Names of clinical trials at times can sound … well, clinical. Occasionally, though, those names hide big news. Such was the case this past June when news broke with results of the Trial Assigning Individualized…
Names of clinical trials at times can sound … well, clinical. Occasionally, though, those names hide big news. Such was the case this past June when news broke with results of the Trial Assigning Individualized Options for Treatment, or TAILORx, which made huge waves in the world of breast cancer.
In the past, most women who’d been diagnosed with breast cancer had been advised to have aggressive chemotherapy in addition to surgery, radiation and hormonal therapies, but as our understanding of the nuances within breast cancer and each patient’s prognosis has increased, it’s opened the door to the possibility of a less-is-more approach to treating many early stage breast cancers.
The TAILORx study followed 10,273 women diagnosed with hormone-receptor-positive, HER2-negative breast cancer that had not spread to the lymph nodes and looked at whether these patients can safely skip chemotherapy treatment. (Hormone-receptor-positive breast cancers are fed by hormones — estrogen, progesterone or both — while HER2 indicates that human epidermal growth factor receptor 2 has been detected on the cancer cells. This growth hormone may be overexpressed in some cases of breast cancer, and tends to lead to cancers that are more aggressive than hormonally-driven breast cancers.)
While the criteria for who may qualify to forego chemotherapy may sound very specific, the upshot is that HR-positive, HER2-negative breast cancer that is diagnosed in stage 1 or 2, before it has spread to the lymph nodes, is the most common type of breast cancer diagnosed in the United States. The American Cancer Society reports that 71 percent of breast cancers are hormone-receptive-positive and HER2-negative. The National Cancer Institute says this totals about 125,000 women.
Historically, most women diagnosed with this kind of breast cancer would have been treated with an aggressive course of chemotherapy, a blunt instrument that kills cancer cells, but can also cause devastating side effects. But there was always a question as to whether that was the best course of action, says Dr. Harold J. Burstein, institute physician at the Dana-Farber Cancer Institute in Boston and associate professor of medicine at Harvard Medical School. “We knew viscerally that not everyone needed chemotherapy. But we didn’t have a tool to figure out who needed chemotherapy and who doesn’t.”
But then in the early 2000s, researchers at Genomic Health, a genetic diagnostics company based in Redwood City, California, developed the Oncotype DX test, “a genetic test that looks at 21 genes that help turn on and turn off cancer cell growth,” says Dr. Marisa C. Weiss, chief medical officer and founder of Breastcancer.org and director of breast radiation oncology and director of breast health outreach at Lankenau Medical Center in Wynnewood, Pennsylvania. This test generates a report that she says is “sort of like an FBI report of the cancer itself,” that scores your chances of recurrence. It gives your doctor “an inside look at what’s going on behind the curtain, and it helps you make the million-dollar decision of whether you need chemotherapy or not.” Using this test on a large pool of women, the TAILORx study aimed to determine whether these Oncotype DX scores could determine definitively who needed chemo and who didn’t.
“In the TAILORx study, women who had estrogen-receptor-positive, lymph-node-negative breast cancer, the most common kind diagnosed in America, were assigned their treatment based on this Oncotype DX test,” Burstein says. For women with a low score — less than 11 on a scale of 1 to 100 — they received surgery, radiation and hormone therapy, but not chemotherapy “because no one imagined adding chemotherapy would add value.” For women who had high Oncotype DX scores — over 25 — “they got chemotherapy, because everyone assumed they would need chemotherapy.” The group in the middle — those with scores between 11 and 25 — “were randomly assigned to hormone therapy by itself or chemotherapy and hormone therapy combined.” These women had long been in a gray zone, lacking hard evidence about the value of chemotherapy. But Burstein says the results of the TAILORx study were “very clear. For women who have ER-positive, node-negative breast cancers that are HER-negative, if the score is 25 or less, there’s no role for chemotherapy. Full stop.”
These findings will affect a lot of women. The NCI reports that about 70 percent of the women with this kind of breast cancer can safely skip chemotherapy — upwards of 60,000 or more women per year. This applies to women who are older than 50 who have a recurrence score of 11 to 25, women of any age with a recurrence score of 0 to 10 and those 50 years old or younger with a recurrence score of 11 to 15. The study found that chemotherapy should be considered for the other 30 percent of women with HR-positive, HER2-negative, node-negative breast cancer — specifically, women of any age with a recurrence score of 26–100 and those 50 years old or younger with a recurrence score of 16–25.
