Wie in jedem Jahr hat auch in diesem Jahr die onkologische Fachwelt mit Spannung neue Therapiedaten von der 41. Jahrestagung der American Society of Clinical Oncology erwartet. Dabei haben das Mammakarzinom und die gynäkologischen Malignome wieder einmal einen breiten Raum eingenommen.
Abstract Background: We previously demonstrated that the majority of women ≤45 years experienced chemotherapy-induced ovarian failure (CIOF) after CT for EBC. Age, CT regimen, duration and dose-density influenced the rate of CIOF. The regain of premenopausal Follicle-Stimulating Hormone (FSH) and Estradiol (E2) levels after chemotherapy is not equivalent to fertility restoration. The Anti-Muellerian Hormone (AMH) assessment seems to be more accurate than other hormones in predicting the ovarian reserve. FSH, E2 and AMH have been prospectively assessed in young patients receiving (neo)adjuvant CT. Methods: 740 patients (pts) aged ≤45yrs treated with anthracycline or taxane-based CT for EBC from 4 German neoadjuvant/adjuvant trials were included. Blood samples were collected at baseline before CT (N=740), end of treatment (EOT n=740), 6 (n=177), 12 (n=113), 18 (n=69), 24 (n=47) months (m) after EOT. Only the full set of samples of a given patient was included. FSH, E2 and AMH were centrally assessed. Postmenopausal hormone levels of FSH and E2 according to the central laboratory were defined as FSH>12.4IU/l and E2<52.2ng/l; fertile level of AMH as ≥0.22ng/ml. Regain of premenopausal hormone levels was defined as the time point from EOT to premenopausal FSH and E2 level regain and was assessed only for those pts with postmenopausal FSH and E2 levels at EOT. Pts with no regain have been censored at the date of the last hormone assessment. Results: Median age was 40yrs (range 21-45); 57.2% had BMI 18.5-<25, 41.1% ≥25; 32% had luminal-like, 35.9% HER2+, 32.0% triple-negative BC. Median hormone levels at different time points are presented in Table 1. Before chemotherapy 14.2% of pts had non-fertile hormone levels of AMH despite premenopausal levels of FSH and E2 compared to 77.3% of pts with postmenopausal levels (p<0.001); at EOT 77.4% vs 99.8% (p<0.001); at 6m 82.1% vs 100% (p<0.001); at 12m 80.7% vs 98.4% (p=0.002); at 18m 66.7% vs 100% (p<0.001); at 24 m 72.4% vs 100% (p=0.017). Similar results were observed in 47 pts with all time point samples available. Of 147 pts with postmenopausal hormone levels of FSH and E2 at EOT, 32.7% (95%CI 25.7%-40.9%) regained premenopausal hormone levels within 6m, 51.0% (95%CI 42.3%-60.4%) within 12m, 66.6% (95%CI 55.2%-77.6%) within 18m and 69.9% (95%CI 57.8%-81.3%) within 24m. Conclusion: Nearly 70% of women regain premenopausal hormone levels of FSH and E2 within 2 years after end of CT. Despite that, only less than one third maintain their fertility potential as predicted by AMH. AMH is a very sensitive marker for the prediction of fertility function after CT for EBC. Table 1 Median and range of FSH, E2 and AMH levels per time pointsTimepointFSH,IU/lE2, ng/mLAMH, ng/ml% of pts with AMH levels above dtBaseline6.0 [dt-142.7]88.0 [dt-2375.0]0.96 [dt-16.18]95.4EOT76.1 [1.9-225.0]dt [dt-632.0]dt [dt -3.11]15.66 m41.4 [1.1-190.6]10.0 [dt-929.0]dt [dt -3.11]26.112 m28.7 [1.1-146.0]11.0 [dt-947.0]dt [dt -2.81]29.218 m20.6 [0.8-172.3]19.0 [dt-624.0]dt [dt -1.89]34.824 m16.30 [dt-93.9]44.0 [dt-11795.0]dt [dt -1.75]38.3Abbreviations: dt, detectable threshold, EOT, end of treatment; m, month; pts, patients. Detectable threshold: FSH<0.1IU/l, E2<5ng/l, AMH<0.03ng/ml Citation Format: Furlanetto J, Thode C, Huober J, Denkert C, Bassy M, Hanusch C, Jackisch C, Kümmel S, Schneeweiss A, Untch M, Fasching PA, Karn T, Marmé F, van Mackelenbergh M, Müller V, Schem C, von Minckwitz G, Strik D, Nekljudova V, Loibl S. Changes in hormone levels (E2, FSH, AMH) and fertility of young women treated with neoadjuvant chemotherapy (CT) for early breast cancer (EBC) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD7-09.
