Hopkins Kimmel Cancer Center researchers are studying
whether delivering chemotherapy drugs directly to breast
"plumbing" might make treatment of early breast cancer
easier on the patient and at least as good as surgery or
A report on successful tests of intraductal therapy in
rats and mice published in the Jan. 15 issue of Cancer
Research has paved the way for one of the first preliminary
clinical trials in women with breast cancer, which is
currently under way in women with breast cancer scheduled
for a mastectomy at Johns Hopkins.
For more than a decade, researchers have been studying
how to diagnose breast cancer earlier by extracting fluid
from the vast network of tiny milk-producing ducts in the
breast. The idea is based on the finding that most breast
cancers sprout from cells lining the milk ducts. This same
idea led Kimmel Cancer Center researcher Saraswati Sukumar
to explore the possibility of treating early breast cancers
by using hair-thin catheters to inject chemotherapy through
openings at the nipple directly into the place where they
started — the milk ducts.
Sukumar likens the procedure to pouring detergent down
the kitchen sink to rid the pipes of unwanted material.
Because early breast cancers are less likely to have
escaped the ducts, intraductal therapy may have at least as
good a chance to cure as radiation or surgery.
"We'd like to develop a treatment option for early
breast cancers that minimizes disfigurement and spares
normal tissues," said Sukumar, who is the Barbara B.
Rubenstein Professor of Oncology.
Standard treatments for early breast cancer, called
ductal carcinoma in situ, or DCIS, include radiation and
surgery to remove the tumor via a lumpectomy or mastectomy.
Chemotherapy, reserved for disease that has spread beyond
the ducts, is not typically used to treat DCIS because
conventional methods of delivering the drugs through an arm
or chest vein would unnecessarily send the toxic chemicals
coursing throughout the entire body.
"We found that, in animal models, injecting
chemotherapy into the milk ducts confines most of the drug
to the breasts, leaving other tissues unharmed," Sukumar
Building on observations made by her lab on rat models
using drugs that block estrogen, Sukumar began tests in
mouse models three years ago by using a chemotherapy drug
called doxorubicin. The mice were bred to develop breast
cancers that were genetically similar to
treatment-resistant ones in humans.
First, researchers injected mice that had palpable
tumors with a slow-release formulation of low-dose
doxorubicin directly into their mammary ducts. At the end
of the observation period, this group had tumors less than
half the size of those receiving the drug intravenously.
Then, the scientists increased the drug dose and,
initially, tumors in both groups remained small. But that
changed 56 days later, when tumors in the IV group
ballooned — almost as large as those in control mice
getting no treatment — while tumors in the
intraductal group fared much better. Eight of 10 tumors in
the intraductal group disappeared in 20 days. Some of the
tumors grew back but remained small compared with the IV
group. At the end of the 91-day study period, four of the
10 tumors had not come back.
Sukumar also believes that injecting chemotherapy
agents or prevention drugs like tamoxifen into the breast
ducts could be one option for women at high risk for the
To test this premise, her team injected doxorubicin
via IV or intraductally into 40 mice bred to develop breast
cancer. Control mice received injections of saline or no
treatment. Mice receiving IV therapy were twice as likely
to develop breast cancer (32 tumors in 170 mammary glands)
than those receiving a single intraductal dose (13 tumors
in 196 glands). Increasing the number of intraductal
injections to two per mammary gland completely protected
all 10 mice (100 glands) from developing the cancer, while
all intravenously treated mice succumbed to the disease.
The scientists found similar results using a derivative of
tamoxifen in rat models.
Phase I studies in breast cancer patients have begun
to test the feasibility and safety of the procedure. Among
the potential side effects that Sukumar's team, headed by
Vered Stearns, breast cancer specialist at the Kimmel
Cancer Center, will be studying in the trial are pain,
inflammation and changes in the structure of the duct
network. Other areas for study include image-guided
injections that could be rigged as "duct-detectors" to help
pinpoint early lesions, as well as different chemotherapy
drugs and dosing schedules.
More than 200,000 cases of breast cancer are diagnosed
in the United States annually. DCIS accounts for 20 percent
to 40 percent of these cases, according to researchers.
This research was funded by the American Cancer
Society, Department of Defense, Susan G. Komen Foundation
and National Cancer Institute.
Additional authors are Satoshi Murata, from the Shiga
University of Medical Science; and Scott Kominsky, Mustafa
Vali, Zhe Zhang, Elizabeth Garrett-Mayer, Dorian Korz,
David Huso, Sharyn D. Baker, James Barber, Elizabeth Jaffee
and R. Todd Reilly, all of Johns Hopkins.