Primary Breast Cancer Pts Research Articles

HRD signature and HRD genomic landscape of tumors from 896 patients with early-stage breast cancer (BC).

539 Background: Pathologic mutations in BRCA1, BRCA2 and PALB2 lead to impaired homologous recombination repair (HRR). Cells with defects in HRR are dependent on non-homologous DNA end joining for DNA repair through the poly(ADP-ribose) polymerase (PARP) catalytic activity. PARP inhibitors (olaparib, talazoparib) are FDA-approved therapies that are toxic to tumors with HRR deficiency (HRD) and are recommended as adjuvant therapy in high-risk germline BRCA (g BRCA) positive BC. Despite the clinical implications of HRD, the prevalence of HRR alterations and HRD signature in early-stage primary BC and its association with hormone receptor (HR) status has not been well characterized. Methods: This study used the nationwide (US-based, ~280 US cancer clinics) de-identified Flatiron Health-Foundation Medicine BC clinico-genomic database and included patients (pts) who underwent tissue comprehensive genomic profiling (FoundationOne/FoundationOneCDx) between 2014 and 2022. The analysis included all pts with BC who presented with “early” stage I-III disease), had a primary tissue specimen collected within 3 months of diagnosis, and had a reportable novel scar-based HRD signature (HRDsig). Results: A total of 896 primary BC pts with stage I-III met our inclusion criteria. Of these early BC pts 21% (188/896) were HRDsig+ (stage I: 17% (32/188); stage II: 22% (84/376); and stage III: 22% (72/332)). For early BC pts, high rates of HRDsig+ were seen in g BRCA (87% [34/39]), somatic BRCA (s BRCA, 78% [14/18]), and g PALB2 (71% [5/7]) mutated tumors, with a lower rate seen with other HRR genes [16% (10/63); ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, sPALB2, RAD51B, RAD51C, RAD51D and RAD54L]. HRDsig+ was also detected in 16% (135/832) of BC without g/s BRCA or g PALB2 mutations. BC pts who presented with stage I-III disease has similar prevalence of HRDsig+ when compared to those with stage IV disease (21% [188/896] vs 23% [177/767], p = 0.31), with similar trends in HR+ disease (HR+/HER2+: 7% [4/57] vs 9% [4/45], p = 0.73; and HR+/HER2-: 17% [78/466] vs 18% [82/463], p = 0.73). Conversely, in HR- cohorts, decreased prevalence of HRDsig+ was observed in the stage I-III vs stage IV cohort (HR-/HER2+: 3% [1/38] vs 18% [6/33], p = 0.04; HR-/HER2-: 31% [99/321] vs 38% [83/216], p = 0.08). Conclusions: In this study, HR+/HER2- group was the most common early BC subtype, followed by HR-/HER2-, HR+/HER2+, and HR-/HER2+. This distribution is similar to the SEER study, and closely reflects that of the general population. We observed the expected high rates of HRDsig+ in early-stage BC pts with g/s BRCA or g PALB2 mutations where clinical trial data already support the use of PARP inhibitors for early and advanced disease. Importantly, HRDsig positivity was also seen in 16% of early BC without g/s BRCA or g PALB2, and clinical trials will be needed to determine if these pts could also benefit from HRD directed therapies.

Abstract P3-13-03: NEOS: A randomized, open label, phase 3 trial of adjuvant chemotherapy for postmenopausal breast cancer patients who responded to neoadjuvant letrozole: First report of long-term outcome and prognostic value of response to neoadjuvant endocrine therapy

