Research into the causes, prevention, and treatment of breast cancer 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. Scientists are also exploring how common gene variations may affect breast cancer risk. Each gene variant has only a modest effect in risk (10 to 20%), but when taken together they may potentially have a large impact.
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) like 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.
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.
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 outlook 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 outlook. 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. Right now, it is not being used as much as IHC or FISH.
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 that is still being studied to see if it will be useful in finding breast cancers. Some radiologists believe it may helpful 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 outside of a clinical trial.
Treatment
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
The number of women with breast cancer choosing breast conservation therapy has been steadily increasing, but 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,
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).
Large studies are being done to determine if these techniques are as effective as standard radiation in helping prevent cancer recurrences.
New chemotherapy drugs
Advanced breast cancers are often hard to treat, so researchers are always looking for newer drugs.
Erubulin (Halaven™) is a new drug for breast cancer that comes from the sea sponge. It works in a way that is similar to the taxanes (like docetaxel/Taxotere and paclitaxel/Taxol). It has been shown to help women with advanced breast cancer who have already been treated with both a taxane and an anthracycline (such as doxorubicin/Adriamycin and epirubicin/Ellence). In a clinical trial, women (who had been previously treated with those drugs) who were given erubulin lived longer than those treated with other chemo drugs. Common side effects of this drug include low blood counts, fatigue (tiredness), hair loss, nausea, and constipation. The drug also can cause nerve damage (neuropathy), leading to problems like numbness, tingling, or even pain in the hands and feet. Erubulin is given as an injection into a vein.
A drug class has been developed that targets cancers caused by BRCA mutations. This class of drugs is called PARP inhibitors and they have shown promise in clinical trials 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: There are 2 drugs approved for use that target excess HER2 protein, trastuzumab (Herceptin) and lapatinib (Tykerb). Studies continue to see which of these is best for treating early breast cancer. Other drugs that target the HER2 protein are being tested in clinical trials, including TDM-1, pertuzumab and neratinib. Researchers are also looking at using a vaccine to target the HER2 protein.
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 example of anti-angiogenesis drug. Although the value of bevacizumab for breast cancer is currently uncertain, clinical trials are currently testing several other anti-angiogenesis drugs.
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 targeted therapy drug that is approved to treat kidney cancer. In one study, letrozole plus everolimus 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, but 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).
Some studies have suggested that zoledronic acid may help other systemic therapies, like hormone treatment and chemo) work better. In one study, the women getting zolendric acid with chemo had their tumors shrink more than the women treated with chemo alone. In other studies, giving zoledronic acid reduced the risk of the cancer coming back. 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 (Xgeva™, Prolia™) inhibits (acts against) RANKL and can help protect bones. When given to patients with breast cancer that had spread to the bone, it helped prevent problems like fractures (breaks) better than zoledronic acid (Zometa). It also seems to help even after bisphosphonates stop working. Denosumab was recently approved to treat patients with cancer that has spread to bone. This drug is given as an injection under the skin every 4 weeks. Side effects include low blood levels of calcium and phosphate, as well as the jaw bone problem known as osteonecrosis of the jaw. Studies continue to see if giving denosumab to patients with early breast cancer can help prevent the disease from spreading.
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