Research into the causes, prevention, and treatment of breastcancer is under way in many medical centers throughout the world.

Causes of breast cancer

Studies continue to uncover lifestyle factors and habits that alter breast cancer risk. Ongoing studies are looking at the effect of exercise, weight gain or loss, and diet on breast cancer risk.

Studies on the best use of genetic testing for BRCA1 and BRCA2 mutations continue at a rapid pace. Other genes that contribute to breast cancer risk are also being identified. This will occur more rapidly now that the human genome has been sequenced.

Potential causes of breast cancer in the environment have also received more attention in recent years. While much of the science on this topic is still in its earliest stages, this is an area of active research.

A large, long-term study funded by the National Institute of Environmental Health Sciences (NIEHS) is now being done to help find the causes of breast cancer. Known as the Sister Study, it has enrolled 50,000 women who have sisters with breast cancer. This study will follow these women for at least 10 years and collect information about genes, lifestyle, and environmental factors that may cause breast cancer. An offshoot of the Sister Study, the Two Sister Study, is designed to look at possible causes of early onset breast cancer. To find out more about these studies, call 1-877-4-SISTER (1-877-474-7837) or visit the Sister Study Web site (www.sisterstudy.org).

Chemoprevention

Results of several studies suggest that selective estrogen-receptor modulators (SERMs) such as tamoxifen and raloxifene may lower breast cancer risk in women with certain breast cancer risk factors. But so far, many women are reluctant to take these medicines because they are concerned about possible side effects.

Newer studies are looking at whether aromatase inhibitors -- drugs such as anastrozole, letrozole, and exemestane -- can reduce the risk of developing breast cancer in post-menopausal women. These drugs are already being used as adjuvant hormone therapy to help prevent breast cancer recurrences, but none of them is approved for reducing breast cancer risk at this time.

Fenretinide, a retinoid, is also being studied as a way to reduce the risk of breast cancer (retinoids are drugs related to vitamin A). In a small study, this drug reduced breast cancer risk as much as tamoxifen. Other drugs are also being studied to reduce the risk of breast cancer.

For more information, see the American Cancer Society document, Medicines to Reduce Breast Cancer Risk.

New laboratory tests

Gene expression studies

One of the dilemmas with early-stage breast cancer is that doctors cannot always accurately predict which women have a higher risk of cancer coming back after treatment. That is why almost every woman, except for those with small tumors, receives some sort of adjuvant treatment after surgery. To try to better pick out who will need adjuvant therapy, researchers have looked at many aspects of breast cancers.

In recent years, scientists have been able to link certain patterns of genes with more aggressive cancers -- those that tend to come back and spread to distant sites. Some lab tests based on these findings, such as the Oncotype DX and MammaPrint tests, are already available, although doctors are still trying to determine the best way to use them. These tests are explained in the section "How is breast cancer diagnosed?" Other tests are being developed as well.

Classifying breast cancer

Research on patterns of gene expression has also suggested some newer ways of classifying breast cancers. The current types of breast cancer are based largely on how tumors look under a microscope. A newer classification, based on molecular features, may be better able to predict prognosis and response to several types of breast cancer treatment. The new research suggests there are 4 basic types of breast cancers:

Luminal A and luminal B types: The luminal types are estrogen receptor (ER)–positive, usually low grade, and tend to grow fairly slowly. The gene expression patterns of these cancers are similar to normal cells that line the breast ducts and glands (the lining of a duct or gland is called its lumen). Luminal A cancers have the best prognosis. Luminal B cancers generally grow somewhat faster than the luminal A cancers and their prognosis is not quite as good.

HER2 type: These cancers have extra copies of the HER2 gene and several other genes. They usually have a high-grade appearance under the microscope. These cancers tend to grow more quickly and have a worse prognosis, although they often can be treated successfully with targeted therapies such as trastuzumab (Herceptin) and lapatinib (Tykerb).

Basal type: Most of these cancers are of the so-called triple-negative type, that is, they lack estrogen or progesterone receptors and have normal amounts of HER2. The gene expression patterns of these cancers are similar to cells in the deeper basal layers of breast ducts and glands. This type is more common among women with BRCA1 gene mutations. For reasons that are not well understood, this cancer is also more common among younger and African-American women.

These are high-grade cancers that tend to grow quickly and have a poor prognosis. Hormone therapy and anti-HER2 therapies like trastuzumab and lapatinib are not effective against these cancers, although chemotherapy can be helpful. A great deal of research is being done to find better ways to treat these cancers.