Burstein says these findings mean thousands of women can be spared unnecessary chemotherapy because their chances of recurrence were not improved by adding chemotherapy to hormonal and other standard treatments such as surgery. It’s important to note that this study looked only at the value of adding chemotherapy. “All these women also had surgery and the vast majority also had radiation,” he says, “so this is really part of a multi-disciplinary package. These women still need surgery, and if they have an intact breast,” meaning they had a lumpectomy instead of a mastectomy, “they still need radiation therapy after the lumpectomy. The sole purpose of this test is to ask the question, ‘should this woman also receive chemotherapy as part of her multi-modality treatment plan?'”
The findings were such big news because they came out of a long-range, prospective study that followed a large group of women for a long enough time to provide solid evidence that skipping chemo is a viable option in many cases. All of this means women with this form of breast cancer now can make decisions based on evidence, “not the old question of, ‘if it was your wife what would you do?'” a question that women have long asked their doctors when wading through these difficult decisions, Weiss says. “I mean, that was really how a lot of these decisions were made. That’s not how we should be making decisions about whether to use these powerful, important therapies. You only want to have chemotherapy if you really need it,” she says, because the side effects can be so debilitating.
As a breast cancer survivor herself who had the Oncotype DX test, Weiss says getting a low-risk score on her test was a big relief that helped her make better decisions about the course of her care. She had scored 16 on the test, and was considered low-risk for recurrence. “There was no added benefit to chemotherapy. So that was hugely meaningful to me, because I didn’t want chemo. But if I needed it, I would have done it.”
This is the crux of the conundrum and why the new guidelines that have come out of the TAILORx study are such big news, Burstein says. Most of us would be willing to do just about anything to keep cancer from coming back, but why do something that’s not going to help? “The test frames the likelihood of benefit from chemotherapy. Many women who are diagnosed with breast cancer imagine that if they get chemotherapy, they’ll be cured and if they don’t [have chemo], they’ll die.” But the test shows “that sort of extreme analysis just is not the case. For most people adding chemotherapy is a marginal improvement over not adding chemotherapy, and this test shows you that,” and puts hard numbers to the discussion of risk and benefit. “Before we had the test, we would talk with patients and say things like, ‘chemo probably does reduce your chances of recurrence 4 or 5 percent,” but there wasn’t enough evidence to say for sure that was the case. The test eliminates much of the guesswork involved in prescribing the best course of treatment.
Now, Burstein says, he can have a conversation with a patient where he says “‘this test indicates your tumor has a risk of recurrence of 20 percent. And the test predicts that chemotherapy will reduce that chance from 20 percent to 16 percent.’ Well those are real numbers,” and you can have a conversation about whether chemotherapy offers enough benefit to be worth the side effects. “Before the test, it’s not that we made up stuff, but our guesses were all over the map. It has transformed our ability to have meaningful conversations with patients.” Especially when the test returns the result that chemotherapy offers zero benefit. That makes the decision much easier to make.
It also helps women move on emotionally and know that they made the best decision possible, Weiss says. “It’s always good when you can base these decisions on something that’s substantive that will support what you did. And when you look back, you can say to yourself, ‘I did the best I could and it was still a good decision.'”
Weiss encourages anyone who’s been diagnosed with breast cancer to find out whether you qualify for the Oncotype DX test and who will be handling that process. The test takes a couple weeks to return, and while it can be hard to wait for the results, “generally these are not emergencies so it’s important to wait for this result to come back in order to make this important decision on solid ground,” she says.
Nevertheless, you can help speed things along a bit by “staying on top of it. Call the doctor’s office to make sure the test goes out at the appropriate time. It usually doesn’t go out until the pathology report is back from the main surgery and there’s verification that you qualify for it,” and some patients may need to wait for insurance approvals before the test can be sent out. “So there are some tricky aspects to it, but the main thing is stay on it,” she says. In some hospitals, the surgeon’s office orders the test, in others, the oncologist’s office does it. “Don’t make any assumptions. Find out who’s going to order it. Find out when it’s authorized. And stay on it, because if you don’t, it could be easily delayed.” Minimizing that period of uncertainty can help you feel less anxious about the next step while also offering you comfort that you’re going to get the right care for your particular situation.