disease-free survival endpoint, this strategy might be a valid approach to select patients not requiring chemotherapy., Funding: F Hoffmann-La Roche., Competing Interests: Declaration of interests JMP-G reports a consulting role for Roche and Lilly, travel expenses from Roche, and is a part-time employee of Medica Scientia Innovation Research. GG reports research funding from Roche paid to their institution and that an immediate family member received personal fees from Roche. MRB reports a consulting role for Novartis, Pfizer, and Merck-Sharpe & Dohme (MSD), and being part of the speaker bureau for Pfizer, Novartis, Roche, Lilly, and AstraZeneca. AS reports a consulting role for Roche and Eisai, being part of the speaker bureau for Roche and Eisai, and reports expert testimony for Eisai and Roche, and travel expenses from Roche and Pfizer. BB reports a consulting role for Genentech and MSD, being part of the speaker bureau for Genentech, and travel expenses from Pfizer. PS reports honoraria from Pfizer, AstraZeneca, Novartis, Roche, Merck, and Boehringer Ingelheim; a consulting role for Pfizer, AstraZeneca, Novartis, Roche, Merck, Boehringer Ingelheim, Bayer, Eisai, Celgene, and Puma; and a grant to their institution from Roche, Genentech, Oncogenex, and Novartis. FM reports honoraria from Roche–Genentech, Novartis, Pfizer, AstraZeneca, Tesaro, Clovis Oncology, Eisai, Celgene, Genomic Health, PharmaMar, Amgen, CureVac, MSD Oncology, Janssen-Cilag, and ImmunoMedics (to their institution); research funding to their institution from Roche–Genentech, Novartis, AstraZeneca, Eisai, Tesaro, Clovis, MSD Oncology, and Vaccibody; travel compensations from Roche, Pfizer, Novartis, PharmaMar, and AstraZeneca; and a consulting role for Tesaro, Pfizer, Novartis, GenomicHealth, CureVac, Amgen, Celgene, Eisai, Janssen-Cilag, AstraZeneca (to their institution), Roche (to their institution), Vaccibody (to their institution), and Immunomedics (to their institution) during this study. SE-d-R reports a consulting role for Roche, Pierre-Fabre, and Eisai; research funding from Synthon and Roche; and travel expenses from Roche, Pierre-Fabre, and Daiichi Sankyo. AP reports honoraria from Pfizer, Novartis, Roche, MSD Oncology, Lilly, Daiichi Sankyo, and Amgen; a consulting role for Amgen, Roche, Novartis, Pfizer, Bristol-Myers-Squibb, Boehringer, PUMA Biotechnology, Oncolytics Biotech, Daiichi Sankyo, Abbvie, and NanoString Technologies; research funding to their institution from Roche, Novartis, Incyte, and PUMA Biotechnology; intellectual property (PCT/EP2016/080056: HER2 as a predictor of response to dual HER2 blockade in the absence of cytotoxic therapy; WO/2018/096191: Chemoendocrine score based on PAM50 for breast cancer with positive hormone receptors with an intermediate risk of recurrence); travel expenses from Daiichi Sankyo; other funding from Oncolytics, and Peptomyc; and that an immediate family member is an employee of Novartis. MC reports a consulting role for Pierre-Fabre, Pfizer, OBI Pharma, Celldex, and AstraZeneca; and honoraria from Novartis. NA reports a consulting role for Pfizer, Novartis, Roche, AstraZeneca, and Lilly; and travel expenses from Pfizer, Novartis, Roche, and AstraZeneca. SDC reports fees for medical education from Novartis and Pierre-Fabre; being a recipient of the IG20774 grant from Fondazione Associazione Italiana Ricerca contro il Cancro), and is a part-time employee of MEDSIR during this study. MS-C reports honoraria and a consulting role for from MEDSIR, Syntax for Science, and Nestlé; being part of the speaker bureau for MEDSIR, Syntax for Science, and Roche; research funding from MEDSIR, Syntax for Science, and Roche; travel expenses from MEDSIR, Syntax for Science, and Roche; and is a part-time employee of MEDSIR during this study. AM is a full-time employee of MEDSIR. JC reports a consulting role for Roche, Celgene, Cellestia, AstraZeneca, Biothera Pharmaceutical, Merus, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Servier, MSD, GlaxoSmithKline (GSK), Leuko, Bioasis, and Clovis Oncology; honoraria from Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, MSD, and Daiichi Sankyo; research funding to their institution from Roche, Ariad Pharmaceuticals, AstraZeneca, Baxalta GMBH–Servier Affaires, Bayer healthcare, Eisai, F Hoffman-La Roche, Guardant Health, MSD, Pfizer, Piqur Therapeutics, Puma C, and Queen Mary University of London; and intellectual property for MEDSIR. AL-C reports leadership for Eisai, Celgene, Lilly, Pfizer, Roche, Novartis, and MSD; intellectual property for MEDSIR and Initia-Research; a consulting role for Lilly, Roche, Pfizer, Novartis, Pierre-Fabre, GenomicHealth, and GSK; being part of the speaker bureau for Lilly, AstraZeneca, and MSD; research funding from Roche, Foundation Medicine, Pierre-Fabre, and Agendia; and travel expenses from Roche, Lilly, Novartis, Pfizer, and AstraZeneca. LC, NR, NM, CA, FD, and KK declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Currently, the most frequent approach in the oncologic applications of positron emission tomography (PET) is detecting the hypermetabolic activity of the cancer tissue. A more specific approach, which may be complementary, is detecting the overexpression of receptors. In this review article, we aim to evaluate the results that are currently available for PET imaging of the sex hormone receptors in clinical oncology. The indication of PET and now PET/CT has been more disputed in breast carcinoma than in many other primary cancers (e.g., lung, head and neck, colorectal, lymphoma). 