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Tamoxifen monotherapy may mean undertreatment for some luminal breast cancer patients

SABCS 2019

Age plays a key role in evaluating the right therapy as it has emerged that women between 40 and 50 years old who suffer from hormone receptor (HR)-positive, human epidermal growth factor 2 (HER2)-negative breast cancer, a high clinical risk, and low genomic risk had a greater benefit from chemotherapy than those aged >50 years.

In the MINDACT trial, the utility of the 70-gene signature commercial diagnostic test MammaPrint was compared with common clinical-pathological criteria to select breast cancer patients with 0 to 3 positive nodes for adjuvant chemotherapy. An unplanned analysis of MINDACT was performed, aiming to determine whether the addition of chemotherapy had an age-dependent impact on distant metastasis-free survival (DMFS) among certain breast cancer patients [1]. The reason for this analysis were recent findings of the TAILORx trial, which demonstrated that patients aged <50 years had an estimated chemotherapy benefit in reducing distant recurrence at 9 years if they had an Oncotype DX recurrence score (RS) of 16-20 with high clinical risk, or a recurrence score of 21-25 irrespective of clinical risk. A total of 1,264 patients aged >40 years were included in this subgroup analysis, of which 399 patients were aged 40-50 years and 865 patients >50 years.

The estimated 5-year DMFS among patients aged >50 years was similar between those who did receive chemotherapy (95.2%) and those who did not (95.4%). In patients aged 40-50 years, the estimated 5-year DMFS for patients who received chemotherapy was 96.2% compared with 92.6% for patients who did not receive chemotherapy. Researchers noted that similar to the results of the TAILORx trial, women classified as high risk of recurrence by traditional clinical-pathological factors but low risk by MammaPrint had a worse outcome if treated with tamoxifen alone, and that the benefit of chemotherapy may eventually be higher in this group. In both the MINDACT and TAILORx trial almost all women received tamoxifen alone (without ovarian suppression) as adjuvant chemotherapy. This makes it impossible to determine whether results seen in younger women are due to the direct effect of chemotherapy or through chemotherapy-induced ovarian suppression. These results – together with those of TAILORx – suggest that younger women with high clinical risk and low genomic risk (per MammaPrint) or with an intermediate recurrence score (per Oncotype DX) may benefit from additional treatment, although this needs to be confirmed in future studies.

1. Piccart MJ, et al. GS4-05. SABCS 2019.

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