TY  - JOUR
AB  - Introduction: The aim of the present study was to estimate the impact of the addition of internal mammary chain (IMC) irradiation in node-positive left-sided breast cancer (BC) patients undergoing regional nodal irradiation (RNI) and comparatively evaluate excess relative and absolute risks of radiation-induced lung cancer/BC and ischaemic heart disease for intensity-modulated radiotherapy (IMRT) versus 3D conformal radiotherapy (3D-CRT). Methods: Four treatment plans were created (3D-CRT and IMRT-/+ IMC) for each of the 10 evaluated patients, and estimates of excess relative risk (ERR) and 10-year excess absolute risk (EAR) were calculated for radiation-induced lung cancer/BC and coronary events using linear, linear-exponential and plateau models. Results: The addition of IMC irradiation to RNI significantly increased the dose exposure of the heart, lung and contralateral breast using both techniques, increasing ERR for secondary lung cancer (58 vs. 44%, p = 0.002), contralateral BC (49 vs. 31%, p = 0.002) and ischaemic heart disease (41 vs. 27%, p = 0.002, IMRT plans). IMRT significantly reduced the mean cardiac dose and mean lung dose as compared to 3D-CRT, decreasing ERR for major coronary events (64% 3D-CRT vs. 41% IMRT, p = 0.002) and ERR for secondary lung cancer (75 vs. 58%, p = 0.004) in IMC irradiation, without a significant impact on secondary contralateral BC risks. Conclusion: Although IMC irradiation has been shown to increase survival rates in node-positive BC patients, it increased dose exposure of organs at risk in left-sided BC, resulting in significantly increased risks for secondary lung cancer/contralateral BC and ischaemic heart disease. In this setting, the adoption of IMRT seems advantageous when compared to 3D-CRT.
AU  - Figlia, V.*
AU  - Simonetto, C.
AU  - Eidemüller, M.
AU  - Naccarato, S.*
AU  - Sicignano, G.*
AU  - De Simone, A.*
AU  - Ruggieri, R.*
AU  - Mazzola, R.*
AU  - Matuschek, C.*
AU  - Bölke, E.*
AU  - Pazos, M.*
AU  - Niyazi, M.*
AU  - Belka, C.*
AU  - Alongi, F.*
AU  - Corradini, S.*
C1  - 60451
C2  - 49463
CY  - Allschwilerstrasse 10, Ch-4009 Basel, Switzerland
SP  - 358-367
TI  - Mammary chain irradiation in left-sided breast cancer: Can we reduce the risk of secondary cancer and ischaemic heart disease with modern intensity-modulated radiotherapy techniques?
JO  - Breast Care
VL  - 16
IS  - 4
PB  - Karger
PY  - 2021
SN  - 1661-3791
ER  - 

TY  - JOUR
AB  - Background: PITX2 DNA methylation has been shown to predict outcomes in high-risk breast cancer patients after anthracycline-based chemotherapy. To determine its prognostic versus predictive value, the impact of PITX2 DNA methylation on outcomes was studied in an untreated cohort vs. an anthracycline-treated triple-negative breast cancer (TNBC) cohort. Material and Methods: The percent DNA methylation ratio (PMR) of paired-like homeodomain transcription factor 2 (PITX2) was determined by a validated methylation-specific real-time PCR test. Patient samples of routinely collected archived formalin-fixed paraffin-embedded (FFPE) tissue and clinical data from 144 TNBC patients of 2 independent cohorts (i.e., 66 untreated patients and 78 patients treated with anthracycline-based chemotherapy) were analyzed. Results: The risk of 5- and 10-year overall survival (OS) increased continuously with rising PITX2 DNA methylation in the anthracycline-treated population, but it increased only slightly during 10-year follow-up time in the untreated patient population. PITX2 DNA methylation with a PMR cutoff of 2 did not show significance for poor vs. good outcomes (OS) in the untreated patient cohort (HR = 1.55; p = 0.259). In contrast, the PITX2 PMR cutoff of 2 identified patients with poor (PMR >2) vs. good (PMR ≤2) outcomes (OS) with statistical significance in the anthracycline-treated cohort (HR = 3.96; p = 0.011). The results in the subgroup of patients who did receive anthracyclines only (no taxanes) confirmed this finding (HR = 5.71; p = 0.014). Conclusion: In this hypothesis-generating study PITX2 DNA methylation demonstrated predominantly predictive value in anthracycline treatment in TNBC patients. The risk of poor outcome (OS) correlates with increasing PITX2 DNA methylation.
AU  - Napieralski, R.*
AU  - Schricker, G.*
AU  - Auer, G.*
AU  - Aubele, M.*
AU  - Perkins, J.*
AU  - Magdolen, V.*
AU  - Ulm, K.*
AU  - Hamann, M.*
AU  - Walch, A.K.
AU  - Weichert, W.*
AU  - Kiehle, M.*
AU  - Weichert, O.G.*
C1  - 60886
C2  - 49648
CY  - Allschwilerstrasse 10, Ch-4009 Basel, Switzerland
SP  - 523-531
TI  - PITX2 DNA-methylation: Predictive versus prognostic value for anthracycline-based chemotherapy in triple-negative breast cancer patients.
JO  - Breast Care
VL  - 16
IS  - 5
PB  - Karger
PY  - 2021
SN  - 1661-3791
ER  -