A Retrospective Comparison And Analysis Between Metaplastic Breast Carcinoma And Triple-negative Breast Carcinoma

Objectives: Metaplastic breast carcinoma(MBC)is a heterogeneous group of invasive morphology of breast cancer which can be divided into various histological subtypes.Triple negative breast cancer(TNBC)is a subtype of breast cancer,defined by the lack of immunohistochemical expression of the estrogen receptor(ER),progesterone receptor(PR)and human epidermal growth factor receptor-2(HER-2).The purposes of this study are to compare the clinicpathologic features,immunohistochemistry of biologic factors included ER,PR,HER2,P53,CK5/6,EGFR and Ki-67,treatment and prognosis of MBC and TNBC(invasive ductal carcinoma and invasive lobular carcinoma)and to analysis the 3-year overall survival rate and 3-year disease-free survival rate of MBC and TNBC and to provide a reference for the diagnosis and treatment of metaplastic breast carcinoma and triple negative breast carcinoma.Methods: We retrospectively reviewed the cases of 14 patients with metaplastic breast carcinoma and compared them to the cases of 63 patients with triple negative breast carcinoma(invasive ductal carcinoma and invasive lobular carcinoma)between December 2005 and December 2013 in the Second Affiliated Hospital of Dalian Medical University.All the patients are female and confirmed through operation resection and pathology.There were no patients with distant metastasis at the time of diagnosis.Patients who presented with a recurrent tumor,bilateral tumors,previous tumors in other sites were excluded.Standard demographic and clinicopathologic variables including age,tumor size,lymphovascular invasion,histologic type,disease stage.Immunohistochemistry of biologic factors included ER,PR,HER2,P53,CK5/6,EGFR and Ki-67.Treatment information was procured that included method of resection,chemotherapy,radiotherapy,endocrine therapy and anti-HER2 therapy.Local recurrence and metastases were also obtained from electronic medical records.The clinical outcomes examined in this retrospective analysis included 3-year overall survival(3-year OS),3-year disease-free survival(3-year DFS).The DFS period was defined as the interval from the date of diagnosis to the date of the first observation of disease recurrence,either loco-regional or distant metastasis,or the last follow-up date without evidence of distant metastasis.The OS was calculated from the date of diagnosis to the date of death or last follow-up.Univariate analysis of the 3-year disease-free survival(DFS)rate and 3-year overall survival(OS)rate of MBC and TNBC was performed.Multivariate analysis was not performed due to the limited sample size.ER or PR was considered positive when nuclear staining was identified in ≥10% of the tumor cells.HER2 positivity was defined as an immunohistochemistry score of 3+ or gene amplification determined by fluorescence in situ hybridization(FISH)were considered positive.Cells nuclear stained for Ki-67 and p53 were counted and expressed as a percentage.For p53,we rescored as 0-3+(0,negative;1+,≤25%;2+,26-50%;3+,>50%),low expression was considered as p53≤25%;For Ki-67,low expression was considered as Ki-67<14%.CK5/6 expression was interpreted as positive if it shows strong cytoplasmic staining in at least 10% of the tumor cells.EGFR expression was interpreted as positive if it shows strong cytomembrane staining in at least 10% of the tumor cells.The pathologic tumor stage was assessed according to the American Joint Committee on Cancer(AJCC)6 Staging System.The statistical analysis was performed using SPSS22.0 software.In order to compare the clinicopathological characteristics,immunohistochemistry and treatment information between the two groups,we used the Student t-test and χ2 test.The 3-year OS rate and 3-year DFS rate were calculated using the Kaplan-Meier method and comparisons were made between MBC and TNBC patients using the log-rank test.For univariate analysis,Cox regression analysis was used.All statistical tests were two-sided with significance level considered at P < 0.05.Results:1.Clinicopathologic in each group.For the MBC group,squamous type was the most common histological type(57.1%),followed by matrix-producing type(14.3%),spindle cell type(14.3%),and adeno-squamous type(14.3%).For the TNBC group,invasive ductal carcinoma was the most common histological type(88.9%),followed by invasive ductal-lobular carcinoma(6.3%)and invasive lobular carcinoma(4.8%).For the MBC group,the median patient age was 63.6 years,for the TNBC group,the median patient age was 50.3 years,the MBC group presented with an older age than the TNBC group(p=0.001).The MBC group presented with a significantly larger tumor size than the TNBC group(≥T2,85.7% versus 50.8%,P<0.001)and with less lymph node metastasis(positive nodal status,14.2% versus 47.6%,P=0.003).More