Abstract Background: Whether adjuvant chemotherapy is required for patients (pts) with intermediate-risk endocrine-responsive postmenopausal breast cancer (BC) remains unknown. Sufficient data have not been available about the long-term prognosis of patients with neoadjuvant endocrine therapy (ET). NEOS is a randomized phase III study that assessed the long-term prognosis of estrogen receptor positive (ER+) primary breast cancer (PBC) pts who received neoadjuvant ET with/without adjuvant chemotherapy. Methods: Postmenopausal BC pts with ER +/HER2 negative, T1c-2, clinically node negative, under 76 years old were enrolled at primary registration. Pts were treated by leterozole (LET) in weeks 24-28 after primary enrollment. Pts experienced progression (PD) during neoadjuvant phase were excluded at randomization and received any systemic therapy driven by investigators before or after surgery. The long-term prognosis was followed in all registered pts including PD pts. Response to neoadjuvant ET was evaluated as complete response (CR), partial response (PR) or stable disease (SD) using calipers, ultrasound and MRI (or CT) at the baseline and end of treatment before surgery. Pts who met eligibility criteria were randomized 1:1 to LET for 4.5-5 years after chemotherapy or LET alone for 4.5-5 years without chemotherapy after surgery. Pts excluded at second registration were treated any systemic therapies driven by investigators. The primary endpoint was disease-free survival (DFS) and secondary endpoints included overall survival (OS), clinical response rate in neoadjuvant phase, pathological response, and breast-conserving surgery rate. The randomization code have been blinded to the investigators. Results: Between May 2008 and June 2013, 904 patients were enrolled at primary registration from 100 institutions in Japan (median follow-up: 4.0 years) and 24 pts were withdrawn during neoadjuvant phase. The median age was 63 years, T1c:37%, T2:63%, and PgR+:78%. Clinical response rates (CR, PR, SD and PD) were2% (16pts), 48% (421pts), 45% (400pts) and 5% (43pts), respectively and, in each response category, 0% (0/16), 5.5% (23/421), 7.8% (31/400), and 20.9% (9/43) experienced DFS events. DFS in PD pts to neoadjuvant ET were statistically significantly worse than CR, PR, SD pts (p<0.0001, hazard ratio 4.7 (95% CI:2.3-9.5). The prognosis after surgery in 669 randomized pts was good regardless with/without chemotherapy, forty four pts (6.6%) experienced DFS events after surgery. The predictive markers of PD for neoadjuvant ET were yet unclear among evaluated clinical factors. Conclusion: This is the first report of DFS in the largest neoadjuvant ET trial (NEOS). The DFS of postmenopausal, ER+/HER2-, PBC pts excluding PD pts to neoadjuvant ET is highly good regardless with/without chemotherapy. Neoadjuvant ET with utilization of PD response as a prognostic marker can be considered as a standard treatment option for these patients. Clinical trial information: UMIN000001090. Citation Format: Iwata H, Masuda N, Fujisawa T, Toyama T, Ohtani S, Yamamoto Y, Kashiwaba M, Taira N, Sakai T, Hasegawa Y, Nakamura R, Akabane H, Shibahara Y, Sasano H, Yamaguchi T, Ohashi Y. NEOS: A randomized, open label, phase 3 trial of adjuvant chemotherapy for postmenopausal breast cancer patients who responded to neoadjuvant letrozole: First report of long-term outcome and prognostic value of response to neoadjuvant endocrine therapy [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 P3-13-03.

Abstract P6-11-14: Safety and effectiveness of sensor-controlled scalp cooling to prevent alopecia in primary breast cancer patients receiving neoadjuvant or adjuvant epirubicin, taxanes, or both

Abstract Background: Chemotherapy (Ctx)-induced alopecia (CIA), produces a deep psychological distress in many women involved. Sensor-controlled scalp cooling (SCSC) is now approved by the FDA due to both its effectiveness and safety to prevent CIA demonstrated in two randomized trials in patients (pts) with primary breast cancer (PBC). However, SCSC is still infrequently used in many countries due to physicians´ concerns regarding both its safety and feasibility, in particular regarding anthracycline-based Ctx [Nangia et al., 2017]. This retrospective analysis was initiated to obtain more detailed information on the effectiveness and safety of SCSC using the Paxman system (Paxman, Huddersfield, UK) in PBC pts exposed to CIA-inducing neoadjuvant (NACT) or adjuvant Ctx (ACT) based on epirubicin (E), taxanes (T), or both (ET) in the clinical routine. Methods: 79 pts who underwent SCSC alongside with Ctx for PBC from 2014-2017 were identified from our database: NACT, 41 (51.9%); ACT, 38 (48.1%); dose-dense (dd) Ctx, 56 (70.9%); non-dd Ctx 23 (29.1%); premenopausal, 44 (55.7%); postmenopausal, 35 (44.3%). The following Ctx regimens were used: E, 1 (1.3%); T, 23 (29.1%); ET, 55 (69.6%). Pts were subjected to SCSC during each Ctx cycle. CIA was quantified according to the Dean score (DS) determined 3 wks after the last Ctx cycle. Data were analyzed regarding feasibility indicated by the SCSC completion rate, quality of hair preservation (success: DS 0-2, failure: DS 3-4), reasons of SCSC discontinuation, and safety. Moreover, the following parameters were investigated in regard to the success of SCSC: menopausal status (pre- vs postpenopausal), NACT vs ACT, dd Ctx vs non-dd Ctx, E- or ET-based Ctx vs T-based Ctx. Results: 55 pts (69.6%) completed SCSC, with 36 (45.6%) experiencing complete hair preservation (DS 0), and 19 (22.8%) showing partial success (DS 1-2). 24 pts (30.4%) discontinued SCSC, with CIA being the main reason in 18 pts (22.8%). Headache or earache was reported in 2 pts (1.3%) each, and local discomfort in another 4 pts (5.1%). Side effects were all not severe and resolved quickly after cessation of SCSC. SCSC was equally effective in most analyzed subgroups. The relative risk (RR) to experience CIA was 1.11 (CI: 0.82-1.54) for post- vs premenopausal pts, 1.11 (CI: 0.83-1.53) for ACT vs NACT, and 0.99 (CI: 0.72-1.43) for dd Ctx vs non-dd Ctx. Pts receiving E or ET had a significantly higher RR for SCSC failure: 1.39 (CI: 1.04-1.81, p=0.035). However, the success rate in this group was still 62.5%, thus clearly indicating a clinically meaningful benefit. Conclusions: In our study, SCSC was feasible, safe and effective in order to prevent CIA in pts with PBC. All therapeutic subgroups benefited from SCSC. Although patients on E or ET are at higher risk for CIA, the success rate in this subgroup indicates that SCSC can be reasonably offered to patients subjected to NACT or ACT with epirubicin-containing regimens. Citation Format: Kurbacher CM, Kurbacher AT, Herz S, Kolberg G, Kettelhoit N, Schweitzer C, Kurbacher JA, Eichler C. Safety and effectiveness of sensor-controlled scalp cooling to prevent alopecia in primary breast cancer patients receiving neoadjuvant or adjuvant epirubicin, taxanes, or both [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 P6-11-14.

