- Email: [email protected]
Safety of hypofractionated whole breast irradiation after conservative surgery for patients aged less than 60 years: A multi-center comparative study
abstracts 213P
Response to neoadjuvant chemotherapy in HER2 non-overexpressing breast cancer subtypes
S.M. Ilie1, I. Desmoulins1, A. Hennequin1, K. Coure`che-Guillaume1, L. Arnould2, B. Nathalie3, A. Bertaut3, S. Ladoire1 1 Department of Medical Oncology, Centre Georges-Franc¸ois Leclerc (Dijon), Dijon, France, 2Department of Biology and Tumour Pathology, Centre Georges-Franc¸ois Leclerc, Dijon, France, 3Biostatistics and Data Management, Centre Georges-Franc¸ois Leclerc, Dijon, France
214P
Pre-specified interim analysis of the SAFE trial (NCT2236806): A 4-arm randomized, double-blind, controlled study evaluating the efficacy and safety of cardiotoxicity prevention in non-metastatic breast cancer patients treated with anthracyclines with or without trastuzumab
L. Livi1, G. Barletta2, F. Martella3, I. Desideri1, V. Scotti1, C. Becherini1, C. Saieva4, F. Terziani1, C. Bacci3, M. Airoldi5, G. Allegrini6, D. Amoroso7, F. Venditti2, R. Tarquini8, L. Orzalesi9, L. Sanchez9, M. Bernini9, J. Nori10, L. Fioretto3, I. Meattini1 1 Department of Biomedical, Experimental, and Clinical Sciences, University of Florence, Florence, Italy, 2Cardiology Diagnostics - Cardiothoracic & Vascular, Azienda Ospedaliero Universitaria Careggi, Florence, Italy, 3SOC Oncologia Medica, Azienda USL Toscana Centro, Florence, Italy, 4Cancer Risk Factors and Lifestyle Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Florence, Italy, 5 2nd Medical Oncology Division, Department of Oncology, AOU Citt a Della Salute e Della Scienza, Turin, Italy, 6Oncologia, Dipartimento Oncologico - Azienda USL Toscana 7 Nord Ovest, Livorno, Italy, Medical Oncology, Ospedale Versilia USL12, Lido Di a, Camaiore, Italy, 8U.O.C di Medicina Interna Internistica ad indirizzo di Continuit Ospedale San Giuseppe, Empoli, Italy, 9Breast Surgery Unit, Azienda Ospedaliero 10 Universitaria Careggi, Florence, Italy, Diagnostic Senology, Azienda Ospedaliero Universitaria Careggi, Florence, Italy Background: SAFE trial (NCT2236806) is a phase 3 study comparing the effect on subclinical heart damage of bisoprolol (B), ramipril (R), or both drugs (RþB), as compared to placebo (P), in breast cancer treated with (neo)adjuvant anthracyclines þ/trastuzumab. Methods: Primary endpoint is subclinical cardiotoxicity measured with echocardiography and global linear strain (GLS). This interim analysis was pre-specified on the first 120 patients who had completed cardiological assessments at 12-mos. Stopping rules per arm were: dose reduction >15%, study withdraw rate >5%, and no significant impact on 3D-left ventricular ejection fraction (3D-LVEF) as compared to T0 at 12mos assessment. Results: A total of 191 out of 480 patients have been enrolled; overall 123 patients were available for the analysis (P ¼ 34; R ¼ 28; B ¼ 31; RþB¼30). 3D-LVEF decreased at 3mos (-3.3%; p < 0.001), at 6-mos (-5.2%; p < 0.001) and at 12-mos (-3.7%; p ¼ 0.004) respect to T0 in P; at 3-mos (-2.4%; p ¼ 0.001), at 6-mos (-1.9%; p ¼ 0.010), at 12-mos
v72 | Breast Cancer, Early Stage
(-2.2%; p ¼ 0.045) in R. In B and RþB patients no significant changes were observed at 3- and 12-mos, with a decrease at 6-mos (-2.5% and 3.0%, respectively; p ¼ 0.002). Arm differences were significant (p ¼ 0.038). GLS increased at 3-mos (5.7%; p < 0.001), at 6-mos (7.8%; p < 0.001) and at 12-mos (7.1%; p < 0.001) respect to T0 in P; at 3-mos (2.7%; p ¼ 0.002), at 6-mos (3.2%; p ¼ 0.014), but not at 12-mos in R; no significant changes at 3-mos, a significant increase at 6-mos (2.7%; p ¼ 0.035), at 12-mos (3.2%; p ¼ 0.008) in B; no significant changes at 3-, 6-, and 12-mos in RþB. Arm differences were significant (p ¼ 0.002). Both RþB and the R arms showed a withdraw rate of 7%, with a dose reduction rates of 21% and 17%, respectively. R arm showed a significant decrease on 3D-LVEF at 12-mos as compared to T0 and will be evaluate for closure. Conclusions: Following the stopping rules, the closure of the R arm is required and the study will continue with 3 arms. At the interim analysis, a cardioprevention strategy significantly impact on subclinical heart damage. Clinical trial identification: NCT2236806. Legal entity responsible for the study: University of Florence. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
