Cancer Research UK Scotland Centre, University of Edinburgh, Edinburgh, United Kingdom
John MS Bartlett , Keying Xu , Jenna Wong , Gregory Russell Pond , Yi Zhang , Melanie Spears , Ranelle C. Salunga , Elizabeth Mallon , Karen J Taylor , Annette Hasenburg , Christos Markopoulos , Luc Yves Dirix , Caroline M. Seynaeve , Cornelis J.H. Van De Velde , Daniel William Rea , Catherine A Schnabel , Kai Treuner , Jane Bayani
Background: Individual risk assessment of distant recurrence (DR) is particularly relevant for early-stage HR+ breast cancer patients, as they face a prolonged risk of recurrence even after adjuvant endocrine therapy. Previously, we have shown that the Breast Cancer Index (BCI) and BCIN+ risk groups are significantly prognostic for risk of overall (0-10y) and late (5-10y) distant recurrence in N0 and N1 breast cancer patients, respectively, enrolled in the Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial. Here, the prognostic performance of BCI and BCIN+ as a continuous risk score for overall and late distant recurrence was evaluated in the TEAM trial. Methods: BCI testing was performed blinded to clinical outcome with BCI/BCIN+ risk scores calculated as previously described. Cox proportional hazard models adjusted for age, tumor size, grade and treatments were used to estimate hazard ratios (HRs) and the associated 95% confidence intervals (CIs) for BCI/ BCIN+ continuous risk scores. The 10y risk of overall and late DR were estimated as a function of risk scores from the Cox models using Breslow estimates.Results: Continuous risk curves for overall and late DR were obtained in patients who did not receive adjuvant chemotherapy and those who remained DR-free at 5 years regardless of chemotherapy, respectively, to reflect the two key time points for breast cancer treatment decision-making. InN0 patients not treated with chemotherapy (N = 1197), BCI was significantly prognostic for overall DR with a HR of 1.39 (95% CI 1.25-1.54; p < 0.001), while BCIN+ was significantly prognostic in N1 patients who did not receive chemotherapy (N = 1319) with a HR of 4.29 (95% CI 2.93-6.28; p < 0.001). Among patients who remained DR-free at 5 years, in the N0 subset (N = 1285), BCI was significantly prognostic for late DR with a HR of 1.23 (95% CI 1.07-1.42; p < 0.001), while BCIN+ remained to be significantly prognostic in the N1 subset (N = 1762) with a HR of 2.78 (95% CI 1.75-4.43; p < 0.001). Similar results were observed in the HER2- subset for both overall and late DR. Continuous risk curves for BCI and BCIN+ for overall and late DR showed an increasing risk of DR with higher BCI/BCIN+ scores. Conclusions: Results from this largest BCI study to date further support the use of BCI to provide individualized risk estimates for both overall and late DR in women with HR+ breast cancer to aid in personalized decision-making for adjuvant therapy.
N | HR (95% CI) | P value | |||
---|---|---|---|---|---|
Overall DR (0-10y) | All Pts | N0 | 1197 | 1.39 (1.25-1.54) | < 0.001 |
N1 | 1319 | 4.29 (2.93-6.28) | < 0.001 | ||
HER2- | N0 | 978 | 1.52 (1.34-1.73) | < 0.001 | |
N1 | 1132 | 4.04 (2.66-6.13) | < 0.001 | ||
Late DR (5-10y) | All Pts | N0 | 1285 | 1.23 (1.07-1.42) | < 0.001 |
N1 | 1762 | 2.78 (1.75-4.43) | < 0.001 | ||
HER2- | N0 | 1063 | 1.31 (1.11-1.53) | < 0.001 | |
N1 | 1503 | 2.87 (1.17-4.81) | < 0.001 |
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