DISEASE FREE SURVIVAL IN LOBULAR BREAST CANCER IS IMPACTED BY Ki67 BUT NOT RECURRENCE SCORE
In a vast majority of cases, invasive lobular carcinoma (ILC) is hormone receptor positive and Her2 negative. It is generally an indolent disease and, in many series, has been reported as having a better 5-year disease free survival when compared to ductal carcinoma (IDC). Though the Oncotype Dx recurrence score (RS) assists in deciding for or against adjuvant chemotherapy, its use in ILC is somewhat controversial and has not been thoroughly evaluated. For instance, in the prospective TAILORx trial, there has yet been no subgroup analysis for patients with ILC.
The West German Study Group (WSG) PlanB trial (anthracycline-free taxane based chemotherapy (CT) in patients with Her2 negative early breast cancer) is a large prospective, randomized, multicenter, phase 3 trial in patients with Her2 negative breast cancer, and with intermediate-to-high clinical risk features. PlanB was the first clinical trial to assess the Oncotype Dx RS in hormone receptor positive early breast cancer in lymph node positive and negative disease. Currently, on the assumption that the clinical behavior is the same, the treatment of ILC differs little from treatment of IDC. Practice-changing clinical trials such as TAILORx did not pay special attention to those patients with ILC.
PlanB recruited 3193 patients in 93 centers. The subgroup evaluation focused on hormone receptor positive, Her2 negative breast cancers. Fourteen percent (353) were classified as lobular, and 86% (2232) non-lobular. Median follow-up was 60 months. Ninety-eight percent of cases had RS reported. The prevalence of high RSs was 3-fold lower in ILC than nonlobular carcinoma. Only 8% of Lobular carcinomas had a high RS (26-100). The RS was low (0-11) in 20% and intermediate in 72% (12-25). Using data from TAILORx, only 8% of patients with lobular histology would derive significant benefit from chemotherapy given in addition to hormonal therapy.
What was the relationship between RS and Ki67? The authors noted that there was a lower RS in ILC for every given Ki67 level. The authors then asked whether lower RSs could be fully accounted for by lower cell proliferation. Using multiple logistic regression statistical analysis, it was found that lobular histology has a direct influence on lower RS in addition to its indirect effect because of a lower Ki67 values.
The 5-year disease free survival (DFS) estimates were 92.1% and 92.3% for lobular and nonlobular histology. There was also similar 5-year DFS for lobular and nonlobular histology with the same T-status, lymph node status and RS category.
Most importantly, multivariate prognostic parameters impacting disease free survival differed between lobular and nonlobular breast cancer. Prognostic parameters for nonlobular breast cancer included T-value, grade, node status and RS value. For lobular cancer, only tumor size, grade, and node status, but not RS affected disease free survival. Ki67 had a particular effect on disease free survival in in lobular cancer. (see graphs above).