Can Oncotype DX testing be omitted in invasive breast cancer patients with clinicopathologic factors predicting very high pretest probability of a concordant result?

2020 ◽  
Vol 26 (11) ◽  
pp. 2199-2202
Author(s):  
Sonam Kapadia ◽  
Sai Priyanka Gudiwada ◽  
Amy H. Kaji ◽  
Rowan T. Chlebowski ◽  
Rose Venegas ◽  
...  
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tianli Hui ◽  
Chao Shang ◽  
Liu Yang ◽  
Meiqi Wang ◽  
Ruoyang Li ◽  
...  

AbstractEarly reports indicate that metformin, a clinical drug administered to treat type 2 diabetes mellitus (T2DM), was found to be associated with a better prognosis of cancer. The objective of this study was retrospectively analyzed the effect of metformin on the outcomes of Chinese breast cancer patients with T2DM. A total of 3757 primary invasive breast cancer patients who underwent surgery from January 2010 to December 2013 were enrolled. According to the medication treatment, all the patients were divided as non-diabetes group, metformin group and insulin group. The follow-up data for disease-free survival (DFS) and overall survival (OS) were obtained from 3553 patients (median follow up of 85 months) and estimated with the Kaplan–Meier method followed by a log-rank test. Multivariate Cox proportional hazards regression model was applied. The results showed that there was a significant survival difference among non-diabetes group, metformin group and insulin group, 5-year DFS was 85.8%, 96.1%, 73.0%, and 5-year OS was 87.3%, 97.1%, 73.3% respectively (P < 0.05). Prognostic analysis showed metformin was significantly associated with better DFS and OS. Our results suggested that metformin may have a good effect on the survival of invasive breast cancer patients with T2DM.


2007 ◽  
Vol 29 (1) ◽  
pp. 25-35
Author(s):  
Emiel A. M. Janssen ◽  
Håvard Søiland ◽  
Ivar Skaland ◽  
Einar Gudlaugson ◽  
Kjell H. Kjellevold ◽  
...  

Background: The prognostic value of the PI3K/Akt/mTOR pathway and PTEN in invasive breast cancer (IBC) is controversial. Cell proliferation, especially the Mitotic Activity Index (MAI), is strongly prognostic in lymph node-negative (LNneg) invasive breast cancer. However, its prognostic value has not been compared with the value of Akt and PTEN expression. Material and Methods: Prognostic comparison of Her2Neu, p110alpha (PIK3CA), Akt, mTOR, PTEN, MAI and cell-cycle regulators in 125 LNneg patients aged <55 years with cyclophosphamide, methotrexate, and 5-fluorouracil (CMF)-based adjuvant systemic chemotherapy. Results: Twenty-one (17%) patients developed distant metastases = DMs (median follow-up: 134 months). p110alpha correlated (p = 0.01) with pAkt but only in PTEN-negatives; pAkt correlated (p = 0.02) with mTOR. PTEN-negativity correlated with high MAI, high grade and ER-negativity (p = 0.009). The MAI was the strongest prognosticator (Hazard Ratio = HR = 2.9, p = 0.01). Her2Neu/p110α/Akt/mTOR features have no additional prognostic value to the MAI. PTEN had additional value but only in MAI < 3 (39/125 = 31%; 8% DMs). 19/39 = 49% of the MAI < 3 patients have combined MAI < 3 / PTEN+ with 0% DMs, contrasting 15% DMs in MAI < 3 / PTEN− (p = 0.03). Conclusions: In T1−3N0M0 adjuvant CMF-treated breast cancer patients aged <55 years, MAI was the strongest survival predictor. The PI3K/Akt/mTOR pathway and cell-cycle regulator characteristics had no additional prognostic value, but PTEN has. Patients with combined MAI < 3 & PTEN-positivity had 100% survival. The small subgroup of MAI < 3 patients that died were PTEN-negative.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12548-e12548
Author(s):  
Xianghou Xia ◽  
Wenjuan Yin ◽  
Jiefei Mao ◽  
Jiejie Hu ◽  
Dehong Zou ◽  
...  

