Abstract
Background: Small-cell carcinoma of the breast is a rare disease with little research outlining molecular targets or optimal therapeutic management. We summarize a young female patient with poorly differentiated high-grade carcinoma with neuroendocrine features/small-cell carcinoma. Case presentation: A 31-year-old female presented with a large left breast mass. Initial biopsy revealed small-cell, triple-negative breast carcinoma. Treatment consisted of cisplatin and etoposide but was poorly tolerated and discontinued after one cycle. Combination abraxane/atezolizumab resulted in transient partial response in tumor size with 7 months of progression-free stability. Worsening metastatic disease was found 8 months after initial biopsy on radiologic studies and the patient expired 10 months after initial biopsy. Conclusion: Transient benefit in response to combination abraxane/atezolizumab was demonstrated.
Plain language summary
Immunotherapy is an emerging area in cancer research which utilizes the body's immune system to target cancerous cells. This offers oncologists an effective alternative to standard chemotherapy options, which often have significant side effects. Additionally, biomarkers including PD-L1 positivity to predict response to immunotherapy are currently under investigation. The patient presented with a rare type of aggressive breast cancer that previously had few treatment options. This report demonstrates the use of biomarker assessment (PD-L1) to predict immunotherapy response. The patient responded well to immunotherapy, and radiologic scans demonstrated tumor reduction. Further research into this field has the implication to improve treatments, decrease side effects of chemotherapy and improve patient outcomes for many cancers.
Papers of special note have been highlighted as: • of interest; •• of considerable interest
References
- 1. . On the carcinoid growth form of the carcinoma mammae, especially the carcinoma solidum (gelatinosum) mammae (in German). Frankf. Z Pathol. 73, 24–39 (1963).
- 2. . Neuroendocrine cancer of the breast: a rare entity. J. Clin. Med. 9(5), 1452 (2020).
- 3. . Neuroendocrine tumors of the breast. Arch. Path. Lab. 141(11), 1577–1581 (2017). • Comprehensive article outlining the historical and current information on pathologic findings and diagnostic criteria.
- 4. . Invasive neuroendocrine carcinoma of the breast: a population-based study from the surveillance, epidemiology and end results (SEER) database. BMC Cancer 14(1), 147 (2014). • Retrospective analysis of 142 cases of neuroendocrine breast carcinomas form the SEER database with the identification prognostic indicators.
- 5. Primary neuroendocrine breast carcinomas are associated with poor local control despite favourable biological profile: a retrospective clinical study. BMC Cancer 17(1), 72 (2017).
- 6. Novel mutations in neuroendocrine carcinoma of the breast: possible therapeutic targets. Appl. Immunohistochem. Mol. Morphol. 23(2), 97–103 (2015).
- 7. . Primary small cell neuroendocrine carcinoma of the breast – a case report and review of the literature. Int. J. Surg. Case Rep. 38, 29–31 (2017). • Analysis of 47 neuroendocrine carcinomas to identify driver mutations.
- 8. Comprehensive clinical and molecular analyses of neuroendocrine carcinomas of the breast. Mod. Pathol. 31(1), 68–82 (2018).
- 9. Comparison of metastatic neuroendocrine neoplasms to the breast and primary invasive mammary carcinomas with neuroendocrine differentiation. Mod. Pathol. 29(8), 788–798 (2016).
- 10. . Metastatic primary neuroendocrine carcinoma of the breast (NECB). J. Can. Res. Prac. 5(1), 38–42 (2018).
- 11. . Immunotherapy in small cell lung cancer. Eur. Med. J. 4(1), 43–53 (2019).
- 12. NCCN guidelines insights: non-small cell lung cancer, version 2.2021. J. Natl Compr. Canc. Netw. 19(3), 254–266 (2021).
- 13. Neuroendocrine and adrenal tumors, version 2.2021, NCCN clinical practice guidelines in oncology. J. Natl Compr. Canc. Netw. 19(7), 839–868 (2021).
- 14. NCCN guidelines® insights: breast cancer, version 4.2021: featured updates to the NCCN guidelines. J. Natl Compr. Cancer Netw. 19(5), 484–493 (2021).
- 15. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N. Engl. J. Med. 379(22), 2108–2121 (2018).
- 16. . Mismatch repair deficiency/microsatellite instability-high as a predictor for anti-PD-1/PD-L1 immunotherapy efficacy. J. Hematol. Oncol. 12(1), 54 (2019).
- 17. Differential regulation of PD-L1 expression by immune and tumor cells in NSCLC and the response to treatment with atezolizumab (anti-PD-L1). Proc. Natl Acad. Sci. 115(43), E10119–E10126 (2018).
- 18. . Immune checkpoint inhibitors in the treatment of patients with neuroendocrine neoplasia. Oncol. Res. Treat. 41(5), 306–312 (2018). •• Suggests PD-L1 inhibition is effective for the treatment of high-grade neuroendocrine tumors.
- 19. Checkpoint inhibitor is active against large cell neuroendocrine carcinoma with high tumor mutation burden. J. Immunother. Cancer 5(1), 75 (2017).
- 20. LBA79 – association between tissue TMB (tTMB) and clinical outcomes with pembrolizumab monotherapy (pembro) in PD-L1-positive advanced NSCLC in the KEYNOTE-010 and -042 trials. Ann. Oncol. 30, v916–v917 (2019).
- 21. PD-L1 immunohistochemistry assay comparison in atezolizumabpPlus nab-paclitaxel-treated advanced triple-negative breast cancer. J. Natl Cancer Inst. 113(12), 1733–1743 (2021).
- 22. Comparison of three scoring methods using the FDA-approved 22C3 immunohistochemistry assay to evaluate PD-L1 expression in breast cancer and their association with clinicopathologic factors. Breast Cancer Res. 22(1), 69 (2020).