NAC can induce shrinkage of the breast tumor, improving its operability and increasing the rate of conserving breast surgery. However, it is difficult to assess residual neoplasia especially in patients who are well responded to treatment [15].
Therapeutic response was assessed on the basis of change in measurement of tumor size before and after treatment. However, significant advances in structural and functional imaging during the past two decades lead to improvement in evaluation of the treatment response [16]. 18F-FDG PET/CT can quickly and efficiently assess malignant tumor response to treatment, including breast cancer, by comparing baseline scan prior to and following 1 or 2 cycles of treatment [17,18,19,20,21,22]. It can demonstrate metabolic changes (much earlier than morphological changes in conventional imaging modalities) semi-quantitatively by calculating the SUVmax which indicates the 18F-FDG uptake [23].
Using PET/CT for the identification of responders to treatment for breast cancer has been investigated in several clinical studies. Previous study by Jones el al. reported that PET predicts complete pathologic response, following a single pulse of chemotherapy, with sensitivity 90% and specificity 74% [24].
Other trial by Coudert et al. showed that early PET/CT was used to identify early responders to neoadjuvant therapy following two cycles, and pathological complete responses were noted in 37 (53.6%, 95% CI 41.2-65.7) of the PET-predicted responders and 6 (24.0%, 95% CI 9.4-45.1) of the non-responders [25].
Also, a prospective study conducted by Pahk et al, over 27 patients of locally advanced breast cancer conclude that interim 18F-FDG PET/CT is a valuable method for predicting early response of neoadjuvant chemotherapy [26].
A study done by Yildirim et al. included 51 of locally advanced breast cancer patients who received NAC and retrospectively analyzed. It revealed that the PET/CT had sensitivity and specificity of 75% and may be useful in predicting the prognosis because none of the patients with a complete response in PET/CT exhibited recurrence. The false positivity was established in 3 out of 15 patients with pCR. Furthermore, out of the 20 patients with a complete response in PET/CT, 12 exhibited true positivity, and 8 exhibited false positivity. There was no significant difference between the mean pretreatment SUVmax values of the patients with or without pCR. There was a significant relationship between the post-treatment SUVmax value and pCR [3].
Although maximum or average SUV has been used in many studies for quantification of tumor FDG uptake, yet, they have specific limitations, and therefore PERCIST criteria used peak SUV (activity concentration in an approximately 1.0 cm volume) corrected for lean body mass (SULpeak), instead of maximum SUV corrected for body weight, to avoid these limitations [27, 28]. PERCIST criteria quantifies therapeutic response as percent change in SULpeak of the most intense lesion between the baseline and post-treatment 18F-FDG PET scans and requires a change greater than 30% to distinguish PMR from SMD and PMD [29].
In the current study, we also correlated our results with the histopathological findings to evaluate accuracy of PET/CT in NAC response monitoring. After neoadjuvant chemotherapy, PET/CT showed 23 responders and 7 non-responders according to the PERCIST 1.0 criteria. Five patients showed complete metabolic response, and eighteen patients showed partial metabolic response (of the 23 responders), while 3 cases showed stable disease and 4 cases showed progressive disease (of the 7 non-responders). Among the 23 responders, 21 were true positive, and 2 were false positive. Among the 7 non-responders, 6 were true negative, and 1 was false negative. Therefore, the sensitivity, specificity, and accuracy of PET/CT for NAC response evaluation were 95.5%, 75%, and 90%, respectively, compared to 81.8%, 75%, and 80%, respectively, achieved by CT alone.
Tateishi et al. also showed that RECIST 1.1 had a sensitivity of 45.5%, specificity of 85.5%, and accuracy of 82.4%, while those values for PERCIST 1.0 were 70.4%, 95.7%, and 90.8%, respectively [4]. However, in another study by Kitajima et al. compared the response classifications RECIST 1.1 and PERCIST 1.0 used to determine pathological response to NAC in breast cancer patients, PERCIST 1.0 showed higher levels of sensitivity and NPV, but lower levels of specificity, PPV, and accuracy when compared to RECIST 1.1 [11].
In several studies, the 18F-FDG uptake values found to be related to tumor biology in various malignancies. Studies comparing the 18F-FDG uptake with histopathological parameters in breast cancer showed that the 18F-FDG uptake values are lower in invasive lobular carcinomas than that in invasive ductal carcinomas. This was attributed to lower intensity of tumor cells in lobular carcinomas, diffuse infiltrative tumor growth patterns, and lower proliferation rates [30]. A comparison could not be made in this study owing to the low number of included patients with invasive lobular carcinoma (one patient).
No significant relationship was observed between the menopausal status of the patient and SULpeak in our study. Although a study by Groheux et al. revealed that the 18F-FDG uptake value was 1.3 times higher in pre-menopausal patients, another study by Kim et al revealed that menopausal status and tumor FDG uptake values were independent [30, 31].
The tumor grade is a significant predictive factor in breast carcinomas. A strong positive correlation has been detected between the 18F-FDG uptake levels and histological grade in a study done by Ekmekcioglu et al. [32]. Although the mean SULpeak values of patients with a grade III disease was higher in our study ,yet, no relationship between the tumor grade and SULpeak values was observed, possibly because of the limited number of patients.
The main limitation of our study was the relatively small sample size due to the high cost of the technique. Therefore, a future prospective trial recruiting a larger number of patients will more clearly define the role of PET/CT-based evaluation of treatment response with more accurate results. Furthermore, only primary breast lesions were analyzed to assess tumor response. In addition, follow-up PET/CT was done in this study after finishing the chemotherapy, while many other studies performed serial PET/CT in the beginning of and during chemotherapy, determining the benefits of administering a new chemotherapy regimen versus prolonged administration of the same chemotherapy regimen in non-responders.