A 68-year-old, postmenopausal, gravida 2, para 2, woman with no family
history of breast cancer initially noticed a left breast lump for around 1
month duration. Her previous mammogram 5 years ago showed benign nodular breast
tissue with scattered punctate calcifications. Her repeat mammogram and
ultrasound of bilateral breasts showed a new heterogeneous solid nodule
measuring 7 mm in the sub-areolar region of the left breast at the site of
palpable nodule. There were scattered calcifications in both breasts, but the
breast parenchyma was heterogeneously dense, limiting mammographic evaluation.
The ultrasound-guided fine needle aspiration of the left breast lesion showed
malignant cells consistent with intermediate to high-grade ductal
adenocarcinoma with mucinous features.
To further evaluate the extent of her disease, she had a breast MRI. The
left breast showed an 8 mm enhancing mass in the sub-areolar region with an
additional 1.9 cm enhancing mass with irregular margins along its posterior
margin. There was a 3 cm segment of linear enhancement in the medial left
breast in a ductal distribution.
In the right breast, there was a 3 cm focal area of asymmetric
enhancement in a band-like distribution in the central right breast with a
dominant 1.2 cm mass-like area of enhancement located centrally within this
regional enhancement. These findings were suspicious for bilateral breast
cancer, including a 2 cm circumscribed high T2 signal right axillary mass,
suspicious for metastatic disease. The core biopsy of her left breast lesion
showed fibrocystic changes with no evidence of malignant disease. However,
biopsy of the right breast mass showed moderately differentiated invasive
ductal carcinoma that was positive for estrogen and progesterone receptors and
negative for HER-2/neu protein. The ultrasound-guided aspiration biopsy of the
right axillary lymph node also showed metastatic ductal carcinoma.
The patient underwent FDG-PET/CT imaging as a part of her staging work
up. This showed a mild diffuse metabolic activity in the bilateral breast
tissue with SUV values of 1.7 on right and 2.1 on the left. There was an
enhancing 1.5 cm nodule in the right breast with SUV of 1.7. The left breast
demonstrated an irregular band of soft tissue in the retroareolar region
showing mild FDG uptake with SUV 2.1. The right axillary lymph node was
hypermetabolic with SUV 6.5. Ultimately, she underwent bilateral mastectomy
with axillary lymph node dissection.
Figure 1. Axial contrast-enhanced CT, PET, fused PET-CT and
maximal intensity projection (MIP) images demonstrate low-grade metabolic
activity corresponding to the biopsy-proven primary ductal carcinoma (arrow).
Lower degree of activity was felt to be at least in part due to mucin
production with resultant volume averaging phenomenon.
Photo courtesy M. Ghesani
Figure 2. Metastatic right axillary lymph node demonstrates
considerably higher degree of metabolic activity. There was no mucin production
in this lymph node.
Photo courtesy M. Ghesani
The role of PET has been increasing in various malignancies. It is now
used in initial staging and prognosis to assess the response to chemotherapy,
as well as in surveillance. PET scanning has been shown to identify breast
cancer lesions with high sensitivity and also helps in differentiating some of
the benign and malignant breast masses. The most commonly used radioisotope is
the 2-fluoro-2-deoxy-D-glucose (FDG), which gets phosphorylated by the
intracellular kinases to FDG-6 phosphate, but cannot be metabolized further.
Thus, we can identify the metabolic activity of the cancer cells and with the
integration of PET with CT it is now possible to accurately define the anatomic
location of the hypermetabolic lesions.
There have been a number of studies in breast cancer to identify the
correlates of FDG uptake in the cancer cells. Bos and colleagues identified
various biological factors related to increased FDG uptake in breast cancer
patients. These included the glucose transporter (Glut-1), hexokinase (HK-1),
and hypoxia inducible factor (HIF-1), which are found to be up regulated in
breast cancer cells. FDG uptake has also been studied with regard to various
prognostic factors in breast cancer; for example, tumor size, grade, histology,
hormone receptor status, cell proliferation index, axillary lymph node status,
etc. There have been mixed results, but generally high FDG uptake has been
shown to be associated with poor prognosis as shown by Ueda.
Invasive ductal carcinomas have been shown to have significantly high
FDG uptake when compared with invasive lobular carcinomas. Crippa showed a
median SUV of 5.6 for invasive ductal carcinoma, which was significantly higher
than that of invasive lobular carcinoma (SUV 3.8, P=.004). This has been
confirmed in several subsequent studies; however, we have not been able to
identify any biological factor for this increase glucose uptake in the invasive
ductal carcinomas. The invasive lobular carcinomas in general are difficult to
identify radiographically and they have been shown to have a higher false
negative rate with PET imaging as well. Avril showed a 65% false negative rate
with invasive lobular carcinomas compared with 24% with invasive ductal
carcinomas. The degree of FDG uptake has also been correlated with prognosis in
predicting relapse rate in breast cancers.
For example, Oshida showed that with a differential absorption rate
(DAR) of less than 3, only one of 49 patients relapsed compared with 8 of 21
patients in the group with a DAR of more than 3. This was also shown to be an
independent prognostic factor in a multivariate analysis. For the patient
presented here, the intensity of uptake in the primary breast carcinoma was
lower than that in the metastatic lymph node. In general, ductal carcinoma
lesions express higher degrees of FDG hypermetabolism. This is likely explained
on the basis of mucin production in the primary malignancy, with resultant
decreased overall uptake, a phenomenon known as volume averaging in radiologic
In conclusion, the role of PET scan in breast cancer has been
increasing, not only in the initial staging, but also in predicting prognosis.
With its non-invasive nature, it provides an important tool for preoperative
assessment of breast cancer lesions and could be used as an independent factor
guiding adjuvant therapy.
Sumit Talwar, MD, is an oncology fellow at St. Lukes-Roosevelt
Munir Ghesani, MD, is associate clinical professor of radiology at
Columbia University College of Physicians and Surgeons and Attending
Radiologist at St. Lukes-Roosevelt Medical Center.
For more information:
- Avril. Clin Positron Imaging. 1999;2(5): 261-271.
- Bos et al. J Clin Oncol 2002;20(2):379-387
- Crippa et al. Eur J Nucl Med (1998) 25:1429-1434
- Oshida et al. Cancer 1998;82:2227-2234
- Ueda et al. Jpn J Clin Oncol 2008;38(4) 250-258