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Treatments for Early-Stage Triple-Negative Breast Cancer (TNBC)

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Published on October 15, 2020

What Treatments Are Available For Early Stage TNBC?

What treatments are available for triple-negative breast cancer (TNBC) patients, particularly those in early stages? What's the standard of care and what new treatments are available? When should early-stage patients consider getting a lumpectomy or mastectomy? Patient Power host Ricki Fairley and Moira Quinn, both TNBC survivors, get the latest treatment news from Dr. Sara Tolaney of the Dana-Farber Cancer Institute.

This is Part 1 of a four-part series. Watch Part 2 (Triple-Negative Breast Cancer Treatment Options By Subtype ), Part 3 (Clinical Trials for Triple-Negative Breast Cancer) and Part 4 (Managing the Side Effects of Triple-Negative Breast Cancer) for more information.

This program is supported by an educational grant from Daiichi Sankyo. This organization has no editorial control. It is produced by Patient Power and Patient Power is solely responsible for program content. 

 

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Transcript | Treatments for Early-Stage Triple-Negative Breast Cancer (TNBC)

What treatments are recommended for early-stage TNBC patients?

Dr. Tolaney:
It definitely varies depending on the exact situation. If you had a patient who has a tumor that's triple-negative that's over two centimeters in size or has lymph node involvement, generally, our recommendation is to do chemotherapy upfront prior to surgery. And right now, the most sort of standard recommendation is getting a combination of what we call anthracycline and taxane-based chemotherapy. Usually, it would be a regimen like doxorubicin (Adriamycin), cyclophosphamide (Cytoxan), and paclitaxel (Taxol).

However, there is a lot of new data, as you suggested, a lot of new drugs that are coming along in this space, and one new agent that's currently under FDA review in this particular space is immunotherapy specifically a trial that had looked at pembrolizumab (Keytruda), which is a drug, an antibody that is supposed to augment your immune response and they study giving that antibody with standard chemo and found that when you added that antibody to the chemo prior to going to surgery, that more patients went to surgery and were found to have no cancer at the time of surgery if that immune drug was added to the chemotherapy.

Currently, this is under FDA review. I think the challenge is that obviously as we add more and more drugs, we do add potential side effects. We have learned a lot - that if someone got some chemotherapy before surgery and at the time of surgery, if we still see there is cancer in the breast, then we do know that giving additional therapy after surgery is important. Currently, the standard drug to give in this setting is a drug called Xeloda or capecitabine, and where we give it for six months in someone who has cancer that's left behind at the time of surgery.

What are the new treatments and medications for metastatic TNBC?

Ricki Fairley:
Can we talk about the new medications or the new treatments for metastatic triple-negative?

Dr. Tolaney:
Yeah, definitely. For metastatic triple-negative breast cancer, I think we've seen a lot of progress, particularly over the last one and a half years. We saw the first approval in breast cancer for immunotherapy come about with the use of immunotherapy. This was based on a trial called the IMpassion130 trial in which patients with metastatic triple-negative breast cancer had been randomized either to get a standard chemo, which we would give, which is a taxane chemo. In this case, it was a drug called nab-paclitaxel, or to get that chemo with an immunotherapy antibody called atezolizumab (Tecentriq).

What they found was that when they gave both drugs, so the chemo and the immunotherapy that patients had their disease controlled longer, and they lived a lot longer than the people who just got the chemo alone. This in our mind was a big breakthrough. I think the challenges of this immunotherapy seemed to only work in triple-negative tumors that also were PD-L1 positive. It is now standard if someone has metastatic triple-negative breast cancer to test the tumor for this receptor called PD-L1. That's seen in about 40% of triple-negative tumors, they have this receptor on it. The idea is this receptor is trying to turn off your body's immune system.

How do immunotherapy antibody drugs work?

Cancer cells want to survive, and they want to figure out a way to outsmart the body and one trick that they have is they say, well, why don't I turn off the immune cells because the immune cells job is to find foreign things that don't belong and so your immune system should be killing your cancer, but again, the cancer doesn't want to be killed so it turns off this blocker, this PD-L1 receptor saying, "Hey, don't kill me, immune system." But these new antibodies can shut that blocker off so your immune system can be activated and kill your cancer.

I will say that it was a big thing for us to see a drug that's going to finally improve survival for women with triple-negative breast cancer and so again, I think a very big breakthrough to have the availability of immunotherapy. Another really exciting change for triple-negative breast cancer is the first approval for an antibody-drug conjugate. The drug is called sacituzumab govitecan (Trodelvy) also known as IMMU-132.

The Trodelvy or sacituzumab govitecan, it's a very clever drug because what it's doing is it's taking an antibody that's targeting a receptor called the TROP2 receptor, which is on the vast majority of triple-negative breast cancers and tagged to that antibody is a very potent chemo drug. Lots of chemo drugs are tagged to that antibody, and so the antibody binds to the cancer cell that has that receptor on it and then that antibody gets taken into the cancer cell and releases the chemotherapy into the cancer cell.

Some people call these kinds of drugs, smart bombs because it's like a very clever way to deliver the chemo just into the cancer cell and kill it. And it has done so very effectively. They compared this drug, the sacituzumab govitecan or Trodelvy to standard chemotherapy in women who have metastatic triple-negative breast cancer and found that not only did it make the response rates higher, it controlled the disease longer, and it allowed women to live significantly longer with their disease.

How do treatment options differ between lumpectomies and mastectomies?

We know that if you get a lumpectomy, you do need radiation therapy. They go hand in hand, you need to radiate your entire breast. If we compare outcomes for someone who got a lumpectomy and radiation compared to a mastectomy, we know that the outcomes are the same, meaning the survival is going to be the same.

Generally speaking, if I have a patient who has a tumor that's small enough for a lumpectomy, I do present them with a choice. Would you like to get a lumpectomy and radiation or choose a mastectomy? Again, we do have that choice left to the patient because again, from our standpoint, the outcomes to the patient will be the same.

The only case I will say that where this discussion also becomes a bit more complex is if someone has an underlying genetic mutation because then the issue isn't just if I have my lumpectomy and radiation will this cancer come back, it's also, could I get a new breast cancer in the breast tissue that's left behind because I have a genetic predisposition and my chances of getting a new cancer are higher than the average patient. Should I get a mastectomy instead of a lumpectomy? Because I know that having a breast, in general, puts me at a higher risk for getting a new cancer. 

That discussion is more complex because then we do start having discussions about having a mastectomy if they have a BRCA mutation, for example, even if they could have gotten a lumpectomy because we're worried about their risk of getting an additional cancer in the future. 


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