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Thursday, February 6, 2014

Irradiating the cancer-free breast

Today, about three quarters of the women who have been diagnosed with breast cancer will live at least another fifteen years. Considering that up to one in every eight women will eventually develop breast cancer, that’s an outstanding achievement, and a real credit to the hard-working doctors and researchers studying the disease.
Unfortunately, about one in six women who live twenty years past their original diagnosis will develop cancer in the second, initially unaffected breast. For this reason, some women choose to have both breasts removed as a prophylactic measure. There are also drug therapies (tamoxifen or aromatase inhibitors for estrogen-receptor positive tumors) that can reduce the risk of secondary cancer, but they can have severe side affects are not effective for all types of cancer.
Columbia University Medical Center researchers led by Igor Shuryak decided to see if they could improve the odds by irradiating the noncancerous breast. This could be particularly important for women with estrogen-receptor negative tumors, and could be used in conjunction with drug therapies for other women.
Of course, as the following graphic shows, finding the right dose of radiation is critical, especially since any amount of radiation can trigger the development of new tumors. Too little or too much radiation will create more new tumors than it kills. The idea is to hit the sweet spot where the radiation kills all the pre-malignant cells that are already hiding in the non-symptomatic breast without inducing new tumors to form. 


Figure 1 Schematic of radiation dose-effects on breast-cancer risk in the contralateral breast of breast cancer patients.
The overall cancer risk is determined by a balance between killing of pre-existing pre-malignant cell clones vs. induction of new pre-malignant cell clones by radiation. The hypothesis underlying the present work is that there is a dose “window” at intermediate doses where killing of pre-existing pre-malignant clones dominates, thus reducing overall cancer risks.
doi:10.1371/journal.pone.0085795.g001
The scientists tested their radiation idea on mice, and found that it worked as expected. At the right dosage of radiation, there were three times fewer new breast tumors in the originally unaffected breast tissue, a significant improvement.
These results are extremely preliminary, but promising enough to start clinical trials on women. As noted above, it will be essential to find the right dose of radiation, and that may well depend on a number of factors, including the age of the woman and the type of cancer she had in her first breast. If this therapy proves to be effective, it may become standard to irradiate the second breast at the time the initial cancer is treated.
I have to say that I love the fact that we’re now thinking, ‘we’d better deal with this problem some of these long term breast cancer survivors are having.’ That says a lot about the state of cancer treatment.

Igor Shuryak, Lubomir B. Smilenov, Norman J. Kleiman, & David J. Brenner (2013). Potential Reduction of Contralateral Second Breast-Cancer Risks by Prophylactic Mammary Irradiation: Validation in a Breast-Cancer-Prone Mouse Model PLoS ONE DOI: 10.1371/journal.pone.0085795.