Primary carcinomas of ectopic breast tissue have been reported in only a small number of cases and the axilla was the most frequent site of the primary tumor (1). Evans et al (2) reported that 71% of ectopic breast cancers were located in the axilla. Marshall et al (3) reported that 58% occurred in the axilla, 18.5% in the parasternal, 8.6% in the subclavicular, 8.6% in the submammary, and 4% in the vulvar; 94.7% of patients were women, and only 5.3% were men. Breast tissues develop from the ectodermal ridges, also known as the milk lines, on the ventral surface of the body, which extend from the axillae to the inguinal regions and end on the medial aspect of the thighs on each side of the body (4). Embryologically, ectopic breast tissue develops as a result of failed resolution of the mammary ridge, an ectodermal thickening that extends from the axilla to the groin (5). Ectopic breast tissue may appear at any site along the milk line, but it occurs most commonly in the axill; less commonly, it may appear in locations outside of the mammary ridge, including the face, middle back, buttock, posterior neck, chest, vulva, hip, posterior, flank and/or lateral thigh, shoulder and upper extremities (4,6).

The diagnostic procedures and therapeutic management of accessory breast carcinoma are not definitively established. The present study aimed to perform an analysis of a series of patients with accessory breast cancer that were treated exclusively with combination chemotherapy and radiotherapy, as well as to review the medical literature with regard to the clinical features, treatment methods and prognosis of this disease. The present study reports 11 such cases, with the goal of contributing valuable information about this unusual tumour to the current literature.

Breast tissue generally develops along the embryonic mammary ridge, also termed the milk line, which extends from the axilla to the groin area and appears in the sixth week of gestation (6,7). The milk line normally disappears, with the exception of the mammary ridge of the thoracic region, where normal breast tissue develops. However, accessory mammary tissue may develop due to an incomplete embryological regression of the mammary ridge, which is composed of a portion of the galactic band that runs from the axilla to the groin (5). The presence of accessory breast tissue is uncommon, with an overall incidence range of 0.22 to 6.00% in the general population (8,9). Women are reported to exhibit a increased incidence of accessory breast tissue compared with men. The most common location of ectopic breast tissue is the axilla. Other less common locations are the face, thighs, perineum, groin, vulva and shoulders (10,11). Ectopic breast tissue may consist of the breast parenchyma, areola, nipple or any combination of these three components (12). This breast tissue is subject to hormonal influences and undergoes physiological changes (13). In addition, a number of different neoplasms, benign and malignant, have been found in axillary breast tissue (14). The most common of these tumours reported in the literature is the fibroadenoma, and there are scattered case reports of other tumours, including phyllodes tumour and mammary carcinoma (14).

Accessory mammary carcinoma is extremely rare, constituting 0.3–0.6% of all breast cancer cases, generally occurring as an axillary tumour (15). Primary breast carcinoma arising in accessory breast tissue of the axilla is the most common clinical presentation, comprising 60–70% of all ectopic breast tumours (16,17). The most common pathology of accessary breast tissue carcinoma, as with normal breast carcinoma, is invasive ductal carcinoma (18). The most common physical manifestation of this carcinoma is a palpable mass. Oedema, tenderness, breast pain and non-specific discomfort are observed less often (19).

Diagnostic procedures and therapeutic management of patients with accessory breast cancer are not unequivocally established (20). The diagnosis of accessory breast cancer is not always considered and is, therefore, often delayed (21). Generally, a diagnosis of accessory breast cancer requires a pathological demonstration of cancerous tissue adjacent to normal breast ducts or lobules that are not connected to the proper mammary gland. It is also necessary to exclude the possibility of a metastatic lesion from another primary cancer (18). An accurate diagnosis of axillary accessory breast carcinoma is important, as it can provide precise staging information for patients with concurrent ipsilateral breast cancer (7). However, this diagnosis can be extremely challenging, if not impossible, since primary breast cancer frequently extends to the axillary tail and metastatic carcinoma may completely replace the involved lymph nodes (19). The differential diagnosis must include other subcutaneous masses, such as fibroadenomas, lipomas, hidradenitis and follicular cysts, as well as lymphadenopathy associated with benign or malignant disease, since aberrant breast tissue is most commonly found in the axilla (22). Therefore, axillary tail breast cancer, axillary lymph node tumour metastasis, occult breast cancer and lymphoma must be excluded prior to a firmly established diagnosis of accessory breast cancer (22).

In the current study, systemic examinations, including CT, MRI, ultrasonography and positron emission tomography/CT, revealed no primary malignant or occult lesions, only the axillary tumour. The presence of a hypoechoic, not well-defined heterogeneous mass, which is differentially diagnosed as a sebaceous cyst, without signs of inflammation, such as in hydradenitis, is considered to be accessory breast cancer (20). Mammography may contribute additional information, such as for the evaluation of the axillae, for micro-calcifications, and the breasts (23). In the case of a suspicious lesion, fine-needle aspiration biopsy or core biopsy of the axillary mass should be performed to harvest cells or tissue for histological diagnosis (8). Since the accessory breast tissue in the present study was found in the axilla, far from the pectoral breast parenchyma, the diagnosis of accessory breast carcinoma was favoured. The identification of normal breast tissue adjacent to the invasive carcinoma in the axilla strongly suggested invasive carcinoma arising in the ectopic breast tissue. The absence of accompanying lymphoid tissue further disfavoured a diagnosis of tumour metastasis in the axillary lymph node from breast cancer. Notably, accessory breast cancer may be macroscopically similar to a lymph node with metastatic carcinoma (20). Therefore, histological examination should be performed for all tissue nodules in the axilla.

