Breast cancer is an evolutionary heterogeneous tumour, and its molecular subtype can convert between bone metastatic lesions and primary tumors [11, 12]. Therefore, it is significant that early detection of bone metastasis and personalized treatment based on molecular subtypes, which can preserve or improve long-term quality of life and functional independence of BC patients with bone metastasis .
Relevant practice guidelines of the National Comprehensive Cancer Network (NCCN), European Society for Medical Oncology (ESMO) and China Anti-cancer Association (CACA) all recommend re-biopsy for suspected metastatic lesions in patients with late-stage breast cancer to confirm diagnosis. After metastasis is confirmed, biological indicators are re-evaluated to confirm potential molecular subtype changes. The results may directly change the treatment plan.
CT guided-BMB is currently the main guidance method for bone biopsy. However, there are some limitations: (1) CT cannot confirm the sampling target for tumors that do not have lesions with abnormal morphology and structure at the early stage. (2) Systemic staging information cannot be obtained, the safest target area cannot be selected, and there is an increase in the incidence of complications (such as pneumothorax, paravertebral hematoma, and nerve damage).
Nuclear medicine molecular imaging, including SPECT/CT and PET/CT, can display anatomic and metabolic information concurrently and has unique advantages with respect to target area selection.
Bone scintigraphy (BS) is different from anatomical imaging. BS, commonly performed with technetium-99m-labeled bisphosphonates such as methylene diphosphonate (99mTc-MDP), is a widely used procedure, provides a whole-body skeletal survey at a relatively low cost, and is the standard initial imaging modality for assessment of bone metastases. It is a kind of imaging examination based on its own function, including blood flow, cell function, cell number, and active level of bone salt metabolism of bone tissue. Metastatic bone tumors are usually detected 3 to 6 months earlier than CT. 99Tcm-MDP BS plays an irreplaceable role in the screening and early diagnosis of bone metastasis.. Numerous reports emphasize the high sensitivity of BS in the diagnosis of osseous metastases.
SPECT/CT has realized the organic combination of metabolic imaging and anatomical imaging, and solved the difficulty of accurate anatomical localization of positive lesions by BS. Meanwhile, CT imaging analysis of lesions can be carried out, which has important clinical value in differentiating benign and malignant bone lesions [16, 17]. For staging of the skeleton, because of the greater contrast resolution of SPECT coupled with the correlation with the morphologic appearance of lesions on CT，further gains in sensitivity and, especially, in specificity and diagnostic confidence were apparent with SPECT/CT [10, 18, 19].
18F-NaF is a bone-specific tracer first described in 1962, and its uptake by bone is secondary to high blood flow locally and osteoblastic activity thus raising the possibility of false positives as with BS. However, the advent of combined PET/CT has improved specificity by allowing morphological correlation at sites of skeletal uptake with better differentiation between benign and malignant abnormalities.
Many studies have used PET/CT for guidance or for guiding biopsy and showed higher success rates and safety. J.J.Cerci et al. evaluated the impact of percutaneous PET/CT-guided biopsies on histological confirmation of PET/CT-positive lesions and confirmed PET/CT-guided biopsy is feasible and may optimize the diagnostic yield of image-guided interventions.Wei et al. reported that PET/CT-guided percutaneous FDG-avid target biopsies offers a new integrated precise re-biopsy algorithm for pathologic confirm and surveillance of molecular subtype shifts of the recurrent breast cancer, which can improve precise individual therapy and prolong survival .Her previous research involving in18F-FDG PET/CT in guiding biopsy of bone metastases in patients with advanced lung cancer also confirmed it is an effective and safe method that yields a high diagnostic success rate in the evaluation of hypermetabolic bone lesions in patients with suspected advanced lung cancer .Bing et al. investigated whether PET/CT-guided bone marrow biopsy adds complementary information for evaluation of bone marrow involvement (BMI) in newly diagnosed lymphomas, and draw a conclusion that PET/CT-guided targeted BMB may complement the results of possible false-positive PET/CT and false-negative iliac crest biopsy findings . Juliano et al verified that PET/CT-guided biopsy is feasible and may optimize the diagnostic yield of image-guided interventions, and PET/CT-positive lesions with no morphological correlation may now be accessible to percutaneous interventions.
However, there are fewer PET/CT apparatuses, thus their application is restricted. Furthermore, SPECT/CT is more common. Owing to that SPECT/CT is organic fusion of metabolic imaging and anatomical imaging, using SPECT/CT-guided biopsy can theoretically increase the accuracy and success rates and can be extensively promoted .There are fewer reports of SPECT/CT-guided biopsy. Zhao et al. applied SPECT/CT for thoracic tumour biopsy and confirmed its safety and reliability.
This study applied SPECT/CT to guide biopsy for suspected bone metastatic lesions in breast cancer. In our study, the relatively safer puncture site that is suspicious on SPECT/CT images was preferred consideration. Thus, the biopsy success rate was 100%, there were no serious complications, and an adequate amount of tissue was obtained in all 49 patients. 5 of 49 patients had no morphological changes on CT and were thus not suitable for CT-guided biopsy, while SPECT/CT identified an accurate biopsy site. Statistical analysis demonstrated that SPECT/CT-guided BMB showed significantly higher sensitivity and NPV when compared to SPECT/CT for determination of bone metastasis.
The possible reasons lie in the principle of 99mTc-MDP and the limitations of SPECT/CT. Abnormal accumulation of 99mTc-MDP is related to changes in local blood flow and osteoblastic activity, but does not reflect the true tumor burden in the bone marrow. The mechanism of accumulation means that the uptake of 99mTc-labeled diphosphonates is not specific for metastatic disease . BS and SPECT/CT sometimes fail to distinguish bone metastases from benign disease , including trauma, inflammation and primary tumor of bone .
The additional radiation dose in this study was from positioning CT. Because of the advantage of fusion images, the tube current and tube voltage were only 20 mA and 120 mV, respectively, and the effective radiation dose was approximately (1.9±0.8) mSv, which was lower than the dose for one-time chest CT scans and doses in literature reports.
In our study, the inconsistency rates between metastatic lesions and primary lesions for ER, PR, and HER-2 expression in 34 metastatic tumors were 32.3% (11/34), 47% (16/34), and 14.7% (5/39) respectively, and the rate of change in the molecular subtype was 54.3% (19/39), a finding that was basically consistent with that in literature reports[6, 26].
In summary, this study suggested that SPECT/CT-guided bone biopsy was safe and feasible and did not significantly increase the radiation dose. It provides breast cancer patients with an opportunity for accurate pathological and heterogeneous diagnosis of suspicious bone metastases. It has high clinical value and is worthy of extensive clinical application.
The limitations of our study were inherent to its retrospective design and small sample population. In addition, pathological benign pathological lesions should be followed up or other examinations should be conducted to exclude the possibility of false negative results. The next step is to conduct a study with a larger sample and continue long-term follow-up verification. Lastly, conventional decalcification in bone biopsy histopathology might influence immunohistochemical results, therefore, the ER, PR, and HER-2 expression results might not be accurate.