Assessment of Long-term Distant Recurrence-Free Survival Associated With Tamoxifen Therapy in Postmenopausal Patients With Luminal A or Luminal B Breast Cancer

Abstract

IMPORTANCE Patients with estrogen receptor (ER)-positive breast cancer have a long-term risk for fatal disease. However, the tumor biological factors that influence the long-term risk and the benefit associated with endocrine therapy are not well understood.OBJECTIVE To compare the long-term survival from tamoxifen therapy for patients with luminal A or luminal B tumor subtype.DESIGN, SETTING, AND PARTICIPANTS Secondary analysis of patients from the Stockholm Tamoxifen (STO-3) trial conducted from 1976 to 1990, which randomized postmenopausal patients with lymph node-negative breast cancer to receive adjuvant tamoxifen or no endocrine therapy. Tumor tissue sections were assessed in 2014 using immunohistochemistry and Agilent microarrays. Only patients with luminal A or B subtype tumors were evaluated. Complete long-term follow-up data up to the end of the STO-3 trial on December 31, 2012, were obtained from the Swedish National registers. Data analysis for the secondary analysis was conducted in 2017 and 2018.INTERVENTIONS Patients were randomized to receive at least 2 years of tamoxifen therapy or no endocrine therapy; patients without recurrence who reconsented were further randomized to 3 additional years of tamoxifen therapy or no endocrine therapy. MAIN OUTCOMES AND MEASURESDistant recurrence-free interval (DRFI) by luminal A and luminal B subtype and trial arm was assessed by Kaplan-Meier analyses and time-dependent flexible parametric models to estimate time-varying hazard ratios (HRs) that were adjusted for patient and tumor characteristics. RESULTSIn the STO-3 treated trial arm, 183 patients had luminal A tumors and 64 patients had luminal B tumors. In the untreated arm, 153 patients had luminal A tumors and 62 had luminal B tumors. Age at diagnosis ranged from 45 to 73 years. A statistically significant difference in DRFI by trial arm was observed (log rank, P < .001 [luminal A subtype, n = 336], P = .04 [luminal B subtype, n = 126]): the 25-year DRFI for luminal A vs luminal B subtypes was 87% (95% CI, 82%-93%) vs 67% (95% CI, 56%-82%) for treated patients, and 70% (95% CI, 62%-79%) vs 54% (95% CI, 42%-70%) for untreated patients, respectively. Patients with luminal A tumors significantly benefited from tamoxifen therapy for 15 years after diagnosis (HR, 0.57; 95% CI, 0.35-0.94), and those with luminal B tumors benefited from tamoxifen therapy for 5 years (HR, 0.38; 95% CI, 0.24-0.59). CONCLUSIONS AND RELEVANCEPatients with luminal A subtype tumors had a long-term risk of distant metastatic disease, which was reduced by tamoxifen treatment, whereas patients with luminal B tumors had an early risk of distant metastatic disease, and tamoxifen benefit attenuated over time.

Acid-base transporters and pH dynamics in human breast carcinomas predict proliferative activity, metastasis, and survival

“…The observation regarding SLC16A3 is notable because high expression worsens (or tends to worsen) patient prognosis in the other breast cancer molecular subtypes ( Figure 10—figure supplement 2C and E–G ). Luminal A breast cancer comprises 50–70% of breast cancer cases in the United States and Europe ( Kulkarni et al, 2019 ; Acheampong et al, 2020 ; Valla et al, 2016 ) and is clinically interesting because distant metastasis occurs throughout follow-up for as long as 25 years after initial diagnosis ( Yu et al, 2019 ). This is different from, for instance, luminal B breast cancer where the risk of metastasis is high the first 5 years after diagnosis but then markedly declines ( Yu et al, 2019 ).…”

Concordance of Immunohistochemistry-Based and Gene Expression-Based Subtyping in Breast Cancer

“…The time-varying patterns of tamoxifen-treatment benefit differs between luminal A and B tumors ( 42 ). We therefore investigated whether this was captured using any of the IHC surrogates, but the answer appeared to be no.…”

FGFR1 amplification or overexpression and hormonal resistance in luminal breast cancer: rationale for a triple blockade of ER, CDK4/6, and FGFR1

“…The relapse pattern of Lum-A and Lum-B cancers (usually several years after the completion of hormonal therapy in the former [1,2,14], and more commonly during or shortly after adjuvant hormonal treatment in the latter [14]) suggests that resistance to hormonal therapy plays a key role in the relapse. Hormonal resistance is a complex phenotype that can be caused by different molecular alterations, reviewed elsewhere [15,16].…”