215P
Safety of hypofractionated whole breast irradiation after conservative surgery for patients aged less than 60 years: A multi-center comparative study
I. Meattini1, L. Livi1, K. Kim2, J. Kim2, W. Jung2, E. Olmetto1, I. Desideri1, C. Saieva3, C. Becherini1, V. Salvestrini1, A. Fourquet4, Y. Kirova4, P. Poortmans4 1 Department of Biomedical, Experimental, and Clinical Sciences, University of Florence, Florence, Italy, 2Radiation Oncology, Ewha Womans University College of Medicine, Seoul, Republic of Korea, 3Cancer Risk Factors and Lifestyle Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical network (ISPRO), Florence, Italy, 4Radiation Oncology, Institut Curie, Paris, France Background: For decades, conventionally fractionated whole breast irradiation (CFWBI) was used after breast conserving surgery (BCS). Pivotal phase 3 trials on hypofractionated-WBI (HF-WBI) showed its non-inferiority as compared to CF-WBI. However, younger patients (<60 years) are not currently worldwide treated with HFWBI. The aim of this multi-center comparative study is to confirm the safety of HFWBI in a real-life series of younger patients. Methods: Between 2010 and 2016, a total of 786 patients aged less than 60 years old with early stage breast cancer were treated with postoperative WBI after BCS in three breast cancer centers: 340 underwent HF-WBI while 446 were treated with CF-WBI. Acute toxicity was evaluated at the end of WBI. Late toxicity was evaluated at 6, 12, 24, and 36 months. Results: At univariate logistic analysis, hypofractionation showed a significant protective effect in terms of acute edema (p ¼ 0.0001), acute wet desquamation (p ¼ 0.009), chronic edema (p ¼ 0.0001), chronic erythema/pigmentation (p ¼ 0.0001), and breast fibrosis (p ¼ 0.0002). At multivariate logistic analysis, hypofractionation was independent significant factor for acute edema (OR 0.09, 95% CI 0.02 to 0.48; p ¼ 0.005), acute wet desquamation (OR 0.07, 95% CI 0.009 to 0.59; p ¼ 0.014), and chronic edema (OR 0.18, 95% CI 0.04 to 0.75; p ¼ 0.018). Significant association between individual characteristics and toxicity (grade 2 or more) are summarized in Table. Conclusions: HF-WBI showed significantly improved toxicity outcomes in terms of both acute skin edema and wet desquamation, and chronic skin edema. HF-WBI after BCS should replace CF-WBI independently of age. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
216P
Usefulness of NT-ProBNP as a biomarker of cardiotoxicity in breast cancer patients treated with trastuzumab
I. Blancas1, C. Martın2, F.J. Martın-Pe´rez2, M. Legere´n1, M. Martos2, S. Sequero1, S. Carnenero1, M.E. Pe´rez-Garcıa1, C.J. Rodrıguez-Gonzalez1, J.M. Jurado1, M. Delgado1, B. Gonzalez-Astorga1, I. Gonzalez-Cebrian1, J.M. Garrido3, C. Prieto1, V. Bayo-Martin1, M.I. Fernandez-Gutie´rrez1, G. Ayala-Carbonero4, S. Reyes-Larzategui5, F. RodrıguezSerrano6 1 Oncology Unit, San Cecilio University Hospital, Granada, Spain, 2Department of Medicine, University of Granada, Granada, Spain, 3Department of Surgery, University of Granada, Granada, Spain, 4Department of Radiology, San Cecilio University Hospital, Granada, Spain, 5Department of General Surgery, San Cecilio University Hospital, Granada, Spain, 6Institute of Biopathology and Regenerative Medicine, University of Granada, Granada, Spain Background: Trastuzumab is a highly efficient drug in HER2-positive breast cancer that increases patient survival. Due to cardiotoxicity is the most important side effect of trastuzumab treatment, cardiac monitoring should be a priority, especially in the presence of comorbidities. Left ventricle ejection fraction (LVEF) determination remains the most used technique to diagnose cardiotoxicity in clinical practice. The purpose of
Volume 30 | Supplement 5 | October 2019
