Even smallest breast tumours may benefit from chemo
Contradicting the common notion that small, early breast tumours are less aggressive, a subgroup analysis of the MINDACT trial reported recently at the European Society for Medical Oncology (ESMO) 2017 Congress in Madrid, Spain, demonstrated that nearly a quarter of such tumours were aggressive by genetic criteria, and patients with those tumours derived a benefit from neoadjuvant chemotherapy.
The MINDACT (Microarray in Node-negative and 1 to 3 Positive Lymph Node Disease May Avoid Chemotherapy) trial was a phase III randomized trial that enrolled 6,693 women with early-stage breast cancer. The aim was to assess whether their genomic risk as determined by the 70-gene signature (MammaPrint) could improve prediction of clinical outcome beyond standard clinical risk assessment with the Adjuvant! Online tool. The investigators concluded that 46 percent of patients with high clinical risk (CH) and low genomic risk (GL) might not require chemotherapy. [N Engl J Med 2016;375:717-729]
The current subgroup analysis focused on node-negative MINDACT patients with T1abN0 disease and tumour size ≤1 cm who had their clinical and genomic risk characterized (n=826). [ESMO 2017, abstract 150O_PR]
“Adjuvant systemic therapy for T1abN0 breast cancer is controversial, as these tumours usually have a low relapse risk. Identification of patients with small tumours at risk of relapse is needed,” said lead author Dr Konstantinos Tryfonidis from the European Organization for Research and Treatment of Cancer (EORTC) in Brussels, Belgium.
“Patients with T1abN0 tumours were mostly hormone receptor [HR]-positive and of luminal A or B subtypes. As expected, 99.3 percent had low clinical risk [CL] based on the Adjuvant! Online criteria,” he reported.
Overall, 624 patients (75.5 percent) were CL/GL, 196 (23.7 percent) were CL/GH, 0.6 percent were CH/GL, and none was CH/GH. Patients characterized as low-risk in both clinical and genomic assessments were spared chemotherapy. Discordant cases were randomized to receive adjuvant chemotherapy or no chemotherapy and followed up for 5 years. Study endpoints were distant metastasis-free survival (DMFS), disease-free survival (DFS) and overall survival (OS).
“Nearly 24 percent of patients were identified as GH-risk by the 70-gene signature. Among those 196 CL/GH patients, 5-year DMFS was 97.3 percent for those who received chemotherapy vs 91.4 percent for those who did not,” said Tryfonidis. “The DFS rates with and without chemotherapy were 92.3 vs 84.5 percent, and OS rates were 98.5 vs 95.8 percent, respectively.”
Although the positive effect of chemotherapy in the CL/GH group of patients with T1abN0 tumours of ≤1 cm was not statistically significant because of the small patient numbers, the data indicate that they might derive a benefit from chemotherapy.
“Our results challenge the assumption that small tumours are less serious and do not require adjuvant chemotherapy. Even the smallest N0 tumours classified as CL-risk can be aggressive, and could be identified by the 70-gene signature,” he suggested. “Biological characteristics of the tumour should be taken into account when deciding on adjuvant treatment in this population, as well as other factors such as performance status, comorbidities, and patient age and preference.”