Dataset Information

High PD-L2 Predicts Early Recurrence of ER-Positive Breast Cancer.

ABSTRACT:

Purpose

T-cell-mediated cytotoxicity is suppressed when programmed cell death-1 (PD-1) is bound by PD-1 ligand-1 (PD-L1) or PD-L2. Although PD-1 inhibitors have been approved for triple-negative breast cancer, the lower response rates of 25%-30% in estrogen receptor-positive (ER+) breast cancer will require markers to identify likely responders. The focus of this study was to evaluate whether PD-L2, which has higher affinity than PD-L1 for PD-1, is a predictor of early recurrence in ER+ breast cancer.

Methods

PD-L2 protein levels in cancer cells and stromal cells of therapy-naive, localized or locoregional ER+ breast cancers were measured retrospectively by quantitative immunofluorescence histocytometry and correlated with progression-free survival (PFS) in the main study cohort (n = 684) and in an independent validation cohort (n = 273). All patients subsequently received standard-of-care adjuvant therapy without immune checkpoint inhibitors.

Results

Univariate analysis of the main cohort revealed that high PD-L2 expression in cancer cells was associated with shorter PFS (hazard ratio [HR], 1.8; 95% CI, 1.3 to 2.6; P = .001), which was validated in an independent cohort (HR, 2.3; 95% CI, 1.1 to 4.8; P = .026) and remained independently predictive after multivariable adjustment for common clinicopathological variables (HR, 2.0; 95% CI, 1.4 to 2.9; P < .001). Subanalysis of the ER+ breast cancer patients treated with adjuvant chemotherapy (n = 197) revealed that high PD-L2 levels in cancer cells associated with short PFS in univariate (HR, 2.5; 95% CI, 1.4 to 4.4; P = .003) and multivariable analyses (HR, 3.4; 95% CI, 1.9 to 6.2; P < .001).

Conclusion

Up to one third of treatment-naive ER+ breast tumors expressed high PD-L2 levels, which independently predicted poor clinical outcome, with evidence of further elevated risk of progression in patients who received adjuvant chemotherapy. Collectively, these data warrant studies to gain a deeper understanding of PD-L2 in the progression of ER+ breast cancer and may provide rationale for immune checkpoint blockade for this patient group.

SUBMITTER: Chervoneva I

PROVIDER: S-EPMC9928763 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Publications

High PD-L2 Predicts Early Recurrence of ER-Positive Breast Cancer.

Chervoneva Inna I Peck Amy R AR Sun Yunguang Y Yi Misung M Udhane Sameer S SS Langenheim John F JF Girondo Melanie A MA Jorns Julie M JM Chaudhary Lubna N LN Kamaraju Sailaja S Bergom Carmen C Flister Michael J MJ Hooke Jeffrey A JA Kovatich Albert J AJ Shriver Craig D CD Hu Hai H Palazzo Juan P JP Bibbo Marluce M Hyslop Terry T Nevalainen Marja T MT Pestell Richard G RG Fuchs Serge Y SY Mitchell Edith P EP Rui Hallgeir H

JCO precision oncology 20230101

<h4>Purpose</h4>T-cell-mediated cytotoxicity is suppressed when programmed cell death-1 (PD-1) is bound by PD-1 ligand-1 (PD-L1) or PD-L2. Although PD-1 inhibitors have been approved for triple-negative breast cancer, the lower response rates of 25%-30% in estrogen receptor-positive (ER+) breast cancer will require markers to identify likely responders. The focus of this study was to evaluate whether PD-L2, which has higher affinity than PD-L1 for PD-1, is a predictor of early recurrence in ER+ ...[more]