Abstract P4-10-17: Changes of bone turnover markers during perioperative anthracycline- and/or taxane-based chemotherapy in pre- and postmenopausal patients with primary breast cancer

Abstract Background: Loss of bone mineral density (BMD) is among the well known sequelae of pharmacological therapy of patients (pts) with primary breast cancer (PBC). Cancer therapy induced bone loss (CTIBL) progresses more rapidly as compared to normal age-related changes of BMD and is best known to be associated with aromatase inhibitors in postmenopausal pts. Chemotherapy (Ctx) may also lead to a deterioration of BMD but in contast to endocrine Tx, this phenomenon is by far less elucidated and, at least in younger pts, mostly interpreted as a secondary effect following Ctx induced ovarian failure. Previous investigations focused on the classical CMF scheme, whereas conclusive data regarding direct effects of more recent Ctx protocols on the bone metabolism of PBC pts are still lacking. This translational project was initiated to gain detailed insights into the influence of anthracycline (A)- and/or taxane (T)-based Ctx on bone turnover of both pre- and postmenopausal PBC pts in the clinical routine. Methods: Data of 109 pts (premenopausal: 49; postmenopausal: 60) with non-metastatic Ctx-naïve PBC exposed to neoadjuvant or adjuvant Ctx were analyzed. 84 pts (75%) had estrogen receptor-positive (ER+) disease, HER2- overexpression was found in 18 pts (17%). 16 pts (15%) received A-based Ctx, 34 pts (31%) received T-based Ctx, and 59 pts (54%) received A/T-based Ctx. Trastuzumab was given to 17 pts (16%) with HER2-positive disease. Serum bone markers including the C-telopeptide of type I collagen (ICTP) indicating osteoclast activity, the N-propeptide of type I collagen (P1NP) measuring osteoblast activity, and alkaline phosphatase (AP) were determined at baseline and prior to each subsequent Ctx cycle (C) up to C6. Changes of ICTP, P1NP, and AP over time were analyzed by repeated-measure ANOVA. Results: 600 Ctx cycles were analyzed. Baseline levels of ICTP (p = 0.0027), P1NP (p = 0.0063), and AP (p = 0.0007) were significantly higher in post- versus premenopausal pts. AP levels remained largely unchanged during Ctx. Trends showing an increase of ICTP from baseline until C6 in premenopausal pts and a decrease in postmenopausal pts did not reach statistical significance. In contrast, P1NP significantly declined in postmenopausal pts from baseline to C6 (p = 0.0152). In premenopausal pts, P1NP declined from baseline to C3 and thereafter increased to C6. These changes were highly significant (p = 0.0024). Conclusions: Our study represents one of the first systematic evaluations of bone turnover in pts exposed to modern A- and/or T-based Ctx for PBC in the clinical routine. Postmenopausal pts presented with higher baseline levels of all three markers which may be attributable to an enhanced bone turnover related to the loss of ovarian function prior to the initiation of Ctx. In postmenopausal pts, Ctx was associated with a sustained suppression of osteoblast activity whereas osteoblast suppression recovered until the end of Ctx in premenopausal pts. Whether these effects will translate into an increased risk of CTIBL remains a matter of further investigations which should clearly focus on the individual menopausal status. Citation Format: Kurbacher CM, Rauschenbach N, Kurbacher AT, Sperling S, Herz S, Monreal K, Kurbacher JA. Changes of bone turnover markers during perioperative anthracycline- and/or taxane-based chemotherapy in pre- and postmenopausal patients with primary breast cancer. [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 P4-10-17.

