Different Prognostic Value of Cytokeratin-19 mRNA–Positive Circulating Tumor Cells According to Estrogen Receptor and HER2 Status in Early-Stage Breast Cancer

Purpose To examine the prognostic value of cytokeratin-19 (CK-19) mRNA–positive circulating tumor cells (CTCs) in early-stage breast cancer patients focusing on clinically relevant subgroups based on estrogen receptor (ER) and HER2 expression. Patients and Methods CK-19 mRNA–positive CTCs were detected by real-time reverse transcriptase polymerase chain reaction in the blood of 444 consecutive, stage I-III, breast cancer patients before initiation of adjuvant chemotherapy. The association between detection of CK-19 mRNA–positive CTCs and clinical outcome was analyzed for patients with ER-positive, ER-negative, triple-negative, HER2-positive, and ER-positive/HER2-negative tumors. Results CK-19 mRNA–positive CTCs were detected in 181 (40.8%) of 444 patients; 109 (41.9%) of 260 patients with ER-positive tumors; 71 (40.6%) of 175 patients with ER-negative tumors; 27 (35%) of 77 patients with triple-negative tumors; 35 (39.8%) of 88 patients with HER2-positive tumors; and 82 (44.1%) of 186 patients with ER-positive/HER2-negative tumors. After a median follow-up of 53.5 months, patients with CK-19 mRNA–positive CTCs experienced reduced disease-free survival (DFS; P < .001) and overall survival (OS; P < .001); this was mainly observed in patients with ER-negative (P < .001 and P < .001, respectively) but not ER-positive tumors (P = .172 and P = .425, respectively) and in patients with triple-negative (P = .008 and P = .001, respectively) and HER2-positive (P = .023 and P = .040, respectively) but not ER-positive/HER2-negative tumors (P = .210 and P = .578, respectively). In multivariate analysis, the interaction between CK-19 mRNA–positive CTCs and ER status was the strongest independent prognostic factor for reduced DFS (hazard ratio [HR], 3.808; 95% CI, 2.415 to 6.003; P < .001) and OS (HR, 4.172; 95% CI, 2.477 to 9.161; P < .001). Conclusion Detection of CK-19 mRNA–positive CTCs before adjuvant chemotherapy predicts poor clinical outcome mainly in patients with ER-negative, triple-negative, and HER2-positive early-stage breast cancer.

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Different prognostic value of cytokeratin-19 mRNA-positive circulating tumor cells according to estrogen receptor status in early breast cancer

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.10500 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 10500-10500

Author(s):

M. Ignatiadis ◽

N. Xenidis ◽

M. Perraki ◽

S. Apostolaki ◽

E. Politaki ◽

...

Keyword(s):

Breast Cancer ◽

Clinical Outcome ◽

Early Breast Cancer ◽

Prognostic Value ◽

Triple Negative ◽

Cytokeratin 19 ◽

Breast Cancer Patients ◽

Poor Clinical Outcome ◽

Er Positive

10500 Background: We have previously shown that the detection of cytokeratin-19 (CK-19) mRNA-positive circulating tumor cells (CTCs) predicts poor clinical outcome in node-negative breast cancer patients. Here, we examined the prognostic value of CK-19 mRNA-positive CTCs in early breast cancer patients focusing on clinically relevant subgroups based on estrogen receptor (ER) status. Methods: We analysed peripheral blood from 448 consecutive patients with stage I-III breast cancer after surgery and before the initiation of any adjuvant treatment for the presence of CK-19 mRNA-positive CTCs using a real-time RT-PCR assay. The effect of CK-19 mRNA-positive CTCs on clinical outcome of patients with ER-positive, ER-negative, and triple-negative (ER/PR/HER2-negative) tumors was investigated. Results: CK-19 mRNA-positive CTCs were detected in 181 (40.4%) of the 448 patients; 109 (41.5%) of 263 patients with ER-positive, 71 (40.6%) of 175 patients with ER-negative and 27 (35%) of 77 patients with triple-negative tumors. There was no significant difference in the proportion of patients with detectable CK-19 mRNA-positive CTCs in the ER-negative and ER-positive subgroups (p=0.856). After a median follow-up of 53 months, patients with CK-19 mRNA-positive CTCs experienced reduced disease-free survival (DFS) (p<0.0005) and overall survival (OS) (p<0.0005); this was mainly observed in patients with ER-negative (p<0.0005 and p<0.0005, respectively) and triple-negative (p=0.008 and p=0.001, respectively) but not with ER-positive (p=0.174 and p=0.364, respectively) tumors. In multivariate analyses, detection of CK-19 mRNA-positive CTCs was the strongest independent prognostic factor associated with reduced DFS and OS in the entire cohort (p<0.0005 and p=0.009, respectively), in ER-negative (p<0.0005 and p=0.003, respectively) and triple-negative (p=0.020 and p=0.022, respectively) but not in ER-positive tumors (p=0.350 and p=0.621, respectively). Conclusions: Detection of CK-19 mRNA-positive CTCs predicts poor clinical outcome at five years follow-up, only in patients with ER-negative and triple-negative, but not with ER-positive, early breast cancer. No significant financial relationships to disclose.

