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A Shot against Breast Cancer

A study in mice suggests that the earliest form of breast cancer may one day be treated without surgery
breast cancer cells
breast cancer cells


Histological sections of normal breast show lobules from a 37-year-old woman (left) and a 76-year-old woman that were stained to show how the expression of a keratin protein (brown) changes with age. In young women, this protein is only in the cells surrounding the milk-producing cells. In older women even the milk-producing cells make the protein, a factor that may increase the potential for malignancies in older women.


Mark LaBarge, Berkeley Lab, and Alexander Barowsky, UC Davis

A recently conducted study in mice may someday help doctors develop new treatments for breast cancer. The results, which were published in Science Translational Medicine earlier this month, suggest that it may be possible to stop some abnormal growths from going on to becoming potentially life-threatening tumors.
 
About 25 percent of newly diagnosed cases of breast cancer in the U.S. consist of ductal carcinoma in situ (DCIS), which has long been thought of as the earliest stage of cancer. Because there is no way to tell if DCIS will ever pose a problem by spreading, however, standard treatment is still a lumpectomy (in which the abnormal growth and some surrounding tissue are surgically removed) or sometimes a mastectomy (breast removal). A lumpectomy is often followed by radiation (recommended), and both lumpectomy and mastectomy can be followed by tamoxifen, an oral hormone therapy that may reduce the risk of recurrence. In any event, treatment side effects include breast pain and fatigue.
 
Many people think there ought to be a better way to deal with DCIS. “A lot of women end up having mastectomies,” says Susan Love of the Dr. Susan Love Research Foundation, which she thinks is excessive considering that perhaps as many as half of DCIS growths are unlikely to spread. The foundation has recently been working on minimally invasive chemotherapy treatments.
 
One such alternative treatment that researchers at Harvard University are exploring would be to use a so-called RNAi therapeutic. By injecting an RNA particle that interferes with or turns off a specific, cancer-causing gene—hence RNA interference, or RNAi—researchers hope to prevent DCIS lesions from turning into invasive tumors.
 
The Harvard group started testing the concept in mice with early-stage DCIS lesions. They used mouse tumor sample data and computational analyses to determine that the gene they needed to target was HoxA1. Past work in human breast cancer research has also shown that HoxA1, which is part of a family of genes involved in normal development of an organism, could become mutated and turn into a cancer-causing oncogene.
 
Working in collaboration at the Wyss Institute for Biologically Inspired Engineering at Harvard, the scientists designed an RNA particle aimed at turning HoxA1 off. They then wrapped that RNA molecule inside a nanoparticle and injected the whole package directly into the nipples of mice with early-stage DCIS. They found that only 25 percent of the animals developed cancerous tumors. In contrast, 100 percent of the control animals’ tumors went on to become malignant. “This study and others suggest that administering agents directly into the breast ductal system may be an effective way to eliminate premalignant lesions and to prevent new cancer formation,” says Vered Stearns, co-director of the Breast Cancer Program at Johns Hopkins University, who was not involved with the research.
 
Not only can RNAi be minimally invasive, but it can also be localized and tailored to a specific genetic mutation, or predisposition, to developing cancer from DCIS. “Localized delivery of a therapeutic opens up new options for patients and doctors,” says co-author Amy Brock of the University of Texas at Austin. Brock hopes that RNAi-based therapy can be used to prevent cancer in high-risk patients in the future. “We see this as a platform technology that can be personalized to individual patients and individual tumor types.”
 

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