An internationally renowned researcher,
V. Craig Jordan focuses on finding the benefit in using estrogen in women with breast cancer -- a role reversal for the hormone known to be responsible for the disease in many women.
Jordan, scientific director and vice chair of the oncology department at the Lombardi Comprehensive Cancer Center, has been dubbed the “father of tamoxifen,” a hormone therapy treatment for breast cancer.
In the 1970s, Jordan found a way to shut down the ability of the estrogen hormone to fuel breast cancer growth. He now believes the same hormone can be given back to women as breast cancer therapy and is out to prove it.
Jordan theorizes that even after tamoxifen, an anti-estrogen, stops working, it allows the return of estrogenic activity in a woman that may keep cancer at bay. He believes that giving women resistant to anti-estrogenic therapy a short course of the hormone can treat recurrence -- a seemingly radical notion that he wants to test in clinical trials.
Looking Back to Reach ForwardSuch a flip-flop view of estrogen in breast cancer may be surprising to some, but not Jordan. “By looking back, you can see the way forward,” he says. “That is how we learn from previous generations.”
Jordan began to look at Alexander Haddow’s 1940s cancer research, in which the scientist had begun to observe that synthetic estrogens could shrink tumors in animals. Haddow eventually found that one-third of postmenopausal women with metastatic breast cancer responded well to high doses of estrogen and that some patients had an extraordinary regression of their cancers.
“Large tumors would just melt away, but you needed sledgehammer doses to do it -- 50 times more than a woman would normally have in her body,” Jordan says.
By the 1970s, Haddow had expressed regret that the mechanism by which the tumors disappeared remained completely unknown. Now, Jordan and his colleagues believe they may have solved that mystery.
From Mystery to Discovery It took Jordan some time to come to his recent conclusions. In the early 1970s, many knew estrogen played a role in breast cancer, but few researchers thought antiestrogen agents could be developed to fight the disease.
“In those days, there was really no optimism about developing effective drugs to treat cancer, Jordan says. “Chemotherapy was king and could cure cancer.”
He eventually collaborated with Arthur Walpole, a scientist at ICI Pharmaceuticals -- now part of AstraZeneca -- who also thought the compounds now know as tamoxifen could have anticancer properties. Jordan wound up showing that the compound could prevent breast cancer in rats. In 1978, the Food and Drug Administration approved the drug for estrogen-receptor-positive breast cancer -- the kind most women develop.
In 1999, Jordan turned his focus to raloxifene. He showed that the drug reduced the risk of breast cancer by 76 percent in postmenopausal women treated for osteoporosis. Tamoxifen and raloxifene were among the first drugs known as selective estrogen receptor modulators (SERMs) -- the pioneers for breast cancer prevention.
“We now understand that after years of SERM therapy, tumors learn how to grow without estrogen as a fuel,” he says. “They find new pathways to grow and can even be stimulated by SERMs themselves.”
But Jordan also found that treating SERM-resistant cancer with low-dose estrogen resulted in tumor cell death.
“No one could have guessed this and for 10 years I couldn’t get grants to further study this finding,” the researcher says.
Today, a $10 million grant from the Department of Defense allows Jordan to advance this discovery. Some of those funds go to collaborating researchers
Anna Riegel, associate director for cancer research education, and
Dr. Anton Wellstein, associate director for basic science and professor of oncology and pharmacology.
“This is an exciting area of research with great potential,” says Riegel, who is also a professor of oncology and pharmacology at Georgetown. “We already have some interesting leads from the research we have done on this so far and will be publishing some papers with Craig on this in the next months.”
Jordan’s achievements have earned him numerous awards, ranging from the American Cancer Society’s 2002 Medal of Honor for Basic Research to being named by Queen Elizabeth II as Officer of the Most Excellent Order of the British Empire. Shortly after being named Lombardi's first scientific director last spring, Jordan was elected to the National Academy of Sciences.
The medical scientist says he’s honored by the accolades, but finding a successful cure will be the main reward.
“I want to be able to say, definitely, that I have solved Dr. Haddow’s problem,” he says, “and that of many women with breast cancer or at risk of developing it,” he says.