It is hoped that these new breast cancer classifications might someday allow doctors to better tailor breast cancer treatments, but more research is needed in this area before this is possible.

Tests of HER2 status

Determining a breast cancer's HER2 status is important to get an idea of how aggressive the cancer might be and to find out if certain drugs that target HER2 can be used to treat the disease.

Two types of tests -- immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) -- are currently used to determine HER2 status. The FISH test is generally thought to be more accurate, but it also requires special equipment, which can make testing more expensive.

A newer type of test, known as chromogenic in situ hybridization (CISH), works similarly to FISH, by using small DNA probes to count the number of HER2 genes in breast cancer cells. But this test looks for color changes (not fluorescence) and doesn't require a special microscope, which may make it less expensive. Unlike other tests, it can be used on tissue samples that have been stored in the lab.

Some studies have suggested that another new test, which measures the amount of HER2 protein in cancer cells more precisely than current tests, may be better able to identify women who are likely to respond to HER2-targeted drugs such as trastuzumab (Herceptin).

Circulating tumor cells

Researchers have found that in many women with breast cancer, cells may break away from the tumor and enter the blood. These circulating tumor cells can be detected with sensitive lab tests. These tests are not yet available for general use, but they may eventually be helpful in determining whether treatment (such as chemotherapy) is working or in detecting cancer recurrence after treatment.

Newer imaging tests

Several newer imaging methods are now being studied for evaluating abnormalities that may be breast cancers.

Scintimammography (molecular breast imaging)

In scintimammography, a slightly radioactive tracer called technetium sestamibi is injected into a vein. The tracer attaches to breast cancer cells and is detected by a special camera.

This is a newer technique. Some radiologists believe it is sometimes useful in looking at suspicious areas found by regular mammograms, but its exact role remains unclear. Current research is aimed at improving the technology and evaluating its use in specific situations such as in the dense breasts of younger women. Some early studies have suggested that it may be almost as accurate as more expensive magnetic resonance imaging (MRI) scans. This test, however, will not replace your usual screening mammogram.

Tomosynthesis (3D mammography)

This technology is basically an extension of a digital mammogram. For this test, a woman lies face down on a table with a hole for the breast to hang through, and a machine takes x-rays as it rotates around the breast. Tomosynthesis allows the breast to be viewed as many thin slices, which can be combined into a 3-dimensional picture. It may allow doctors to detect smaller lesions or ones that would otherwise be hidden with standard mammograms. This technology is still considered experimental and is not yet available.

Several other experimental imaging methods, including thermal imaging (thermography) are discussed in the separate American Cancer Society document, Mammograms and Other Breast Imaging Procedures.

Treatment

Newer types of mastectomy

Newer approaches to mastectomy that try to give better looking results are now being studied.

One approach is the nipple-sparing mastectomy. This is similar to the skin-sparing mastectomy in that the nipple and areola are cut away when the breast tissue is removed, but in this approach the nipple and areola are scraped clean of breast tissue and examined by a pathologist. As long as there are no breast cancer cells found close to the nipple and areola, they are left in place.

Further studies of these techniques are needed to ensure they don't result in an excess risk of cancer developing or returning.

Oncoplastic surgery

Breast-conserving therapy (lumpectomy or partial mastectomy) can often be used for early-stage breast cancers. But in some women, it can result in breasts of different sizes and/or shapes. For larger tumors, it might not even be possible, and a mastectomy might be needed instead. Some doctors address this problem by combining cancer surgery and plastic surgery techniques, known as oncoplastic surgery. This typically involves reshaping the breast at the time of the initial breast-conserving surgery, and may mean operating on the other breast as well to make them more symmetrical. This approach is still fairly new, and not all doctors are comfortable with it.

Breast reconstruction surgery

Although the number of women with breast cancer choosing breast conservation therapy has been steadily increasing, there are some women who, for medical or personal reasons, choose mastectomy. Some of them also choose to have reconstructive surgery to restore the breast's appearance.

Technical advances in microvascular surgery (reattaching blood vessels) have made free-flap procedures an option for breast reconstruction. For more information on the types of reconstructive surgery now available, see the American Cancer Society document, Breast Reconstruction After Mastectomy.