patients in the MBC group than in the TNBC group had stage Ⅱ or stage disease at diagnosis(92.9% versus 39.7%,PⅢ <0.001).2.Comparison of immunohistochemistry of biologic factors between two groups.The MBC group had 78.6% cases with no hormone receptors and HER2 over expression.Over-expression of Ki-67 was more common in the MBC group compared with the TNBC group(Ki-67 ≥14%,71.4% versus 27.0%,P<0.001).The rate of epidermal growth factor receptor(EGFR)over expression was higher in the MBC group compared to that of the TNBC group(78.6% versus 25.4%,P<0.001).There were no differences in CK5/6(57.1% versus 68.3%,p=0.372)and p53 level(42.9% versus 63.5%.p=0.277)between MBC and TNBC groups.3.Comparison of treatment between two groups.12 patients(85.7%)in the MBC group and 48 patients(76.2%)in the TNBC had undergone MRM(modified radical mastectomy),there was no difference in the rates of MRM(P = 0.157)between the two groups.There was no difference in the rates of adjuvant chemotherapy between the MBC group and the TNBC group(85.7% versus 95.2%,P =0.072).There was also no difference in the rates of adjuvant radiotherapy(21.4% versus31.7%,P=0.083)between the MBC group and the TNBC group.4.Comparison and analysis of prognosis between two groups.4.1 Recurrence and distant metastases.During the follow-up of 36 months,20 patients experienced disease recurrence,8 patients(57.1%)in the MBC group and 12 patients(19.0%)in the TNBC group(P <0.001).Patients with local recurrence in the MBC group presented more chest wall recurrence than those in the TNBC group(75% versus 33.3%,P <0.001).Distant metastases were significantly more likely to be in the lung in the MBC group than those in the TNBC group(75% versus 44.4%,P=0.001).4.2 Survival analysis.4.2.1 Three-year disease-free survival(DFS)curveDuring the follow-up of 36 months,8 patients in the MBC group and 12 patients in the TNBC group had disease recurrence.The three-year disease-free survival(DFS)rate was 42.9% in the MBC and 81.0% in the TNBC group(P <0.001).The median disease-free survival of MBC(12 months)was significantly shorter than that of the TNBC(more than 36 months).4.2.2 Three-year overall survival(OS)curveDuring the follow-up of 36 months,7 patients in the MBC group and 8 patients in the TNBC group died.The three-year overall survival(OS)rate was 50% in the MBC and 87.3% in the TNBC group(P <0.001).The median overall survival of MBC(24 months)was significantly shorter than that of the TNBC(more than 36 months).5.Univariate analysis of the 3-year overall survival rate and 3-year disease-free survival rate.In univariate analysis,an age older than 50 years,tumor size≥T2,stage Ⅱor stage Ⅲ,Ki-67≥14%,EGFR over expression and adjuvant radiotherapy were significant prognostic factors for the 3-year disease-free survival rate in MBC.An age older than 50 years,tumor size≥T2,stage Ⅱor stage Ⅲand Ki-67≥14% were significant prognostic factors for the 3-year overall survival rate in MBC.In univariate analysis,an age older than 50 years,tumor size≥T2,lymph node involvement,stage Ⅱor stage Ⅲ,Ki-67≥14%,EGFR over expression,CK5/6 over expression,modified radical mastectomy and adjuvant chemotherapy were significant prognostic factors for the 3-year disease-free survival rate in TNBC.An age older than 50 years,tumor size≥T2,stage Ⅱor stage Ⅲ,lymph node involvement,P53 over expression,EGFR over expression,Ki-67≥14%,modified radical mastectomy and adjuvant chemotherapy or radiotherapy were significant prognostic factors for the 3-year overall survival rate in TNBC.Conclusion:1.Significantly more MBC patients presented with an older age than the TNBC group.The MBC presented with a larger tumor size than the TNBC.More MBC had stage Ⅱor stage Ⅲdisease at diagnosis than the TNBC.MBC are usually associated with a lower incidence of nodal involvement than the TNBC at first diagnosis.Over-expression of Ki-67(Ki-67≥14%)was more common in the MBC compared with the TNBC.The rate of epidermal growth factor receptor(EGFR)over expression was higher in the MBC compared to the TNBC.2.The 3-year disease-free survival rate and the 3-year overall survival rate in MBC were poorer than TNBC,the difference was statistically significant,suggesting that MBC had a higher risk of recurrence and poorer prognosis than TNBC,which had a significant relationship with older age,larger tumor size,later stage,over-expression of Ki-67(Ki-67≥14%)and EGFR.3.MBC presented more chest wall recurrence and lung metastasis.In univariate analysis,age,tumor size,tumor stage,Ki-67≥14% and EGFR over-expression had a significant relationship with the prognosis of both MBC and TNBC.Treatment of metaplastic breast carcinoma was not clear now.For TNBC,radical mastectomy and adjuvant chemotherapy had therapeutic value and the therapeutic value of adjuvant radiotherapy and neoadjuvant chemotherapy need to be further clarified.