Adjuvant chemotherapy in small node-negative triple-negative breast cancer (TNBC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 536-536 ◽  
Author(s):  
Tessa Gerjanne Steenbruggen ◽  
Mette S. Van Ramshorst ◽  
Erik van Werkhoven ◽  
Vincent O. Dezentjé ◽  
Sabine Siesling ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Cox Regression ◽  
Large Population ◽  
Absolute Difference ◽  
Cancer Specific Survival ◽  
Long Term Outcome ◽  
Node Negative ◽  
Netherlands Cancer Registry ◽  
Grade 3

536 Background: International guidelines differ in their recommendation for adjuvant chemotherapy in small node negative TNBC. We evaluated associations of chemotherapy with long-term outcome in a large population-based TNBC cohort. Methods: All patients diagnosed with pT1N0M0 TNBC between 2005 and 2015 were identified from the Netherlands Cancer Registry. Patient, tumor and therapy characteristics were recorded. Date and cause of death were obtained from Statistics Netherlands. We used multivariable cox regression models to evaluate associations of chemotherapy with overall survival (OS) and breast-cancer specific survival (BCSS), adjusted for baseline characteristics. Subgroup analyses were performed by tumor size and grade. Results: We identified 4393 patients: 284 with T1a, 924 with T1b, and 3185 with T1c tumors. Chemotherapy was administered in 53% of patients: 6% with T1a, 17% with T1b and 67% with T1c. Chemotherapy use increased over time and varied by geographic region. Patients receiving chemotherapy were younger, had larger tumors, higher tumor grade, and more often isolated tumor cells (itc) in the lymph nodes. At a median follow-up of 7 years (IQR 5-10 years), 611 patients had died, of whom 287 due to breast cancer. Chemotherapy was associated with improved OS in the whole group (adjusted hazard ratio [aHR] 0.55; 95% CI 0.44–0.69), in the pT1c subgroup (aHR 0.53, 95% CI 0.41-0.67), and in grade 3 tumors (aHR 0.50, 95% CI 0.39-0.65). Associations were not significant for pT1ab or grade 1-2 tumors (table). Findings for BCSS were in line with OS results (table). To illustrate the absolute difference we estimated 10-year OS and BCSS for a 60-year old woman with a pT1cN0(itc+) grade 3 TNBC. The predicted 10-year OS was 67% with chemotherapy and 49% without; predictions for 10-year BCSS were 80% and 66%, respectively. Conclusions: Adjuvant chemotherapy is associated with higher OS and BCSS in small node negative TNBC. Benefit is most evident in grade 3 tumors and tumors > 1cm and not evident in tumors ≤1cm and grade 1-2.[Table: see text]

scholarly journals Four Cycles of Docetaxel-Cyclophosphamide versus Anthracycline-Taxane as Adjuvant Chemotherapy for HER2-Negative, Axillary Lymph Node Negative Breast Cancer: A Real-World Comparison of Alberta Patients Treated 2008–2012

2021 ◽  
Vol 28 (2) ◽  
pp. 1137-1142
Author(s):  
Malek Hannouf ◽  
Atul Batra ◽  
Sasha Lupichuk
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Adjuvant Chemotherapy ◽  
Axillary Lymph Node ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Axillary Lymph ◽  
Cancer Specific Survival ◽  
Node Negative ◽  
Significant Difference

Uncertainty exists around the need to include an anthracycline if taxane-based adjuvant chemotherapy is being used for human epidermal growth factor receptor-2 (HER2) negative and axillary lymph node negative (LNN) breast cancer. We identified all patients who were diagnosed with HER2-negative, LNN breast cancer treated with docetaxel-cyclophosphamide for four cycles (DC4) or an anthracycline-taxane (AT) regimen following surgical resection in Alberta from 2008 through 2012. We used propensity score methods to match each patient treated with AT to up to four patients treated with DC4 on potentially confounding clinicopathologic and treatment variables. We compared the 10-year invasive disease free survival (iDFS), breast cancer specific-survival (BCSS) and overall survival (OS) and assessed the effect of the type of adjuvant chemotherapy on these outcomes using Cox regression. Of the 726 eligible patients, 657 (90.5%) were treated with DC4 and 69 (9.5%) were treated with AT. Matching created a group of 202 women treated with DC4 and eliminated differences in clinicopathologic and treatment factors. There was no statistically significant difference for the treatment effects of matched DC4 patients compared to the AT patients on iDFS (75.7% vs. 76.8%, p = 0.75; hazard ratio (HR) = 1.05, 95% CI = 0.65 to 1.8), BCSS (88.1% vs. 87%, p = 0.8; HR = 0.91, 95% CI = 0.42 to 1.9), or OS (87.1% vs. 86.9%, p= 0.96; HR = 0.98, 95% CI = 0.46 to 2.1). Four cycles of DC as compared with an AT regimen yielded similar 10-year iDFS, BCSS and OS amongst patients with HER2-negative, LNN breast cancer.

