Most estrogen receptor (ER)-positive breast cancers can be classified as luminal A or luminal B subtype. It has been estimated that 1 in 4 patients with ER-positive breast cancer will develop disseminated disease and experience disease-related mortality. While it has been suggested that as many as 1 in 4 patients with ER-positive breast cancer will go on to develop distant metastasis, little is known about the tumor biological factors that contribute to this risk. In the Stockholm Tamoxifen (STO-3) trial (1976-1990), post-menopausal patients with lymph node-negative breast cancer were randomized to receive adjuvant tamoxifen or no endocrine therapy. In this secondary analysis, only patients with luminal A or B subtype were evaluated (n=462) to investigate the long-term survival and benefit of tamoxifen endocrine therapy in patients with luminal A or luminal B tumor subtype. Researchers found that the distant recurrence-free interval (DRFI) was significantly improved in the intervention group for both luminal A (p<0.001) and luminal B (p=0.04) subtypes. The 25-year DRFI for luminal A versus luminal B subtypes was 87% (95% CI 82% to 93%) vs. 67% (95% CI 56% to 82%) for treated patients, and 70% (95% CI 62% to 79%) vs. 54% (95% CI 42% to 70%) for untreated patients, respectively. Researchers also performed a time-varying multivariate analysis of long-term distance recurrence-free survival, and found that patients benefited from tamoxifen therapy for 15 years after diagnosis (HR 0.57, 95% CI 0.35 to 0.94) while those with luminal B tumors benefited from tamoxifen therapy for 5 years (HR 0.38, 95% CI 0.24 to 0.59) when compared to untreated patients of each respective subtype. This study therefore shows that patients with luminal A subtype tumours carry a long-term risk of distant metastatic disease which can be reduced with tamoxifen treatment. Conversely, patients with luminal B tumors may have an early risk of distant metastatic disease, with the benefits of tamoxifen being attenuated over time.
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