New findings are showing progress in hormonal and targeted breast cancer therapies.
Advances in hormonal and biological therapies and optimized chemotherapy dosing for breast cancer will help doctors better treat early-stage breast cancer and breast cancer that has spread to other parts of the body.

More than 2 million women living in the U.S. have been treated for or are living with breast cancer, and more than 40,000 women are expected to die from the disease in 2006. Though breast cancer death rates are declining -- mostly due to earlier diagnosis -- the disease remains the second leading cause of cancer death in women (after lung cancer).

Depending on the characteristics of the tumor, treatment for early-stage breast cancer can include surgery or radiation and may also include the use of hormonal therapy, chemotherapy, or biological ("targeted") therapies. For metastatic breast cancer, or cancer that has spread to other parts of the body, therapies that affect the entire body (systemic therapies) are used, such as hormonal therapy, chemotherapy, or biological therapies. Researchers are focusing on the best way to use these treatments to gain the most favorable results with the least amount of side effects and they are making headway. Experts presented their findings at the 2005 San Antonio Breast Cancer Symposium.

Advances in Hormonal Therapy for Postmenopausal Women

Tamoxifen has been available for the treatment of early-stage breast cancer since the 1980s; but, more recently, a new class of drugs called aromatase inhibitors has been found to produce better results when compared directly with tamoxifen. Aromatase inhibitors, indicated for use in postmenopausal women, act by blocking the formation of estrogen, which fuels the growth of "hormone receptor-positive" breast cancers.

The three aromatase inhibitors approved in the U.S. include Femara, Aromasin, and Arimidex.

Several studies are under way to find out the best strategy for using these agents in patients who have already received tamoxifen. One study presented at the breast cancer symposium reported increased disease-free survival when patients received two to four years of Femara instead of a placebo (sugar pill) after receiving five years of tamoxifen. In particular, patients who had disease that had spread to their lymph nodes seemed to show the greatest benefit from continued Femara use.

Likewise, a study comparing Femara to placebo suggested that patients who took a placebo following five years of tamoxifen therapy and then chose to switch to Femara experienced significantly longer survival -- both disease-free and overall -- than did patients who continued taking placebo. In other words, these results suggest that there is still risk of recurrence after finishing a five-year course of tamoxifen, but that benefit may still be gained from taking Femara even when there is a delay between its initiation and ending tamoxifen.

Positive results have also been demonstrated with Arimidex, another aromatase inhibitor, in the treatment of early-stage breast cancer. One study found that switching to Arimidex after two to three years of tamoxifen was linked to better survival without disease recurrence after five years compared with staying on tamoxifen for five years.

Similar findings have been reported for Aromasin.

Together, these findings help to confirm that aromatase inhibitors provide significant benefit to patients with early-stage breast cancer.

"I think that the message that we should get from these and other recent studies is that tamoxifen has prevented thousands of recurrences and has saved thousands of lives," says Henning Mouridsen, MD, with the Copenhagen University Hospital in Denmark. "But the advent of the new aromatase inhibitors is going to further improve the prognosis of postmenopausal patients with estrogen receptor-positive tumors."

Targeted Cancer Treatments

Perhaps the most important breakthrough in cancer treatment over the past few years has been the introduction of so-called "targeted" therapies. Rather than the sledgehammer effect achieved by traditional therapies, the newer targeted therapies are designed to home in on cancer cells like a missile while leaving the healthy cells untouched. As a result, these agents lack many of the severe side effects associated with chemotherapy.

Herceptin, an effective targeted therapy for breast cancer, attaches to a protein on the surface of breast cancer cells called HER2 that transmits growth-stimulating signals to cells. By blocking the actions of HER2, Herceptin slows or stops the growth of tumor cells. Herceptin is effective in tumors that express large amounts of the HER2 protein (described as HER2-positive), which is the case in about 25% of patients.

Results from several trials of Herceptin in early-stage breast cancer have confirmed the striking effectiveness of this agent when used with or after chemotherapy. However, the results are preliminary, and further studies are needed to determine the best way to combine Herceptin with chemotherapy, how long to give it, and which patients might benefit the most.

At the breast cancer meeting, Dennis Slamon, MD, presented results from a large international trial that evaluated three treatment regimens, two of which contained Herceptin. Both of the Herceptin-containing treatments were more effective in reducing disease recurrence than the non-Herceptin-containing regimen. However, an increased risk of heart problems was seen in both Herceptin-containing groups. Adriamycin, a chemotherapy agent used in one of the Herceptin containing treatments, has also been linked to heart-related side effects -- making researchers particularly cautious about combining Adriamycin with Herceptin. Therefore, it was encouraging to see that both of the Herceptin-containing regimens -- one containing Adriamycin and the other not -- were effective.