scholarly journals Concurrent versus sequential use of trastuzumab and chemotherapy in early HER2+ breast cancer

2020 ◽  
Author(s):  
Gwen M. H. E. Dackus ◽  
Katarzyna Jóźwiak ◽  
Elsken van der Wall ◽  
Paul J. van Diest ◽  
Michael Hauptmann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Cox Regression ◽  
Population Based ◽  
Optimal Timing ◽  
Her2 Positive ◽  
Long Term Outcome ◽  
Her2 Breast Cancer ◽  
Netherlands Cancer Registry ◽  
Significant Difference

Abstract Purpose The addition of trastuzumab to adjuvant chemotherapy has improved the outcome of human epidermal growth-factor receptor 2 (HER2)-positive breast cancer. Uncertainty remains about the optimal timing of trastuzumab treatment. Therefore, we compared long-term outcome after concurrent versus sequential treatment, in a population-based setting, using data from the nationwide Netherlands Cancer Registry. Methods We identified 1843 women diagnosed in The Netherlands from January 1st 2005 until January 1st 2008 with primary, HER2-positive, T1-4NanyM0 breast cancer who received adjuvant chemotherapy and trastuzumab. Kaplan–Meier survival estimates and Cox regression were used to compare recurrence-free survival (RFS) and overall survival (OS) between women who received trastuzumab concurrently with versus sequentially after chemotherapy. Hazard ratios (HR) were adjusted for age, year of diagnosis, grade, pathological T-stage, number of positive lymph nodes, ER-status, PR-status, socio-economic status, radiotherapy, hormonal therapy, ovarian ablation, and type of chemotherapy. Results After a median follow-up of 8.2 years, RFS events had occurred in 224 out of 1235 (18.1%) concurrently treated women and 129 out of 608 (21.2%) sequentially treated women (adjusted-HR 0.91; 95% confidence interval (CI) 0.67–1.24; P = 0.580). Deaths occurred in 182/1235 (14.7%) concurrently treated women and 104/608 (17.1%) sequentially treated women (adjusted-HR 0.92; 95% CI 0.65–1.29; P = 0.635). Conclusions The results of this population-based study are consistent with earlier randomized trials, demonstrating a non-significant difference in outcome for concurrently treated women compared to those who were treated sequentially, suggesting both options are justified.

scholarly journals The Presence of Small Nerve Fibers in the Tumor Microenvironment as Predictive Biomarker of Oncological Outcome Following Partial Hepatectomy for Intrahepatic Cholangiocarcinoma

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3661
Author(s):  
Jan Bednarsch ◽  
Xiuxiang Tan ◽  
Zoltan Czigany ◽  
Dong Liu ◽  
Sven Arke Lang ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Intrahepatic Cholangiocarcinoma ◽  
Cox Regression ◽  
Oncological Outcome ◽  
Nerve Fibers ◽  
Nodal Metastases ◽  
Cancer Specific Survival ◽  
Curative Intent ◽  
Term Outcome ◽  
Long Term Outcome

The oncological role of the density of nerve fibers (NFs) in the tumor microenvironment (TME) in intrahepatic cholangiocarcinoma (iCCA) remains to be determined. Therefore, data of 95 iCCA patients who underwent hepatectomy between 2010 and 2019 was analyzed regarding NFs and long-term outcome. Extensive group comparisons were carried out and the association of cancer-specific survival (CSS) and recurrence-free survival (RFS) with NFs were assessed using Cox regression models. Patients with iCCA and NFs showed a median CSS of 51 months (5-year-CSS = 47%) compared to 27 months (5-year-CSS = 21%) in patients without NFs (p = 0.043 log rank). Further, NFs (hazard ratio (HR) = 0.39, p = 0.002) and N-category (HR = 2.36, p = 0.010) were identified as independent predictors of CSS. Patients with NFs and without nodal metastases displayed a mean CSS of 89 months (5-year-CSS = 62%), while patients without NFs or with nodal metastases but not both showed a median CCS of 27 months (5-year-CSS = 25%) and patients with both positive lymph nodes and without NFs showed a median CCS of 10 months (5-year-CSS = 0%, p = 0.001 log rank). NFs in the TME are, therefore, a novel and important prognostic biomarker in iCCA patients. NFs alone and in combination with nodal status is suitable to identify iCCA patients at risk of poor oncological outcomes following curative-intent surgery.

