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Neuroendocrine carcinoma of the breast: a review of 126 cases in China

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Neuroendocrine carcinoma of the breast (NECB) accounts for approximately 0.3%–0.5% of all breast cancers [1, 2]. Due to the rarity of NECB, current understanding of this disease in China is limited to case reports and small case series, and large data analysis is still lacking. Therefore, we conducted the most comprehensive literature search to date, aiming to analyze the clinicopathologic characteristics as well as treatment and outcome of NECB in the Chinese population.

In the present study, we reported seven NECB cases diagnosed between 1990 and 2015 at the National Cancer Center & Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Additionally, we performed a literature search of the Wanfang and Weipu databases (using the following key words: breast, neuroendocrine, tumor/carcinoma/neoplasm/cancer, primary tumor/carcinoma/neoplasm/cancer, and breast tumor/carcinoma/neoplasm/cancer). Articles published between 2003 and 2015 were collected and reviewed (Table 1). NECB case reports published in non-Chinese journals were not included in this study. The diagnosis was confirmed if (a) more than 50% of the tissue specimens exhibited neuroendocrine markers, and (b) ductal carcinoma in situ was identified and/or imaging examinations and extramammary sites were excluded. Descriptive statistics were calculated for epidemiologic, clinical, and pathologic features, for treatment, and for follow-up.

Table 1 Summary of published articles about neuroendocrine carcinoma of the breast included in this study

The main clinicopathologic features of the seven cases diagnosed at our hospital are summarized in Table 2. There were six female patients and one male patient. The median age was 49 years (range, 33–78 years). All patients presented with breast lump, and one patient developed skin ulceration. Five of seven patients had the well-differentiated subtype of disease, and two patients had poorly-differentiated disease. Five patients had early-stage disease of luminal subtype. Six patients received chemotherapy and surgery, whereas one patient received chemotherapy alone. Patients with positive estrogen receptors (ERs) received endocrine therapy. The follow-up time ranged from 31 to 59 months. Five patients were alive without tumor at the last follow-up, one died of other causes, and one was lost to follow-up.

Table 2 Clinicopathologic features of seven patients with neuroendocrine carcinoma of the breast

Our literature search yielded 126 cases of NECB, including our own. We analyzed the clinicopathologic features of 126 NECB cases in China (Table 3). The patients’ average age was 53.2 years; there were seven male patients (5.6%) and 119 female patients (94.4%). Almost all patients (124/126, 98.4%) presented with a breast lump; six patients (4.8%) had bloody nipple discharge. No unique appearance of NECB was identified on 85 patients who underwent ultrasound examination or 66 patients who underwent mammography examination. Most patients (100/126, 79.4%) underwent mastectomy. A small percentage of patients (18/126, 14.3%) underwent breast-conserving surgery. Seven patients (5.5%) underwent breast surgery; however, the exact type of surgical procedures was not provided in the corresponding reports. One patient (0.8%) received chemotherapy alone. Overall, 55 patients received adjuvant chemotherapy; of these, 53 were initially treated with regimens for infiltrative ductal carcinoma (IDC) of the breast, including 51 receiving anthracycline- and taxane-based regimens and two receiving etoposide- and cisplatin-based regimens, and two were initially treated with the commonly used regimens for small cell carcinoma (Table 4).

Table 3 Clinicopathologic features of 126 patients with neuroendocrine carcinoma of the breast in China
Table 4 Treatment and follow-up of 126 patients with neuroendocrine carcinoma of the breast in China

According to the 2012 World Health Organization (WHO) classification, 52 cases were well-differentiated, and 26 were poorly-differentiated, the remaining 48 had no information of pathology. The percentages of patients with different stage breast cancer were as follows: stage I, 23.8% (30 of 126); stage II, 47.6% (60 of 126); stage III, 11.1% (14 of 126); and stage IV, 3.2% (4 of 126); the remaining 18 had no information about pathology. ER and progesterone receptor were present in 102 (81.0%) and 91 (72.2%) patients, respectively; and human epidermal growth factor receptor 2 (HER2) protein was overexpressed in 19 (15.1%) patients.

All cases were positive for at least one of the neuroendocrine markers (chromogranin A [CgA], synaptophysin [Syn], and neuron-specific enolase [NSE]) in more than 50% of tumor cells. Table 3 summarizes the clinicopathologic features of the 126 cases.

The follow-up time ranged from 4 to 144 months. Disease recurrence was found in 13 cases, including 4 small cell type (poorly-differentiated) cases and 9 non-small cell type (well-differentiated) cases. Seven patients died of NECB, of which four had small cell type disease and three had non-small cell type disease. The treatment and follow-up of the 126 cases are shown in Table 4.

For NECB patients in China, we determined an average age of 53.2 years, which seems to be older than the onset of IDC [3]. Six patients in our study presented with bloody nipple discharge. Kawasaki et al. [4] examined the pathology of 89 patients who came to the hospital for a thorough examination of symptomatic bloody nipple discharge and found that 24 (27.0%) of them had neuroendocrine carcinomas. NECB may account for an important share of breast conditions associated with bloody nipple discharge. In previous reports, NECB showed no difference when compared with IDC based on imaging [5, 6], which was confirmed in the present study. In addition, in our study, most NECB cases showed positive ER expression, which supported the results of recent studies on gene expression profiling [7], suggesting that NECB belongs to the luminal type.

