scholarly journals Evaluation of pathological complete response as surrogate endpoint in neoadjuvant randomised clinical trials of early stage breast cancer: systematic review and meta-analysis

BMJ ◽  
2021 ◽  
pp. e066381
Author(s):  
Fabio Conforti ◽  
Laura Pala ◽  
Isabella Sala ◽  
Chiara Oriecuia ◽  
Tommaso De Pas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Relative Risk ◽  
Pathological Complete Response ◽  
Early Stage ◽  
Disease Free Survival ◽  
Complete Response ◽  
Early Stage Breast Cancer ◽  
Free Survival ◽  
Disease Free

Abstract Objective To evaluate pathological complete response as a surrogate endpoint for disease-free survival and overall survival in regulatory neoadjuvant trials of early stage breast cancer. Design Systematic review and meta-analysis. Data sources Medline, Embase, and Scopus to 1 December 2020. Eligibility criteria for study selection Randomised clinical trials that tested neoadjuvant chemotherapy given alone or combined with other treatments, including anti-human epidermal growth factor 2 (anti-HER2) drugs, targeted treatments, antivascular agents, bisphosphonates, and immune checkpoint inhibitors. Data extraction and synthesis Trial level associations between the surrogate endpoint pathological complete response and disease-free survival and overall survival. Methods A weighted regression analysis was performed on log transformed treatment effect estimates (hazard ratio for disease-free survival and overall survival and relative risk for pathological complete response), and the coefficient of determination (R 2 ) was used to quantify the association. The secondary objective was to explore heterogeneity of results in preplanned subgroups analysis, stratifying trials according treatment type in the experimental arm, definition used for pathological complete response (breast and lymph nodes v breast only), and biological features of the disease (HER2 positive or triple negative breast cancer). The surrogate threshold effect was also evaluated, indicating the minimum value of the relative risk for pathological complete response necessary to confidently predict a non-null effect on hazard ratio for disease-free survival or overall survival. Results 54 randomised clinical trials comprising a total of 32 611 patients were included in the analysis. A weak association was observed between the log(relative risk) for pathological complete response and log(hazard ratio) for both disease-free survival (R 2 =0.14, 95% confidence interval 0.00 to 0.29) and overall survival (R 2 =0.08, 0.00 to 0.22). Similar results were found across all subgroups evaluated, independently of the definition used for pathological complete response, treatment type in the experimental arm, and biological features of the disease. The surrogate threshold effect was 5.19 for disease-free survival but was not estimable for overall survival. Consistent results were confirmed in three sensitivity analyses: excluding small trials (<200 patients enrolled), excluding trials with short median follow-up (<24 months), and replacing the relative risk for pathological complete response with the absolute difference of pathological complete response rates between treatment arms. Conclusion A lack of surrogacy of pathological complete response was identified at trial level for both disease-free survival and overall survival. The findings suggest that pathological complete response should not be used as primary endpoint in regulatory neoadjuvant trials of early stage breast cancer.

scholarly journals The role of functional polymorphisms in oxidative stress-related genes on early-stage breast cancer survival

2021 ◽  
pp. 172460082110111
Author(s):  
Erika Korobeinikova ◽  
Rasa Ugenskiene ◽  
Ruta Insodaite ◽  
Viktoras Rudzianskas ◽  
Jurgita Gudaitiene ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Single Nucleotide Polymorphisms ◽  
Early Stage ◽  
Disease Free Survival ◽  
Early Stage Breast Cancer ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Free Survival ◽  
Disease Free

Background: Genetic variations in oxidative stress-related genes may alter the coded protein level and impact the pathogenesis of breast cancer. Methods: The current study investigated the associations of functional single nucleotide polymorphisms in the NFE2L2, HMOX1, P21, TXNRD2, and ATF3 genes with the early-stage breast cancer clinicopathological characteristics and disease-free survival, metastasis-free survival, and overall survival. A total of 202 Eastern European (Lithuanian) women with primary I–II stage breast cancer were involved. Genotyping of the single nucleotide polymorphisms was performed using TaqMan single nucleotide polymorphisms genotyping assays. Results: The CA+AA genotypes of P21 rs1801270 were significantly less frequent in patients with lymph node metastasis and larger tumor size ( P=0.041 and P=0.022, respectively). The TT genotype in ATF3 rs3125289 had significantly lower risk of estrogen receptor (ER), progesterone receptor (PR) negative, and human epidermal growth factor receptor 2 (HER2) positive status ( P=0.023, P=0.046, and P=0.040, respectively). In both, univariate and multivariate Cox analysis, TXNRD2 rs1139793 GG genotype vs. GA+AA was a negative prognostic factor for disease-free survival (multivariate hazard ratio (HR) 2.248; P=0.025) and overall survival (multivariate HR 2.248; P=0.029). The ATF3 rs11119982 CC genotype in the genotype model was a negative prognostic factor for disease-free survival (multivariate HR 5.878; P=0.006), metastasis-free survival (multivariate HR 4.759; P=0.018), and overall survival (multivariate HR 3.280; P=0.048). Conclusion: Our findings suggest that P21 rs1801270 is associated with lymph node metastasis and larger tumor size, and ATF3 rs3125289 is associated with ER, PR, and HER2 status. Two potential, novel, early-stage breast cancer survival biomarkers, TXNRD2 rs1139793 and ATF3 rs11119982, were detected. Further investigations are needed to confirm the results of the current study.

