Many Women With the Most Common Form of Breast Cancer Can Skip Chemotherapy: Study finds that approximately 70% of patients with this form of the disease do not need adjuvant chemotherapy.

Abstract

CancerVolume 124, Issue 16 p. 3281-2382 CancerScopeFree Access Many Women With the Most Common Form of Breast Cancer Can Skip Chemotherapy Study finds that approximately 70% of patients with this form of the disease do not need adjuvant chemotherapy First published: 24 August 2018 https://doi.org/10.1002/cncr.31671AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat The authors of the Trial Assigning Individualized Options for Treatment (Rx), or TAILORx, say that the study’s findings support the use of specific biomarkers to more effectively guide treatment decisions for the majority of women with the most common form of breast cancer. The researchers confirmed that the Oncotype DX Breast Recurrence Score assay, a 21-gene expression test, can effectively assess whether or not women with hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, axillary node-negative breast cancer will benefit from the addition of chemotherapy to their treatment. “The important thing about this study is that for a long time we’ve known we were overtreating some women with breast cancer,” says Otis Brawley, MD, chief medical and scientific officer of the American Cancer Society, who was not involved in the study. “Now we’re able to distinguish with precision medicine who needs therapy and who doesn’t.” The TAILORx results were published in The New England Journal of Medicine and were presented at the American Society of Clinical Oncology’s annual conference in June.1 The phase 3 clinical trial, which opened in 2006, enrolled 10,273 women with this type of breast cancer at 1182 sites in the United States, Australia, Canada, Ireland, New Zealand, and Peru. Two-thirds of the participants were 51 to 75 years old, whereas the remaining third were 50 years old or younger. Although earlier TAILORx findings released in 2015 indicated cases in which some patients could skip chemotherapy, the 2018 findings add significant strength to those results and also show that even more patients can skip chemotherapy, according to lead author Joseph Sparano, MD, associate director for clinical research at the Albert Einstein Cancer Center and Montefiore Health System in New York City. “Physicians have been using the test for about 15 years, but those results were based on information from a relatively small number of patients in 2 studies that were done retrospectively,”he says. “This trial needed to be done in the context of the most modern chemotherapy. We’re now also confirming after 9 years of follow-up that women in the lowest-risk group still have a very low rate of distant recurrence with endocrine therapy alone.” Dr. Sparano adds that the notion of using biomarkers in breast cancer treatment is not new. Clinicians have used them to guide hormone therapy for estrogen receptor (ER)-positive breast cancer for approximately 30 years and have done the same in treating HER2/neu overexpression with trastuzumab (Herceptin) for approximately 13 years, he says, noting, “What this study does is provide an unprecedented level of evidence regarding using these biomarkers to determine chemotherapy in this clinical situation.” Patients who enrolled in the trial underwent the Oncotype DX Breast Recurrence Score test, which assesses for recurrence on the basis of the expression or overexpression of 21 genes previously linked to breast cancer (including ER and HER2/neu). On the basis of individual results, each participant was assigned a risk score of 0 to 100 for cancer recurrence. Evidence gleaned from earlier trials found that women scoring in the low-risk range (0–10) could receive hormone therapy only, whereas those in the high-risk range (≥26) should be treated with both hormone therapy and chemotherapy. In accordance with these findings, TAILORx participants were assigned to either hormone therapy alone or hormone therapy and chemotherapy according to whether they were in the lowor high-risk range. What was unknown until now, however, was whether women scoring in the midrange (11–25) could receive hormone therapy alone and avoid chemotherapy. To determine that answer, trial participants scoring in that range were randomly assigned to receive either hormone therapy alone or hormone therapy with adjuvant chemotherapy. Many Midrange Scorers Can Skip Chemotherapy Researchers found that the proportions of women who had not died or developed a recurrence of a second primary cancer were very similar in the 2 groups. Specifi cally, 5 years after treatment, the rate of invasive disease-free survival was 92.8% for those who had hormone therapy alone and 93.1% for those who also had chemotherapy. At 9 years, the rate was 83.3% for the group that had hormone therapy alone and 84.3% for the group that had both therapies. Neither of these diff erences was considered statistically signifi cant. Similarly, the rates of overall survival