Similarly to primary breast cancer, accessory breast cancer is treated surgically, which is supplemented with pre- or post-operative chemotherapy, radiotherapy and endocrine therapy. It is controversial as to whether the breast located on the same side as the accessory breast cancer should be removed as well (22,24). Certain studies have recommended radical mastectomy of the ipsilateral breast if the regional lymph nodes are diagnosed with carcinoma (11,24). However, Cogwells and Czerny reported that ipsilateral mastectomy does not result in an improved prognosis for patients with ectopic breast carcinoma (25). Evans and Guyton suggested that radical or modified radical surgery offered no advantage over local excision combined with axillary dissection or radiation with respect to outcome (2). It has been proposed that the surgical procedure of choice for ectopic breast carcinoma involves a wide resection of the tumour with surrounding tissue, including the skin and regional lymph nodes (3,26). Mastectomy is not indicated if clinical examination, mammography and ultrasonography of the anatomic breast reveal no signs of disease, but should be performed when differential diagnosis is challenging (17,27). If mastectomy is not performed, particularly careful follow-up is necessary to exclude any later manifestations of an occult primary neoplasm in the breast.

The present study hypothesizes that, when the accessory breast tissue is closely connected to normal breast tissue, the indications for surgery should be the same as those for a tumour anatomically situated in the breast. By contrast, when the accessory gland constitutes a separate anatomical structure, the resection of normal breast tissue appears to be unnecessary. There have been few studies on neoadjuvant chemotherapy as a treatment for locally advanced accessory breast cancer (20,28). Chemotherapy with anthracycline and taxane is generally recommended for the treatment of locally advanced accessory breast cancer, as it is for the usual form of breast cancer (7). The principles of post-operative treatment are also the same as those for normal breast carcinoma (9). External radiotherapy of the tumour site must be performed to enable increased local control. However, radiation of the homolateral anatomic breast is not systematically performed (29). In the present study, 3 patients were administered with radiation therapy subsequent to surgery, while the safety and predictability have not yet been elucidated. In addition, there is a lack of evidence assessing the middle- and long-term efficacy of radiation therapy. Systemic adjuvant therapy is more frequently required due to the common occurrence of lymph node disease and is performed following the same guidelines as those used for anatomic breast carcinoma treatment (17).

In breast cancer, homolateral axillary and internal mammary nodes are considered possible sites of lymphatic metastasis (5). The lymphatic spread of axillary breast cancer is likely to only occur towards the homolateral axillary nodes and then towards the supraclavicular nodes, as this is the normal lymphatic drainage pathway of the subcutaneous and cutaneous tissues of the armpit (8). It has been reported that 37% of cases occurred prior to the age of 45 years, and due to early metastatic spread, demonstrated an even higher incidence of lymph node involvement (59–88%) compared with primary breast carcinoma located in the external superior sector (51%) (7). The prognosis of accessory breast carcinoma is challenging to establish, primarily due to absent or limited follow-up data as well as small sample sizes. In addition, it is challenging to identify a clear histopathological and clinical distinction between accessory and normal breast carcinoma (23). Certain studies have hypothesized that accessory breast tissue is more prone to malignancy compared with the normal breast parenchyma (30,31). Marshall et al reported that the poorer outcomes in ectopic breast cancer relative to general breast cancer reflected less effective clinical disease management compared with the disease process itself (3). Certain studies have reported that the outcomes of ectopic breast cancer are poorer than those of normal breast cancer as the tumour is located near the axillary lymph nodes and is therefore associated with early metastasis to these nodes (32).

Follow-up data is provided for a limited number of patients, indicating a four-year post-treatment survival of 9.4%, which has been calculated in a meta-analysis (2). At the time of diagnosis, the majority of patients with accessory breast carcinoma were in an advanced clinical stage, with nodal metastases or an unresectable tumour due to size (20,28). Thus, the prognosis of accessory breast cancer may be worse compared with the prognosis of breast cancer arising in the proper mammary gland, although no long-term follow-up data regarding the prognosis of accessory breast cancer are available (15).

The present study reported the cases of 11 patients with rare breast carcinoma that arose in an accessory mammary gland. Due to the rarity of this disease and the consequential lack of clinical awareness, the administration of appropriate disease management is often delayed. The possibility of accessory mammary carcinoma should be considered even in male patients with neoplasms located in the axilla. The correct identification of accessory breast tissue is an important factor in the differential diagnosis of axillary tumours. Recognition of this disease by clinicians and pathologists and close communication between the two are important to prevent a misdiagnosis of malignancy and performing unnecessarily extensive surgery.