Donor
Immune Cells Attack Metastatic Breast Cancer
New
Approach Holds Promise
In
patients with metastatic breast cancer, immune cells from a genetically
matched donor can attack and shrink tumors, researchers from the National
Cancer Institute (NCI) announced at the annual meeting of the
American Society of Clinical Oncology.
This
is the first time researchers have clearly demonstrated this type of
immune response, known 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," says Dr. Michael Bishop, of NCI's
Center for Cancer Research and the lead author on the study.
"Breast cancer,
however, has generally been resistant to immune-based therapies,"
Dr. Bishop says. "Although the tumors of patients in this study
were not completely eliminated by the treatment, the responses we saw
provide hope that immunotherapies for breast cancer are worth pursuing."
Breast cancer is
the most common cancer among women, excluding non-melanoma skin cancer.
Currently, approximately 3 million women in the US are living with the
disease, including 2 million who have already been diagnosed, and another
1 million who do not yet know they have the disease.
Approach
Used in Metastatic Breast Cancer
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 transplant.
The design of this
clinical trial, however, allowed researchers to attribute 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 cancer.
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 infusions over the next two months.
Transplanted
T Cells Led to Tumor Death
Because T cells
were not given immediately following chemotherapy, researchers were
able to attribute any tumor cell death to the transplanted T cells rather
than to anti-tumor 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
optimistic that further study could lead to effective immunotherapies
for women with breast cancer.
Always consult your
physician for more information.
What
Is Immunotherapy?
Immunotherapy (also
called biological therapy, biological response modifier therapy, or
biotherapy) uses the body's immune system to fight cancer.
The cells, antibodies,
and organs of the immune system work to protect and defend the body
against foreign invaders, such as bacteria or viruses.
Physicians and researchers
have found that the immune system might also be able to both determine
the difference between healthy cells and cancer cells in the body, and
to eliminate the cancer cells.
Biological therapies
are designed to boost the immune system, either directly or indirectly,
by assisting in the following:
- making cancer
cells more recognizable by the immune system, and therefore more susceptible
to destruction by the immune system
- boosting the
killing power of immune system cells
- changing the
way cancer cells grow, so that they act more like healthy cells
- stopping the
process that changes a normal cell into a cancerous cell
- enhancing the
body's ability to repair or replace normal cells damaged or destroyed
by other forms of cancer treatment, such as chemotherapy or radiation
- preventing cancer
cells from spreading to other parts of the body
Always consult your physician for more information.
FDA-Approved
Immunotherapy Drug for Breast Cancer
A immunotherapy
drug approved in 1998 for recurrent breast cancer is called trastuzumab
(Herceptin®). This monoclonal antibody works against a protein that
encourages breast cancer cells to grow.
According to the
American Cancer Society (ACS), Herceptin® attaches
to a growth- promoting protein known as HER2/neu, which is present in
small amounts on the surface of normal breast cells and most breast
cancers.
About one-third of breast cancers have too much of this
protein and tend to grow and spread more aggressively. Herceptin®
can prevent the HER2/neu protein from making breast cancer cells grow
and may also stimulate the immune system to more effectively attack
the cancer.
This drug can shrink some breast cancer metastases that
return after chemotherapy or continue to grow during chemotherapy. And
treatment that combines Herceptin® with chemotherapy may be more
effective than chemotherapy alone in some patients.
Treatment with Herceptin® is generally started after
standard hormone therapy and/or chemotherapy is no longer effective,
but clinical trials are now in progress to see if using it with adjuvant
chemotherapy can reduce the risk of recurrence and help women live longer.
Always consult your physician for more information.
Online
Resources
American
Cancer Society
American
Society for Clinical Oncology
Centers
for Disease Control and Prevention (CDC)
National
Cancer Institute (NCI)
National
Human Genome Research Institute
National
Institutes of Health (NIH)
National
Women's Health Information Center
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July 2003
In
This Issue:
Donor
Immune Cells Attack Metastatic Breast Cancer
Approach
Used in Metastatic Breast Cancer
Transplanted
T Cells Led to Tumor Death
What
Is Immunotherapy?
FDA-Approved
Immunotherapy Drug for Breast Cancer
Studies
Suggest MRI an Effective Screening Tool for Women at High Risk for
Breast Cancer
Reports
from the Annual Meeting of the American Society for Clinical Oncology
Online
Resources
Other
Resources:
St.
John's Mercy Cancer Services
Find
a St. John's Mercy Physician
Breast
Health Information
Women's
Health Information
St.