4P - Influence of anthracycline- and/or taxane-based chemotherapy on bone metabolism of patients with primary breast cancer

Background: Cancer therapy-induced bone loss (CTIBL) is well-known sequela of adjuvant endocrine therapy in postmenopausal patients (pts) with primary breast cancer (PBC). Pts exposed to chemotherapy (Ctx) with alkylators for lymphoma/leukemia own a high risk of premature CTIBL which as in premenopausal PBC pts may be mainly an indirect endocrine effect of Ctx. In contrast, data on direct effects of modern perioperative Ctx on bone metabolism are limited. This retrospective study was initiated to gain more detailed insights into the influence of perioperative anthracycline (A)- and/or taxane (T)-based Ctx on bone turnover of pts with pre- and postmenopausal PBC.Methods: A total of 109 pts (premenopausal: 49; postmenopausal: 60) receiving 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) indicating the osteoblast activity, and bone alkaline phosphatase (BALP) were determined at baseline and prior to each subsequent Ctx cycle (C) up to C6. Changes of ICTP, P1NP, and BALP over time were analyzed by repeated-measure ANOVA.Results: A total of 600 Ctx cycles were analyzed. Baseline levels of ICTP, P1NP, and BALP were significantly higher in post- versus premenopausal pts. ICTP and BALP did not significantly change during Ctx. Both an increase of ICTP from baseline until C6 in premenopausal pts and a decrease in postmenopausal pts did not reach statistical significance. In contrast, P1NP significantly declined in postmenopausal pts from baseline to C6 (p = 0.0152). In premenopausal pts, P1NP declined from baseline to C3 and then increased until C6. These changes were highly significant (p = 0.0024).Conclusion: Our study demonstrates that A- and/or T-based Ctx for PBC exhibits direct effects on bone metabolism. In postmenopausal pts, Ctx was associated with a sustained suppression of osteoblast activity. In premenopausal pts, early osteoclast suppression completely recovered during C4-6. Whether these effects will translate into an increased risk to further develop CTIBL needs to be clarified by long-term observations.Disclosure: All authors have declared no conflicts of interest. Background: Cancer therapy-induced bone loss (CTIBL) is well-known sequela of adjuvant endocrine therapy in postmenopausal patients (pts) with primary breast cancer (PBC). Pts exposed to chemotherapy (Ctx) with alkylators for lymphoma/leukemia own a high risk of premature CTIBL which as in premenopausal PBC pts may be mainly an indirect endocrine effect of Ctx. In contrast, data on direct effects of modern perioperative Ctx on bone metabolism are limited. This retrospective study was initiated to gain more detailed insights into the influence of perioperative anthracycline (A)- and/or taxane (T)-based Ctx on bone turnover of pts with pre- and postmenopausal PBC. Methods: A total of 109 pts (premenopausal: 49; postmenopausal: 60) receiving 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) indicating the osteoblast activity, and bone alkaline phosphatase (BALP) were determined at baseline and prior to each subsequent Ctx cycle (C) up to C6. Changes of ICTP, P1NP, and BALP over time were analyzed by repeated-measure ANOVA. Results: A total of 600 Ctx cycles were analyzed. Baseline levels of ICTP, P1NP, and BALP were significantly higher in post- versus premenopausal pts. ICTP and BALP did not significantly change during Ctx. Both an increase of ICTP from baseline until C6 in premenopausal pts and a decrease in postmenopausal pts did not reach statistical significance. In contrast, P1NP significantly declined in postmenopausal pts from baseline to C6 (p = 0.0152). In premenopausal pts, P1NP declined from baseline to C3 and then increased until C6. These changes were highly significant (p = 0.0024). Conclusion: Our study demonstrates that A- and/or T-based Ctx for PBC exhibits direct effects on bone metabolism. In postmenopausal pts, Ctx was associated with a sustained suppression of osteoblast activity. In premenopausal pts, early osteoclast suppression completely recovered during C4-6. Whether these effects will translate into an increased risk to further develop CTIBL needs to be clarified by long-term observations. Disclosure: All authors have declared no conflicts of interest.