18F-fluorodeoxyglucose (FDG), the glucose analogue for PET imaging, has a limited sensitivity to detect the primary breast tumors in case of lobular or in situ forms or small sized tumors localised on systematic mammography, and to identify minimal node invasion in the axilla. Using 16α-[¹⁸F]fluoro-17β-estradiol (FES), a fluorinated estradiol analogue, PET is able to detect the over-expression of the oestrogen receptor (ER) in lesions, at a whole-body level. FES and FDG appear complementary for a better diagnostic performance in staging locally advanced breast cancer or restaging recurrent or metastatic breast cancer. Another potential indication is predicting the response to starting or resuming hormone therapy in patients with metastatic breast cancer, in relation with the ER status of all lesions revealed by FES PET. In two retrospective studies, FDG PET was also able to predict the response to hormone therapy, on basis of a metabolic flare, observed either after 7-10 days of treatment or during an estradiol challenge. A prospective comparison of those approaches is warranted. One study reported predicting response to neoadjuvant chemotherapy thanks to a low value of FES SUV(max) or FES/FDG SUV(max) ratio. The presence of ER in uterine tumors, including the benign ones, in ovarian cancers or even in meningiomas, may have therapeutic consequences and FES PET could have a clinical utility in those settings; only initial results are available. The indication of PET and PET/CT has been even more disputed in prostate carcinoma, due to the lack of significant FDG uptake in most cases, at least before the castration-resistant stage. Using FDHT, a fluorinated testosterone analogue, PET is able to detect the over-expression of the androgen receptor (AR) in lesions, at a whole-body level. At least partly due to the rather large number of alternative tracers that are in development or even routinely available in some countries, few FDHT studies have been published until now. From absorbed dose values previously published for FES by the team of University of Washington School of Medicine at Seattle, and for FDHT by the teams of Memorial Sloan-Kettering Cancer Center at New York and of Washington University at St. Louis, we applied the coefficients of ICRP publication 103 and calculated an effective dose per unit of injected activity of 0.023 mSv/MBq for FES and 0.018 mSv/MBq for FDHT. The radiation exposure is of the same order of magnitude as with FDG.

Background: An effective and well tolerated treatment is needed for patients with early HER2-positive breast cancer who do not achieve a pathological complete response after neoadjuvant therapy. The AVATAXHER trial aimed to predict pathological complete response early with the use of PET and to investigate whether the addition of bevacizumab could improve the proportion of patients achieving a pathological complete response in patients unlikely to respond to treatment., Methods: AVATAXHER was a randomised, open-label, non-comparative, multicentre phase 2 study that enrolled women (≥18 years of age) with early-stage HER2-positive breast cancer from 26 oncology centres in France. Patients initially received two cycles of neoadjuvant docetaxel (100 mg/m(2) intravenously every 3 weeks) plus trastuzumab (8 mg/kg intravenously every 3 weeks then 6 mg/kg intravenously every 3 weeks for the second course). Before the first and second cycles, [(18)F]-fluorodeoxyglucose (FDG) PET was done and the change in standardised uptake value was used to predict pathological complete response in each patient. Patients who were predicted to be responders on PET continued to receive standard therapy. Predicted non-responders were randomly assigned (2:1) to receive four cycles of docetaxel (100 mg/m(2) intravenously every 3 weeks) and trastuzumab (6 mg/kg intravenously every 3 weeks) plus bevacizumab (15 mg/kg intravenously every 3 weeks; group A) or continue on docetaxel plus trastuzumab alone (group B). Randomisation was open label and was done by an adaptive minimisation method. Although investigators and patients were aware of group assignment, the anatomo-pathologist in charge of centralised review of surgical samples and lymph nodes was masked to treatment assignment. The primary endpoint was centrally assessed pathological complete response according to the Chevallier classification. Efficacy analyses were done in the intention-to-treat population. Safety analyses in this Article were done on all patients who received at least one dose of treatment starting from cycle 3. Survival outcomes are not yet mature. This study is registered with ClinicalTrials.gov (NCT01142778) and EUDRACT (2009-013410-26)., Findings: Between May 19, 2010, and Oct 1, 2012, 152 patients were recruited for the study. Ten patients were subsequently excluded, leaving 142 patients in the intention-to-treat population. Of these 142 patients, 69 were predicted by [(18)F]-FDG PET to be treatment responders after two cycles of treatment. The 73 predicted non-responders