The American Society of Clinical Oncology has issued an
updated guideline on the use of adjuvant hormone therapy for postmenopausal
women with hormone-receptor–positive breast cancer. Specifically, it
recommends the use of an aromatase inhibitor at some point during adjuvant
therapy, whether as front-line therapy or as sequential or extended therapy
after the use of tamoxifen. The update committee concluded that the use of an
aromatase inhibitor improves DFS in this patient population compared with the
use of tamoxifen alone.
The recommendation was published in the Journal of
Clinical Oncology.
“One of the most important treatments for
women
with postmenopausal breast cancer is anti-estrogen therapy,” said
breast cancer specialist Harold J. Burstein, MD, PhD, co-chair of
ASCO’s Endocrine Therapy for Breast Cancer Update Committee and associate
professor of medicine at Harvard Medical School and Dana-Farber Cancer
Institute. “Our panel carefully reviewed the explosion of research that
has emerged in the past 5 years on anti-estrogen drugs and filled in gaps in
our understanding of how best to use these newer treatments and what the
trade-offs and side effects of therapy would be.”
Reviewing evidence
The committee members reviewed relevant randomized
trials relating to endocrine therapy in postmenopausal HR-positive breast
cancer. Primary outcomes of interest to the committee were DFS, OS and time to
contralateral breast cancer. They reviewed outcomes in all the literature,
focusing on 12 major trials.
Data from these studies indicated that using an
aromatase inhibitor alone or combined with tamoxifen therapy reduced the risk
of recurrence and DFS compared with tamoxifen alone.
Patients using an aromatase inhibitor will experience a
different adverse effect profile than a woman taking tamoxifen. The differences
in side effects may affect patient treatment preference.
“The panel emphasized the importance of discussing
side effects of these drugs with patients, to help patients better understand
and choose between the treatments and do all we can to maximize compliance with
these important therapies,” said Jennifer Griggs, MD,MPH,
co-chair of ASCO’s Endocrine Therapy for Breast Cancer Update
Committee and associate professor in the University of Michigan department of
internal medicine, division of hematology/oncology.
New recommendations
As an update from its previously released guidelines in
2004, the committee made several new recommendations, including:
- Most postmenopausal women should consider taking an aromatase
inhibitor at some point during the course of therapy, either as the initial
adjuvant therapy or after 2 to 3 years of tamoxifen. Women can take up to 5
years of an aromatase inhibitor therapy. Aromatase inhibitor therapy can also
begin after 5 years of tamoxifen therapy. In that setting, a woman could
receive up to 10 years of hormone treatment to reduce the risk of recurrence.
- Tamoxifen should be given to all pre- and perimenopausal women;
aromatase inhibitors are only effective in postmenopausal women. The guideline
recommends that women who are pre- or perimenopausal at the time of diagnosis
be treated with 5 years of tamoxifen.
- The committee found no clinically important differences in effectiveness
among the three commercially available aromatase inhibitors (anastrozole,
letrozole and exemestane). This is the first update in which data are available
for each in all three clinical settings (primary, sequential or extended
adjuvant).
The guideline also includes a review characterizing side effect profiles
of tamoxifen and aromatase inhibitors, compiled from the 12 trials considered.
Although the two drug classes work differently, overall, most women have
relatively mild side effects with either drug. When compared with tamoxifen,
aromatase inhibitors may reduce the chance of thromboembolism and uterine
cancer and may increase the risk for osteoporosis and fractures.
The guideline committee found no evidence that validated
the use of a specific biomarker to determine which treatment strategy would be
better for patients.
However, it suggested several areas in which additional
research is needed:
- Tumor marker or pathology studies aimed at finding
whether there are certain types of HR-positive breast cancers that respond
better to one treatment approach or drug compared with the other.
- Ongoing studies comparing 5 years of aromatase inhibitor therapy vs.
longer durations and studies comparing the optimal time to switch from
tamoxifen to an aromatase inhibitor.
- Definitive analyses of the role of drug metabolism and pharmacogenetics
as predictors of benefit or treatment options.
- Strategies to improve adherence to therapy.
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