38 Comparing Risk Stratification and Radiotherapy Benefit for Patients With DCIS Using a 7-Gene Biosignature as Compared to a Clinicopathologic Nomogram

Publication
Article
Miami Breast Cancer Conference® Abstracts Supplement40th Annual Miami Breast Cancer Conference® - Abstracts
Volume 37
Issue suppl 4
Pages: 43-44

Background

Multiple prospective trials show over 70% of women with ductal carcinoma in situ (DCIS) do not recur after breast-conserving surgery (BCS) alone and radiotherapy (RT) had a clinically meaningful reduction in 10-year risk after BCS. Clinicopathologic (CP) factor–based criteria or nomograms have been used to select for whom to deescalate treatment, assessing the 10-year ipsilateral breast recurrence (IBR) rate after BCS. In this study, we compared the classification of women by a CP model similar to the MSKCC DCIS nomogram with the 7-gene biosignature and their associated total 10-year IBR rates with and without RT.

Materials and Methods

DCIS patients (n = 926) from 4 international cohorts treated with BCS (negative margins) with (n = 641) and without RT (n = 335) were evaluated for clinicopathological models and the 7-gene biosignature with residual risk subtype (RRt). Formalin-fixed, paraffin-embedded tissue samples for each patient were analyzed at a CLIA lab for the 7-gene biosignature, DCISionRT with RRt. The biosignature reported a decision score (DS) of 0-10 and the presence/absence of the RRt subtype. The CP model used MSKCC DCIS nomogram factors and weighting but omitted the number of excisions and close margin and was categorized using a score <220 as CP low risk. The MSKCC-like score was calculated using the equation score = 100*(RT = 0) + 76*(ET = 0) + FAMHX(pos)*30 + Detection(clinical)*34 + (Grade ≥ 2)*26 + Necrosis (Present)*12 + Year of Diagnosis (≤1998)*58 + (134-1.49*AGE); margin (no-ink on tumor) = 0, number of excisions ≥3 (incomplete) = 0, evaluate with RT = 0). 10-year total IBR rates were evaluated using Cox proportional hazards and Kaplan-Meier analysis by treatment and risk groups in patients treated with and without RT.

Results

The biosignature classified 37% of women treated with BCS as low risk (n = 338) and 63% (n = 588) were classified into the combined Elevated/Residual Risk group. The 10-year IBR rate for patients who did not receive RT in the low-risk group was 5.6% (95% CI, 2.5%-12.1%). RT did not reduce the IBR rate in the low-risk group (P = .71), where the 10-year IBR rate was 4.8% (95% CI, 2.5%-9.1%) after RT. The CP model classified 320 (34%) as CP low risk (score <220) with an 8.3% 10-year IBR rate for BCS without RT and a non-significant slightly lower rate with RT (4.7%; HR, 0.5; 95% CI, 0.2-1.2, P = .12). Eighty-seven percent (n = 277) of the MSKCC low-risk group patients were treated with endocrine therapy (ET), whereas 32% (n = 124) of the biosignature low-risk patients were treated with ET. Thirty-seven percent (n = 124) of the biosignature low-risk and 30% (n = 98) of the MSKCC low-risk patients were not treated with RT. The biosignature reclassified 63% of these CP low-risk patients as DS elevated risk, with 10-year IBR rates of 12.3% for BCS without RT and 4.8% with RT (HR, 0.2; 95% CI, 0.1-0.8, P <.01).

Conclusions

Using 10-year outcome data (n = 926) from multiple contemporary published validation studies, the biosignature reclassified nearly two-thirds of patients in the CP low-risk (MSKCC-like nomogram) group as elevated risk. The re-classified CP low-risk patients had elevated 10-year IBR rates after BCS without RT and had an 80% relative benefit from RT, demonstrating they potentially could have been undertreated. This demonstrates the ability of the 7-gene biosignature to better risk-stratify patients with DCIS following BCS and identify patients with low-risk CP who may benefit from RT.

