INTRODUCTION

Metaplastic breast carcinomas (MBCs) encompass a heterogeneous group  of breast cancers characterised histologi­cally by intimate admixture of adenocar­cinoma with dominant areas of spindle cell, squamous, and/or mesenchymal differentiation (Devilee & Tavasoli 2003). The tumour may present in pure form of metaplastic spindle cell or squamous cell component without recognizable adeno­carcinoma. It can be categorised into purely epithelial (when it is composed of squamous cell carcinoma only or adeno­carcinoma and squamous cell) or mixed epithelial and mesenchymal e.g. carcino­sarcoma. These tumours are rare, ac­counting for less than 1% of all breast cancer cases with mean age of presen­tation at 55 years old (Devilee &Tavasoli  2003). Between 1984 to 2005, there were only 16 published reports of 505 cases discussing the clinical and pathological characteristics of this tumour (Beatty et al. 2006). Due to its rarity, data on the current understanding and management of metaplastic breast carcinomas are scanty. We report our experience in managing six cases of metaplastic breast carcinomas encountered at our centre over an 8-year study period. The histo­pathological features and clinical out­comes from these patients are reviewed.

MATERIALS AND METHODS

Cases were retrieved from the Breast Cancer Database at The Breast and En­docrine Unit, Universiti Kebangsaan Ma­laysia Medical Center (UKMMC). Infor­mation on the demographics, diagnosis, tumour grade, oestrogen (ER) and progesterone (PR) receptors status, HER2 expression, clinical staging, treat­ment, recurrence status and patient sur­vival was recorded. Information on the patients’ survival details were obtained from the medical records and through telephone conversations with their family members. The patients were grouped according to tumour types; epithelial and biphasic histological subtypes. Disease free survival was defined as the time from diagnosis to distant recurrence (or death from cancer in the absence of re­currence) or last follow-up. Overall sur­vival was defined as the time from diag­nosis to the time of death from the cancer or date of last contact for patients who are still alive or who had died from other causes.

RESULTS

A total of 471 breast cancer patients were operated between 2000 and 2007 at our institution, of which six female pa­tients were histologically confirmed to have MBCs, giving an incidence rate of 1.3%. Ethnically, the patients comprised four Malays and two Indians. The mean age of our patients was 51 years with the epithelial only group being slightly younger age (42 years) than the biphasic group (55 years). The mean tumour size was 9.5cm with the epithelial only group presenting with slightly bigger tumor size (13cm) compared to the biphasic group (8 cm). Histologicaly, three of the six pa­tients had epithelial only tumours com­posed of both adenocarcinoma and squamous cell carcinoma while the other three patients were diagnosed with tu­mours of the biphasic type expressing both carcinoma and sarcomatoid compo­nents. All patients had grade 3 tumours and all tumours were ER and PR negative. Only four patients had the HER2 status tested, all of which were negative. Axillary nodal involvement was found in all epithelial only group and one in the biphasic group.  Four patients underwent mastectomy with axillary clearance, one patient had mastectomy only and one had wide local excision with axillary clearance. Two patients received neoadjuvant chemotherapy while another three had adjuvant chemotherapy. One patient refused chemotherapy. All of the patients had tumour recurrence with mean time of recurrence of 9 months. Five of them died two to three months after tumour recurrence. Table 1 summa­rises the relevant clinicopathological findings.

DISCUSSION

Metaplastic breast carcinomas (MBCs) are rare types of breast cancer which are difficult to diagnose clinically as they do not have specific imaging patterns. They are also challenging to the pathologists as the tumours have a wide range of histo­pathological features and the metaplastic area may dominate the whole tumour or occupy a very small area within the lesion. In this report, we identified six metaplas­tic breast carcinomas and evaluated their clinicopathological parameters. We record an incidence rate of 1.3% which concurs with the reported incidence of 1-2% elsewhere (Roses 2005). Interes­tingly, the six patients in our series were comprised of four Malay and two Indian ethnicity with no MBC diagnosed among Chinese patients. Similar ethnic differ­ences in risks for MBCs was reported in an earlier study which reported a higher percentage of MBCs among Afri­can Americans or Hispanics (Pezzi et al. 2007). The reason for this observation is unclear but probably suggests that racial or genetic factors may underlie the in­creased risk for MBCs.

