Functional Genetic Tests for Breast Cancer Diagnosis

描述（由申请人提供）：乳腺癌是美国女性中最常见的癌症，占女性人口的12%，是55岁以下女性癌症死亡的主要原因。目前的乳腺癌治疗通常包括手术切除肿瘤，然后是放疗或化疗，试图消除手术后残留的任何肿瘤细胞。大约50-70%的乳腺癌被归类为雌激素受体（ER）阳性，这些患者接受他莫昔芬或相关药物雷洛昔芬的治疗。他莫昔芬是一种选择性雌激素受体调节剂（SERM），可抑制雌激素受体阳性、雌二醇依赖的乳腺癌细胞的生长，已被明确证明是一种有效的术后辅助药物，可预防或延缓癌症缓解。

DESCRIPTION (provided by applicant): Breast cancer is the most common form of cancer in women in the U.S., occurring in 12% of the female population, and is the leading cause of cancer deaths in women under age 55. Current breast cancer therapy typically involves surgical removal of the tumor, followed by radiation or chemotherapy in an attempt to eliminate any tumor cells remaining after surgery. Approximately 50-70% of breast cancers are classified as estrogen receptor alpha (ER) positive, and these patients are treated with tamoxifen, or the related drug raloxifene. Tamoxifen is a selective estrogen receptor modulator (SERM) that inhibits the growth of estrogen receptor-positive, estradiol-dependent breast cancer cells and has been clearly demonstrated to be an effective post-surgery adjuvant to prevent or delay cancer remission. Because of the effectiveness and low toxicity of tamoxifen, essentially all breast cancers are currently tested for ER status. The current standard diagnostic tests are immunohistochemical (IHC) assays, and approximately 200,000 IHC tests are performed annually in the US on breast tumor biopsies. There is considerable variability of assay conditions and reagents between testing labs, as well as different staining cutoffs used in reporting ER positive status. More importantly, these assays merely measure the presence of the protein. A large number of mutations and splice variants of the ER have been observed in breast tumors, and many of these alterations affect protein function. Loss of function, constitutively active (estradiol independent), increased hormone responsiveness and altered cofactor affinity has all been observed. During Phase I research, functional genetic tests of ER status will be developed that are more quantitative and informative than current IHC assays. With these tests, the responsiveness of the tumor specific ER to estradiol, or other hormones, can be measured and, furthermore, the response of individual ER variants to cofactors can be determined. The increased information generated with these new tests will facilitate prescribing the most appropriate (hormonal) therapy for the particular breast cancer. These improved diagnostics should increase the effectiveness of both currently available therapeutics and those developed in the future by matching ER functional status of the breast cancer to available therapeutic compounds.