Efficacy of perioperative pembrolizumab for triple-negative breast cancer with apocrine feature or metaplastic carcinoma

BACKGROUND: The KEYNOTE-522 (KN522) trial demonstrated significantly improved outcomes with neoadjuvant chemotherapy (NAC) combined with pembrolizumab in high-risk triple-negative breast cancer (TNBC). However, the efficacy of this chemoimmunotherapy for histologically uncommon TNBC subtypes, such as invasive ductal carcinoma (IDC) with apocrine feature (IDCapo) or metaplastic carcinoma, remains unclear. PATIENTS AND METHODS: This retrospective study examined clinicopathological characteristics and outcomes of patients with clinical stage II or III TNBC treated with either the KN522 regimen or conventional NAC without immunotherapy at the National Cancer Center Hospital East between August 2014 and December 2024. Patients pathologically diagnosed with IDC, IDCapo, or metaplastic carcinoma were included. We compared outcomes of the KN522 regimen among histologic subtypes and evaluated its efficacy versus conventional NAC in patients with IDCapo or metaplastic carcinoma. RESULTS: Seventy-two patients with TNBC received the KN522 regimen: 58 IDC, 10 IDCapo, and 4 metaplastic carcinoma. The pathological complete response (pCR) rate was significantly lower in IDCapo than in IDC (3/10 [30.0%] vs. 41/58 [70.7%], P = 0.027), and this difference remained after adjustment for clinical factors. There were no metaplastic carcinoma patients with pCR (0/4, 0%). Compared with conventional NAC, the KN522 regimen yielded a higher pCR rate in IDCapo (3/10 [30.0%] vs. 0/19 [0%], P = 0.033), but not in metaplastic carcinoma (0/4 [0%] vs. 1/10 [10.0%], P = 1.00). CONCLUSION: The pCR rate of NAC with pembrolizumab was significantly lower in IDCapo than in IDC but was improved compared with conventional NAC. No meaningful benefit was observed in metaplastic carcinoma. IMPLICATIONS FOR PRACTICE: This study suggests that neoadjuvant chemoimmunotherapy can improve pathological complete response rate in invasive ductal carcinoma with apocrine feature, known as therapeutically resistant uncommon histology of the breast cancer. Pathological complete response rates of the neoadjuvant chemoimmunotherapy is dismal in metaplastic breast carcinoma, which sheds light to highly unmet need of novel therapeutic strategies for such aggressive breast cancer.