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Prognostic and predictive value of neutrophil/lymphocyte ratio in patients with triple-negative and HER2-positive breast cancer undergoing neoadjuvant systemic therapy.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e12620 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e12620-e12620

Author(s):

Agnieszka I. Jagiello-Gruszfeld ◽

Magdalena Jodkiewicz ◽

Maria Kowalska ◽

Wojciech Michalski ◽

Wojciech P Olszewski ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Prognostic Value ◽

Triple Negative ◽

Early Stage ◽

Breast Cancer Patients ◽

Her2 Positive ◽

Neutrophil Lymphocyte Ratio ◽

Carboplatin Auc ◽

Positive Breast Cancer

e12620 Background: Preoperative neutrophil-lymphocyte ratio (NLR) have been suggested to be correlated with the prognosis of patients with breast cancer (BC). However, the results still remain controversial. The goal of our study was to evaluate the predictive and prognostic value of NLR in early stage triple negative and HER2-pos breast cancer patients undergoing NAC. Methods: 96 female patients (pts) with histologically proven breast cancer (51 TNBC, and 45 HER2 pos) were analysed in this retrospective analysis. The NLR before the initiation of NAC was documented. Histopathological response in surgically removed specimens was evaluated using the Residual Cancer Burden (RCB) Calculator (by MD Anderson Cancer Center). The pCR was defined as no invasive tumor in primary tumor bed and lymph nodes. The NLR variable was analyzed as both continuous and categorical. The impact on pCR and RCB was tested using Mann-Whitney, Kruskal-Willis or the Chi-2 test, respectively. Results: Only 4 categories of NAC were used: in TNBC 4 x ACdd followed by 12 x PCL (38 pts) or 4 x ACdd followed by 12 x PCL+ carboplatin AUC 1.0-2 (13 pts), in HER2-pos 39 pts received 6 x TCH (docetaxel + tratuzumab + carboplatin AUC 6) and 6 pts 4 x ACdd followed by 12 x PCL iv + 4 x trastuzumab. In 27 pts (53%) with TNBC and 24 pts (53%) with HER2-pos breast cancer pCR was obtained after NAC. RCB distribution was: 0-53.1%, 1-22%, 2-17.6%, 3-7.3%. No association with NLR and pCR could be observed (p > 0.26). No association with NLR and RCB could be observed (p > 0.18). Conclusions: In our retrospective analysis we could not demonstrate predictive or prognostic value of NLR in the cohort of early stage triple negative and HER2-positive breast cancer patients treated with NAC. Further studies are planned in a group of patients with Luminal B, HER2 – negative breast cancer, who received NAC.

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The prognostic value of IL10 and TNF alpha functional polymorphisms in premenopausal early-stage breast cancer patients

BMC Genetics ◽

10.1186/s12863-015-0234-8 ◽

2015 ◽

Vol 16 (1) ◽

Cited By ~ 13

Author(s):

Erika Korobeinikova ◽

Dana Myrzaliyeva ◽

Rasa Ugenskiene ◽

Danguole Raulinaityte ◽

Jurgita Gedminaite ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Prognostic Value ◽

Early Stage ◽

Early Stage Breast Cancer ◽

Tnf Alpha ◽

Breast Cancer Patients ◽

Functional Polymorphisms

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Impact of 70-Gene Signature Use on Adjuvant Chemotherapy Decisions in Patients With Estrogen Receptor–Positive Early Breast Cancer: Results of a Prospective Cohort Study

Journal of Clinical Oncology ◽

10.1200/jco.2016.70.3959 ◽

2017 ◽

Vol 35 (24) ◽

pp. 2814-2819 ◽

Cited By ~ 21

Author(s):

Anne Kuijer ◽

Marieke Straver ◽

Bianca den Dekker ◽

Annelotte C.M. van Bommel ◽

Sjoerd G. Elias ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Estrogen Receptor ◽

Early Stage ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Gene Signature ◽

