Abstract PD2-01: Personalized serial circulating tumor DNA (ctDNA) analysis in high-risk early stage breast cancer patients to monitor and predict response to neoadjuvant therapy and outcome in the I-SPY 2 TRIAL

594 Background: Breast Cancer Index (BCI) is a continuous risk index based on the combination of HOXB13:IL17BR (H:I) and the Molecular Grade Index (MGI) that estimates the individual risk of recurrence in ER+, LN- breast cancer patients. In the current study, a modified BCI model was developed using untreated breast cancer patients in order to evaluate its pure prognostic value, and to better optimize BCI for both early and late risk assessment. Methods: A model was built by linearly combining H:I and MGI weighted by their corresponding Cox regression coefficients using ER+ LN- patients from the untreated arm of the prospective Stockholm trial (N=283). Validation was performed in 2 independent ER+, LN- cohorts: the TAM arm of the Stockholm trial (N=317), and a multisite cohort of TAM-treated patients (N=358). Correlation of BCI with distant metastasis was evaluated by Kaplan-Meier analysis using the log rank test, and multivariate analysis adjusting for standard prognostic factors was performed using Cox proportional hazards. Results: The BCI linear model was significantly associated with risk of cumulative (0-10y), early (<5y) and late (≥5y) distant metastasis. Based on pre-specified cutpoints, BCI classified 64% and 55% patients as low-, 21% and 22% as intermediate-, and 16% and 23% as high-risk, with 10-y rates of distant recurrence (95% CI) of 4.8% (1.7-7.8%) and 6.6% (2.9–10.0%), 11.7% (3.1–19.5%) and 23.3% (12.3-33.0%), 21.1% (18.5–32.0%) and 35.8% (24.5–45.5%), in the Stockholm TAM and multisite cohort, respectively. Conclusions: BCI demonstrated significant prognostic performance beyond clinicopathological factors to predict cumulative, early and late risk of recurrence in early stage breast cancer patients. Use of BCI at diagnosis should enable clinicians to identify patients who are at high risk of late recurrence and may benefit from an additional 5y of hormonal therapy. [Table: see text]

Download Full-text

Circulating tumor DNA as a predictive marker of recurrence for patients with stage II-III breast cancer treated with neoadjuvant therapy

10.21203/rs.3.rs-598665/v1 ◽

2021 ◽

Author(s):

Po-Han Lin ◽

Ming-Yang Wang ◽

Chiao Lo ◽

Li-Wei Tsai ◽

Tzu-Chun Yen ◽

...

Keyword(s):

Breast Cancer ◽

Risk Factors ◽

Neoadjuvant Therapy ◽

Cancer Patients ◽

Pathologic Complete Response ◽

Circulating Tumor Dna ◽

Stage Ii ◽

Breast Cancer Patients ◽

Her2 Breast Cancer ◽

Tumor Dna

Abstract Background:Patients with stage II to III breast cancer have a high recurrence rate. The early detection of recurrent breast cancer remains a major unmet need. Circulating tumor DNA (ctDNA) has been shown to be a marker to detect disease progression in metastatic breast cancer. We aimed to evaluate the prognostic value of ctDNA in the setting of neoadjuvant therapy (NAT).Methods:Plasma was sampled at the initial diagnosis (defined as before NAT) and after NAT and breast surgery (defined as after NAT). We extracted ctDNA from the plasma and performed deep sequencing of a target gene panel. The detection of alterations, such as mutations and copy number variations, were considered to indicate ctDNA positivity.Results:A total of 95 patients were enrolled in this study; 60 patients exhibited ctDNA positivity before NAT, and 31 patients had ctDNA positivity after NAT. A pathologic complete response (pCR) was observed in 13 patients, including one ER(+)Her2(-) patient, six Her2(+) patients and six triple-negative breast cancer (TNBC) patients. Among the entire cohort, multivariate analysis showed that an N3 classification and ctDNA positivity after NAT were independent risk factors that predicted recurrence (N3, hazard ratio (HR) 3.34, 95% confidence interval (CI) 1.26 – 8.87, p = 0.016; ctDNA, HR 4.29, 95% CI 2.06 – 8.92, p < 0.0001). The presence of ctDNA before NAT did not affect the rate of recurrence-free survival. For patients with Her2(+) or TNBC, non-pCR breast cancer patients were associated with a trend of higher recurrence (p = 0.105). Advanced nodal status and ctDNA positivity after NAT were significant risk factors for recurrence (N2 – 3, HR 3.753, 95% CI 1.146 – 12.297, p = 0.029; ctDNA, HR 3.123, 95% CI 1.139 – 8.564, p = 0.027). Two patients who achieved a pCR had ctDNA positivity after NAT; one TNBC patient had hepatic metastases six months after surgery, and one Her2(+) breast cancer patient had brain metastasis 13 months after surgery.Conclusions:This study suggested that the presence of ctDNA after NAT is a robust marker for predicting relapse in stage II to III breast cancer patients.

Download Full-text