Despite increased public awareness, it is still common to see patients who present with LABC. Many patients with LABC have symptoms such as local pain, bleeding from ulcerative lesions, or tumour infection [4]. An effective treatment is urgently needed to improve their symptoms. The guidelines recommend standard therapy [3]; however, systemic toxicity remains high, with significant risks of cardiotoxicity or immune suppression as well as a high incidence of local recurrence after surgery or radiotherapy. Alternatively, arterial infusion chemotherapy has been used as a neoadjuvant therapy for LABC since the 1960s [5]. Anti-neoplastic agents are administered to the tumour after surgical cannulation through the internal thoracic and subclavian arteries [5, 6, 10,11,12]. With advances in catheter techniques, percutaneous transarterial administration has been introduced, yielding better clinical results [13,14,15,16,17,18,19]. Compared with systemic chemotherapy, regional chemotherapy attempts to deliver higher doses of chemotherapeutic agents to the tumour, directly perfusing the tumour mass via its arterial supply [20,21,22]. Embolization of the tumour-supplying artery immediately after infusion of anti-neoplastic agents was combined to help retain drugs within tumours, resulting in better local control of LABC [8, 22,23,24].

After selective catheter insertion, a CT scan along with selective contrast injection is a reliable method to confirm the arterial supply to the tumours and to allocate the dose of anticancer drugs to each artery [25, 26]. For this reason, an angio-suite combined with cone-beam CT function or an angio-CT hybrid system is desirable for safe and efficient treatment.

Since the initial report by Yamada, TACE has become a standard method for treating hepatocellular carcinoma [27]. However, it has seldom been introduced for the treatment of extrahepatic malignancies for fear of serious complications such as skin necrosis caused by embolic material, which is a combination of Lipiodol and gelatine sponges[28]. Damage to skin or normal tissues is a major concern for maintaining the quality of life (QoL) of patients. On the other hand, HepaSphere microspheres, which are larger than 50 microns, cannot occlude capillary circulation in the skin or normal organs. In fact, no patients developed skin necrosis after the embolization of breast tumours in this study. In this treatment, the purpose of embolization using HepaSphere microspheres was not to achieve ischaemic effects but to achieve sufficient retention of antineoplastic agents inside targeted tumours. The reason for using HepaSphere cells was that they possess drug-release capabilities and can exert long-term anti-tumour effects.

The major blood supply to the medial aspect of the breast arises from the perforating branches of the internal mammary artery. The lateral aspect is variably supplied by branches from the subclavian artery [14, 17, 20, 29]. The lateral thoracic artery is the main artery, but there are many anatomical variations. In one-third of patients, breast tumours are supplied from a serpiginous vessel from the brachial artery, which is an uncommon but not rare circulation to the breast tissue [17, 22, 30].

In previous reports [11, 17, 20, 29], a dye was infused to confirm blood circulation to the tumour area. Immediately after infusion, the discolouration of the skin was checked to estimate the feeding area of each tumour-related artery. This method is not reliable because it involves observing skin discolouration but not the distribution of dye in breast tumours. In this study, angio-CTs were carried out in all the patients to determine the blood supply to the target tumours and lymph node metastases.

The main blood supply to the axillary lymph node metastases was the lateral thoracic and/or thoracodorsal arteries.

The drugs used in this study were standard drugs for treating breast cancer. The proposed main drugs were anthracycline or taxane. In previous studies [11, 12, 14, 18], anthracyclines (doxorubicin, epirubicin, and mitoxiantrone) were commonly used, but they caused skin reactions and pigmentation [4, 14, 20]. Recently, taxanes have become standard drugs [21], but they may cause alopecia or immunosuppression even if at low doses. Small doses of cisplatin (10–20 mg), fluorouracil (250 mg), irinotecan (20–40 mg), mitomycin (2–4 mg), or bevacizumab (100–200 mg), all standard drugs for treating breast cancer, were combined. If the reduction in tumour volume was not adequate or allergic reactions were detected during the evaluation one month after treatment, the drugs were switched to others. The choice and optimal dose of anticancer drugs need to be clarified in future studies. It may also be necessary to adopt a method of selecting the most appropriate drug through gene panel testing.

Comparisons of treatment results with various reports were difficult because the patients’ backgrounds, treatment strategies, and evaluations differed. Without the combination of other treatments, the control rates after 6 months and 12 months were 100% and 88%, respectively. The survival benefit in this study was comparable to that in previous reports [2, 20, 22]. The one-year and two-year survival rates were 87.1% and 67.6%, respectively. Even though a cure cannot be expected with this treatment, achieving local control is important.

Only a few reports [8, 23, 31, 32] have described axillary lymph node metastases, even though they are very important from a clinical perspective. More than 90% of LABC cases are associated with regional lymph node metastases [21, 24], a finding observed in 87% of cases in this study. Axillary lymph node metastases were also supplied by branches from the subclavian artery as primary breast lesions. Successful control of axillary lymph node metastases was achieved without serious complications, as in primary tumours.

Side effects were almost negligible, except for a mild skin rash caused by anthracyclines for a few days after treatment [4, 8, 20, 21]. Moreover, pigmentation lasting a couple of months was sometimes cosmetically problematic. Some complications, such as pain, upper limb atrophy, or headache, have been reported [24, 31] when high doses of anti-cancer drugs are used. The low incidence of adverse events in this study is probably due to the low drug doses administered. In the trial using Callisphere, embolization was completed through complete eradication of the supplying artery. On the other hand, embolization was terminated when the blood flow became slow in this study. The local irritability of HepaSphere microspheres, which have high elasticity [33], should be investigated and compared with that of other solid microspheres in clinical studies.

This study is retrospective but not comparative. Multi-institutional comparative studies between TACE and systemic chemotherapy for LABC are necessary. More precise analyses of not only histopathological information but also molecular factors are necessary. The proper drugs, combinations, and doses for intra-arterial administration also need to be clarified in future studies.