scholarly journals Early prediction of pathologic response to neoadjuvant treatment of breast cancer: use of a cell-loss metric based on serum thymidine kinase 1 and tumour volume

2019 ◽  
Author(s):  
Bernhard Tribukait ◽  
Jonas Bergh ◽  
Thomas Hatschek
Keyword(s):  
Breast Cancer ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Tumour Response ◽  
Cell Loss ◽  
Tumour Volume ◽  
Tumour Cells ◽  
Early Prediction ◽  
Cytotoxic Treatment ◽  
A Cell

Abstract Background After neoadjuvant chemotherapy of breast cancer pathologic complete response (pCR) indicates a favourable prognosis. Among non-selected patients, pCR is, however, achieved in only 10-30%. Early evaluation of tumour response to treatment would facilitate individualized therapy, with ineffective chemotherapy interrupted or changed. The methodology for this purpose is still limited. Tumour imaging and analysis of macromolecules, released from disrupted tumour cells are principle alternatives.Objective To investigate whether a metric of cell-loss, defined as the ratio between serum concentration of thymidine kinase1 (sTK1) (ng x ml -1 ) and tumour volume (cm 3 ), can be used in the early prediction of pathologic response.Methods 104 women with localized breast cancer received neoadjuvant epirubicin/docetaxel in 6 cycles, supplemented with bevacizumab in cycles 3-6. The cell-loss metric was established at baseline (n=104), prior to cycle 2 (n=57) and 48h after cycle 2 (n=104). The performance of the metric was evaluated by association with pathologic tumour response at surgery ̴ 16 weeks later.Results Means for the three points of the metric were 0.007, 0.084 and 0.107 units. For each individual, the baseline value was subtracted from the 48-h value and patients were grouped into quartiles. Means of these were: 0.002, 0.011, 0.030 and 0.357 units. The cell-loss metric was associated with the pCR in the quartiles: 11%, 11%, 23% and 46% (p=0.01). In the 80 patients with remaining tumour, pathologic tumour size was inversely related to the metric (p=0.002). In the subgroup of 57 patients, data obtained prior to the 2nd cycle indicated a higher predictive value than the data obtained 48h after this treatment.Conclusion A cell-loss metric, established by combining serum levels of TK1, released from disrupted tumour cells, and tumour volume, reveal tumour response early during neoadjuvant treatment. The metric appears to reflect a tumour property that differ greatly between patients and determines the sensitivity to cytotoxic treatment. The findings point to the significance of cell loss for the growth rate of tumours. The metric should be considered in personalized oncology and in the evaluation of new therapeutic modalities.

scholarly journals Early prediction of pathologic response to neoadjuvant treatment of breast cancer: use of a cell-loss metric based on serum thymidine kinase 1 and tumour volume

2020 ◽  
Author(s):  
Bernhard Tribukait
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Treatment ◽  
Tumour Response ◽  
Cell Loss ◽  
Tumour Volume ◽  
Pathologic Response ◽  
Tumour Cells ◽  
Early Prediction ◽  
Cytotoxic Treatment ◽  
A Cell

Abstract Background: After neoadjuvant chemotherapy of breast cancer pathologic complete response (pCR) indicates a favorable prognosis. Among non-selected patients, pCR is, however, achieved in only 10-30%. Early evaluation of tumour response to treatment would facilitate individualized therapy, with ineffective chemotherapy interrupted or changed. The methodology for this purpose is still limited. Tumour imaging and analysis of macromolecules, released from disrupted tumour cells, are principal alternatives. Objective: To investigate whether a metric of cell-loss, defined as the ratio between serum concentration of thymidine kinase1 (sTK1, ng x ml-1) and tumour volume, can be used for early prediction of pathologic response. Methods: 104 women with localized breast cancer received neoadjuvant epirubicin/docetaxel in 6 cycles, supplemented with bevacizumab in cycles 3-6. The cell-loss metric was established at baseline (n=104), 48h after cycle 2 (n=104) and prior to cycle 2 (n=57). The performance of the metric was evaluated by association with pathologic tumour response at surgery 4 months later. Results: Treatment caused a rise in sTK1, a reduction in tumour volume and a marked increase in the cell-loss metric. Patients were subdivided into quartiles according to the baseline cell-loss metric. For these groups, baseline means were 0.0016, 0.0042, 0.0062, 0.0178 units. After subtraction of baselines, means for the quartiles 48h after treatment 2 were 0.002, 0.011, 0.030 and 0.357 units. pCR was achieved in 24/104, their distribution in the quartiles (11%, 11%, 23% and 46%) differed significantly (p=0.01). In 80 patients with remaining tumour, tumour size was inversely related to the metric (p=0.002). In 57 patients studied before treatment 2, positive and negative predictive values of the metric were 77.8% and 83.3%, compared to 40.5% and 88.7% 48h after treatment 2. Conclusion: A cell-loss metric, based on serum levels of TK1, released from disrupted tumour cells, and tumour volume, reveal tumour response early during neoadjuvant treatment. The metric reflect tumour properties that differ greatly between patients and determine the sensitivity to cytotoxic treatment. The findings point to the significance of cell loss for tumour growth rate. The metric should be considered in personalized oncology and in the evaluation of new therapeutic modalities.

