One of the most important strategies for treating women with estrogen-positive breast cancer is to block the action of estrogen. In estrogen positive (ER+) breast cancers, the natural estrogen in the body attaches to the estrogen receptors on cancer cells and stimulates them to divide, which makes breast tumors grow.
Once the initial treatment of breast cancer is completed, (surgery, chemotherapy, radiation), it is usually recommended that patients with ER+ tumors undergo long-term treatment with drugs like tamoxifen, which blocks estrogen activity, and aromatase inhibitors – Aromasin, Arimidex and Femara – which block the synthesis of estrogen in fat tissue in the body. These estrogen-blocking drugs work well for most women, but unfortunately, not all women respond to them, and it is not unusual for tumors to develop resistance to these drugs.
We are now learning more about why estrogen-blocking drugs may not work all the time, and one of the mechanisms comes from a surprising source: cholesterol! Like most molecules in the body, cholesterol gets metabolically transformed into other molecules by various enzymes in our body. One of the molecules that is derived from cholesterol, and which is present in fairly high levels in the body, is 27-hydroxycholesterol (27-HC). This interesting molecule can attach to and actually stimulate estrogen receptors in the body. Patients with ER+ breast cancer have higher amounts of 27-HC in the normal tissue in their breasts than women who have not been diagnosed with ER+ breast cancer. And the amount of 27-HC in breast tumors is even higher. This is because the enzyme that converts cholesterol to 27-HC is found in high levels in some breast cancer cells, especially in higher-grade tumors (higher grade tumors tend to grow rapidly and spread faster than lower grade tumors), and also in immune cells called macrophages, that sometimes infiltrate breast tumors.
