Impact of chemotherapy-induced ovarian failure (CIOF) on disease-free survival (DFS) and overall survival (OS) in young women with early breast cancer (EBC)

Background The addition of adjuvant trastuzumab to chemotherapy has significantly improved outcomes for people with human epidermal growth factor receptor 2 (HER2)-positive, early, potentially curable breast cancer. Twelve months’ trastuzumab, tested in registration trials, was adopted as standard adjuvant treatment in 2006. Subsequently, similar outcomes were demonstrated using 9 weeks of trastuzumab. Shorter durations were therefore tested for non-inferiority. Objectives To establish whether or not 6 months’ adjuvant trastuzumab is non-inferior to 12 months’ in the treatment of HER2-positive early breast cancer using a primary end point of 4-year disease-free survival. Design This was a Phase III randomised controlled non-inferiority trial. Setting The setting was 152 NHS hospitals. Participants A total of 4088 patients with HER2-positive early breast cancer who it was planned would receive both chemotherapy and trastuzumab took part. Intervention Randomisation (1 : 1) to 6 months’ or 12 months’ trastuzumab treatment. Main outcomes The primary end point was disease-free survival. The secondary end points were overall survival, cost-effectiveness and cardiac function during treatment with trastuzumab. Assuming a 4-year disease-free survival rate of 80% with 12 months’ trastuzumab, 4000 patients were required to demonstrate non-inferiority of 6 months’ trastuzumab (5% one-sided significance, 85% power), defining the non-inferiority limit as no worse than 3% below the standard arm. Costs and quality-adjusted life-years were estimated using a within-trial analysis and a lifetime decision-analytic model. Results Between 4 October 2007 and 31 July 2015, 2045 patients were randomised to 12 months’ trastuzumab and 2043 were randomised to 6 months’ trastuzumab. Sixty-nine per cent of patients had ER-positive disease; 90% received anthracyclines (49% with taxanes; 41% without taxanes); 10% received taxanes without anthracyclines; 54% received trastuzumab sequentially after chemotherapy; and 85% received adjuvant chemotherapy (58% were node negative). At 6.1 years’ median follow-up, with 389 (10%) deaths and 566 (14%) disease-free survival events, the 4-year disease-free survival rates for the 4088 patients were 89.5% (95% confidence interval 88.1% to 90.8%) in the 6-month group and 90.3% (95% confidence interval 88.9% to 91.5%) in the 12-month group (hazard ratio 1.10, 90% confidence interval 0.96 to 1.26; non-inferiority p = 0.01), demonstrating non-inferiority of 6 months’ trastuzumab. Congruent results were found for overall survival (non-inferiority p = 0.0003) and landmark analyses 6 months from starting trastuzumab [non-inferiority p = 0.03 (disease-free-survival) and p = 0.006 (overall survival)]. Six months’ trastuzumab resulted in fewer patients reporting adverse events of severe grade [365/1929 (19%) vs. 460/1935 (24%) for 12-month patients; p = 0.0003] or stopping early because of cardiotoxicity [61/1977 (3%) vs. 146/1941 (8%) for 12-month patients; p < 0.0001]. Health economic analysis showed that 6 months’ trastuzumab resulted in significantly lower lifetime costs than and similar lifetime quality-adjusted life-years to 12 months’ trastuzumab, and thus there is a high probability that 6 months’ trastuzumab is cost-effective compared with 12 months’ trastuzumab. Patient-reported experiences in the trial highlighted fatigue and aches and pains most frequently. Limitations The type of chemotherapy and timing of trastuzumab changed during the recruitment phase of the study as standard practice altered. Conclusions PERSEPHONE demonstrated that, in the treatment of HER2-positive early breast cancer, 6 months’ adjuvant trastuzumab is non-inferior to 12 months’. Six months’ treatment resulted in significantly less cardiac toxicity and fewer severe adverse events. Future work Ongoing translational work investigates patient and tumour genetic determinants of toxicity, and trastuzumab efficacy. An individual patient data meta-analysis with PHARE and other trastuzumab duration trials is planned. Trial registration Current Controlled Trials ISRCTN52968807, EudraCT 2006-007018-39 and ClinicalTrials.gov NCT00712140. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 40. See the NIHR Journals Library website for further project information.

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Evaluation of disease-free survival (DFS) as a surrogate for overall survival (OS) in the adjuvant therapy of HER2-positive early breast cancer (EBC) calls for individual-patient data (IPD)

The Breast ◽

10.1016/s0960-9776(17)30113-3 ◽

2017 ◽

Vol 32 ◽

pp. S26

Author(s):

E. Saad ◽

S. Delaloge ◽

D. Mavroudis ◽

E. Perez ◽

M. Piccart-Gebhart ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Adjuvant Therapy ◽

Early Breast Cancer ◽

Individual Patient Data ◽

Disease Free Survival ◽

Patient Data ◽

Her2 Positive ◽

Free Survival ◽

Disease Free

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

The International Journal of Biological Markers ◽

10.1177/17246008211011177 ◽

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.

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Neutrophil-lymphocyte index as prognostic factor for overall survival and disease-free survival in breast cancer patients

Revista de Senología y Patología Mamaria ◽

10.1016/j.senol.2020.06.004 ◽

2020 ◽

Vol 33 (4) ◽

pp. 137-144

Author(s):

Guillermo Peralta-Castillo ◽

Antonio Maffuz-Aziz ◽

Mariana Sierra-Murguía ◽

Sergio Rodriguez-Cuevas

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Prognostic Factor ◽

Cancer Patients ◽

Disease Free Survival ◽

Breast Cancer Patients ◽

Free Survival ◽

Disease Free

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Development of prognostic nomograms using institutional data for patients with triple-negative breast cancer

Future Oncology ◽

10.2217/fon-2021-0677 ◽

2021 ◽

Author(s):

Jie-Yu Zhou ◽

Kang-Kang Lu ◽

Wei-Da Fu ◽

Hao Shi ◽

Jun-Wei Gu ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Predictive Accuracy ◽

Area Under The Curve ◽

Disease Free Survival ◽

Discriminative Ability ◽

Free Survival ◽

Disease Free

Background: Triple-negative breast cancer (TNBC) is an aggressive disease. Nomograms can predict prognosis of patients with TNBC. Methods: A total of 745 eligible TNBC patients were recruited and randomly divided into training and validation groups. Endpoints were disease-free survival and overall survival. Concordance index, area under the curve and calibration curves were used to analyze the predictive accuracy and discriminative ability of nomograms. Results: Based on the training cohort, neutrophil-to-lymphocyte ratio, positive lymph nodes, tumor size and tumor-infiltrating lymphocytes were used to construct a nomogram for disease-free survival. In addition, age was added to the overall survival nomogram. Conclusion: The current study developed and validated well-calibrated nomograms for predicting disease-free survival and overall survival in patients with TNBC.

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