Invasive carcinoma with mixed ductal and lobular features

BOSTON — In patients with invasive ductal carcinoma (IDC), lobular morphology may be an unfavorable histologic feature and, in fact, may represent a distinct variant of the common infiltrative breast cancer, David P. Arps, MD, reported last week at the American Society for Clinical Pathology (ASCP) 2012 Annual Meeting.

In a study comparing the biologic phenotype and clinical behavior of 183 cases of IDC with lobular features (IDC-L) treated at the University of Michigan Health System (UMHS) from 1996-2011 with that of 1499 cases of IDC and 375 cases of pure invasive lobular carcinomas (ILC) identified from the UMHS breast cancer tumor registry from 1996-2007, patients with IDC-L had a higher frequency of lymph node metastases despite the presence of features typically considered to be prognostically favorable, including estrogen receptor (ER) and progesterone receptor (PR) positivity and low histologic grade, according to Dr. Arps, a resident in the Department of Pathology at UMHS in Ann Arbor. "Our findings are consistent with those of previous studies suggesting [IDC-L] may behave differently than pure ductal carcinomas and similarly to pure lobular carcinomas," he said.

To better understand the prognostic significance of IDC-L, Dr. Arps and colleagues reviewed the available slides (n = 150) and quantified the lobular component (20% or less, 21% - 50%, 51%-80%, more than 80%), and they analyzed the clinical and pathologic characteristics of IDC-L on the basis of the proportion of lobular component — defined as small cells individually dispersed, arranged in linear cords, or in loose aggregates without the formation of tubules or cohesive nests.

For confirmation of ductal origin in cases with available tissue blocks, the investigators assessed, via immunostain, the expression of epithelial cadherin (E-cadherin), which is common in most cases of IDC and few cases ILC, Dr. Arps explained. They used Chi-square test or Fisher exact test to analyze categorical prognostic factors, ANOVA to compare groups with continuous prognostic factors, and multivariate Cox regression to model survival as a function of the prognostic factors, he said.

In the comparison of IDC-L to IDC, IDC-L was more likely to have a lower histologic grade, Dr. Arps reported. Also, "96% of the IDC-L cases were positive for ER compared with 70% of the IDC cases, and 84% compared with 57%, respectively, were more likely to be positive for PR," he said. Additionally, IDC-L was less likely to overexpress human epidermal growth factor receptor 2 (HER2/neu), at a rate of 12% vs 23%. Finally, the frequency of nodal metastasis was higher for IDC-L than IDC, at 51% vs 35%, even after adjusting for size, he said.

Compared with ILC, IDC-L was more likely to have a higher histologic grade and was more likely to be PR positive (84% vs 74%), Dr. Arps stated, noting, however, "there were no significant differences in ER and HER-2/neu expression, tumor size, or frequency of nodal metastases." Additionally, he said that no significant differences were observed in tumor stage at presentation or in rates of local, regional, and distant recurrence between patients with IDC and IDC-L, and ILC and IDC-L.

Among the four groups of IDC-L separated by the relative proportion of lobular component, "there were no statistically significant differences in mean patient age, tumor size, lymph node status, disease stage at presentation, [ER] status, 5-year recurrence, or 5-year survival rates," Dr. Arps stated. With respect to survival by histologic subtype, there were no differences in disease-specific survival for IDC-L, IDC, and ILC in either univariate or multivariate analysis, but IDC-L had a worse disease-free survival compared with IDC, "even after adjustment for prognostic factors," he said, noting that disease-free survival for IDC-L and ILC were statistically similar.

Of the IDC-L cases, 92% demonstrated immunoreactivity for E-cadherin in both the ductal and lobular components, indicating that IDC-L is more similar clinicopathologically to ILC than to IDC, according to Dr. Arps.

The findings suggest that IDC-L and IDC have different biologic phenotypes and clinical behavior, whereas IDC-L and ILC are similar, independent of the relative proportion of lobular component, Dr. Arps concluded. The distinction of IDC-L from IDC appears to be important, and as such, he said, defined criteria and uniform terminology for their diagnosis is warranted.

"The behavior of mixed ductal/lobular tumors seems to demonstrate some important differences from pure ductal counterparts," according to Krishna A. Rao, MD, PhD, associate professor of internal medicine at Southern Illinois School of Medicine in Springfield.

In an earlier investigation, Dr. Rao (who was not involved in this study) and his colleagues demonstrated similar clinocopathologic differences between IDC and IDC-L, as well as a lower rate of metastatic spread for IDC-L but a higher rate of second primary breast cancers (World J Surg Oncol 2010;8:51). "It is clear that mixed ductal/lobular carcinomas are a distinct clinicopathologic entity that incorporates features from both ductal and lobular carcinomas," he told Medscape Medical News. On the basis of immunohistochemistry, "they may very well represent another variant of IDC."

Dr. Arps and Dr. Rao have disclosed no relevant financial relationships.

American Society for Clinical Pathology 2012 Annual Meeting: Poster 143. Presented November 2, 2012.

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