MBCs were thought to have either ori­ginated as a single entity or clone that originates in the myoepithelial cells or its precursor, or those arising from pre-ex­isting lesions such as papillomas, com­plex sclerosing lesions and nipple ade­noma (Denley et al. 2000; Gobbi et al. 2003; Popnikolov et al. 2003; Reis-Filho et al. 2003). This has been further sup­ported by the fact that these neoplastic cells express vimentin, smooth muscle actin, muscle specific actin and p63 that are commonly associated with myoepi­thelial cells (Schnitt & Collins2008). Cyto­keratin positivity is seen in the epi­thelial and mesenchymal component of this tumour and it is thought that it is the metaplasia of the epithelial elements of a carcinoma that could have given rise to the sarcomatous changes (Saxena et al. 2004).

In most literatures, MBCs are ER and PR negative, as was the case in all pa­tients reported here (Kuo et al. 2000; Khan et al. 2003; Luini et al. 2007; Pezzi et al. 2007). Similarly, most of the MBCs in our series did not express HER2 which is in keeping with a previous study (Barnes et al. 2005). The reported inci­dences of lymph node involvement in these tumors were between 8%-56% (Kurian & Al-Nafussi 2002; Khan et al. 2003). In this series of cases, axillary nodal involvement was found in the entire epithelial only group and only one of the patients in the biphasic group had nodal metastases. The distinctive lymph node negativity was observed in the presence of spindle cell component which may be due to the nature of sarcoma that tends to metastasize haematogenously rather than through lymphatic channels (Sneige et al. 2001; Gobbi et al. 2003). Despite the lower incidence of axillary lymph node involvement, these tumours had high metastatic potential either locally, to distant organs or both, in more than 50% of cases (Wargotz et al. 1989; Wargotz & Norris 1989a; Rayson et al. 1999). Most distant metastases involve lung or bone (Wargotz et al. 1989; Wargotz & Norris 1989b; Kurian & Al-Nafussi 2002). In our series, we had five patients with distant metastases and one local recurrence (Table 1).

The average size of the tumours in this series was 9.5cm which was bigger than the usual size of infiltrating ductal carci­nomas. This is most likely due to the ag­gressive nature of the tumours with rapid growth rates. Most of these patients had poorly differentiated or undifferentiated tumours (compared to infiltrating ductal carcinoma) which will further lead to rapid growth rates (Pezzi et al. 2007). We were unable to do a statistical analysis on whether the epithelial only group tumours were larger than the biphasic group due to the limited number of cases. However, in this series the mean tumour size for the epithelial group was greater than the biphasic group. Five of our patients had mastectomy due to the large size of the tumours. Five of the patients had sys­temic therapy (one refused) and most of them died within a year after surgery. In our series, the mean time of recurrence was 9 months and survival after recur­rence was short. This concurs with other studies that showed that MBCs are less responsive to therapy with the conven­tional regimes that are usually used for infiltrating ductal carcinoma (Wargotz & Norris 1989a; Rayson et al. 1999). There is no survival advantage either with che­motherapy or radiotherapy for distant metastases (Wargotz & Norris 1989a). The median survival after metastases is 8 months after systemic treatment (Rayson et al. 1999). This means that the optimal systemic therapy for metaplastic breast carcinoma still needs further de­fining.

CONCLUSION

Metaplastic breast carcinomas are rare types of breast cancers usually affecting the post menopausal age group. These tu­mours have aggressive clinical beha­viour, present with locally advanced dis­ease, are large in size, high grade tu­mours and triple negative. Despite treat­ment with chemotherapy and radiothe­rapy, the patients have a high risk of local recurrence and distant metastases which are potentially fatal.