e12548 Background: Pyroptosis is a type of inflammatory cell death mediated by gasdermins. Pyroptosis is critical for macrophage against pathogen infection. Recently growing evidences show that pyroptosis may affect development and progression of many cancers. We aim to explore the expression and related function of pyroptosis executioner Gasdermin D (GSDMD) in breast cancer. Methods: We investigated the expression level of GSDMD using TNM plotter and Breast Cancer landscape proteome with TCGA, GTEx and TARGET databases, and the prognostic value of GSDMD in invasive breast cancer using Kaplan-Meier plotter with TCGA, GEO and EGA databases. The treatment response prediction values of GSDMD in invasive breast were calculated using ROC-plotter with GEO database. Further validation of the prognostic value and chemotherapy response prediction value of GSDMD were carried out with immunohistochemical staining on tissues from 165 cases of breast cancer patients receiving neoadjuvant chemotherapy in our cancer center. Results: TNM plotter and breast cancer landscape proteome portal analysis shows that overall expression level of GSDMD in invasive breast cancer tissue is 1.67 folds higher than it is in breast normal tissues ( p=1.05*e-06). Expression of GSDMD in LuminalB subtype (p=0.019) and Her2 subtype(p=0.04) is significantly higher than it is in TNBC subtype. Calculations with Kaplan-Meier plotter show expression of GSDMD is negatively correlated with overall survival(OS), HR=0.61(0.4−0.95) p=0.027 and relapse free survival (RFS), HR =0.65(0.58−0.63), p=8.7*e-14 and distant metastasis free survival (DMFS) HR =0.75(0.61−0.91), p=0.0038 in breast cancer patients. ROC-plotter calculations show high GSDMD expression is a powerful endocrine therapy (AUC=0.731 p=6*e-09 ) and chemotherapy response (AUC=0.64 p=8*e-05 ) predictor based on 5-year RFS in overall breast cancer patients. Our IHC staining analysis shows consistent prognostic and chemotherapy prediction value of GSDMD expression in TNBC patients. Conclusions: In conclusion, our findings suggest that high expression of GSDMD is positively correlated with prognosis and therapeutic response in breast cancer. GSDMD is a promising prognostic marker and therapeutic response predictor in invasive breast cancer.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12520-e12520
Author(s):  
Keerthi Tamragouri ◽  
Ethan M. Ritz ◽  
Ruta D. Rao ◽  
Cristina O'Donoghue

e12520 Background: Oncotype Dx (ODX) is a commercial diagnostic test primarily used to predict the likely benefit from chemotherapy in ER+, HER2-, and node negative breast cancer. The prognostic value (recurrence risk) has also been demonstrated to apply to early stage lymph node positive (LN+) disease in a number of retrospective and prospective studies. The ongoing RxPONDER trial aims to clarify the predictive value of RS in LN+ population. In light of the initial results, we analyzed the practice patterns and outcomes for HR+/Her2 -/node positive breast cancer patients receiving ODX testing in the years from 2010-2017 with RS 14-25 in a retrospective observational study of the NCDB. Methods: Women with HR+/Her2 -/node positive breast cancer receiving ODX testing from 2010-2017 were identified in the NCDB using TAILORx and RxPONDER patients’ inclusion criteria: ages 18-75, 6-50mm invasive tumors, N1, M0, ER+/HER2 -. The impact of ODX results in the high-intermediate range (14-25) and other clinico-pathologic variables on the receipt of chemotherapy were compared. Additionally, we examined the impact of chemotherapy on overall survival (OS). Frequencies, Kaplain-Meier analysis, and changepoint analysis using the Contal and O’Quigley method were utilized. Results: There were 109,652 T1-2 and N1 patients of whom 32,506 (29.6%) received ODX testing. 13,461 (41.4%%) women had scores in the high-intermediate (14-25) range. The majority tended to have only 1 LN involved (1LN: 77.2%, 2LNs: 17.5%, 3LNs: 5.3%), had a mean age of 57.8y, were Caucasian (86.4%), and were preferentially tested at academic or comprehensive community cancer programs (79.2%). 6,610 (49.3%) patients were recommended chemotherapy, the median ODX score for all women who were recommended chemotherapy was 20 compared to 17 for those whom chemotherapy was not recommended. 5,068 (76.7%) women had documentation of receiving chemotherapy which correlated with improved OS regardless of age. Conclusions: In the group of women with HR+/Her2 -/node positive breast cancer, clinicians appear to utilize ODX testing in less than one-third of patients, possibly finding RS to be most useful in guiding adjuvant therapy recommendations when only 1LN is involved. Both the recommendation and receipt of chemotherapy correlated linearly with increasing RS, as expected based on the current NCCN guideline recommendations. We identified an OS benefit when chemotherapy was administered, regardless of patient age. Long-term follow-up in the RxPONDER trial will likely continue to clarify the predictive value of RS < 25 in the ER+/HER2-/node positive breast cancer population.


Author(s):  
Nicholas M. Gunn ◽  
Mark Bachman ◽  
Edward L. Nelson ◽  
G.-P. Li

Rationally designed, individualized therapeutic strategies have long been a desired objective for breast cancer patients and clinicians as an estimated 178,480 new cases of invasive breast cancer will be diagnosed among women in the United States this year and over 40,000 women are expected to die from the disease. [1] The increasing appreciation of breast tumor cellular heterogeneity raises fundamental questions as to the relative contributions of cellular subsets to the biologic behavior of an individual patient’s tumor. [2] As such, it has become increasingly clear that in many cases, an individualized strategy for the treatment of breast cancer would be of great benefit, and that the ability to isolate relevant cellular subsets from the main tumor population is one of the critical limits to accomplishing this goal.


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