PMID: 36652667

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Project description:ImportanceThere are insufficient data comparing 16α-18F-fluoro-17β-estradiol (FES) positron emission tomography (PET) computed tomography (CT) with standard-of-care imaging (SOC) for staging locally advanced breast cancer (LABC) or evaluating suspected recurrence.ObjectiveTo determine the detection rate of FES PET/CT and SOC for distant metastases in patients with estrogen receptor (ER)-positive LABC and recurrences in patients with ER-positive BC and suspected recurrence.Design, setting, and participantsThis diagnostic study was conducted as a single-center phase 2 trial, from January 2021 to September 2023. The study design provided 80% power to find a 20% detection rate difference. Participants included patients with ER-positive LABC (cohort 1) or suspected recurrence (cohort 2). Data were analyzed from September 2023 to February 2024.ExposureParticipants underwent both SOC imaging and experimental FES PET/CT. When there were suspicious lesions on imaging, 1 was biopsied for histopathological reference standard to confirm presence (true positive) or absence (false positive) of malignant neoplasm.Main outcomes and measuresThe outcome of interest was the detection rate of FES PET CT vs SOC for distant metastases and recurrences.ResultsA total of 124 patients were accrued, with 62 in cohort 1 (median [IQR] age, 52 [32-84] years) and 62 in cohort 2 (median [IQR] age, 66 [30-93] years). In cohort 1, of 14 true-positive findings, SOC imaging detected 12 and FES detected 11 (P > .99). In cohort 2, of 23 true-positive findings, SOC detected 16 and FES detected 18 (P = .77). In 30 patients with lobular histology, of 11 true-positive findings, SOC detected 5 and FES detected 9 (P = .29). There were 6 false-positive findings on SOC and 1 false-positive finding on FES PET/CT (P = .13).Conclusions and relevanceIn this diagnostic study with pathological findings as the reference standard, no difference was found between FES PET/CT and current SOC imaging for detecting distant metastases in patients with ER-positive LABC or recurrences in patients with ER-positive tumors and suspected recurrence. FES PET/CT could be considered for both clinical indications, which are not part of current Appropriate Use Criteria for FES PET. The findings regarding FES PET/CT in patients with lobular tumors, and for lower false positives than current SOC imaging, warrant further investigation.

Project description:The 21-gene recurrence score (RS) predicts risk of locoregional recurrence (LRR) in node-negative, estrogen receptor (ER)-positive breast cancer. We evaluated the association between RS and LRR in node-positive, ER-positive patients treated with adjuvant chemotherapy plus tamoxifen in National Surgical Adjuvant Breast and Bowel Project B-28. B-28 compared doxorubicin/cyclophosphamide (AC X 4) with AC X 4 followed by paclitaxel X 4. Tamoxifen was given to patients age 50 years or older and those younger than age 50 years with ER-positive and/or progesterone receptor-positive tumors. Lumpectomy patients received breast radiotherapy. Mastectomy patients received no radiotherapy. The present study includes 1065 ER-positive, tamoxifen-treated patients with RS assessment. Cumulative incidence functions and subdistribution hazard regression models were used for LRR to account for competing risks including distant recurrence, second primary cancers, and death from other causes. Median follow-up was 11.2 years. All statistical tests were one-sided. There were 80 LRRs (7.5%) as first events (68% local/32% regional). RS was low: 36.2%; intermediate: 34.2%; and high: 29.6%. RS was a statistically significant predictor of LRR in univariate analyses (10-year cumulative incidence of LRR = 3.3%, 7.2%, and 12.2% for low, intermediate, and high RS, respectively, P < .001). In multivariable regression analysis, RS remained an independent predictor of LRR (hazard ratio [HR] = 2.59, 95% confidence interval [CI] = 1.28 to 5.26, for a 50-point difference, P = .008) along with pathologic nodal status (HR = 1.91, 95% CI = 1.20 to 3.03, for four or more vs one to three positive nodes, P = .006) and tumor size (HR = 1.28, 95% CI = 1.05 to 1.55, for a 1 cm difference, P = .02). RS statistically significantly predicts risk of LRR in node-positive, ER-positive breast cancer patients after adjuvant chemotherapy plus tamoxifen. These findings can help in the selection of appropriate candidates for comprehensive radiotherapy.

