Taking Aim at Breast
Cancer
Nurse Felinda Villa checks on breast cancer
patient Tracy Schuster.
Breast cancer - the mention of those very words strikes fear in the hearts
of many women.
Lynn Baird is no exception.
"It was hard to believe," she recalls, after learning she
had breast cancer five years ago. "My breasts were dense and hard
to image with mammography, so the doctor ordered an ultrasound. The ultrasound
revealed a suspicious looking lesion, which the radiologist biopsied."
For Baird, the news wasn't good - the lesion was malignant. The good
news, however, was that the lesion was found early while it was still small
and had not metastasized. This gave her more treatment options, she says.
After undergoing aggressive treatment and surgery, the 49-year-old
Baird is now cancer-free. "It was a miracle they found it early,"
she says gratefully. "I feel lucky to be alive."
Each year, more than 183,000 women (and 1,000 men) are diagnosed with
breast cancer, and more than 44,000 women will die as a result. Although
the number of new diagnoses still remains high, the long-term prognosis
for women with breast cancer is steadily improving, thanks to early detection
and improved treatments.
But research is perhaps the single-greatest factor contributing to
the increased survival rate of women with breast cancer.
"We have made tremendous progress over the last several decades.
Our previous research efforts are paying off and more women are surviving
this terrible disease," says Dr. Gabriel N. Hortobagyi, chairman of
the Department of Breast Medical Oncology and director of the Breast Cancer
Research Program.
For more than 50 years, M. D. Anderson has been at the forefront in
breast cancer research and, subsequently, in the development of new therapies.
With unwavering tenacity, researchers have contributed significantly
to the identification and understanding of key genes associated with the
development of breast cancer, including p53 and HER-2/neu, as well as provided
valuable information about familial breast cancer which led others to isolate
and clone the BRCA-1 and BRCA-2 genes.
Scientists also have pioneered new chemotherapy treatments - including
pre-operative chemotherapy that aims to reduce tumors prior to surgery
- and are among the first to use donor peripheral stem cell transplantation
to restore damaged bone marrow. In addition, they have played a major role
in the development and use of the taxanes - Taxol and Taxotere, and are
among few cancer centers conducting Tamoxifen chemoprevention trials for
women at high risk.
Further, they are among the nation's first to perform breast-preserving
surgery, demonstrating that lumpectomy with radiation was just as effective
as a radical mastectomy. Immediate breast reconstruction after surgery
was also first available 10 years ago.
While standard therapies of drugs, radiation and surgery are working,
researchers are continually challenged to find a "magic bullet,"
one that will lead to a cure. As elusive as a cure may seem, scientists
are looking to our genes for answers. And therein may lie the antidote.
Breast cancer is essentially the result of multiple genetic mutations,
says Dr. Hortobagyi, who holds the Nylene Eckles Professorship in Breast
Cancer Research. For instance, the p53 gene is mutated in about 50 percent
of breast cancer and mutations in BRCA-1 and BRCA-2 genes account for 50-60
percent of all familial breast cancer. In addition, an oncogene known as
HER-2/neu, previously cloned by Dr. Mien-Chie Hung and his colleagues,
was found to be overexpressed in 20-30 percent of breast cancer.
"Through research, we're making a difference every day,"
says Dr. Hung, director of the Breast Cancer Basic Research Program and
holder of the Hubert L. and Olive Stringer Professorship in Cancer Research.
"With the knowledge gained in the laboratory, we are able to design
new drug therapies, and develop new detection, prognostic and prevention
strategies that directly impact patient care."
While researchers are continuing to understand the molecular mechanisms
involved in turning a normal cell into a cancer cell and investigating
how certain external factors like a high-fat diet and environmental carcinogens
may initiate tumor development, a large part of what they are doing is
developing specific genetic-based therapeutic interventions.
For instance, an enormous amount of research focusing on the HER-2/neu
oncogene is ongoing. As a normal functioning gene within cells, HER-2/neu
regulates cell growth. When it becomes overexpressed, however, it becomes
permanently activated, allowing cells to grow without proper regulation.
Two gene therapy strategies aimed at preventing this uncontrolled cell
growth involve the transfer of a monoclonal antibody and a tumor suppressor
gene (the E1A gene) into tumor cells that overexpress this oncogene. Early
studies indicate both these approaches, which are currently undergoing
Phase III and Phase I trials, respectively, effectively down regulate the
mutated cell's function.
"There is a lot of excitement about this genetic approach to treating
breast cancer," Dr. Hortobagyi says, "not because it's going
to cure breast cancer today, but because it proves a concept that you can
target a genetic abnormality and turn it into a successful therapeutic
intervention."
As overexpression of the HER-2/neu oncogene disrupts normal cell functioning,
so do anomalies in tumor suppressor genes. Several studies examining ways
to genetically induce reactivation of the p53 and BRCA-1 and BRCA-2 genes
are under way.
While the application of gene therapy is still in its infancy, researchers
also are busily developing new anti-cancer drugs, hormonal agents and cytotoxic
compound agents that are effective against drug-resistant tumors, as well
as testing new chemotherapy combinations and doses.
They also are investigating immunologic approaches to treating breast
cancer. Research into the development of a vaccine that triggers the immune
system to target specific genetic mutations like HER-2/neu; treatment involving
the transplantation of autologous (one's own) or donor peripheral stem
cells to reconstitute damaged bone marrow; and the transfer of drug-resistant
genes and antigen-stimulating factors into bone marrow cells are all under
way.
For the last several decades, such intensive "research has been
the driving force for change in how we manage breast cancer today,"
says Dr. S. Eva Singletary, chief of the Surgical Breast Section. "Without
research and its answers, we wouldn't have advanced as far as we have."