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Chemotherapy may not be necessary for intermediate-risk, early-stage breast cancer

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March 17, 2017

Women with early-stage breast cancer and an intermediate risk recurrence score from a 21-gene expression assay may be able to avoid chemotherapy, according to a retrospective study published in Cancer.

“Through years of research discoveries, it became clear that we were overtreating many women with breast cancer, especially those with early-stage breast cancer,” Carlos H. Barcenas, MD, assistant professor of breast medical oncology at The University of Texas MD Anderson Cancer Center, said in a press release. “In addition to chemotherapy’s obvious side effects, there were also long-term complications for these women as survivors.”

Carlos H. Barcenas

Historically, women with stage I and stage II breast cancer have been treated aggressively with chemotherapy. However, a 2015 international clinical trial called TAILORx demonstrated that women with hormone receptor–positive, HER-2–negative, lymph node–negative early-stage disease could omit chemotherapy if they had 21-gene recurrence score (Oncotype DX, Genomic Health) of 0 to 10.

Barcenas and colleagues evaluated whether women with this type of breast cancer and an intermediate recurrence score of 11 to 25, who were treated with endocrine therapy, also could abstain from chemotherapy.

“This study evolved out of my patients’ frustration that I could not provide a definitive answer to their paramount question: ‘Do I need chemotherapy?’” Barcenas said. “We decided to look at [MD Anderson Cancer Center’s] own experience to glean insight on how best to care for these women with an intermediate-risk recurrence score.”

Researchers collected data from 1,424 women (median age 56 years; 72.8% white) diagnosed with hormone receptor–positive, HER-2–negative, lymph node–negative breast cancer between 2005 and 2011. The researchers charted the patients’ invasive DFS, RFS, distant RFS and OS.

In total, 297 women had a recurrence score of 0 to 10, of whom 1.7% received chemotherapy; 894 had a recurrence score of 11 to 25, of whom 15% received chemotherapy; and 233 had a recurrence score greater than 25, of whom 73.4% received chemotherapy.

Women in the recurrence score 11 to 25 group who received chemotherapy tended to be younger and have larger and more stage II tumors than those who did not receive chemotherapy.

At a median follow-up of 58 months, women with a recurrence score of 11 to 25 achieved a 5-year invasive DFS rate of 92.6% (95% CI, 89.6-94.7), which was comparable between women who received chemotherapy and those who did not (89% vs. 93%).

Similarly, women who received chemotherapy and those who did not achieved comparable 5-year RFS (95% vs. 96%), distant RFS (96% vs. 96%) and OS (98% vs. 98%).


The effect of chemotherapy demonstrated HRs of 1.64 (95%, 0.73-3.71) for invasive DFS, 1.46 (95% CI, 0.41-5.23) for RFS, 1.25 (95% CI, 0.32-4.91) for distant RFS and 2.19 (95% CI, 0.44-11) for OS.

Barcenas and colleagues noted a relatively short follow-up of 58 months and the low number of women who underwent chemotherapy in the intermediate-risk recurrence score group as limitations of the study and indicated their findings should not be considered practice-changing.

“Our research is likely the most comprehensive data we will have about this patient population until the international randomized trial is published,” Barcenas said. “Hopefully, our findings will serve as a discussion point between physicians and patients as they are making critical decisions regarding a woman’s breast cancer care.” – by Chuck Gormley

Disclosure: An MD Anderson Cancer Center grant from NCI funded this study. One researcher reports an advisory role with Agendia, which markets the MammaPrint assay.

itj+ Perspective

Antoinette R. Tan

Multiparameter genomic assays are available for decision-making regarding utility of adjuvant chemotherapy in early-stage breast cancer. Both ASCO and the National Comprehensive Cancer Network (NCCN) recommend the use of the 21-gene expression assay (Oncotype DX, Genomic Health) in the management of hormone receptor–positive, HER-2–negative and node-negative early-stage breast cancer. Results from the prospective TAILORx (Trial Assigning Individualized Options for Treatment) trial showed that the subset of patients with hormone receptor–positive, HER-2–negative, node-negative breast cancer with a low recurrence score (RS) — defined as 10 or less using the 21-gene expression assay — can be spared adjuvant chemotherapy due to very low rates of recurrence.

Prospective data are not yet available regarding the benefit of adding chemotherapy to adjuvant endocrine therapy for patients with an intermediate RS between 11 to 25 — a cutoff used in TAILORx, but lower than what is defined commercially. Barcenas and colleagues provide retrospective data in this subset of patients with breast cancer, which included 1,424 patients with stage I and II breast cancer. Of them, 297 (21%) scored 0 to 10, 1.7% of whom received chemotherapy; 894 (63%) scored 11 to 25, 15% of whom received chemotherapy; and 233 (16%) scored greater than 25, 73.4% of whom received chemotherapy.

Overall, those with a RS of 11 to 25 had a 5-year invasive DFS rate of 92.6%, regardless of whether patients received chemotherapy. Researchers estimated a 5-year invasive DFS rate of 93% and 5-year OS rate of 98% for those who did receive chemotherapy, which appeared comparable to those who did receive chemotherapy (invasive DFS, 89%; OS, 98%).

In clinical practice, an intermediate RS is a challenging and complex discussion. Results from this analysis add to the thoughtful information exchange that takes place between oncologists and their patients about the risks vs. potential benefit and whether to give chemotherapy. When making these treatment decisions, one often also considers other factors, including tumor size and grade, patient concerns, age, comorbidities and long-term effects of chemotherapy-related toxicities.

Current NCCN guidelines for the intermediate-risk RS group recommend adjuvant endocrine therapy or adjuvant chemotherapy followed by endocrine therapy. Although helpful to have this dataset available, the study is limited in being a retrospective single-institution study. Any small incremental benefit from chemotherapy cannot be ruled out, as this analysis had short follow-up, few events and a low number treated with chemotherapy. It would be interesting to know the reason so few patients received chemotherapy and whether they had a RS at the higher end of the cutoff.  

Discussion of this retrospective dataset with our patients is helpful and relevant while we await additional follow-up results from TAILORx, which we hope will add clarity to the use of chemotherapy in patients with breast cancer and midrange RS.


Harris LN, et al. J Clin Oncol. 2016;doi:10.1200/JCO.2015.65.2289.

Sparano JA, et al. N Engl J Med. 2015;doi:10.1056/NEJMoa1510764.

Antoinette R. Tan, MD, MHSc, FACP

HemOnc Today Editorial Board Member

Levine Cancer Institute

Carolinas HealthCare System

Disclosure: Tan reports no relevant financial disclosures.