scholarly journals Explainable machine learning can outperform Cox regression predictions and provide insights in breast cancer survival

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Arturo Moncada-Torres ◽  
Marissa C. van Maaren ◽  
Mathijs P. Hendriks ◽  
Sabine Siesling ◽  
Gijs Geleijnse
Keyword(s):  
Breast Cancer ◽  
Machine Learning ◽  
Explicit Knowledge ◽  
Cox Regression ◽  
Metastatic Breast ◽  
Gradient Boosting ◽  
Support Vector ◽  
Netherlands Cancer Registry ◽  
Extreme Gradient Boosting ◽  
The Impact

AbstractCox Proportional Hazards (CPH) analysis is the standard for survival analysis in oncology. Recently, several machine learning (ML) techniques have been adapted for this task. Although they have shown to yield results at least as good as classical methods, they are often disregarded because of their lack of transparency and little to no explainability, which are key for their adoption in clinical settings. In this paper, we used data from the Netherlands Cancer Registry of 36,658 non-metastatic breast cancer patients to compare the performance of CPH with ML techniques (Random Survival Forests, Survival Support Vector Machines, and Extreme Gradient Boosting [XGB]) in predicting survival using the $$c$$ c -index. We demonstrated that in our dataset, ML-based models can perform at least as good as the classical CPH regression ($$c$$ c -index $$\sim \,0.63$$ ∼ 0.63 ), and in the case of XGB even better ($$c$$ c -index $$\sim 0.73$$ ∼ 0.73 ). Furthermore, we used Shapley Additive Explanation (SHAP) values to explain the models’ predictions. We concluded that the difference in performance can be attributed to XGB’s ability to model nonlinearities and complex interactions. We also investigated the impact of specific features on the models’ predictions as well as their corresponding insights. Lastly, we showed that explainable ML can generate explicit knowledge of how models make their predictions, which is crucial in increasing the trust and adoption of innovative ML techniques in oncology and healthcare overall.

Cost Effectiveness of Molecular Profiling for Adjuvant Decision Making in Patients With Node-Negative Breast Cancer

2014 ◽  
Vol 32 (31) ◽  
pp. 3513-3519 ◽  
Author(s):  
Julia Bonastre ◽  
Sophie Marguet ◽  
Beranger Lueza ◽  
Stefan Michiels ◽  
Suzette Delaloge ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Decision Making ◽  
Cost Effectiveness ◽  
Adjuvant Chemotherapy ◽  
Cost Effective ◽  
Gene Signature ◽  
Node Negative ◽  
Node Negative Breast Cancer ◽  
Life Years ◽  
Er Positive

Purpose To conduct an economic evaluation of the 70-gene signature used to guide adjuvant chemotherapy decision making both in patients with node-negative breast cancer (NNBC) and in the subgroup of estrogen receptor (ER) –positive patients. Patients and Methods We used a mixed approach combining patient-level data from a multicenter validation study of the 70-gene signature (untreated patients) and secondary sources for chemotherapy efficacy, unit costs, and utility values. Three strategies on which to base the decision to administer adjuvant chemotherapy were compared: the 70-gene signature, Adjuvant! Online, and chemotherapy in all patients. In the base-case analysis, costs from the French National Insurance Scheme, life-years (LYs), and quality-adjusted life-years (QALYs) were computed for the three strategies over a 10-year period. Cost-effectiveness acceptability curves using the net monetary benefit were computed, combining bootstrap and probabilistic sensitivity analyses. Results The mean differences in LYs and QALYs were similar between the three strategies. The 70-gene signature strategy was associated with a higher cost, with a mean difference of €2,037 (range, €1,472 to €2,515) compared with Adjuvant! Online and of €657 (95% CI, −€642 to €3,130) compared with systematic chemotherapy. For a €50,000 per QALY willingness-to-pay threshold, the probability of being the most cost-effective strategy was 92% (76% in ER-positive patients) for the Adjuvant! Online strategy, 6% (4% in ER-positive patients) for the systematic chemotherapy strategy, and 2% (20% in ER-positive patients) for the 70-gene strategy. Conclusion Optimizing adjuvant chemotherapy decision making based on the 70-gene signature is unlikely to be cost effective in patients with NNBC.