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Background: Pathologic complete response (pCR) is a surrogate marker of a better relapse-free (RFS) and overall survival (OS), particularly in HER2 overexpressing and triple-negative breast cancer (TNBC) subtypes. Our aim is to assess the impact of HER2 expression level on pCR, in patients with luminal or TNBC treated with neoadjuvant chemotherapy (NAC). Methods: We conducted a retrospective analysis in luminal and TN non-metastatic breast cancer patients, addressed to cancer center Georges Franc¸ois Leclerc in Dijon for NAC. Hormone receptor and HER2 expression were centrally assessed according to CAP/ASCO criteria. The pathologic response was dichotomized in pCR and non-pCR and evaluated according to Chevalier classification. Results: Between 2007 and 2018, 761 patients (pts) were recorded, of which 263 (34.5%) had TNBC and 498 (65.5%) luminal-HER2 negative BC. Among TNBC, 189 pts (70.8%), 54 pts (20.2%) and 24 pts (8.9%) had respectively score 0, 1 and 2, and negative FISH. In luminal tumors these results were respectively 246 (49.3%), 181 (36.3%) and 21 (4.2%). Median age, size of primary tumour and lymph node involvement were similar in both subpopulations. Regarding NAC, 20.9% received only taxanes, 22.1% only anthracyclines and 55.1% both agents. The combination was more often recommended in TNBC 74.2% vs 59.3% (p ¼ 0.03). pCR rate in the primary tumour and lymph nodes was 29% (157 pts) in the whole cohort. This rate varied according to HER2 expression (0, 1þ, 2þ) from respectively 48.6% (51pts), 36.4% (8pts) and 28.6% (4pts) (p ¼ 0.256) in TNBC and from 8.5% (7pts), 5.3% (5pts) and 4.1% (2pts) (p ¼ 0.532) among luminal tumors. Both OS and RFS were associated with a good Chevalier pathologic response (p < 0.001) in TNBC but not in luminal tumours (p ¼ 0.5257 and p ¼ 0.9845). Neither pCR, nor the Chevalier response was statistically correlated with HER2 score. Conclusions: No correlation between pCR and the level of HER 2 expression was found neither in luminal nor in TNBC patients. In TNBC patients, differences in terms of pCR were noticed between the 3 HER expression groups. The predictive role of HER2 expression should be further explored in early localized TNBC in a larger population. Editorial acknowledgement: Isabel Gregoire, medical writer, Department of Biostatistics Georges Francois Leclerc Cancer Center, Dijon, France. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Annals of Oncology
abstracts
Annals of Oncology
Table: 215P N
Protective factor
p-value
OR (95%CI)
Risk factor
p-value
OR (95%CI)
Acute edema
43
0.0001 0.001
0.09 (0.03-0.30) 0.16 (0.06-0.46)
Chemotherapy
0.002
2.63 (1.42-4.90)
Chronic edema
50
0.0001 0.003
0.20 (0.09-0.44) 0.31 (0.14-0.66)
Acute erythema/ pigmentation
163
Hypofractionation Dmax/Prescribed dose <107% Hypofractionation Dmax/Prescribed dose <107% HER2 positive status Trastuzumab
0.002 0.022
0.30 (0.14-0.63) 0.39 (0.18-0.87)
Chronic erythema/ pigmentation
110
Hypofractionation Dmax/Prescribed dose <107%
0.0001 0.001
0.40 (0.25-0.63) 0.45 (0.28-0.73)
Acute wet desquamation
20
0.009 0.047
0.14 (0.03-0.61) 0.29 (0.08-0.99)
0.0001 0.032 0.003 0.001 0.038 0.002 0.0001 0.002 0.007 0.034 -
3.0 (1.66-5.46) 9.02 (1.21-67.45) 2.67 (1.41-5.05) 2.14 (1.37-3.32) 2.60 (1.06-6.41) 1.78 (1.24-2.54) 2.39 (1.54-3.71) 3.47 (1.56-7.71) 15.43 (2.08-114.3) 1.58 (1.04-2.41) -
Breast fibrosis
117
Hypofractionation Dmax/Prescribed dose <107% Hypofractionation Tumor grade Ki67 index Dmax/Prescribed dose <107%
EIC presence Boost dose >10 Gy Breast size >492 cc Smoking habits Boost dose >10 Gy Breast size >492 cc EIC presence Positive FSM Boost dose >10 Gy Breast size >492 cc -
0.0002 0.022 0.023 0.017
0.44 (0.29-0.68) 0.53 (0.31-0.92) 0.60 (0.38-0.93) 0.58 (0.37-0.91)
EIC presence Boost dose >10 Gy Breast size >492 cc
0.0001 0.022 0.0001
3.03 (1.99-4.62) 6.76 (2.04-22.45) 2.84 (1.83-4.41)
this study is to analyse the usefulness of NT-ProBNP as a biomarker of cardiotoxicity in breast cancer patients treated with trastuzumab. Methods: The study included 66 patients who received trastuzumab. We collected the LVEF and NT-proBNP values measured during the course of treatment, and cardiovascular risk factors including diabetes, hypertension, smoking, hypercholesterolemia and BMI. Cardiotoxicity was diagnosed during the follow-up program considering a decrease of the LVEF from baseline or clinical manifestation of congestive heart failure. According to the literature, NT-proBNP cut-off points were considered to stablish normal or abnormal values in terms of patent age. Results: 174 paired LVEF/NT-proBNP values were found. 27.3% of patients suffered cardiotoxicity during trastuzumab treatment and most of cases were diagnosed based on cardiac symptomatology (66.7 %). Logistic regression analysis of NT-proBNP and the cardiovascular risk factors showed a significant association of diabetes mellitus (OR 5.9, 95% CI 1.2 - 28.5, p ¼ 0.028) and NT-proBNP (OR 22.0, 95% CI 5.7 - 85.4, p ¼ 0.000) with the development of cardiotoxicity during trastuzumab treatment, whereas the other variables were not statistically significant. Conclusions: Diabetes and NT-proBNP values seem to be associated with an increased risk of cardiotoxicity in breast cancer patients during trastuzumab treatment. In diabetics, glycaemic control and a more intense cardiac monitoring could provide objective benefits during the treatment. Moreover, NT-proBNP determination could become an accessible way to evaluate cardiac risk in this context. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
