Advances in precision medicine help refine – and redefine – cancer care

Study details

All of the women with hormone receptor-positive, HER2-negative, node-negative, early-stage breast cancer enrolled in TAILORx met National Comprehensive Cancer Network guidelines for receiving adjuvant chemotherapy. About 69% had an intermediate recurrence score (11-25) and were randomized. All of the 17% with a low recurrence score (0-10) were given only endocrine therapy, and all of the 14% with a high recurrence score (26-100) were given both adjuvant chemotherapy and endocrine therapy.

Of note, the recurrence scores used to define midrange were adjusted downward from those conventionally used to account for exclusion of patients with higher-risk HER2-positive disease and to minimize potential for undertreatment, Dr Sparano explained.

In the women with midrange scores who were randomized, the hazard ratio of 1.08 for invasive DFS with endocrine therapy alone compared with chemotherapy plus endocrine therapy fell well within the predefined hazard ratio for noninferiority (1.322). The 9-year rate of invasive DFS was 83.3% with endocrine therapy and 84.3% with chemotherapy plus endocrine therapy.

The groups had similar rates of freedom from distant recurrence (94.5% vs 95.0%; HR, 1.10; P = .48) and distant or locoregional recurrence (92.2% vs 92.9%; HR, 1.11; P = .33), and similar OSs (93.9% vs 93.8%; HR for death, 0.99; P = .89).

In exploratory analyses, there was an interaction of age and recurrence score (P = .004) whereby women aged 50 years or younger derived some benefit from chemotherapy if they had a recurrence score of 16-20 (9% fewer invasive DFS events, including 2% fewer distant recurrences) or a recurrence score 21-25 (6% fewer invasive DFS events, mainly distant recurrences). “This is information that could drive some younger women who have a recurrence score in this range to accept chemotherapy,” Dr Sparano said.

The 9-year rate of distant recurrence averaged 5% in women with midrange scores overall. It was 3% in those with a low recurrence score given endocrine therapy alone, but it was still 13% in those with a high recurrence score despite receiving both endocrine therapy and chemotherapy. The latter finding may “indicate the need to explore potentially more effective therapies in this setting,” he proposed.

Tailoring treatment: ‘not too much and not too little’

“These are important data because this is the most common form of breast cancer in the United States and other developed countries, and the most challenging decision we make with these patients is whether or not to recommend adjuvant chemotherapy with all its side effects and potential benefits,” said ASCO expert Harold Burstein, MD, PhD, FASCO. “The data show that the majority of women who have this test performed on their tumor can be told that they don’t need chemotherapy, and that can be said with tremendous confidence and reassurance.”

The recurrence score has been used for a decade, but the trial was necessary because the score was originally developed in patients who were receiving older chemotherapy regimens and older endocrine therapies, and because there have been few data to guide decision making in the large group of patients with midrange scores, he said. “Now we can say with confidence ... that the patients got contemporary chemo regimens and still saw no benefit from chemotherapy.

“This is not so much about de-escalation ... the goal of this study was not to just use less treatment but to tailor treatment. The investigators chose the title very aptly,” said Dr Burstein, a medical oncologist at the Dana-Farber Cancer Institute and associate professor of medicine at the Harvard Medical School, Boston.

“This is extraordinary data for breast cancer doctors and women who have breast cancer. It allows you to individualize treatment based on extraordinary science, which now has tremendous prospective validation,” he said. Overall, “women with breast cancer who are getting modern therapy are doing well, and this test shows us how to tailor that management so that they get exactly the right amount of treatment – not too much and not too little.”