THE BIOLOGY OF BREAST CANCER

https://doi.org/10.1016/S0889-8588(05)70058-7Get rights and content
Under a Creative Commons license
open archive

Breast cancer is the most frequently diagnosed cancer among women in the western world, with approximately 180,000 new cases identified annually in the United States alone. It is currently a leading cause of cancer mortality in women, second only to lung cancer. The ultimate goal in studying breast cancer biology is to reduce mortality by identifying women at risk for the disease, predicting the prognosis of existing disease, and predicting response to different therapies. This article focuses primarily on the latter two.

Many of the current therapies for breast cancer are standard cytotoxic agents which are used to treat a variety of cancer types. However, one of the most widely used and effective agents in the battle against breast cancer is the anti-estrogen, tamoxifen. The efficacy of this comparatively nontoxic hormonal therapy is based on the specific biology of breast cancer. About two thirds of breast tumors express the estrogen receptor-α (ER); many of these tumors are dependent on estrogen for growth and survival and thus respond to treatment with anti-estrogens. Unfortunately, the remaining one third of breast cancers which are ER-negative at the time of diagnosis generally do not respond to endocrine therapy. Acquired resistance to tamoxifen in ER-positive tumors is also quite common. For these patients, there is clearly a need for new and better treatment options. It is hoped that improving the understanding of the basic biology of breast cancer will lead to the identification of new targets for the treatment or perhaps even to the prevention of breast cancer. Ideally, novel therapeutic or prophylactic agents would specifically target critical biological pathways in breast tumor cells.

During the process of breast tumorigenesis, mammary cells undergo numerous genotypic and phenotypic changes that allow the cells to bypass the normal controls of tissue homeostasis. Breast tumorigenesis requires a variety of genetic changes, such as activation or amplification of oncogenes or loss of tumor suppressor genes. Progression of the tumor to an aggressive, metastatic cancer depends on additional changes that permit invasion, migration, angiogenesis, and evasion of the immune system. Changes that promote genetic instability may also play a critical role in breast tumor progression, especially given the recent discovery that the protein products of the familial breast cancer genes, BRCA1 and BRCA2, associate with the DNA repair machinery of the cell. Many sporadic breast cancers also show altered expression of these genes. Although all these topics are of critical importance, they are beyond the scope of this article and are well reviewed elsewhere.7, 9, 22, 26, 27, 34, 74

This article focuses on the hormonal (endocrine, paracrine, and autocrine) regulation of breast development and the way that abrogations in those pathways may contribute to breast tumorigenesis by promoting inappropriate growth and survival of breast epithelial cells. Special attention is paid to how the pathways relate to or interact with estrogen signaling, because anti-estrogens have already proven themselves to be effective in the prevention and therapy of some breast cancers. Determining whether other hormonal pathways may play a role in inherent or acquired resistance to tamoxifen could lead to novel therapies that could be used either in combination with tamoxifen or after failure of tamoxifen treatment.

Cited by (0)

Address reprint requests to Nancy E. Davidson, MD, Oncology Center, The Johns Hopkins University School of Medicine, 422 N. Bond Street, Baltimore, MD 21231

Part of this work was supported by the National Cancer Institute, the United States Army Research and Materiel Command, and the Susan G. Komen Breast Cancer Foundation.

*

Oncology Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland