scholarly journals A nomogram for predicting probability of low risk of MammaPrint results in women with clinically high-risk breast cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Young Joo Lee ◽  
Young Sol Hwang ◽  
Junetae Kim ◽  
Sei-Hyun Ahn ◽  
Byung Ho Son ◽  
...  

AbstractWe aimed to develop a prediction MammaPrint (MMP) genomic risk assessment nomogram model for hormone-receptor positive (HR+) and human epidermal growth factor receptor-2 negative (HER2–) breast cancer and minimal axillary burden (N0-1) tumors using clinicopathological factors of patients who underwent an MMP test for decision making regarding adjuvant chemotherapy. A total of 409 T1-3 N0-1 M0 HR + and HER2– breast cancer patients whose MMP genomic risk results and clinicopathological factors were available from 2017 to 2020 were analyzed. With randomly selected 306 patients, we developed a nomogram for predicting a low-risk subgroup of MMP results and externally validated with remaining patients (n = 103). Multivariate analysis revealed that the age at diagnosis, progesterone receptor (PR) score, nuclear grade, and Ki-67 were significantly associated with MMP risk results. We developed an MMP low-risk predictive nomogram. With a cut off value at 5% and 95% probability of low-risk MMP, the nomogram accurately predicted the results with 100% positive predictive value (PPV) and negative predictive value respectively. When applied to cut-off value at 35%, the specificity and PPV was 95% and 86% respectively. The area under the receiver operating characteristic curve was 0.82 (95% confidence interval [CI] 0.77 to 0.87). When applied to the validation group, the nomogram was accurate with an area under the curve of 0.77 (95% CI 0.68 to 0.86). Our nomogram, which incorporates four traditional prognostic factors, i.e., age, PR, nuclear grade, and Ki-67, could predict the probability of obtaining a low MMP risk in a cohort of high clinical risk patients. This nomogram can aid the prompt selection of patients who does not need additional MMP testing.

2021 ◽  
Vol 11 ◽  
Author(s):  
Mi Jeong Kwon ◽  
Jai Min Ryu ◽  
Soo Youn Cho ◽  
Seok Jin Nam ◽  
Seok Won Kim ◽  
...  

BackgroundThe prognostic or predictive value of commonly used multigene assays in young patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) early breast cancer is unclear. In this study, we assessed the prognostic value of the GenesWell BCT assay according to age group.MethodsWe identified patients with pN0-1, HR+/HER2− breast cancer in a prospective cohort of women who underwent surgery between 2005 and 2017. The GenesWell BCT assay was performed on tissue samples from selected patients. Distant metastasis-free survival (DMFS) and disease-free survival (DFS) were compared between the risk groups assigned by the BCT score.ResultsA total of 712 patients were eligible for analysis. The median follow-up time was 7.47 years. The BCT score was prognostic in patients aged ≤50 years (n = 404) and those aged >50 years (n = 308). In both age groups, the 10-year DMFS and DFS rates for patients classified as high risk by the BCT score were significantly lower than those for patients classified as low risk. A multivariate analysis revealed that the BCT score was an independent prognostic factor for DFS in patients aged ≤50 years (hazard ratio, 1.28; 95% CI, 1.05–1.56; P = 0.015), as well as those aged >50 years.ConclusionThe BCT score could be used to identify low-risk patients who will not benefit from adjuvant chemotherapy to treat HR+/HER2− early breast cancer regardless of age. A further prospective study to assess the prognostic and predictive value of the BCT score is required.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12555-e12555
Author(s):  
Reiki Nishimura ◽  
Tomofumi Osako ◽  
Yasuhiro Okumura ◽  
Masahiro Nakano ◽  
Mamiko Fujisue ◽  
...  

e12555 Background: Overexpression and/or amplification of HER2 is observed in 15–20% of all invasive breast cancer cases. Breast cancer patients with HER2 overexpression can benefit from anti-HER2 therapy. HER2 IHC results are generally divided into four values (range, 0 to 3+). The cases with a HER2 (2+) value should be assessed using FISH. The aim of this retrospective study was to evaluate the biological variables and prognosis of HER2 (2+) cases according to the FISH status. Methods: Primary breast cancer patients (n = 5419) were enrolled in this study from January 2002 to September 2019. The factors investigated included nodal status, tumor size, nuclear grade, ER/PgR and HER2 status, p53 overexpression, and the Ki-67 index values. Positive for HER2 is categorized as having a HER2 value of 3 + or FISH amplified in equivocal cases. Results: The HER2 3+ rate in non-invasive carcinoma was higher than the rate in the invasive carcinoma cases (16.4% vs 12.9%; p < 0.0001). The distribution of HER2 IHC status in invasive carcinoma cases was 3+ (12.9%), 2+ (5.8%) and negative (84.3%). The FISH positive rate of the HER2 2+ cases was 57.0 % (158 cases). HER2 positivity significantly correlated with ER/PgR negative, p53 overexpression, higher Ki-67 value and nuclear grade. The FISH positivity of the HER2 2+ cases significantly correlated with PgR negative, p53 overexpression and higher grade. There were significant differences in biological variables between IHC 3+ and 2+/FISH positive, and between IHC 2+/FISH negative and IHC negative. Patients with HER2 3+ had significantly worse disease-free survival (DFS) rates than the cases before the approval of trastuzumab in Japan. However, there was no difference after trastuzumab was approved. Moreover, there was no difference in DFS according to the FISH status in HER2 2+ cases. Conclusions: HER2 positivity indicated a higher degree of malignancy. HER2 2+ had different independent biological characteristics from HER2 negative (0 & 1+) or positive (3+) cases. Therefore, the difference in biology of HER2 2+ cases may influence the prognosis and should be reconsidered in breast cancer cases.


2017 ◽  
Vol 24 (3) ◽  
pp. 176 ◽  
Author(s):  
M. Rushton ◽  
C. Johnson ◽  
S. Dent

Background Trastuzumab has improved survival for women with her2-positive breast cancer, but its use is associated with an increased risk of cardiotoxicity. With increased survivorship, the long-term effects of cancer treatment are an important consideration for clinicians and patients. We reviewed the current literature on predicting trastuzumab-related cardiotoxicity and tested a clinical risk score (crs) in a real-world breast cancer population to assess its utility in predicting permanent cardiotoxicity.Methods In this retrospective exploratory cohort study of breast cancer patients referred to a cardio-oncology clinic at a tertiary care centre between October 2008 and August 2014, a crs was calculated for each patient, and a sensitivity analysis was performed.Results Of the 143 patients included in the study, 62 (43%) experienced a cardiac event, and of those 62 patients, 43 (69%) experienced full recovery of cardiac function. In applying the crs, 119 patients (83%) would be considered at low risk, 14 (10%) at moderate risk, and 10 (7%) at high risk to develop heart failure or cardiomyopathy. When applied to the study population, the high-risk cut-off score had a sensitivity of 0.13 [95% confidence interval (ci): 0.08 to 0.20] and a specificity of 0.94 (95% ci: 0.87 to 0.97). The positive predictive value was 0.07 (95% ci: 0.03 to 0.13), and the negative predictive value was 0.93 (95% ci: 0.87 to 0.96).Conclusions The crs demonstrated good specificity and negative predictive value for the development of permanent cardiotoxicity in a real-world population of breast cancer patients, suggesting that intensive cardiac monitoring might not be warranted in low-risk patients, but that high-risk patients might benefit from early referral to cardio-oncology for optimization. Further study using the crs in a larger breast cancer population is warranted to identify patients at low risk of long-term trastuzumab-related cardiotoxicity.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 564-564
Author(s):  
Atsushi Yoshida ◽  
Yasuyuki Kojima ◽  
Mizuho Tazo ◽  
Naoko Matsuda ◽  
Koichiro Tsugawa ◽  
...  

564 Background: There is a recent trend of performing minimum axillary surgery considering the prognostic value and fewer complications for primary breast cancer patients since the results of ACOSOG Z011. Nodal status after NAC is not be useful for postoperative treatment in most of cN0 patients. Therefore, sentinel node biopsy (SNB) may be omitted if ypN0 after NAC can be predicted in cN0 patients. We assessed clinicopathological factors associated with ypN0 after NAC in cN0 primary breast cancer patients. Methods: Two-institutional retrospective cohort study of clinically N0 breast cancer patients before NAC and who underwent breast surgery was conducted, including 419 consecutive patients between 2009 and 2016 in St. Luke's International Hospital and St. Marianna University School of Medicine hospital. Each institutional review board approved this study. In the patients with or without nodal metastasis on SNB after NAC, we compared clinicopathological factors including Estrogen Receptor (ER), Progesterone Receptor (PgR), human epidermal growth factor receptor 2 (HER2), Ki-67 on needle biopsy specimens, and tumor size before and after NAC on MRI findings. Results: Of the 419 patients, 380 patients (90.7%) were ypN0 and 39 patients (9.3%) were ypN+ after NAC. In univariate analysis, clinical complete response of primary tumor on MRI findings (MRI-CR) (p<0.01), ER-negative (p<0.01), PgR-negative (p<0.01), and high-Ki-67 >30% (p<0.01) were significantly associated with ypN0 on SNB after NAC. In multivariate analysis, MRI-CR (HR 5.12, p<0.01) and high-Ki-67 (HR 2.86, p<0.01) were independent predictive factors of ypN0 after NAC.According to breast cancer subtype, only one of 72 ER-negative and HER2-positive had significantly low risk of ypN+ (1.3%) comparing other subtypes (p<0.01). Conclusions: Achieving cCR of primary tumor after NAC and high-Ki67 in cN0 patients, especially in HER2 type breast cancer, might have ypN0. We are conducting prospective study to omit SNB for these populations based on these results,