scholarly journals Pre-treatment Haemoglobin Concentration is a Prognostic Factor in Patients with Early-stage Breast Cancer

2005 ◽  
Vol 33 (3) ◽  
pp. 319-328 ◽  
Author(s):  
EG Kandemir ◽  
A Mayadagli ◽  
O Turken ◽  
M Yaylaci ◽  
A Ozturk
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Prognostic Factor ◽  
Early Stage ◽  
Haemoglobin Concentration ◽  
Disease Free Survival ◽  
Early Stage Breast Cancer ◽  
Free Survival ◽  
Pre Treatment ◽  
Disease Free

We investigated the prevalence of anaemia (haemoglobin concentration < 12 g/dl) in 336 women with early-stage breast cancer and its association with other known prognostic factors. The median follow-up period was 60.5 months (range 9-123 months). Seventy-nine women (23.5%) had a low pre-treatment haemoglobin concentration, but anaemia was not correlated with age, tumour size, nodal status, histological grade or hormone receptor status. Univariate analysis revealed that disease-free survival and overall survival were shorter in patients with anaemia at the time of diagnosis than in patients with normal haemoglobin concentrations. Anaemia remained a significant prognostic factor for disease-free survival and overall survival in the multivariate analysis (relative risk, 1.884 and 1.785, respectively). These results suggest that pre-treatment haemoglobin concentration is an independent prognostic factor in patients with early-stage breast cancer.

scholarly journals Clinical outcomes and surgical preferences for breast-conserving surgery and mastectomy: a propensity score-matched analysis

2019 ◽  
Vol 13 (3) ◽  
pp. 95-100
Author(s):  
Mawin Vongsaisuwon ◽  
Krit Pongpirul ◽  
Kris Chatamara
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Propensity Score ◽  
Early Stage ◽  
Disease Free Survival ◽  
Breast Conserving Surgery ◽  
Early Stage Breast Cancer ◽  
Free Survival ◽  
Disease Free ◽  
Selection Of

Abstract Background While numerous randomized controlled trials have demonstrated long-term survival rates for patients with early-stage breast cancer treated with breast-conserving surgery (BCS) comparable to mastectomy, the latter remains the most prevalent surgical option to treat early-stage breast cancer in Thailand. Objectives To investigate the potential determinants affecting the decision on selecting BCS or mastectomy for the treatment of early-stage breast cancer and to compare the disease-free survival and overall survival between the treatments using a propensity score-matched analysis. Methods Patients diagnosed nonmetastatic breast cancer at the Queen Sirikit Breast Cancer Center from January 2006 to December 2015, were retrospectively identified and grouped intro patients who received BCS or mastectomy. After propensity score matching, 356 BCS and 209 mastectomy patients were identified, and statistical analysis was conducted to determine treatment selection factors and compare disease-free and overall survival. Results Disease-free survival and overall survival in months comparing BCS and mastectomy were not statistically different with P values of 0.11 and 0.77, respectively. Determinants of treatment selection found that younger age, surgeon preference, smaller tumor size, and lower tumor grade were statistically significant factors in the selection of BCS over mastectomy. The majority of surgeons had a preference for one treatment over the other (P < 0.001). Conclusion The outcome of BCS is comparable to mastectomy in early-stage breast cancer patients. Key determinants affecting the selection of treatment were identified to be patient age, characteristics of the tumor, and surgeon’s preference.

Overview of randomized perioperative polychemotherapy trials in women with early-stage breast cancer.