This study also identified certain genetic changes in breast tumors that may indicate increased susceptibility of the tumor -- meaning a better response -- to Adriamycin treatment. In patients with these types of tumors (about 30% of the patients tested), researchers suggested that the added risk of heart problems from Herceptin and Adriamycin might be worthwhile given the superior treatment effect, although these data need further confirmation.

One question that remains unanswered with regard to Herceptin is how long patients should keep taking the drug. Given the high cost and the potential for rare but serious heart side effects, it is important to know if patients would also benefit from a shorter course of the therapy. An intriguing study presented at the meeting found that Herceptin given for only nine weeks alongside a chemotherapy regimen was also able to decrease breast cancer recurrence. The tentative conclusion of the study indicated that short-term use of Herceptin appears to be effective and may be better tolerated than a longer one-year regimen.

Advances in hormonal and biological therapies and optimized chemotherapy dosing for breast cancer will help doctors better treat early-stage breast cancer and breast cancer that has spread to other parts of the body.

More than 2 million women living in the U.S. have been treated for or are living with breast cancer, and more than 40,000 women are expected to die from the disease in 2006. Though breast cancer death rates are declining -- mostly due to earlier diagnosis -- the disease remains the second leading cause of cancer death in women (after lung cancer).

Depending on the characteristics of the tumor, treatment for early-stage breast cancer can include surgery or radiation and may also include the use of hormonal therapy, chemotherapy, or biological ("targeted") therapies. For metastatic breast cancer, or cancer that has spread to other parts of the body, therapies that affect the entire body (systemic therapies) are used, such as hormonal therapy, chemotherapy, or biological therapies. Researchers are focusing on the best way to use these treatments to gain the most favorable results with the least amount of side effects and they are making headway. Experts presented their findings at the 2005 San Antonio Breast Cancer Symposium.

Advances in Hormonal Therapy for Postmenopausal Women

Tamoxifen has been available for the treatment of early-stage breast cancer since the 1980s; but, more recently, a new class of drugs called aromatase inhibitors has been found to produce better results when compared directly with tamoxifen. Aromatase inhibitors, indicated for use in postmenopausal women, act by blocking the formation of estrogen, which fuels the growth of "hormone receptor-positive" breast cancers.

The three aromatase inhibitors approved in the U.S. include Femara, Aromasin, and Arimidex.

Several studies are under way to find out the best strategy for using these agents in patients who have already received tamoxifen. One study presented at the breast cancer symposium reported increased disease-free survival when patients received two to four years of Femara instead of a placebo (sugar pill) after receiving five years of tamoxifen. In particular, patients who had disease that had spread to their lymph nodes seemed to show the greatest benefit from continued Femara use.

Likewise, a study comparing Femara to placebo suggested that patients who took a placebo following five years of tamoxifen therapy and then chose to switch to Femara experienced significantly longer survival -- both disease-free and overall -- than did patients who continued taking placebo. In other words, these results suggest that there is still risk of recurrence after finishing a five-year course of tamoxifen, but that benefit may still be gained from taking Femara even when there is a delay between its initiation and ending tamoxifen.

Positive results have also been demonstrated with Arimidex, another aromatase inhibitor, in the treatment of early-stage breast cancer. One study found that switching to Arimidex after two to three years of tamoxifen was linked to better survival without disease recurrence after five years compared with staying on tamoxifen for five years.

Similar findings have been reported for Aromasin.

Together, these findings help to confirm that aromatase inhibitors provide significant benefit to patients with early-stage breast cancer.

"I think that the message that we should get from these and other recent studies is that tamoxifen has prevented thousands of recurrences and has saved thousands of lives," says Henning Mouridsen, MD, with the Copenhagen University Hospital in Denmark. "But the advent of the new aromatase inhibitors is going to further improve the prognosis of postmenopausal patients with estrogen receptor-positive tumors."

Oral Chemotherapy Agents

A recently approved drug for kidney and stomach cancer is emerging as a potential treatment for breast cancer. Sutent, like Avastin, also stops the development of the tumor's blood supply but is given orally. This agent has demonstrated its effectiveness when used alone, without additional chemotherapy or hormonal therapy, in patients with previously treated metastatic breast cancer. In one study of 64 patients treated, 16% responded favorably.

Findings about an experimental oral drug, lapatinib, were also presented at the meeting. Like Herceptin, lapatinib targets HER2, but it also targets a related protein called EGFR, meaning that it could have a broader range of effectiveness or could be especially effective when added to Herceptin. One small study evaluated the combination of lapatinib and Herceptin in patients with metastatic breast cancer. The researchers reported no additional or unexpected side effects with the combination. Moreover, a good percentage of this difficult-to-treat population responded to the treatment.

"We are very excited about the results of all of these studies with these new agents, and they clearly demonstrate a role for this type of therapy in the treatment of metastatic breast cancer," Miller says. "We also expect an even greater benefit for these therapies when used for earlier-stage disease as opposed to the metastatic setting."