Factors Predictive of Distant Metastases in Patients With Breast Cancer Who Have a Pathologic Complete Response After Neoadjuvant Chemotherapy

Purpose To identify clinicopathological factors predictive of distant metastasis in patients who had a pathologic complete response (pCR) after neoadjuvant chemotherapy (NC). Methods Retrospective review of 226 patients at our institution identified as having a pCR was performed. Clinical stage at diagnosis was I (2%), II (36%), IIIA (27%), IIIB (23%), and IIIC (12%). Eleven percent of all patients were inflammatory breast cancers (IBC). Ninety-five percent received anthracycline-based chemotherapy; 42% also received taxane-based therapy. The relationship of distant metastasis with clinicopathologic factors was evaluated, and Cox regression analysis was performed to identify independent predictors of development of distant metastasis. Results Median follow-up was 63 months. There were 31 distant metastases. Ten-year distant metastasis-free rate was 82%. Multivariate Cox regression analysis using combined stage revealed that clinical stages IIIB, IIIC, and IBC (hazard ratio [HR], 4.24; 95% CI, 1.96 to 9.18; P < .0001), identification of ≤ 10 lymph nodes (HR, 2.94; 95% CI, 1.40 to 6.15; P = .004), and premenopausal status (HR, 3.08; 95% CI, 1.25 to 7.59; P = .015) predicted for distant metastasis. Freedom from distant metastasis at 10 years was 97% for no factors, 88% for one factor, 77% for two factors, and 31% for three factors (P < .0001). Conclusion A small percentage of breast cancer patients with pCR experience recurrence. We identified factors that independently predicted for distant metastasis development. Our data suggest that premenopausal patients with advanced local disease and suboptimal axillary node evaluation may be candidates for clinical trials to determine whether more aggressive or investigational adjuvant therapy will be of benefit.

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Analysis of CK5/6 and EGFR and Its Effect on Prognosis of Triple Negative Breast Cancer

Frontiers in Oncology ◽

10.3389/fonc.2020.575317 ◽

2021 ◽

Vol 10 ◽

Author(s):

Zhen Wang ◽

Lei Liu ◽

Ying Li ◽

Zi’an Song ◽

Yi Jing ◽

...

Keyword(s):

Breast Cancer ◽

Regression Analysis ◽

Neoadjuvant Chemotherapy ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Cox Regression ◽

Multivariate Logistic Regression Analysis ◽

Pathological Examination ◽

Cox Regression Analysis ◽

Tumor Stages

BackgroundTriple-negative breast cancer (TNBC) is considered to be higher grade, more aggressive and have a poorer prognosis than other types of breast cancer. Discover biomarkers in TNBC for risk stratification and treatments that improve prognosis are in dire need.MethodsClinical data of 195 patients with triple negative breast cancer confirmed by pathological examination and received neoadjuvant chemotherapy (NAC) were collected. The expression levels of EGFR and CK5/6 were measured before and after NAC, and the relationship between EGFR and CK5/6 expression and its effect on prognosis of chemotherapy was analyzed.ResultsThe overall response rate (ORR) was 86.2% and the pathological complete remission rate (pCR) was 29.2%. Univariate and multivariate logistic regression analysis showed that cT (clinical Tumor stages) stage was an independent factor affecting chemotherapy outcome. Multivariate Cox regression analysis showed pCR, chemotherapy effect, ypT, ypN, histological grades, and post- NAC expression of CK5/6 significantly affected prognosis. The prognosis of CK5/6-positive patients after NAC was worse than that of CK5/6-negative patients (p=0.036). Changes in CK5/6 and EGFR expression did not significantly affect the effect of chemotherapy, but changes from positive to negative expression of these two markers are associated with a tendency to improve prognosis.ConclusionFor late-stage triple negative breast cancer patients receiving NAC, patients who achieved pCR had a better prognosis than those with non- pCR. Patients with the change in expression of EGFR and CK5/6 from positive to negative after neoadjuvant chemotherapy predicted a better prognosis than the change from negative to positive group.

