Hormone therapy against breast cancer is often limited by cancer drug resistance. Leading oncologist and precision medicine expert discusses new methods. How to overcome drug resistance in breast cancer? Hormonal treatment of breast cancer.

Let's talk about breast cancer. Over 75% of breast cancers express estrogen and or progesterone receptors. Endocrine cancer therapies are used to treat such breast cancers. Unfortunately, not every patient with breast cancer is responsive to those treatments. We also see that there is a molecular escape of tumors from the influence of the endocrine cancer therapy. Dr. Anton Titov, MD. You study endocrine cancer therapy. How can it help to treat people, especially patients with metastatic breast cancer? Dr. Anton Titov, MD. All women with breast cancer express the hormone receptors, estrogen receptor or progesterone receptor. Patients who have metastatic breast cancer, receive hormone therapy. We know that with time all such breast cancer patients will develop resistance to cancer therapy. The question is, why? Dr. Anton Titov, MD. Until a few years ago no one knew what was the major mechanism of resistance for breast cancers. In 2013 our lab simultaneously with two other labs in the world discovered new mutation in the estrogen receptor. This mutation is very special. This mutation confers endocrine resistance. Dr. Ido Wolf, MD. That means that breast cancer cells that express these mutated proteins can live even without estrogen around them. These breast cancer cells are resistant to all endocrine cancer therapy. Dr. Ido Wolf, MD. That was a major discovery. We now know that about 30 to 40% of all breast cancer patients develop endocrine cancer therapy resistance. They develop resistance due to this specific mechanism. This is important, because the first step in treating someone with cancer is knowing the cause of cancer. Identification of that specific mutation has opened new avenues for breast cancer treatment. Now there are several companies working on specific inhibitors of that specific receptor. It always takes time. From the time you find a mutation to the time cancer treatment goes to the clinic. But the discovery of it was of major importance. We also know now that the mutation is important not just in mediating resistance. It also makes breast cancer tumor much more aggressive. This explains why women who develop endocrine resistance suddenly have cancer this is much more aggressive. Breast cancer spreads with more metastases that develop rapidly. Because that mutation makes the cancer cells grow much faster in many places in the body. Dr. Ido Wolf, MD. Medications could be developed addressing or targeting that mutation. Would they restore the sensitivity of tumors to cancer endocrine therapy? Dr. Anton Titov, MD. Would they help with the therapy be directed at those tumors that have the mutation, without the need of endocrine therapy? Dr. Anton Titov, MD. Dr. Ido Wolf, MD. There are now new cancer medications developed that can inhibit the mutated estrogen receptor. Dr. Ido Wolf, MD. Breast cancer medications in use now cannot bind that endocrine receptor. The new generation of breast cancer medications will be able to bind mutated estrogen receptor and inhibit cancer. Dr. Ido Wolf, MD. That would be also effective in a so-called triple negative breast cancer? Dr. Anton Titov, MD. Probably not, because these medications will target only ER, the estrogen receptor. Triple negative breast cancers do not express the estrogen receptor at all. Dr. Ido Wolf, MD. For these breast cancers we need a whole new array of medications. But clearly that will advance our ability to treat the tumors this express the estrogen or progesterone receptors. We should be able to find another endocrine cancer therapy instead of switching to breast cancer chemotherapy. It will not only prolong life. It will improve significantly quality of life. It is going to be much easier for women to take hormonal therapy of new generation than to switch to chemotherapy.