From the Journals

PAM50-based score identifies low-risk subset with node-positive early-stage breast cancer

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Findings could lead to de-escalation of adjuvant therapy

The study by Laenkholm et al. provides encouraging data for the clinical utility of molecular assays to aid decision making for node-positive disease.

The investigators were able to select a subset of patients with node-positive disease with an estimated 10-year distant recurrence risk of less than or equal to 5%, based on the PAM50 risk of recurrence score. It could be argued that the data do not address the issue of whether chemotherapy would offer some benefit (predictive) in a node-positive population; however, a counterargument is that whatever small added benefit may be derived from adjuvant chemotherapy would be offset by adverse effects, resulting in a net gain of zero. The collective data from evaluation of other assays in this population suggest that patients with ER-positive disease, one to three positive nodes, and a low recurrence score can safely avoid adjuvant chemotherapy and receive endocrine therapy alone. This supports the current NCCN guidelines, which indicate the recurrence score assay can be considered in patients with one to three positive nodes. The more definitive answer on whether adjuvant chemotherapy adds benefit to endocrine therapy will be determined from the RxPONDER study, in which patients with ER+ disease, one to three positive nodes, and a recurrence score less than or equal to 25 will be randomly assigned to chemotherapy or not.

Ricardo L. B. Costa, MD, MS, is with the H. Lee Moffitt Cancer Center, Tampa. William J. Gradishar, MD, is with Northwestern University, Chicago. Dr. Costa disclosed ties with Bristol-Myers Squibb. Dr. Gradishar reported having no relevant financial disclosures. Their comments were adapted from an editorial (J Clin Oncol. 2018 Jan 25. doi: 10.1200/JCO.2017.76.9802).


 

FROM JOURNAL OF CLINICAL ONCOLOGY

The PAM50-based risk of recurrence (ROR) score enabled selection of a subset of patients with estrogen receptor (ER)–positive early-stage breast cancer with node-positive or node-negative disease with an estimated 10-year distant recurrence (DR) absolute risk of less than 5%, investigators reported.

This subset of patients with one to three positive lymph nodes presented a sufficiently low risk of disease recurrence and could safely avoid chemotherapy, reported Anne-Vibeke Laenkholm, MD, and her associates. The report was published in the Journal of Clinical Oncology.

The PAM50-based ROR score (Prosigna Score; Nanostring Technologies, Seattle) is a comparative gene expression profile of the tumor, relative to each of the four PAM50 molecular profiles (luminal A, luminal B, basal, and HER2 enriched) to determine the degree of similarity. The Prosigna assay currently has Food and Drug Administration clearance for prognostic use.

Postmenopausal women diagnosed with ER-positive/HER2-negative early-stage breast cancer in Denmark between 2000 and 2003, and who received adjuvant treatment with tamoxifen or an aromatase inhibitor without chemotherapy were eligible for this cohort study.

The primary endpoint was time to DR, defined as the interval from breast cancer surgery until DR or death as a result of breast cancer. Secondary endpoints included overall survival and time to any recurrence. “The median age of patients was 63 years (range, 50-89 years); 45.5% were node negative, and 54.5% had one to three positive nodes. Tumor characteristics including nodal status, tumor size, malignancy grade, and lymphovascular invasion were all associated with DR, whereas treatment adherence was not,” wrote Dr. Laenkholm of the department of surgical pathology, Zealand University Hospital, Denmark, and her colleagues.

“With a median follow-up of approximately 9 years, 26% of the patients with node-positive disease were categorized as having a low ROR score corresponding to a DR of 3.5% at 10 years compared with those with an intermediate ROR score with a DR of 11.5% and those with a high ROR score corresponding to a DR risk of 22%. In the node-negative group, those with a low ROR score had a 10-year DR risk of 5% and those with an intermediate ROR score had a 7.3% 10-year DR risk, compared with a DR of 17.8% in those with a high ROR score,” Dr. Laenkholm and her associates reported.

The data are entirely prognostic and do not address whether chemotherapy might offer some benefit in a node-positive population (i.e., one to three nodes), or whether adjuvant chemotherapy–associated adverse effects may offset the added benefit, if any, the investigators said.

Nonetheless, genomic assay–based scoring tools are an important aid in clinical decision making readily available to the physician at the patient’s bedside, they said.

Nanostring Technologies funded the study. Laboratory work flow was executed at the department of surgical pathology, Zealand University Hospital. Several authors reported ties with Roche and other pharmaceutical companies.

SOURCE: Laenkholm et al. J Clin Oncol. 2018 Jan 25. doi: 10.1200/JCO.2017.74.6586.

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