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Pathologic Response Rates for Breast Cancer Stages as a Predictor of Outcomes in Patients Receiving Neoadjuvant Chemotherapy Followed by Breast-Conserving Surgery

10.21203/rs.3.rs-111293/v1 ◽

2020 ◽

Author(s):

Chang-Yun Lu ◽

Ho-Min Chen ◽

Szu-Yuan Wu

Keyword(s):

Neoadjuvant Chemotherapy ◽

Cox Regression ◽

Ductal Carcinoma ◽

Pathologic Complete Response ◽

Response Rates ◽

Complete Response ◽

Breast Conserving Surgery ◽

Pathologic Response ◽

Cox Regression Analysis ◽

All Cause Mortality

Abstract PURPOSE: To determine easy-to-use predictors of overall survival (OS), locoregional recurrence (LRR), and distant metastasis (DM) in patients with breast invasive ductal carcinoma (IDC) receiving neoadjuvant chemotherapy (NACT) followed by breast-conserving surgery (BCS), we obtained pathologic response rates (PRRs) for combined primary and nodal diseases (American Joint Committee on Cancer [AJCC] stages) from clinical and pathologic reports, and we used these as predictors.PATIENTS AND METHODS: We enrolled patients with IDC who had received NACT followed by BCS. Cox regression analysis was used to calculate hazard ratios (HRs) and confidence intervals (CIs) for the patients’ PRRs; other independent predictors were controlled for or stratified in the analysis.RESULTS: We analyzed 1047 patients with IDC (611, 260, and 176 patients in clinical stages IIB, IIIA, and IIIB-C, respectively) receiving NACT and BCS. After multivariate Cox regression analyses, the adjusted HRs (aHRs; 95% CI) in patients with pathologic complete response (ypT0N0) were 0.26 (0.13–0.56), 0.36 (0.15–0.85), and 0.15 (0.08–0.31) for all-cause mortality, LRR, and DM, respectively. The aHRs (95% CI) in patients with downstaging of AJCC stages were 0.55 (0.35–0.89), 0.91 (0.62–0.96), and 0.63 (0.43–0.91) for all-cause mortality, LRR, and DM, respectively. The aHRs (95% CI) in patients with upstaging of AJCC stages were 1.77 (1.06–2.24), 1.08 (1.03–1.82), and 1.19 (1.07–2.01) for all-cause mortality, LRR, and DM, respectively.CONCLUSION: The impacts of AJCC-stage PRRs are useful predictive tools and strong predictors for OS, LRR, and DM in patients with breast IDC receiving NACT followed by BCS.

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Pathologic Response Rates for Breast Cancer Stages as a Predictor of Outcomes in Patients Receiving Neoadjuvant Chemotherapy Followed by Breast-Conserving Surgery

10.21203/rs.3.rs-97674/v1 ◽

2020 ◽

Author(s):

jiaqiang Zhang ◽

Chang-Yun Lu ◽

Ho-Min Chen ◽

Szu-Yuan Wu

Keyword(s):

Neoadjuvant Chemotherapy ◽

Cox Regression ◽

Ductal Carcinoma ◽

Pathologic Complete Response ◽

Response Rates ◽

Complete Response ◽

Breast Conserving Surgery ◽

Pathologic Response ◽

Cox Regression Analysis ◽

All Cause Mortality

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Does biologic subtype and pathologic response after neoadjuvant chemotherapy predict locoregional recurrence?