AFFILIATIONS:

Julie Margenthaler,1 Karuna Mittal,2 Frank Vicini,3 Chirag Shah,4 Rachel Rabinovitch,5 Pat Whitworth,6 Brian Czerniecki,7 David Dabbs,2 G. Bruce Mann,8 Fredrik Wärnberg,9 Sheila Weinmann,10 Michael Leo,10 Steven C. Shivers,2 Troy Bremer2

1Washington University School of Medicine, St. Louis, MO.

2PreludeDx, Laguna Hills, CA.

3GenesisCare, Farmington Hills, MI.

4Cleveland Clinic, Cleveland, OH.

5University of Colorado, Colorado Springs, CO.

6Nashville Breast Center, Nashville, TN.

7Moffitt Cancer Center, Tampa, FL.

8University of Melbourne, Melbourne, Australia.

9University of Gothenburg, Gothenburg, Sweden.

10Kaiser Permanente Center for Health Research, Portland, OR.

Articles in this issue

1 Elacestrant Versus Fulvestrant or Aromatase Inhibitor in a Phase 3 Trial Evaluating Elacestrant, an Oral Selective Estrogen Receptor Degrader Versus Standard-of- Care Endocrine Monotherapy for ER+/HER2– Advanced/Metastatic Breast Cancer
1 Elacestrant Versus Fulvestrant or Aromatase Inhibitor in a Phase 3 Trial Evaluating Elacestrant, an Oral Selective Estrogen Receptor Degrader Versus Standard-of- Care Endocrine Monotherapy for ER+/HER2– Advanced/Metastatic Breast Cancer
2 Molecular Characterization of HER2-Low Patients Identifies Basal-Enriched Subset With Poor Clinical Outcomes in Real-world Data
2 Molecular Characterization of HER2-Low Patients Identifies Basal-Enriched Subset With Poor Clinical Outcomes in Real-world Data
3 Real-world Outcomes of Sacituzumab Govitecan in Metastatic Breast Cancer Patients: A Single Institution Experience
3 Real-world Outcomes of Sacituzumab Govitecan in Metastatic Breast Cancer Patients: A Single Institution Experience
4 Datopotamab Deruxtecan (Dato-DXd) + Durvalumab (D) as First-Line (1L) Treatment for Unresectable Locally Advanced/ Metastatic Triple-Negative Breast Cancer (a/mTNBC): Updated Results From BEGONIA, a Phase 1b/2 Study
4 Datopotamab Deruxtecan (Dato-DXd) + Durvalumab (D) as First-Line (1L) Treatment for Unresectable Locally Advanced/ Metastatic Triple-Negative Breast Cancer (a/mTNBC): Updated Results From BEGONIA, a Phase 1b/2 Study
5 Treatment Patterns and Clinical Outcomes in Patients Receiving Palbociclib Combinations as First- Line Treatment for Advanced or Metastatic Breast Cancer in Realworld Settings in Argentina and Colombia: Results from the IRIS Study
5 Treatment Patterns and Clinical Outcomes in Patients Receiving Palbociclib Combinations as First- Line Treatment for Advanced or Metastatic Breast Cancer in Realworld Settings in Argentina and Colombia: Results from the IRIS Study
7 EMERALD Phase 3 Trial of Elacestrant Versus Standard-of- Care Endocrine Therapy in Patients With ER+/HER2– Metastatic Breast Cancer: Updated Results by Duration of Prior CDK4/6i in Metastatic Setting
7 EMERALD Phase 3 Trial of Elacestrant Versus Standard-of- Care Endocrine Therapy in Patients With ER+/HER2– Metastatic Breast Cancer: Updated Results by Duration of Prior CDK4/6i in Metastatic Setting
8 Datopotamab Deruxtecan (Dato-DXd) in Advanced Triple- Negative Breast Cancer (TNBC): Updated Results From the Phase 1 TROPION-PanTumor01 Study
8 Datopotamab Deruxtecan (Dato-DXd) in Advanced Triple- Negative Breast Cancer (TNBC): Updated Results From the Phase 1 TROPION-PanTumor01 Study
