Should the Recurrence Score for Downstaging Breast Cancer Be Expanded?

By Marilynn Larkin

June 14, 2021

NEW YORK (Reuters Health) - The American Joint Committee on Cancer (AJCC)'s pathologic prognostic staging system low-risk Recurrence Score (RS) for downstaging breast cancer should be expanded from < 11 to less than < 18, researchers suggest.

"We are increasingly understanding the importance of tumor biology in breast cancer, and the added prognostic value of genomic assays, including the OncotypeDX Breast Recurrence Score, in hormone receptor-positive/HER2-negative (HR+HER2-) breast cancer," Dr. Olga Kantor of Brigham and Women's Hospital in Boston told Reuters Health by email.

"Randomized data from the TAILORx trial suggested that node-negative patients with RS <26 do not benefit from the addition of chemotherapy to endocrine therapy, and a growing body of evidence is showing that a low RS in node-positive patients is associated with a favorable prognosis," she said. "Taken together, these data suggest that RS results may be useful in identifying an expanded group of low-risk patients."

Given the study results, she added, "we would advocate for further modification of . . . the prognostic pathologic stage IA criteria to include patients with RS of <18 for both N0 and N1 disease of any T category."

"For example, a grade 3 T2N1 HR+HER2- breast cancer with an RS of 14 would be anatomic stage IIB and pathologic prognostic stage IIA using the current staging system," she said. "Application of our data suggests that this patient's prognosis is statistically similar to other pathologic prognostic stage IA patients and could be further downstaged to pathologic prognostic stage IA."

As reported in the Journal of the National Cancer Institute, Dr. Kantor and colleagues analyzed Surveillance, Epidemiology, and End Results (SEER) data to identify patients with T1-3N0-3M0 HR-positive/HER2-negative breast cancer treated from 2010 to 2015 with follow-up data through 2016.

Among more than 154,000 patients, most (74%) were older than 50 years and had ductal histology (74%), T1 tumors (68%) and node-negative disease (71%).

Overall, 33% received chemotherapy; 55% were anatomic stage IA and 73% were PPS IA.

The primary outcome was five-year disease-specific survival (DSS) of patients with low-risk RS results not already pathologic prognostic stage IA, determined by T and N categories per the AJCC 8th edition. Median follow-up was 49 months.

RS results were obtained for 40% of participants: <11 in 22%; 11-17 in 37%; 18-25 in 27%; and 26 or more in 13%.

Five-year DSS for patients with pathologic prognostic stage IA disease (75% of the patients) was 99%. Among N0-1 patients with RS<18 not staged as pathologic prognostic stage IA by current criteria, five-year DSS was not statistically significantly different than for pathologic prognostic stage IA patients (97.2%-99.7%).

For those with RS 18-25, there was a small decrease in DSS for T2N0 (2.3%) and a modest decrease for T1-2N1 (4.2%-6.4%) compared with patients with pathologic prognostic stage IA disease.

The authors conclude, "Patients with RS<18 have excellent 5-year DSS regardless of T category for N0-1 disease suggesting further modification of the AJCC staging system using this cutoff."

Dr. Kantor added, "Next steps include validation of this retrospective data with prospective randomized clinical trial data and further investigation of the RS 18-25 group of patients."

Surgical oncologist Dr. Andrea Porpiglia, Assistant Professor at Fox Chase Cancer Center in Philadelphia, commented in an email to Reuters Health, "I do not agree with changing the cutoff of RS<18 on future AJCC staging based on this study."

"This is a retrospective review, and with this (there is a) potential for selection bias," she told Reuters Health by email. "In addition, the SEER database may not completely capture the true number of patients who received chemotherapy, thereby potentially biasing the study results."

Therefore, she said, "it is too premature to change current guidelines. We need more prospective data to justify modifying the cutoff."

SOURCE: Journal of the National Cancer Institute, online May 19, 2021.