scholarly journals Real-World Outcomes of Adjuvant Chemotherapy for Node-Negative and Node-Positive HER2-Positive Breast Cancer

2019 ◽  
Vol 17 (1) ◽  
pp. 47-56 ◽  
Author(s):  
Zachary Veitch ◽  
Omar F. Khan ◽  
Derek Tilley ◽  
Domek Ribnikar ◽  
Xanthoula Kostaras ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Real World ◽  
Her2 Positive ◽  
Node Negative ◽  
Node Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

scholarly journals Tumor-Biological Factors Upa and PAI-1 as Stratification Criteria of a Multicenter Adjuvant Chemotherapy Trial in Node-Negative Breast Cancer

2000 ◽  
Vol 15 (1) ◽  
pp. 73-78 ◽  
Author(s):  
A. Prechtl ◽  
N. Harbeck ◽  
C. Thomssen ◽  
C. Meisner ◽  
M. Braun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Plasminogen Activator ◽  
Systemic Therapy ◽  
Axillary Node ◽  
Breast Cancer Patients ◽  
Node Negative ◽  
Node Negative Breast Cancer ◽  
Pai 1

In axillary node-negative primary breast cancer, 70% of the patients will be cured by locoregional treatment alone. Therefore, adjuvant systemic therapy is only needed for those 30% of node-negative patients who will relapse after primary therapy and eventually die of metastases. Traditional histomorphological and clinical factors do not provide sufficient information to allow accurate risk group assessment in order to identify node-negative patients who might benefit from adjuvant systemic therapy. In the last decade various groups have reported a strong and statistically independent prognostic impact of the serine protease uPA (urokinase-type plasminogen activator) and its inhibitor PAI-1 (plasminogen activator inhibitor type 1) in node-negative breast cancer patients. Based on these data, a prospective multicenter therapy trial in node-negative breast cancer patients was started in Germany in June 1993, supported by the German Research Association (DFG). Axillary node-negative breast cancer patients with high levels of either or both proteolytic factors in the tumor tissue were randomized to adjuvant CMF chemotherapy versus observation only. Recruitment was continued until the end of 1998, by which time 684 patients had been enrolled. Since then, patients have been followed up in order to assess the value of uPA and PAI-1 determination as an adequate selection criterion for adjuvant chemotherapy in node-negative breast cancer patients. This paper reports on the rationale and design of this prospective multicenter clinical trial, which may have an impact on future policies in prognosis-oriented treatment strategies.

Frequency of First Metastatic Events in Breast Cancer: Implications for Sequencing of Systemic and Local-Regional Treatment

1999 ◽  
Vol 17 (9) ◽  
pp. 2649-2649 ◽  
Author(s):  
Howard D. Thames ◽  
Thomas A. Buchholz ◽  
Cynthia D. Smith
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Neoadjuvant Treatment ◽  
Distant Metastases ◽  
Distant Disease ◽  
Primary Tumors ◽  
Node Negative ◽  
Size Dependent ◽  
Optimal Sequencing ◽  
Metastasis Development

PURPOSE: The sequencing of treatment for early breast cancer is controversial. The purpose of this study was to quantify the risk of delaying surgery, using estimates of the frequency of first metastases from breast primary tumors. PATIENTS AND METHODS: The probability that 560 (node-negative), 657 (with one to three positive nodes), and 505 (with more than three positive nodes) women treated without adjuvant chemotherapy would be free of distant disease at presentation was fit to a mathematical model of the seeding of distant metastases and combined with estimates of the growth rate to calculate the frequency of first distant disseminations per month. RESULTS: Frequencies of first distant metastases were approximately 1% to 2% per month, 2% to 4% per month, and 3% to 6% per month in T1 patients who were node-negative, had one to three positive nodes, or more than three positive nodes, respectively. As a result, the typical patient with T1 disease, who has a 70% to 80% chance of being free of distant disease, runs a 1% to 4% risk of distant dissemination for each month surgery is delayed. Assuming a 30% reduction in mortality caused by adjuvant chemotherapy, the model predicts that T1 patients treated with neoadjuvant chemotherapy would potentially have a higher rate of distant metastasis development than those treated with an initial surgical resection followed by adjuvant chemotherapy. CONCLUSION: We formulate the hypothesis that optimal sequencing of surgery and systemic treatment of breast cancer may be size-dependent, with a disadvantage or no benefit from neoadjuvant treatment for T1 patients but an increasing benefit with increasing size of the primary tumor.

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