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.26_suppl.65 ◽

2014 ◽

Vol 32 (26_suppl) ◽

pp. 65-65

Author(s):

T. Jonathan Yang ◽

Monica Morrow ◽

Shanu Modi ◽

Kate Krause ◽

Chun Siu ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Locoregional Recurrence ◽

Cox Regression ◽

Breast Cancer Subtype ◽

Univariate Analysis ◽

Pathologic Complete Response ◽

High Risk Population ◽

Cox Regression Analysis ◽

Her2 Breast Cancer

65 Background: The relative contribution of biological subtype and response to neoadjuvant chemotherapy (NAC) to locoregional recurrence (LRR) is uncertain. We aim to determine if these factors identify a high risk population for LRR. Methods: 233 patients received anthracycline/taxane-based NAC, mastectomy and postmastectomy radiation therapy (PMRT) in 2000-2009 for Stage II-III breast cancer. 53% (n=123) were HR+ (ER or PR+/HER2-), 23% (53) HER2+ (HER2+/HR+ or HR-), and 24% (57) TN (HR-/HER2-). 76% of HER2+ received trastuzumab. Median PMRT dose was 50 Gy to chest wall and regional nodes. Pathologic complete response (pCR) rates were compared using Fisher's exact test. Rates of LRR and distant recurrence (DR) were estimated by Kaplan-Meier methods. Cox regression analysis was performed. Results: Median follow-up was 62 months (range 7-161) with 21 LRR, 84 DR and 58 deaths. pCR rate and 5-year LRR rates were 14% and 7% in the entire cohort, respectively. Significantly more TN and HER2+ patients achieved pCR than HR+ patients (Table 1, p=0.003). TN patients had higher 5-year LRR rate compared to HR+ and HER2+ patients (18% vs. 4% and 6%, p=0.02). The 5-year LRR rate was 0% in pCR patients versus 9% in non-pCR patients (p=0.06). In patients without pCR, TN subtype was associated with increased LRR (23% at 5-year vs. 4% HR+ and 7% HER2+; p=0.001). TN patients without pCR were also associated with increased DR (48% at 5-year vs. 29% HR+ and 30% HER2+, p=0.02). On univariate analysis, TN subtype (HR=2.0, p=0.008), pathologic stage (HR=2.2, p=0.02), and pN+ status (HR=9.3, p=0.03) were associated with increased LRR. Conclusions: Although response to NAC strongly correlates with breast cancer subtype, patients with HR+ and HER2+ breast cancer had favorable rates of LRR regardless of response to NAC, perhaps because of additional postoperative targeted therapy. In contrast, while no LRR was seen in TN patients with pCR, those with poor response to NAC had significantly higher LRR risk, underscoring the need for potential new treatment strategies to improve local control in this population. [Table: see text]

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Residual cancer burden (RCB) is practical and may be more informative than pathological response following neoadjuvant chemotherapy (NC) for locally advanced breast cancer (LABC)

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.21103 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 21103-21103

Author(s):

D. Sivasubramaniam ◽

R. Komrokji ◽

S. Dhaliwal ◽

V. Sundarajan ◽

Z. Nahleh

Keyword(s):

