A report on Tamoxifen, Breast cancer, HER2/neu and Endometrial cancer

Tamoxifen, sold under the brand name Nolvadex among others, is a selective estrogen receptor modulator used to prevent breast cancer in women and treat breast cancer in women and men.

Amplification or over-expression of this oncogene has been shown to play an important role in the development and progression of certain aggressive types of breast cancer.

The medications tamoxifen or raloxifene may be used in an effort to prevent breast cancer in those who are at high risk of developing it.

Tamoxifen increases the risk of postmenopausal bleeding, endometrial polyps, hyperplasia, and endometrial cancer; using tamoxifen with an intrauterine system releasing levonorgestrel might increase vaginal bleeding after 1 to 2 years, but reduces somewhat endometrial polyps and hyperplasia, but not necessarily endometrial cancer.

Over-expression is also known to occur in ovarian, stomach, adenocarcinoma of the lung and aggressive forms of uterine cancer, such as uterine serous endometrial carcinoma, e.g. HER2 is over-expressed in approximately 7-34% of patients with gastric cancer and in 30% of salivary duct carcinomas.

Risk factors for endometrial cancer include obesity, insulin resistance and diabetes mellitus, breast cancer, use of tamoxifen, never having had a child, late menopause, high levels of estrogen, and increasing age.

Normally, estradiol and tamoxifen acting through the estrogen receptor down-regulate the expression of HER2.

Tamoxifen needs to block growth factor proteins such as ErbB2/HER2 because high levels of ErbB2 have been shown to occur in tamoxifen resistant cancers.

The Her2/neu oncogene, which indicates a poor prognosis, is expressed in 20% of endometrioid and serous carcinomas.

The selective estrogen receptor modulators reduce the risk of breast cancer but increase the risk of thromboembolism and endometrial cancer.

New or potentially new markers for breast cancer include BRCA1 and BRCA2 to identify people at high risk of developing breast cancer, HER-2, and SCD1, for predicting response to therapeutic regimens, and urokinase plasminogen activator, PA1-1 and SCD1 for assessing prognosis.