FORT LAUDERDALE, FloridaA 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:
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.
Retrospective evidence suggests that
anthracycline-containing adjuvant chemotherapy regimens may be superior in
tumors that overexpress HER-2/neu.
Information on HER-2 expression influences whether
trastuzumab (Her-ceptin) therapy is considered in women who have recurrent
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 (Taxol) should be included within the list of adjuvant
chemotherapy regimens that could be considered.
"But because we found the data too earlyit hasn’t
been peer reviewed and published yetwe concluded that it was not appropriate
to emphasize it out of proportion to other chemotherapy regimens," Dr.
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 (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
therapycyclophosphamide, epirubicin, fluorouracil (CEF) over
cyclophosphamide, methotrexate, fluorouracil (CMF) in patients with
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.