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or taxane-based chemotherapy for primary breast cancer
Abstracts
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on method of assessment. Immunohistochemistry, automatic quantitative analysis and polymerase chain reaction all showing similar results for both DFS and OS (p for subgroup difference=0.41 and 0.45; respectively). Conclusion: EGFR over-expression is more common in women with triple negative breast cancer. Additionally, the negative prognostic impact of EGFR over-expression appears greatest in patients with triple negative disease. No conflict of interest. 1974 POSTER Pretreatment neutrophil-to-lymphocyte ratio (NLR) correlates with response to neoadjuvant chemotherapy and survival in breast cancer: A pilot study ˜ Gomez2 , C. Salvador2 , E. Reche2 , C. Escoin2 , G. Bruixola1 , O. Nino D. Akhoundova2 , L. Palomar2 , H. De la Cueva2 , F. Ripoll2 , A. Garcia ´ Mart´ınez2 , A. Santaballa2 . 1 Hospital Universitario y Politecnico La Fe, Medical Oncology, Valencia, Spain; 2 La Fe University and Polytechnic Hospital, Medical Oncology, Valencia, Spain Background: Systemic neoadjuvant therapy is the treatment of choice for patients with locally advanced breast cancer (LABC). A pathologic complete response (pCR) is the main independent prognostic factor for survival in this setting. The pretreatment neutrophil-to-lymphocyte ratio (NLR) is a simple measure of systemic inflammation. A high RNL has been described as poor prognosis factor in breast cancer. Aim: to determine prognostic value of pretreatment RNL and its correlation with pCR in LABC patients (pts) treated with neoadjuvant therapy. Material and Methods: Retrospective review of 47 LABC pts treated with systemic neoadjuvant therapy (2010–2014). Baseline RNL, pCR rate, disease-free survival (DFS) and overall survival (OS) were assessed. The NRL cut-off for survival was calculated by time-dependent receiver operating characteristic curves (ROC). Univariate and multivariate analyses of prognostic factors for DFS and OS were performed. Table 1: Baseline characteristics N = 47. n (%) Median age, yrs (range) Tumor size (cm), median (range) Tumor size (T) (TNM) T1 T2 T3 T4 Node (N) (TNM) N0 Nmic N1 Nuclear grade Grade 1 Grade 2 Grade 3 Not available Histologic subtype Luminal A Luminal B HER2 enriched Triple negative RNL, median (range) Tumor pCR achieved (Miller and Paine) Grade 1 Grade 2 Grade 3 Grade 4 Grade 5 Node pCR achieved (Miller and Paine) A B C D
46.1 (25.6–49.2) 3.66 (1−9) 12 (25.5) 24 (48.9) 7 (14.9) 5 (10.6) 19 (40.4) 20 (43.6) 8 (17.0) 5 (10.6) 12 (25.5) 23 (48.9) 7 (14.9) 8 (17.0) 17 (36.2) 11 (23.4) 11 (23.4) 2.3 (0.16–11.2) 5 (10.6) 7 (14.9) 6 (12.8) 19 (40.4) 10 (21.2) 18 (38.3) 8 (17.1) 11 (23.4) 10 (21.2)
Results: The optimal NLR cut-off for the prediction of OS by ROC analysis was 2.6 (AUC 0.817). We achieved a rpC rate of 20%. With a median follow-up of 37.5 months (mts) (range 10.6–65.3), the median DFS was 11.9 mts (95% CI 5.4–18.3); median OS has not been reached yet, but estimated 3-year OS was 85%. Univariate DFS analysis showed RNL >2.6 as independent poor prognostic factor (p = 0.012). Univariate OS analysis found as independent poor prognostic factors RNL >2.6 (p = 0.026), no pCR (p = 0.004), histologic subtype (p = 0.003) and TNM stage III vs II