217P
The routine use of sentinel lymph node biopsy in high risk DCIS lesions is not justified
F. Preat, A. Bohlok, V. Donckier, J.M. Nogaret Surgery, Institute Jules Bordet, Brussels, Belgium Background: The use of sentinel lymph node biopsy (SLNB) during breast surgery for ductal carcinoma in situ (DCIS) is controversial. It is accepted in high risk lesions (high histological grade, palpable, large >25 mm, and multifocal lesions) since it avoids a second operation if the definitive diagnosis reveals infiltrating ductal carcinoma (IDC) and its recommended due to some technical obligations in patients with planned total mastectomy or with tumor localization to the upper outer quadrant.. We aimed to evaluate the use of SLNB in patients with preoperative diagnosis of high risk DCIS lesions. Methods: A monocentric retrospective study was conducted on 467 patients with primary diagnosed DCIS operated for partial or total mastectomy with or without SLNB. The frequency of each risk factor, and the incidence of IDC were calculated in the overall series. The predictive value of each risk factor is calculated by comparing these
Volume 30 | Supplement 5 | October 2019
factors in the groups depending to the definitive pathology (IDC vs DCIS) using the chi square test. A value of p < 0.05 was considered significant. Results: Breast surgery was done within a median of 42 6 23 days of DCIS diagnosis. Median age was 576 10 years. High risk DCIS lesions accounted for 73.1% of all cases (342/468). Grade III lesion, multifocal, palpable and larger than 25 mm lesions were present in 263 (56.3%), 61 (13.1%), 86 (18.4%) and 99 (21.2%) respectively. IDC was diagnosed in 95/468 patients (20.3%) in the global series and in 75patients/342 (22%) in the patients with high risk lesions. A palpable lesions and a tumor diameter >25 mm were associated with higher risk of invasive carcinoma (p ¼ 0.007 and p ¼ 0.017 respectively).Overall SLNB was done in 383 patients (82%), of which 318 patients (83%) had high risk lesions. A Positive SLN was detected in overall 5 patients (1.3%), all of which had high risk lesions (5/318: 1.6%). Conclusions: In our study, the preoperative classification of high risk lesion showed a 79% sensitivity (75/95) and a 22% specificity (75/342) of detecting IDC. A positive SLN was found in only 1.6% of patients with high risk CDIS lesions operated for SLNB. The use of SLNB in patients with high risk DCIS avoids reoperation in 22% of cases. Nevertheless the low risk of positive SLN finding in this setting cannot justify its routine use. Legal entity responsible for the study: Jean Marie Nogaret. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
218P
Oncological impact of re-excision for positive margin status after breast conserving surgery in invasive breast cancer
K. Jimbo, C. Watase, U. Nakadaira, T. Murata, S. Shiino, S. Takayama, A. SutoBreast Surgery Division, National Cancer Center, Tokyo, Japan Background: Positive margin of breast-conserving surgery (BCS) is well known to be a risk factor for ipsilateral breast tumor recurrence (IBTR). SSO/ASTRO guidelines defined ink on invasive cancer or DCIS as positive margin and recommend considering doing re-excision of the site of positive margin. However, whether re-excision can reduce IBTR has not been fully investigated yet. The aim of this study was to retrospectively assess the oncological impact of re-excision for positive margin status after BCS in invasive breast cancer. Methods: The subjects were 196 invasive breast cancer patients who underwent BCS, and who were found to have positive margin. Of the 196 patients, 55 underwent reexcision after initial BCS (group A), and 139 did not (group B). We analyzed IBTR free survival in each group and evaluated the predictors for IBTR and overall survival (OS) using Cox proportional hazards modeling.