Persistance of circulating tumor cells (CTCs) in peripheral blood of breast cancer (BC) patients two years after primary diagnosis

554 Background: In metastatic BC, CTCs have shown to predict treatment efficacy and reduced survival. Recent data also indicate a potential prognostic relevance of CTCs after adjuvant chemotherapy. The SUCCESS trial evaluates the role of persisting CTCs two years after diagnosis in primary BC patients treated with zoledronate. Methods: We analyzed 23 mL of peripheral blood in N+ and high-risk N- primary BC pts receiving 3xFEC(500/100/500)-3xDoc100 q3w vs. 3xFEC(500/100/500)-3xDocgemcitabine (75/1000 d1+8) chemotherapy followed by 2 yrs (4mg q3mx24m) vs. 5 yrs (4mg q3mx24m followed by q6mx36m) of zoledronate. CTC results after two years are shown. CTCs were assessed with the CellSearchSystem (Veridex, Warren, USA). After immunomagnetic enrichment with an anti-Epcam-antibody, cells were labelled with anti-cytokeratin (8,18,19) and anti-CD45 antibodies. Pts were examined after a mean of 29 months (range 20–43). Results: The data of 579 pts two years after diagnosis are available. 4.3% of pts (n = 25) presented with >1CTC in peripheral blood. In pts with the detection of CTCs, the mean number of cells was 1 (range 1–29). While we found 1 CTC in 5.9% and 2 CTCs in 1.6% of pts, 1.5% had 3–5 CTCs, 1.2% >5 CTCs. The presence of >1CTC did not correlate with tumor size (p = 0.41), nodal status (p = 0.41), grading (p = 0.45), hormonal status (p = 0.92) or HER-2-Status of the tumor (p = 0.59). In this patient group, 9.7% and 6.9% of pts had presented with >1CTC at primary diagnosis and after chemotherapy, respectively. While the presence of CTCs at diagnosis was associated with CTCs after two years (p = 0.03), there was no correlation of CTCs after chemotherapy with the results at primary diagnosis (p = 0.08) or at two years (p = 0.23). In 184 postmenopausal HR+ pts endocrine treatment data was analyzed. CTCs at two years were detected in 6.8% of pts on tamoxifen (n = 9), while 1.9% of pts were positive on anastrozole treatment (n = 1; p = 0.19). Conclusions: CTCs persisting cytostatic, endocrine and zoledronate treatment, can be observed in a relevant number of clinically recurrence-free BC patients. Longer follow-up within the German SUCCESS study will give further insight in their prognostic relevance and show whether they can be used for real time tumor phenotyping or serve as treatment target. [Table: see text]

Influence of zoledronic acid on disseminated tumor cells (DTC) in primary breast cancer patients.

Abstract Abstract #2048 Background: The presence of disseminated tumor cells (DTC) in the bone marrow is associated with an increased risk for subsequent bone metastases. Bisphosphonates reduce the occurence of bone metastases in patients (pts) with primary breast cancer (BC) with DTC. The aim of this trial was to evaluate the effect of adjuvant zoledronic acid (ZOL) on DTC in the bone marrow and the Patients and methods: Eligibilty criteria for this prospective, randomized multicenter trial were primary BC pts (pT1-4, N1-2, M0) with positive bone marrow status as determined by a standardized immunocytochemistry staining procedure. Ninety-eight pts were enrolled between April 2002 and January 2006. Randomization and medication had to be started within 28 days of primary surgery. Consenting pts were randomized to the treatment arm (ZOL 4mg i.v. q 4 weekly) or control arm. During the study, all pts received adjuvant treatment in the form of chemotherapy ± hormonal therapy or hormonal therapy alone. Bone marrow aspirations were performed to analyze the presence of DTC at surgery (baseline) and 12 months later. Efficacy and tolerability of intravenous ZOL in pts with primary Result: Bone marrow status was available for 76 patients both at baseline and 12 months after surgery. At baseline a median of 2.0 / range 1-6 (mean 2.1±1.1) DTC were detected in the ZOL group and a median of 2.0 / range 1-35 (mean 2.9±5.5) DTC in the control group. In both groups the number of detected tumor cells decreased during the 12 months follow-up with 0.5±0.8 (median 0.0; 0-2) DTC in the ZOL group and 0.9±0.8 (median 1.0; 0-2) DTC in the control group. By ANCOVA analysis a trend was seen towards a reduction of the number of DTC in the ZOL group compared with the control group (p=0.066). In addition, bone marrow-positive pts treated with ZOL were more likely to become bone marrow negative after 12 months (66.7% versus 35.1%, (p=0.009) compared to the control group. Most frequently reported AEs were musculoskeletal,arthralgia and myalgia in Conclusions: In this first prospective, randomized, multicenter trial we were able to show, that both treatment groups have a reduction in the number of DTC after 12 months as compared to baseline. There is a tendency to more reduction of DTC in the ZOL group. More pts under ZOL achieved a change from positive to negative bone marrow status than controls (p=0.009). Treatment with ZOL was safe and well tolerated. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2048.