(p = 0.010). In the multivariate DFS analysis only RNL >2.6 remained as independent poor prognostic factor (p = 0.039); however, independent prognostic factors identified in multivariate analysis for OS were RNL >2.6 (p = 0.035), no pCR (p = 0.045), histologic subtype (p = 0.011) and TNM stage III vs II (p = 0.043). RNL and pCR showed a mild correlation statistically significant (R Spearman = 0.431; p = 0.009) Conclusions: RNL has shown a promising prognostic value and correlates with pCR in LABC treated with neoadjuvant systemic therapy; further investigations are required to validate it and to establish the NLR optimal threshold. No conflict of interest. 1975 POSTER Changes of bone metabolism induced by perioperative anthracycline- and/or taxane-based chemotherapy for primary breast cancer C.M. Kurbacher1 , N. Rauschenbach1 , A.T. Kurbacher1 , S. Herz1 , K. Monreal1 , C. Bartling2 , A. Quade2 , J.A. Kurbacher3 . 1 Gynecologic Center Bonn-Friedensplatz, Gynecologic Oncology, Bonn, Germany; 2 MVZ Labor Dr. Quade & Kollegen, Central Laboratory, Cologne, Germany; 3 Gynecologic Center Bonn-Friedensplatz, General Gynecology and Obstetrics, Bonn, Germany Background: Cancer therapy-induced bone loss (CTIBL) is a well-known complication of adjuvant endocrine therapy in postmenopausal patients (pts) with primary breast cancer (PBC). In contrast, the knowledge of direct effects of modern chemotherapy (Ctx) regimens on bone metabolism of PBC pts is still limited. This translational study was initiated to gain more insights into the influence of perioperative anthracycline (A)- and/or taxane (T)-based Ctx on bone turnover of pts with PBC in regard to their menopausal status. Methods: A total of 109 pts (premenopausal: 49; postmenopausal: 60) subjected to neoadjuvant or adjuvant A- and/or T-based Ctx were included. Serum markers of bone metabolism including C-telopeptide of type I collagen (ICTP) indicating the osteoclast activity, N-propeptide of type I collagen (P1NP) measuring the osteoblast activity, and bone alkaline phosphatase (BALP) were determined at baseline and prior to each subsequent Ctx cycle (C) up to C6. Differences of baseline levels of all three parameters between pre- and postmenopausal pts were compared by student’s t-tests. Changes of ICTP, P1NP, and BALP over time were analyzed by repeated-measure ANOVA with p < 0.05 indicating significance for all statistics. Results: A total of 600 Ctx cycles were analyzed. Baseline levels of ICTP (4.9 vs 3.7 mg/L, p = 0.0063), P1NP (55.4 vs 40.5 mg/L, p = 0.0027), and BALP (77.3 vs 60.2 IU/L, p = 0.0007) were significantly higher in postmenopausal pts. However, changes of all markers over time were largely comparable between both groups of pts. A slight increase of BALP did not reach statistical significance as did not both an constant increase of ICTP in premenopausal pts and a decrease in postmenopausal pts. In contrast, P1NP significantly declined in both groups, in postmenopausal pts from baseline to C6 (p = 0.0152) and in premenopausal pts from baseline to C3−4 and then revovered completely (p = 0.0024). Conclusion: Our study represents one of the very few systematic evaluations of direct effects of modern Ctx for PBC on bone matobilsm by which we were able to detect a profound deterioration of osteoblast activity in both pre- and postmenopausal pts. Whether these effects will translate into an increased risk to further develop CTIBL needs to be clarified by long-term observations. No conflict of interest. 1976 POSTER Significance of PIK3CA mutations in patients with early breast cancer treated with adjuvant chemotherapy: A Hellenic Cooperative Oncology Group (HeCOG) study G. Papaxoinis1 , V. Kotoula1 , Z. Alexopoulou2 , E. Charalambous1 , F. Zagouri1 , E. Timotheadou1 , H. Gogas1 , G. Pentheroudakis1 , A. Koutras1 , C. Christodoulou1 , D. Bafaloukos1 , G. Aravantinos1 , K.T. Kalogeras1 , D. Pectasides1 , G. Fountzilas1 . 1 Hellenic Cooperative Oncology Group, Data Office, Athens, Greece; 2 Health Data Specialists Ltd, Biostatistics, Athens, Greece Background: The PI3K/Akt pathway is frequently activated in breast cancer. The aim of the present study was to examine the role of different types of PIK3CA mutations in combination with molecular biomarkers related to PI3K/Akt signaling in patients with early breast cancer. Material and Methods: Tumor tissues from 1,008 lymph node positive early breast cancer patients treated with anthracycline-based adjuvant
