- The MINDACT:
- Is a randomized, controlled, prospective, phase III, clinical trial:
- Evaluating the use of a 70-gene signature test (MammaPrint):
- To aid in directing chemotherapy treatment of women with early-stage breast cancer
- The goal of this study was:
- To reduce the overtreatment of early-stage breast cancer
- To determine if genomic risk (as defined by the 70-gene signature test) can be utilized to predict recurrence and possibly avoid chemotherapy in patients with a low genomic risk
- Evaluating the use of a 70-gene signature test (MammaPrint):
- Is a randomized, controlled, prospective, phase III, clinical trial:
- Patients were designated as high or low risk for recurrence based on two categories:
- Clinical / pathologic high-risk features:
- Positive lymph nodes
- High-grade tumors
- T2 tumors
- Premenopausal diagnosis
- Genomic risk:
- As defined by the 70-gene signature test
- Clinical / pathologic high-risk features:
- Women who were low risk in both categories:
- Were not given chemotherapy
- Women who were high risk in both categories:
- Were given chemotherapy in addition to endocrine therapy
- The patients who were deemed discordant between the two categories:
- Were randomized to use either:
- Clinical / pathologic or genomic risk to determine chemotherapy recommendations
- Patients who had a low genomic risk had a 94.7% 5-year distant-metastasis-free survival without chemotherapy:
- Even in the presence of high-risk clinical / pathologic factors
- The authors concluded that:
- Selected patients with low genomic risk may be spared chemotherapy
- However, in an accompanying editorial:
- Critics of this trial have noted the survival advantage of 1.5% for high-risk patients who received chemotherapy, and that the study was underpowered to accurately analyze differences between these groups
- They noted that small differences in survival may be more significant to certain patients:
- Thus, the decision to forgo standard treatment based on genomic assays is a very personalized decision
- Were randomized to use either:
- Similar results were reported with the 21-gene recurrence score assay (e.g., Oncotype DX):
- With regard to benefit of adjuvant chemotherapy based on genomic risk stratification:
- For women with estrogen receptor-positive, lymph node-negative breast cancer:
- Patients with a high recurrence score via the 21-gene recurrence score assay had a significant benefit from chemotherapy with a decrease in 10-year distant recurrence rates, while patients with a low score showed minimal benefit
- For women with estrogen receptor-positive, lymph node-negative breast cancer:
- With regard to benefit of adjuvant chemotherapy based on genomic risk stratification:
- While they differ in the individual genes used to determine their output score:
- Both of these genomic assays support the concept of directing adjuvant therapy for breast cancer:
- Based on the biology and genetics of the tumor itself rather than only the clinical and / or pathologic factors
- Both of these genomic assays support the concept of directing adjuvant therapy for breast cancer:
References
1. Cardoso F, van’t Veer LJ, Bogaerts J, Slaets L, Viale G, Delaloge S, et al; MINDACT Investigators. 70-gene signature as an aid to treatment decisions in early-stage breast cancer. N Engl J Med. 2016;375(8):717-729.
2. Hudis CA, Dickler M. Increasing precision in adjuvant therapy for breast cancer. N Engl J Med. 2016;375(8):790-791.
3. Paik S, Tang G, Shak S, Kim C, Baker J, Kim W, et al. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol. 2006;24(23):3726-3734.
Rodrigo Arrangoiz MS, MD, FACS, FSSO 