Cost analysis of febrile neutropenia (FN) management in three tumour types in Germany

20651 Background: FN is the most frequent dose-limiting toxicity of myelosuppressive chemotherapy (CT). To date there are few data on the costs of FN management in Germany. Methods: Prospective, multicentre, observational, longitudinal study with lymphoma, non small cell lung cancer (NSCLC) and primary breast cancer (PBC) patients (pts). Pts were enrolled consecutively at the start of 1st or 2nd line (immuno-)CT in 4 German hospitals (01/05–12/06). FN was defined as fever >38ºC and ANC <1 × 109/L. If nadir ANC was unavailable, febrile leukopenia (FL) was assessed (fever >38ºC and LC <2 × 109/L). Clinical and resource use data were collected from medical charts. FN associated costs are presented from the provider perspective. Results: Medical charts from 325 pts (47% lymphoma; 37% NSCLC; 16% PBC; 46% women; 38% age ≥65 yrs) were reviewed. FN/FL occurred in 22% of lymphoma, 8% of NSCLC, 27% of PBC and 18% of all pts. In total, 68 FN/FL episodes were identified in 58 pts (see table). Fifty-five FN/FL episodes were associated with ≥1 hospital stay (lymphoma n=34, NSCLC n=10, PBC n=11). Mean±SD cost per FN/FL episode requiring hospital treatment amounted to €3950±4961 (95% CI: 2569, 5331) and varied between €4808±5839 for lymphoma (95% CI: 2666, 6949), €3627±4120 for NSCLC (95% CI: 680, 6574) and €1827±795 for PBC (95% CI: 1293, 2361). Basic hospital costs represented 55% of total costs in lymphoma, 71% in NSCLC and 83% in PBC. Drug treatment made up 22% of total costs in lymphoma, 11% in NSCLC and 9% in PBC pts. Diagnostics generated 8–11% of total direct costs. Conclusions: FN/FL costs vary by tumour type and are highest for pts with lymphoma. Main cost drivers are hospitalisation and drugs. FN/FL pts (%) All (n=58) Lymphoma (n=35) NSCLC (n=9) PBC (n=14) Regimen 54% CHOP-like 80% platinum-based 100% anthracycline-based Female 33 (57) 16 (46) 3 (33) 14 (100) Age ≥ 65 22 (38) 16 (46) 3 (33) 3 (21) ECOG ≥ 2 6 (10) 4 (11) 2 (22) 0 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen Amgen Amgen Amgen, Eli Lilly

Circulating tumor cells (CTCs) in peripheral blood of primary breast cancer patients

10595 Background: Detection of CTCs has been shown to predict decreased PFS and OAS in metastatic breast cancer, whereas only limited data has been published in the adjuvant setting. We evaluate the role of CTCs in peripheral blood at primary diagnosis and during adjuvant chemotherapy, endocrine and bisphophonate treatment within the SUCCESS-Trial (n=3,658 pts). Methods: We analyzed 23ml of peripheral blood from 1767 N+ and high risk N- primary breast cancer pts before systemic treatment. 852 of these pts have undergone follow-up blood sampling after completion of chemotherapy. The presence of CTCs was assessed with the CellSearchSystem (Veridex, Warren, USA). Briefly, after immunomagnetic enrichment with an anti-Epcam-antibody, cells were labelled with anti-cytokeratin (8,18,19) and anti-CD45 antibodies to distinguish epithelial cells and leukocytes. Results: 10% of pts with a blood sampling before systemic treatment (n=170) showed &gt;1CTC before the start of systemic treatment (mean 13, range 2–827). While we found 2 CTCs in 5% of pts, 3% had 3–5 CTCs and 1% 6–10 and &gt;10 CTCs each. The presence of CTCs did not correlate with tumor size (p=.07), grading (p=.30), hormonal status (p=.54) or Her2-Status of the primary tumor (p=.26). However, we observed a significant correlation with the presence of lymph node metastases (p=.015). None of 24 healthy individuals showed more than 1 CTC. Among those 852 pts with follow-up blood sampling after the completion of cytostatic treatment, 11% were CTC positive before starting systemic treatment (mean 7, range 2–166), while 7% of patients presented with &gt;1CTC after completion of chemotherapy (mean 6, range 2–84). Of those, initially CTC positive, 10% remained positive (n=9) and 90% had a negative CTC test after chemotherapy (n=82). Of those initially CTC negative, 93% remained negative (n=711), whereas 7% returned with a positive CTC test (n=50) (p=.24). Conclusions: Our data show good feasibility of this highly standardized and easily applicable approach for the detection of CTCs in a large number of primary breast cancer patients. In a considerable number of patients, persistent CTCs can be detected after completion of cytostatic treatment. Whether this finding is prognostically relevant will have to been shown with longer follow-up of the SUCCESS-trial. No significant financial relationships to disclose.