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on method of assessment. Immunohistochemistry, automatic quantitative analysis and polymerase chain reaction all showing similar results for both DFS and OS (p for subgroup difference=0.41 and 0.45; respectively). Conclusion: EGFR over-expression is more common in women with triple negative breast cancer. Additionally, the negative prognostic impact of EGFR over-expression appears greatest in patients with triple negative disease. No conflict of interest. 1974 POSTER Pretreatment neutrophil-to-lymphocyte ratio (NLR) correlates with response to neoadjuvant chemotherapy and survival in breast cancer: A pilot study ˜ Gomez2 , C. Salvador2 , E. Reche2 , C. Escoin2 , G. Bruixola1 , O. Nino D. Akhoundova2 , L. Palomar2 , H. De la Cueva2 , F. Ripoll2 , A. Garcia ´ Mart´ınez2 , A. Santaballa2 . 1 Hospital Universitario y Politecnico La Fe, Medical Oncology, Valencia, Spain; 2 La Fe University and Polytechnic Hospital, Medical Oncology, Valencia, Spain Background: Systemic neoadjuvant therapy is the treatment of choice for patients with locally advanced breast cancer (LABC). A pathologic complete response (pCR) is the main independent prognostic factor for survival in this setting. The pretreatment neutrophil-to-lymphocyte ratio (NLR) is a simple measure of systemic inflammation. A high RNL has been described as poor prognosis factor in breast cancer. Aim: to determine prognostic value of pretreatment RNL and its correlation with pCR in LABC patients (pts) treated with neoadjuvant therapy. Material and Methods: Retrospective review of 47 LABC pts treated with systemic neoadjuvant therapy (2010–2014). Baseline RNL, pCR rate, disease-free survival (DFS) and overall survival (OS) were assessed. The NRL cut-off for survival was calculated by time-dependent receiver operating characteristic curves (ROC). Univariate and multivariate analyses of prognostic factors for DFS and OS were performed. Table 1: Baseline characteristics N = 47. n (%) Median age, yrs (range) Tumor size (cm), median (range) Tumor size (T) (TNM) T1 T2 T3 T4 Node (N) (TNM) N0 Nmic N1 Nuclear grade Grade 1 Grade 2 Grade 3 Not available Histologic subtype Luminal A Luminal B HER2 enriched Triple negative RNL, median (range) Tumor pCR achieved (Miller and Paine) Grade 1 Grade 2 Grade 3 Grade 4 Grade 5 Node pCR achieved (Miller and Paine) A B C D
46.1 (25.6–49.2) 3.66 (1−9) 12 (25.5) 24 (48.9) 7 (14.9) 5 (10.6) 19 (40.4) 20 (43.6) 8 (17.0) 5 (10.6) 12 (25.5) 23 (48.9) 7 (14.9) 8 (17.0) 17 (36.2) 11 (23.4) 11 (23.4) 2.3 (0.16–11.2) 5 (10.6) 7 (14.9) 6 (12.8) 19 (40.4) 10 (21.2) 18 (38.3) 8 (17.1) 11 (23.4) 10 (21.2)
Results: The optimal NLR cut-off for the prediction of OS by ROC analysis was 2.6 (AUC 0.817). We achieved a rpC rate of 20%. With a median follow-up of 37.5 months (mts) (range 10.6–65.3), the median DFS was 11.9 mts (95% CI 5.4–18.3); median OS has not been reached yet, but estimated 3-year OS was 85%. Univariate DFS analysis showed RNL >2.6 as independent poor prognostic factor (p = 0.012). Univariate OS analysis found as independent poor prognostic factors RNL >2.6 (p = 0.026), no pCR (p = 0.004), histologic subtype (p = 0.003) and TNM stage III vs II
(p = 0.010). In the multivariate DFS analysis only RNL >2.6 remained as independent poor prognostic factor (p = 0.039); however, independent prognostic factors identified in multivariate analysis for OS were RNL >2.6 (p = 0.035), no pCR (p = 0.045), histologic subtype (p = 0.011) and TNM stage III vs II (p = 0.043). RNL and pCR showed a mild correlation statistically significant (R Spearman = 0.431; p = 0.009) Conclusions: RNL has shown a promising prognostic value and correlates with pCR in LABC treated with neoadjuvant systemic therapy; further investigations are required to validate it and to establish the NLR optimal threshold. No conflict of interest. 