scholarly journals Early prediction of pathologic response to neoadjuvant treatment of breast cancer: use of a cell-loss metric based on serum thymidine kinase 1 and tumour volume

2020 ◽  
Author(s):  
Bernhard Tribukait
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Treatment ◽  
Tumour Response ◽  
Cell Loss ◽  
Tumour Volume ◽  
Tumour Cells ◽  
Early Prediction ◽  
Predictive Values ◽  
Cytotoxic Treatment ◽  
A Cell

Abstract Background: After neoadjuvant chemotherapy of breast cancer pathologic complete response (pCR) indicates a favorable prognosis. Among non-selected patients, pCR is, however, achieved in only 10-30%. Early evaluation of tumour response to treatment would facilitate individualized therapy, with ineffective chemotherapy interrupted or changed. The methodology for this purpose is still limited. Tumour imaging and analysis of macromolecules, released from disrupted tumour cells, are principal alternatives.Objective: To investigate whether a metric of cell-loss, defined as the ratio between serum concentration of thymidine kinase1 (sTK1, ng x ml-1) and tumour volume, can be used for early prediction of pathologic response.Methods: 104 women with localized breast cancer received neoadjuvant epirubicin/docetaxel in 6 cycles, supplemented with bevacizumab in cycles 3-6. The cell-loss metric was established at baseline (n=104), 48h after cycle 2 (n=104) and prior to cycle 2 (n=57). The performance of the metric was evaluated by association with pathologic tumour response at surgery 4 months later.Results: Treatment caused a rise in sTK1, a reduction in tumour volume and a marked increase in the cell-loss metric. Patients were subdivided into quartiles according to the baseline cell-loss metric. For these groups, baseline means were 0.0016, 0.0042, 0.0062, 0.0178 units. After subtraction of baselines, means for the quartiles 48h after treatment 2 were 0.002, 0.011, 0.030 and 0.357 units. pCR was achieved in 24/104, their distribution in the quartiles (11%, 11%, 23% and 46%) differed significantly (p=0.01). In 80 patients with remaining tumour, tumour size was inversely related to the metric (p=0.002). In 57 patients studied before treatment 2, positive and negative predictive values of the metric were 77.8% and 83.3%, compared to 40.5% and 88.7% 48h after treatment 2.Conclusion: A cell-loss metric, based on serum levels of TK1, released from disrupted tumour cells, and tumour volume, reveal tumour response early during neoadjuvant treatment. The metric reflect tumour properties that differ greatly between patients and determine the sensitivity to cytotoxic treatment. The findings point to the significance of cell loss for tumour growth rate. The metric should be considered in personalized oncology and in the evaluation of new therapeutic modalities.Trial registration: PROMIX (Clinical Trials.gov NCT000957125).https://clinicaltrials.gov/ct2/show/NCT00957125

scholarly journals Early prediction of pathologic response to neoadjuvant treatment of breast cancer: use of a cell-loss metric based on serum thymidine kinase 1 and tumour volume

