Using Multigene Tests to Select Treatment for Early-Stage Breast Cancer (original) (raw)
Journal of the National Comprehensive Cancer Network
Oncotype DX, PAM50, and MammaPrint are multigene tests that are being used clinically for early-stage breast cancer to predict recurrence risk and guide adjuvant chemotherapy decisions. These tests have been validated in multiple retrospective studies, and prospective clinical trials are in progress. The TAILORx trial uses the Oncotype DX recurrence score to assign estrogen receptor-positive (ER+), node-negative patients to chemotherapy plus hormonal therapy versus hormonal therapy alone. The RxPONDER (SWOG S1007) trial uses Oncotype DX in a similar approach but on node-positive patients, and it includes the PAM50 test as a secondary analysis. The MINDACT trial uses Mamma-Print and Adjuvant! Online for treatment arm assignments. MINDACT has very broad eligibility criteria and 2 secondary randomizations for selecting chemotherapy and hormonal therapy regimens. This article discusses how the latest results on cancer genome sequencing apply to early-stage breast cancer. Several hundred breast cancers have already undergone genome sequencing, and the somatic DNA changes found in the tumor, compared with the patient's normal DNA, have been identified. Higher rates of point mutations and chromosomal translocations are found in aromatase inhibitor-resistant ER+ cancers and in the basal-like and HER2-enriched breast cancer subtypes. Correlations of somatic mutations with neoadjuvant aromatase inhibitor response are discussed. Genome sequencing can potentially identify the molecular abnormalities that underlie the poor risk identified by multigene tests and provide potential new targets for therapy, but more clinical trials correlating clinical outcome and somatic DNA changes are needed. (JNCCN 2013;11:174-182) NCCN: Continuing Education Accreditation Statement This activity has been designated to meet the educational needs of physicians and nurses involved in the management of patients with cancer. There is no fee for this article. No commercial support was received for this article. The National Comprehensive Cancer Network (NCCN) is accredited by the ACCME to provide continuing medical education for physicians. NCCN designates this journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. NCCN is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center`s Commission on Accreditation. This activity is approved for 1.0 contact hour. Approval as a provider refers to recognition of educational activities only and does not imply ANCC Commission on Accreditation approval or endorsement of any product. Accredited status does not imply endorsement by the provider of the education activity (NCCN). Kristina M. Gregory, RN, MSN, OCN, is our nurse planner for this educational activity. All clinicians completing this activity will be issued a certificate of participation. To participate in this journal CE activity: 1) review the learning objectives and author disclosures; 2) study the education content; 3) take the posttest with a 70% minimum passing score and complete the evaluation at http://education.nccn.org/ node/11346; and 4) view/print certificate.
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