were randomly assigned to group A (n=48) and group B (n=25). Pathological complete responses were noted in 37 (53·6%, 95% CI 41·2-65·7) of the PET responders, 21 (43·8%, 29·5-58·8) of those in group A, and six (24·0%, 9·4-45·1) of those in group B. Incidences of grade 3-4 adverse events were similar in all three groups. The most common grade 3-4 adverse events were neutropenia (four in PET responders, five in group A, and three in group B), febrile neutropenia (one, three, and one, respectively), and myalgia (four, none, and one, respectively). Overall, 24 serious adverse events were reported in 15 patients (PET responders: nine events in four [6%] of 67 patients; group A: 14 events in ten [21%] of 47 patients; group B: one event in one [4%] of 25 patients). No deaths occurred during the study., Interpretation: In patients with HER2-positive breast cancer, early PET assessment can help to identify non-responders to neoadjuvant docetaxel plus trastuzumab therapy. In these patients, the addition of bevacizumab can increase the proportion of patients achieving a pathological complete response. This potential new role for PET and the activity of bevacizumab in this setting need to be confirmed in larger phase 3 trials., Funding: Roche France., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Unlabelled: The aim of this study was to compare the effectiveness of a hand-held preoperative compact imager (POCI) camera with conventional lymphoscintigraphy using a γ-camera for sentinel lymph node (SLN) detection in breast cancer., Methods: The main objective was to demonstrate the noninferiority of the POCI relative to conventional lymphoscintigraphy and to compare the number of SLNs detected by the 2 imaging devices. Our study, a clinical prospective, double-blind, noninferiority study, planned to include 200 patients with early breast cancer and started in January 2006. A standard SLN protocol (4 periareolar injections of 37 MBq of (99m)Tc-nanocolloids, 2 h before lymphoscintigraphy) was performed preoperatively using a conventional γ-camera and then the POCI camera. Scans were obtained by 2 different nuclear medicine physicians unaware of each other's results. The day after, in the operating room, the surgeon, after receiving the previous results, used the counting probe for surgical SLN biopsy. The number and localization of axillary SLNs obtained by lymphoscintigraphy and the POCI and the duration of the whole procedure were determined., Results: Among the 162 patients included, 138 were evaluable. The POCI detected more SLNs than did lymphoscintigraphy in 50 patients (36%), the same number of in 54 patients (39%), and fewer SLNs in 34 patients (25%), representing 84 (61%) discordant pairs. The noninferiority of preoperative compact imaging of axillary SLNs numbers was found to be statistically significant (95% confidence interval, 30%-52%, P = 0.025) using the McNemar test. The duration of acquisition was shorter using the POCI (<10 min in 84% [n = 117] of patients; mean, 7.5 ± 3.3 min) than lymphoscintigraphy (13% [n = 18] of patients; mean, 15.7 ± 3.4 min), with P < 0.001 using the McNemar test for paired proportions., Conclusion: Preoperative compact imaging using a hand-held camera was able to predict the number and localization of breast cancer SLNs and was not inferior to conventional lymphoscintigraphy in this study. Further studies will determine whether preoperative compact imaging could replace lymphoscintigraphy, especially in surgical centers without an on-site nuclear medicine department.

Background: Occult invasive disease could be found at definitive histology in patients initially diagnosed with large ductal carcinoma in situ (DCIS). Sentinel lymph node (SLN) biopsy is a reliable and minimally invasive procedure providing axillary information and avoiding a second operation in this particular group of patients. The aim of our study was to assess the value of SLN biopsy in patients with large DCIS who are at highest risk for being upstaged to invasive carcinoma., Patients and Methods: The study included 195 patients diagnosed with DCIS upon initial core biopsy and undergoing SLN biopsy. Many features were correlated with the presence of unsuspected invasive disease and positive SLN biopsy using univariate and multivariate analyses., Results: Of the 110 patients with pure DCIS, seven patients (6%) had a metastatic lymph node; 31 patients (16%) were found to have invasive disease upon final histology. Univariate analysis of predictors of unsuspected invasive carcinoma showed that patients having a preoperative biopsy that indicated DCIS with microinvasion (DCISM) or large DCIS were at a higher risk of invasive carcinoma after histological examination of the operative specimen. Of the 31 patients who were upstaged to invasive carcinoma at final histology, seven patients (22%) had a positive SLN biopsy. The analysis of predictors of positive SLN in our study shows that diffuse DCIS requiring mastectomy is the main risk factor for SLN metastasis., Conclusion: There are no real predictive factors for invasive disease in patients with an initial diagnosis of DCIS or DCISM. Our study supports the value of SLN biopsy in patients with a preoperative DCISM biopsy or patients with a large pure DCIS biopsy requiring mastectomy.

