SABCS: A Call to Scrap Anthracyclines for Breast Cancer
Marilyn Mann
By Michael Smith, North American Correspondent, MedPage Today
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of
Medicine, University of California, San Francisco Earn CME/CE credit
for reading medical news
Dennis Slamon, M.D., Ph.D., UCLA
SAN ANTONIO, Dec. 13 -- The anthracycline drugs -- long a mainstay of
breast cancer chemotherapy -- only benefit a minority of women and
should be mostly scrapped, a researcher said here.
The continued use of the drugs "on a one-size-fits-all approach is
just crazy and it's medically dangerous," said Dennis Slamon, M.D.,
Ph.D., of the University of California at Los Angeles.
Both retrospective and prospective data show that the anthracyclines
only benefit women with amplification of both the HER2 receptor and
the topoisomerase IIa gene (Topo IIa), Dr. Slamon told an oral session
at the San Antonio Breast Cancer Symposium. Action Points
The amplification of Topo IIa appears only to occur when HER2 is
amplified, but not always, he said, so that women with both changes
account for about 8% of all women with breast cancer.
"When we didn't have an alternative and when we didn't know how to
identify the women who would benefit, it made sense to use the drugs,"
he said.
Now, he said, anthracycline-based adjuvant treatment should be
reserved for women who don't have access to therapy targeted to the
HER2 receptor, which doesn't apply to women in the U.S.
The anthracyclines -- notably doxorubicin (Adriamycin) -- yield about
a 5% improvement in survival overall, Dr. Slamon said, but they are
also associated with cardiac and bone marrow morbidity and mortality.
"The reality is that there's probably a 25% to 30% benefit for a small
subgroup" while the remaining patients do not benefit, Dr. Slamon
said.
The reason, he said, is that the Topo IIa protein is a "major target"
of the anthracyclines and the Topo IIa gene is amplified only in a
minority of women who are also HER2-positive.
Dr. Slamon said data from the registrational trial of trastuzumab
(Herceptin), which he led, showed clearly that patients with co-
amplified Topo IIa were the only ones who benefited from
anthracyclines.
Among HER2-positive women treated with doxorubicin and
cyclophosphamide (Cytoxan), those with a normal or deleted Topo IIa
gene had a median survival of 18.2 months. In contrast, women with
amplified Topo IIa had a median survival of 38.5 months -- a
difference that was significant at P=0.004.
When trastuzumab was added in the experimental arm of the study, the
difference disappeared, he said.
Similar results have been seen in eight other studies, he said,
leading to his conclusion that HER2-positive women with amplified Topo
IIa are a "unique niche" in which the anthracycline drugs can be
used.
But it may be too soon to consign the drugs to the scrap heap,
countered Eric Winer, M.D., of Boston's Dana-Farber Cancer Center, who
moderated the session and was not involved in Dr. Slamon's research.
"It will make me very happy if we can get rid of Adriamycin and its
inherent cardiac toxicity," Dr. Winer said. "But I'm not ready to say
that this is an agent that doesn't have a role -- yet."
Dr. Winer said the debate doesn't signal a "rift in the breast cancer
community."
Instead, he said, it's a question of timing: "Most people feel they'll
be using a lot less in the way of anthracycline-based therapy in the
years ahead," he said, "and there are some people who are running to
that goal post."
Others, he said, are waiting for more than "a bunch of retrospective
studies and one prospective trial."
The research was supported by the Revlon Foundation, Genentech, and
Amgen. Dr. Slamon reported financial relationships with Genentech and
sanofi-aventis.
Primary source: Breast Cancer Research and Treatment
Source reference:
Slamon DJ, et al "Role of anthracycline-based therapy in the adjuvant
treatment of breast cancer: efficacy analyses determined by molecular
subtypes of the disease" Breast Cancer Res Treat 2007; 106 (Supp1):
Abstract 13.
Andrew B. Chung, MD/PhD
..having seen too many iatrogenic cardiomyopathies from
anthracyclines.
Be hungry... be healthy... be hungrier... be blessed:
http://TheWellnessFoundation.com/BeHealthy
Prayerfully in the infinite power and might of the Holy Spirit,
Andrew <><
--
Andrew B. Chung, MD/PhD
Lawful steward of http://EmoryCardiology.com
Bondservant to the KING of kings and LORD of lords.