Background:

Early stage breast cancer patients with micrometastatic spread (cM0(i+) per the 2010 TNM staging), detected either in the bone marrow (disseminated tumor cells, DTC) or in the blood (circulating tumor cells, CTC) are at higher risk of distant relapse and death. Loco-regional relapses were also more frequently observed in patients with DTC and, recently, with CTC (IMENEO study, Bidard et al, SABCS 2016). In that context, we analyzed whether DTC detection would be a predictive factor for the benefit of comprehensive loco-regional irradiation.

Methods:

Patients with localized breast cancer were eligible for this IRB-approved prospective cohort after informed written consent. DTC status was prospectively assessed by trained pathologists after immunocytostaining following ISHAGE criteria, at time of surgery or prior to any primary systemic therapy. Irradiation volumes (breast or chest wall +/- regional lymph nodes) were defined per standard of care. Locoregional relapse was defined as documented ipsilateral invasive relapse occurring in the breast, chest wall and/or in regional lymph nodes, prior to any distant metastatic relapse. Locoregional relapse-free interval (LRFI) was defined as the time elapsed between breast surgery and locoregional relapse. Cumulative incidence rates and hazard ratio were obtained using both Cox and Fine-Gray models, taking into account metastatic relapse and death as competitive events. Interaction tests were performed to confirm the predictive value of DTC status in a multivariate analysis.

Results:

From 11.1998 to 09.2005, a total of 620 patients with non-metastatic breast cancer were included in this prospective cohort. Median FU was 11.7 years. Overall, 94 patients (15.1%) were DTC-positive and 50 patients (8.1%) experienced a locoregional relapse during follow-up. DTC detection was significantly associated with shorter LRFI in univariate and multivariate analyses (Cox, HR=2.6 [1.4;4.8], p=0.004 ; Fine-Gray, HR=1.76 [1.04;3.0], p=0.04). In the multivariate subgroup analysis, locoregional lymph node irradiation was associated with a longer LRFI for DTC-positive patients, but not for DTC-negative patients (interaction test in multivariate analysis: p=0.03). Similar results were obtained when taking locoregional relapses synchronous with distant metastatic disease into account (interaction test: p=0.02). Importantly, the predictive value of DTC status for the benefit of locoregional irradiation was independent of other clinical and pathological characteristics, including locoregional nodal (pN) status.

Conclusion:

This long term analysis confirms the independent long-term prognostic value of DTC on locoregional relapses. Moreover, the finding that cM0(i+) status is a predictive marker for the efficacy of locoregional lymph node irradiation promises a new opportunity to better tailor adjuvant radiation therapy in early stage breast cancer patients.

Citation Format: Bidard F-C, Mignot F, Poortmans P, Dureau S, Berger F, Loirat D, Proudhon C, Vincent-Salomon A, Pierga J-Y, Kirova Y. Disseminated tumor cells as predictive factor of benefit of lymph node irradiation to prevent loco-regional relapse [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-09-02.