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

Sep 22, 2026

Background: The KEYNOTE-522 (KN522) trial showed improved outcomes with neoadjuvant chemotherapy plus pembrolizumab in high-risk triple-negative breast cancer, but effectiveness for histologically uncommon TNBC subtypes remains unclear. Patients and methods: A retrospective study compared clinicopathological characteristics and outcomes of stage II–III TNBC treated with KN522 versus conventional NAC without immunotherapy, focusing on IDC with apocrine features and metaplastic carcinoma. Results: KN522 produced a lower pCR rate in IDCapo versus IDC, yet a higher pCR rate than conventional NAC in IDCapo, with no meaningful benefit in metaplastic carcinoma.

LanguageEnglish

CategoryResearch & Report

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Pages10

Reading Time25 min

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Abstract

Background

Patients and methods

Results

Conclusion

Implications for Practice

Key words

The Oncologist, 2026, 31, oyag159 [https://doi.org/10.1093/oncolo/oyag159](https://doi.org/10.1093/oncolo/oyag159) [Published: 26 April 2026](Published: 26 April 2026) Original Article Efficacy of perioperative pembrolizumab for triple-negative breast cancer with apocrine feature or metaplastic carcinoma Nobuyuki Takahashi1,2, , Chikako Funasaka1,3,*, , Mai Shimura1, Akira Hirota1, Mao Uematsu1, Misao Fukuda1, Kaede Baba4, Kanako Mamishin4, Hiromichi Nakajima1,3,5, Chihiro Kondoh1, Kenichi Harano1,3, Nobuaki Matsubara1, , Ako Hosono1, Toshikatsu Kawasaki4, Tatsuya Onishi6, Yoichi Naito1,3,5, , Toru Mukohara1,*, 1 Department of Medical Oncology, National Cancer Center Hospital East, Kashiwa, Chiba 277-8577, Japan 2 Minamiakatsuka Clinic, Mito, Ibaraki, 311-4153, Japan 3 Department of Experimental Therapeutics, National Cancer Center Hospital East, Kashiwa, Chiba, 277-8577, Japan 4 Department of Pharmacy, National Cancer Center Hospital East, Kashiwa, Chiba, 277-8577, Japan 5 Department of General Internal Medicine, National Cancer Center Hospital East, Kashiwa, Chiba, 277-8577, Japan 6 Department of Breast Surgery, National Cancer Center Hospital East, Kashiwa, Chiba, 277-8577, Japan *Corresponding authors. Chikako Funasaka, Department of Medical Oncology, National Cancer Center Hospital East, Kashiwa, Chiba 277-8577, Japan; Department of Experimental Therapeutics, National Cancer Center Hospital East, Kashiwa, Chiba, 277-8577, Japan. E-mail: [cfunasak@east. ncc.go.jp](cfunasak@east. ncc.go.jp); Toru Mukohara, Department of Medical Oncology, National Cancer Center Hospital East, Kashiwa, Chiba 277-8577, Japan. E-mail: [tmukohar@east. ncc.go.jp](tmukohar@east. ncc.go.jp). Abstract 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 atthe 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. Key

FAQs

What question does the study address about pembrolizumab in triple-negative breast cancer?

It evaluates how neoadjuvant chemoimmunotherapy with perioperative pembrolizumab performs in histologically uncommon TNBC subtypes, specifically invasive ductal carcinoma with apocrine features and metaplastic carcinoma.

How were patients grouped in this retrospective study?

Patients with clinical stage II or III TNBC received either the KN522 regimen or conventional NAC without immunotherapy, and included tumors pathologically diagnosed as IDC, IDCapo, or metaplastic carcinoma.

What were the main findings regarding pathological complete response (pCR)?

The pCR rate was significantly lower in IDCapo than in IDC, and no metaplastic carcinoma patient achieved pCR. Compared with conventional NAC, KN522 improved pCR in IDCapo but not in metaplastic carcinoma.

Sep 22, 2026

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