Patient Demographics and Clinical Findings
All patients were female. Patients with mixed ductal/lobular tumors ranged from ages 32 to 90, with an average age of 62.28 years. Patients ranged in stages from I to IV. The majority of patients were stage I, with a percentage of 50% (25/50) presenting at this early stage. Stage II patients occurred at a frequency of 38% (19/50 cases), while stage III (3/50) and stage IV (2/50) comprised of 6% of cases and 4% of cases, respectively. Our control group of IDCs was comprised of 100 age-matched cases. The ages ranged from 31 to 90, with an average age of 59.07 years. The frequency of the various stages was stage I (48%), stage II (35%), stage III (15%), and stage IV (1%). Further patient characteristics are outlined in Table .
Pathologically, 14% of the tumors in the mixed ductal/lobular group were grade I, 52% were grade II, 24% were grade III, and 10% were listed with an unknown grade. In the group of patients with invasive ductal carcinoma, 16% of patients had grade I tumors, 43% had grade II tumors, 30% had grade III tumors and 11% had an unknown grade. The average size of the primary tumors in the mixed ductal/lobular group was 22.1 mm with a range in size from 5 mm to 50 mm. In the ductal group, the average tumor size was 19.4 mm, with a range in size from 7 mm to 55 mm. This variable did differ significantly between the two groups when analyzed by ANOVA (p = 0.022). Axillary lymph nodes were involved in 26% of mixed ductal/lobular cases and 24% of ductal cases, respectively. Purely ductal carcinomas were 67% ER positive, 18% ER unknown, and 15% ER negative. They were 52% PR positive, 20% unknown, and 28% PR negative. Mixed ductal/lobular carcinomas were 74% ER positive, 10% ER unknown, and 16% ER negative. Mixed ductal/lobular carcinomas were 48% PR positive, 40% PR negative, and 12% PR unknown. Pathologic characteristics are outlined in Table .
On review of the 7 available cases of mixed ductal/lobular carcinoma pathology, the average percentage of ductal carcinoma was 54.57% and the average percentage of lobular carcinoma was 45.28%. The individual percentage of lobular and ductal histology is listed for each case in Table . Figures and illustrate a case of mixed ductal/lobular histology, while Figures and illustrate the E-cadherin staining on that specimen, confirming E-cadherin presence in the ductal and lobular component of the tumor. Although the E-cadherin staining is weaker in the lobular regions of the tumor, it is nonetheless present. Overall, 90% (6/7) of the cases displayed E-cadherin positivity.
H&E of a mixed ductal/lobular tumor. 200× magnification of an H/E stained section of mixed ductal/lobular histology tumor. Ductal histology is noted.
H&E of a mixed ductal/lobular tumor. 200× magnification of an H/E stained section of mixed ductal/lobular histology tumor. Lobular histology is noted.
E-cadherin immunostaining of the ductal components of the tumor. E-cadherin staining on the same specimen displays the presence of E-cadherin in the ductal areas of the tumor.
Figure 4 E-cadherin immunostaining of the lobular components of the tumor. E-cadherin staining on the same specimen displays the presence of E-cadherin in the lobular component of the tumor, suggesting that this mixed ductal/lobular tumor is indeed a variant of (more ...)
Post-surgical clinical treatment was subdivided into chemotherapy, radiation therapy, and hormonal therapy. Twenty-eight percent of the mixed ductal/lobular tumor patients and 30% of the ductal patients received chemotherapy. In the mixed ductal/lobular group receiving chemotherapy, 15.4% patients received doxorubicin, 30.8% received doxorubicin/cyclophosphamide, 38.4% received cyclophosphamide/methotrexate/5-FU, 7.7% received 5-FU/leucovorin/methotrexate, and 7.7% received methotrexate. In the invasive ductal group receiving chemotherapy, 3.7% received 5-FU, 11% received doxorubicin/cyclophosphamide, 26% received cyclophosphamide/doxorubicin/5-FU, 55.6% received cyclophosphamide/5-FU/methotrexate, and 3.7% received 5-FU/leucovorin/methotrexate. Thirty-two percent of the mixed ductal/lobular tumor patients and 31% of the IDC patients received radiation. Radiation consisted of 5040 cGy in 28 treatment fractions given to the whole breast followed by a 1000 cGy boost to the tumor in post-lumpectomy patients. Post-mastectomy patients requiring radiation received 5040 cGy in 28 treatment fraction to the involved chest wall. Hormonal therapy was given to 36% of patients in the mixed ductal/lobular histology group and 35% of patients in the purely ductal histology group. Virtually, all patients treated with hormonal therapy received tamoxifen in either group.
