Predictive Value of PET Scans in Breast Cancer
June 1, 2000 4 minutes read
Predictive Value of PET Scans in Breast Cancer
ABSTRACTs & COMMENTARY
Synopsis: Two recent reports highlight the potential use of positron electron tomography in the setting of primary treatment of large breast tumors.
Sources: Smith IC, et al. J Clin Oncol 2000;18:1676-1688. Schelling M, et al. J Clin Oncol 2000; 18:1689-1695.
Two papers were published recently examining the role of positron emission tomography (PET) scan in the management of primary breast cancer. The premise was that PET scans might be able to predict chemotherapy response in the neoadjuvant setting, and thus identify which patients are likely to benefit from more prolonged presurgical therapy and which should proceed to surgery.
The first report from Smith and colleagues at the University of Aberdeen, United Kingdom, includes data from 30 patients with large ( > 3 cm), non-inflammatory breast cancer who received eight cycles of neoadjuvant chemotherapy. PET scans were performed immediately before the first, second, and fifth doses, and after the last dose of treatment. Primary tumors and involved axillary nodes were identified and a semi-quantitative assessment of the uptake of the labeled deoxyglucose (dose uptake ratio, [DUR]) was determined. Pathological response was determined after chemotherapy by evaluation of the surgical resection specimens.
One patient had two primary tumors and thus, there were data available on 31 breast tumors. Eight of the lesions were no longer visible, even microscopically, after the eight cycles of chemotherapy. For these eight lesions, the calculated DUR prior to treatment was significantly higher (P < 0.037) than for the remainder of tumors. The mean reduction in DUR after the first cycle of chemotherapy correlated well with response. There was a significant decline in DUR for those that achieved a partial response (P = 0.013) and an even greater decline for those that went on to complete clinical remission (P = 0.003) or complete pathologic remission (P = 0.001). The PET scan was able to predict a complete pathologic response after the first cycle of chemotherapy with a sensitivity of 90% and a specificity of 74%.
The second paper by Schelling and colleagues in Hamburg, Germany, involved a slightly different protocol and a different chemotherapy program, but the results were quite similar. Twenty-two patients (with 24 primary breast cancers [> 3cm]) had PET scans before and after the first and second cycles of chemotherapy, and then went on to complete either three or four courses of chemotherapy prior to surgical resection. As with the UK study, significant differences in tracer uptake were seen between those with chemo-responding tumors and those nonresponding, as early as after the first cycle of chemotherapy. If there were reductions by 55% or more of uptake in the tumor, chemotherapy responders were correctly identified with a sensitivity of 100% and a specificity of 85%. Those with complete histopathologic response could be predicted with 88% accuracy, and this rose to 91% if the PET scan data after the second cycle was included.
COMMENT BY WILLIAM B. ERSHLER, MD
Chemotherapy administered prior to surgery for primary breast cancer has been shown to be an effective way to manage large breast lesions.1,2 The need for this alternative sequence of interventions is based upon the high rate of local, regional, and distant metastatic disease with conventional approaches.3,4 By administering chemotherapy first, primary tumors may be downstaged and occult metastatic disease eradicated. Nonetheless, survival for patients who require such treatment remains low, and this may be because some fraction of the patients do not respond to the initial chemotherapy. It has been established that for those with histologic evidence of minimal residual disease after chemotherapy, survival is enhanced.5,6 For those that do not respond, initial effective therapy may be delayed by several months of ineffective chemotherapy. If those patients could be identified early, alternative tumor eradicating approaches might be undertaken producing an increased likelihood of survival.
The purpose of the two reports was to examine the potential role of PET scanning in this regard. The results were quite similar and indicated that this technique is capable of discriminating, by the completion of the first cycle of chemotherapy, those who are likely to reach "minimal residual disease" after the full course of chemotherapy from those who are not. Thus, for those who do not have a PET scan indication of likely response, clinicians may choose to intervene with alternative approaches, such as immediate surgery, radiation, or alternative chemotherapies.
These papers provide useful clinical information. PET scanners are becoming increasingly used, even in busy clinical settings, and it now appears that their indications will be expanding. By identifying (by PET scan) a subset of patients with large primary tumors who did not respond to initial chemotherapy, clinical investigators may now have a suitable population to develop alternative treatment strategies.
References
1. Bonnadonna G, et al. CA Cancer J Clin 1995;45:227-243.
2. Wang H, et al. Semin Surg Oncol 1996;12:59-66.
3. Carter CL, et al. Cancer 1989;63:181-187.
4. Clavel M, et al. Eur J Cancer 1993;29A:598-604.
5. Machiavelli MR, et al. Cancer J Sci Am 1998;4:125-131.
6. Honkoop AH, et al. Br J Cancer 1998;77:621-626.
Which of the following statements about the use of positron electron tomography (PET) in the management of primary breast cancer is true?
a. Increased uptake of the tracer (deoxyglucose) prior to neoadjuvant chemotherapy is a negative prognostic indicator.
b. A drop in the uptake of the tracer of 55% or more after the first cycle of neoadjuvant chemotherapy is associated with a high likelihood of complete remission, confirmed histologically.
c. An increase in the uptake of 30% or more after the first cycle of neoadjuvant chemotherapy is associated with a high likelihood of complete remission, confirmed histologically.
d. It is neither sensitive nor specific enough to be of clinical value at this time.
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