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Neoadjuvant Endocrine Therapy Will Become More Mainstream in Breast Cancer Care, Expert Says

Shannon Connelly
Published Online:5:47 PM, Tue August 22, 2017

Frankie Ann Holmes, MD
Many patients undergoing treatment for breast cancer think adjuvant chemotherapy is the best and only treatment option if they are going to beat the disease. This same mentality often extends to the physicians who are treating these patients. However, the truth is that chemotherapy is not the best option across the board, says Frankie Ann Holmes, MD.

In an interview with Targeted Oncology during the 16th Annual International Congress on the Future of Breast Cancer West, Holmes stressed that finding the right treatment for the right patient is becoming increasingly more important in breast cancer. In the neoadjuvant setting, some patients may benefit more from endocrine therapy.

“Neoadjuvant endocrine therapy—giving hormone therapy first before chemotherapy—isn't just for old, frail people or patients who have very strong ideas about not wanting to take chemotherapy,” she said. “Increasingly, it will become a mainstream therapy and the way it will do that is by us defining specifically which patients’ tumor is not going to be affected by chemotherapy.”

During the interview, Holmes, a physician with Texas Oncology, discussed which patients can benefit from endocrine therapy and the challenges that still exist with deciding between chemotherapy and endocrine therapy for each patient.

Targeted Oncology: Can you give an overview of your presentation on neoadjuvant endocrine therapy?

Holmes: I was honored to be asked to speak about neoadjuvant endocrine therapy. It's an old idea that has come to the forefront. We have always had patients who are too elderly, too frail, or, for reasons of their own choosing, do not want to receive chemotherapy for tumors that may be too large to be removed by surgery. If they had treatment before the surgery, it might shrink the tumor and make it easier to remove, so that instead of a mastectomy, they might be able to have a lumpectomy. 

Chemotherapy was originally the first way we could give systemic, or total body, therapy, but in the beginning, it was found for certain patients that chemotherapy didn't work very well. That was a group of patients with invasive lobular cancer. We have now come to learn that breast cancer can be divided into different subtypes. The luminal A subtype responds to depravation of estrogen more than giving chemotherapy because it's not a fast-growing tumor, and chemotherapy works best on fast-growing tumors. For this subset of patients—not just invasive lobular, even invasive ductal—there is a group that requires estrogen to grow. However, it grows at a very slow rate. The idea with this group of patients is to give them anti-hormone therapy to stop the tumor from getting the hormones it needs to grow.

Targeted Oncology: In the area of neoadjuvant chemotherapy, what challenges do you think are most pressing?

Holmes: Physicians have become so accustomed to feeling that the only and best treatment is chemotherapy, because it's a very dramatic and devastating treatment. Even patients say the same thing. Increasingly in breast cancer, it has to be the right treatment for the right disease. Breast cancer is different subtypes.

Even in the clinic, when a patient comes to us after having had surgery with a small tumor that involves the lymph nodes, is hormone positive, and has a slow growth rate, we struggle with deciding if she should be given chemotherapy or if she should be treated more appropriately with anti-hormone therapy.

This is a big issue that we struggle with in early breast cancer. Generally, tumors are larger. Patients say I must have to get that chemotherapy, or you're not giving me the right treatment. It's a matter of getting the information out there that it's the right treatment for the right disease.
The second part of that is identifying those patients, because there are certain features, such as a low growth rate and very strong hormone receptors, but now more than ever we are using genomic classifiers to look at the genes that are the hard wiring of the tumor. I think the challenges for the future are to let people understand that, as Lance Armstrong said, it's not just the bike. Breast cancer is not just chemotherapy, it's targeted therapy. It’s the right drug for the right disease and then it’s figuring out the disease by getting these new tests that are helping us to integrate the clinical picture of the size, the lymph nodes, the growth rate and other gene components to the tumor. 

Targeted Oncology: What advice would you give to physicians that are trying to explain to their patients that chemotherapy might not be the best option for them?

Holmes: The most important thing in communicating with patients is to keep it simple. And secondly, as every physician has learned, you have to have good analogies to help people understand things concretely and apply it. For example, if you are someone who loves to parachute, you would prepare for your parachute by getting on your jumpsuit and making sure you have your parachute on your back before you jump out of the plane. You wouldn't go to the parachute drop wearing your jogging clothes.

Just like people are very different, we have to tailor our approach to each tumorindividually, and then we have to tailor it to each individual's personal situation.

Targeted Oncology: You mentioned genomic testing. Where do you think that is headed?

Holmes: It's just thrilling what has happened in the past decade and more. Back in the 2000s, the 21-gene recurrence score came out and caused a huge paradigm shift. With breast cancer, what you see is not always what you get. It’s important to see what's under the hood with this cancer. And that's what genomic testing is. It allows us to look under the hood, and it's only getting better. In the beginning, we had the 21-gene score and then the 70-gene score came out. One of the things that we all had to learn is bigger isn't better. There are different ways of getting to the same situation. 

I was just at a conference and I heard one physician saying they were not sure if they trust the new gene testing algorithm because not one of the genes they are testing is estrogen receptor or HER2, the ones that we are used to testing. As our understanding of biology has progressed, you don't need to have the estrogen receptor if you see what's downstream. The estrogen receptor is like a line of dominos where you hit the first one, and what you really care about is that last domino that's going to press on something, or the bridge will fall. Now we know we can pick out the genes that are at the end of the pathway and you'll have an even better readout of what is happening. Whether the estrogen receptor is mutated, doesn't work properly, or gets interfered with, if that pathway has been set in motion, if the fuse has been lit, you are looking to see if that signal travels all the way down to the end of that fuse where the bomb explodes. 

Targeted Oncology: What would you like the main takeaway to be for those who attended your presentation?

Holmes: Neoadjuvant endocrine therapy—giving hormone therapy first before chemotherapy—isn't just for old, frail people or patients who have very strong ideas about not wanting to take chemotherapy. Increasingly, it will become a mainstream therapy and the way it will do that is by us defining specifically which patients’ tumors are not going to be affected by chemotherapy. The second thing is, more and more we are learning about the negative effects of some of our treatments. We've always known that chemotherapy has a very small incidence of leukemia. If you're taking anthracyclines, there's a small incidence of heart problems down the line.

We've also learned some devastating information that fitness declines normally with aging. After age 25, unless you work hard to stem the tide, we lose about 1% of our fitness per year. With chemotherapy, it's been shown with one of our most common regimens, anthracycline-cyclophosphamide and taxanes, that patients can lose 10% of their fitness. That is equivalent to aging 10 years. We can do a lot of good with chemotherapy, we can save lives, but if patients don't need it, then we don't want to be doing that, because it's not going to help them. The takeaway is that if we can continue to see breast cancer as a collection of diseases for which we need to find exactly the right treatment and that not giving chemotherapy isn't copping out and giving a worse therapy, it's giving the right treatment for the right disease. 

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