2021 ◽  
Vol 49 (3) ◽  
pp. 030006052199101
Author(s):  
Jie Ding ◽  
Hongyan Xiao ◽  
Weiwei Deng ◽  
Fengjiao Liu ◽  
Rongrong Zhu ◽  
...  

Objective To evaluate the feasibility of quantitative enhancing lesion volume (ELV) for evaluating the responsiveness of breast cancer patients to early neoadjuvant chemotherapy (NAC) using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Methods Seventy-five women with breast cancer underwent DCE-MRI before and after NAC. Lesions were assessed by ELV, response evaluation criteria in solid tumors 1.1 (RECIST 1.1), and total lesion volume (TLV). The diagnostic and pathological predictive performances of the methods were compared and color maps were compared with pathological results. Results ELV identified 29%, 67%, and 4% of cases with partial response, stable disease, and progressive disease, respectively. There was no significant difference in evaluation performances among the methods. The sensitivity, specificity, positive predictive value, negative predictive value (NPV), and accuracy of ELV for predicting pathologic response were 72%, 92%, 81.8%, 86.8%, and 85.3%, respectively, with the highest sensitivity, NPV, and accuracy of the three methods. The area under the receiver operating characteristic curve was also highest for ELV. Pre- and post-NAC color maps reflecting tumor activity were consistent with pathological necrosis. Conclusions ELV may help evaluate the responsiveness of breast cancer patients to NAC, and may provide a good tumor-response indicator through the ability to indicate tumor viability.


2019 ◽  
Vol 20 (2) ◽  
pp. 37-41
Author(s):  
Md Hasanuzzaman ◽  
Md Johirul Lslam ◽  
AZM Mostaque Hossain ◽  
Md Rassell ◽  
Md Mafizur Rahman ◽  
...  

Background: Carcinoma of the breast is one of the most common malignancies in women worldwide. Objective: The current study was conducted to evaluate the role of Ki-67 as a prognosticmarker in two definite groups of breast cancer patients (ER+ve, PR+ve, HER-ve& triple negative)in Bangladesh perspective. Methods: Sixty nine female breast cancer patients operated at the surgical oncology departmentof National Institute of Cancer Research & Hospital were selected by non-probabilitysampling method and operated specimens were sent for immunohistochemical study of theER, PR, Her2/neu receptors and Ki-67 protein analysis. Statistical analysis was conductedusing SPSS version 17 for Windows software. P-value 0.05 or less was considered as significant. Result: The mean age of the patients was 46.96 years with SD of± 13.13 years. Histopathologyreports revealed that 94.2% (65/69) were suffering from duct cell carcinoma (DCC) whilelobular varieties were found in 2 cases. Majority of the patients with ER+, PR+ and Ki-67 +vestatus were between 36-50 years of age. But for Her2/neu positive cases most of patientswere above 50 years of age. In Luminal A category cancer patients 69.7% showed positiveKi-67 expression but in case of triple negative cases this percentage was 87.5%. However, thisdifference was not statistically significant. Conclusion: Scores based upon staining of ER, PR, Her2/neu and Ki-67 collectively known asIHC4 which can be used as prognostic markers in breast cancer patients. Journal of Surgical Sciences (2016) Vol. 20 (2) :37-41


