Research Report

Current Status and Progress of Breast Adenoid Cystic Carcinoma  

Z.W. Zhai1 , S.R. You1 , B.Z. Zhao1 , J.Y.  Zhang1 , Dongwei Zhang1, 2
1 The Second Hospital of Harbin Medical University, Harbin, 150081, China
2 Heilongjiang Academy of Medical Sciences, Harbin, 150081, China
Author    Correspondence author
Cancer Genetics and Epigenetics, 2017, Vol. 5, No. 2   doi: 10.5376/cge.2017.05.0002
Received: 31 Oct., 2017    Accepted: 06 Nov., 2017    Published: 20 Nov., 2017
© 2017 BioPublisher Publishing Platform
This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Preferred citation for this article:

Zhai Z.W., You S.R., Zhao B.Z., Zhang J.Y., and Zhang D.W., 2017, Current status and progress of breast adenoid cystic carcinoma, Cancer Genetics and Epigenetics, 5(2): 6-10 (doi: 10.5376/cge.2017.05.0002)


Adenoid cystic carcinoma (ACC) of the breast is a rare subtype of breast cancer. Despite its triple-negative status, this tumor has a very good prognosis. Breast-conserving treatment including postoperative radiotherapy seems to be equivalent to mastectomy alone with respect to survival. Routine axillary lymph node staging is not recommended since lymph node metastases are extremely rare. The value of adjuvant systemic therapies is not established. Late relapses can occur, so long-term follow-up is mandatory for these patients.

Adenoid cystic carcinoma; Breast cancer; Radiotherapy; Surgery; Therapy


Adenoid cystic carcinoma (ACC) is an epithelial malignancy occurring in the salivary gland, submandibular gland, trachea, lungs, breast, skin and other parts of the body (Jang et al., 2014). The histological type of the typical mammary gland ACC is similar to that of the well-known salivary gland-derived tumor, but the prognosis for ACC of the breast is better when compared to the salivary gland. ACC of the breast belongs to the basal cell subgroup of breast cancer, and its immunohistochemical features are consistent with triple-negative breast cancer with basal-like features, but it usually exhibits low aggressive and inert clinical behavior. These unique clinicopathological features make it different from other triple-negative breast cancer. This review summarizes the important advances in epidemiology, clinical features, histomorphology, immunohistochemical features, treatment and prognosis of breast adenoid cystic carcinoma.


1 Epidemiology

ACC of the breast is a rare type of breast cancer, representing less than 0.1% of breast malignancies (Lakhani et al., 2012). ACC of the breast occurs between 19 and 97 years of age and more common in women in their fifth and sixth decade of life (Canyilmaz et al., 2014). 338 cases of breast adenoid cystic carcinoma in the past 30 years were analyzed, and the age-adjusted incidence rate was determined to be 0.92 / 100 million person / year. Blacks were 39 percent less likely than whites' morbidity (Ghabach et al., 2010). Most cases are female, but occasionally there are male cases reported (Tang et al., 2015), and domestic literatures report less.


2 Clinical Manifestations

Most of the patients were characterized by a single, well-defined tumor, but there were also a few cases of the multifocal breast of ACC reported (Franceschini et al., 2010). Other rare symptoms include breast pain and nipple depression. Most patients´ lesions occur in the areola area or upper outer quadrant. Tumour size is variable with an average of 2-3 cm and up to 15 cm. (Defaud-Henon et al., 2010). Preoperative fine-needle aspiration cytology can be useful for the diagnosis (Boujelbene et al., 2012). Mammography X-ray and ultrasound and other imaging studies are all lacking specificity and may be misdiagnosed as benign lesions (Glazebrook et al., 2010).


3 Pathology

3.1 Naked eye view

Most cases are macroscopically well-circumscribed. Occasionally, pink, tan, or gray microcysts are evident. ACC usually presents as a localized disease of pathologic T1 or T2 (Miyai et al., 2014).


3.2 Mirror view

The histology of ACC of the breast is similar to that of their salivary gland counterparts. Tumor tissue arranged in cribriform type, small tube - trabecular and solid type, the three architectural patterns are often mixed. In each structure, there was a mixture of glandular epithelium and myoepithelial-basal cells (Lakhani et al., 2012). The glandular epithelium and myoepithelial-basal cells were respectively composed of the two different structures: true and false glandular spaces. Luminal cells, characterized by round nuclei and eosinophilic cytoplasm, surround true gland Lumina containing euphoria neutral mucin. On the other hand, the myoepithelial-basal cells exhibit central oval nuclei and scant cytoplasm, and form pseudo Lumina, which result from intraluminal invaginations of the stroma.


3.3 Immunohistochemistry

A variety of markers detected in salivary adenoid cystic carcinoma are also expressed in breast of ACC. The luminal cells are positive for CK7, CK8/18, epithelial membrane antigen, and CD117(c - kit) (Franzese et al., 2013). The myoepithelial-basal cells’ marker includs CK5, CK5/6, CK14, CK17, and it also expresses partial myoepithelial cell markers such as p63, actin, calponin, S-100 protein, vimentin and epidermal growth factor receptor (EGFR) are often positive (Reyes et al., 2013). The glandular epithelial cells and myoepithelial-basal cells of Adenoid cystic carcinoma of the breast are most often hormone receptor [estrogen receptor (ER) and progesterone receptor (PR)] negative, do not express human epidermal growth factor receptor 2 (Her2) (Kulkarni et al., 2013). The immunohistochemical characteristics of breast of ACC are very consistent with the three negative breast cancer with basal cell-like characteristics.


