Potential reduction of contralateral second breast-cancer risks by prophylactic mammary irradiation: validation in a breast-cancer-prone mouse model.
Potential reduction of contralateral second breast-cancer risks by prophylactic mammary irradiation: validation in a breast-cancer-prone mouse model.
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DOI：
10.1371/journal.pone.0085795
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Brenner DJ
中科院分区：
文献类型：
--
作者：
Shuryak I;Smilenov LB;Kleiman NJ;Brenner DJ
长期乳腺癌幸存者患对侧第二乳腺癌的风险很高（20岁时6人中有1人）。这种高风险与原发性乳腺癌诊断时对侧乳腺中存在多个癌前细胞克隆有关。机制分析表明，对侧乳房进行中等剂量的x射线照射可以杀死这些恶性前克隆，因此，在适当的预防性乳房照射（PMI）剂量下，乳腺癌幸存者患对侧乳腺癌的长期风险将大大降低。检验PMI剂量与恶性肿瘤高风险乳腺肿瘤风险之间的预测关系。我们使用MMTV-PyVT乳腺肿瘤易感小鼠来测试PMI概念。每只老鼠一侧的乳腺被x射线照射，而另一侧的乳腺则被屏蔽。未被屏蔽的乳腺分别接受0、4、8、12和16Gy剂量的4- gy剂量。在暴露于PMI设计的辐射剂量（12和16 Gy）的高危乳腺中，与暴露于极低辐射剂量的屏蔽腺体相比，在12 Gy时肿瘤发病率分别降低了2.2 （95% CI, 1.1-5.0）和16 Gy时的肿瘤发病率分别降低了3.1 （95% CI, 1.3-8.3）。与零剂量对照相比，暴露于pmi的乳腺也出现了相同的模式。PMI降低癌症风险的模式与机制预测一致。因此，对侧乳房PMI可能有望作为一种有空间针对性的保乳选择，以降低当前对侧第二乳腺癌的高风险。对于雌激素受体阳性的原发性肿瘤，PMI可能最好与系统给药的化学预防药物（如他莫昔芬或芳香酶抑制剂）联合使用，而对于雌激素受体阴性的肿瘤，PMI可能单独使用。
Long-term breast-cancer survivors have a highly elevated risk (1 in 6 at 20 years) of contralateral second breast cancer. This high risk is associated with the presence of multiple pre-malignant cell clones in the contralateral breast at the time of primary breast cancer diagnosis. Mechanistic analyses suggest that a moderate dose of X-rays to the contralateral breast can kill these pre-malignant clones such that, at an appropriate Prophylactic Mammary Irradiation (PMI) dose, the long-term contralateral breast cancer risk in breast cancer survivors would be considerably decreased. To test the predicted relationship between PMI dose and cancer risk in mammary glands that have a high risk of developing malignancies. We tested the PMI concept using MMTV-PyVT mammary-tumor-prone mice. Mammary glands on one side of each mouse were irradiated with X-rays, while those on the other side were shielded from radiation. The unshielded mammary glands received doses of 0, 4, 8, 12 and 16Gy in 4-Gy fractions. In high-risk mammary glands exposed to radiation doses designed for PMI (12 and 16 Gy), tumor incidence rates were respectively decreased by a factor of 2.2 (95% CI, 1.1-5.0) at 12 Gy, and a factor of 3.1 (95% CI, 1.3-8.3) at 16 Gy, compared to those in the shielded glands that were exposed to very low radiation doses. The same pattern was seen for PMI-exposed mammary glands relative to zero-dose controls. The pattern of cancer risk reduction by PMI was consistent with mechanistic predictions. Contralateral breast PMI may thus have promise as a spatially targeted breast-conserving option for reducing the current high risk of contralateral second breast cancers. For estrogen-receptor positive primary tumors, PMI might optimally be used concomitantly with systemically delivered chemopreventive drugs such as tamoxifen or aromatase inhibitors, while for estrogen-receptor negative tumors, PMI might be used alone.
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影响因子：
3.7
作者：
Arrington, Amanda K.;Jarosek, Stephanie L.;Tuttle, Todd M.
通讯作者：
Tuttle, Todd M.
DOI：
10.1002/mpo.1122
发表时间：
2001-05-01
期刊：
MEDICAL AND PEDIATRIC ONCOLOGY
影响因子：
--
作者：
Boice, JD
通讯作者：
Boice, JD
影响因子：
168.9
作者：
Davies, C.;Godwin, J.;Gray, R.;Clarke, M.;Darby, S.;McGale, P.;Wang, Y. C.;Peto, R.;Pan, H. C.;Cutter, D.;Taylor, C.;Ingle, J.
通讯作者：
Ingle, J.
影响因子：
64.8
作者：
Asselin-Labat, Marie-Liesse;Vaillant, Francois;Visvader, Jane E.
通讯作者：
Visvader, Jane E.
影响因子：
5.3
作者：
GUY, CT;CARDIFF, RD;MULLER, WJ
通讯作者：
MULLER, WJ