Study Finds Lobular Breast Cancer Associated with Distinct Characteristics

The collective study findings suggested that for risk assessment, the recurrence score needs to be complemented by clinicopathologic parameters for therapy decision making.

A study published in Cancer confirmed that lobular breast cancer is associated with distinct characteristics, including lower histologic grade, lower Ki67, and low or intermediate recurrence score results but higher tumor classification.

Further, the study also suggested that lobular breast cancer has a 3-fold lower prevalence of high recurrence score results, however 5-year disease-free survival is similar in lobular and nonlobular breast cancers. The effect of recurrence score in lobular breast cancer therefore appears to be distinct from that observed in nonlobular breast cancer.

Given these findings, researchers suggested that for risk assessment, the recurrence score needs to be complemented by clinicopathologic parameters for therapy decision making.

“Compared with histologic grade, the gene expression profiling-based [recurrence score] was of limited prognostic value and should be interpreted with caution in patients who have lobular [breast cancer],” the authors noted. “The correct histologic classification of [breast cancer] subtypes thus may be a prerequisite for the adequate clinical use of prognostic gene expression profiles.”

Using the large, prospective, West German Study Group PlanB trial, researchers retrospectively studied prognostic parameters in 2585 patients who had hormone receptor-positive early breast cancer. After central review of the breast cancers, 353 (14%) patients were classified as lobular and 2232 were classified as nonlobular (86%). Median follow-up was 60 months.

Overall, lobular breast cancer was correlated with a higher tumor classification, higher lymph node status, lower histologic grade, lower Ki67 index, and low or intermediate recurrence score. Moreover, the prevalence of high recurrence score (recurrence score range, 26-100) was 3-fold lower in patients who had lobular breast cancer compared with those who had nonlobular breast cancer (8% vs 24%; P < .001). However, 5-year disease-free survival estimates for lobular and nonlobular breast cancer were similar (92.1% and 92.3%, respectively; P = .673).

“This is in line with other recent findings indicating that clinical parameters need to be carefully weighed against expression profiling-based risk assessment,” the authors wrote.

In multivariate analyses, prognostic parameters for disease-free survival in lobular breast cancer included grade 3 (HR, 5.06; 95% CI, 1.91-13.39) and a pathologic lymph node status (pN) of pN3 (HR, 12.16; 95% CI, 3.87-38.24), but not recurrence score. Contrastingly, prognostic parameters in nonlobular breast included grade 3 (HR, 1.65; 95% CI, 1.11-2.44), pN3 (HR, 3.68; 95% CI, 1.60-8.46), and high recurrence score (HR, 2.49; 95% CI, 1.69-3.68).

Importantly, the researchers suggested that before a solid final conclusion on prognostic parameters in lobular breast cancer can be drawn, the current study findings should be confirmed by a similar subgroup analyses in larger, prospective clinical trials using the Oncotype DX assay. In addition, other molecular profiling assays may also offer different prognostic implications for lobular breast cancer.

“Further studies also are warranted to investigate whether the direct influence of the lobular [breast cancer] subtype on lower [recurrence score] results is related to differential expression of specific assay target genes,” the authors wrote.


Christgen M, Gluz O, Harbeck N, et al. Differential Impact of Prognostic Parameters in Hormone Receptor-Positive Lobular Breast Cancer. Cancer. doi: 10.1002/cncr.33104

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