Scintimammography

Gabriel Soudry, M.D.

J. Anthony Parker, M.D., Ph.D.

January 31, 1995

Case Presentation:

A 45 year old women with large fibrocystic breasts was found to have a questionable small lump in the left breast. The mammogram was negative. She was refered for a scintimammogram (immediate anterior, one hour anterior, and left anterior oblique, 41k bytes) prior to biopsy.

Findings:

Scintimammogram showed a small focus of abnormal tracer uptake in the outer upper quadrant of the left breast (arrow, 41k bytes). Biopsy of that abnormality following the scan was positive for breast carcinoma.

Discussion:

Breast carcinoma is the second most common malignancy in American women with approximately 150,000 new cases every year. Early detection has been shown to reduce mortality by 30%. Currently, a women undergoing a screening procedure for the detection of breast carcinoma will be evaluated with physical examination and mammography. The detection of an abnormality is often followed with a breast biopsy witch is associated with significant physical discomfort and emotional stress (1). The risk and cost of performing biopsies are also to be taken in consideration (2). A noninvasive technique to select those who would benefit most from breast biopsy and reduce the number of negative biopsies would clearly be of value.

A new Nuclear Medicine imaging procedure, scintimammography, has been introduced, with the potential of assisting in the differentiation of benign and malignant breast abnormalities by measuring radiotracer uptake in the lesions as compared with surrounding breast tissues.

X-ray Mammography:

The basic abnormalities assessed by radiologists interpreting mammograms are masses and calcifications. Other more subtle signs include architectural distortion, parenchymal asymmetry and neodensity in the breast. The following descriptors are highly associated with malignancy. For masses: inhomogenous density, irregular shape, spiculated borders; for calcifications: many calcifications, microcalcifications, linear or branching patterns, and high spatial density. The following descriptors are associated with benignity. For masses: homogenous density, oval shape, sharp or lobulated borders; for calcifications: solid, round, coarse, irregularly shaped, scattered in distribution. It should be noted that the breast of young women are composed primarily of dense fibroglandular tissue that significantly limits the accuracy of mammography. When that tissue is replaced by radiolucent fat in older women, abnormal densities can be detected more readily (3,4).

The reported sensitivity of mammography in detecting breast cancer in symptomatic patients is on average 90% (2). Of the 10% false negative mammograms, 50% prove to be erroneous mammographic diagnoses due to suboptimal technique, lack of experience of the reader, failure to compare with previous studies. The remaining 50% are truly mammographically occult cancers and cannot be recognized on the mammogram even in retrospect. Histologic characteristics of those tumors include a diffuse invasive pattern, poor desmoplastic reaction with poorly outlined tumor margins, lack of calcifications (which occur only in 50% of breast cancers) (5).

In a study attempting to assess whether or not a systematic review of mammographic descriptors would result in improved classification of nonpalpable lesions, the prelocalization mammograms of 200 consecutive patients who had 231 biopsies were reviewed by 4 radiologists experienced in mammography. Readers indicated their over-all rating of each lesion from definitely benign to definitely malignant. Ratings were compared with the pathologic findings (181 benign, 50 malignant). If biopsies had not been performed on those patients who were judged to have most likely benign lesions, one could reduce the number of biopsies by 48 to 69%; however 18 to 46% of malignancies would be missed. It was concluded that diagnoses based on a systematic review of descriptors are not sufficiently accurate to reduce the number of mammary biopsies (3).

Surgeons must maintain a reasonable benign to malignant ratio for breast biopsies for nonpalpable mammographic abnormalities in order not to expose the patient to excessive risk or cost by performing biopsies for questionable indications or failing to perform biopsies on cancerous lesions. A screening program reported by the Illinois Division of the American Cancer Society involving 80 Chicago metropolitan area mammographic facilities revealed that, of the 9307 women undergoing screening mammography, 82% had results that were negative for malignancy, 16% had inconclusive results, and only 2% had suspicious results. There were 206 patients in the suspicious group, of which 147 underwent biopsy, with 39 (27%) cancers found. This represented a very credible benign-to-malignant biopsy ratio of 3.8 to 1. On the other hand, 1450 patients had inconclusive mammograms, 136 underwent biopsies, and only 8(6%) cancer were found. This represented a benign-to-malignant biopsy ratio of 17 to 1 which is considered too high by most standards (6).

Scintimammography imaging technique:

Two imaging methods described in recent papers will be summarized.

1. Waxman et al (7):

Radioisotope: Thallium-201 chloride.
Dose: 3 mCi.
Injection IV in opposite arm from known breast lesion.
Patient in a supine position.
Large field of view camera.
Images begun 2 minutes after injection.
Two sequential 10 minutes anterior chest images with arms raised.
Then right and left anterior oblique 10 minutes views of the affected breast including axilla.
Five minutes marker views (nipple and lesion) in similar positions.
Final 10 min anterior chest image obtained approximately 1 hour postinjection.

2.Khalkhali et al (8):

Radioisotope: Technetium-99m Sestamibi.
Dose: 20 mCi.
Injection IV in opposite arm from known breast lesion.
Patient in a prone position with breast freely dependent from the imaging table (maximum separation of breast tissue from myocardium and liver).
Rectangular single head gamma camera.
Images begun 5 minutes after injection.
Ten minutes lateral image of the breast with suspected lesion.
If lesion seen near the chest wall, 30-degree posterior oblique image.
Ten minutes lateral image of the controlateral breast.
Lateral images repeated one hour post injection.
Final 10 minutes anterior chest image in the upright position with arm raised.

