scholarly journals Assessing the Clinical Benefit of Systemic Adjuvant Therapies for Early Breast Cancer

2017 ◽  
Vol 77 (10) ◽  
pp. 1079-1087 ◽  
Author(s):  
Volker Möbus ◽  
Susanne Hell ◽  
Marcus Schmidt

AbstractOncologic therapy is currently undergoing significant changes. A number of innovative targeted medications currently in clinical development have raised high expectations. With that in mind, discussions about terms such as “clinical benefit” and “clinical relevance” are highly topical. This also applies to further developments in the field of adjuvant systemic therapies for early-stage breast cancer. As the treatment aim is curative, assessment of the clinical benefit of adjuvant therapies must be largely based on efficacy outcomes. The focus must be on improving disease-free survival rates and lowering the risk of recurrence. Because of the current low mortality rates, statements about overall survival rates are only possible after very long observation periods. Consequently, new drugs in adjuvant therapies should be considered as offering a clinical benefit, if they reduce the risk of recurrence below current low levels of risk. The evidence for established adjuvant therapy standards in early-stage breast cancer can be used as objective criteria for comparison. This review article considers the requirements for clinical benefit of new adjuvant therapies for early breast cancer, based on examples from adjuvant endocrine therapy, adjuvant polychemotherapy and adjuvant anti-HER2 therapy.

2021 ◽  
pp. 172460082110111
Author(s):  
Erika Korobeinikova ◽  
Rasa Ugenskiene ◽  
Ruta Insodaite ◽  
Viktoras Rudzianskas ◽  
Jurgita Gudaitiene ◽  
...  

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.


ESMO Open ◽  
2020 ◽  
Vol 5 (5) ◽  
pp. e000743 ◽  
Author(s):  
Shani Paluch-Shimon ◽  
Nathan I Cherny ◽  
Elisabeth G E de Vries ◽  
Urania Dafni ◽  
Martine J Piccart ◽  
...  

Click here to listen to the PodcastBackgroundThe European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS) is a validated value scale for solid tumour anticancer treatments. Form 1 of the ESMO-MCBS, used to grade therapies with curative intent including adjuvant therapies, has only been evaluated for a limited number of studies. This is the first large-scale field testing in early breast cancer to assess the applicability of the scale to this data set and the reasonableness of derived scores and to identify any shortcomings to be addressed in future modifications of the scale.MethodRepresentative key studies and meta-analyses of the major modalities of adjuvant systemic therapy of breast cancer were identified for each of the major clinical scenarios (HER2-positive, HER2-negative, endocrine-responsive) and were graded with form 1 of the ESMO-MCBS. These generated scores were reviewed by a panel of experts for reasonableness. Shortcomings and issues related to the application of the scale and interpretation of results were identified and critically evaluated.ResultsSixty-five studies were eligible for evaluation: 59 individual studies and 6 meta-analyses. These studies incorporated 101 therapeutic comparisons, 61 of which were scorable. Review of the generated scores indicated that, with few exceptions, they generally reflected contemporary standards of practice. Six shortcomings were identified related to grading based on disease-free survival (DFS), lack of information regarding acute and long-term toxicity and an inability to grade single-arm de-escalation scales.ConclusionsForm 1 of the ESMO-MCBS is a robust tool for the evaluation of the magnitude of benefit studies in early breast cancer. The scale can be further improved by addressing issues related to grading based on DFS, annotating grades with information regarding acute and long-term toxicity and developing an approach to grade single-arm de-escalation studies.


2019 ◽  
Vol 1 (2) ◽  
pp. 115-121
Author(s):  
Renata Faermann ◽  
Jonathan Weidenfeld ◽  
Leonid Chepelev ◽  
Wayne Kendal ◽  
Raman Verma ◽  
...  

Abstract Purpose To determine surgical outcomes and breast cancer disease-free survival outcomes of women with early stage breast cancer with and without use of preoperative breast MRI according to breast tissue density. Methods Women with early stage breast cancer diagnosed from 2004 to 2009 were classified into 2 groups: 1) those with dense and heterogeneously dense breasts (DB); 2) those with nondense breasts (NDB) (scattered fibroglandular and fatty replaced tissue). The 2 groups were reviewed to determine who underwent preoperative MRI. Breast tissue density was determined with mammography according to ACR BI-RADS. Patients were compared according to tumor size, grade, stage, and treatment. Survival analysis was performed using Kaplan-Meier estimates. Results In total, 261 patients with mean follow-up of 85 months (25–133) were included: 156 DB and 105 NDB. Disease-free survival outcomes were better in the DB group in patients with MRI than in those without MRI: patients with MRI had significantly fewer local recurrences (P < 0.016) and metachronous contralateral breast cancers (P < 0.001), but this was not the case in the NDB group. Mastectomies were higher in the DB group with preoperative MRI than in those without MRI (P < 0.01), as it was in the NDB group (P > 0.05). Conclusions Preoperative breast MRI was associated with reduced local recurrence and metachronous contralateral cancers in the DB group, but not in the NDB group; however, the DB patients with MRI had higher mastectomy rates.


2017 ◽  
Vol 19 (1) ◽  
Author(s):  
Jan Poleszczuk ◽  
Kimberly Luddy ◽  
Lu Chen ◽  
Jae K. Lee ◽  
Louis B. Harrison ◽  
...  

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