1975 POSTER Changes of bone metabolism induced by perioperative anthracycline- and/or taxane-based chemotherapy for primary breast cancer C.M. Kurbacher1 , N. Rauschenbach1 , A.T. Kurbacher1 , S. Herz1 , K. Monreal1 , C. Bartling2 , A. Quade2 , J.A. Kurbacher3 . 1 Gynecologic Center Bonn-Friedensplatz, Gynecologic Oncology, Bonn, Germany; 2 MVZ Labor Dr. Quade & Kollegen, Central Laboratory, Cologne, Germany; 3 Gynecologic Center Bonn-Friedensplatz, General Gynecology and Obstetrics, Bonn, Germany Background: Cancer therapy-induced bone loss (CTIBL) is a well-known complication of adjuvant endocrine therapy in postmenopausal patients (pts) with primary breast cancer (PBC). In contrast, the knowledge of direct effects of modern chemotherapy (Ctx) regimens on bone metabolism of PBC pts is still limited. This translational study was initiated to gain more insights into the influence of perioperative anthracycline (A)- and/or taxane (T)-based Ctx on bone turnover of pts with PBC in regard to their menopausal status. Methods: A total of 109 pts (premenopausal: 49; postmenopausal: 60) subjected to neoadjuvant or adjuvant A- and/or T-based Ctx were included. Serum markers of bone metabolism including C-telopeptide of type I collagen (ICTP) indicating the osteoclast activity, N-propeptide of type I collagen (P1NP) measuring the osteoblast activity, and bone alkaline phosphatase (BALP) were determined at baseline and prior to each subsequent Ctx cycle (C) up to C6. Differences of baseline levels of all three parameters between pre- and postmenopausal pts were compared by student’s t-tests. Changes of ICTP, P1NP, and BALP over time were analyzed by repeated-measure ANOVA with p < 0.05 indicating significance for all statistics. Results: A total of 600 Ctx cycles were analyzed. Baseline levels of ICTP (4.9 vs 3.7 mg/L, p = 0.0063), P1NP (55.4 vs 40.5 mg/L, p = 0.0027), and BALP (77.3 vs 60.2 IU/L, p = 0.0007) were significantly higher in postmenopausal pts. However, changes of all markers over time were largely comparable between both groups of pts. A slight increase of BALP did not reach statistical significance as did not both an constant increase of ICTP in premenopausal pts and a decrease in postmenopausal pts. In contrast, P1NP significantly declined in both groups, in postmenopausal pts from baseline to C6 (p = 0.0152) and in premenopausal pts from baseline to C3−4 and then revovered completely (p = 0.0024). Conclusion: Our study represents one of the very few systematic evaluations of direct effects of modern Ctx for PBC on bone matobilsm by which we were able to detect a profound deterioration of osteoblast activity in both pre- and postmenopausal pts. Whether these effects will translate into an increased risk to further develop CTIBL needs to be clarified by long-term observations. No conflict of interest. 1976 POSTER Significance of PIK3CA mutations in patients with early breast cancer treated with adjuvant chemotherapy: A Hellenic Cooperative Oncology Group (HeCOG) study G. Papaxoinis1 , V. Kotoula1 , Z. Alexopoulou2 , E. Charalambous1 , F. Zagouri1 , E. Timotheadou1 , H. Gogas1 , G. Pentheroudakis1 , A. Koutras1 , C. Christodoulou1 , D. Bafaloukos1 , G. Aravantinos1 , K.T. Kalogeras1 , D. Pectasides1 , G. Fountzilas1 . 1 Hellenic Cooperative Oncology Group, Data Office, Athens, Greece; 2 Health Data Specialists Ltd, Biostatistics, Athens, Greece Background: The PI3K/Akt pathway is frequently activated in breast cancer. The aim of the present study was to examine the role of different types of PIK3CA mutations in combination with molecular biomarkers related to PI3K/Akt signaling in patients with early breast cancer. Material and Methods: Tumor tissues from 1,008 lymph node positive early breast cancer patients treated with anthracycline-based adjuvant