New Diagnostic Techniques for Breast Cancer Detection

Radionuclide Imaging Techniques

This technique utilizes (¹⁸F)2-fluoro-2-deoxy-D-glucose (FDG), a substrate that is rapidly utilized by malignant cells that display a higher metabolic rate as compared with normal tissues. Thus, malignant cells show increased uptake of FDG on PET scan.^[52]

PET is limited by its inability to detect lesions smaller than 1 cm, although it is not affected by breast density, previous breast surgery or irradiation to breast. It also has very limited usefulness in detection of ductal carcinoma in situ, lobular cancer and multicentric tumors.^[53] PET appears to have no role in the diagnosis of primary breast cancer, although it appears to be promising in detection of distant metastasis and recurrence of breast cancer (Figure 4). It may also be used to monitor response to chemotherapy by evaluating change in tumor size. A complete or partial response to treatment is indicated by reduced FDG uptake on PET as compared with nonresponsive breast tumor, where FDG uptake remains unchanged.^[54] Some tumors have low uptake, while some inflammatory lesions lead to false-positive results.

A study by Grahek et al. for detecting suspected breast cancer recurrence by PET scan reported sensitivity and specificity of 84 and 78%, respectively, as compared with 63 and 61% for conventional imaging.^[55]

Thus, the major role of PET scanning seems to be detection of distant metastasis, local recurrence and monitoring response to treatment.

This technique allows anatomical localization of the increased tracer uptake seen on PET scan. For primary breast tumor detection, this technique may have a role in dense breasts, breasts with implants and in those patients where mammography is indeterminate and breast biopsy is not a desirable option.^[56]

It may also be useful in localizing and differentiating between malignant and reactive axillary and internal mammary lymph nodes.^[57] One report investigated the role of PET-computed tomography in evaluation of breast cancer, and concluded that its major role is in detecting metastatic disease, tumor recurrence and evaluating response to treatment.^[58]

Several radiopharmaceuticals have been used, with variable success, as an adjunct for imaging breast masses. They have shown some promise in characterizing indeterminate palpable breast masses and axillary nodal metastasis, although they have limited ability in the detection of subcentimetric tumor masses.

Planar Scintigraphy Single-photon-emission Computerized Tomography. Planar scintigraphy takes images with a conventional γ-camera after injecting an agent labeled with Tc-99m (technetium) into the subject. For single-photon-emission computerized tomography, these planar images are rotated at a 180-360° arc around the patient and 3D images are obtained.

Scintimammography. Technetium 99m methoisobutyl isonitryl (Tc-MIBI) is a radiopharmaceutical agent that is sequestrated in the cytoplasm and mitochondria of cancer cells, owing to strong electrostatic attraction between Tc-MIBI and mitochondria. The sequestration depends on cellular perfusion, as a result of which slow-growing cancer cells may not take up the tracer, and hence may give false-negative results, while highly vascular inflammatory conditions may give rise to false-positive results.^[59] A meta-analysis of breast cancer diagnosis by scintimammography (SMM) showed that the overall sensitivity and specificity of SMM in detecting palpable breast cancer was 85.2 and 86.6%, respectively, while for nonpalpable lesions it was 66.8 and 86.9%, respectively.^[60] The major limitations of this technique are its inability to detect lesions less than 1 cm and difficulty in detecting ductal carcinoma in situ.

This technique may have a potential role in identification of multidrug resistance in tumors; sestamibi can be used as a substrate for the multidrug resistance P-glycoprotein system, which transports sestamibi out of tumor cells. Negative scans may be indicative of multidrug resistance and lack of response to treatment.^[61]

The expense involved and risk of exposing patients to ionizing radiation has to be titrated against the benefit obtained by this study.

For detection of primary breast cancer, SMM, single-photon-emission computerized tomography or ¹⁸F-FDG PET has similar diagnostic accuracies, but for detection of axillary lymph nodes, PET is more sensitive. For more accurate results, mammography should be studied in combination with SMM; this may lead to a combined sensitivity of 92% and specificity of 80%.^[62] In patients receiving neoadjuvant chemotherapy, SMM may have a role in assessing tumor response to treatment.^[63] A positive Tc-MIBI scan was predictive of residual disease on completion of treatment.^[64]

Radiolabeled Nucleoside & Amino Acids.¹⁸F-fluorothymidine (¹⁸F-FLT) is a nucleoside substrate that reflects the thymidine kinase-1 activity in cells; its uptake correlates well with the number of actively dividing cells. As proposed by Shields et al., it can be used to image tumor proliferation in vivo by PET.^[65]

In future, ¹⁸F-FLT may hold promise to measure cellular proliferation and for early assessment of therapeutic effectiveness in breast cancer.

Various radiolabeled amino acids (RAA) have been developed and used with PET for breast cancer studies. Amano et al.^[66] and Huovinen et al.^[67] demonstrated that during chemotherapy courses the uptake of RAA is increased in progressive disease, and vice versa. This led to the conclusion that changes in the uptake of RAA, as measured by PET, preceded the clinical response.

Estrogen Receptor Expression. 17α-iodovinyl-11-ß-methoxyestradiol (MIVE) scintigraphy may be used to assess the presence of the estrogen receptor in primary and metastatic breast cancer. Those patients who have shown low uptake and incomplete blockage of MIVE after being treated with tamoxifen have shown reduced disease-free periods compared with those with high uptake of the tracer.^[68] These estrogen ligands can potentially be used to assess disease recurrence in patients with known estrogen receptor-positive tumors.

Future Oncol. 2008;4(4):501-503. © 2008  Future Medicine Ltd.

Cite this: New Diagnostic Techniques for Breast Cancer Detection - Medscape - Aug 01, 2008.