Treatment for breast cancer has changed dramatically in the last twenty years; the discovery that cancers respond to stimulation of certain cellular receptors has led to the development of new therapies that prevent the recurrence of breast cancer and improve survival.
How Do the Receptors on Cells Function?
Many cells have receptors on their surfaces that help them perform their daily tasks. These receptors are designed to be “switched on” when they come in contact with specific molecules in their environment.
For example, immune cells carry receptors that attach to cytokines or antigens from infectious organisms; when these receptors are stimulated, the cells are activated to respond to external threats.
Muscle and fat cells possess receptors that respond to insulin; when insulin molecules come in contact with these receptors, the cells absorb and store glucose.
Other tissues (e.g., bone, ovary, uterus, and breast) carry receptors that respond to hormones like estrogen and progesterone. These receptors are important for directing cellular growth and division.
How Receptors Influence Cancer Growth
While some cancerous cells lose their receptors—or their receptors mutate—others retain their original “switches.” Cancers that still possess their original receptors tend to be “well-differentiated”—that is, they are similar in many ways to the normal tissues from which they arose.
When the receptors on these cells are switched to the "on" position, the cells may grow more quickly.
Cancers that have lost their receptors or that express abnormal ones tend to be “poorly differentiated.” Another word for poorly-differentiated cancers is “anaplastic.” Even though these tumors no longer possess "on" switches, their anaplastic nature often makes them very aggressive and likely to spread (metastasize) quickly.
Specific Receptors in Breast Cancers, and What They Mean
Scientists have learned that if a receptor that stimulates a cell to grow can be blocked, cellular growth and division can be slowed. This has obvious implications in the treatment of breast cancer.
Estrogen and Progesterone Receptors
- About 75% of breast cancers possess estrogen and progesterone receptors when first diagnosed. These cancers respond to hormones that are circulating in the bloodstream: More circulating estrogen usually means faster cancer growth.
- Breast cancers that have estrogen and progesterone receptors are generally easier to treat and carry a better prognosis. This is because many of these cancers are still relatively well-differentiated, and drugs can be used to block the receptors and slow the cancer’s growth (or prevent the recurrence of cancer once it has been treated).
- Tamoxifen, a selective estrogen receptor modulator (SERM), was the first drug approved in the United States for blocking estrogen receptors in breast cancers. Other SERMs have since been developed.
Human Epidermal Growth Factor Receptor-2 (HER-2)
- Another receptor in breast cancer cells, called HER-2 (human epidermal growth factor receptor-2), has also been shown to stimulate cellular growth and division. This receptor, too, can be blocked with drugs.
- About 25 – 30% of breast cancers test positive for HER-2; they tend to be more aggressive and are less likely to respond to hormone-blocking therapies. However, they can be treated with HER-2 blockers (Herceptin or Tykerb), and they respond to specific combinations of chemotherapy.
Receptor Status and Prognosis
While every breast cancer patient (regardless of receptor status) must be treated on an individual basis, there are some general principles that apply:
- Women with estrogen and/or progesterone receptor-positive tumors respond to hormonal therapy (more accurately, hormone blocking therapy) more readily than those whose cancers are receptor-negative.
- If a cancer is both estrogen and progesterone receptor positive (ER+ and PR+), the chance of response to hormonal therapy (e.g., with Tamoxifen, etc.) is around 70%.
- If a cancer has only one kind of hormone receptor (ER+/PR- or ER-/PR+), the chance of a response to hormonal therapy is about 33%.
- If a cancer has neither estrogen nor progesterone receptors (or if the status is unknown), the chance of responding to hormonal therapy is 10% or less.
- So-called “triple-negative” tumors (negative for ER, PR, and HER-2) tend to be more aggressive—perhaps because they are poorly-differentiated—but even some of these tumors are “low-grade” (i.e., not likely to have spread at the time of diagnosis). (American Roentgen Ray Society, April 11, 2008. A diagnosis of triple-negative breast cancer doesn't always mean cancer spread)
Breast cancers are not all alike. The types and numbers of receptors on a cancer’s cells help to guide therapy and predict a patient’s prognosis. As new agents are developed—and as new receptors are identified—even more patients will be cured of this disease.
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