2020 ◽  
Author(s):  
Bernhard Tribukait ◽  
Jonas Bergh ◽  
Thomas Hatschek
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Treatment ◽  
Tumour Response ◽  
Cell Loss ◽  
Tumour Volume ◽  
Pathologic Response ◽  
Tumour Cells ◽  
Early Prediction ◽  
Cytotoxic Treatment ◽  
A Cell

Abstract Background: After neoadjuvant chemotherapy of breast cancer pathologic complete response (pCR) indicates a favourable prognosis. Among non-selected patients, pCR is, however, achieved in only 10-30%. Early evaluation of tumour response to treatment would facilitate individualized therapy, with ineffective chemotherapy interrupted or changed. The methodology for this purpose is still limited. Tumour imaging and analysis of macromolecules, released from disrupted tumour cells, are principal alternatives. Objective: To investigate whether a metric of cell-loss, defined as the ratio between serum concentration of thymidine kinase1 (sTK1, ng x ml-1) and tumour volume, can be used for early prediction of pathologic response. Methods: 104 women with localized breast cancer received neoadjuvant epirubicin/docetaxel in 6 cycles, supplemented with bevacizumab in cycles 3-6. The cell-loss metric was established at baseline (n=104), 48h after cycle 2 (n=104) and prior to cycle 2 (n=57). The performance of the metric was evaluated by association with pathologic tumour response at surgery 4 months̴ later.Results: Treatment caused a rise in sTK1, a reduction in tumour volume and a marked increase in the cell-loss metric. Patients were subdievided into quartiles according to the baseline cell-loss metric. For these groups, baseline means were 0.0016, 0.0042, 0.0062, 0.0178 units. After subtraction of baselines, means for the quartiles 48h after treatment 2 were 0.002, 0.011, 0.030 and 0.357 units. pCR was achieved in 24/104, their distribution in the quartiles (11%, 11%, 23% and 46% ) differed significantly (p=0.01).In 80 patients with remaining tumour, tumour size was inversely related to the metric (p=0.002). In 57 patients studied before treatment 2, positive and negative predictive values of the metric were 77.8% and 83.3%, compared to 40.5% and 88.7% 48h after treatment 2. Conclusion: A cell-loss metric, based on serum levels of TK1, released from disrupted tumour cells, and tumour volume, reveal tumour response early during neoadjuvant treatment. The metric reflect tumour properties that differ greatly between patients and determine the sensitivity to cytotoxic treatment. The findings point to the significance of cell loss for tumour growth rate. The metric should be considered in personalized oncology and in the evaluation of new therapeutic modalities.

scholarly journals BRCA1/2 Mutations and Bevacizumab in the Neoadjuvant Treatment of Breast Cancer: Response and Prognosis Results in Patients With Triple-Negative Breast Cancer From the GeparQuinto Study

2018 ◽  
Vol 36 (22) ◽  
pp. 2281-2287 ◽  
Author(s):  
Peter A. Fasching ◽  
Sibylle Loibl ◽  
Chunling Hu ◽  
Steven N. Hart ◽  
Hermela Shimelis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Strong Predictor ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Disease Free Survival ◽  
Hazard Ratio ◽  
Brca1 And Brca2 ◽  
Mutation Carriers

Purpose BRCA1/2 mutations are frequent in patients with triple-negative breast cancer (TNBC). These patients are often treated with primary systemic chemotherapy. The aim of this study was to analyze the effects of BRCA1/2 mutations on pathologic complete response (pCR) and disease-free survival (DFS) in a cohort of patients with TNBC treated with anthracycline and taxane–containing chemotherapy, with or without bevacizumab. Patients and Methods Germline DNA was sequenced to identify mutations in BRCA1 and BRCA2 in 493 patients with TNBC from the GeparQuinto study. The pCR rates were compared in patients with and without mutation, as well as in patients treated with and without bevacizumab. In addition, the influence of BRCA1/2 mutation status and pCR status on DFS was evaluated relative to treatment. Results BRCA1/2 mutations were detected in 18.3% of patients with TNBC. Overall, patients with mutations had a pCR rate of 50%, compared with 31.5% in patients without a mutation (odds ratio [OR], 2.17; 95% CI, 1.37 to 3.46; P = .001). The pCR rate among patients treated with bevacizumab was 61.5% for BRCA1/2 mutation carriers and 35.6% for those without mutations (OR, 2.90; 95% CI, 1.43 to 5.89; P = .004). pCR was a strong predictor of DFS for patients without BRCA1/2 mutations (hazard ratio, 0.18; 95% CI, 0.11 to 0.31) but not for patients with BRCA1/2 mutations (hazard ratio, 0.74; 95% CI, 0.32 to 1.69). Conclusion The addition of bevacizumab may increase the pCR after standard neoadjuvant chemotherapy for patients with TNBC with BRCA1/2 mutations. In patients treated with anthracycline and taxane–based chemotherapy (with or without bevacizumab), pCR was a weaker predictor of DFS for BRCA1/2 mutation carriers than for patients without mutations.

