Washington: Treating breast cancer by delivering chemotherapy through the nipple is highly effective in animal models of early breast cancer, and has no major side effects in human patients, a new study led by an Indian-origin researcher has found.
“Our results support the theory that by treating the breast tissue directly we can reach a much more potent drug concentration where it is needed, with far fewer adverse effects on tissues outside the breasts,” says oncologist Vered Stearns, M.D., Ph.D., the Breast Cancer Chair in Oncology and co-director of the Breast Cancer Program at the Johns Hopkins Kimmel Cancer Center, who supervised the clinical part of the study.
Saraswati Sukumar, the Barbara B. Rubenstein Professor of Oncology at the Kimmel Cancer Center, and co-director with Stearns of the Breast Cancer Program, began intraductal research more than a decade ago, reasoning that because most breast cancers originate from cells lining the milk ducts, early or preventive therapies should be delivered directly to the ducts via the nipple, rather than intravenously.
In 2006, Sukumar and her colleagues reported on an initial successful test of the technique using the chemotherapy drug doxorubicin against early ductal breast cancers in rats.
For the current study, Stearns set up a small clinical trial to determine the feasibility of Sukumar’s technique in 17 breast cancer patients.
Starting first with dextrose -- essentially sugar water -- and later with escalating doses of the same doxorubicin formulation used on Sukumar’s rats (pegylated liposomal doxorubicin, or PLD), she was able to infuse patients’ breast ducts via a small catheter placed into the nipple. The technique wasn’t used in this case to treat cancer; the patients in the study all had established breast tumors and were awaiting mastectomies.
But Stearns was able to establish that single doses of PLD to breast ducts caused only mild side effects including mild nipple pain and breast fullness.
A comparison of 12 patients receiving PLD intraductally with three patients treated with PLD by the standard intravenous route also was revealing, Stearns said. “Intraductal delivery of PLD resulted in much higher concentration in the breast compared to the circulation, whereas in the women with intravenous doses we saw relatively high concentrations in the blood but very little if any in the breast,” she noted.
In the animal portion of the study, Sukumar’s lab examined the intraductal effectiveness of four standard anticancer drugs, 5-fluorouracil (5FU), carboplatin, methotrexate and paclitaxel, all compared with PLD. Of these drugs, intraductal 5FU prevented the most cancers compared to no drug or to intravenous delivery. It also shrank established breast tumors with striking effectiveness, completely eliminating them in 10 of 14 treated rats, she said.
The study has been published in the journal Science Translational Medicine.