MANY WOMEN WITH HORMONE-DRIVEN early breast cancer can forgo chemotherapy following surgery without worsening their chance of cure, thanks to a test that can pinpoint an individual’s need for the treatment. To help prevent cancer’s recurrence after surgery, women with this disease typically take endocrine treatments that suppress the body’s production or use of the hormone estrogen, and they often also receive chemotherapy. This post-surgical treatment is known as adjuvant therapy.
The tumor tissue test looks for 21 cancer-associated gene mutations and can determine which women have a low risk of recurrence and don’t need chemotherapy and which face a higher risk and can benefit from the treatment.
The findings, presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in June, were generated by the phase 3 TAILORx study. The data are expected to save thousands of women — about 70 percent of those with hormone-driven early breast cancer — from overtreatment with chemotherapy.
“These are very important data, because this is the most common form of breast cancer in the United States and developed countries, and the most challenging decision we make with these patients is whether or not to recommend adjuvant chemotherapy with all of its side effects and with its potential benefits,” ASCO expert Harold A. Burstein, M.D., Ph.D., of Boston’s Dana-Farber Cancer Institute, said following the presentation. “What the data provided here today show, from this massive National Cancer Institutesponsored trial, is that the vast 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 women who participated in the trial had hormone receptor-positive, early-stage breast cancer that did not overexpress the protein HER2. The cancer had not spread to their lymph nodes.
The median age of the participants was 55; 33 percent were 50 or younger. More than half of the patients (57 percent) had intermediate-grade disease, and 63 percent had a 1- to 2-centimeter tumor.
Estrogen receptor (ER)-positive, HER2-negative, nodenegative breast cancer is one of the most common types, accounting for up to 50 percent of cases of the disease, noted lead study author Joseph A. Sparano, M.D., the associate director for clinical research at the Albert Einstein Cancer Center in the Bronx, a bureau of New York City. Up to 30 percent of patients with these tumors typically experience a recurrence within 10 years of initial treatment. Although adjuvant chemotherapy is recommended for these patients, the benefit is typically very small. Across the board in this population without gene profiling, Sparano said, adding chemotherapy to endocrine therapy prevents 3 to 5 percent of the women from developing a breast cancer recurrence within 10 years of initial treatment, as compared with giving endocrine therapy alone.
The 21-tumor gene expression assay, Oncotype DX Breast Recurrence Score test, helps predict the benefit of chemotherapy based on patient scores from zero to 100. Patients with a score of 26 to 100 have a higher risk of recurrence and benefit from adding chemotherapy to endocrine therapy, whereas those with a score of zero to 10 (low risk) derive little, if any, benefit. It’s uncertain whether adding chemotherapy helps patients with scores of 11 to 25 (intermediate risk).
Between April 2006 and October 2010, 10,273 women were registered for the study, which is the largest adjuvant breast cancer trial to date, according to Sparano. “It was performed in six countries, four continents, over 1,100 sites … and includes a total of 30 co-authors,” said Sparano, who also serves as vice chair of the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Research Group, which designed and conducted the study.
The participants who could be evaluated were divided into groups based on recurrence score. Those with a low score (1,629 patients) received endocrine therapy alone. Women with a high score (1,389) received endocrine therapy in combination with standard adjuvant chemotherapy.
Of 6,711 women with an intermediate score, 3,399 were randomized to receive just endocrine therapy, and 3,312 were randomized to receive the standard treatment of chemotherapy followed by endocrine therapy. The women were divided into subgroups based on menopausal status, planned chemotherapy, planned radiation and recurrence score groupings of 11 to 15, 16 to 20, and 21 to 25.
Sparano pointed out that the trial followed women in real time and reflected current standards for chemotherapy and endocrine therapy. Burstein added that prior studies employing the 21-gene test were based on older standards, such as age and tumor size and grade. Therefore, the new findings helped validate the role of adjuvant endocrine therapy with or without chemotherapy in the setting of modern regimens.
The study’s primary goal involved assessing rates of invasive-free survival, which refers to the amount of time before cancer spreads into healthy tissues. At nine years, patients with intermediate recurrence scores receiving endocrine therapy alone and chemotherapy followed by endocrine therapy had similar invasive-free survival rates, both close to and far from the disease’s original location. In these women, the invasive-free survival rate was 83.3 percent with endocrine therapy alone and 84.3 percent with endocrine therapy plus chemotherapy.
The two intermediate-score groups also had similar amounts of time without disease recurrence distant from the original site (94.5 percent with just endocrine therapy versus 95 percent with added chemotherapy); time without any recurrence (92.2 percent versus 92.9 percent); and overall survival (93.9 percent versus 93.8 percent).
Among patients with low recurrence scores, there was a 3 percent rate of distant recurrence (for example, spread of the cancer to the lungs, liver or bones) with endocrine therapy alone, and patients in the high-score group had a 13 percent rate of distant recurrence with added chemotherapy. A secondary analysis of the two mid-range recurrence score groups considered factors that may determine which patients would benefit from added chemotherapy. Although there was no significant association between recurrence score and menopause, tumor size or grade (a measurement of the abnormality of cancer cells based on how they look under a microscope), there was an association between recurrence score and age. In women 50 years or younger with a score of 16 to 20, there were 2 percent fewer distant recurrences among those who received chemotherapy compared with those who did not, and 7 percent fewer recurrences in those with a score of 21 to 25 who took chemotherapy versus those who did not.
“The younger women who had a recurrence score of 16 to 25 had some chemo benefit,” Sparano said. “This was information that could drive some younger women who have a recurrence score in this range to accept chemotherapy.”
The TAILORx trial once again confirmed that patients of any age with this type of breast cancer and a score of zero to 10 would be recommended for endocrine therapy alone (16 percent of patients), and all women in this population with a score of 26 to 100 (17 percent) would be recommended for added chemotherapy.
Women over age 50 with a score of 11 to 25 (45 percent) and patients 50 or younger who have a score of 11 to 15 (8 percent) should be given strictly endocrine therapy as an adjuvant treatment.
“In terms of the big picture of the impact on care, application of this test in clinical practice to this population would be estimated to spare chemotherapy in about 70 percent and to select chemotherapy in about 30 percent, on average,” Sparano said. Burstein added that, for the small group of women who are under age 50 and have intermediate scores from 20 to 25, there will be discussion about whether chemotherapy is warranted or whether using an alternative endocrine approach, such as ovarian suppression, might accomplish the same goals.
“The goal of this study was not just to use less treatment; the goal was to tailor treatment … with the idea of saying some women are going to need more of one kind of therapy and less of another, and others will get a different treatment based on the biology of their disease,” Burstein said. “So, this is an extraordinary day for breast cancer doctors and for women who have breast cancer. It allows us to individualize treatment based on extraordinary science, which now has tremendous prospective validation.”