Breast Cancer - Background
Breast cancer is the most frequent malignant disease of women in the Western countries. It affects 350,000 women each year within the EU and US. Thus, every eighth woman gets breast cancer during her lifetime. Risk factors for the development of this disease include age and lifetime exposure to unopposed estrogen (early menarche, late menopause, late first pregnancy, prolonged use of estrogen-based oral contraceptives). Other environmental factors, such as diet, alcohol intake and obesity, have also been suspected to contribute to an increased risk [1].
About 5% of all cases are caused by inherited mutations, in the majority of the cases mutations of the tumor suppressor genes BRCA1 or BRCA2 are found, but other, less penetrant, genes may contribute to cases of hereditary breast cancer [2].
Treatment
Breast cancer treatment usually includes surgical removement of the primary tumor, followed by a so-called adjuvant therapy to eliminate metastases and microscopic remnants of the primary tumor. Such treatment my involve radiation therapy, cytotoxic chemotherapy and removement of lymph nodes. About two thirds of breast cancers express the estrogen receptor. These tumors can be treated by selective estrogen response modulators, such as Tamoxifen, which disrupt the hormone-dependent signaling and thus inhibit growth of tumor cells. Tamoxifen is also used for prevention in high risk patients [3].
HER-2
HER-2 (also called ERBB2, p185 or HER-2/neu for its homology to the rat neu oncogene) is a cell surface protein belonging to the epidermal growth factor (EGF) receptor family. HER-2 is present in low concentrations on all epidermal cell types, but is overexpressed in 30-40% of all breast cancers. This overexpression leads to the continuous generation of a growth signal inside the cell [4].
HER-2 overexpression significantly correlates with reduced survival of breast cancer patients. Moreover, it has been shown to confer lack of response to endocrine therapy or chemotherapy [5]. To overcome these difficulties, a monoclonal anti-HER2 antibody, Trastuzumab or Herceptin®, has been developed. Trastuzumab disrupts the growth signal generation of HER-2. It is successfully used in combination with chemotherapy or Tamoxifen [6].
A more extended review on recent developments in breast cancer treatment is found in [7].
References
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McPherson K., Steel C.M., Dixon J.M.:
ABC of breast diseases. Breast cancer epidemiology, risk factors, and genetics.
Br. Med. J. 321, 624-628 (2000). [Full text] -
Nathanson K.N., Wooster R., Weber B.L.:
Breast cancer genetics: What we know and what we need.
Nat. Med. 7(5), 552-556 (2001). [PubMed] -
Hortobagyi G.N.:
Developments in chemotherapy of breast cancer.
Cancer 88, 3073-3079 (2000). [Abstract] -
Klapper L.N., Kirschbaum M.H., Sela M., Yarden Y.:
Biochemical and clinical implications of the ErbB/HER signaling network of growth factor receptors.
Adv. Cancer Res. 77, 25-79 (2000). [PubMed] -
Slamon, D.J., Clark G.M., Wong S.G., Levin W.J., Ullrich A., McGuire W.L.:
Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene.
Science 235, 177-182 (1987). [PubMed] -
Slamon D.J., Leyland-Jones B., Shak S., Fuchs H., Paton V., Bajamonde A., Fleming T., Eiermann W.,
Wolter J., Pegram M., Baselga J., Norton L.:
Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2.
N. Engl. J. Med. 344, 783-792 (2001). [Abstract] -
Bange J., Zwick E., Ullrich A.:
Molecular targets for breast cancer therapy and prevention.
Nat Med 7(5), 548-552 (2001). [PubMed]
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