Home > Oncology > ASCO 2022 > Breast Cancer > 7-gene biosignature: Benefits of endocrine therapy and radiotherapy in breast cancer risk groups

7-gene biosignature: Benefits of endocrine therapy and radiotherapy in breast cancer risk groups

Presented by
Dr Pat Whitworth, Nashville Breast Cancer Center, TN, USA
Conference
ASCO 2022
Doi
https://doi.org/10.55788/e4b6f35d
A 7-gene predictive ductal carcinoma in situ (DCIS) biosignature named ‘DCISionRT with integrated Residual Risk subtype (RRt)’ revealed a prognostic and predictive response to radiotherapy for patients who were classified as ‘elevated-risk’ or ‘residual-risk’ patients but not for ‘low-risk’ patients. However, in the residual-risk patients, the risk of recurrence remained high after radiotherapy, irrespective of whether patients received endocrine therapy.

“Clinicopathologic features have not been able to successfully stratify patients with breast cancer into low- and high-risk categories of recurrence after they receive radiotherapy following breast conserving surgery,” explained Dr Pat Whitworth (Nashville Breast Cancer Center, TN, USA). A clinically meaningful biomarker could fill this gap.

The 7-gene DCIS biosignature score combines 7 biomarkers and 4 clinicopathologic factors and has been validated as a prognostic tool for ipsilateral breast tumour recurrence (IBTR) and as a predictor for radiotherapy benefit in patients with breast cancer [1]. A central pathology review and biosignature testing was performed on formalin-fixed paraffin embedded tissue at a CLIA-certified lab (Laguna Hills, CA). The biosignature reported a “decision score” and residual risk subtype status. The current study included 926 patients from 4 cohorts with a pre-defined DCIS biosignature risk group of either low-risk (37%), elevated-risk (43%), or residual-risk (20%) to analyse the 10-year IBTR-rate [2]. The low-risk group had a decision score of ≤2.8, the elevated-risk group had a decision score of >2.8 without residual risk subtype, and the residual-risk group had a decision score of >2.8 with residual risk subtype.

IBTR-risk was reduced in the elevated-risk group (4.9% vs 20.6%) and the residual-risk group (14.7% vs 42.1%) but not in the low-risk group (4.8% vs 5.6%) if patients received radiotherapy after breast-conserving surgery compared with patients who had not received radiotherapy after surgery. Importantly, the risk of recurrence after radiotherapy was significantly higher in the residual-risk group compared with the elevated-risk group (P<0.001).

Furthermore, in the elevated-risk group, endocrine therapy reduced the risk of IBTR significantly, regardless of whether patients received radiotherapy (HR 0.34; P=0.023). This was not the case in the residual-risk group (HR 0.76; P=0.46) or in the low-risk group (HR 0.65; P=0.41). If patients in the elevated-risk group had received radiotherapy, the administration of endocrine therapy still trended towards a significant reduction in the IBTR rate (HR 0.40; P=0.059).

In summary, 3 risk groups were identified by means of the 7-gene DCIS biosignature. In the low-risk group, IBTR was not significantly reduced after radiotherapy and/or endocrine therapy, whereas in the elevated-risk group IBTR was reduced. In the residual-risk group, radiotherapy reduced the IBTR rate, but endocrine therapy had no effect.

  1. Wärnberg F, et al. Cancers. 2021;13(23):6103.
  2. Whitworth P, et al. Assessing the benefit of adjuvant endocrine therapy in patients following breast-conserving surgery with or without radiation stratified by a 7-gene predictive DCIS biosignature. Abstract 502, ASCO 2022 Annual Meeting, 3‒7 June, Chicago, IL, USA.

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