> Emerging Areas in Chemotherapy, Hormone Therapy and Targeted Therapy
Research is ongoing to improve chemotherapy, hormone therapy and targeted therapy for breast cancer. New therapies are being studied in clinical trials, and the results of these studies will determine whether the therapies become part of standard care. After discussing the benefits and risks with your health care provider, you should consider joining clinical trials of new therapies.
For more information, visit the Clinical Trials section.
For information on promising, new treatments for metastatic breast cancer, visit the Emerging Areas in Metastatic Breast Cancer section.
Gene expression profiling
Gene expression profiling is a promising area in breast cancer treatment. This technology uses the genetic profiles of cancer tumors to predict which cancers may be more aggressive and, therefore, more likely to benefit from chemotherapy [20]. These tests do not show a genetic profile of your personal traits, but rather a profile of your tumor. Those whose tumor gene profiles show a high risk of recurrence may be more likely to choose chemotherapy, as they stand to benefit from it more than those whose profiles show a low risk of recurrence. People at low risk may choose to avoid chemotherapy altogether, choosing instead hormone therapy (for hormone receptor-positive cancer) or observation alone. At this time, the gene profiling test OncotypeDx can be used to help make chemotherapy treatment decisions in people with lymph node-negative, estrogen receptor-positive cancers [21]. Other genetic profiles and their use in guiding treatment plans are still under study [22].
Subtypes of breast cancer
There is a growing interest in understanding the molecular and genetic differences in breast cancers to guide the development of new targeted therapies. One current theory divides breast cancers into four molecular/genetic subtypes: luminal A, luminal B, triple negative/basal-like and HER2/neu-positive. At this time, subtypes are not used in clinical settings and are used only in the context of a research study. For more information on subtypes of breast cancer, visit the Diagnosis section.
CYP2D6 and tamoxifen
More and more, therapies are being tailored to treat each person’s breast cancer. Factors related to the tumor itself (for example, hormone receptor status) can guide treatment. And now there is early evidence that information about some genetic factors may prove helpful when choosing treatment for a person. One possible factor is the gene CYP2D6, which appears to affect how the body metabolizes (breaks down and uses) tamoxifen. Some people have a genetic variation (a certain form of the gene) that results in little or no CYP2D6 function. Others have a variation leading to higher than normal CYP2D6 function. Some small studies have looked at the CYP2D6 gene in postmenopausal women with breast cancer being treated with tamoxifen. These studies found that women with gene variations related to less CYP2D6 function had a higher risk of recurrence than women with genes related to normal or high CYP2D6 function [23-25].
Although some insurance companies cover genetic testing for CYP2D6, it is not a part of standard care now. While having high levels of CYP2D6 enzyme may show that a person has a better chance of responding to tamoxifen, having less of the enzyme does not mean that tamoxifen will not be effective. Also, the best way to test for the CYP2D6 variation is still not known since many different types of genetic variations may be involved. At this time, testing can be considered for postmenopausal women with hormone receptor-positive tumors who are trying to decide between tamoxifen and an aromatase inhibitor [25]. For premenopausal women with hormone receptor-positive breast cancer, tamoxifen is the only hormone therapy option.
Certain medicines can interfere with CYP2D6 enzyme function and should be avoided while taking tamoxifen [23]. For example, some antidepressants, such as fluoxetine (Prozac) and paroxetine (Paxil), can interact with CYP2D6 and may affect how tamoxifen works in the body [23]. Women are who are considering taking tamoxifen should talk with their health care provider about potential drug interactions. For more on tamoxifen, visit the Hormone Therapy section.
Bisphosphonates
Bone-strengthening therapy using bisphosphonates is an established treatment for women with bone metastases (more) [26]. Bisphosphonates are also used to help prevent bone density loss (osteoporosis) in women with a history of breast cancer [27].
New studies suggest that bisphosphonates may also play a role in breast cancer survival. A recent randomized clinical trial studied the use of zoledronate (Zometa) in premenopausal women with hormone receptor-positive breast cancer treated with a combination of ovarian suppression and hormone therapy (either tamoxifen or an aromatase inhibitor), and who did not have adjuvant chemotherapy. Findings from this study showed that zoledronate increased four-year disease-free survival among these premenopausal women [28]. Not all prior studies reached these conclusions and so further trials are needed to confirm these results. Therefore, at this time, bisphosphonates are not a part of standard therapy.
All these findings are preliminary and more research is needed. Bisphosphonate therapy for the prevention of bone metastases or the treatment of early breast cancer should only be given as part of a clinical trial. For more information, visit the Clinical Trials section.
Though rare, bisphosphonates appear to increase the risk of a serious jaw bone disorder called osteonecrosis. Having a dental exam prior to treatment with bisphosphonates may reduce this risk [29].
PARP inhibitors
Poly(ADP-ribose) polymerase (PARP) inhibitors are a new class of drugs under study for many types of cancer, including breast cancer. PARP is an enzyme involved in DNA repair. Some chemotherapy drugs damage DNA. Adding a PARP inhibitor to these chemotherapy plans may lower the chances that cancer cells become resistant to the chemotherapy. This is most often a problem for those with metastatic breast cancer. PARP inhibitors are also being studied for the treatment breast cancers related to gene mutations such as BRCA1 and BRCA2 as well as triple negative breast cancers [130].
At this time, data on PARP inhibitors and the treatment of breast cancer are very limited. Although the results look promising, these drugs are in the early stages of study and are only offered in clinical trials.
Read comments on the potential uses of PARP inhibitors from our Chief Scientific Advisor, Dr. Eric Winer.
Other drugs
Other drugs, including capecitabine (Xeloda), are being studied to treat early breast cancer. Capecitabine is a chemotherapy drug currently used to treat metastatic breast cancer. It is now being studied for use in the treatment of early breast cancer in both the neoadjuvant and adjuvant setting [30].
High-dose chemotherapy/bone marrow transplant
High-dose chemotherapy (sometimes called bone marrow transplant) was an experimental therapy in which high doses of drugs were given to try and kill a large number of cancer cells. It was thought that the more intensive chemotherapy might kill cancer cells better than standard chemotherapy. Despite early hopes for this approach, randomized trials in the 1990s showed that high-dose chemotherapy was no more effective than standard dose chemotherapy in the treatment of breast cancer [31-35]. High-dose chemotherapy also has more serious side effects, such as liver, lung and bone marrow problems. And it was found to be fatal in about six percent of people [35]. At this time, high-dose chemotherapy is not a part of standard treatment of breast cancer.
Updated 10/16/09
