HER2-negative luminal breast cancer is relatively common but less responsive to chemotherapy; in this setting, NAC is less likely to achieve pCR. Nonetheless, NAC can be frequently considered for patients with this subtype to obtain better surgical outcomes such as breast conservation. Therefore, good predictive markers in this subtype are needed for selecting chemotherapy before or after surgery.
Various factors have been proposed for the risk stratification of patients with breast cancer when considering adjuvant chemotherapy, such as tumor burden (T and N stage), histological grade, HR status, Ki67 expression index, and recently, gene signatures. However, these pathological predictors can be fully applied only after complete surgical excision and therefore have limited value in the neoadjuvant setting. On the other hand, 18F-FDG PET/CT can provide quantitative information about tumor glucose metabolism and be a valuable adjunct to conventional preoperative clinical assessment. In the current study, pSUVmax on PET images was relatively higher in cases with low ER expression and high Ki67 expression index and served as a potential predictive marker for pCR to NAC in patients with HER2-negative luminal breast cancer subtypes, regardless of clinical stage or pathologic characteristics.
18F-FDG PET/CT using tumor glucose metabolism has been widely used for diagnosis, surveillance, or prognosis of various malignant tumors [], but still has limited evidence of utility in breast cancer: the NCCN guidelines currently do not recommend its use in the staging of early breast cancer (www.nccn.org). Nonetheless, several studies have proven the association between SUV and breast cancer tumor burden, histological type, and aggressiveness [[14, 23–25]] and suggested that 18F-FDG PET/CT can predict treatment response in aggressive subtypes of breast cancer [[26–28]]. Furthermore, based on demonstration of the prognostic impact of pSUVmax among patients with various stages of breast cancer [], we hypothesized its predictive role predicting treatment outcomes for specific treatment, particularly in the neoadjuvant setting. Although some prior studies demonstrated a change of SUV in response to chemotherapy as a predictive factor in aggressive breast cancer, such as the HER2 subtype [], few studies have evaluated the predictive value of the pSUVmax in response to chemotherapy only in HER2-negative luminal breast cancer patients. While patients with luminal type breast cancer are believed to have a lower chance of pCR to NAC compared to those with HER2-positive and TNBC subtypes [[29, 30]], the current findings suggest that 18F-FDG PET/CT may allow the identification of good responders to chemotherapy among patients with luminal subtype breast cancer; further studies for its use in breast cancer should be considered.
Meanwhile, achieving pCR is associated with better prognosis in patients with aggressive tumor subtypes and thus pCR has been accepted as a surrogate marker for long-term survival. However, this prognostic value was not found in a study involving luminal subtype tumors . Similarly, in the current study, a high pCR rate in the group with high pSUVmax did not connote better survival. Instead, the pathologic stage of the residual tumors was significantly associated with survival when the patients achieving pCR were excluded (data not shown). These findings may indicate that luminal breast cancers are heterogeneous, having different levels of glucose metabolism, and the tumors with high pSUVmax may be more responsive but have a different clinical course compared to the others.
Currently, the luminal type is further subdivided into subtypes based on molecular expression: luminal A, B HER2 negative, and luminal B HER2 positive. The latter two subtypes have worse outcomes and need systemic chemotherapy even for early stage cancers []. However, in clinical practice, the assay cannot be routinely applied to identify subtype due to the cost of DNA/RNA analysis; therefore, immunohistochemical analysis with 4 markers (ER, PR, HER2, and Ki67) has been generally accepted as a substitute tool for defining subtypes of breast cancer [[20, 31, 32]]. Thus, considering the limitations of IHC assay and specimens from core needle biopsy in the neoadjuvant setting, pSUVmax may be an alternative to molecular assays for identifying specific subtypes, potentially avoiding ineffective chemotherapies and permitting other treatment options such as neoadjuvant endocrine therapy or immediate surgery.
Meanwhile, the cutoff value requires further refinement in future studies, as the current values are too variable for use as a marker. Additionally, the PET technique enables metabolic pathway visualization of the increased glucose consumption in malignant tumors [] and the activities of diverse glucose transporters such as glucose transporter I (GLUT-1) and intracellular glucose metabolic enzymes such as hexokinases have been shown to determine the level of FDG uptake in cancer tissue []. Therefore, further studies of the associations between these molecules and 18F-FDG PET/CT are warranted.
The small sample size and relatively lower incidence of pCR compared to that of other NAC studies limit definite conclusions. The lower incidence of pCR can be explained by the higher proportion of luminal A subtype in the study population. Nevertheless, despite the unproven role of PET scanning and its decreasing use in our region, this study may stimulate new insights into PET scanning. Moreover, the number of enrolled patients with HER2-negative luminal early breast cancer is high compared to that of other studies of the role of PET in the neoadjuvant setting, and, to our knowledge, this study is the first to establish the role of initial pSUVmax as a noninvasive predictive marker of pCR to NAC.