Association of NBS1 expression with improved pathologic complete response rate in HER2-overexpressing breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11534-e11534
Author(s):  
Fatma Sen ◽  
Ekrem Yavuz ◽  
Gulcin Yegen ◽  
Hasan Karanlik ◽  
Sitki Tuzlali ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Expression ◽  
Response Rate ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Complete Response ◽  
Protein Loss ◽  
Paraffin Sections ◽  
Her2 Breast Cancer

e11534 Background: Our aim was to investigate potential correlation between expression levels of Nijmegen breakage syndrome1 (NBS1) protein and phosphatidylinositol-3 kinase (PI3K) and pathologic complete response (pCR) rate to neoadjuvant treatment in locally advanced HER2+ breast cancer. We also assess possible association between NBS1 and PI3K expressions. Methods: Totally 42 patients (median age 49 years), received neoadjuvant treatment due to locally advanced HER2+ breast cancer, were included. Immunohistochemical analyses were performed on paraffin sections, obtained during initial diagnosis. Paraffin sections were stained with anti-NBS1 (P95-NBS1 antibody, Y112, ab32074) and anti-PI3K (PI3-Kinase p85 alpha+gamma antibody, ab741369) antibodies to determine positivity of related proteins. Results: NBS1 protein loss was detected in 19 (%45) patients whereas p85 loss was shown in 25 (%60). There was no initial clinicopathologic variable predicting pCR. Fifteen of 30 patients, received neoadjuvant trastuzumab, had pCR, whereas only 1 of 12 patients, not received trastuzumab, achieved pCR (P = 0.012). p85 loss did not predict treatment response, however NBS1 protein expression positively correlated with increased response rate to neoadjuvant treatment (P = 0.007). Conclusions: NBS1 protein expression associates with increased pCR rate in HER2+ breast cancer. However, P85 positivity did not associate with pCR rate or NBS1 overexpression.

Impact of dual anti-HER2 therapy on pathologic complete response rate in breast cancer in a minority-enriched population.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e18111-e18111 ◽  
Author(s):  
Jenny Jing Li ◽  
Hsiao Ching Li ◽  
Ang Gao ◽  
Samira K. Syed ◽  
Nisha Unni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Complete Response Rate ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Complete Response ◽  
Safety Net ◽  
Her2 Breast Cancer ◽  
Race Ethnicity ◽  
Pathologic Complete Response Rate ◽  
Racial Ethnic