Clinical follow-up was available for all patients and ranged from 10 to 17 years. In the mixed ductal/lobular group, the disease-free survival rate currently stands at 42% (21/50). Overall survival stands at 46%. Another 38% (19/50) patients have expired without any evidence of recurrence. Overall survival for this group averaged 12.2 years with a range of 10 to 17 years. Disease-free survival was an average of 8 years with a range of 0 to 15.25 years. Three patients were deemed "never disease-free", constituted 6% of the population, and have expired. An additional 6% (3/50) of patients had local or regional relapse of their tumor, and one of these patients has been successfully treated and remains disease-free. The rate of distant metastatic spread was 8% (4/50), and sites of metastasis included bone (2 patients) and lung (2 patients).
In the group of patients with ductal histology, the disease-free survival rate remains at 36%. Overall survival is 39%. Another 32% have expired without any evidence of recurrence. Eight percent of patients had a local or regional recurrence, 2% of patients had a recurrence that was not further specified, 3% were never disease-free, and 19% of patients developed distant metastatic spread. Liver metastases were present in 3% of patients. Lung metastases developed in 5% of patients. Bone metastases developed in another 11% of patients. Overall survival for the ductal group was 9.23 years with a range of 1 month to 17.8 years. Disease-free survival ranged from 0 months to 16.9 years with an average of 8.42 years. Interestingly, 30% (15/50) of the patients with mixed ductal/lobular histology breast cancer and 11% of the patients with ductal histology had a second primary breast cancer. There were 12 patients with mixed ductal/lobular breast carcinoma who had MRI of the breast, and 2 out of 12 patients (16.66%) had suspicious contralateral lesions. On review of the pathology, one case had carcinoma in-situ and other case had benign, fibrocystic changes in the contra-lateral breast. Thus, there was no case of contralateral invasive breast cancer. The 12 cases of invasive ductal breast carcinoma also had no contralateral breast cancer on review of the radiology results. One patient did have a benign fibroadenoma, but there were no cases of in-situ or invasive malignancy. Patient characteristics for these two groups are listed in Table .
Clinical characteristics and MRI findings
Statistical analysis was performed on the data from both sets of patients. Logistic regression analysis using SPSS software was performed. Holding the occurrence of a second primary breast cancer as a regression variable, age at diagnosis, pathologic tumor grade, tumor size, and TNM stage were not significant prognostic factors with β significance values of 0.447, 0.158, 0.490, and 0.424, respectively. However, the β value for tumor histology did achieve a significance of 0.05 and appears to be a strong predictor of secondary breast cancer development. The odds ratio of developing a second primary breast cancer was 7.95 with the mixed ductal/lobular histology using a Chi-square statistical model. Cox regression analysis was performed on the data set to determine if histology impacted overall survival or disease-free survival.
Although TNM stage and tumor grade were both significant factors impacting overall survival and disease-free survival, histology was not a significant variable for both of these parameters, with a significance level of 0.728 with respect to overall survival and a significance level of 0.721 with respect to disease-free survival. Figure depicts the overall survival curve for the two groups while Figure depicts the disease-free survival for the two groups.
Overall Survival. Kaplan-Meier plot of overall survival of patients with mixed ductal/lobular histology tumors and patients with purely invasive ductal carcinomas reveals no significant difference between the two groups.
Disease-Free Survival. Kaplan-Meier plot of disease-free survival of patients with mixed ductal/lobular histology tumors and patients with purely invasive ductal carcinomas reveals no significant between the two groups as well.