metaplastic breast cancer ( mbc ) is a rare malignancy characterized by the histologic presence of two or more cellular types , commonly a mixture of epithelial and mesenchymal components [ 16 ] .
mbc represents 0.251% of breast cancers diagnosed annually [ 1 , 7 , 8 ] .
due to its relative rarity and heterogeneous histologic presentation , the pathologic diagnosis of mbc is difficult . the world health organization ( who ) recognized mbc as a unique pathologic entity in 2000 . since then , the incidence of mbc has risen , likely representing an increased recognition by pathologists [ 8 , 9 ] .
overall , greater than 70% of patients with mbc present with american joint committee on cancer ( ajcc ) stage ii or greater disease as compared to approximately 50% of patients with idc .
compared to patients with idc , those with mbc have worse outcomes with 5-year survival rates ranging from 49% to 68% [ 1 , 10 , 11 ] .
management of mbc has largely paralleled that of idc , despite growing evidence that mbc is a distinct entity that lies along the spectrum of basal - like breast cancers .
this paper serves as a summation of current literature and approaches to the multimodality treatment of patients with mbc .
the surgical treatment of mbc has largely paralleled that of idc . with the publication of nsabp b-06 trial results , the surgical approach to idc shifted from mastectomy to breast conservation therapy for appropriate patients .
large tumors ( 5  cm ) are a relative contraindication to breast conservation therapy   and even less extensive tumors may preclude breast conservation in smaller - breasted patients .
these guidelines are particularly important for mbc patients , as they typically present with larger tumors compared to their idc counterparts [ 8 , 13 ] .
as one might expect , relative to those with idc , a higher percentage of patients with mbc receive mastectomy rather than lumpectomy [ 8 , 14 ] . despite the larger tumor size at presentation
tseng and martinez found no difference in overall or disease - specific survival whether mbc patients were treated with mastectomy or lumpectomy , even after controlling for known prognostic factors .
similarly , dave et al . found no difference in overall or disease - free survival between patients with mbc undergoing either modified radical mastectomy or breast conservation therapy .
lymph node staging of patients with mbc is evolving , reflective of the changes in approach to axillary staging of patients with idc .
however , sentinel lymph node biopsy ( slnb ) has largely replaced alnd due to lower associated morbidity with similar accuracy in the detection of regional metastasis . prior to the american college of surgeons oncology group ( acosog )
z0011 trial , all patients with a positive slnb subsequently went on to receive a completion alnd . however , based on the results of this trial , completion alnd may not be indicated in a select group of women with early stage breast cancers undergoing lumpectomy and subsequent whole breast radiation .
therefore , data regarding the sensitivity and specificity of sentinel lymph node biopsy among mbc patients are unknown , as are data regarding the need for completion alnd for patients with sentinel lymph node metastasis .
several studies have demonstrated lower rates of axillary lymph node involvement among patients with mbc relative to idc [ 8 , 13 ] .
pezzi et al . also demonstrated axillary lymph node metastases in 22% of those with mbc versus 34% of those with idc and further noted that nodal positivity was more common among the carcinosarcoma variant . despite this , beatty et al . demonstrated that slnb and alnd are used equally in patients with mbc relative to women with idc .
showed that women with locally advanced mbc ( i.e. , primary tumors > 5  cm and/or four or more metastatic axillary nodes ) who underwent postmastectomy radiation therapy had improved survival relative to those not receiving such radiation . because completion alnd is often the only way to document 4 lymph node metastases and because patients undergoing mastectomy were not included in the acosog z0011 trial , it would be prudent to recommend completion alnd for mbc patients undergoing mastectomy if they have documented sentinel lymph node metastasis .
there are little data that standard breast cancer chemotherapy regimens utilized for idc are effective for women with mbc . compared to stage - matched women with idc ,
nevertheless , 33%86% of mbc patients receive chemotherapy and are , in fact , twice as likely to receive chemotherapy as similarly matched patients with idc [ 8 , 11 , 19 ] . single institution retrospective studies and genomic
a report from the mayo clinic detailed 27 patients treated at their center over 20 years in which 33% received chemotherapy .
ten different regimens were used , resulting in one partial response . this resistance to chemotherapies is likely a product of the complex genetic and nongenetic mechanisms within mbc that result in phenotypically diverse subclones and intratumoral heterogeneity .  
hormonal therapy is just as ineffective as chemotherapy , and generally has no role in the management of patients with mbc .
there is a high incidence of hormone receptor negativity as well as lower her-2/neu overexpression in mbc .
mbcs are often classified along the spectrum of basal - type breast cancers of which 7585% are triple negative ( estrogen receptor , progesterone receptor , and her-2/neu overexpression negative ) [ 21 , 22 ] .
patients with triple - negative mbc have poor 3-year disease - free survival compared to a similar group of triple - negative idc patients receiving identical chemotherapy regimens .  
variations in histologic types may partially account for the observed resistance to standard idc chemotherapeutic regimens as well as poorer survival .
a study by tseng et al . included tumors with heterogeneous histologic diagnoses representing histologic subtypes including metaplastic carcinoma not otherwise specified , carcinosarcoma , malignant myoepithelioma , adenosquamous carcinoma , epithelial - myoepithelial , and adenocarcinoma with squamous / cartilaginous / and spindle cell metaplasia .