Analysis of serum HER-2/neu levels (S-HER2) in breast cancer (BC) patients (pts)

20092 Background: Circulating serum levels of the extracellular domain of the HER-2/neu receptor have been described in up to 15–30% of pre-surgical BC pts and 45% of metastatic BC (MBC) pts. S-HER2 has been reported to have a potential prognostic and predictive role in BC pts. Methods: We conducted a prospective evaluation of the S-HER2 levels in BC pts with the aim of studying its prognostic role and correlation with the clinical situation.The S-HER-2 levels were measured by an ELISA immunometric test (cut-off 13 ng/ml) at the first visit and then every 3 months.All pts gave a written informed consent. Results: From Jan ‘05 97 consecutive BC pts [68 st I-III; 29 (1 male) st.IV; median age at entry: 60y (28–83)] have been accrued and a total of 196 serum samples have been tested for S-HER2 (mean = 2/pt).Preliminary results are reported.Elevated S-HER2 levels at the first dosage (bS-HER2) were present in 25% of primary and 52% of MBC pts.In 68 primary BC pts the tumor HER2 status was 0/1+ in 54% (bS-HER2 &gt;13 ng/ml = 22%) and 2+/3+ in 22% (bS-HER2 &gt;13 ng/ml = 27%); there was no correlation between bS-HER2 with tumor HER2 status, size,axillary nodes, ER status, grading according to the Fisher’s exact test. In 29 MBC pts the tumor HER2 status was 0/1+ in 24% (bS-HER2 &gt;13 ng/ml = 24%) and 2+/3+ in 48% (bS-HER2 &gt;13 ng/ml = 21%); there was no correlation between S-HER2 and sites of metastases/n.of sites even if the S-HER2 median value was 18 and 12.5 ng/ml in visceral vs no visceral metastases.We also observed in 35% of MBC pts experiencing progression of disease that S-HER2 sequential values increased from baseline;in 21% of MBC pts that experienced complete remission the S-HER2 values decreased &lt;13 from baseline. Conclusions: This analysis showed no definite association between bS-HER-2 and clinical parameters.Further evaluations in a larger group of pts and association with response,survival and changes of S-HER2 status will be conducted. No significant financial relationships to disclose.

Cyclophosphamide, epirubicin and fluorouracil followed by docetaxel (CEF-DOC) as preoperative chemotherapy in primary operable breast cancer: Evaluation of chemotherapeutic response by breast MRI

812 Background: Preoperative systemic chemotherapy (PST) is used increasingly in the treatment of operable breast cancer. The purpose of this study was to evaluate the feasibility and safety as well as clinical and pathological response of Cyclophosphamide, Epirubicin and Fluoraouracil followed by Docetaxel (CEF-DOC) as PST in pts. with operable breast cancer. Especially, chemotherapeutic response was evaluated by breast MRI. Methods:Primary breast cancer pts. with T1c-3N0M0 or T1–3N1M0, age 20–60, PS 0–1 were eligible for this study. Preoperative chemotherapy consisted of 4 cycles of CEF (500mg/m2, 100mg/m2, 500mg/m2) every 3 weeks followed by 4 cycles of DOC (75mg/m2) every 3 weeks prior to surgery (either modified radical mastectomy or breast-conserving surgery). Breast MRI was performed for three times in 30 pts.(prechemo, after CEF and after DOC), and no adjuvant therapy except radiation, hormone therapy was allowed. Results: Since June 2002, 128 pts. were enrolled in this study, and at the time of this analysis, 50 pts. were evaluable for safety and efficacy. Of 400 planned cycles, 96.5% were administered, and median dose intensity (DI) delivered for epirubicin and DOC reached 91% and 86% of planned DI, respectively. The overall clinical response was 74.0% (20% CR, 54% PR), and 8 pts. (18%) resented SD and two PD (8%).. Diagnostic accuracy of breast MRI was 93.3% (28/30). MRI correctly detected multifocal lesion of the disease. Of note, 8 pts. (16%) improved the response of CEF with DOC, and breast conservation was achieved in 88% of pts. Conclusions: This regimen is active and well tolerated, and breast MRI is a valuable method to monitor accurate response of chemotherapy and helpful to determine appropriate surgical planning. No significant financial relationships to disclose.

