Purpose/Objective(s) In the phase 3 ADRIATIC study (NCT03703297) in patients (pts) with LS-SCLC without progression after concurrent chemoradiotherapy (cCRT), D as consolidation tx significantly improved OS and PFS vs placebo (P) at the first planned interim analysis. D was well tolerated and AEs were consistent with the known safety profile. Here we present pneumonitis/radiation pneumonitis and imAEs. Materials/Methods 530 eligible pts with stage I–III LS-SCLC (stage I/II inoperable), WHO PS 0/1, and no progression after cCRT, were randomized 1–42 days after cCRT to D 1500 mg or P every 4 weeks until investigator-determined progression or intolerable toxicity, or for a maximum of 24 months. Safety was a secondary endpoint. Given the similar clinical presentation of pneumonitis resulting from prior RT (radiation pneumonitis) or immunotherapy (immune-mediated pneumonitis), these events were analyzed as a grouped term to better estimate their frequency. imAEs were also assessed. Results 262 pts received D and 265 received P. Pneumonitis/radiation pneumonitis (preferred terms of immune-mediated lung disease, interstitial lung disease, pneumonitis, radiation fibrosis–lung, and radiation pneumonitis) occurred in 38% (n=100) vs 30% (n=80) of pts in the D vs P arm (maximum grade 3/4 3% vs 3%; grade 5 0.4% vs 0%; leading to tx discontinuation 9% vs 3%). Median time from first study drug dose to onset (mTTO) of pneumonitis/radiation pneumonitis was 56 days (range 1–594) vs 56 days (2–228) in the D vs P arm; 40/100 events in the D arm and 23/80 in the P arm had resolved at data cutoff (Jan 15, 2024). imAEs occurred in 32% vs 10% of pts in the D vs P arm (maximum grade 3/4 5% vs 2%; grade 5 0.4% vs 0%; leading to tx discontinuation 7% vs 3%). 14% vs 6% of pts in the D vs P arms received high-dose steroids and 1% vs 0.4% received immunosuppressants to manage imAEs. The table shows mTTO, resolution, and median time to resolution (mTTR) for the most common imAEs. Conclusion In ADRIATIC, pneumonitis/radiation pneumonitis was common in both arms in this population who had received prior RT, and imAEs were as expected in the D arm; these events were mainly low grade and led to low rates of tx discontinuation, supporting the favorable benefit-risk profile for consolidation D after cCRT in LS-SCLC.

Purpose or ObjectiveTo analyze the impact of simulation by PET-CT versus RMI & CT on gross tumor volume (GTV) and planning target volume (PTV) in nasopharyngeal carcinoma (NFC) patients. Material and MethodsFrom 2014 to 2016, 20 consecutive nasopharyngeal carcinoma patients were enrolled.All of them underwent a full body 18F-FDG-PET-TC, by a hybrid PET-CT with automatic image fusion (Discovery 600, General Electric), to staging or re-staging and at least another diagnostic image; 12 a contrast CT, 16 a MRI and 7 both.In patients without distant metastases a late cervical selective study (85 min-3.3h after injection of 18F-FDG) for RTP was performed using laser positioning and the required immobilization devices.In order to evaluate the differences, we recorded and compared the volumes of GTV and PTV (in cc) contoured with the diagnostic RMI and CT and those contoured using the tree explorations, PET/TC, RMI and CT.The volumes automatically contoured based on relative thresholds of the maximum tumor intensity standardized uptake value (SUV) (40% and 50% SUVmax) were also collected.Differences between the volumes were evaluated using paired Wilkoxon signed rank test for continuous variables and McNemar test for dichotomized variables.Statistical analyses were performed using SPSS_22. ResultsAge: Mean 43 years (range 31-57).Gender: 12 males and 8 females.Histology: Non-Keratinizing differentiated carcinoma 9 patients (45%), Non-Keratinizing undifferentiated carcinoma 9 patients (45%), and Keratinizing carcinoma 2 patients (20%).Metastatic disease was detected in 5 (25%), therefore 15 patients were analyzed.Besides, the nodal stage was changed in 7 patients.All volumes were reduced with a significant difference.The GTV PET/CT was lower in 13 cases (60% of the patients) with a median reduction of 13 cc (range: 0-23 cc) (p=0,004).The volume of concordance between GTV CT and GTV PET/CT had a median value of 19 cc (range: 15-27) which means that it matches 80% with final GTV PET/CT.The PTV PET/CT was lower in 15 cases (100%) with a median reduction of 59 cc (range: 20-70) (p=0.001).An important reduction (p=0,001) of the GTV PET-CT volumes contoured automatically with 40% and 50% SUVmax: 14 cc (range: 10-31) and 10 cc (range: 5-17), respectively was observed, being the GTV 40% SUVmax the most similar to the final GTV PET/CT.( Table1) (Figure1).