Currently, there is no standard therapy for NECB. Most treatments of NECB reported in the literature and in the present study are similar to the treatment of ductal-type carcinoma, with surgery as the first-line therapy, followed by anthracycline- and taxane-based chemotherapy and endocrine therapy [1, 8]. However, whether NECB patients can benefit from chemotherapy is unknown. Current data provide little evidence to support the use of regimens for either small cell or non-small cell carcinoma.

Conflicting results of the prognosis of patients with NECB have been reported [8,9,10]. Among 126 Chinese cases included in the present study, nine of 18 patients (50.0%) with the small cell carcinoma were alive without tumor relapse, whereas the percentage was 85.0% (51/60) for those with non-small cell carcinoma. Overall, 57.1% (4/7) of patients who died of NECB had small cell breast cancer.

In summary, since NECB was first listed by the WHO in 2003 as a separate unique category, many NECB cases remain to be elucidated about their etiology and treatment. In this study, we found that the onset age of NECB patients in China seems to be older than that of IDC patients. Bloody nipple discharge may indicate the existence of NECB. Most NECB patients have the luminal subtype disease. Surgery is used as the first-line therapy, and the role of chemotherapy is still unknown. The small cell subtype may be associated with more frequent relapse and a higher mortality compared with the non-small cell subtype.



neuroendocrine carcinoma of the breast


infiltrative ductal carcinoma


World Health Organization


estrogen receptor


human epidermal growth factor receptor 2


chromogranin A




neuron specific enolase


  1. 1.

    Lopez-Bonet E, Alonso-Ruano M, Barraza G, Vazquez-Martin A, Bernado L, Menendez JA. Solid neuroendocrine breast carcinomas: incidence, clinico-pathological features and immunohistochemical profiling. Oncol Rep. 2008;20(6):1369–74.

    PubMed  Google Scholar 

  2. 2.

    Gunhan-Bilgen I, Zekioglu O, Ustun EE, Memis A, Erhan Y. Neuroendocrine differentiated breast carcinoma: imaging features correlated with clinical and histopathological findings. Eur Radiol. 2003;13(4):788–93.

    PubMed  Google Scholar 

  3. 3.

    Fan L, Strasser-Weippl K, Li JJ, St Louis J, Finkelstein DM, Yu KD, et al. Breast cancer in China. Lancet Oncol. 2014;15(7):e279–89.

    Article  PubMed  Google Scholar 

  4. 4.

    Kawasaki T, Mochizuki K, Yamauchi H, Yagata H, Kondo T, Tsunoda H, et al. High prevalence of neuroendocrine carcinoma in breast lesions detected by the clinical symptom of bloody nipple discharge. Breast. 2012;21(5):652–6.

    Article  PubMed  Google Scholar 

  5. 5.

    Richter-Ehrenstein C, Arndt J, Buckendahl AC, Eucker J, Weichert W, Kasajima A, et al. Solid neuroendocrine carcinomas of the breast: metastases or primary tumors? Breast Cancer Res Treat. 2010;124(2):413–7.

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Rovera F, Masciocchi P, Coglitore A, La Rosa S, Dionigi G, Marelli M, et al. Neuroendocrine carcinomas of the breast. Int J Surg. 2008;6(Suppl 1):S113–5.

    Article  PubMed  Google Scholar 

  7. 7.

    Shin SJ, De Lellis RA, Ying L, Rosen PP. Small cell carcinoma of the breast: a clinicopathologic and immunohistochemical study of nine patients. Am J Surg Pathol. 2000;24(9):1231–8.

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Wei B, Ding T, Xing Y, Wei W, Tian Z, Tang F, et al. Invasive neuroendocrine carcinoma of the breast: a distinctive subtype of aggressive mammary carcinoma. Cancer. 2010;116(19):4463–73.

    Article  PubMed  Google Scholar 

  9. 9.

    Tian Z, Wei B, Tang F, Wei W, Gilcrease MZ, Huo L, et al. Prognostic significance of tumor grading and staging in mammary carcinomas with neuroendocrine differentiation. Hum Pathol. 2011;42(8):1169–77.

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    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. 2014;148(3):637–44.

    CAS  Article  PubMed  Google Scholar 

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Authors’ contributions

BX conceived of and designed the study; YL conducted the literature search, performed data extraction, and wrote the manuscript; WZ performed data analysis; and FD contributed to the revising of the manuscript. All authors read and approved the final manuscript.


No grants supported this study.

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The authors declare that they have no competing interests.

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Correspondence to Binghe Xu.

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Li, Y., Du, F., Zhu, W. et al. Neuroendocrine carcinoma of the breast: a review of 126 cases in China. Chin J Cancer 36, 45 (2017).

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  • Small Cell Carcinoma
  • Neuroendocrine Carcinoma
  • Peking Union Medical College
  • Neuroendocrine Marker
  • Infiltrative Ductal Carcinoma