9 Phase 1 TROPION-PanTumor01 Study Evaluating Datopotamab Deruxtecan (Dato-DXd) in Unresectable or Metastatic Hormone Receptor–Positive/ Human Epidermal Growth Factor Receptor 2–Negative Breast Cancer
9 Phase 1 TROPION-PanTumor01 Study Evaluating Datopotamab Deruxtecan (Dato-DXd) in Unresectable or Metastatic Hormone Receptor–Positive/ Human Epidermal Growth Factor Receptor 2–Negative Breast Cancer
11 Real-world Treatment Patterns and Effectiveness of Palbociclib Plus an Aromatase Inhibitor in Patients With Metastatic Breast Cancer Aged 75 Years or Above
11 Real-world Treatment Patterns and Effectiveness of Palbociclib Plus an Aromatase Inhibitor in Patients With Metastatic Breast Cancer Aged 75 Years or Above
12 TIP HARMONIA SOLTI-2101/ AFT-58: A Head-to-Head Phase III Study Comparing Ribociclib (RIB) and Palbociclib (PAL) in Patients (pts) With Hormone Receptor– Positive/HER2-Negative/HER2- Enriched (HR+/HER2−/HER2-E) Advanced Breast Cancer (ABC)
12 TIP HARMONIA SOLTI-2101/ AFT-58: A Head-to-Head Phase III Study Comparing Ribociclib (RIB) and Palbociclib (PAL) in Patients (pts) With Hormone Receptor– Positive/HER2-Negative/HER2- Enriched (HR+/HER2−/HER2-E) Advanced Breast Cancer (ABC)
13 Improved Sensitivity in Identification of ER- and HER2- Expressing Metastatic Breast Cancers With a Combination of Cell & Cell-Free Liquid Biopsy Analysis
13 Improved Sensitivity in Identification of ER- and HER2- Expressing Metastatic Breast Cancers With a Combination of Cell & Cell-Free Liquid Biopsy Analysis
15 Updated Expert Consensus Recommendations for Managing Hyperglycemia and Rash in Patients With PIK3CA-Mutated, Hormone Receptor–Positive (HR+), Human Epidermal Growth Factor Receptor 2–Negative (HER2–) Advanced Breast Cancer Treated With Alpelisib
15 Updated Expert Consensus Recommendations for Managing Hyperglycemia and Rash in Patients With PIK3CA-Mutated, Hormone Receptor–Positive (HR+), Human Epidermal Growth Factor Receptor 2–Negative (HER2–) Advanced Breast Cancer Treated With Alpelisib
16 Primary Results From the Randomized Phase II RIGHT Choice Trial of Premenopausal Patients With Aggressive HR+/HER2− Advanced Breast Cancer Treated With Ribociclib + Endocrine Therapy vs Physician’s Choice Combination Chemotherapy
16 Primary Results From the Randomized Phase II RIGHT Choice Trial of Premenopausal Patients With Aggressive HR+/HER2− Advanced Breast Cancer Treated With Ribociclib + Endocrine Therapy vs Physician’s Choice Combination Chemotherapy
17 A Clinical Systematic Literature Review of Treatments Among Patients With Advanced/ Metastatic HER2+ Breast Cancer
17 A Clinical Systematic Literature Review of Treatments Among Patients With Advanced/ Metastatic HER2+ Breast Cancer
20 TIP ELONA: An Open-Label, Phase 1b-2 Study of Elacestrant, in Combination With Onapristone in Patients With Estrogen Receptor– Positive, Progesterone Receptor– Positive, HER2-Negative Advanced or Metastatic Breast Cancer
20 TIP ELONA: An Open-Label, Phase 1b-2 Study of Elacestrant, in Combination With Onapristone in Patients With Estrogen Receptor– Positive, Progesterone Receptor– Positive, HER2-Negative Advanced or Metastatic Breast Cancer
Related Content