The Value of 18F-FDG PET/CT Imaging Combined With Pretherapeutic Ki67 for Early Prediction of Pathologic Response After Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer

Abstract

To evaluate the value of 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG PET/CT) and pretherapeutic Ki67 in predicting pathologic response in locally advanced breast cancer (LABC) after neoadjuvant chemotherapy (NAC).As a training set, total 301 LABC patients treated with NAC were retrospectively analyzed to evaluate the potential predictive value of pretherapeutic Ki67 for pathologic complete response (pCR) after NAC. Another 60 LABC patients were prospectively included as a validation set to evaluate the value of Ki67 combined PET/CT as pCR predictors. Ki67 was assessed in pretherapy core needle biopsy specimens and PET/CT scans were performed at baseline (before initiating NAC), after the 2nd, and 4th cycle of NAC. Maximum standardized uptake value (SUVmax) and its changes relative to baseline (ΔSUVmax%) were used as parameters of PEC/CT.In the training set, Ki67 was a predictor of pCR to NAC, with area under the curve (AUC) of 0.624 (P = 0.003) in receiver-operating characteristic (ROC) analysis. In the validation set, Ki67 alone did not show significant value in predicting pCR in the validation set. ΔSUVmax% after then 2nd or 4th course are predictors of pCR to NAC with the AUC of 0.774 (P = 0.002) and 0.791 (P = 0.002), respectively. When combined with ΔSUVmax% after the 2nd and 4th course NAC, Ki67 increased the value of ΔSUVmax% in predicting pCR with the AUC of 0.824 (P = 0.001). Baseline SUVmax and after 2nd, 4th course NAC had no predictive value for pCR, but SUVmax after the 2nd and 4th course showed remarkable predictive value for nonpathologic response (Grade 1 in Miller-Payne Grading System) with the AUC of 0.898 (P = 0.0001) and 0.801 (P = 0.003).Both PET/CT and Ki67 can predict pCR to NAC in LABC patients in the early phases of treatment. PET/CT combined Ki67 is a better pCR predictor for response to NAC. This helps the physician to predict the probability of pCR, and facilitates the optimization of individual treatment plan in case of ineffective and/or excessive chemotherapy.

Evaluation of the Usefulness of FDG-PET/CT for Nodal Staging of Breast Cancer

“…A correlation between all volumetric parameters and the Ki-67 index was found when our cohort was evaluated as a whole, with the strongest interactions occurring with the SUV LN and the mean quantitative hormonal status expression being lower in the "high Ki-67" cases. A high Ki-67 index indicates a high rate of mitosis and proliferation, and it has also been reported to be associated with the response to treatment, local recurrence, and metastasis (51,52). According to our results, there is also a reverse association between Ki-67 and hormone receptor status, such that if the Ki-67 index is positive, OR/PR expression will likely be lower in the malignant tissue, in conformity of such a biological association with SUV max measurements.…”

Elevated Soluble Galectin-3 as a Marker of Chemotherapy Efficacy in Breast Cancer Patients: A Prospective Study

“…A low-grade or localized tumor may be treatable with minimal chemotherapy after surgical removal (adjuvant) while a high-grade tumor may require initial aggressive chemotherapy to shrink the mass prior to surgery (neoadjuvant) [1]. Monitoring of therapy efficacy is essential, so that treatment may be continually optimized to reduce remaining cancer burden and possibility of disease relapse [2,3]. However, continuing presence of cancer has proven difficult to determine.…”

“…Various measurements have been developed, including (1) size and cellularity of the primary tumor and nodal metastases [3], (2) imaging techniques such as MRI and PET/CT imaging [2,4], and (3) circulating tumor cell DNA (ctDNA) detection [5]. Tissue-based biomarkers such as estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2) and measurement of mitotic activity through Ki67 assay are also commonly used at the time of diagnosis to determine effectiveness of treatment options [2,6]. More recently, absence of Galectin-3 (Gal-3), a glycan-binding lectin, has been associated with higher in vivo growth in murine breast tumors [7] and poor prognosis in node-positive breast cancers [8].…”

Elevated soluble Galectin-3 as a marker of chemotherapy efficacy in Breast cancer patients; a prospective study

“…A low-grade or localized tumor may be treatable with minimal chemotherapy after surgical removal (adjuvant) while a high-grade tumor may require initial aggressive chemotherapy to shrink the mass prior to surgery (neo-adjuvant) [1]. Monitoring of therapy efficacy is essential, so that treatment may be continually optimized to reduce remaining cancer burden and possibility of disease relapse [2,3]. However, continuing presence of cancer has proven difficult to determine.…”

“…Various measurements have been developed, including 1) size and cellularity of the primary tumor and nodal metastases [3]; 2) imaging techniques such as MRI and PET/CT imaging [2,4]; and 3) circulating tumor cell DNA (ctDNA) detection [5]. Tissue-based biomarkers such as Estrogen receptor (ER), Progesterone receptor (PR) and Human epidermal growth factor receptor (HER2) and measurement of mitotic activity through Ki67 assay are also commonly used at the time of diagnosis to determine effectiveness of treatment options [2,6]. More recently, absence of Galectin-3 (Gal-3), a glycan-binding lectin, has been associated with higher in vivo growth in murine breast tumors [7] and poor prognosis in node-positive breast cancers [8].…”