Breast Cancer ◽

Regression Analysis ◽

Neoadjuvant Chemotherapy ◽

Advanced Breast Cancer ◽

Cox Regression ◽

Locally Advanced Breast Cancer ◽

Locally Advanced ◽

Pathological Response ◽

P Value ◽

Cox Regression Analysis

21103 Background: Complete pathological response (pCR) has been considered a reliable endpoint to assess the benefit of NC. However, different pathological responses ranging from near complete response to resistance would likely indicate different prognostic groups. Method: We studied patients with locally advanced breast cancer (LABC) who received NC between 2001–2006 at the University of Cincinnati. Pathological response to therapy was evaluated. In addition, RCB was quantified according to MD Anderson RCB Calculator index that combines pathologic measurements of primary tumor (size and cellularity) and nodal metastases (number and size). We examined the correlation between pCR, RCB, event-free survival (EFS) and over all survival (OS) by Cox regression analyses. Result: Pathological slides of 32 patients were analyzed. Median age 52, 38% white and 62% African American. Stage IIB 12% , Stage IIIA 19%, Stage IIIB 53% and Stage IIIC 16% . 72% invasive ducal, 6% invasive lobular and 22% inflammatory cancer. Forty seven percent of tumors were ER +/or PR+ , 53% ER-/PR-, 28% HER-2 /neu + ( IHC 3+ or FISH HER2 gene to chromosome 17 ration > 2.2). Tumor response was as follows: 22% (n=7) achieved pCR , RCB scores ranged between 0- 4.87. By univariate Cox regression analysis, RCB correlated with EFS {Hazard ratio (HR) 1.57 (95% CI 1.04–2.38), p-value 0.018}, and with OS {HR 1.74 (95% CI 0.91 -3.32), p value-0.09}. However, pCR did not seem to correlate with EFS {HR 0 .24 (95%CI 0.03 -1.86–2.38), p-value .172} or OS {HR 0.03 (95% CI 0–89),p value-0.40}. By multivariate Cox regression analysis, RCB was noted to be an independent predictive variable for EFS {HR 1.59 (95% CI 1.04–2.43), p value-0.033} while pCR was not {HR 0.90 (95% CI 0.52–1.57), p value-0.7. Conclusion: RCB was easily quantifiable and appears to be a better predictor of outcome following neoadjuvant chemotherapy in LABC compared to pCR. Higher RCB scores were associated with higher EFS and lower rate of OS. Prospective trials are needed to further evaluate the role of RCB as an endpoint following NC. No significant financial relationships to disclose.

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Association of pathologic non-complete response of axillary node with outcome after neoadjuvant chemotherapy in node positive breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e12101 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e12101-e12101

Author(s):

Shin-Cheh Chen ◽

Hsien-Kun Chang ◽

Yung-Chang Lin ◽

Shih-Che Shen ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Cox Regression ◽

Medical Center ◽

Pathologic Complete Response ◽

Metastatic Breast ◽

Complete Response ◽

Axillary Node ◽

Predicting Factors ◽

The Impact

e12101 Background: The pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) correlates with better outcome in specific subtype of breast cancer and the axillary nodal pCR (N-pCR) rate are more common than breast pCR (B-pCR). While only a few studies to compare the survival in terms of B-pCR and N-pCR, and no study compare between the outcome for those non pCR either in breast or axillary node. Methods: A cohort of 968 cytologically proved nodal metastatic breast cancer (cT1~4N1~2) received NAC in a single medical center between 2005~2017 were analyzed retrospectively. NAC regimen included anthracycline and taxanes in all patients, Trastuzumab was used in 308(70.3%) HER2(+) patients. The percentage of both breast and axillary pCR (T-pCR) 、B-pCR and N-pCR were compared in different subtypes. The impact of T-pCR、B-pCR and N-pCR to DFS and OS were analyzed using univariate and multivariate Cox proportional hazard model. Results: The median follow-up time was 45 months. The median age was 49 years old, average tumor size was 4.2cm, and 543 (56.1%) patients were N1 disease. 382(39.5%) patients were HR(+) HER2(-), 222(22.9%)were HR(+)HER2(+),216(22.3%) were HR(-)HER2(+) and 148(15.3%) were HR(-)HER2(-). After NAC, T-pCR was found in 213 (22.0%) patients, B-pCR and N non-pCR in 31 patients, N-pCR and B non-pCR in 245 patients and T non-pCR in 479 patients. N-pCR rate(47.3%) were significantly higher than B-pCR(25.2%) and this trend found in all subtypes ( P<0.0001).The predicting factors of N-pCR were N1,HER2(+) and HR(-). In survival analysis the pCR (either T,B or N) patients had significantly better 5-year DFS and OS than non- pCR(T-pCR v.s T non-pCR, DFS,85.1% v.s 58.4%;OS,91.2% v.s 73.6%,p<0.0001). B-non pCR had a significant better DFS than T non Pcr(65.1% v.s 58.4%,p=0.041) and non- significant. Cox better 5-year OS(78.9% v.s73.6%,p=0.059). Cox regression model demonstrated that T4,N2,grade 3, HR(-) and T non-pCR were poor prognostic factors in DFS and OS. Conclusions: The study demonstrated higher N-pCR rates than B-pCR in all subtypes after NAC, either T-pCR;B-pCR or N-pCR were associated with better outcome than non pCR. The worst outcome found in those T non-pCR or N non-pCR.

