Progesterone Gives Clues to Breast Cancer Behavior & Tamoxifen Resistance

Progesterone Receptor Gives Clues to Breast Cancer Behavior and Tamoxifen Resistance

According to a study published in the Journal of the National Cancer Institute, breast cancers that are estrogen receptor-positive and progesterone receptor-negative (ER+/PR-) are more aggressive and more likely to have high levels of specific growth factor receptors than breast cancers that are estrogen receptor-positive and progesterone receptor-positive (ER+/PR+); the altered growth factor receptor levels may contribute to tamoxifen resistance.

When breast cancer is diagnosed, tests are performed to further describe the cancer. One of these tests determines if cancer development was supported by the hormones estrogen and progesterone. Determining whether the cancer cells have receptors for estrogen and progesterone helps determine whether hormonal therapies, such as tamoxifen, are likely to be effective against the cancer. Breast cancers that are ER+/PR- have been reported to be less responsive to tamoxifen than cancers that are ER+/PR+.

Tests may also be performed to determine whether cancer cells have altered levels of specific growth factor receptors that play a role in the growth and replication of cancer cells. Two of these growth factor receptors are HER1 and HER2. Altered levels of HER1 and HER2 may indicate more aggressive cancer and may also influence progesterone receptor levels and responsiveness to tamoxifen.

In order to explore the relationships among progesterone receptor status, HER1 and HER2 status, tumor characteristics, and response to tamoxifen, researchers in Texas evaluated 31,415 patients with ER+/PR+ breast cancer and 13,404 patients with ER+/PR- breast cancer. Cancers that were ER+/PR- tended to be more aggressive and to have higher levels of HER1 and HER2 than cancers that were ER+/PR+. Among women with ER+/PR- cancers, elevated levels of HER1 and HER2 were associated with worse survival after treatment with tamoxifen. Among women with ER+/PR+ cancers, level of HER1 and HER2 did not influence survival after tamoxifen.

The researchers conclude that ER+/PR- breast cancers are more aggressive than ER+/PR+ breast cancers and may have altered growth factor activity that contributes to tamoxifen resistance. If this is confirmed, the researchers suggest that future studies of ER+/PR- breast cancer should evaluate the effect of therapy with both tamoxifen and a drug that targets growth factor activity. The researchers also raise the possibility that response to drugs that target HER2 may differ by PR status.

Reference: Arpino G, Weiss H, Lee AV et al. Estrogen receptor-positive, progesterone receptor-negative breast cancer: association with growth factor receptor expression and tamoxifen resistance. Journal of the National Cancer Institute. 2005;97:1254-1261.

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