Excellent prognosis for breast cancer patients with ultra-low-risk gene signature

An analysis of 1,000 patients in the MINDACT trial identified patients with ultra-low risk for distant recurrence. These patients could be candidates for further de-escalation of treatment.

Gene signatures have proven successful in identifying patients with a low risk of distant recurrence who could forego chemotherapy [1]. Currently, these signatures are included in international treatment guidelines for breast cancer. For the 70-gene signature (MammaPrint), an additional threshold was established within the low-risk category to identify patients with an ultra-low risk of distant recurrence [2]. In independent cohorts, these patients had excellent breast cancer-specific survival at 15 years, suggesting that ultra-low risk cancers represent indolent diseases [3].

Dr Josephine Lopes Cardozo (Netherlands Cancer Institute, the Netherlands) presented the survival results of patients with an ultra-low-risk 70-gene signature who participated in the randomised, phase 3 MINDACT trial (NCT00433589) [4]. Of the 6,693 patients enrolled, profiling revealed an ultra-low-risk 70-gene signature in 1,000 patients (15%). Among these, 67% were ≥50 years, 81% had tumours <2 cm, 80% were lymph node-negative, 96% had grade 1 or 2 tumours, and 99% were ER-positive. Of patients with an ultra-low risk according to the 70-gene signature, 741 had a low clinical risk and 259 had a high clinical risk. Systemic therapy was received by 83% of patients (69% endocrine therapy, 14% endocrine therapy plus chemotherapy) and 16% received no adjuvant systemic treatment.

After a median follow-up of 8.7 years, 8-year distant metastasis-free interval in the patients with ultra-low risk was 97.0% (vs 94.5% for patients with low-risk signature and 89.2% for patients with high-risk signature; see Figure). Breast cancer-specific survival rate at 8 years was 99.6%, 98.2%, and 93.7%, respectively. The difference in distant metastasis-free interval between patients with ultra-low-risk signature and clinical low risk (n=741) versus ultra-low-risk signature and clinical high risk (n=259) was small: 97.6% versus 95.0%. No difference in breast cancer-specific survival was observed in genomic ultra-low-risk patients by clinical risk: 99.7% versus 99.2%. Distant metastasis-free interval in genomic ultra-low-risk patients who had received no adjuvant systemic treatment was 97.8% versus 97.4% in ultra-low-risk patients who had received adjuvant endocrine systemic therapy and 94.9% in ultra-low-risk patients who had received adjuvant endocrine therapy and chemotherapy.

Figure: Excellent distant metastasis-free interval rates for genomic low-risk and ultra-low-risk patients [4]



Based on these results, Dr Lopes Cardozo concluded that “the 70-gene signature MammaPrint can identify early breast cancer patients who have an ultra-low risk for distant recurrence. These patients could be candidate for further de-escalation of treatment, further reducing overtreatment and the risk of side effects.”

1. 
   
   1. Piccart M, et al. Lancet Oncol. 2021;22:476-488.
   2. Esserman LJ, et al. JAMA Oncol. 2017;3:1503-1510.
   3. Delahaye LJMJ, et al. BC Res Treat. 2017;164:461-466.
   4. Lopes Cardozo J, et al. Outcome of patients with an ultralow risk 70-gene signature in the MINDACT trial. Abstract 500, ASCO 2021 Virtual Meeting, 4–8 June.

 

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Posted on 12 August, 20213 September, 2021