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Predictors of Distant Metastases in Triple-Negative Breast Cancer Without Pathologic Complete Response After Neoadjuvant Chemotherapy

Journal of the National Comprehensive Cancer Network ◽

10.6004/jnccn.2019.7366 ◽

2020 ◽

Vol 18 (3) ◽

pp. 288-296 ◽

Cited By ~ 2

Author(s):

William R. Kennedy ◽

Christopher Tricarico ◽

Prashant Gabani ◽

Ashley A. Weiner ◽

Michael B. Altman ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Triple Negative Breast Cancer ◽

Distant Metastasis ◽

Triple Negative ◽

Residual Disease ◽

Pathologic Complete Response ◽

Complete Response ◽

Hazard Ratio ◽

Lymphovascular Space Invasion

Background: Pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) for triple-negative breast cancer (TNBC) predicts decreased distant metastasis. However, most patients do not experience pCR, and other risk factors for distant metastasis after NAC are poorly characterized. This study investigated factors predictive of distant metastasis in TNBC without pCR after NAC. Methods: Women with TNBC treated with NAC, surgery, and radiation therapy in 2000 through 2013 were reviewed. Freedom from distant metastasis (FFDM) was compared between patients with and without pCR using the Kaplan-Meier method. In patients without pCR, univariate and multivariable Cox analyses were used to determine factors predictive of distant metastasis. Results: We identified 153 patients with median follow-up of 4.0 years (range, 0.5–14.0 years). After NAC, 108 had residual disease (pCR, 29%). Five-year FFDM was 98% and 55% in patients with and without pCR, respectively (P<.001). Factors independently predicting FFDM in patients without pCR were pathologic nodal positivity (hazard ratio, 3.08; 95% CI, 1.54–6.14; P=.001) and lymphovascular space invasion (hazard ratio, 1.91; 95% CI, 1.07–3.43; P=.030). Patients with a greater number of factors had worse FFDM; 5-year FFDM was 76.5% for patients with no factors (n=38) versus 54.9% and 27.5% for patients with 1 (n=44) and 2 factors (n=26), respectively (P<.001). Conclusions: Lack of pCR after NAC resulted in worse overall survival and FFDM, despite trimodality therapy. In patients with residual disease after NAC, pathologic lymph node positivity and lymphovascular space invasion predicted worse FFDM.

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Atorvastatin in Treating Patients With Stages IIb-III Triple Negative Breast Cancer Who Did Not Achieve a Pathologic Complete Response After Receiving Neoadjuvant Chemotherapy

Case Medical Research ◽

10.31525/ct1-nct03872388 ◽

2019 ◽

Author(s):

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Pathologic Complete Response ◽

Complete Response

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Identification and development of an independent immune-related genes prognostic model for breast cancer

BMC Cancer ◽

10.1186/s12885-021-08041-x ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Lin Chen ◽

Yuxiang Dong ◽

Yitong Pan ◽

Yuhan Zhang ◽

Ping Liu ◽

...