[ 26 ] , who subcategorized mbc into five types : matrix producing , spindle like , squamous with ductal origin , metaplastic with osteoclastic giant cells , and carcinosarcoma . in the analysis by tseng et al .
, carcinosarcoma was associated with both poorer overall survival ( hr 1.52 , ci 1.132.04 , p = 0.005 ) and disease - specific survival ( hr 1.63 , ci 1.162.31 , p = 0.005 ) in multivariate analysis .
these findings likely reflect biological differences between the nonepithelial sarcomatous elements found in carcinosarcoma as compared to the nonepithelial components of the other histological variants .  
recent studies have investigated receptors that may potentially serve as novel targets for chemotherapy regimens .
leibl and moinfar   examined 20 different mbc samples ( 8 heterogeneous elements , 7 spindle cell , 4 carcinosarcoma , and 1 matrix - producing ) with immunohistochemical staining for the four members of the egfr / her family .
they found that 14 of the 20 samples were positive for her-1 whereas only 1 sample was positive for her-2 , an inverse finding to that of idc .
this would suggest that targeted protein kinase inhibitors such as gefitinib might be effective for some patients with mbc .
likewise , other novel strategies have emerged to target the nonepithelial component of mbc tumors .
one such strategy is the use of ifosfamide and etoposide for carcinosarcoma variants of mbc .
hennessy et al . , in an evaluation of sarcomatoid mbc patients treated at a single institution , reported no recurrence in the 3 patients that received doxorubicin and ifosfamide treatment .
information regarding the role of adjuvant radiation therapy ( rt ) for the treatment of mbc is sparse [ 15 , 25 ] . in a series of 43 patients with mbc , dave et al .  
total radiation consisted of 5066  gy with use of tangential fields and additional anteroposterior supraclavicular fields when regional nodes were treated .  
analysis utilizing the seer database suggested that adjuvant radiation improved both overall and disease - specific survival for all patients undergoing treatment for mbc , regardless of the type of operation performed ( lumpectomy versus mastectomy ) .
patients receiving rt demonstrated 36% and 26% decreases in death from any cause and breast - related mortality , respectively .
results of multivariate analyses excluding patients with metastatic disease paralleled these findings , demonstrating 38% and 34% decreases in death from any cause and breast - related mortality , respectively .
this is in accordance with a meta - analysis demonstrating that for prevention of local recurrences will improve overall and disease - specific survival .   
setting , rt is recommended to patients with four or more metastatic axillary nodes , large ( 5  cm ) primary tumors and chest wall invasion [ 2729 ] .
tseng et al . described mastectomy patients who had received rt demonstrating a 33% decreased risk of death from any cause .
subgroup analysis of  high  and  normal  risk patients undergoing mastectomy demonstrated that specifically , patients undergoing mastectomy with tumors 5  cm or four or more metastatic axillary lymph nodes derived a 47% and 42% decreased risk of death from all - cause and breast - related mortality , respectively .
patients undergoing mastectomy with tumors 5  cm and less than 4 metastatic axillary lymph nodes , however , derived no benefit from rt .
this data would suggest that rt should be considered as a component of multimodality therapy for mbc patients undergoing mastectomy with these advanced features .
due to its rarity and heterogeneity , there is no  standard  therapy for all patients with mbc .
surgical treatment and axillary staging parallel that of idc with breast conservation therapy being appropriate for a select group of patients .
traditional chemo- and hormonal therapies for idc are ineffective against mbc and often associated with poorer survival , while histology specific novel chemotherapeutic strategies may offer a survival advantage . targeted therapies based on individualized gene profiling , while promising for the future , are not commonly utilized . finally , adjuvant radiation , regardless of the type of surgery ,
clinical trials comparing standard therapies for idc in patients with mbc are needed , but are unlikely to be accomplished due to the rarity of the disease .
 metaplastic breast cancer ( mbc ) is a malignancy characterized by the histologic presence of two or more cellular types , commonly a mixture of epithelial and mesenchymal components . 
 mbc is rare relative to invasive ductal carcinoma ( idc ) , representing less than 1% of all breast cancers . 
 other than a lower rate of lymph node metastases , mbc tumors display poorer prognostic features relative to idc . due to its low incidence and pathological variability , 
 the ideal treatment paradigm for mbc is unknown . because of its rarity 
 , mbc has been treated as a variant of idc . despite similar treatment regimens , however , patients with mbc have worse outcomes . 
 recent research is focused on biological differences between mbc and idc and potential novel targets for chemotherapeutic agents . 
 this paper serves as a summation of current literature on approaches to the multidisciplinary treatment of patients with mbc . 
1. Introduction
2. Surgical Therapy
3. Chemotherapeutic and Hormone Therapy Approaches
4. Radiation Therapy
5. Conclusion