New drug delivery system for early-stage breast cancer may reduce side effects

March 5, 2014
New drug delivery system for early-stage breast cancer may reduce side effects
Compounds now used in the treatment of early-stage breast cancer and novel compounds developed at SDSU are being tested using pig breast tissue on this bank of nine receptacles.

One of every eight women in the United States will develop breast cancer. Though the incidence of breast cancer began decreasing in 2000, it is still the second-leading cause of cancer death in women.

Better screening techniques, increased awareness and improved treatments have increased the 5-year survival rate to nearly 100 percent for women with early-stage cancer.

In 2013, an estimated 65,000 women were diagnosed with carcinoma in situ, a non-invasive breast cancer that affects the milk ducts and lobules of the breast, according to the American Cancer Society.

While nearly everyone diagnosed at this stage can be cured, professor Om Perumal, head of the pharmaceutical sciences department, points out that the from the drugs used to combat this disease are pretty significant.

Doctoral student Kaushalkumar Dave puts a buffer solution into the receiving compartment. Any drug that passes through the nipple will be captured in this buffer.

He and doctoral student Kaushalkumar Dave are developing a new method to deliver cancer-fighting drugs directly to the milk ducts, where more than 95 percent of breast cancer originates. The patent pending technology has been licensed to Tranzderm Solutions, a Brookings-based start-up company. Perumal is the company's chief scientific officer.

This method promises to reduce side effects and to deliver large doses of medication directly to the affected tissues. The research has been supported by the Translational Cancer Center, one of the 2010 South Dakota Governor's Research Centers. It provides seed money for high-risk, high-reward research.

Using this data, Perumal has teamed with researchers and clinicians from Johns Hopkins University and Mayo Clinic to apply for an $800,000 Department of Defense grant.

Delivering drugs through milk ducts

Anti-cancer drugs, such as tamoxifen, are normally administered through an oral tablet, so the medication must travel through the bloodstream before reaching the breast tissue, explains Perumal.

Side effects of tamoxifen, for example, include increased risk of uterine cancer, cataracts, stroke and cardiovascular disease. Patients diagnosed with precancerous cells or lesions may take tamoxifen anywhere from three months to five years.

New drug delivery system for early-stage breast cancer may reduce side effects
This microscope image shows the distribution of a fluorescent dye in the nipple ducts in the pig breast tissue section.

These significant side effects may be mitigated through a more direct, localized drug delivery method, according to Perumal.

The researcher proposes applying a medication-containing gel or lotion to the nipple. The drug will then be absorbed through openings in the nipples directly into the milk ducts.

When the project began, Perumal thought that breast anatomy was well understood, "but it's not," he explains. The number of openings in the nipple varies based on the individual, but the range is usually 10 to 15 openings per nipple. The number of openings gives the scientists an indication of how much drug can be delivered.

Receiver vials are then stored and the amount of radioactive material measured so that professor Om Perumal and doctoral student Kaushalkumar Dave know how much of a specific drug compound can be absorbed through the openings in the nipple.

Next, the researchers looked at which molecules could be delivered. To do this, they used pig breast tissue. Surprisingly, they found that even large molecules, such as proteins, can be transported through these openings, making a wide range of medications deliverable.

Validating the model

Feedback from a proposal submitted to the National Institute of Health confirmed that the researchers needed to use human breast tissue to prove the feasibility of the pig model.

"Animal skin is usually thinner and more permeable than human tissue," Perumal explains. "We need repeatability." Pigs have on average six to seven pairs of mammary glands, but the team would needed at least three pairs of human breasts—at a cost of more than $700 per set—to validate the model.

Fortunately, Perumal was able to obtain the human breast tissue he needed free of charge through the Lions Eye and Tissue Bank in Sioux Falls. Director Marcy Dimond says her organization provides tissue to qualified South Dakota programs conducting medical research.

"We have a progressive medical community and being able to contribute to research programs that have the potential to be far-reaching is a wonderful opportunity," says Dimond. Not everyone can be a transplant donor, so this is a way those patients who truly want to be donors can contribute to research.

The donation of breast tissue was integral to advancing the project.

"Without them, we wouldn't have made a lot of progress," Perumal says. Having local access to tissues was "a big help to move things forward."

