Clinical-pathologic characteristics and response to neoadjuvant chemotherapy in triple-negative low Ki-67 proliferation (TNLP) breast cancers

Triple-negative breast cancers (TNBCs) often have a high Ki-67 proliferation index and respond favorably to neoadjuvant chemotherapy (NACT) with pathologic complete response (pCR) resulting in ~40% of cases. Nevertheless, morbidity/mortality remain high, mostly due to recurrence in patients with residual disease. In contrast, the incidence and clinical features of TNBC with low proliferation (TNLP), defined as TNBC with a Ki-67 index of ≤30% remains unknown. We report 70 cases of TNLP identified at our center from 2008 to 2018, including 18 treated with NACT. TNLP tumors represent <1% of all breast cancers, and ~5–10% of TNBCs. Ninety percent of carcinomas were grade I/II and 70% were either pure apocrine or showed apocrine differentiation. Fifty cases had available immunohistochemistry results; 80%, 84%, 22%, and 20% were positive for AR, INPP4B, nestin, and SOX10, respectively. With a median follow-up of 72 months, 14% experienced recurrence, and 11% died of breast cancer. The tumor stage was prognostic. Among 39 stage-I patients, 18 (46%) received chemotherapy, but this did not impact survival. There was a trend for improved recurrence-free survival with chemotherapy in stage-II patients. Of the 18 patients treated with NACT, 2 (11%) showed pCR; these were notable for either high stromal TILs or a high mitotic count despite a low Ki-67 index. TNLPs are enriched in low to intermediate-grade carcinomas with apocrine features. Due to overall good prognosis of stage-I TNLP and the lack of clear benefit of chemotherapy, de-escalation of chemotherapy may be considered in select patients with stage-I TNLP.