doi:10.1093/annonc/mdz240 | v73
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Toxicity
Response to neoadjuvant chemotherapy in HER2 non-overexpressing breast cancer subtypes
S.M. Ilie1, I. Desmoulins1, A. Hennequin1, K. Coure`che-Guillaume1, L. Arnould2, B. Nathalie3, A. Bertaut3, S. Ladoire1 1 Department of Medical Oncology, Centre Georges-Franc¸ois Leclerc (Dijon), Dijon, France, 2Department of Biology and Tumour Pathology, Centre Georges-Franc¸ois Leclerc, Dijon, France, 3Biostatistics and Data Management, Centre Georges-Franc¸ois Leclerc, Dijon, France
214P
Pre-specified interim analysis of the SAFE trial (NCT2236806): A 4-arm randomized, double-blind, controlled study evaluating the efficacy and safety of cardiotoxicity prevention in non-metastatic breast cancer patients treated with anthracyclines with or without trastuzumab
L. Livi1, G. Barletta2, F. Martella3, I. Desideri1, V. Scotti1, C. Becherini1, C. Saieva4, F. Terziani1, C. Bacci3, M. Airoldi5, G. Allegrini6, D. Amoroso7, F. Venditti2, R. Tarquini8, L. Orzalesi9, L. Sanchez9, M. Bernini9, J. Nori10, L. Fioretto3, I. Meattini1 1 Department of Biomedical, Experimental, and Clinical Sciences, University of Florence, Florence, Italy, 2Cardiology Diagnostics - Cardiothoracic & Vascular, Azienda Ospedaliero Universitaria Careggi, Florence, Italy, 3SOC Oncologia Medica, Azienda USL Toscana Centro, Florence, Italy, 4Cancer Risk Factors and Lifestyle Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Florence, Italy, 5 2nd Medical Oncology Division, Department of Oncology, AOU Citt a Della Salute e Della Scienza, Turin, Italy, 6Oncologia, Dipartimento Oncologico - Azienda USL Toscana 7 Nord Ovest, Livorno, Italy, Medical Oncology, Ospedale Versilia USL12, Lido Di a, Camaiore, Italy, 8U.O.C di Medicina Interna Internistica ad indirizzo di Continuit Ospedale San Giuseppe, Empoli, Italy, 9Breast Surgery Unit, Azienda Ospedaliero 10 Universitaria Careggi, Florence, Italy, Diagnostic Senology, Azienda Ospedaliero Universitaria Careggi, Florence, Italy Background: SAFE trial (NCT2236806) is a phase 3 study comparing the effect on subclinical heart damage of bisoprolol (B), ramipril (R), or both drugs (RþB), as compared to placebo (P), in breast cancer treated with (neo)adjuvant anthracyclines þ/trastuzumab. Methods: Primary endpoint is subclinical cardiotoxicity measured with echocardiography and global linear strain (GLS). This interim analysis was pre-specified on the first 120 patients who had completed cardiological assessments at 12-mos. Stopping rules per arm were: dose reduction >15%, study withdraw rate >5%, and no significant impact on 3D-left ventricular ejection fraction (3D-LVEF) as compared to T0 at 12mos assessment. Results: A total of 191 out of 480 patients have been enrolled; overall 123 patients were available for the analysis (P ¼ 34; R ¼ 28; B ¼ 31; RþB¼30). 3D-LVEF decreased at 3mos (-3.3%; p < 0.001), at 6-mos (-5.2%; p < 0.001) and at 12-mos (-3.7%; p ¼ 0.004) respect to T0 in P; at 3-mos (-2.4%; p ¼ 0.001), at 6-mos (-1.9%; p ¼ 0.010), at 12-mos
v72 | Breast Cancer, Early Stage
(-2.2%; p ¼ 0.045) in R. In B and RþB patients no significant changes were observed at 3- and 12-mos, with a decrease at 6-mos (-2.5% and 3.0%, respectively; p ¼ 0.002). Arm differences were significant (p ¼ 0.038). GLS increased at 3-mos (5.7%; p < 0.001), at 6-mos (7.8%; p < 0.001) and at 12-mos (7.1%; p < 0.001) respect to T0 in P; at 3-mos (2.7%; p ¼ 0.002), at 6-mos (3.2%; p ¼ 0.014), but not at 12-mos in R; no significant changes at 3-mos, a significant increase at 6-mos (2.7%; p ¼ 0.035), at 12-mos (3.2%; p ¼ 0.008) in B; no significant changes at 3-, 6-, and 12-mos in RþB. Arm differences were significant (p ¼ 0.002). Both RþB and the R arms showed a withdraw rate of 7%, with a dose reduction rates of 21% and 17%, respectively. R arm showed a significant decrease on 3D-LVEF at 12-mos as compared to T0 and will be evaluate for closure. Conclusions: Following the stopping rules, the closure of the R arm is required and the study will continue with 3 arms. At the interim analysis, a cardioprevention strategy significantly impact on subclinical heart damage. Clinical trial identification: NCT2236806. Legal entity responsible for the study: University of Florence. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
215P
Safety of hypofractionated whole breast irradiation after conservative surgery for patients aged less than 60 years: A multi-center comparative study
