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27-01-2022 | Breast cancer | News

Genetic ultralow-risk breast cancers ‘have the best prognosis’

Author: Laura Cowen


medwireNews: Individuals with 70-gene signature ultralow-risk breast cancers are significantly less likely to experience distant metastasis or breast cancer-related death than those with low-risk tumors, show data from the phase 3 MINDACT trial.

The study included 6693 women with nonmetastatic, clinical stage T1, T2, or operable T3 primary breast cancer and up to three positive lymph nodes who had their clinical and genomic risks determined using Adjuvant! Online and the MammaPrint 70-gene signature, respectively.

Patients with high clinical and genomic risk were treated with chemotherapy while those with dual low risks were not. Individuals with discordant clinical and genomic risks were randomly assigned to receive chemotherapy or not based on either their clinical or genomic risk.

Just under half (49%) of the participants had tumors with a low-risk 70-gene signature, 36% were categorized as high-risk, and the remaining 15% had an ultralow-risk 70-gene signature.

Laura van 't Veer (UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California, USA) and co-authors note in the Journal of Clinical Oncology that the “[p]atients with ultralow-risk tumors had favorable clinical-pathologic characteristics.”

Specifically, 67% were over 50 years of age, 81% had tumors that were 2 cm or smaller, 80% were lymph node-negative, 96% had grade 1 or 2 tumors, and 99% were estrogen receptor (ER)-positive.

The majority (69%) of participants with ultralow-risk tumors received endocrine therapy, 14% received endocrine therapy plus chemotherapy, 1% received another systemic treatment, and 16% received no adjuvant systemic treatment.

At 8 years of follow-up, 97.0% of women with ultralow-risk tumors were alive and free from distant metastases, compared with 94.5% and 89.2% of those with low- and high-risk tumors, respectively.

The 8-year breast cancer-specific survival rates were a corresponding 99.6%, 98.2%, and 93.7%.

After adjustment for genomic risk, age, lymph node status, tumor size and grade, and treatment, the team found that individuals with ultralow-risk tumors had a significant 35% lower risk for distant metastases or breast cancer-related death than those with low-risk tumors.

van 't Veer et al also looked at the impact of treatment on outcomes in the women with ultralow-risk tumors. They found that 97.8% of the 157 participants who received no adjuvant systemic therapy (97% also had low clinical risk) were alive and distant metastasis-free at 8 years, as were 97.4% of the 685 individuals (83% low clinical risk) who received endocrine therapy only.

For the 144 participants who received chemotherapy (92% high clinical risk), the corresponding rate was slightly lower, at 94.9%.

However, the investigators stress that this was an exploratory analysis of the MINDACT trial and “there was no random assignment to treatment specifically in the ultralow-risk patients, which complicates any comparison of treatment effect in this group.”

Nonetheless they conclude: “Patients with ultralow-risk tumors could be candidates for further de-escalation of treatment, further reducing overtreatment and the risk of side effects.”

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group

J Clin Oncol 2022; doi:10.1200/JCO.21.02019