The following article features coverage from the 2020 San Antonio Breast Cancer Symposium. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

The classification of triple-negative breast cancer (TNBC) by DNA damage immune response (DDIR) signature and homologous recombination deficiency (HRD) status identified biology-driven prognostic categories in patients who were treated with adjuvant doxorubicin plus cyclophosphamide (AC), according to the results of an analysis of SWOG S9313 data presented at the 2020 Virtual San Antonio Breast Cancer Symposium (SABCS).

All women who were considered to be DDIR signature–positive — or immune-enriched — had improved survival with adjuvant AC regardless of HRD status.

“Immunologic and DNA repair-mediated therapeutic vulnerabilities, though related, may be independent,” said presenter Shane R. Stecklein, MD, University of Kansas Medical Center.

The trial looked at 425 TNBC cases from the SWOG S9313 trial. DDIR signature, HRD status (score of 42 or greater = HRD positive), and stromal tumor infiltrating lymphocytes (sTIL) were assessed. All 3 markers were available for evaluation in 77% of patients.


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Based on the results, cases were classified as DDIR+/HRD+ (Class 1, 45%), DDIR+/HRD- (Class 2, 16%), DDIR-/HRD+ (Class 3, 23%), DDIR-/HRD- (Class 4, 16%).

The combined DDIR/HRD classification scheme was prognostic within this cohort, Dr Stecklein said. Five-year disease-free survival and overall survival were superior for Class 1.

Five-year disease-free survival was similar for DDIR+/HRD+ (80.9%), DDIR+HRD- (74.7%), and DDIR-/HRD+ (74%) groups. Five-year overall survival was also similar at 87.5%, 85.5%, and 83.1%, respectively. However, 5-year disease free survival and overall survival were significantly lower in the DDIR-/HRD- group at 56.4% and 69.1%, respectively.  

“We speculated that the favorable outcome of the Class 1 TNBC was due to both effective antitumor immunity and hypersensitivity to DNA-damaging chemotherapy,” Dr Stecklein said. “The favorable intermediate outcome of Class 2 and Class 3 tumors was due to the presence of 1 but not both of these therapeutic vulnerabilities.”

These findings need to be validated in other cohorts of patients treated with contemporary chemotherapy regimens.

Read more of Cancer Therapy Advisor‘s coverage of the 2020 SABCS meeting by visiting the conference page.

Reference

Stecklein SR, Barlow W, Pusztai L, et al. Classification of triple negative breast cancer (TNBC) by DNA damage immune response (DDIR) signature and homologous recombination deficiency (HRD) status: analysis of SWOG S9313 adjuvant trial. Presented at: 2020 Virtual San Antonio Breast Cancer Symposium (SABCS); December 8-11, 2020. Abstract GS3-05.