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23021-e23021
Author(s):  
Marek Sochor ◽  
Petra Basova ◽  
Michal Pesta ◽  
Jiri Bartos ◽  
Tomas Stopka

e23021 Background: Early breast cancer is a frequent female disease with different outcomes. New approaches are needed in order to improve its prognosis. MicroRNAs (miRs) are modulators of gene expression and act as oncogenes and function to inhibit tumor suppressors and to promote metastasizing. Monitoring of miRs could be of benefit to the prognosis of EBC patients. Methods: We prospectively collected sera from 133 EBC patients (follow-up 53,25 months) in 3 time points (before I and after surgery II, after therapy III). Patients were stratified into high and low-risk groups according to HR, HER2, Ki-67, grade, LN. For RNA isolation serum was used followed by RT-qPCR and was applied longitudinal multivariate data analysis. Aim of the project was to determine serum expression of miR-155, miR-19a, miR-181b, miR-24 in 3 time points, to find difference in expressions between high and low-risk groups, to find association between miRs and clinical/pathological risk factors and associations in miRs expression and prognosis of EBC. Results: EBC patients significantly over-express miRs in time point I. In time point II the levels of miR-155, miR-181b, miR-24 significantly decreased ( p< 0.05). miR-19a decreased in time point III ( p= 0.00869). Levels of miR-155, miR-19a, miR-181b, miR-24 are significantly more abundant in high-risk in comparison to low-risk patients ( p< 0.05) and decrease upon therapy. The multivariate GEE model revealed that miR-155, miR-24 were predictive of the relapse ( p= 0.025 and 0.041). miR-19a, miR-181b are insignificant with respect to the relapse ( p> 0.05). Triple-negativity, HER2+, grade III, LN+ have no effect on the probability of relapse ( p> 0.05) when miRs are simultaneously taken into an account. The only risk factor that makes the prediction of relapse more precise is Ki-67 > 20% ( p= 0.013 in case of miR-155 and p= 0.023 in case of miR-24). Conclusions: OncomiRs are significantly more abundant in EBC patients at diagnosis and decline after therapy. Differences in miR levels reflect EBC risk groups. The data shows that miR-155 and miR-24 enable monitoring of EBC and predict relapse independently of clinical/pathological risk factors. Combining the miR levels with Ki-67 expression further specifies the relapse probability.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13673-e13673
Author(s):  
Chen Tian ◽  
Lili Fu ◽  
Jiyu Wei ◽  
Pengfei Yin ◽  
Henghui Zhang

e13673 Background: Ki-67 is widely used for risk stratification in patients with ER+/HER2- breast cancer. The multigene assay, MammaPrint/BluePrint (MP/BP) test, is validated as a good predictor of recurrence in patients with Luminal type breast cancer and a good tool of molecular subtyping classification. Previous study showed that MP/BP test was able to re-stratify 54% of patients with a Luminal-B pathological subtyping (PS) to a low-risk Luminal A-type group. But there is no study directly show the comparison between Ki67 and MP/BP test result. Here in this study, we compare Ki-67 with MP/BP test result in Chinese patients with luminal type breast cancer. Methods: Formalin-fixed, paraffin-embedded (FFPE) tumour samples or fresh tumour samples from 1008 eligible breast cancer patients were collected from 122 hospitals in China. Tumor RNAs were isolated from samples and analyzed using RNA sequencing technology. Ki-67 protein expression were assessed in FFPE tissue blocks by IHC. The pathology subtyping of patient was categorized based on the 2013 St. Gallen. Comparison of MP/BP result with Ki-67 IHC was performed. Concordance between subtyping by the MP/BP and PS was also evaluated. Results: Of 1008 patients with ER+/HER2- breast cancer, 640 were MP Low-Risk and 368 were MP High-Risk. MammaPrint index was significantly associated with Ki-67 expression (p < 0.001). Among the patients with Ki-67 value lower than 15%, 81.11% were MP Low-Risk, while 65.12% of patients with Ki-67 value between 15%-20% and 46.67% of patients with Ki-67 value between 21%-30% were MP Low Risk. Of the patients with Ki-67 value higher than 30%, 77.24% were MP High-Risk. Among the 453 patients with PS Luminal-A tumours, 77 (17%) were categorized as Luminal-B by MP/BP test. While among the 555 patients with PS Luminal-B tumours, 265 (48%) were categorized as Luminal-A by MP/BP test. Conclusions: Our results show that for the patients with low Ki-67 value ( < 15%) or high Ki-67 value ( > 30%), the risk prediction by MP test are mostly agree with Ki-67 IHC, while for the patients with intermediate Ki-67 value (15-30%), MammaPrint test may provide more information. And compare with the traditional pathological factors, MP/BP test can help to identify a large group of patient with low risk of recurrence.


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