Is Tumor Gene Testing Effective with Lobular Breast Cancer?

Is Tumor Gene Testing Effective with Lobular Breast Cancer?

Gene Testing Effectiveness

The two most frequently diagnosed types of breast cancer are invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC). ILC makes up approximately 15% of all breast cancers, with IDC making up most of the remainder. There are several features of ILC not shared by other types of breast cancer; for example, over 90% are estrogen receptor positive compared with 65-70% of IDCs. ILCs are more difficult to diagnose on mammography, and there is a tendency to have second cancers in the opposite breast at the time of presentation. However, most importantly, ILC is thought to not respond well to chemotherapy. In addition, the tumor gene tests such as Oncotype DX and MammaPrint used to determine whether patients will benefit from chemotherapy are also thought to be less effective and, therefore, less frequently used by oncologists. Unfortunately, this assumption may result in withholding beneficial chemotherapy from many patients who could benefit.

A recent study published in the journal Cancer by Weiser et al. evaluated the use of Oncotype DX 21-gene recurrence score (RS) in a very large group of patients with both IDC and ILC. The researchers used the massive National Cancer Database. They identified 115,833 breast cancer patients, of which 15,763 had ILC. Those with ILC were less frequently treated with chemotherapy (CT) than those with IDC (17% vs. 24.6%). Patients with ILC tended to be slightly older (59 vs. 57), had fewer comorbidities, and had higher incomes. Patients with ILC had larger tumors (22mm vs. 16 mm) and appeared less aggressive when viewed under the microscope, though they had similar rates of lymph node involvement.

As a review, Oncotype DX RS scores are reported as low, intermediate, or high. There was a lower percentage of high RS in patients with ILC (6.6% vs. 16.0%). ILC Patients with intermediate or high RS were also less likely to receive CT with or without involved lymph nodes.

Does RS impact prognosis?
In patients with ILC and negative lymph nodes, there was little difference in 5-year survival. However, when studying the RS in patients with ILC and positive nodes, the 5-year survival rate was similar for the low and intermediate RS (95.5% for each); there was a substantial drop in survival in those patients with high RS (83.8%). Patients with either IDC or ILC who had high RS and received CT had a comparable improvement in 5-year overall survival.

Prognostic value of RS in ILC
Patients with low RS had a 96.9% 5-year survival rate compared to 94.4% in those with a high RS. In contrast, patients with positive nodes and a low or intermediate RS had a 5-year survival rate of 95.5% compared to 83.3% for those with a high RS.

Predictive value of RS with ILC
Patients with ILC and IDC with high RS had comparable survival improvement with CT receipt. There was no difference in survival in patients with ILC and IDC who did not receive chemotherapy. Patients with positive nodes and low and intermediate RS showed no survival advantage with CT.

The authors demonstrated that the distribution of RS in patients with ILC is different than in those with IDC. Far fewer patients with ILC had a high RS than those with IDC. Although there is a tendency by oncologists to underplay the significance of RS in ILC, the authors demonstrated that in this very large sample of patients (1037), RS was a prognostic factor. Although patients with ILC and a high RS are infrequent, this study emphasizes the importance of their identification and “consider treatment intensification for these patients.”