Project description:ImportanceYoung patients with breast cancer with estrogen receptor (ER)-positive, ERBB2-negative tumors have a poor prognosis. Understanding factors influencing late recurrence is crucial for improving management and outcomes.ObjectiveTo determine whether age is an independent factor associated with late distant recurrence (DR) in young patients with ER-positive, ERBB2-negative cancers without distant metastasis within 5 years from surgery.Design, setting, and participantsThis multicenter retrospective cohort study analyzed clinical records of patients with breast cancer who underwent surgery from January 2000 to December 2011 with at least 5 years of follow-up. The study was conducted at Samsung Medical Center, Gangnam Severance Hospital, and Seoul National University Hospital, including patients aged 45 years or younger with ER-positive, ERBB2-negative tumors, no DR within 5 years after surgery, no neoadjuvant chemotherapy, and at least 2 years of endocrine therapy. The data analysis period was from January 4, 2023, to March 21, 2024.ExposureAge, grouped as 21 to 35 years, 36 to 40 years, and 41 to 45 years.Main outcomes and measuresThe primary outcome was the incidence of late DR at 5 to 10 years after surgery. Survival outcomes, including late distant metastasis-free survival (DMFS), were evaluated in different age groups.ResultsAmong 2772 patients included, 370 (13.3%) were aged 21 to 35 years, 885 (31.9%) were aged 36 to 40 years, and 1517 (54.7%) were aged 41 to 45 years. The median (range) follow-up was 10.8 (5.0-21.4) years. The youngest group had a poorer histologic grade (eg, histologic grade 3: 107 patients aged 21-35 years [28.9%]; 149 patients aged 36-40 years [16.8%]; 273 patients aged 41-45 years [18.0%]) and more frequent chemotherapy (307 patients aged 21-35 years [83.0%]; 697 patients aged 36-40 years [78.8%]; 1111 patients aged 41-45 years [73.2%]). The youngest patients had significantly worse rates of locoregional recurrence-free survival (patients aged 21-35 years, 90.1% [95% CI, 86.8%-93.3%]; patients aged 36-40 years, 94.6% [95% CI, 93.0%-96.2%]; patients aged 41-45 years, 97.7% [95% CI, 96.9%-98.5%]), disease-free survival (patients aged 21-35 years, 79.3% [95% CI, 75.0%-83.9%]; patients aged 36-40 years, 88.7% [95% CI, 86.5%-91.0%]; patients aged 41-45 years, 94.4% [95% CI, 93.2%-95.7%]), and late DMFS (patients aged 21-35 years, 89.3% [95% CI, 86.0%-92.9%]; patients aged 36-40 years: 94.2% [95% CI, 92.5%-95.9%]; patients aged 41-45 years: 97.2% [95% CI, 96.3%-98.1%]) but not overall survival (patients aged 21-35 years, 96.9% [95% CI, 95.0%-98.9%]; patients aged 36-40 years, 98.2% [95% CI, 97.2%-99.2%]; patients aged 41-45 years, 98.9% [95% CI, 98.3%-99.5%]). Multivariable analysis showed lower hazard for late DR in the older groups compared with the youngest group (age 36-40 years: hazard ratio, 0.53; 95% CI, 0.34-0.82; P = .001; age 41-45 years: hazard ratio, 0.30; 95% CI, 0.20-0.47; P < .001).Conclusions and relevanceIn this retrospective cohort study, age was an independent factor associated with late DR in young patients with ER-positive, ERBB2-negative breast cancer. Younger age was associated with worse locoregional recurrence-free survival, disease-free survival, and late DMFS, highlighting the importance of long-term monitoring and potential for personalized treatment approaches based on age, particularly for younger patients with ER-positive, ERBB2-negative breast cancer.

Dataset Information

High PD-L2 Predicts Early Recurrence of ER-Positive Breast Cancer.

Purpose

Methods

Results

Conclusion

Publications

High PD-L2 Predicts Early Recurrence of ER-Positive Breast Cancer.

Similar Datasets

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