Keyword(s):

Breast Cancer ◽

Regression Analysis ◽

Cox Regression ◽

Gene Set Enrichment Analysis ◽

Risk Scores ◽

Validation Dataset ◽

Immune Gene ◽

Cox Regression Analysis ◽

Immune Genes ◽

Immune Related Genes

Abstract Background Breast cancer is one of the main malignant tumors that threaten the lives of women, which has received more and more clinical attention worldwide. There are increasing evidences showing that the immune micro-environment of breast cancer (BC) seriously affects the clinical outcome. This study aims to explore the role of tumor immune genes in the prognosis of BC patients and construct an immune-related genes prognostic index. Methods The list of 2498 immune genes was obtained from ImmPort database. In addition, gene expression data and clinical characteristics data of BC patients were also obtained from the TCGA database. The prognostic correlation of the differential genes was analyzed through Survival package. Cox regression analysis was performed to analyze the prognostic effect of immune genes. According to the regression coefficients of prognostic immune genes in regression analysis, an immune risk scores model was established. Gene set enrichment analysis (GSEA) was performed to probe the biological correlation of immune gene scores. P < 0.05 was considered to be statistically significant. Results In total, 556 immune genes were differentially expressed between normal tissues and BC tissues (p < 0. 05). According to the univariate cox regression analysis, a total of 66 immune genes were statistically significant for survival risk, of which 30 were associated with overall survival (P < 0.05). Finally, a 15 immune genes risk scores model was established. All patients were divided into high- and low-groups. KM survival analysis revealed that high immune risk scores represented worse survival (p < 0.001). ROC curve indicated that the immune genes risk scores model had a good reliability in predicting prognosis (5-year OS, AUC = 0.752). The established risk model showed splendid AUC value in the validation dataset (3-year over survival (OS) AUC = 0.685, 5-year OS AUC = 0.717, P = 0.00048). Moreover, the immune risk signature was proved to be an independent prognostic factor for BC patients. Finally, it was found that 15 immune genes and risk scores had significant clinical correlations, and were involved in a variety of carcinogenic pathways. Conclusion In conclusion, our study provides a new perspective for the expression of immune genes in BC. The constructed model has potential value for the prognostic prediction of BC patients and may provide some references for the clinical precision immunotherapy of patients.

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The Investigation of Associations between TP53 rs1042522, BBC3 rs2032809, CCND1 rs9344, EGFR rs2227983 Polymorphisms and Breast Cancer Phenotype and Prognosis

Diagnostics ◽

10.3390/diagnostics11081419 ◽

2021 ◽

Vol 11 (8) ◽

pp. 1419

Author(s):

Justina Bekampytė ◽

Agnė Bartnykaitė ◽

Aistė Savukaitytė ◽

Rasa Ugenskienė ◽

Erika Korobeinikova ◽

...

Keyword(s):

Breast Cancer ◽

Regression Analysis ◽

Cox Regression ◽

Cancer Prognosis ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Cox Regression Analysis ◽

Pcr Rflp ◽

Oncological Diseases ◽

Cancer Phenotype

Breast cancer is one of the most common oncological diseases among women worldwide. Cell cycle and apoptosis—related genes TP53, BBC3, CCND1 and EGFR play an important role in the pathogenesis of breast cancer. However, the roles of single nucleotide polymorphisms (SNPs) in these genes have not been fully defined. Therefore, this study aimed to analyze the association between TP53 rs1042522, BBC3 rs2032809, CCND1 rs9344 and EGFR rs2227983 polymorphisms and breast cancer phenotype and prognosis. For the purpose of the analysis, 171 Lithuanian women were enrolled. Genomic DNA was extracted from peripheral blood; PCR-RFLP was used for SNPs analysis. The results showed that BBC3 rs2032809 was associated with age at the time of diagnosis, disease progression, metastasis and death. CCND1 rs9344 was associated with tumor size, however an association resulted in loss of significance after Bonferroni correction. In survival analysis, significant associations were observed between BBC3 rs2032809 and OS, PFS and MFS. EGFR rs2227983 also showed some associations with OS and PFS (univariate Cox regression analysis). However, the results were in loss of significance (multivariate Cox regression analysis). In conclusion, BBC3 rs2032809 polymorphism was associated with breast cancer phenotype and prognosis. Therefore, it could be applied as potential markers for breast cancer prognosis.

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