Summary of Reported Accuracy:

1. Waxman et al (7):

Patients: 81 females with palpable breast mass referred for thallium testing.
Controls: 30 patients with other types of cancer undergoing thallium images.
All patients with palpable breast mass underwent breast biopsy.
Sensitivity: 96% (45 positive thallium studies/ 47 cancers).
Specificity: 91% (3 adenomas with thallium uptake-34 benign masses).
Accuracy: 94%.

Of note:

Twenty-one patients had axillary metastasis; of these, 12 were detected on the thallium scan (sensitivity 57%).
Among 19 patients with fibrocystic disease, none demonstrated positive thallium uptake.
Among the 30 controls patients, there were no false positive thallium uptake in the breasts.
The intensity of thallium uptake in patients with adenomas could not be separated scintigraphically from patients with malignancy.
The malignant breast lesions ranged in size from 1.3 to 3.2 cm in largest diameter.
The two lesions not detected on the thallium scans measured 2 and 1.6 cm in largest diameter. One was located deep in a large pendulous breast, the other was located in the high posterior tail of the breast tissue adjacent to the axilla.

2. Khalkhali et al(8):

Patients: 59 women with either positive finding on mammography or mass palpated on physical examination referred for Tc-99m Sestamibi mammoscintigraphy.
All patients underwent biopsy or fine needle aspiration of the breast or both.
Sensitivity: 95.8% (23 positive Sestamibi studies/24 cancers).
Specificity: 86.8% (2 fibroadenomas, 3 fibrocystic disease with sestaMIBI uptake-38 benign abnormalities.
Accuracy: 90.3%.

Of note:

The only false negative result was observed in a patient with a cluster of microcalcifications without an associated mass. The pathology was microscopic ductal carcinoma.
Three out 17 patients with fibrocystic disease had MIBI uptake. Hypercellularity with extensive florid hyperplasia and adenosis was a common pathologic feature in those patients.
The size of the lesions was moderate: 2.3 x 1.8 cm in largest diameter.
The uptake of Sestamibi was independent of the presence of dense breasts seen on mammography.

3. Lee et al(9):

Group A: 30 patients (28 females, 2 males) found to have 32 breast abnormalities and scheduled for biopsy or surgery, referred for Thallium-201 mammoscintigraphy.
- Sensitivity: 80% (7 positive thallium studies/9 cancers).
- Specificity: 96% (1 hemangioma with thallium uptake/ 23 benign abnormalities).
- Accuracy: 90.6%.
Group B: 7 patients with subcutaneous nodules following mastectomy or lumpectomy for breast cancer.
- Five patients had true positive thallium scans with recurrence of carcinoma.
- One patient had a false negative thallium scan. This patient's biopsy indicated a microscopic focus of tumor recurrence.
- One patient had a true negative thallium scan.

4. Kao et al(10):

Patients: 38 female patients with palpable breast masses who underwent TC-99m sestaMIBI breast scintigraphy.
Sensitivity: 84% (27 positive scan/32 cancer).
Specificity: 100% (O positive scan/6 benign lesions).
Accuracy: 87% .

We have seen that in the best scenario, only one of four suspicious lesions detected on the mammogram will turn out to be malignant upon biopsy. The cost of biopsy procedures ranges between $3000 and $5000 per surgical biopsy.

The data presented above suggests that mammoscintigraphy can significantly increase or decrease the suspicion of malignancy in patients with breast abnormalities detected by physical exam and/or mammography and may help triage patients who need immediate biopsies from those who could be followed closely.

Conclusions:

Scintimammography with thallium-201 or Tc-99m sestaMIBI has high sensitivity and specificity in the detection of breast cancer.
In patients who have mammograms considered difficult to interpret (dense or dysplastic breasts, post radiation changes), or in patients with mammographically occult palpable breast masses, scintimammography may help to assess which patient should be evaluated surgically and reduced the number of breast biopsies that yield negative results for carcinoma.

References:

1. Potchen EJ, Bisesi MA, Sierra AE, Potchen JE. Mammography and malpractice. AJR 1991; 156:475-480.

2. Winchester DP. Evaluation and management of breast abnormalities. Cancer 1990; 66:1345-1347.

3. Monostori Z, Herman PG, Carmody DP et al. Limitations in distinguishing malignant from benign lesions of the breast by systematic review of mammograms. Surg Gynecol Obset 1991; 173:438-42.

4. Bassett LW, Gambhir S. Breast imaging for the 1990s. Semin Oncol 1991; 18:80-86.

5. Holland R, Hendricks JH, Mravunac M. Mammographically occult breast cancer. A pathologic and radiologic study. Cancer 1983; 52:1810-1819.

6. Winchester DP, Lasky HJ, Sylvester TL, Maher ML. A television promoted mammographic screening pilot project. CA 1988; 38:291-309.

7. Waxman AD, Ramanna L, Memsic LD et al. Thallium scintigraphy in the evaluation of abnormalities of the breast. J Nucl Med 1993; 34:18-23.

8. Khalkhali I, Mena I, Jouanne E et al. Prone scintimammography in patients with suspicion of carcinoma of the breast. J Am Coll Surg 1994; 178:491-497.

9. Lee VW, Sax EJ, McAneny et al. A complementary role for thallium-201 scintigraphy with mammography in the diagnosis of breast cancer. J Nucl Med 1993; 34:2095-2100.

10. Kao CH, Wang SJ, Liu TJ. The use of technetium-99m methoxyisobutylisonitrile breast scintigraphy to evaluate palpable breast masses. Eur J Nucl Med 1994; 21:432-436.

Click here to go to Joint Program in Nuclear Medicine home page and Copyright notice.

J. Anthony Parker, MD PhD, Tony_Parker@bih.harvard.edu