The 21-gene recurrence score (RS) assay predicts the likelihood of distant recurrence and chemotherapy benefit in early-stage, estrogen receptor (ER)-positive, HER2-negative breast cancer. Data on the RS of special histologic subtypes of invasive breast carcinoma with favorable prognosis are limited.

We reviewed our institutional database to identify patients with special histologic subtypes of breast cancer associated with favorable prognosis and available RS results. Our cohort consists of fifty-seven women: thirty-three patients with pure mucinous carcinoma (MC), ten with tubular carcinoma (TC), nine with encapsulated papillary carcinoma (EPC), and five with solid papillary carcinoma (SPC).

Most (44/57, 77.2%) carcinomas had low RS (≤17), and none had high RS (≥31). All EPCs had low RS, but other subtypes had RS 18-30. Higher RS was associated with lower progesterone receptor (PR) expression by immunohistochemistry and lower PR mRNA scores (P ≤ 0.007). No morphologic feature (tumor grade, biopsy site changes, cellular stroma, inflammatory cells) was associated with RS ≥ 18. At a median follow-up of 40 months, the distant recurrence-free survival was 100%. One patient with SPC developed locoregional recurrence at 22 months.

As the largest series to date, our study raises the question of whether the RS assay is necessary for breast cancers with favorable histology. Reflex testing of node-negative, ER+/HER2- breast cancers may be deferred for these special histologic subtypes, emphasizing the need for multidisciplinary discussions between breast pathologists and other members of the breast cancer team.