I. Meattini1, L. Livi1, K. Kim2, J. Kim2, W. Jung2, E. Olmetto1, I. Desideri1, C. Saieva3, C. Becherini1, V. Salvestrini1, A. Fourquet4, Y. Kirova4, P. Poortmans4 1 Department of Biomedical, Experimental, and Clinical Sciences, University of Florence, Florence, Italy, 2Radiation Oncology, Ewha Womans University College of Medicine, Seoul, Republic of Korea, 3Cancer Risk Factors and Lifestyle Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical network (ISPRO), Florence, Italy, 4Radiation Oncology, Institut Curie, Paris, France Background: For decades, conventionally fractionated whole breast irradiation (CFWBI) was used after breast conserving surgery (BCS). Pivotal phase 3 trials on hypofractionated-WBI (HF-WBI) showed its non-inferiority as compared to CF-WBI. However, younger patients (<60 years) are not currently worldwide treated with HFWBI. The aim of this multi-center comparative study is to confirm the safety of HFWBI in a real-life series of younger patients. Methods: Between 2010 and 2016, a total of 786 patients aged less than 60 years old with early stage breast cancer were treated with postoperative WBI after BCS in three breast cancer centers: 340 underwent HF-WBI while 446 were treated with CF-WBI. Acute toxicity was evaluated at the end of WBI. Late toxicity was evaluated at 6, 12, 24, and 36 months. Results: At univariate logistic analysis, hypofractionation showed a significant protective effect in terms of acute edema (p ¼ 0.0001), acute wet desquamation (p ¼ 0.009), chronic edema (p ¼ 0.0001), chronic erythema/pigmentation (p ¼ 0.0001), and breast fibrosis (p ¼ 0.0002). At multivariate logistic analysis, hypofractionation was independent significant factor for acute edema (OR 0.09, 95% CI 0.02 to 0.48; p ¼ 0.005), acute wet desquamation (OR 0.07, 95% CI 0.009 to 0.59; p ¼ 0.014), and chronic edema (OR 0.18, 95% CI 0.04 to 0.75; p ¼ 0.018). Significant association between individual characteristics and toxicity (grade 2 or more) are summarized in Table. Conclusions: HF-WBI showed significantly improved toxicity outcomes in terms of both acute skin edema and wet desquamation, and chronic skin edema. HF-WBI after BCS should replace CF-WBI independently of age. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
216P
Usefulness of NT-ProBNP as a biomarker of cardiotoxicity in breast cancer patients treated with trastuzumab
I. Blancas1, C. Martın2, F.J. Martın-Pe´rez2, M. Legere´n1, M. Martos2, S. Sequero1, S. Carnenero1, M.E. Pe´rez-Garcıa1, C.J. Rodrıguez-Gonzalez1, J.M. Jurado1, M. Delgado1, B. Gonzalez-Astorga1, I. Gonzalez-Cebrian1, J.M. Garrido3, C. Prieto1, V. Bayo-Martin1, M.I. Fernandez-Gutie´rrez1, G. Ayala-Carbonero4, S. Reyes-Larzategui5, F. RodrıguezSerrano6 1 Oncology Unit, San Cecilio University Hospital, Granada, Spain, 2Department of Medicine, University of Granada, Granada, Spain, 3Department of Surgery, University of Granada, Granada, Spain, 4Department of Radiology, San Cecilio University Hospital, Granada, Spain, 5Department of General Surgery, San Cecilio University Hospital, Granada, Spain, 6Institute of Biopathology and Regenerative Medicine, University of Granada, Granada, Spain Background: Trastuzumab is a highly efficient drug in HER2-positive breast cancer that increases patient survival. Due to cardiotoxicity is the most important side effect of trastuzumab treatment, cardiac monitoring should be a priority, especially in the presence of comorbidities. Left ventricle ejection fraction (LVEF) determination remains the most used technique to diagnose cardiotoxicity in clinical practice. The purpose of
Volume 30 | Supplement 5 | October 2019
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Background: Pathologic complete response (pCR) is a surrogate marker of a better relapse-free (RFS) and overall survival (OS), particularly in HER2 overexpressing and triple-negative breast cancer (TNBC) subtypes. Our aim is to assess the impact of HER2 expression level on pCR, in patients with luminal or TNBC treated with neoadjuvant chemotherapy (NAC). Methods: We conducted a retrospective analysis in luminal and TN non-metastatic breast cancer patients, addressed to cancer center Georges Franc¸ois Leclerc in Dijon for NAC. Hormone receptor and HER2 expression were centrally assessed according to CAP/ASCO criteria. The pathologic response was