Early Stage Breast Cancer ◽

Er Positive ◽

Test Result

Purpose Gene-expression profiles increasingly are used in addition to conventional prognostic factors to guide adjuvant chemotherapy (CT) decisions. The Dutch guideline suggests use of validated gene-expression profiles in patients with estrogen receptor (ER) –positive, early-stage breast cancer without overt lymph node metastases. We aimed to assess the impact of a 70-gene signature (70-GS) test on CT decisions in patients with ER-positive, early-stage breast cancer. Patients and Methods In a prospective, observational, multicenter study in patients younger than 70 years old who had undergone surgery for ER-positive, early-stage breast cancer, physicians were asked whether they intended to administer adjuvant CT before deployment of the 70-GS test and after the test result was available. Results Between October 1, 2013, and December 31, 2015, 660 patients, treated in 33 hospitals, were enrolled. Fifty-one percent of patients had pT1cN0, BRII, HER2-Neu-negative breast cancer. On the basis of conventional clinicopathological characteristics, physicians recommended CT in 270 (41%) of the 660 patients and recommended withholding CT in 107 (16%) of the 660 patients. For the remaining 43% of patients, the physicians were unsure and unable to give advice before 70-GS testing. In patients for whom CT was initially recommended or not recommended, 56% and 59%, respectively, were assigned to a low-risk profile by the 70-GS (κ, 0.02; 95% CI, -0.08 to 0.11). After disclosure of the 70-GS test result, the preliminary advice was changed in 51% of patients who received a recommendation before testing; the definitive CT recommendation of the physician was in line with the 70-GS result in 96% of patients. Conclusion In this prospective, multicenter study in a selection of patients with ER-positive, early-stage breast cancer, 70-GS use changed the physician-intended recommendation to administer CT in half of the patients.

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Patterns of relapse in older women diagnosed with estrogen receptor (ER)–positive early-stage breast cancer (BC) treated with lumpectomy without adjuvant endocrine therapy (ET)

Journal of Radiation Oncology ◽

10.1007/s13566-019-00405-y ◽

2019 ◽

Vol 8 (3) ◽

pp. 349-353

Author(s):

Manjeet Chadha ◽

T. Shao ◽

S. Cate ◽

S. Malamud ◽

C. White ◽

...

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Older Women ◽

Endocrine Therapy ◽

Early Stage ◽

Adjuvant Endocrine Therapy ◽

Early Stage Breast Cancer ◽

Er Positive

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Suboptimal Therapy Following Breast Conserving Surgery in Triple Negative and HER2-Postive Breast Cancer Patients

10.21203/rs.3.rs-459747/v1 ◽

2021 ◽

Author(s):

Jeffrey E. Johnson ◽

Paula D Strassle ◽

Guilherme C de Oliveira ◽

Chris B. Agala ◽

Philip M. Spanheimer ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Systemic Therapy ◽

Triple Negative ◽

Early Stage ◽

Breast Cancer Patients ◽

Her2 Positive ◽

Optimal Therapy ◽

Her2 Positive Breast Cancer ◽

Positive Breast Cancer

Abstract Purpose To assess potential disparities in guideline-concordant care delivery among women with early stage triple-negative and HER2-positive breast cancer treated with breast conserving therapy. Methods Women ≥40 years old diagnosed with pT2N0M0 triple-negative or HER2-positive breast cancer treated with primary surgery and axillary staging between 2012 and 2017 were identified using the National Cancer Database (NCDB). The primary outcome was receipt of adjuvant systemic therapy and radiation concordant with current guidelines. Multivariable log binomial regression was used to assess the prevalence of optimal therapy use across patient and cancer characteristics. Kaplan-Meier curves were used to assess 5-year overall survival. Multivariable Cox proportional hazards regression was used to compare the impact of optimal therapy on 5-year mortality. Results 11,785 women were included with 7,843 receiving optimal therapy. Receipt of optimal therapy decreased with age even after adjusting for comorbidities and cancer characteristics; other sociodemographic factors were not associated with differences in receipt of optimal therapy. Among patients who did not receive adjuvant systemic therapy, most were not offered the treatment (49%) or refused (40%). Overall 5-year survival was higher among women who received optimal therapy (89% [95% CI 88.0-89.3] vs. 66% [95% CI 62.9-68.5]). Patients who received suboptimal therapy were over twice as likely to die within 5-years of their diagnosis (adjusted HR 2.44, 95% CI 2.12-2.82). Conclusion Age is the primary determinant of the likelihood of a woman to receive optimal adjuvant therapies in high-risk early stage breast cancer. Patients who did not receive optimal therapy had significantly diminished survival.

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