Patterns of early and late recurrence across breast cancer subtypes in the CCTGMA.32 trial.

534 Background: An ongoing constant risk of recurrence out to 20 years is well established in hormone receptor positive breast cancer (BC) less so in other BC subtypes. This study aims to describe patters of early (≤ 5 years of BC diagnosis) and late recurrence (&gt; 5 years of BC diagnosis) across immunohistochemically defined BC subtypes - luminal (ER/PgR+HER2-), triple negative (TN: ER/PgR/HER2-) and HER2+ (any ER/PgR) in CCTGMA.32 (NCT01101438) which investigated metformin vs placebo in patients enrolled 2010-2013. Methods: 3649 patients with high-risk non-metastatic BC were enrolled and followed for first locoregional and distant recurrence, new primary cancers and death. Annual rates of these events were calculated in each BC subtype and averaged for early (years 0-5) and late (after 5 years) post randomization. Results: In luminal (n = 2104), TN (n = 925), HER2+ (n = 620) BC the median follow-ups were 96.2 (range 0.2 to 120.7), 94.5 (0.03 to 120.5), 95.2 months (0.03 to 119.8), respectively. Patterns of events varied across subtypes and early vs late. In luminal BC, the early vs late annual invasive cancer event rates (ICERs) was 3.04 vs. 2.31 % (late rate 0.76 of early rate). The annual early vs late rates of distant recurrence (DR) were 2.33 vs 1.72% (late rate 0.74 of early rate). Bone was the most common site of DR both early and late. In the TN BC, the early vs late annual ICERs were 4.6 and 1.21% (late rate 0.35 of early rate). Annual early vs late DR rates were 3.09 vs. 0.20 % (late rate 0.28 of early rate). Visceral metastases (lung, liver, CNS) were most common early. In HER2+, early vs late annual ICERs were 2.93 vs 1.47% (late rate 0.50 of early rate). Annual early vs late DR rates were 2.25 vs 0.71% (late rate 0.32 of early rate). Bone and visceral metastases were common early. CNS was rare after 5 years in all BC subtypes. Second primary cancers (new BC and non-primary BC) were frequent across BC subtypes, with no fall-off over time; they were responsible for the majority of late events in TN and HER2+ BC. Conclusions: In luminal BC, risk of late ICER remains high (annual rate about three-quarters of early rate), while risk of late events was lower in TN and HER2+BC (late rates one quarter to one-third of early rates). Risk of second primary cancers did not decrease over time, and second primaries were the most frequent late events in TN and HER2+BC. Clinical trial information: NCT01101438 . Luminal TN HER2+ Annual event rate (%) Annual event rate (%) Annual event rate (%) Year 0-5 Year 5+ Year 0-5 Year 5+ Year 0-5 Year 5+ Any Invasive Cancer Event 3.04 2.31 4.60 1.21 2.93 1.47 Locoregional Event 0.50 0.29 1.15 0.26 0.64 0.15 Distant Recurrence* 2.08 1.29 3.09 0.20 2.03 0.57 Sites of First Metastasis: Bone 1.40 0.88 1.13 0.10 0.65 0.42 Lung 0.59 0.56 1.73 0.20 0.83 0.07 Liver 0.71 0.56 0.73 0.00 0.50 0.21 CNS 0.18 0.06 0.65 0.00 0.61 0.00 Second Primary Cancer** 0.66 0.92 0.96 0.90 0.60 0.74 *Including distant recurrence after a local regional events. **Non-breast cancer and new breast cancer events. </jats:f