Cyclophosphamide, epirubicin and fluorouracil followed by docetaxel (CEF-DOC) as preoperative chemotherapy in primary operable breast cancer: Evaluation of chemotherapeutic response by breast MRI

812 Background: Preoperative systemic chemotherapy (PST) is used increasingly in the treatment of operable breast cancer. The purpose of this study was to evaluate the feasibility and safety as well as clinical and pathological response of Cyclophosphamide, Epirubicin and Fluoraouracil followed by Docetaxel (CEF-DOC) as PST in pts. with operable breast cancer. Especially, chemotherapeutic response was evaluated by breast MRI. Methods:Primary breast cancer pts. with T1c-3N0M0 or T1–3N1M0, age 20–60, PS 0–1 were eligible for this study. Preoperative chemotherapy consisted of 4 cycles of CEF (500mg/m2, 100mg/m2, 500mg/m2) every 3 weeks followed by 4 cycles of DOC (75mg/m2) every 3 weeks prior to surgery (either modified radical mastectomy or breast-conserving surgery). Breast MRI was performed for three times in 30 pts.(prechemo, after CEF and after DOC), and no adjuvant therapy except radiation, hormone therapy was allowed. Results: Since June 2002, 128 pts. were enrolled in this study, and at the time of this analysis, 50 pts. were evaluable for safety and efficacy. Of 400 planned cycles, 96.5% were administered, and median dose intensity (DI) delivered for epirubicin and DOC reached 91% and 86% of planned DI, respectively. The overall clinical response was 74.0% (20% CR, 54% PR), and 8 pts. (18%) resented SD and two PD (8%).. Diagnostic accuracy of breast MRI was 93.3% (28/30). MRI correctly detected multifocal lesion of the disease. Of note, 8 pts. (16%) improved the response of CEF with DOC, and breast conservation was achieved in 88% of pts. Conclusions: This regimen is active and well tolerated, and breast MRI is a valuable method to monitor accurate response of chemotherapy and helpful to determine appropriate surgical planning. No significant financial relationships to disclose.

Using novel protein antibodies on tissue microarrays (TMAs) for breast cancer prognostication

9629 Background: Estrogen receptor (ER) and progesterone receptor (PR) are important prognostic and predictive factors for breast cancer patients (pts). Murine monoclonal antibodies (MuAb) are currently used in immunohistochemistry (IHC) assays to determine ER/PR status. Rabbit monoclonal antibodies (RAb) may have greater affinity for human antigens than MuAb. We compared the concordance of MuAb- and RAb-based IHC assays of ER and PR and the prognostic value of these and other factors in pts with Stage I-III breast cancer. Methods: TMAs were produced from formalin-fixed paraffin-embedded tissue sections of primary breast cancer pts. IHC assays were performed for the following: ER/PR status using RAb SP1CLONE (Labvision™) and using MuAb (Ventana™), fascin (a tumor cell motility protein) using clone 55K-2 (DAKO/M3567™), cytokeratin 5/6 (CK5/6) using clone D5/164B (Roche Biomed/1273396™), and HER2 using CB11. These were correlated with stage, progression-free (PFS) and overall survival (OS). ER/PR positivity was defined as ≥5% estimated proportion of positive-staining tumor cells. Results: 199 pts were evaluable for ER/PR. The concordance rate for RAb- and MuAb- assessed ER status was 90% (180/199). The level of agreement for RAb- and MuAb- assessed PR status was 81% (162/199). ER/PR positivity by RAb correlated with each other, HER2 negativity and earlier stage. In 159 pts with evaluable follow up, pts with ER positivity by RAb had better 5-year PFS (p<.001) and OS (p=.03), similar to ER positivity by MuAb. Pts with PR positivity by RAb had superior 5-year PFS (p=.001) and OS (p=.04) and correlated better with survival than PR positivity by MuAb. Fascin was expressed in 34 pts. Using univariate analysis, fascin expression correlated with higher stage, negative ER/PR, shorter PFS and OS. CK5/6 positivity did not correlate with any variable, except ER/PR positivity by RAb. After multivariate analysis, significant factors for PFS were stage, HER2, and PR by RAb, and for OS were stage, HER2, and fascin positivity. Conclusion: 1) The RAb for PR may be superior to the MuAb in predicting prognosis. 2) Fascin deserves further investigation as a prognostic factor. No significant financial relationships to disclose.