With 8.7 years median follow-up, a subgroup of patients included in the MINDACT study with stage I oestrogen receptor (ER)-positive, HER2-negative, low-risk breast cancer who received no adjuvant systemic therapy had a good 8-year distant metastasis-free interval (DMFI) rate, although a slightly better outcome and lower rates of locoregional recurrence and contralateral breast cancer were observed in patients who received endocrine therapy. Considering the natural history of ER-positive, HER2-negative breast cancer and the projected long-term survival effects of endocrine therapy, the observed effect of adjuvant endocrine therapy as well the side effects should be discussed with patients even at a very low risk of distant metastasis according to Prof. Emiel J.T. Rutgers of the Netherlands Cancer Institute in Amsterdam, The Netherlands and colleagues who published the findings on 30 November 2021 in the Annals of Oncology.
In the randomised, phase III MINDACT study, treatment allocation and randomisation was based on risk stratification. Standard clinical-pathological characteristics were used to determine clinical risk and the 70-gene signature MammaPrint was used to determine genomic risk. Patients identified as low-risk by both methods, did not receive chemotherapy as per study design. These patients were treated according to local guidelines, with most ER-positive patients receiving endocrine therapy.
However, there is also a group of patients in MINDACT who received no adjuvant systemic therapy. As the Netherlands was the largest recruiter for the MINDACT study, and their national guideline permits the omission of all adjuvant systemic therapies in a subgroup of low-risk patients, the majority of the patients in MINDACT who received no adjuvant systemic therapy came from the Netherlands.
The aim of this analysis was to evaluate the survival of patients with breast cancer who participated in the MINDACT study and did not receive any type of adjuvant systemic therapy and compare their outcomes to those patients with similar characteristics who received endocrine therapy.
The authors wrote in the background that adjuvant systemic therapy reduce mortality, but have associated short- and long-term toxicities. Therefore, careful selection of patients likely to benefit from adjuvant systemic therapy is needed.
Patients with ER-positive, HER2 negative, lymph node negative tumours ≤2cm who received no adjuvant systemic therapy were matched 1:1 to patients with similar tumour characteristics treated with adjuvant endocrine therapy, using propensity score matching and exact matching on age, genomic risk (70-gene signature) and grade.
In a posthoc analysis, DMFI and overall survival (OS) were assessed by Kaplan-Meier analysis and hazard ratios (HR) by Cox regression. Cumulative incidences of locoregional recurrence and contralateral breast cancer were assessed with competing risk analyses.
At 8 years, DMFI rates were 94.8% (95% confidence interval [CI] 92.7-96.9%) in 509 patients receiving no adjuvant systemic therapy, and 97.3% (95% CI 95.8-98.8%) in 509 matched patients who received only endocrine therapy with absolute difference of 2.5% (HR 0.56; 95% CI 0.30-1.03).
No statistically significant difference was seen in 8-year OS rates, 95.4% (95% CI 93.5-97.4%) in patients receiving no adjuvant systemic therapy, and 95.6% (95% CI 93.8-97.5%) in patients receiving only endocrine therapy with absolute difference of 0.2% (HR 0.86; 95% CI 0.53-1.41).
Cumulative incidence rates of locoregional recurrence and contralateral breast cancer were 4.7% (95% CI 3.0-7.0%) and 4.6% (95% CI 2.9-6.9%) in patients receiving no adjuvant systemic therapy versus 1.4% (95% CI 0.6-2.9%) and 1.5% (95% CI 0.6-3.1%) in patients receiving only endocrine therapy.
The authors concluded that in patients with stage I low-risk breast cancer, the effect of endocrine therapy on DMFI was limited, but overall significantly fewer breast cancer events were observed in patients who received endocrine therapy, after the relatively short follow-up of 8 years. These benefits and side effects of endocrine therapy should be discussed with all patients, even those at a very low risk of distant metastasis.
The authors acknowledged the contribution of the European Organisation for Research and Treatment of Cancer and the Breast International Group.
Lopes Cardozo JMN, Byng D, Drukker CA, et al. Outcome without any adjuvant systemic treatment in stage I ER+/HER2- breast cancer patients included in the MINDACT trial. Annals of Oncology; Published online 30 November 2021. DOI: https://doi.org/10.1016/j.annonc.2021.11.014