Moderate Doses of Radiotherapy to Unaffected Breast May Prevent Second Breast Tumors

Breast cancer patients have a one in six possibility of developing breast cancer in the other breast. However, a study conducted in lab mice suggests that survivors can drastically slash that risk through treatment with moderate doses of radiation to the unaffected breast at the same time that they receive radiation therapy to their affected breast. The treatment, if it performs as well in humans as in lab mice, could prevent tens of thousands of second breast tumors.

The study was conducted by researchers from Columbia University Medical Center (CUMC; New York, NY, USA). “Over the past decades, we’ve had great success in treating breast cancer, and the 15-year survival rate is now 77%,” said study leader David J. Brenner, PhD, director of CUMC’s Center for Radiological Research and a professor of radiation biophysics. “Unfortunately, breast cancer survivors have a several times higher risk of developing cancer in their other breast, compared with healthy women of the same age.”

The study’s findings were published on December 20, 2013, in the online journal PLOS ONE. “While drugs such as tamoxifen and aromatase inhibitors can reduce the risk somewhat, at least for women with estrogen receptor-positive tumors, the long-term risks of a second breast cancer in the unaffected breast remain high. Because of these risks, approximately 10%–20% of breast cancer survivors in the US undergo prophylactic mastectomy of their other breast,” said Dr. Brenner.

The conception for prophylactic mammary irradiation (PMI) of the unaffected breast stems from earlier research of conventional whole-breast irradiation after lumpectomy. In that study, Dr. Brenner found that radiation is highly effective at destroying premalignant cells, not only in the quadrant of the breast where the first tumor was located, but additionally in the other three quadrants, where premalignant cells are typically though to be unconnected to the primary tumor. “So, we thought why can’t we treat the other breast with a moderate dose of radiation and kill any premalignant cells that could lead to second cancers?” said Dr. Brenner.

The crucial question was whether treating the breast with a moderate dose of radiation would in fact lower the overall risk of a second cancer. “We know that there will be a balance between radiation killing premalignant cells and radiation producing premalignant cells, but it seemed that using the right radiation dose would put the balance strongly toward lowering the cancer risk,” Dr. Brenner said.

This research project evaluated this therapy by performing PMI on transgenic mice that have a high risk of developing breast cancer, simulating the unaffected breast of a breast cancer survivor. Lead shields were placed so that one side of each mouse was shielded from the radiation. As projected, a moderate dose of radiation reduced the breast cancer risk in the treated side by a factor of approximately three. The researchers are now planning to assess PMI in a clinical trial.

If PMI demonstrates itself to be effective in patients, it could be used as an adjunct to tamoxifen or aromatase inhibitors for women with estrogen receptor-positive tumors and as a standalone therapy for those with estrogen-receptor negative tumors, who do not benefit from drug therapy. PMI, in ether instance, could be performed simultaneously with radiotherapy of the affected breast.

PMI could have a considerable clinical impact. At present, there are more than 2.6 million breast cancer survivors in the United States according to the American Cancer Society. “About 160,000 of these women are likely to develop cancer in their other breast,” said Dr. Brenner. “If PMI does, in fact, reduce the incidence of cancer by three-fold, as suggested by our results, about 100,000 cases of breast cancer could be prevented. Whether PMI would work for women with BRACA1 or BRACA2 mutations, which greatly increase one’s risk for breast and/or ovarian cancer, is another story. We don’t know that. Our next mouse study will look at the effects of PMI in BRACA1 mice.”

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