In a long-term analysis of the EORTC 10041/BIG 03-04 MINDACT trial reported in the Journal of Clinical Oncology, Alaeikhanehshir et al found that the 70-gene signature was not independently predictive of locoregional recurrence among women undergoing breast-conserving surgery for early breast cancer.
Study Details
The exploratory substudy included 5,470 patients who underwent breast-conserving surgery out of a total of 6,693 enrolled patients (81.7%); of those undergoing breast-conserving surgery, 97.8% received adjuvant radiotherapy, 39.7% received adjuvant chemotherapy, and 77.4% received adjuvant endocrine therapy. The primary endpoint was locoregional recurrence at 8 years.
Key Findings
At 8-year follow-up, 189 patients had locoregional recurrence, yielding an 8-year cumulative incidence of 3.2% (95% confidence interval [CI] = 2.7%–3.7%). Among 3,578 patients with low-risk 70-gene signature scores, the 8-year cumulative incidence of locoregional recurrence was 2.7% (95% CI = 2.1%–3.3%). Among those with a high-risk score, the cumulative incidence was 4.2% (95% CI = 3.3%–5.2%).
In univariate analysis adjusted for adjuvant chemotherapy, 5 of 12 potential predictive factors were significantly associated with risk of locoregional recurrence:
- High- vs low-risk 70-gene score (hazard ratio [HR] = 1.77, 95% CI = 1.23–2.55, P = .002)
- Receipt vs no receipt of adjuvant endocrine therapy (HR = 0.44, 95% CI = 0.33–0.59, P = .001)
- Tumor grade 3 vs 1 (HR = 2.01, 95% CI = 1.25–3.24, P = .003)
- Progesterone receptor–positive status (HR = 0.63, 95% CI = 0.46–0.86, P = .004)
- Estrogen receptor–positive status (HR = 0.41, 95% CI = 0.28–0.60, P < .0001).
On multivariate analysis, significant factors were:
- Receipt of adjuvant endocrine therapy (HR = 0.42, 95% CI = 0.30–0.59, P < .0001)
- Receipt of adjuvant chemotherapy (HR = 0.60, 95% CI = 0.41–0.89, P = .011)
- Tumor size: first vs third quartile (HR = 1.58, 95% CI = 1.06–2.35, P = .023)
- Tumor grade 3 vs 1 (HR = 1.89, 95% CI = 1.14–3.13, P = .044).
The investigators concluded: “This exploratory analysis of the MINDACT trial estimated an 8-year low locoregional recurrence rate of 3.2% after breast-conserving surgery. The 70-gene signature was not independently predictive of locoregional recurrence perhaps because of the low number of events observed and currently cannot be used in clinical decision-making regarding locoregional recurrence. The overall low number of events does provide an opportunity to design trials toward de-escalation of local therapy.”
Emiel J.T. Rutgers, MD, PhD, of the Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Cancer Research UK and KWF Kankerbestrijding. For full disclosures of the study authors, visit ascopubs.org.
