The use of genetic testing for selecting the best treatment for early-stage breast cancer

The aim of this article was to discuss the way in which the latest results on cancer DNA research apply to early-stage breast cancer. Genome analysis is highly likely to play a growing role in the future but more clinical trials are needed.

Breast cancer is a disease with multiple symptoms and consequences that are not fully predicted by routine clinical and pathologic features. Major efforts have been made to develop predictors of recurrence and the benefits of adjuvant (after surgery) chemotherapy for patients with early-stage breast cancer. Clinical trials are beginning to determine if multigene tests can guide adjuvant chemotherapy decisions at this stage of breast cancer.

This article reviews available data on 3 multigene tests: Oncotype DX, PAM50 and MammaPrint.

Oncotype DX is a test that measures 21 genes whose modifications are frequently found in breast cancer. Patients are classified in 3 categories based on their cancer recurrence risk (RS): low risk (RS<18), intermediate risk (RS 18-30) or high risk (RS>=31). Studies have shown that Oncotype DX's risk categories were strongly associated with the 10-year rates of breast cancer death. Also, high-risk patients had a significant benefit from adjuvant chemotherapy, whereas low-risk patients had minimal or no benefit. This may suggest that in low-risk patients Oncotype DX may identify women who will not benefit from chemotherapy despite the presence of positive lymph nodes.

The PAM50 test is based on biologic subtypes of breast cancer. It categorizes tumors into 4 subtypes and provides a score to estimate the probability of relapse at 5 years. This test was predictive for the benefit of Tamoxifen (drug that acts against the estrogen receptors present in breast cancer cells) in women before menopause.

MammaPrint is a test for 70 genes, developed for node-negative breast cancer. The test assigns patients to either having low or high-risk for distant metastases (spread of cancer) at 5 years. The high risk patients should receive chemotherapy while low-risk ones may not need it.

Correlating DNA changes with clinical results is just the beginning. The use of Oncotype DX and MammaPrint testing for early stage cancer has helped guide decisions regarding the use of adjuvant chemotherapy.