1997 ◽  
Vol 15 (7) ◽  
pp. 2526-2535 ◽  
Author(s):  
P C Clahsen ◽  
C J van de Velde ◽  
A Goldhirsch ◽  
J Rossbach ◽  
M R Sertoli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Clinical Trials ◽  
Early Stage ◽  
Disease Free Survival ◽  
Early Stage Breast Cancer ◽  
Free Survival ◽  
Node Negative ◽  
Disease Free

PURPOSE To determine whether perioperative polychemotherapy (PeCT) can significantly prolong the overall survival of women with early-stage breast cancer. METHODS A meta-analysis that used updated individual patient data from all available randomized trials of PeCT, both published and unpublished, was conducted. Data on 6,093 patients (1,124 deaths and 1,912 recurrences) from five clinical trials were available (median follow-up duration, 5.3 years; maximum, 11.3 years). RESULTS No significant effect of PeCT on overall survival was observed. However, patients who received PeCT had a significantly longer disease-free survival (hazards ratio [HR], 0.89; 95% confidence interval [CI], 0.82 to 0.98; P = .02). Time to local recurrence was significantly prolonged in the PeCT arm (HR, 0.68; 95% CI, 0.58 to 0.80; P < .0001). Likewise, there was a borderline significant difference in favor of PeCT in terms of time to distant metastases (HR, 0.90; 95% CI, 0.81 to 1.00; P = .05). Subgroup analyses suggest that node-negative women benefited the most from treatment. CONCLUSION At present, there is no evidence that PeCT is able to prolong overall survival in patients with early-stage breast cancer; however, further follow-up evaluation is required. PeCT significantly prolongs disease-free survival, especially in node-negative women, which emphasizes once more the need for clinical trials in this subgroup.

scholarly journals Neoadjuvant radiotherapy of early-stage breast cancer and long-term disease-free survival

2017 ◽  
Vol 19 (1) ◽  
Author(s):  
Jan Poleszczuk ◽  
Kimberly Luddy ◽  
Lu Chen ◽  
Jae K. Lee ◽  
Louis B. Harrison ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Disease Free Survival ◽  
Early Stage Breast Cancer ◽  
Neoadjuvant Radiotherapy ◽  
Free Survival ◽  
Disease Free

PS02.115: PERIOPERATIVE CHEMOTHERAPY VERSUS NEOADJUVANT CHEMORADIATION FOR PATIENTS WITH ADENOCARCINOMA OF THE DISTAL OESOPHAGUS IN AUSTRIA

2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 153-153
Author(s):  
Oliver Koch ◽  
Andreas Tschoner ◽  
Richard Partl ◽  
Alexander Perathoner ◽  
Philipp Gehwolf ◽  
...  
Keyword(s):  
Overall Survival ◽  
Pathological Complete Response ◽  
Disease Free Survival ◽  
Complete Response ◽  
Neoadjuvant Chemoradiation ◽  
Type I ◽  
Perioperative Chemotherapy ◽  
Free Survival ◽  
One Year ◽  
Disease Free

Abstract Background The aim of this study is to compare the outcome of patients with adenocarcinoma of the distal oesophagus (AEG Type I) treated with perioperative chemotherapy or neoadjuvant chemoradiation. Methods A retrospective analysis of eligible patients from four Austrian centers was conducted. All patients with AEG type I treated between January 2007 and October 2017 with chemotherapy (EOX-protocol) or chemoradiation (CROSS-protocol, or 5-FU/Cisplatin), followed by oesophagectomy were included in the study. Primary outcomes overall survival, and disease free survival as well as secondary outcomes, achievement of pathological complete response pCR (ypT0N0M0) or downstaging of T- or N-stage were analyzed. Primary outcomes were calculated by the Kaplan-Meier-method. Results Data of 117 patients were analyzed, 59 received chemoradiation (50/59 CROSS and 9/59 5-FU/Cisplatin) and 58 patients received perioperative chemotherapy (EOX). Complete data at time of submission were available in 40 patients in the chemoradiation group and in 37 patients in the chemotherapy group. The median follow-up time in the chemoradiation group was 13,0 months (CI 95%: 11,0–15,0) and in the chemotherapy group 45,0 months (CI 95%: 28,8–61,3). Overall survival rate in the EOX group after ½, 1, 3 and 5 years was 92%, 83%, 63% and 34%. So far long term data are not available after chemoradiation, after ½ year overall survival was 84% and after one year 60%. Disease free survival rate in the EOX group after ½, 1, 3 and 5 years was 91%, 81%, 54% and 32%, in the chemoradiation group after ½ and one year 80% and 50%. A significant difference was found in the pathological complete response (pCR) rate, it was achieved in 19% of patients after chemoradiation and in 3% after chemotherapy (P = 0000). Conclusion Concerning major response of the primary tumor there are clear advantages for chemoradiation. In regards to systemic tumor control there seems a tendency in favor for chemotherapy. Disclosure All authors have declared no conflicts of interest.

Sign in / Sign up

Export Citation Format

Share Document