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  • American Association for Cancer Research (AACR)  (2)
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  • American Association for Cancer Research (AACR)  (2)
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  • 1
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 73, No. 24_Supplement ( 2013-12-15), p. PD2-2-PD2-2
    Abstract: Background: Obesity is associated with an increased risk of breast cancer (BC) and a poorer outcome. We assessed the impact of BMI on response to NACT according to BC subtypes. Methods: We retrospectively evaluated 8874 BC patients treated in 7 neoadjuvant trials with an anthracycline-taxane based chemotherapy from June 1999 to June 2011. The dosage of the chemotherapy was not adapted for BMI. We defined pCR1 as ypT0 ypN0, pCR2 as ypT0/is ypN0, overall survival (OS) as time from diagnosis to death of any cause, and disease-free survival (DFS) as time from diagnosis to recurrence of tumor or death from any cause. BC subtypes were defined as Luminal A/B (hormone receptor HR-pos/HER2-neg), HER2/Luminal (HR-pos/HER2-pos), HER2/like (HR-neg/HER2-pos), and TNBC (HR-neg/HER2-neg). BMI1 ( & lt;25kg/m2), BMI2 (25-29.9kg/m2), and BMI3 (≥30kg/m2) were defined according to WHO classification. We performed univariate analyses (cross-tabulation and X2-test) and multivariate logistic regression analyses (including HR and HER2 status, tumor and nodal stage) to investigate the effect of BMI on pCR1-2. Kaplan-Meier analyses were used to estimate survival over time. Results: Distribution of subtypes did not differ significantly by BMI (p = 0.994), with approx. 23.5% of TNBC, 48.5% of Luminal A/B, 16% of HER2/luminal and 12% of HER2/like in all BMI groups. Univariate analysis found a significant association between BMI groups and pCR2 rate (22.5% for BMI1, 21.2% for BMI2, and 18.3% for BMI3; p = 0.002), but only a trend in association with pCR1 (p = 0.101). Association with pCR2 was also significant in Luminal A/B patients (n = 3250, p = 0.046). In TNBC (n = 1570) only a marginal trend in association was found (p = 0.104). No association was found in HER2/Luminal (n = 1077, p = 0.483) and HER2/like (n = 806, p = 0.358). In multivariate analyses, BMI groups predicted pCR2 (p = 0.035; BMI2 OR = 0.94, CI 0.82-1.08, p = 0.416; BMI3 OR = 0.80, CI 0.67-0.95, p = 0.009), but not pCR1 (p = 0.494). Survival analyses showed a significant decrease in OS and DFS for obese patients (OS 98.6 months for BMI1, 97.6 for BM2 and 94.1 for BMI3, overall p & lt;0.001; DFS 91.3, 90.0 and 86.2 months respectively, overall p = 0.005). In Luminal A/B patients OS was 103.9, 99.0 and 97.1 months respectively (overall p = 0.001) and DFS was 96.4, 92.1 and 90.5 months, respectively (overall p = 0.025). In TNBC patients OS was 85.0, 90.3 and 73.2 months respectively (overall p = 0.008) and DFS was 77.5, 77.7 and 66.7 months (p = 0.014), respectively (overall p = 0.050). No statistical differences were observed in HER2/Luminal (OS p = 0.354, DFS p = 0.094) and HER2/like (OS p = 0.449, DFS p = 0.179). For 6984 patients with residual invasive cancer after neoadjuvant treatment, OS was 94.6 months for BMI1, 95.8 for BMI2 (p = 0.858), and 90.9 for BMI3 (overall p & lt;0.001). DFS was 87.2, 87.6 and 83.1 months, respectively (overall p = 0.005). No statistical differences were observed in patients who achieved a pCR irrespective of the definition. Conclusion: Our data demonstrate a lower pCR2 rate in obese/overweight BC patients receiving NACT and a detrimental impact of obesity on OS and DFS, especially in patients with residual disease. Results are consistent among TNBC and Luminal A/B patients. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr PD2-2.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2013
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
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  • 2
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 76, No. 4_Supplement ( 2016-02-15), p. P3-07-55-P3-07-55
    Abstract: Background: The epigenetic profile of triple-negative breast cancer (TNBC) showed a wide prevalence of MGMT promoter methylation.Aberrant methylation of MGMT seems to be an independent predictor of poor survival in patients with basal-like breast cancer. Moreover, patients with MGMT-negative basal-like tumors who received cyclophosphamide had asignificantly improved DFS and OS compared with MGMT-positive tumors.However, the impact of MGMT methylation in the context of modern therapy concepts is not clear. Methods: We retrospectively evaluated 174 TNBC tumors of patients enrolled into the neoadjuvantGeparSixtotrial from 08/2011 to 12/2012. Patients were randomized to receive 18 weeks of neoadjuvant treatment with paclitaxel (80mg/m2/week) and non-pegylated liposomal doxorubicin (20mg/m2/week) with or without addition of carboplatin (AUC 2.0-1.5/week).Hormone-receptor status, HER2status, and Ki67 were centrally confirmed prior to randomization. We defined pathological complete response (pCR)as ypT0/is ypN0. MGMT promoter methylation status was determined by PCR using EZ DNA Methylation Kit™ (Zymo Research); TNBCtumors were considered to be methylated if they had an average methylation ≥10%, some tumors were considered borderline due to high heterogeneity among GpC islands.We investigated the effect of MGMT methylation on pCR and its correlation with baseline characteristics. Results: A total of210 tumors from the TNBC cohort of the GeparSixtotrial(n=315) were available with a tumor content & gt;20%. In 174 tumors the methylation assay was performed successfully. The number of tumorswith methylated MGMT was similar in carboplatin vs. non-carboplatin treated cohorts. In the carboplatin group 19.3% (17/88) of TNBC were methylated, 65.5% (58/88)unmethylated, and 14.8% (13/88) borderline.In the non-carboplatin group 20.9% (18/86) of TNBC were methylated, 62.8% (54/86)unmethylated, and 16.3% (14/86) borderline.In the entire cohort,there was no association between MGMT methylation status and pCR (p=0.522).Non-carboplatin cohort: 33.3% (6/18) of patients with methylated MGMT achieved pCR vs. 51.9% (28/54) of unmethylatedand 21.4% (3/14) of borderline (p=0.079).Carboplatin cohort: 52.9% (9/17) of patients with methylated MGMT achieved pCR vs. 55.2% (32/58) of unmethylatedand 76.9% (10/13) of borderline (p=0.320). In TNBC patients with methylated MGMT, the addition of carboplatin resulted in a 20% increased pCR rate (p=0.241). Conclusion: In this study no statistically significant association between MGMT methylation andpCR was found.Patients with MGMT methylation seemed to have a lower possibility to achieve a pCR and the addition of carboplatin seemed to reverse this effect. However, a clear classification of the borderline MGMT samples and further studies in larger series of TNBC are warranted. Citation Format: Fontanella C, Gehlhaar C, Denkert C, Schneeweiss A, Heppner B-I, Koch I, Blohmer J-U, Jackisch C, Lederer B, Fasching PA, Müller V, Untch M, Aprile G, Puglisi F, Nekljudova V, Heppner F, von Minckwitz G, Loibl S. Predictive value of O6-methylguanine-DNA methyltransferase (MGMT) promoter gene methylation in triple-negative breast cancer patients receiving carboplatin. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-07-55.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2016
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    Location Call Number Limitation Availability
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