Molecular Test Can Predict Both the Risk of Breast Cancer Recurrence and Who Will Benefit From Chemotherapy
A new test can predict both the risk of breast cancer recurrence
and may identify women who will benefit most from chemotherapy,
according to research supported by the National Cancer Institute
(NCI), part of the National Institutes of Health, and performed
in collaboration with the National Surgical Adjuvant Breast and
Bowel Project (NSABP) and Genomic Health Inc. These results suggest
that almost half of 43,000 U.S. women diagnosed with estrogen-dependent,
lymph-node negative breast cancer every year are at low risk for
recurrence and may not need to go through the discomfort and side
effects of chemotherapy.
The test is based on levels of expression (increased or decreased)
of a panel of cancer-related genes. This panel is used to predict
whether estrogen-dependent breast cancer will come back, according
to a study that will be published online in the New England Journal
of Medicine on Friday, December 10, 2004*.
Scientists on this study also will present new results on that day
at San Antonio Breast Cancer Symposium indicating that the same
test can predict which women benefit most from chemotherapy. Women
with low risk of breast cancer recurrence-about half of the women
in the recent study-do not appear to derive much benefit from chemotherapy.
The researchers used tissue samples and medical records from women
enrolled in clinical trials of the cancer drug tamoxifen, which
blocks the effect of estrogen on breast cancer cells. These women
had a kind of breast cancer defined as estrogen receptor-positive,
lymph node-negative. Each year, 43,000 women are diagnosed with
this kind of breast cancer, which needs estrogen to grow but has
not spread to the lymph nodes. Currently, many women with this type
of breast cancer in the United States do receive chemotherapy in
addition to hormonal therapy.
Using samples from 447 patients and a collection of 250 genes in
three independent preliminary studies, 16 cancer-related genes were
found that worked best. The scientists created a formula that generates
a "recurrence score" based on the expression patterns
of these genes in a tumor sample. Ranging from 1 to 100, the recurrence
score is a measure of the risk that a given cancer will recur**.
Prior to this research, analysis of the expression of genes was
performed on tumor specimens that were frozen rather than tissue
prepared for routine pathologic evaluation (fixed and embedded).
The expression analysis depended on measurement of RNA (the molecule
necessary for the translation of a gene into a protein), and RNA
is altered when tissues are fixed and embedded. Frozen tissues are
generally not readily available in routine practice. Researchers
at Genomic Health, Inc. developed a method for performing these
analyses on tissues embedded in paraffin wax. Their method allows
them to use the altered RNA that is found in fixed tissue.
The results published in the New England Journal of Medicine validate
the ability of the recurrence score to predict risk of recurrence.
Using biopsy tissue and medical records from another NSABP tamoxifen
trial, researchers divided 668 women into low, intermediate, and
high risk of recurrence groups. Fifty-one percent were in the low
risk group (with a score of less than 18); 22 percent were at intermediate
risk (recurrence score 18 or higher but less than 31); 27 percent
were at high risk (a score of 31 or higher).
These risk group divisions correlated well with the actual rates
of recurrence of breast cancer after 10 years. There was a significant
difference in recurrence rates between women in the low and high
risk groups. In the low risk group, there was a 6.8 percent rate
of recurrence at 10 years; in the intermediate and high risk categories
these rates were 14.3 and 30.5 percent, respectively. Up to a recurrence
score of 50, rates of recurrence increased continuously as the recurrence
score increased. These trends held across age groups and tumor size.
* Print version: Paik S, Shak S, Wolmark
N, et al. A multigene assay to predict recurrence of node-negative,
estrogen-receptor-positive breast cancer in tamoxifen-treated patients.
New England Journal of Medicine, 351(27). December 30, 2004.
** This technology is called the