Molecular Subtyping of Invasive Breast Cancer Using a PAM50-Based Multigene Expression Test-Comparison with Molecular-Like Subtyping by Tumor Grade/Immunohistochemistry and Influence on Oncologist's Decision on Systemic Therapy in a Real-World Setting.

In intermediate risk hormone receptor (HR) positive, HER2 negative breast cancer (BC), the decision regarding adjuvant chemotherapy might be facilitated by multigene expression tests. In all, 142 intermediate risk BCs were investigated using the PAM50-based multigene expression test Prosigna® in a prospective multicentric study. In 119/142 cases, Prosigna® molecular subtyping was compared with local and two central (C1 and C6) molecular-like subtypes relying on both immunohistochemistry (IHC; HRs, HER2, Ki-67) and IHC + tumor grade (IHC+G) subtyping. According to local IHC, 35.4% were Luminal A-like and 64.6% Luminal B-like subtypes (local IHC+G subtype: 31.9% Luminal A-like; 68.1% Luminal B-like). In contrast to local and C1 subtyping, C6 classified >2/3 of cases as Luminal A-like. Pairwise agreement between Prosigna® subtyping and molecular-like subtypes was fair to moderate depending on molecular-like subtyping method and center. The best agreement was observed between Prosigna® (53.8% Luminal A; 44.5% Luminal B) and C1 surrogate subtyping (Cohen's kappa = 0.455). Adjuvant chemotherapy was suggested to 44.2% and 88.6% of Prosigna® Luminal A and Luminal B cases, respectively. Out of all Luminal A-like cases (locally IHC/IHC+G subtyping), adjuvant chemotherapy was recommended if Prosigna® testing classified as Prosigna® Luminal A at high / intermediate risk or upgraded to Prosigna® Luminal B.

Radiologic complete response (rCR) in contrast-enhanced magnetic resonance imaging (CE-MRI) after neoadjuvant chemotherapy for early breast cancer predicts recurrence-free survival but not pathologic complete response (pCR).

BACKGROUND: Patients with early breast cancer (EBC) achieving pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) have a favorable prognosis. Breast surgery might be avoided in patients in whom the presence of residual tumor can be ruled out with high confidence. Here, we investigated the diagnostic accuracy of contrast-enhanced MRI (CE-MRI) in predicting pCR and long-term outcome after NACT. METHODS: Patients with EBC, including patients with locally advanced disease, who had undergone CE-MRI after NACT, were retrospectively analyzed (n = 246). Three radiologists, blinded to clinicopathologic data, reevaluated all MRI scans regarding to the absence (radiologic complete remission; rCR) or presence (no-rCR) of residual contrast enhancement. Clinical and pathologic responses were compared categorically using Cohen's kappa statistic. The Kaplan-Meier method was used to estimate recurrence-free survival (RFS) and overall survival (OS). RESULTS: Overall rCR and pCR (no invasive tumor in the breast and axilla (ypT0/is N0)) rates were 45% (111/246) and 29% (71/246), respectively. Only 48% (53/111; 95% CI 38-57%) of rCR corresponded to a pCR (= positive predictive value - PPV). Conversely, in 87% (117/135; 95% CI 79-92%) of patients, residual tumor observed on MRI was pathologically confirmed (= negative predictive value - NPV). Sensitivity to detect a pCR was 75% (53/71; 95% CI 63-84%), while specificity to detect residual tumor and accuracy were 67% (117/175; 95% CI 59-74%) and 69% (170/246; 95% CI 63-75%), respectively. The PPV was significantly lower in hormone-receptor (HR)-positive compared to HR-negative tumors (17/52 = 33% vs. 36/59 = 61%; P = 0.004). The concordance between rCR and pCR was low (Cohen's kappa - 0.1), however in multivariate analysis both assessments were significantly associated with RFS (rCR P = 0.037; pCR P = 0.033) and OS (rCR P = 0.033; pCR P = 0.043). CONCLUSION: Preoperative CE-MRI did not accurately predict pCR after NACT for EBC, especially not in HR-positive tumors. However, rCR was strongly associated with favorable RFS and OS.