When Hormones Fuel Breast Cancer

Women who have been recently diagnosed with breast cancer are often overwhelmed with the amount of information they need to make informed decisions about their care. First there are decisions about surgery, and then decisions about follow-up treatment to help prevent recurrence. One highly important piece of information, which helps determine future treatment, is the cancer's hormone-receptor status. By testing for the estrogen-receptor and progesterone-receptor proteins, pathologists can determine whether a particular breast cancer uses hormones to stimulate its growth. Breast cancers that require hormones to grow are called hormone-receptor positive, and can be treated with different hormonal treatments that block or otherwise inhibit the circulation of estrogen in the body.
Below, Dr. D. Lawrence Wickerham, the associate chairman of the National Surgical Adjuvant Breast and Project (NSABP) and an associate professor of human oncology at Drexel University in Pittsburgh, discusses the significance of hormone receptor status.

How long have doctors understood the role of the female hormone estrogen in breast cancer?
The impact of estrogen on breast cancer has been known for over 100 years. One of the initial therapies for advanced breast cancer was removing the ovaries (which normally produce estrogen in premenopausal women). We knew that some women responded to the removal of those ovaries and others didn't. It wasn't until the late 60s and early 70s, when we were able to show in the laboratory that estrogen receptors were able to predict which women would respond to hormonal treatments and which wouldn't, that we could be more precise. But indeed, estrogens have been around for a long time as a factor in breast cancer.

Do you find that patients generally understand what's meant by their hormone receptor status?
It's important for patients to understand what is meant by their hormone receptor status. Some but not all breast cancers depend on estrogen, the normal female hormone estrogen, to continue to grow. We can identify which breast cancers need estrogen and which don't based on a simple laboratory test for the estrogen receptor, which is a protein, that is done in almost all breast cancers. Breast cancers that have the estrogen receptor tend to grow more slowly and have a good prognosis. They are also the breast cancers in which we use hormonal treatments.


What role does estrogen normally play in a woman's body?
Estrogen is present in almost all women, obviously, and is responsible for a variety of different activities at different times in the woman's life. It's responsible for developing the secondary sex characteristics at puberty, such as breast development. It's also responsible for, with ovulation, the ability to reproduce and bear children.

As you get older, estrogen is also important for maintaining general health, particularly bone health and cardiovascular health.
What percentage of breast cancers are hormone-receptor positive?
The percentage of breast cancers that are hormone-receptor positive varies a little bit depending on age. In premenopausal women, it's probably about 50 percent. In women after menopause, it can be as high as 70 percent.

What role does estrogen play in breast cancers that are estrogen-receptor positive?
In breast cancers that are estrogen-receptor positive, this protein, the estrogen receptor, combines with normal circulating estrogen in the woman's body. It's this combination of estrogen and estrogen receptor that is necessary for the breast cancer to continue to grow. If we interrupt that combination, that binding, we can actually stop the progress of breast cancer growth.

How is the receptor status actually determined?
The estrogen receptors are determined in a laboratory test that takes a small amount of the breast cancer tissue and examines whether or not this protein is present. Increasingly, in the United States, it's done through a technique called immunohistochemistry, which allows the estrogen receptor to be visualized under the microscope. It's either there or it's not, and then we can get a sense of how much of the receptor is present.


How and when is the hormone receptor status of breast cancer determined?
At the time of original biopsy of a breast cancer, we routinely test for hormonal receptor status. That information is rapidly available to not only women's doctors, but to the patients themselves and can be critical in making choices about the therapy. The test is often repeated at the time of complete surgery, but it's rare for there to be major differences in the test findings.

In the United States, laboratories do this every day. This test is not experimental, and hormone-receptor status is a critical piece of the information that we have relative to prognosis and treatment choices in breast cancer.

Are the tests accurate?
Like anything in medicine, there is the potential for inaccuracy. It's important that hormone-receptor evaluations be done in a laboratory that does such studies frequently. Those are easy to obtain in the United States, unlike some developing countries where it can be more difficult.

Do you only look for progesterone receptors as well as estrogen receptors?
There are a variety of hormone receptors. The estrogen receptor is probably the dominant one relative to choice of therapy. We also measure progesterone receptors fairly routinely, and that gives us additional insight into whether a tumor will respond to particular therapies.

We may occasionally see a patient who has an estrogen-receptor negative breast cancer, but has progesterone receptors present, and that is a possible circumstance where hormonal treatments could be still be used in someone who is estrogen-receptor negative.

What decisions are made once the hormone receptor status is known?
When hormone receptors are present in a particular cancer, the idea of hormonal treatment is discussed. For premenopausal women, the standard hormonal therapy, in this country at least, has been tamoxifen. It's a pill. It's given for five years and is a highly effective treatment for breast cancer. It's been around now for 25 or 30 years and has been studied in, quite literally, millions of women.

In postmenopausal women, the options are a little bit broader now. Tamoxifen is still an effective therapy, but we also have a newer class of treatments called aromatase inhibitors. Although aromatase inhibitors have been around for a long time, there is now a newer third generation of these agents that are very effective and better tolerated, and in head-to-head comparisons with tamoxifen, they are more effective and have fewer side effects.

There are three aromatase inhibitors that are now available in this country. They are all fairly similar. They have slightly different mechanisms of action, but are a relatively new addition to the armamentarium of breast cancer treatment.

What treatment options are available to a woman who has hormone-receptor negative breast cancer?
Options for a woman who is receptor negative are usually chemotherapies that can be combinations of chemotherapy or various sequences of chemotherapy over time. Even individuals who are receptor positive are potential candidates for chemotherapy, but those are usually done in combination with hormonal treatments.

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