Hüseyin GÖBÜT, Çağrı BÜYÜKKASAP

Predictors for axillary lymph node metastasis in primary neuroendocrine carcinomas of the breast and neuroendocrine differentiated breast cancers

Aims: Primary neuroendocrine carcinomas of the breast (NEC) and neuroendocrine differentiated breast cancers are rare entities. The aim of this study was to investigate clinical and histopathological findings and predictors for axillary lymph node metastasis (ALNM) in primary neuroendocrine carcinomas of the breast (NEC) and neuroendocrine differentiated breast cancers (NEBC). Methods: Patients with a diagnosis of breast cancer with histopathological neuroendocrine features between the years 2015 and 2022 were retrospectively screened. The patients were divided into two main groups, the NEC and NEBC groups. The two groups were evaluated in terms of their clinical and histopathological characteristics and predictive factors for axillary lymph node. Results: A total of 35 patients [NEBC group: 24 patients, NEC group: 11 patients) were evaluated. At the time of diagnosis, the median age was 57 (NEC: 49 years, NEBC: 57.5). Of the 35 patients, 15 (57.1%) had ALNM, and lymphovascular invasion was detected in 16 (45.7%). When the whole patient population was evaluated for ALNM, it was found that lymphovascular invasion had an effect on ALNM (p=0.005). In the NEBC group, the rate of ALNM was associated with an increase in tumor diameter (p=0.035). Additionally, the tumor diameter was found to be predictive of ALNM in the ROC analysis (AUC: 0.753, 95% CI: 0.557-0.950, cut-off: 2.35 cm, p=0.035). Analyses of correlation revealed a low-level correlation between age and Ki-67 in the study cohort ( ρ= -0.341, p=0.45). Conclusion: NECs and NEBCs of the breast are uncommon tumors with a high ALNM potential. Patients with lymphovascular invasion and a large tumor diameter should be carefully evaluated for ALNM. Further research is required to determine the most appropriate treatment strategy for these rare subtypes of breast cancers.

Keywords:

Neuroendocrine, breast cancer axillary lymph node metastasis, nodal status,

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Kayadibi Y, Erginoz E, Cavus GH, Kurt SA, Ozturk T, Velidedeoglu M. Primary neuroendocrine carcinomas of the breast and neuroendocrine differentiated breast cancers: relationship between histopathological and radiological features. Eur J Radiol. 2022;147:110148. doi:10.1016/j.ejrad.2021.110148
Trevisi E, La Salvia A, Daniele L, et al. Neuroendocrine breast carcinoma: a rare but challenging entity. Med Oncol. 2020;37(8):70. doi:10.1007/s12032-020-01396-4
Bussolati G, Badve S. Carcinomas with neuroendocrine features. WHO Classification of Tumours of the Breast. 2012;4:62-3.
Tan PH, Ellis I, Allison K, et al. The 2019 World Health Organization classification of tumours of the breast. Histopathology. 2020;77(2):181-185. doi:10.1111/his.14091
Hacking SM, Yakirevich E, Wang Y. Defining triple-negative breast cancer with neuroendocrine differentiation (TNBC-NED). J Pathol Clin Res. 2023;9(4):313-321. doi:10.1002/cjp2.318
Gradishar WJ, Moran MS, Abraham J, et al. NCCN Guidelines® Insights: Breast Cancer, Version 4.2023. J Natl Compr Canc Netw. 2023;21(6):594-608. doi:10.6004/jnccn.2023.0031
Lakhani SR, Ellis IO, Schnitt S, Tan PH, van de Vijver M. WHO Classification of Tumours of the Breast. WHO; 2012.
Rosen LE, Gattuso P. Neuroendocrine tumors of the breast. Arch Pathol Lab Med. 2017;141(11):1577-1581. doi:10.5858/arpa.2016-0364-RS
Wang J, Wei B, Albarracin CT, Hu J, Abraham SC, Wu Y. Invasive neuroendocrine carcinoma of the breast: a population-based study from the surveillance, epidemiology and end results (SEER) database. BMC Cancer. 2014;14:147. doi:10.1186/1471-2407-14-147
Krawczyk N, Röwer R, Anlauf M, et al. Invasive breast carcinoma with neuroendocrine differentiation: a single-center analysis of clinical features and prognosis. Geburtshilfe Frauenheilkd. 2022;82(1):68-84. doi:10.1055/a-1557-1280
Makretsov N, Gilks CB, Coldman AJ, Hayes M, Huntsman D. Tissue microarray analysis of neuroendocrine differentiation and its prognostic significance in breast cancer. Hum Pathol. 2003;34(10):1001-1008. doi:10.1053/s0046-8177(03)00411-8
van Krimpen C, Elferink A, Broodman CA, Hop WC, Pronk A, Menke M. The prognostic influence of neuroendocrine differentiation in breast cancer: results of a long-term follow-up study. Breast. 2004;13(4):329-333. doi:10.1016/j.breast.2003.11.008
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017;67(1):7-30. doi:10.3322/caac.21387
Pan H, Gray R, Braybrooke J, et al. 20-year risks of breast-cancer recurrence after stopping endocrine therapy at 5 years. N Engl J Med. 2017;377(19):1836-1846. doi:10.1056/NEJMoa1701830
Lux MP, Schneeweiss A, Hartkopf AD, et al. Update breast cancer 2020 part 5-moving therapies from advanced to early breast cancer patients. Geburtshilfe Frauenheilkd. 2021;81(4):469-480. doi:10.1055/a-1397-7170
Lavigne M, Menet E, Tille JC, et al. Comprehensive clinical and molecular analyses of neuroendocrine carcinomas of the breast. Mod Pathol. 2018;31(1):68-82. doi:10.1038/modpathol.2017.107
Wei B, Ding T, Xing Y, et al. Invasive neuroendocrine carcinoma of the breast: a distinctive subtype of aggressive mammary carcinoma. Cancer. 2010;116(19):4463-4473. doi:10.1002/cncr.25352
Rovera F, Lavazza M, La Rosa S, et al. Neuroendocrine breast cancer: retrospective analysis of 96 patients and review of literature. Int J Surg. 2013;11(S1):79-83. doi:10.1016/s1743-9191(13)60023-0
Zhang Y, Chen Z, Bao Y, et al. Invasive neuroendocrine carcinoma of the breast: a prognostic research of 107 Chinese patients. Neoplasma. 2013;60(2):215-222. doi:10.4149/neo_2013_029
Cloyd JM, Yang RL, Allison KH, Norton JA, Hernandez-Boussard T, Wapnir IL. Impact of histological subtype on long-term outcomes of neuroendocrine carcinoma of the breast. Breast Cancer Res Treat. ı2014;148(3):637-644. doi:10.1007/s10549-014-3207-0
Kwon SY, Bae YK, Gu MJ, et al. Neuroendocrine differentiation correlates with hormone receptor expression and decreased survival in patients with invasive breast carcinoma. Histopathology. 2014;64(5):647-659. doi:10.1111/his.12306
Park YM, Wu Y, Wei W, Yang WT. Primary neuroendocrine carcinoma of the breast: clinical, imaging, and histologic features. AJR Am J Roentgenol. 2014;203(2):221-230. doi:10.2214/ajr.13.10749
Bogina G, Munari E, Brunelli M, et al. Neuroendocrine differentiation in breast carcinoma: clinicopathological features and outcome. Histopathology. 2016;68(3):422-432. doi:10.1111/his.12766
Roininen N, Takala S, Haapasaari KM, et al. Primary neuroendocrine breast carcinomas are associated with poor local control despite favourable biological profile: a retrospective clinical study. BMC Cancer. 2017;17(1):72. doi:10.1186/s12885-017-3056-4
Metovic J, Cascardi E, Uccella S, et al. Neuroendocrine neoplasms of the breast: diagnostic agreement and impact on outcome. Virchows Archiv. 2022;481(6):839-846. doi:10.1007/s00428-022-03426-0
Yang L, Lin H, Shen Y, et al. Clinical outcome and therapeutic impact on neuroendocrine neoplasms of the breast: a national cancer database study. Breast Cancer Res Treat. 2023;doi:10.1007/s10549-023-07052-5
Howlader N, NA KM, Miller D, et al. SEER Cancer Statistics Review, 1975-2016. National Cancer Institute; 2019.
Sawaki M, Yokoi K, Nagasaka T, et al. Prognostic importance of neuroendocrine differentiation in Japanese breast cancer patients. Surg Today. 2010;40(9):831-835. doi:10.1007/s00595-009-4179-2
Zhu X, Chen L, Huang B, et al. The prognostic and predictive potential of Ki-67 in triple-negative breast cancer. Sci Rep. 2020;10(1):225. doi:10.1038/s41598-019-57094-3
Eble JN, Tavassoli FA, Devilee P. Pathology and genetics of tumours of the breast and female genital organs. IARC; 2003.