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Please note: This article is part of the Cancer Center's News Archive and is here for historical
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Richard L. Wahl, M.D.,
Professor of Internal Medicine and Radiology
Director, General Nuclear Imaging
Director, Radiopharmaceuticals Program
The most common methods to detect and diagnose breast cancer
are physical examination and mammography. These very important
and useful methods detect cancer because a mass has developed
in the breast - an anatomic change. While anatomic methods
are extremely useful, they do not assess the more fundamental
changes in tumor metabolism within the mass, nor do they tell
us with certainty whether masses are malignant or benign.
My research group has been studying the use of positron emission
tomography (PET) scanning as a method to detect, characterize
and follow the treatment of breast cancer. PET scanning is
a very sensitive method in which changes in the molecular
biology and physiology of tumors are assessed non-invasively
by imaging. PET scanning involves the intravenous injection
of a short-lived positron emitting radiotracer, which preferentially
accumulates in cancers. As an example, FDG, a short-lived
analog of glucose (sugar), will preferentially accumulate
in breast cancers due to their increased glucose metabolism,
allowing for their detection with a specialized scanning camera
called a PET camera. This camera not only scans the breast,
but can scan the entire body. A wide variety of other positron
emitting radiotracers can be used to detect physiological
alterations in breast cancer such as increased blood flow,
increased protein synthesis, increased DNA synthesis, and
decreased oxygen concentrations.
This ability to non-invasively look into the breast at molecular
changes instead of just anatomy allows PET to be both a promising
research tool and a useful clinical tool in a growing number
of challenging cases.
a: Anterior PET scan view of 45-year-old woman with newly diagnosed right breast cancer. Tumor has high FDG uptake.
b: Same patient after two cycles of chemotherapy. Tumor uptake of FDG is nearly absent, consistent with excellent response to therapy. Tracer uptake in left chest is normal heart.
Patient with past history of breast cancer who now has left arm pain and weakness. FDG PET scan shows intense uptake in tumor in left bracial plexus.
Progress in Understanding PET
We have made progress in answering many of these questions,
but much remains to be accomplished.
To date, we have learned that PET:
- can detect breast cancers throughout the entire body;
- has excellent sensitivity for detecting soft tissue recurrences, such as in the nerves of the neck and thorax;
- fails to detect small primary tumors due to limitations of current PET scanners, which are not of high enough resolution or designed specifically for breast imaging;
- can predict treatment response, but studies are ongoing to determine how accurate these early predictions are;
- can detect otherwise hidden tumors in the hard-to-visualize internal mammary nodal chain, which we believe will provide unique staging data to modify treatment regimens;
- is more sensitive than MRI for finding soft tissue tumors;
- can see through silicone implants.
The U-M currently is leading a multi-center trial in which
>220 women have been entered to define the accuracy of PET
in non-invasive staging of lymph nodes. In addition, newly
developed PET biopsy and probe devices are under study.
Positron emission tomography scanning of the breast is one
example of a growing family of tests that image the molecular
alterations in tumors as alterations in tumor and organ function
as opposed to simply the "form" of the lesion, or anatomy.
While we have learned a good deal regarding the role of PET,
much more study is necessary to refine the clinical role of
Because of the cost of PET imaging (currently >$1500/scan),
it is not a suitable screening test in most patients, particularly
if high-resolution scanners are not available. However, the
ability to non-invasively image and quantitate tumor physiology,
on repeated instances, with a very low radiation dose, suggests
that PET will have a growing and important role in breast
cancer management, both in research and clinical studies over
the coming years.
If you have a patient with newly diagnosed breast cancer scheduled
for lymph node dissection, a patient scheduled for a bone
marrow transplant for breast cancer, or a patient who will
be receiving chemo-therapy for known tumor recurrence, they
may be eligible for a PET research study. Please call 800-865-1125
for more information.
Since describing the use of PET to image primary and metastatic
breast cancer nearly a decade ago, we have been addressing
a number of questions. The major questions currently under
- Can initial PET scan results predict out-come in patients with newly diagnosed breast cancer?
