Published June 2003
Sue Heffelfinger, MD, PhD, associate professor in the
UC Department of Pathology and Laboratory Medicine, found that
inhibiting angiogenesis (the growth of new blood vessels) in rats was
as effective in preventing the development of breast cancer as was
tamoxifen, an anti-estrogen treatment and preventive therapy used to
prevent and slow breast cancer in humans. To Dr. Heffelfinger's
knowledge, this is one of the first comparisons of angiogenic inhibitor
and anti-estrogen drugs.
In earlier studies, a research team headed by Dr.
Heffelfinger found that the number of tiny blood vessels in women's
breasts increased as breast tissue progressed from normal to
precancerous to full-blown cancer. Using a widely studied rat model of
breast cancer, she was able to see that the ability of the rats'
mammary tissue to induce new blood vessel growth actually preceded the
first visible steps toward the development of breast cancer.
In this study, estrogen-receptor positive breast cancer
was studied. Young female rats in the earliest stages of breast cancer
were given a potent angiogenic inhibitor to prevent the growth of new
blood vessels. The anti-angiogenesis treatment, called TNP-470, also
inhibited the development of late pre-invasive and invasive breast
cancer by 84 percent and 90 percent respectively. These decreases were
as significant as those caused by tamoxifen.
Since the two treatments work through completely
different mechanisms, TNP-470 slowing the growth of new blood vessels
and tamoxifen slowing the estrogen to which the precancerous and
cancerous tissues respond, the researchers reasoned that using both
would have an additive effect, but found this to be incorrect. When
used with TNP-470, tamoxifen performed less effectively than usual. The
UC researchers believe this may be true because, by inhibiting new
vessel growth, TNP-470 also inhibited delivery of tamoxifen to the
Dr. Heffelfinger suggests that combinations of agents
be carefully studied in new studies involving animals, using various
dosing and scheduling protocols, to determine maximum benefit.