Combination therapy, utilizing Aromatase Inhibitors (AIs) alongside targeted agents, has emerged as one of the promising approaches in the treatment of hormone-sensitive breast cancer in postmenopausal women. This is because endocrine or hormonal therapy was found effective in hormone-sensitive breast cancer for a considerable period of time; however, despite the effectiveness of endocrine therapy, some tumors develop resistance over time, posing challenges in patient management.
Understanding the reasons behind these challenges has led scientists to consider combining AIs with other targeted medications for effective treatment. This article explores all the combination therapies with AIs and targeted agents found effective in clinical trials for postmenopausal breast cancer.
Rationale for Combination Therapy
Endocrine therapy is the main treatment for hormone-sensitive breast cancer, but sometimes tumors become resistant to it over time. This happens because the cancer cells find ways to keep growing even without the hormone. There are different reasons for this, like becoming extra sensitive to estrogen or using other growth signals to survive.
1. Sensitivity
Even when cancer becomes resistant to endocrine therapy, the cells with estrogen receptors (ER) can still be active. Some studies show that when cancer becomes resistant to one type of hormone therapy, it can still respond to another hormone treatment. This means that even though cancer is resistant, the estrogen receptor is still working. But in the lab, researchers found that after being deprived of estrogen for a long time, breast cancer cells can become super sensitive to even tiny amounts of estrogen. This might be one reason why cancer becomes resistant to aromatase inhibitors, which are medications that lower estrogen levels.
2. Using other Growth Signals
Another way cancer cells become resistant is by using other growth signals. When cancer cells don't have enough estrogen, they might start using signals like epidermal growth factor receptor (EGFR) or human epidermal growth factor receptor 2 (HER-2) to keep growing. These signals activate pathways inside the cells that help cancer grow, even without estrogen.
Blocking these signals has been shown to halt cancer cell growth effectively. As a result, researchers are actively developing new innovative medications to inhibit these signals alongside medications that target the estrogen receptor. This is where the concept of combination therapy becomes crucial. By combining these medications, there is potential to prevent or delay resistance to hormone therapy, ultimately leading to improved outcomes for women with hormone-sensitive breast cancer.
Combination Therapy: Aromatase Inhibitors (AIs) with Targeted Agents
1. EGFR signal blocker + AIs
There are targeted medications that block growth signals in cancer cells. For example, Gefitinib and Erlotinib block a signal called the Epidermal Growth Factor Receptor (EGFR). In the lab and some clinical studies, they seem to work better on breast cancer cells that are resistant to tamoxifen, another hormone therapy medication. So, Combining gefitinib with AIs like anastrozole (such as Altraz 1mg Tablet, Anabrez 1mg Tablet) showed promise in reducing tumor size in some patients.
2. HER2 signal blocker + AIs
Trastuzumab is a medication that targets a signal called HER2, which is often found in breast cancer. When used with AIs, it has shown good results in patients with hormone-sensitive, HER2-positive metastatic breast cancer.
Some medications can target both EGFR and HER2 signals simultaneously. Lapatinib is one of these medications. It has shown good results in stopping tumor growth in patients with HER2-positive metastatic breast cancer. Research is ongoing to see if combining lapatinib with AIs like letrozole can be even more effective.
3. PI3K/Akt pathway blockers + AIs
Another strategy is to target a pathway called PI3K/Akt, which is often activated in breast cancer. Medications like Temsirolimus and Everolimus block this pathway. When used with Letrozole (AI), they have shown promise in stopping tumor growth. However, not all studies have shown the same results, and some large trials have been stopped because they didn't show benefits.
4. VEGF inhibitor + AIs
Finally, medications that target tumor blood vessel growth, like Bevacizumab (vascular endothelial growth factor inhibitor), are also being explored. When combined with Letrozole (AI), bevacizumab has shown promise in some patients with metastatic breast cancer.
Conclusion
In summary, combining AIs with other medications that target different pathways involved in breast cancer growth is a promising approach. However, more research is needed to understand which combinations work best and for whom. In the future, doctors will give each patient the combination of treatments that works best for them. Ongoing clinical studies are determining whether combining AIs with other medications should be the new standard for treating hormone-sensitive breast cancer.