e18111 Background: The addition of pertuzumab (P) to a neoadjuvant trastuzumab (H) plus chemotherapy combination has been shown to significantly improve the pathologic complete response rate (pCR) in localized HER2+ breast cancer; however, minorities have been under-represented in these trials. Racial/ethnic disparities have also been shown to affect outcomes of cancer treatment. This study is aimed to assess the impact of neoadjuvant dual HER2-blockade in an unselected minority-enriched population. Methods: A retrospective chart review was conducted of women with stage I to III HER2+ breast cancer who received neoadjuvant treatment between 2007 and 2017 at an academic institution and its affiliated safety net health system. Data on stage, chemotherapy, race/ethnicity, site of therapy (academic vs safety net hospital), and hormone receptor status were collected. All patients underwent surgery after completion of neoadjuvant chemotherapy. pCR was defined as ypT0/is, ypN0. Chi-squared test and univariate/multivariate logistic regression were used for statistical analysis. Results: The study population included 261 women with the following race/ethnic distribution: 37.7% Non-Hispanic Whites, 34.6% Hispanics, 20.6% Blacks, and 7% other racial/ethnic origin. Ninety-five patients (36%) received chemotherapy-H vs 166 patients (64%) received chemotherapy-HP. Patients at the safety net health system had higher stage at diagnosis compared to the academic site. Site of care and race/ethnicity did not impact the choice of neoadjuvant treatment. The pCR rate was significantly higher for the chemotherapy-HP group (55.4%) compared to the chemotherapy-H group (34.7%) (p = 0.001). There was no association between race/ethnicity, or site of treatment (academic vs safety net), and the probability of achieving pCR. Multivariate analysis showed only dual anti-HER2 therapy (OR: 2.67, CI: 1.55-4.59, p = 0.0004) and hormone-receptor negative status (OR: 2.18, CI: 1.30-3.67, p = 0.0031) to correlate with pCR. Conclusions: Neoadjuvant dual anti-HER2 therapy was more likely to result in a pCR in our minority enriched population. Our data also suggests the combination of chemotherapy-HP confers similar benefit irrespective of race/ethnicity or site of care.

Pathologic response to neoadjuvant therapy with nabpaclitaxel plus carboplatin followed by anthracycline regimen in triple-negative breast cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12117-e12117
Author(s):  
Juan David Cardenas ◽  
Carmen Esteban ◽  
Iciar Garcia Carbonero ◽  
Adriana Rosero ◽  
Katherin Martinez Barroso ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Hormone Receptors ◽  
Triple Negative ◽  
Clinical Stage ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Conservative Surgery ◽  
Stage Ii ◽  
Hematologic Toxicity

e12117 Background: Triple-negative breast cancer (TNBC) remains a poor prognosis subtype of breast cancer (BC). We are lacking of definitive effective combinations in this tumor. So, it is warranted to explore new combinations. Neo-adjuvant setting is one of the most effective scenarios to explore a treatment efficacy. We aimed to evaluate efficacy of Nab-paclitaxel plus Carboplatin followed byanthracycline regimen by pathologic complete response (pCR: no disease in breast and axilla) in women with TNBC. Secondary endpoints were toxicity profile and breast conserving surgery. Methods: Women with stage II or III disease were included. Hormone receptors and HER2 negativity was confirmed by immunohistochemistry and/or FISH. Patients received Nab-paclitaxel 125 mg/m2 plus Carboplatin AUC 2 intravenously on days 1, 8 every 21 for four cycles followed by Epirubicin 90 mg/m2 and Cyclophosphamide 600 mg/m2 intravenously every 2 weeks for 4 cycles and subsequent surgery. Breast Magnetic Resonance was done in all cases at diagnosis and before surgery. We obtained informed consent from all patients. Results: Thirty-two patients with confirmed clinical stage II (56.3%) or III (43.7%) TNBC were treatedbetween January 2015 and February 2019. The median age of the patients was 53.1 years (30.3-77.6 years). The average of received chemotherapy was 12 doses (7-14). The mean dose of nab-paclitaxel plus carboplatin was 8 doses. All patients received surgery with or without radiotherapy. There was only one case (3.1%) of progression during neoadjuvant treatment. The rate of pCR was 50% (16) in breast and axilla, partial response 43.8% (14) and stable disease 3.1% (1). Conservative surgery was performed in 50% of patients (16). The 3/4 grade toxicities were asthenia 3.1% (1), nausea/vomiting 6.3% (2), thrombocytopenia 6.3% (2), leukopenia 6.3% (2), neutropenia 40.6% (13), febrile neutropenia 6.3% (2), diarrhea 3.1% (1), allergy 3.1% (1), peripheral neurotoxicity 3.1% (1). After a median follow-up of 18.3 months (5.0–41.9) 93.8% (30) of patients are alive. Two patients (6.3%) had early local relapse and distant relapse, respectively, and are deceased due to progression disease. Conclusions: Nab-paclitaxel plus carboplatin followed by anthracycline regimencombination as neoadjuvant treatment in TNBC achieved an encouraging rate of pCR, allowing conservative surgery in half of our patients. Toxicities were not severe in most patients and hematologic toxicity was manageable with G-CSF.

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