3.4 Graded

In a way akin to the ACC of the salivary gland, ACCs of the breast are graded according to the proportion of solid growth: tumors with either cribriform or tubular-trabecular pattern and without solid elements are considered grade II, tumors with ≤ 30% of solid growth are classified as grade II, and tumors having more than 30% solid growth are designated grade III, and that tumors with a solid pattern (grade II and III) had a larger tendency (Miyai et al., 2014).


3.5 Precancerous lesions

The incidence of the breast of ACC may be associated with a variety of benign lesions, including micro-gland adenosis, tubular adenoma, adenomyoblastoma and fibroadenoma (Canyilmaz et al., 2014). The breast of ACC rarely incorporates other types of breast cancer, but there are also cases of coexistence of breast of ACC and invasive ductal carcinoma (Righi et al., 2011).


4 Differential Diagnosis

The breast of ACC is the representative breast disease with the sieve structure, often need to be identified with the disease such as cribriform ductal carcinoma in situ and invasive cribriform carcinoma and breast benign disease collagenous spherulosis etc (Zhang and Bu, 2014).


5 Treatment

So far, there is still no uniform optimal treatment regimen for breast of ACC, and the choice of specific treatment regimens varies greatly in clinical practice.


5.1 Surgical treatment

Surgical treatment is one of the main treatment methods of breast of ACC, and there are many kinds of surgical methods. Radical mastectomy, then modified radical mastectomy was the most reported surgical procedures for ACC of the breast, simply because it used to be the standard treatment for common breast cancers. Currently based on its low invasiveness and metastatic potential and good prognosis, breast ACC commonly used breast-conserving surgery. Local excision alone was performed occasionally in the past with recurrence rates varying from 6% to 37% (Boujelbene et al., 2012). At present, multiple authors recommend extended resection or quadrant resection with or without radiation therapy for margin negative tumors (Khanfir et al., 2012). When breast-conserving surgery cannot be achieved, it is recommended to use a breast resection with a higher grade of invasive carcinoma (Miyai et al., 2014).


5.2 Axillary management

The frequency of axillary lymph node metastases is very low, around 0-2% (Boujelbene et al., 2012). Except for the clinical evidence of axillary lymph node metastasis, axillary lymph node dissection is not recommended (Wei et al., 2014). The preoperative clinical examination did not touch the lymph nodes and color Doppler ultrasound exploration found no suspicious axillary lymph node metastasis, sentinel node biopsy is required, especially combined with other types of invasive cancer, higher tumor grade or tumors larger than 3 cm (Thompson et al., 2011).


5.3 Radiotherapy

The importance of radiotherapy after breast conserving surgery with ACC of breast has not been recognized until recently. A large sample of studies in recent years showed that postoperative adjuvant radiotherapy improves overall survival (Coates et al., 2010). Radiation therapy can significantly improve the 5-year local control rate of the breast-conserving surgery group, and surgical margin or tumor involvement does not affect the treatment effect, the curative effect of breast conserving surgery with postoperative adjuvant radiotherapy and simple mastectomy is close. Therefore, regardless of how the margin is, it is recommended that local mastectomy with postoperative adjuvant radiotherapy be performed to avoid mastectomy (Khanfir et al., 2012).


5.4 Chemotherapy

There are very few reports about breast of ACC chemotherapy. Some doctors recommend patients with axillary lymph node metastasis and distant metastasis receive systemic adjuvant chemotherapy, and patients with higher tumor grade or those with tumor size greater than 3 cm may also choose chemotherapy (Goldhirsch et al., 2011). However, there is no unified conclusion on the efficacy of chemotherapy and the choice of specific chemotherapy regimens in patients with breast of ACC.


5.5 Targeted therapy

With the development of targeted therapy, cancer therapy has entered a new stage, but there is still no targeted therapy for breast of ACC into clinic. In recent years, the discovery and intensive study of the characteristic fusion gene MYB-NFIB of adenoid cystic carcinoma have brought hope for molecular targeted therapy of breast adenoid cystic carcinoma (Ding et al., 2015).


5.6 Endocrine therapy

The breast of ACC hormone receptor is negative and endocrine therapy is ineffective (Goldhirsch et al., 2011). Few cases of endocrine therapy have been reported in the literature.


6 Prognosis

The contrast of ACC with other three negative breast and salivary gland ACC is characterized by good prognosis, rare metastasis of lymph nodes and important organs (Li et al., 2012). The 10 year survival rate of breast of ACC was 90%-100%. The most frequent site of metastasis is lung (Wei et al., 2014). When ACC patients have local recurrence or distant metastasis, they still show a sustained and slow progression. Because a longer course of disease increases the risk of recurrence and distant metastasis, the long term follow-up is required (Kim et al., 2014).


Authors’ contributions
Z.D.W. read and approved the final manuscript. Z.Z.W. wrote the manuscript. Y.S.R. contributes to translation. Z.J.Y and Z.B.Z. collected materials. All authors read and approved the final manuscript.



This work was supported by the Science Innovation Project (201613) and special fund for Excellent Academic Leader of Harbin (2017RAXQJ076).



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