Documenting similar trends

Comparing the absorption rate of the nipple with the surrounding breast skin, twice the amount of drug can be delivered through the nipple, Perumal explains. "It's a direct port of entry." Plus, the medication does not enter the bloodstream.

Though different drug quantities are absorbed, pig and human show similar trends, Perumal explains. As a result, the researchers can now use pig tissue to optimize and test various drug formulations. Dave, who will finish his dissertation within a year, has already begun some animal studies. He recently received a grant from Women and Giving at the SDSU Foundation to support his work.

A variety of compounds show promise in fighting the many types of breast cancer. Perumal points to a natural compound developed by former colleague and Distinguished Professor Emeritus Chandradhar Dwivedi to prevent skin cancer—as having the potential to prevent breast cancer.

Additional methods are also being used in Perumal's lab to increase the penetration of the compounds through the nipple. The successful studies in animals may lead to clinical testing in humans.

"If this approach is successful, the impact will be huge in terms of reducing side effects." says Perumal. Once perfected, this unique technology developed at SDSU will help improve the lives of women battling early-stage .

Explore further: FDA warns against nipple test for breast cancer screening

Related Stories

FDA warns against nipple test for breast cancer screening

December 14, 2013
(HealthDay)—A new test marketed as an alternative to a mammogram for breast cancer detection is not an effective screening TOOL, U.S. health officials say.

Sparing the body, breast cancer treatment via nipple injection

October 4, 2013
On October 4, JoVE, the Journal of Visualized Experiments, will publish a new technique for breast cancer treatment and prevention—injection of therapeutics via the nipple. The procedure, demonstrated on mice, offers direct ...

Osteoporosis drug may treat breast and liver cancers

February 19, 2014
(Medical Xpress)—A drug used to prevent and treat osteoporosis in post-menopausal women may also be able to treat some breast and liver cancers, according to a new study from Oregon State University.

Through-the-nipple breast cancer therapy shows promise in early tests

October 26, 2011
Delivering anticancer drugs into breast ducts via the nipple is highly effective in animal models of early breast cancer, and has no major side effects in human patients, according to a report by Johns Hopkins Kimmel Cancer ...

New data contradict current recommendations for management of breast biopsy abnormalities

January 30, 2014
Contrary to existing understanding, long-term follow-up of patients with two types of breast tissue abnormalities suggests that both types of abnormalities have the same potential to progress to breast cancer, according to ...

Drug cuts breast cancer cases by more than 50 percent in high risk women

December 12, 2013
Taking the breast cancer drug anastrozole for five years reduced the chances of post-menopausal women at high risk of breast cancer developing the disease by 53% compared with women who took a placebo, according to a study ...

Recommended for you

Discovery could lead to better results for patients undergoing radiation

July 19, 2017
More than half of cancer patients undergo radiotherapy, in which high doses of radiation are aimed at diseased tissue to kill cancer cells. But due to a phenomenon known as radiation-induced bystander effect (RIBE), in which ...

Definitive genomic study reveals alterations driving most medulloblastoma brain tumors

July 19, 2017
The most comprehensive analysis yet of medulloblastoma has identified genomic changes responsible for more than 75 percent of the brain tumors, including two new suspected cancer genes that were found exclusively in the least ...

Novel CRISPR-Cas9 screening enables discovery of new targets to aid cancer immunotherapy

July 19, 2017
A novel screening method developed by a team at Dana-Farber/Boston Children's Cancer and Blood Disorders Center—using CRISPR-Cas9 genome editing technology to test the function of thousands of tumor genes in mice—has ...

Combining CAR T cells with existing immunotherapies may overcome resistance in glioblastomas

July 19, 2017
Genetically modified "hunter" T cells successfully migrated to and penetrated a deadly type of brain tumor known as glioblastoma (GBM) in a clinical trial of the new therapy, but the cells triggered an immunosuppressive tumor ...

How CD44s gives brain cancer a survival advantage

July 19, 2017
Understanding the mechanisms that give cancer cells the ability to survive and grow opens the possibility of developing improved treatments to control or cure the disease. In the case of glioblastoma multiforme, the deadliest ...

New way found to boost immunity in fight cancer and infections

July 19, 2017
An international research team led by Université de Montréal medical professor Christopher Rudd, director of research in immunology and cell therapy at Maisonneuve-Rosemont Hospital Research Centre, has identified a key ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.