John's Mercy Classes and Programs
Studies
Suggest MRI an Effective Screening Tool for Women at High Risk for
Breast Cancer
Physicians
now know that the risk of breast cancer increases with a family history
of the disease, including abnormalities in the BRCA genes. Mutations
in the BRCA1 and BRCA2 are associated with about 5 percent to 10 percent
of all breast cancers, according to press statement of the American
Association of Clinical Oncology (ASCO).
For
women with a high risk of breast cancer, experts recommend that they
have their first mammogram at age 30, or five years before the earliest
onset of the disease in their family.
However,
while mammography is the best tool for detecting breast cancer in
women at an average risk for the disease, experts are still debating
the best type of imaging technique that should be used to screen women
at high risk.
Some
research has suggested the use of magnetic resonance imaging (MRI)
in addition to mammography to screen women at high risk for breast
cancer. An MRI uses a magnetic field to produce the image of an internal
organ on a computer.
Reports
from the Annual Meeting of the American Society for Clinical Oncology
Study 1: To determine whether MRI should be added
as a screening method in high-risk populations, researchers led by
Dr. Christiane Kuhl of the University of Bonn in Germany studied 462
women who were found to be carriers of BRCA1 or BRCA2 or who, based
on their personal history or strong family history, were suspected
to be carriers of BRCA1 or BRCA2.
In this study, a strong family history
was defined as any of the following: a relative with a breast cancer
diagnosis at age 35 or younger; a relative with ovarian cancer diagnosed
at age 40 or younger; both breast and ovarian cancer in a relative;
or at least two relatives with breast and/or ovarian cancer, one of
whom was diagnosed at age 50 or younger.
All women in the study were screened
with a clinical breast examination, mammography, high-resolution ultrasound
of the breast - a technique that uses sound waves to detect abnormalities
in body tissues - and an MRI. For the first five years of the study,
researchers found 51 breast cancers in 45 patients.
MRI offered the highest sensitivity for
diagnosing breast cancer at 96.1 percent, compared with 42.8 percent
for mammography, 47 percent for ultrasound, and 25 percent during
a clinical breast exam.
MRI was also associated with the lowest
rate of unnecessary biopsies, a procedure that removes a small piece
of tissue for examination under the microscope to help detect cancer.
Because of these findings, the researchers
who conducted this study concluded that MRI of the breast should replace
mammography to screen women with a strong family history of the disease
or women who have known BRCA .
Study
2: A team of Dutch researchers reported similar findings.
As part of the Dutch MRI Screening Study (MRISC), researchers evaluated
the benefit of twice-yearly clinical breast examinations, yearly mammography,
and yearly MRI in 1,905 women at high risk of breast cancer due to
a mutation in the BRCA1 or BRCA2 gene or a strong family history of
the disease.
Following the study, the researchers
said, "We recommend the routine use of MRI in addition to mammography,
especially in women with proven mutations in the BRCA1/2 genes, because
these women generally develop rapidly growing tumors and show the
lowest sensitivity to mammography because of their young age and dense
breast tissue." Dr. Jan G.M. Klijn, chairman of the Rotterdam
Family Cancer Clinic was a lead investigator of the study.
However, while MRI was found to be more
effective at detecting tumors of the breast than both mammography
and clinical breast examination, it was also found to be slightly
less specific. Lower specificity means that it is more likely to produce
false positive results. False positives can lead to unnecessary biopsies
and anxiety for patients.
Study
3: Experts leading a third study evaluating the benefit of
MRI for women at high risk for breast cancer said that MRI needs to
be refined before its use can be recommended, even for women at high
risk for the disease, due to a high rate of false positives.
"The psychological impact of a false-positive
MRI is not trivial," said Dr. Mark E. Robson, of Memorial Sloan-Kettering
Cancer Center and lead investigator of the study.
In a trial of 53 women with BRCA mutations
who participated in MRI screening, researchers found that MRI was
100 percent sensitive for detecting both ductal carcinoma in situ
- a precancerous breast condition - as well as breast cancer. However,
it was only 81 percent specific.
"The improved sensitivity of MRI
screening is very encouraging," said Dr. Robson. "MRI can
clearly detect breast abnormalities that are not seen by mammography.
Unfortunately, we are finding that many of these abnormalities are
not cancers."
Until the specificity of an MRI can be
improved, Dr. Robson recommends that women who are considering an
MRI be aware of the significant risk of false-positive results.
Always consult your physician for more
information.
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