Selective service.

Top Line: When Oncotype DX was first developed in 2003, little did we know the far reaches of its powers.

The Study: Anyone who thinks treating breast cancer is “easy” has never performed a consultation with a young woman on the pros and cons of adjuvant radiation for ductal carcinoma in situ (DCIS). Granted, if you treat enough, you will eventually save a life. But wouldn’t it be nice to know who is most likely to benefit in big ways? Enter Oncotype DX to save the day once again, this time leaping way outside its comfort zone to try to inform the benefit of radiation for DCIS. This retrospective analysis performed the 21-gene Oncotype DX on 1362 DCIS lumpectomy specimens. Remember, the 21-gene assay is designed to assess risk of distant mets as opposed to the 12-gene assay typically studied for DCIS that is designed to detect the more obvious risk of local recurrence. A high recurrence score (>25) was detected in 30% of cases, including 25% of clinically low-risk cases. Among those <50 years old, a high recurrence score was associated with an 11-fold increased risk of breast cancer mortality, translating to a nearly 10% risk of breast cancer mortality at 20 years with surgery alone (note: n=32 here which means 3 deaths). Even more intriguing, receipt of radiation—completely non-randomized, of course—was associated with a 71% relative reduction and a 5% absolute reduction in breast cancer mortality among high recurrence scores. Importantly, this huge reduction in breast cancer mortality exceeds the impact on invasive breast cancer recurrences, which may signal other confounding factors at play that could not be remedied with propensity matching. So while this all generates quite the fascinating hypothesis, we find it unlikely that someone will put in 30 years of randomizing patients with clinically low-risk / Oncotype high-risk DCIS to +/- radiation and waiting for a survival difference.

TBL: Notwithstanding the inherent limitations of such a study design, this is among the first data to demonstrate a, that’s right, survival benefit for DCIS with any therapy, in this case radiation for genomically-selected bad actors. | Rakovitch, J Natl Cancer Inst 2020


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