10511 Background: The polyadenosine diphosphate [ADP]-ribose polymerase-1 (PARP-1) plays a key role in the genomic stability, transcription, chromatin remodelling and apoptosis. Increased expression is considered to be associated with resistance to DNA damage- inducing therapeutic agents. We investigated PARP expression in various hormone (HR) / HER2 receptor subtypes of early breast cancer. Methods: Tissue microarrays from core biopsies of 646 patients recruited to the phase III GeparTrio trial, who received neoadjuvant 6-8 cycles TAC/NX chemotherapy, were centrally stained immunohistochemically for PARP, ER, PgR and HER2. Cytoplasmatic and nuclear staining of PARP was assessed with regard to intensity and percentage and scored as low, medium or high expression. Its predictive value for pathological complete response (pCR; defined as no invasive residuals in breast and nodes) was evaluated. Results: Overall, cytoplasmatic PARP expression was high in 23.7%, medium in 50.6% and low in 25.7% of patients. High expression was found in 18.8% of 309 HR+/HER2-, 20.0% of 145 HR+/HER2+, 34.4% of 61 HR-/HER2+ and 34.2% of 114 HR-/HER2- tumours (p=0.001). High PARP expression was significantly correlated with undifferentiated tumour pattern (p<0.001), non-lobular cancers (p<0.001), negative HR (p<0.001). PCR rate was 26.5% (95% CI: 20.1-30.0), 19.1% (95% CI: 15.2-23.7), and 8.9% (95% CI: 4.7-13.2) in patients with high, medium, or low cytoplasmatic expression, respectively (p<0.0005). Cytoplasmatic PARP expression reached statistically significance (p<0.0005) in univariate logistic regression analysis. In multivariate regression analysis age, hormone, and HER2 receptor status remained significant predictors of pCR, and cytoplasmatic PARP expression revealed borderline significance (p=0.078). Tumor grade lost all its predictive value. No such correlations were found regarding nuclear PARP staining. Conclusions: Cytoplasmatic PARP expression can be detected by immunohistochemistry in all subtypes of early breast cancers and is correlated with an aggressive biological tumour pattern. Cytoplasmatic PARP expression predicts pCR to neoadjuvant taxane-anthracycline-based chemotherapy. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, AstraZeneca, Bristol-Myers Squibb, Roche, sanofi-aventis Amgen, AstraZeneca, Roche, sanofi-aventis
Several scores have been developed in order to estimate the prognosis of patients with brain metastases (BM) by objective criteria. The aim of this analysis was to validate all three published graded-prognostic-assessment (GPA)-scores in a subcohort of 882 breast cancer (BC) patients with BM in the Brain Metastases in the German Breast Cancer (BMBC) registry. The median age at diagnosis of BM was 57 years. All in all, 22.3% of patients (n = 197) had triple-negative, 33.4% (n = 295) luminal A like, 25.1% (n = 221) luminal B/HER2-enriched like and 19.2% (n = 169) HER2 positive like BC. Age ≥60 years, evidence of extracranial metastases (ECM), higher number of BM, triple-negative subtype and low Karnofsky-Performance-Status (KPS) were all associated with worse overall survival (OS) in univariate analysis (p < 0.001 each). All three GPA-scores were associated with OS. The breast-GPA showed the highest probability of classifying patients with survival above 12 months in the best prognostic group (specificity 68.7% compared with 48.1% for the updated breast-GPA and 21.8% for the original GPA). Sensitivities for predicting 3 months survival were very low for all scores. In this analysis, all GPA-scores showed only moderate diagnostic accuracy in predicting the OS of BC patients with BM.
