HER2-overexpressing breast cancer: FDG uptake after two cycles of chemotherapy predicts the outcome of neoadjuvant treatment.
BACKGROUND
Pathologic complete response (pCR) to neoadjuvant treatment (NAT) is associated with improved survival of patients with HER2+ breast cancer. We investigated the ability of interim positron emission tomography (PET) regarding early prediction of pathology outcomes.


METHODS
During 61 months, consecutive patients with locally advanced or large HER2+ breast cancer patients without distant metastases were included. All patients received NAT with four cycles of epirubicin+cyclophosphamide, followed by four cycles of docetaxel+trastuzumab. ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG)-PET/computed tomography (CT) was performed at baseline (PET₁) and after two cycles of chemotherapy (PET₂). Maximum standardised uptake values were measured in the primary tumour as well as in the axillary lymph nodes. The correlation between pathologic response and SUV parameters (SUVmax at PET₁, PET₂ and ΔSUVmax) was examined with the t-test. The predictive performance regarding the identification of non-responders was evaluated using receiver operating characteristics (ROC) analysis.


RESULTS
Thirty women were prospectively included and 60 PET/CT examination performed. At baseline, 22 patients had PET+ axilla and in nine of them ¹⁸F-FDG uptake was higher than in the primary tumour. At surgery, 14 patients (47%) showed residual tumour (non-pCR), whereas 16 (53%) reached pCR. Best prediction was obtained when considering the absolute residual SUVmax value at PET₂ (AUC=0.91) vs 0.67 for SUVmax at PET₁ and 0.86 for ΔSUVmax. The risk of non-pCR was 92.3% in patients with any site of residual uptake >3 at PET₂, no matter whether in breast or axilla, vs 11.8% in patients with uptake ≤3 (P=0.0001). The sensitivity, specificity, PPV, NPV and overall accuracy of this cutoff were, respectively: 85.7%, 93.8%, 92.3%, 88.2% and 90%.


CONCLUSIONS
The level of residual ¹⁸F-FDG uptake after two cycles of chemotherapy predicts residual disease at completion of NAT with chemotherapy+trastuzumab with high accuracy. Because many innovative therapeutic strategies are now available (e.g., addition of a second HER2-directed therapy or an antiangiogenic), early prediction of poor response is critical.
Nuclear Medicine, Saint-Louis Hospital, 1 avenue Claude Vellefaux, Paris 75475, France. dgroheux@yahoo.fr
D
D
Groheux
S
S
Giacchetti
M
M
Hatt
M
M
Marty
L
L
Vercellino
A
A
de Roquancourt
C
C
Cuvier
F
F
Coussy
M
M
Espié
E
E
Hindié
D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001692:Biological Transport; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D003520:Cyclophosphamide / Q000627:therapeutic use; D000077143:Docetaxel; D015251:Epirubicin / Q000627:therapeutic use; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D020360:Neoadjuvant Therapy; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D015996:Survival Rate; D043823:Taxoids / Q000627:therapeutic use; D000068878:Trastuzumab; D016896:Treatment Outcome
D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D003520:Cyclophosphamide; D000077143:Docetaxel; D015251:Epirubicin; D019788:Fluorodeoxyglucose F18; D019275:Radiopharmaceuticals; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D000068878:Trastuzumab; C508053:ERBB2 protein, human