Analysis
Shows Women with High Breast Cancer Recurrence Scores Benefit from Chemo

For women
with the most common type of early-stage breast cancer and high scores on the
Oncotype DX test, receiving chemotherapy with hormone therapy after surgery can
lead to excellent long-term outcomes. That’s the conclusion of a new data
analysis from the U.S. Department of Health and Human Services affiliated
NCI-funded TAILORx clinical trial.

The
10,000-patient trial investigated the use of the Oncotype DX test
to help guide the care of women with hormone receptor‒positive,
HER2-negative breast cancer that has not spread to lymph nodes. This diagnosis
accounts for half of all breast cancer cases in the United States each year.

What is
Oncotype DX test

The Oncotype
DX test is used to assign each women’s cancer a score for recurrence risk on a
scale of 0‒100. Women in the TAILORx trial with a high recurrence score on the
test (26 and above) were assigned to receive chemotherapy and hormone therapy
after surgery. According to the new analysis, an estimated 96% of women in this
group were still alive at 5 years.

“This
analysis solidifies the standard recommendation that chemotherapy should be
offered to women with a recurrence score in the 26‒100 range,” said Larissa
Korde, M.D., head of Breast Cancer Therapeutics in NCI’s Division
of Cancer Treatment and Diagnosis, which funded the study. “It
shows that patients who receive chemotherapy have good outcomes and that there
are a wide range of effective chemotherapy options that are available to these
patients.”

The
researchers also used statistical models to estimate what the outcomes would
have been for women in the high-risk group if they had been treated with
hormone therapy alone.

In this
comparison, they found that women who were treated with both chemotherapy and
hormone therapy were less likely to have a recurrence of their breast cancer at
a distant site than would be expected for women treated only with hormone
therapy.

New
Analysis from a Groundbreaking Trial

TAILORx was
launched in 2006 and designed and led by what is now the ECOG-ACRIN Cancer
Research Group. The trial was developed to see if the Oncotype DX test, which
assesses the expression of 21 different genes in a patient’s tumor to calculate
a recurrence-risk score, could be used to help determine the most appropriate
and effective adjuvant treatment for women with early-stage breast cancer.

Based on
data from earlier trials, women in TAILORx with scores in the low-risk range
(0‒10) received hormone therapy alone after surgery, and women with recurrence
scores of 26 and above received both chemotherapy and hormone therapy. Women
with scores in the intermediate range (11‒25), for whom there was less data and
who made up the largest group in the trial, were randomly assigned to receive
either hormone therapy alone or hormone therapy and chemotherapy.

TAILORx
findings published in 2018 showed that, for most women in the intermediate-risk
group, there was no benefit from receiving chemotherapy in addition to hormone
therapy.

Joseph A.
Sparano, M.D., of the Albert Einstein Cancer Center and the trial’s lead
investigator, said at the time that the findings confirmed the test could help
spare some women from unnecessary treatment.

Predicting
Chemotherapy Benefit

In the new
analysis, published September 30 in JAMA Oncology, the researchers wanted to
determine the outcomes of the women in the trial with high recurrence scores,
who were assigned to receive both hormone therapy and chemotherapy.

Analyzing
data from the 1,389 women in TAILORx with high recurrence scores, the
researchers estimated that, at 5 years, more than 90% of the women had not had
their cancer return near the site of their original tumor or elsewhere in the
body, such as the brain or liver, and 95.9% were still alive.

The findings
also showed that the choice of chemotherapy regimen did not seem to
influence outcomes. Clinicians treating women in the trial could select one of
several chemotherapy regimens. The most common included a taxane and
cyclophosphamide (42%), an anthracycline without a taxane (24%), and an
anthracycline and a taxane (18%). After 5 years, women who had treatment with
any of these regimens, along with hormone therapy, had similar rates of
remaining free from cancer recurrence.

When many of
the regimens commonly used for treatment do similarly well in a study, it
offers clinicians a lot of good choices for treatment, Dr. Korde said, adding
that this finding, and the analysis in general, offer some welcoming
reassurances.

“It’s always
nice to have these large trials that confirm hypotheses and treatment decisions
that we’ve been making for a long time,” she said. “When you counsel a patient,
it’s helpful to say we have very good contemporary data that says if we do
this, this is what we think the outcome will be.”

Estimating
Expected Outcomes with Hormone Therapy Alone

Because all
women in the trial with high recurrence scores were assigned to receive
chemotherapy and hormone therapy, their outcomes couldn’t be compared with
those of similar patients who received hormone therapy alone. So the
researchers used a statistical method to predict the outcomes for women with
high recurrence scores if they had received hormone therapy alone.

The
statistical method combined recurrence data from TAILORx with data on
chemotherapy benefit from an analysis of an earlier trial.

“We took the
treatment effect that was seen in that earlier analysis and we applied it to
this population to estimate what the outcomes would have been had they only
received [hormone] therapy,” Dr. Sparano said.

Using the
statistical method, the researchers estimated that 78.8% of the women who
received hormone therapy alone would be free of recurrence at 5 years.

This
comparison

“is not a
substitute for a randomized trial, but we’ll never be able to do a randomized
trial in this specific population because the benefits of chemotherapy for this
group are very clear,” Dr. Sparano explained. “What this analysis provides is a
better assessment of what the benefit from chemotherapy is in patients who have
a recurrence score within the 26‒100 range.”

He added
that despite receiving chemotherapy, the women with high recurrence scores had
worse outcomes than the women with intermediate scores who received hormone
therapy alone. “However, we can see that the outcomes are much better than they
would have been if this group of patients had [hormone] therapy alone,” he
said.

“One of the
major strengths of this analysis is that it’s the largest prospective trial
that’s ever been conducted in patients who have high recurrence scores, and the
use of chemotherapy by the clinicians reflects real-world practice,” he added.

More
Information for Treatment Decisions

For women
with early-stage breast cancer who have recurrence scores either
just below or just above 26, the data from TAILORx can inform treatment
decisions, Dr. Korde said.

“These data
give us very strong evidence that the cut points that were chosen are
meaningful. But for every patient, the decision of whether to pursue
chemotherapy is an individual one,” she said. “A patient with a recurrence
score of 28 may have compelling reasons not to have chemotherapy. And there
could be a very young premenopausal woman with a lower score, under 26 but
close to 26, for whom some of the data in the trial suggest there might be a
small benefit from chemotherapy.”

“It’s always a nuanced conversation,” she said, “and I think the more information we have from well-designed studies, the better we are able to counsel our patients with that in mind.”

“Analysis Shows Women with High Breast Cancer Recurrence Scores Benefit from Chemo was originally published by the National Cancer Institute.”

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