dichotomized in pCR and non-pCR and evaluated according to Chevalier classification. Results: Between 2007 and 2018, 761 patients (pts) were recorded, of which 263 (34.5%) had TNBC and 498 (65.5%) luminal-HER2 negative BC. Among TNBC, 189 pts (70.8%), 54 pts (20.2%) and 24 pts (8.9%) had respectively score 0, 1 and 2, and negative FISH. In luminal tumors these results were respectively 246 (49.3%), 181 (36.3%) and 21 (4.2%). Median age, size of primary tumour and lymph node involvement were similar in both subpopulations. Regarding NAC, 20.9% received only taxanes, 22.1% only anthracyclines and 55.1% both agents. The combination was more often recommended in TNBC 74.2% vs 59.3% (p ¼ 0.03). pCR rate in the primary tumour and lymph nodes was 29% (157 pts) in the whole cohort. This rate varied according to HER2 expression (0, 1þ, 2þ) from respectively 48.6% (51pts), 36.4% (8pts) and 28.6% (4pts) (p ¼ 0.256) in TNBC and from 8.5% (7pts), 5.3% (5pts) and 4.1% (2pts) (p ¼ 0.532) among luminal tumors. Both OS and RFS were associated with a good Chevalier pathologic response (p < 0.001) in TNBC but not in luminal tumours (p ¼ 0.5257 and p ¼ 0.9845). Neither pCR, nor the Chevalier response was statistically correlated with HER2 score. Conclusions: No correlation between pCR and the level of HER 2 expression was found neither in luminal nor in TNBC patients. In TNBC patients, differences in terms of pCR were noticed between the 3 HER expression groups. The predictive role of HER2 expression should be further explored in early localized TNBC in a larger population. Editorial acknowledgement: Isabel Gregoire, medical writer, Department of Biostatistics Georges Francois Leclerc Cancer Center, Dijon, France. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Annals of Oncology
abstracts
Annals of Oncology
Table: 215P N
Protective factor
p-value
OR (95%CI)
Risk factor
p-value
OR (95%CI)
Acute edema
43
0.0001 0.001
0.09 (0.03-0.30) 0.16 (0.06-0.46)
Chemotherapy
0.002
2.63 (1.42-4.90)
Chronic edema
50
0.0001 0.003
0.20 (0.09-0.44) 0.31 (0.14-0.66)
Acute erythema/ pigmentation
163
Hypofractionation Dmax/Prescribed dose <107% Hypofractionation Dmax/Prescribed dose <107% HER2 positive status Trastuzumab
0.002 0.022
0.30 (0.14-0.63) 0.39 (0.18-0.87)
Chronic erythema/ pigmentation
110
Hypofractionation Dmax/Prescribed dose <107%
0.0001 0.001
0.40 (0.25-0.63) 0.45 (0.28-0.73)
Acute wet desquamation
20
0.009 0.047
0.14 (0.03-0.61) 0.29 (0.08-0.99)
0.0001 0.032 0.003 0.001 0.038 0.002 0.0001 0.002 0.007 0.034 -
3.0 (1.66-5.46) 9.02 (1.21-67.45) 2.67 (1.41-5.05) 2.14 (1.37-3.32) 2.60 (1.06-6.41) 1.78 (1.24-2.54) 2.39 (1.54-3.71) 3.47 (1.56-7.71) 15.43 (2.08-114.3) 1.58 (1.04-2.41) -
Breast fibrosis
117
Hypofractionation Dmax/Prescribed dose <107% Hypofractionation Tumor grade Ki67 index Dmax/Prescribed dose <107%
EIC presence Boost dose >10 Gy Breast size >492 cc Smoking habits Boost dose >10 Gy Breast size >492 cc EIC presence Positive FSM Boost dose >10 Gy Breast size >492 cc -
0.0002 0.022 0.023 0.017
0.44 (0.29-0.68) 0.53 (0.31-0.92) 0.60 (0.38-0.93) 0.58 (0.37-0.91)
EIC presence Boost dose >10 Gy Breast size >492 cc
0.0001 0.022 0.0001
3.03 (1.99-4.62) 6.76 (2.04-22.45) 2.84 (1.83-4.41)
this study is to analyse the usefulness of NT-ProBNP as a biomarker of cardiotoxicity in breast cancer patients treated with trastuzumab. Methods: The study included 66 patients who received trastuzumab. We collected the LVEF and NT-proBNP values measured during the course of treatment, and cardiovascular risk factors including diabetes, hypertension, smoking, hypercholesterolemia and BMI. Cardiotoxicity was diagnosed during the follow-up program considering a decrease of the LVEF from baseline or clinical manifestation of congestive heart failure. According to the literature, NT-proBNP cut-off points were considered to stablish normal or abnormal values in terms of patent age. Results: 174 paired LVEF/NT-proBNP values were found. 27.3% of patients suffered cardiotoxicity during trastuzumab treatment and most of cases were diagnosed based on cardiac symptomatology (66.7 %). Logistic regression analysis of NT-proBNP and the cardiovascular risk factors showed a significant association of diabetes mellitus (OR 5.9, 95% CI 1.2 - 28.5, p ¼ 0.028) and NT-proBNP (OR 22.0, 95% CI 5.7 - 85.4, p ¼ 0.000) with the development of cardiotoxicity during trastuzumab treatment, whereas the other variables were not statistically significant. Conclusions: Diabetes and NT-proBNP values seem to be associated with an increased risk of cardiotoxicity in breast cancer patients during trastuzumab treatment. In diabetics, glycaemic control and a more intense cardiac monitoring could provide objective benefits during the treatment. Moreover, NT-proBNP determination could become an accessible way to evaluate cardiac risk in this context. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
