Breaking Down a Groundbreaking Breast Cancer Trial

BREAST CANCER DEATH rates have dropped dramatically over the past 15 years. This is largely due to more widespread screening to detect cancer at its earliest stages, as well as the use chemotherapy and hormonal therapy after surgery to reduce the risk of cancer recurrence in other parts of the body.




Traditionally, this strategy included recommending chemotherapy for many women with estrogen receptor positive breast cancer that did not involve lymph nodes at the time of surgery. This represents half of all breast cancers, or about 135,000 women in the U.S. each year. However, only about 4 in 100 women were having recurrence of breast cancer prevented by chemotherapy, indicating that we were overtreating the vast majority of women with chemotherapy to benefit a few.

So, how can we identify those 4 in 100 who will benefit from chemotherapy?

Obtaining the answer was one of our goals when designing the first precision medicine trial of its kind, the TAILORx clinical trial. TAILORx was sponsored by the U.S. National Cancer Institute and coordinated by the ECOG-ACRIN Cancer Resource Group.

The TAILORx trial recruited more than 10,000 women with early-stage breast cancer between 2006 and 2010. We used a molecular test called Oncotype DX Recurrence Score, which measures the expression of 21 genes in tumor tissue removed at the time of breast surgery, to guide the use of chemotherapy given after surgery. The Recurrence Score provides prognostic information about the risk of an incurable breast cancer recurrence in other parts of the body on a scale of zero to 100.

When we launched the trial, we used information we had about the 21-gene test to guide therapy.

• The 17 percent who had a low recurrence score of 0 to 10 were assigned to receive endocrine therapy alone. This was based on prior studies showing that a low score was associated with a very low risk of recurrence with endocrine therapy alone at 10 years (about 3 percent recurrence risk).
• The 17 percent who had a high recurrence score of 26 to 100 were assigned to chemotherapy in addition endocrine therapy. This was based on prior studies showing that a high score was associated with a larger benefit from chemotherapy (a 25 percent absolute reduction in recurrence risk, from 63 to 88 percent at 10 years).

The remaining 65 percent, or 6,711 trial participants, fell into the middle/intermediate range of 11 to 25. These are individuals who would normally be recommended to receive or at least consider chemotherapy. We randomized these participants to have treatment with endocrine therapy alone or in combination and chemotherapy. We then tracked their health outcomes for nine years.

We found that chemotherapy was not beneficial in women older than 50 and had a recurrence score of 0 to 25, or in women 50 or younger with a recurrence score of 0 to 15.

These results were presented at the American Society for Clinical Oncology, an annual scientific meeting, and were published in the New England Journal of Medicine.

The study provides much needed clarity and confidence for women and their doctors regarding who benefits from chemotherapy, and who doesn't.

While forgoing chemotherapy made many headlines, there are important nuances and facts that need to be considered:

• The Oncotype DX 21-gene Recurrence Score test is applicable to women with early-stage estrogen receptor positive breast cancer that does not overexpress the HER-2 gene and has not spread to axillary lymph nodes at the time of surgery. This applies to about one-half of all breast cancers in the U.S. diagnosed each year.
• Women older than 50 with a midrange risk – gene score of 11 to 25 on a tumor test – can skip chemotherapy and just have endocrine therapy, especially if there are negative axillary nodes.
• If a patient is considered at "low risk" for recurrence, meaning a score of zero to 10, the risk of recurrence was about 3 percent with endocrine therapy alone in older and younger women with negative axillary nodes.
• Chemotherapy was associated with some benefit for women younger than 50 who had a recurrence score between 15 and 25. The benefits were much smaller than those who had a score of 26 or higher.
• About 40 percent of women 50 or under whose score was zero to 15 had an excellent prognosis with endocrine therapy.
• Endocrine therapy includes pills that block the effects estrogen (e.g., tamoxifen) or lower estrogen levels (e.g., aromatase inhibitors in postmenopausal women), or sometimes pills in combination with injections for premenopausal women. The excellent outcomes require that endocrine therapy be prescribed and taken for at least five years.

Identifying the best cancer treatment is an extremely personal decision, and we couldn't come this far without the many inspiring women who volunteered to participate in this study.

While these study results provide more science-based evidence than ever before to determine treatment, every person facing breast cancer must speak with their doctor to see what therapy might be best for them. We have come a long way, but there's more work to be done to help every person feel as empowered as can be when making cancer treatment decisions.

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