The poliovirus receptor (PVR) is an immune checkpoint protein expressed on tumor cells. It has been reported to mediate activation of T cells via CD226 or inhibition through binding to T-cell Ig and ITIM domain (TIGIT). TIGIT competes with CD226 for binding to PVR, and exhibits stronger affinity for PVR. Recently we have found that PVR is highly expressed in SCLC cell lines. Characterizing the expression and significance of the PVR-TIGIT axis in SCLC will help us to better understand the immunology of SCLC and may lead to novel therapeutic strategies to combine checkpoint blocking agents for improved SCLC immunotherapy.

Abstract Background. Bones constitute the most frequent localization of distant failure in breast cancer patients. Treatment of bone metastases is virtually palliative, but in a proportion of patients can effectively prolong survival and improve quality of life. Currently, there are no effective strategies to prevent bone dissemination with systemic adjuvant therapies. Thus, better molecular selection and identification of patients who have particularly high risk of skeletal metastases may facilitate designing future clinical trials. In this study we analyzed expression of selected tumor proteins potentially associated with skeletal metastases in breast cancer patients. Patients and methods. The study group included 184 metastatic breast cancer patients; 113 with clinically diagnosed bone metastases and 71 with exclusively other sites of metastases, respectively. In all patients, using tissue microarrays technology, IHC expression of the following proteins was evaluated in the primary tumor: estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), Ki67, cyclooxygenase 2 (COX2), chemokine receptor CXCR4, osteopontin (OPN), calcium sensing receptor (CaSR), cytokeratins 5/6 (CK5/6) and parathyroid hormone-related protein receptor 1 (PTHrPR1). Additionally based on ER/PR, HER2 and Ki67 expression, following molecular breast cancer subtypes were selected: luminal A, luminal B HER2-negative, luminal B HER2-positive, nonluminal HER2-positive and triple negative. Results. Median survival in patients with bone vs. other site of metastases was 56 vs. 37 months respectively (p = 0.0098). ER expression was more common in patients who did, compared with those who did not develop bone metastases (74.% vs. 45% respectively; p = 0.0001), whereas cytoplasmic overexpression of OPN (1.9% vs. 14% respectively; p = 0.002) and PTHrPR1 (16% vs. 34% respectively; p = 0.007) was more common in patients with other sites of metastases. The impact of ER and cytoplasmic OPN expression on the risk of bone dissemination was confirmed in the multivariate analysis (Table 1). Luminal A breast cancer subtype (43% vs. 23% respectively; p = 0.009) and luminal B HER2-positive (16% vs. 4.9%, respectively; p = 0.032) were more common among patients with bone dissemination, whereas triple negative tumors prevailed in patients with other sites of metastases (16% vs. 38%; p = 0.002). Median survival of patients with luminal A subtype was significantly longer than that with remaining subtypes (67 vs. 38 months respectively; p = 0.0004). Conclusions. These results suggest that ER expression and lack of OPN expression are independent factors predicting increased risk of bone dissemination in breast cancer patients. Bone metastases are specifically associated with luminal A and luminal B HER2-positive subtypes. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-13-03.

Abstract Background: About 10–30% of breast cancer patients will develop brain metastases. In untreated patients with brain metastases the median survival is 1–2 months, and in those undergoing palliative radiotherapy — 3–6 months. The mechanism of brain metastases remains largely unknown. The identification of molecular markers might help in selecting high risk patients, and enable active surveillance, prevention and early treatment. The aim of this study was to analyze predictive value of expression of selected tumor proteins for the risk of brain metastases in breast cancer patients. Material and methods: This study included 198 advanced breast cancer patients treated between 2001 and 2007 in 11 oncology centers in Poland, including 96 woman with and 102 without overt brain metastases, respectively. The median age at diagnosis in these two groups was 52 and 60 years, respectively, with 52% and 32% of patients being premenopausal. Stage at diagnosis was similar in both groups and ductal carcinoma was a dominant histological type (76% and 86% of cases, respectively). Immunohistochemistry was performed on formalin-fixed paraffin embedded microarray cores derived from the primary tumor. Expression analysis included ER, PR, HER2, Ki67, CK5/6, EGFR, HER3, CXCR4, RAD51, E-cadherin, and claudin 3 and 4. Cox regression model was used to estimate the relative risk of brain metastases. Results: Expression of HER2, CK5/6, EGFR, RAD51 (both cytoplasmatic and nuclear staining), CXCR4 (cytoplasmatic staining) and Ki67 ≥14%, as well as ER or PR negativity was associated with increased risk of brain metastases in the univariate analysis (Table 1). Of those, Ki67 ≥14% (HR 2.76 [95%CI 1.70–4.48]; p < 0.001), cytoplasmatic expression of double strand DNA repair gene RAD51 (HR 1.87 [95%CI 1.14–3.08]; p = 0.014) and ER negativity (HR 1.72 [95%CI 0.36–0.94]; p = 0.029) were found to be significantly related to the risk of brain relapse in the multivariate analysis. Four molecular profiles composed of the latter three markers were created, of which a profile including ER, Ki67 and RAD51 was associated with the highest risk of brain metastases (HR 4.43 [95%CI 2.69–7.27]; p < 0.001). Molecular subtype analysis showed the highest risk of BM in the ER/PR/ HER2-negative (triple negative) subset (HR 1.21 [95%CI 1.11–1.32]; p < 0.001). Conclusion: Expression of proteins related to high tumor proliferation, DNA repair and ER negativity is associated with increased risk of brain metastases in breast cancer patients. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-12-09.