217P
The routine use of sentinel lymph node biopsy in high risk DCIS lesions is not justified
F. Preat, A. Bohlok, V. Donckier, J.M. Nogaret Surgery, Institute Jules Bordet, Brussels, Belgium Background: The use of sentinel lymph node biopsy (SLNB) during breast surgery for ductal carcinoma in situ (DCIS) is controversial. It is accepted in high risk lesions (high histological grade, palpable, large >25 mm, and multifocal lesions) since it avoids a second operation if the definitive diagnosis reveals infiltrating ductal carcinoma (IDC) and its recommended due to some technical obligations in patients with planned total mastectomy or with tumor localization to the upper outer quadrant.. We aimed to evaluate the use of SLNB in patients with preoperative diagnosis of high risk DCIS lesions. Methods: A monocentric retrospective study was conducted on 467 patients with primary diagnosed DCIS operated for partial or total mastectomy with or without SLNB. The frequency of each risk factor, and the incidence of IDC were calculated in the overall series. The predictive value of each risk factor is calculated by comparing these
Volume 30 | Supplement 5 | October 2019
factors in the groups depending to the definitive pathology (IDC vs DCIS) using the chi square test. A value of p < 0.05 was considered significant. Results: Breast surgery was done within a median of 42 6 23 days of DCIS diagnosis. Median age was 576 10 years. High risk DCIS lesions accounted for 73.1% of all cases (342/468). Grade III lesion, multifocal, palpable and larger than 25 mm lesions were present in 263 (56.3%), 61 (13.1%), 86 (18.4%) and 99 (21.2%) respectively. IDC was diagnosed in 95/468 patients (20.3%) in the global series and in 75patients/342 (22%) in the patients with high risk lesions. A palpable lesions and a tumor diameter >25 mm were associated with higher risk of invasive carcinoma (p ¼ 0.007 and p ¼ 0.017 respectively).Overall SLNB was done in 383 patients (82%), of which 318 patients (83%) had high risk lesions. A Positive SLN was detected in overall 5 patients (1.3%), all of which had high risk lesions (5/318: 1.6%). Conclusions: In our study, the preoperative classification of high risk lesion showed a 79% sensitivity (75/95) and a 22% specificity (75/342) of detecting IDC. A positive SLN was found in only 1.6% of patients with high risk CDIS lesions operated for SLNB. The use of SLNB in patients with high risk DCIS avoids reoperation in 22% of cases. Nevertheless the low risk of positive SLN finding in this setting cannot justify its routine use. Legal entity responsible for the study: Jean Marie Nogaret. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
218P
Oncological impact of re-excision for positive margin status after breast conserving surgery in invasive breast cancer
K. Jimbo, C. Watase, U. Nakadaira, T. Murata, S. Shiino, S. Takayama, A. SutoBreast Surgery Division, National Cancer Center, Tokyo, Japan Background: Positive margin of breast-conserving surgery (BCS) is well known to be a risk factor for ipsilateral breast tumor recurrence (IBTR). SSO/ASTRO guidelines defined ink on invasive cancer or DCIS as positive margin and recommend considering doing re-excision of the site of positive margin. However, whether re-excision can reduce IBTR has not been fully investigated yet. The aim of this study was to retrospectively assess the oncological impact of re-excision for positive margin status after BCS in invasive breast cancer. Methods: The subjects were 196 invasive breast cancer patients who underwent BCS, and who were found to have positive margin. Of the 196 patients, 55 underwent reexcision after initial BCS (group A), and 139 did not (group B). We analyzed IBTR free survival in each group and evaluated the predictors for IBTR and overall survival (OS) using Cox proportional hazards modeling.
doi:10.1093/annonc/mdz240 | v73
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Toxicity