after 5 years were 98.0% for the hormone therapy-alone group and 98.1% for the group receiving both therapies. At 9 years, the respective overall survival rates were 93.9% and 93.8%, respectively. In addition, women in the lowest range (0–10) had very low recurrence rates with hormone therapy alone (3%), and this confi rmed earlier TAILORx fi ndings. Researchers also found that women scoring from 26 to 100 had a distant recurrence rate of 13% despite receiving both therapies, and this indicated a need to develop more eff ective therapies for this group. On the basis of their results, the authors made the following recommendations for women with this type of breast cancer. Chemotherapy can be avoided in those who are diagnosed when they are: Older than 50 years with a recurrence score of 11 to 25 (45% of all cases); At any age with a recurrence score of 0 to 10 (16% of all cases); Fifty years old or younger with a recurrence score of 11 to 15 (8% of all cases). “It’s most important for this group of patients with low recurrence scores of up to 25 to know that these good outcomes are highly dependent on their use of endocrine therapy,” Dr. Sparano says. “It’s critical that they take this therapy to get the greatest benefi t.” Chemotherapy should still be considered for the remaining 31% of women with hormone receptor–positive, HER2-negative, node-negative breast cancer who are diagnosed when they are: At any age with a recurrence score of 26 to 100 (17% of all cases); Fifty years old or younger with a recurrence score of 16 to 25 (14% of all cases). Dr. Sparano adds that women who were age 50 years or younger in the study were divided into 3 diff erent groups: those scoring 11 to 15, those scoring 16 to 20, and those scoring 21 to 25. Participants in the 21 to 25 group had a 6% to 7% distant recurrence rate without chemotherapy and, therefore, would still benefi t from it, whereas those in the 11 to 15 group had no benefi t from the addition of chemotherapy, and those in the 16 to 20 range showed a 2% reduction in the rate of distant recurrence with the addition of chemotherapy. Sorting out the recurrence risks for younger women scoring in the 16 to 20 range can be challenging, he adds. A woman with a larger (ie, 3.5 cm), high-grade tumor would be more likely to receive a chemotherapy recommendation than another with a small (ie, 1.5 cm), low-grade tumor, for example. For that reason, Dr. Sparano notes that researchers are working to recalibrate the Recurrence Score Pathology Clinical Index to integrate age, tumor pathology, and recurrence score into a recurrence risk estimate to provide further guidance to clinicians in making this chemotherapy determination. He expects that the tool will be available within a year. Uncertainties for Some Younger Women Remain One question to which scientists do not yet know the answer is whether the chemotherapy benefi t that occurred for some women 50 years old or younger was the result of the cytotoxic eff ect of the drugs or the result of the drugs’ inducing early menopause and having an anti-estrogen eff ect, he says, noting that additional studies would be required to answer that question. Although clinicians have known that chemotherapy is potentially curative, they also have known that only 3% to 5% of women with this type of breast cancer actually benefi t from it, Dr. Sparano notes. As Dr. Brawley elaborates, “I was treating 100 women with chemotherapy knowing that 89 were not going to get any of the benefi ts yet would still get side eff ects from it, while 8 would still relapse, and only 3 would benefi t. Th is test helps me tell a good number of the 89 patients that they don’t need chemo.” Fran Visco, president of the National Breast Cancer Coalition, an advocacy organization based in Washington, DC, says that the results are a positive step. “We’ve known for a long time that this particular population of survivors does well with hormonal therapy and that most don’t need chemotherapy, but the medical oncology community hasn’t moved away from chemo. Hopefully, this will give doctors the evidence they need to stop overtreating women.” Although other genetic recurrence tests for this type of breast cancer exist, Oncotype DX has dominated the market, clinicians say. Meanwhile, another study, the Rx for Positive Node, Endocrine-Responsive Breast Cancer (RxPONDER) trial, is assessing whether patients with ER-positive, HER2-negative breast cancer; 1 to 3 positive lymph nodes; and recurrence scores ranging from 0 to 25 can also receive hormonal therapy alone and avoid chemotherapy. Th is study has completed enrollment, and fi nal results may be available in a few years, Dr. Sparano says. Reference 1Sparano J, Gray R, Makower D, et al. Adjuvant chemotherapy guided by a 21- gene expression assay in breast cancer [published online ahead of print June 3, 2018]. New Engl J Med. https://doi.org/10.1056/NEJMoa1804710. Volume124, Issue16August 15, 2018Pages 3281-2382 This article also appears in:CancerScope Archive 2014-2019 ReferencesRelatedInformation