FORT LAUDERDALE, Florida—A panel of breast cancer experts has revised the National Comprehensive Cancer Network (NCCN) breast cancer guideline to reflect an evolution rather than change. "The differences between this and last year’s guidelines are overall meaningful but subtle," Robert W. Carlson, MD, of Stanford Hospitals and Clinics, said at the Sixth Annual NCCN Conference.
The 2001 guideline calls for the prospective determination of levels of HER-2/neu oncogene expression, citing three reasons:
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In women with small, node-negative tumors, HER-2 expression is one of the features medical oncologists consider in making the decision about whether to use adjuvant therapy.
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Retrospective evidence suggests that anthracycline-containing adjuvant chemotherapy regimens may be superior in tumors that overexpress HER-2/neu.
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Information on HER-2 expression influences whether trastuzumab(Drug information on trastuzumab) (Her-ceptin) therapy is considered in women who have recurrent disease.
The panel questioned drug companies’ claims of an oncology breakthrough with the addition of taxanes to adjuvant chemotherapy. Stephen B. Edge, MD, of Roswell Park Cancer Institute, said that the panel agreed that the available data are compelling enough so that AC (Adriamycin/cyclophosphamide) plus paclitaxel(Drug information on paclitaxel) (Taxol) should be included within the list of adjuvant chemotherapy regimens that could be considered.
"But because we found the data too early—it hasn’t been peer reviewed and published yet—we concluded that it was not appropriate to emphasize it out of proportion to other chemotherapy regimens," Dr. Edge said.
According to Dr. Carlson, the wisdom of that approach is that the data from AC plus or minus paclitaxel studies are becoming less positive with time. So, the jury is out on taxanes.
The NCCN panel’s recommendation: "Early evidence suggests that AC plus paclitaxel may be superior to AC alone. Mature data are needed before definitive recommendations can be made. [The recommendation is] limited to node-positive disease."
The committee added epirubicin(Drug information on epirubicin) (Ellence) to its list of adjuvant therapies for node-positive breast cancer. The panel cited the NCIC CTG MA.5 Trial, which established the efficacy of epirubicin-based adjuvant therapy—cyclophosphamide, epirubicin, fluorouracil(Drug information on fluorouracil) (CEF) —over cyclophosphamide(Drug information on cyclophosphamide), methotrexate(Drug information on methotrexate), fluorouracil (CMF) in patients with node-positive tumors.
High-Dose Chemotherapy
While previous NCCN guidelines had acknowledged that some nonrandomized trials of high-dose chemotherapy/transplantation looked favorable, the 2001 guideline took a step back. The evidence today supporting high-dose chemotherapy with bone marrow or stem cell transplantation "is not compelling," Dr. Carlson said. "The guidelines should not be interpreted to say that we are not supportive of clinical trials of high-dose therapy; simply, at this point in time, we see no need to emphasize those trials disproportionately. High-dose therapy or transplant for breast cancer outside the confines of a clinical trial should be rare."
The treatment of elderly breast cancer patients continues to be a gray area. "The guideline states that there are insufficient data from randomized clinical trials to make a strict recommendation for women over age 70," Dr. Carlson said.
The 2001 guideline questions the use of axillary node dissections in certain breast cancer patients, including older women, since the procedure has not been shown to confer a significant survival advantage. "If it’s not going to affect your selection of therapy, why do it?" Dr. Carlson asked. "It’s the most morbid part of breast surgery." Hence the guidelines state: "In the absence of definitive data demonstrating superior survival for performance of axillary lymph node dissection, patients who have particularly favorable tumors, patients for whom the selection of adjuvant therapy is unlikely to be effective, for the elderly, or for those with serious co-morbid conditions, the performance of axillary lymph node dissection may be considered optional."
Dr. Edge said there was a vigorous discussion about how oncologists should document complete excision of ductal carcinoma in situ (DCIS). "It’s now a category 3 recommendation [denoting major disagreement among panel members] that patients should have postex-cision mammography prior to the start of radiation therapy for DCIS," he said.
Finally, the 2001 guideline has added magnetic resonance imaging (MRI) for possible use in the initial workup of breast cancer. The equipment must include a dedicated coil, and the technician must be highly experienced in its use. MRI may supplement the use of physical examination, ultrasound, and mammography imaging in certain situations where the extent of the disease is uncertain.