Background: Since the introduction of sentinel node (SN) mapping in breast cancer, extra-axillary lymph node sites of breast tumor drainage are discovered in about one-quarter of cases, especially after intraparenchymal injection. In most such cases, an ipsilateral axillary SN is associated with an extra-axillary SN. Non visualization of ipsilateral axillary SN and extra-axillary SN drainage are often associated with an increased risk of axillary involvement., Case: We report a case of contralateral axillary SN drainage on lymphoscintigraphy in a breast cancer patient with a history of bilateral reduction mammoplasty and no ipsilateral axillary lymph node involvement., (Copyright 2004 Wiley-Liss, Inc.)

Breast cancer represents the disease with the highest incidence in the female population. In the last years there was observed, in western countries, an increase of morbidity by breast tumors and in the same time, a decrease of mortality in direct relation with an earlier diagnosis. Until the spread at distance, breast cancer it's a loco-regional disease that can be curable by surgical treatment and adjuvant therapy, like chemotherapy or radiotherapy. The principal goal is to diagnose it before distal metastases appear, most frequently bone metastasis. Certain role has nuclear medicine in the diagnosis and prognosis of breast cancer because it's more sensitive and gives functional imaging. The aim of this study is to answer the question: what technique, in what indication. The detection of sentinel lymph node has now a clear place in the algorithm, the scintimammography test is important, especially for prediction of tumor resistance to chemotherapy. The bone scintigraphy (which explores the entire body in one time)is generally used in the detection of bony metastases and FDG tomoscintigraphy for the evaluation of local and distal recurrences, or response to chemotherapy. The measure of the isotopic ejection fraction, actually considered the gold standard, is very useful and also very easy to perform, in patients who will receive chemotherapy.

Prognosis and management of patients with recurrent breast cancer depend on the spread of the disease. The aim of this study was to evaluate the performance of fluorine-18 fluorodeoxyglucose gamma camera positron emission tomography (FDG-GPET) in detecting breast cancer recurrence, its clinical impact and the relevance of induced changes in management. Patients (n = 134) with suspicion of recurrence either clinically or on conventional imaging (suspected recurrence: SR) or with an isolated increase in tumour marker levels (occult recurrence: OR) underwent FDG-GPET on a coincidence gamma camera. The reference standard for evaluation of accuracy, either histology (n = 26) or follow-up for 1 year (n = 49), was available in 75 (56%) patients. A questionnaire was sent to the referring clinician to evaluate the impact of FDG on management. Responses were obtained for 75 patients. Information regarding both approaches was available for 46 patients (46/134 = 34%). At the patient level, the sensitivity of FDG-GPET was 84%, significantly higher than the 63% sensitivity for conventional modalities, and the specificity was 78% versus 61%. The values for FDG-GPET were 81% and 86% respectively in the SR group and 90% and 73% respectively in the OR group, without any significant difference between these settings. The rate of change in management was 44% overall, 43% in the SR group and 45% in the OR group. Within the two groups, intermodality (major) changes were more frequent than intramodality (minor) changes. In the 46 patients for whom both approaches were available, 93% of management modifications were relevant (validated by biopsy or clinical follow-up). The results of this retrospective study show that FDG-GPET has an important role to play in patient management by confirming and evaluating the extent of recurrence or by localising occult recurrence.

The presented case is part of a pilot study performed in the Biophysics and Nuclear Medicine Service from the Tenon Hospital (Paris), chief Department Prof. J.N. Talbot. A 46 years patient, with mastectomy for a left breast cancer in 1999, followed by radiotherapy, is detected, in January 2004, through CT scan, with a tumoral mass at the left thoracic base. To confirm the rib osteolysis hypothesis a standard Rx was done; the result was the detection of a pathologic IX left rib fracture and a lacuna site on the L1 vertebra. The following bone scintigraphy make evidence of two hot spots (rib and vertebra) and also of a new pathologic site on the sternum. An 18FFDG PET image detects, despite the three known sites, another one on the left iliac bone crest. In conclusion, an extensive scintigraphic examination, including PET, is necessary to optimize the osteofil cancer metastases detection.