Impact of adjuvant breast radiotherapy on the risk and the survival of second primary lung cancer: a large population-based study.

BACKGROUND

This study aimed to quantify the long-term risk of second primary lung cancer (SPLC) following adjuvant breast radiotherapy (RT) and to evaluate its clinical significance in determining the appropriate duration of lung cancer screening among breast cancer survivors.

METHODS

A total of 370 782 female patients who underwent loco-regional breast adjuvant RT after breast cancer surgery were included for analysis using the US SEER-9 Plus database from 1975 to 2018. Additionally, survival analyses were conducted to compare patients with SPLC following adjuvant breast RT with those with only first primary lung cancer (PLC). PLC patients, defined as those diagnosed with only primary lung cancer and no other malignancies throughout their lifetime, were derived from the same SEER database for the survival analysis, not from external published data.

RESULTS

SPLC diagnosed at least 5 years after breast cancer was observed in 5632 patients (1.52%), comprising 2630 patients (1.55%) in the RT cohort and 3002 patients (1.49%) in the non-radiotherapy cohort. RT was associated with an increased risk of SPLC (adjusted hazard ratio [HR], 1.28; 95% CI, 1.22-1.35; P < .001). The median overall survival time for SPLC after breast RT was longer than that for primary lung cancer (18.0 months [95% CI, 17.0-20.0] vs. 14.0 months [95% CI, 13.0-16.0], P = .008). The 10-year overall survival rate of the SPLC patients after breast RT was significantly higher than that of primary lung cancer (14.3% [95% CI, 12.6-16.2] vs. 13.1% [95% CI, 11.6-14.8], P = .008), with an HR of 0.92 (95% CI, 0.86-0.98, P = .008).

INTERPRETATION: RT for loco-regional breast cancer was associated with an increased risk of developing SPLC. Given this increased risk, routine screening for SPLC should be considered for this population, particularly within 5-15 years following breast cancer diagnosis.