TY - JOUR
T1 - A composite 18F-FDG PET/CT and HER2 tissue-based biomarker to predict response to neoadjuvant pertuzumab and trastuzumab in HER2-positive breast cancer (TBCRC026)
AU - Hennessy, Maeve A.
AU - Cimino-Mathews, Ashley
AU - Carter, Jodi M.
AU - Kachergus, Jennifer M.
AU - Ma, Yaohua
AU - Leal, Jeffrey P.
AU - Solnes, Lilja B.
AU - Abramson, Vandana G.
AU - Carey, Lisa A.
AU - Rimawi, Mothaffar
AU - Specht, Jennifer
AU - Storniolo, Anna Maria
AU - Vaklavas, Christos
AU - Krop, Ian
AU - Winer, Eric
AU - Denbow, Rita
AU - Valero, Vincente
AU - Wolff, Antonio C.
AU - Wahl, Richard L.
AU - Huang, Chiung Yu
AU - Stearns, Vered
AU - Thompson, E. Aubrey
AU - Connolly, Roisin M.
N1 - Publisher Copyright:
© 2025 The Authors
PY - 2025/6
Y1 - 2025/6
N2 - Background: Early metabolic change on PET/CT was predictive of response to neoadjuvant trastuzumab/pertuzumab (HP) in TBCRC026. We hypothesized that a composite biomarker incorporating PET/CT and HER2 tissue-based biomarkers could improve biomarker performance. Methods: 83 patients with estrogen receptor-negative/HER2-positive breast cancer received neoadjuvant HP alone [pathologic complete response (pCR) 22 %]. PET/CT was performed at baseline and 15 days post initiation of therapy (C1D15). Promising imaging biomarkers included ≥40 % SULmax decline between baseline and C1D15, and C1D15 SULmax ≤3. Baseline tissue-based biomarkers included HER2-enriched intrinsic subtype (72 %, 46/64; NanoString), tumor HER2 protein abundance (median log2 13.5, range log2 7.1–15.9; NanoString DSP), and HER2 3+ (83 %, 64/77; immunohistochemistry). Logistic regressions were fitted to predict pCR with HER2/PET-CT biomarkers. The C statistic assessed overall prediction power. The optimal composite score cut-off was determined by maximizing Youden's index. Results: Factors most predictive for pCR in single predictor models included C1D15 SULmax (OR 0.43; p = 0.007, c = 0.77), % reduction in SULmax (OR 1.03, p = 0.006, c = 0.72) and tumor HER2 protein abundance (OR 1.75; p = 0.01, c = 0.76). The composite of C1D15 SULmax and % reduction in SULmax and their interaction term, had improved probability (c = 0.89 from c = 0.78), with high sensitivity (100 %) and negative predictive value (100 %). The addition of tumor HER2 protein did not further improve prediction power (c = 0.90). Conclusion: The HER2/PET-CT biomarker had high prediction power for pCR, however was not superior to the prediction power of PET/CT alone. Non-invasive PET/CT biomarkers may facilitate a response-guided approach to neoadjuvant therapy, allowing intensification and de-intensification of treatment, pending further evaluation.
AB - Background: Early metabolic change on PET/CT was predictive of response to neoadjuvant trastuzumab/pertuzumab (HP) in TBCRC026. We hypothesized that a composite biomarker incorporating PET/CT and HER2 tissue-based biomarkers could improve biomarker performance. Methods: 83 patients with estrogen receptor-negative/HER2-positive breast cancer received neoadjuvant HP alone [pathologic complete response (pCR) 22 %]. PET/CT was performed at baseline and 15 days post initiation of therapy (C1D15). Promising imaging biomarkers included ≥40 % SULmax decline between baseline and C1D15, and C1D15 SULmax ≤3. Baseline tissue-based biomarkers included HER2-enriched intrinsic subtype (72 %, 46/64; NanoString), tumor HER2 protein abundance (median log2 13.5, range log2 7.1–15.9; NanoString DSP), and HER2 3+ (83 %, 64/77; immunohistochemistry). Logistic regressions were fitted to predict pCR with HER2/PET-CT biomarkers. The C statistic assessed overall prediction power. The optimal composite score cut-off was determined by maximizing Youden's index. Results: Factors most predictive for pCR in single predictor models included C1D15 SULmax (OR 0.43; p = 0.007, c = 0.77), % reduction in SULmax (OR 1.03, p = 0.006, c = 0.72) and tumor HER2 protein abundance (OR 1.75; p = 0.01, c = 0.76). The composite of C1D15 SULmax and % reduction in SULmax and their interaction term, had improved probability (c = 0.89 from c = 0.78), with high sensitivity (100 %) and negative predictive value (100 %). The addition of tumor HER2 protein did not further improve prediction power (c = 0.90). Conclusion: The HER2/PET-CT biomarker had high prediction power for pCR, however was not superior to the prediction power of PET/CT alone. Non-invasive PET/CT biomarkers may facilitate a response-guided approach to neoadjuvant therapy, allowing intensification and de-intensification of treatment, pending further evaluation.
KW - Breast cancer
KW - F-FDG PET/CT
KW - HER2-Biomarkers
KW - Neoadjuvant
UR - http://www.scopus.com/inward/record.url?scp=85219269450&partnerID=8YFLogxK
U2 - 10.1016/j.breast.2025.104432
DO - 10.1016/j.breast.2025.104432
M3 - Article
C2 - 40049115
AN - SCOPUS:85219269450
SN - 0960-9776
VL - 81
JO - Breast
JF - Breast
M1 - 104432
ER -