For several years, concern over a possible link between breast implants and immune system diseases has discouraged some women from choosing implants as a method of breast reconstruction. Recent studies have found that although implants can cause some side effects (such as firm or hard scar tissue formation), women with implants do not have any greater risk for immune system diseases than women who have not had this surgery.

Similarly, the concern that breast implants increase the risk of breast cancer recurrence or formation of new cancers is not supported by current evidence.

Radiation therapy

For women who need radiation after breast-conserving surgery, newer techniques such as hypofractionated radiation or accelerated partial breast irradiation may be as effective while offering a more convenient way to receive it (as opposed to the standard daily radiation treatments that take several weeks to complete). These techniques are described in more detail in the section "How is breast cancer treated?"

Large studies are being done to determine if these techniques are as effective as standard radiation in helping prevent cancer recurrences.

New chemotherapy drugs

Because advanced breast cancers are often hard to treat, researchers are always looking for newer drugs.

A drug has been developed that targets cancers caused by BRCA mutations. It is called olaparib and it was successful in treating breast, ovarian, and prostate cancers that had spread and were resistant to other treatments. Further studies are underway to see if this drug can help patients without BRCA mutations.

Targeted therapies

Targeted therapies are a group of newer drugs that specifically take advantage of gene changes in cells that cause cancer.

Drugs that target HER2: Trastuzumab (Herceptin) is a monoclonal antibody (a man-made version of a specific immune system protein) used to treat women with breast cancer. It works by preventing the HER2 protein from promoting excessive growth of breast cancer cells and may also help the immune system fight the cancer.

Lapatinib (Tykerb) is a small-molecule targeted therapy pill, which was approved by the FDA for use in women with HER2-positive advanced breast cancer whose cancer is growing despite the use of trastuzumab. Newer studies are looking at using this drug instead of trastuzumab for early-stage breast cancer.

Other drugs that target the HER2 protein are being tested in clinical trials.

Anti-angiogenesis drugs: In order for cancers to grow, blood vessels must develop to nourish the cancer cells. This process is called angiogenesis. Looking at angiogenesis in breast cancer specimens can help predict prognosis. Some studies have found that breast cancers surrounded by many new, small blood vessels are likely to be more aggressive. More research is needed to confirm this.

Bevacizumab (Avastin) is an anti-angiogenesis drug that can be used in combination with the chemotherapy drug paclitaxel (Taxol) in patients with metastatic breast cancer.

Other new drugs are also being developed that may be useful in preventing new blood vessels from forming. Several of these drugs are now being tested in clinical trials.

Drugs that target EGFR: The epidermal growth factor receptor (EGFR) is another protein found in high amounts on the surfaces of some cancer cells. Some drugs that target EGFR, such as cetuximab (Erbitux) and erlotinib (Tarceva), are already used to treat other types of cancers, while other anti-EGFR drugs are still considered experimental. Studies are now under way to see if these drugs might be effective against breast cancers.

Other targeted drugs: Everolimus (Afinitor^®) is a new type of targeted therapy drug that was recently approved to treat kidney cancer. In one study, letrozole plus evirolimus worked better than letrozole alone in shrinking breast tumors before surgery. More studies using this drug are planned.

Many other potential targets for new breast cancer drugs have been identified in recent years. Drugs based on these targets are now being studied, although most are still in the early stages of clinical trials.

Bisphosphonates

Bisphosphonates are drugs that are used to help strengthen and reduce the risk of fractures in bones that have been weakened by metastatic breast cancer. Examples include pamidronate (Aredia) and zoledronic acid (Zometa).

A recent study suggested that when combined with hormone therapy to treat early-stage breast cancer, zoledronic acid may reduce the risk of cancer recurrence. More studies are needed to determine if bisphosphonates should become part of standard therapy for early- stage breast cancer.

Vitamin D

A recent study found that women with early-stage breast cancer who were vitamin D deficient were more likely to have their cancer recur in a distant part of the body and had a poorer outlook. More research is needed to confirm this finding, and it is not yet clear if taking vitamin D supplements would be helpful. Still, you may want to talk to your doctor about testing your vitamin D level to see if it is in the healthy range.

Denosumab

When cancer spreads to the bone, it causes increased levels of a substance called RANKL, which is important in bone metabolism. Higher levels stimulate cells called osteoclasts to destroy bone. A newer drug called denosumab inhibits (acts against) RANKL and can help protect bones. In early studies it seems to help even after bisphosphanates stop working. More studies are ongoing.

Last Medical Review: 09/18/2009
Last Revised: 09/18/2009