as a graft-versus-tumor effect, acting

against breast cancer.

“Graft-versus-tumor effects have

been shown to be useful in treating

cancers of the blood, such as leukemia

and lymphoma. Breast cancer, howev-

er, has generally been resistant to

immune-based therapies,” said

Michael Bishop, MD, of NCI’s Center

for Cancer Research, the lead author

on the study. “Although the tumors of

patients in this study were not com-

pletely eliminated by the treatment,

the responses we saw provide hope

that immunotherapies for breast can-

cer are worth pursuing.”

Tumor regression has been

observed in the past in some patients

with metastatic breast cancer who

received stem cell transplants, but it

was unclear whether immune cells had

attacked the tumor or the tumor was

shrinking in response to chemotherapy

drugs administered prior to the trans-

plant. The design of this clinical trial,

however, allowed researchers to attrib-

ute tumor regression to a true graft-

versus-tumor effect.

Each of the 13 patients in the Phase

I trial had received multiple previous

treatments for metastatic breast can-

cer. In the study, patients first received

conventional doses of chemotherapy

to kill cancer cells and reduce the cells

in their immune system so that donor

cells could replace them. They then

received stem cells from the blood of

HLA-matched siblings. HLA-matched

donor cells, which have the same set of

proteins (known as human leukocyte-

associated antigens) on their surface as

the patient’s own cells, are much more

likely to be accepted by the patient’s

body.

T cells, specialized immune cells

that recognize and kill foreign cells

that have invaded the body, were

removed from the pool of donated

stem cells prior to transplant. These T

cells were given to patients later, in an

initial infusion 42 days after stem cell

transplant, then in two follow-up infu-

sions over the next two months.

Because T cells were not given imme-

diately following chemotherapy,

researchers were able to attribute any

tumor cell death to the transplanted T

cells rather than to antitumor effects of

the chemotherapy drugs.

In four patients, tumors shrunk at

least 50 percent in response to the

treatment. A minor response was seen

in three of the other patients.

Although not all patients in the study

responded to treatment, and none of

the tumors was eliminated entirely, the

results of the trial provide evidence

that transplanted T cells can attack

tumors in patients with metastatic

breast cancer. Researchers are opti-

mistic that further study could lead to

effective immunotherapies for these

patients.

Study Estimates MoreThan 2 Million WomenCould Benefit FromTamoxifen

More than 10 million women in

the U.S. have a high enough

risk of developing breast cancer that

they could consider taking the breast

cancer chemoprevention drug tamox-

ifen, according to Andrew N. Freed-

man, PhD, and his colleagues at the

National Cancer Institute (NCI).

When the scientists examined this

group of women using a risk-benefit

analysis of the drug, they found that

more than 2 million women would be

likely to derive overall benefit from the

drug without undue risks. The results

were reported in the April 2, 2003,

issue of the Journal of the National

Cancer Institute.

Tamoxifen was approved five years

ago as the first drug to prevent breast

cancer. It can halve the incidence of

breast cancer in women who are most

likely to develop the disease. As with

all medicines, tamoxifen has side

effects that may affect some women

and not others. In this case, the effects

are rare, but serious—endometrial

cancer, stroke, deep vein thrombosis

and pulmonary embolism. The deci-

sion to take tamoxifen will depend on

a woman’s age, breast cancer risk fac-

tors, family history, how she weighs

the benefits and risks and her specific

medical situation, lifestyle, personal

values, and preferences, said one of the

co-investigators on the NCI study.

“Tamoxifen therapy may not be appro-

priate for all women who are at

increased risk for breast cancer.”

Tamoxifen was approved as a

chemoprevention drug for breast can-

August | September 2003 AWHONN Lifelines 315