Estrogen receptor (ER) status is
all-important in determining not only which breast cancer
patients will respond to endocrine therapy like tamoxifen,
but also which stand to benefit most from chemo.
Breast cancer research has been
fixated for several years now on the question of estrogen
receptor status. No longer is it safe to apply findings
to breast cancer patients in general, because what's
true for estrogen node-positive (ER-positive) patients
is rarely true for those who are node-negative (ER-negative).
In fact, in treatment terms, breast cancer is beginning
to look more and more like two distinct diseases.
"The benefit of chemotherapy for
ER-negative tumours is surprisingly dramatic in the
same way that tamoxifen's effect is substantial for
ER-positive tumours," said Dr Donald Berry of the University
of Texas M D Anderson Cancer Center, lead author of
a compelling study on the subject published in the Journal
of the American Medical Association on April 13.
IT'S
ALL IN THE NODE
The study analyzed data from over 6,600 patients, randomized
to a range of chemotherapy strategies including cyclophosphamide
and doxorubicin alone; cyclophosphamide, doxorubicin
and fluorouracil; cyclophosphamide and doxorubicin followed
by paclitaxel; and cyclophosphamide, doxorubicin and
paclitaxel concurrently.
Of the ER-positive patients, most
were also prescribed tamoxifen after chemotherapy. But
not enough received it to allow for meaningful analysis
of its benefits. The studies ran to six, nine, and 17
years' follow-up.
The researchers' real goal was
not head-to-head comparison of different chemo regimens,
but rather to understand the interaction between estrogen
receptor status and response to chemotherapy in general.
Their findings contain both good
and bad news for patients in both categories. The benefits
of tamoxifen in ER-positive patients are clear, and
explain the improved survival seen in these patients
in recent years. But the benefits of tamoxifen are so
considerable that they have masked a harder reality
— ER-positive patients are getting much poorer
results from chemotherapy than ER-negative patients
are.
This is good news, in a brutal
way, for ER-negative patients. It means that almost
all of the improvements in survival seen with modern
chemo are concentrated in their subgroup. That's a startling
finding, because for several years these patients seemed
to be left high and dry by advances in breast cancer
treatment.
WORTH
THE WOE?
In hard numbers, chemotherapy alone brought an absolute
improvement in five-year disease-free survival of nearly
23% for ER-negative patients, but just 7% for ER-positive
patients. This explains, the authors suggest, why recent
data shows ER-negative patients are achieving very similar
outcomes to ER-positive patients.
"This tells us that breast oncology
has made enormous strides in treating patients with
ER-negative tumours, a finding which contradicts the
prevailing wisdom that with the development of tamoxifen
and newer selective estrogen receptor modulator drugs,
the benefits of medical science have been primarily
focused on ER-positive tumours," explained Dr Berry.
The downside is that thousands
of ER-positive women are being routinely assigned to
difficult chemotherapy regimens with little hope of
benefit. The researchers suspect that further, unidentified
patient characteristics within this group will determine
who stands to benefit and who's wasting their time with
chemo.
"The benefits of intensive and
extensive chemotherapy for unselected patients who have
ER—positive disease treated with tamoxifen are
modest at best. Whether such patients should opt for
chemotherapy will depend on their attitudes toward the
associated negative sequelae. In the years ahead, it
is likely that we will have better predictors that will
allow clinicians to determine which patients with ER—positive
disease truly benefit from the addition of chemotherapy,"
the authors wrote.
"It's true that tamoxifen changed
the landscape for ER-positive tumours, but the playing
field has now been levelled somewhat given the fact
that ER-negative tumours respond well to modern improvements
in chemotherapy regimens," said Dr Berry. "Our analysis
shows that tamoxifen works very well for a number of
years and taken as a group, there's little or no benefit
of even the cumulative effects of modern improvements
in chemotherapy for women with ER-positive tumours."
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