Selection of optimal adjuvant endocrine therapy for early-stage breast cancer

Abstract

Oophorectomy was found to cause regression of advanced breast cancer toward the end of the 19th century. Decades later, the discovery that estrogen plays a central role in this process eventually led to two important consequences: first, different modalities were developed to suppress or antagonize estrogen; and second, the ability to detect estrogen receptor in breast cancer tissue became a predictor of response to treatment--probably the best marker for response among all solid tumors. Tamoxifen, which works by competitively antagonizing hormonal receptors in breast cancer cells, has been for the past three decades the standard of care for adjuvant therapy for any woman with hormone receptor-positive early breast cancer, regardless of nodal status or menopausal setting. But as we strive to improve the utility of antagonizing or suppressing estrogen, new modalities are being developed. In the premenopausal setting, the advent of gonadotropin hormone-releasing hormone (also known as luteinizing hormone-releasing hormone) analogues has allowed for medical and reversible suppression of ovarian function. This method has already been proven as effective as chemotherapy in preventing recurrence, and ongoing trials are aiming to better define its role in the adjuvant setting. In the postmenopausal setting, aromatase inhibitors (AIs) have revolutionized the adjuvant treatment of hormone-responsive cancers of all stages. The current standard of care has come to include AIs, as an alternative, in sequence, of after 5 years of tamoxifen. Ongoing research continues to develop agents to overcome hormonal therapy resistance.

Medical Chemistry to Spy Cancer Stem Cells from Outside the Body

“…Although standard chemotherapy kills most cells in a tumor, cancer stem cells remain viable [29][30][31][32]. This model is consistent with some clinical observations.…”

Tumor dormancy of primary and secondary cancers

“…Estrogen, for example, can stimulate breast cancer cell proliferation and survival directly, but can also indirectly stimulate tumor growth by promoting tumor angiogenesis (60–63). Oophorectomy or pharmacologic strategies that reduce estrogen receptor signaling can promote regression of hormone receptor‐positive tumor cells (64–67). Endocrine therapy does not completely eliminate tumor cells but can produce long‐term remission when combined with other forms of therapy such as surgery.…”

In Vitro and In Vivo Effects of Xanthorrhizol on Human Breast Cancer MCF-7 Cells Treated With Tamoxifen

“…In breast tissue, tamoxifen acts as an estrogen antagonist and competitively inhibits estrogen binding to ERs, which blocks the actions of estrogen on breast cancer cells (6). Recent investigations have shown that tamoxifen promptly stimulates the activation of ERK1/2 in an ER-positive breast cancer cell line (MCF-7) (7), and this causes both cell-cycle arrest and apoptosis via an induction of signaling that leads to a modulation of the MAPK and mitochondria/caspase pathways in breast cancer cells (8).…”