- Can quantification of the PET scan metabolic rates in breast cancer before and during chemotherapy predict whether a specific tumor in a specific patient will respond to that specific therapy?
- Can PET predict response to therapy for primary or metastatic tumors?
- Can PET reliably assess treatment response in bone lesions?
- Can PET detect cancer in radiodense breasts of younger women in which mammograms have problems?
- Can PET detect breast cancer recurrence when mammograms are confusing?
- Can PET measure changes in tumor blood flow to predict efficacy of treatment?
- Can PET non-invasively stage the axilla for tumor involvement to eliminate the need for axillary dissection?
- Can PET see through silicone implants?
- Can PET detect metastatic disease?
- What is the smallest tumor PET can detect, and can it reliably separate malignant from benign changes?
- Can PET direct biopsies of lesions seen only with PET?
- Can PET-sensitive probes guide the surgeon to remove only the cancer in the breast at the time of surgery, thus mini- mizing deformity?
- Can the PET method work in multi-center trials?
- What are the basic science correlates of the signal seen on PET imaging?
- What is the best PET tracer for breast cancer?
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Wahl RL. Overview of the current status of PET in breast cancer
imaging. Quarterly Journal of Nuclear Medicine. 42(1):1-7,
Sugawara Y, Fisher SJ, Zasadny KR, Kison PV, Baker LH, Wahl
RL. Preclinical and clinical studies of bone marrow uptake
of fluorine-1-fluorodeoxyglucose with or without granulocyte
colony-stimulating factor during chemotherapy. Journal of
Clinical Oncology. 16(1):173-80, 1998.
Adler LP, Faulhaber PF, Schnur KC, Al-Kasi NL, Shenk RR. Axillary
lymph node metastases: screening with [F-18]2-deoxy-2-fluoro-D-glucose
(FDG) PET. Radiology. 203(2):323-7, 1997.
Wahl RL. "Clinical Oncology Update: The Emerging Role of PET."
In: Principles & Practices of Oncology, 5th edition. DeVita
VT, Hellman S, Rosenberg SA, (eds), Lippincott-Raven, Philadelphia,
Avril N, Dose J, Janicke F, Ziegler S, Romer W, Weber W, Herz
M, Nathrath W, Graeff H, Schwaiger M. Assessment of axillary
lymph node involvement in breast cancer patients with positron
emission tomography using radiolabeled 2-(fluorine-18)-fluoro-2-deoxy-D-glucose.
Journal of the National Cancer Institute. 88(17):1204-9, 1996.
Avril N, Dose J, Janicke F, Bense S, Ziegler S, Laubenbacher
C, Romer W, Pache H, Herz M, Allgayer B, Nathrath W, Graeff
H, Schwaiger M. Metabolic characterization of breast tumors
with positron emission tomography using F-18 fluorodeoxyglucose.
Journal of Clinical Oncology. 14(6):1848-57, 1996.
Dehdashti F, Mortimer JE, Siegel BA, Griffeth LK, Bonasera
TJ, Fusselman MJ, Detert DD, Cutler PD, Katzenellenbogen JA,
Welch MJ. Positron tomographic assessment of estrogen receptors
in breast cancer: comparison with FDG-PET and in vitro receptor
assays. Journal of NuclearMedicine. 36(10):1766-74, 1995.
Wahl RL, Helvie MA, Chang AE, Andersson I. Detection of breast
cancer in women after augmentation mammoplasty using fluorine-18-fluorodeoxyglucose-PET.
Journal of Nuclear Medicine. 35(5):872-5, 1994.
Wahl RL, Zasadny KR, Helvie M, Hutchins GD,Weber B, Cody R.
Metabolic monitoring of breast cancer chemohormonotherapy
using positron emission tomography (PET): Initial evaluation.
Journal of Clinical Oncology. 11(11):2101-2111, 1993.
Wahl RL, Cody R, Hutchins GD, Mudgett E. Primary and metastatic
breast carcinoma: Initial clinical evaluation with PET with
the radiolabeled glucose analog 2-[F-18]-fluoro-deoxy-2-D-glucose
(FDG). Radiology. 179:765-770, 1991.
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