e11001 Background: Particular molecular subtypes of BC have been shown to manifest various clinical behaviors and treatment outcomes. Small BCs with no lymph node metastasis have a favorable prognosis. The proportion of these tumors is increasing as a result of mammographic screening. In a large consecutive series of early BC patients (pts) we investigated clinical characteristics of small (pT1a/b pN0) vs. larger invasive BCs. Methods: Early BC cases (I and II clinical stage) were divided into four phenotypes: triple negative BC (TNBC), characterized by negativity of both hormone receptors (HR) and HER2 (0-2+ by immunohistochemistry), HR+/HER2-, HR+/HER2+ and HR-/HER2+. All pts underwent curative surgery between January 2003 and December 2007, followed by radiation and/or systemic therapy according to current standards. Clinicopathological features of < 1 cm versus > 1 cm tumors were compared using chi2 test. Results: Of the 783 tumors, 520, 50, 48 and 165 were classified as HR+/HER2-, HR+/HER2+, HR-/HER2+ and TNBC, respectively. We identified 86 pts with pT1a or T1b pN0 BC, after excluding 1 pt who received induction chemotherapy. Most tumors were detected accidentally. Small tumors included significantly higher proportion of G1 cases (38% vs. 12%; p < 0.001) and lower proportion of medullary type (0% vs 7.4%; p = 0.017) compared to tumors > 1 cm. Small tumor group included also significantly fewer unfavorable phenotypes: HER2+: 3.4% vs. 14% (p < 0.001); TNBC: 7% vs. 23% (p < 0.001). Other characteristics including age (mean 57.1 vs. 59.1 years) and menopausal status (27% vs. 28% of premenopausal pts) showed no difference. Conclusions: Small invasive BC present favorable phenotypes which can largely contribute to good prognosis. However, these data should be confirmed in larger series. No significant financial relationships to disclose.

10584 Background: IGF1R plays an important role in pathogenesis and progression of many malignancies. We studied the occurrence and prognostic value of IGF1R PE, GCN and their combination in resected SCLC. Methods: PE and GCN were evaluated on a tissue microarray containing multiple cores from 90 SCLC patients (pts). Median age was 57 years; males 74%; stage IA 7%, IB 29%, IIA 6%, IIB 14%, IIIA 27%, IIIB 12%, IIIB/IV 1%, unknown 1%; median overall survival (OS) 17.8 months. PE was evaluated by immunohistochemistry (IHC) using the IGF1R specific G11 antibody (Ventana Medical Systems, Inc. (VMSI), Tucson, AZ) and GCN was evaluated using an experimental IGF1R silver in-situ hybridization (SISH) probe (VMSI). Two pathologists and one reader scored PE using an H-score from 0 to 400. Two pathologists scored GCN in 50 non-consecutive nuclei for each core and the mean number of IGF1R copies/nucleus/core was determined. Cores with the highest value for either PE or GCN were used for subsequent analyses. Results: At least one core with a valid score for PE, GCN and both was obtained in 84, 81 and 79 pts, respectively. There was excellent concordance between all the evaluators for PE and GCN. The median H-score was 90 (range 0-400). There was no significant correlation between scores above or below the median and pathoclinical characteristics or OS (p = 0.69 and 0.48 in univariate and multivariate analysis, respectively). Median GCN was 2.4 (range 1.3-18.4), 15 pts had 4 or more copies of IGF1R per nucleus, of those 5 pts had clusters (amplification). GCN above the median tended to associate with an increased age (p = 0.053) but not with other characteristics. There were no OS differences for those above or below the median (p = 0.36 and 0.40 for univariate and multivariate analysis). There was moderate not statistically significant correlation between PE and GCN (r = 0.49). No association with pathoclinical characteristics or OS was found. Conclusions: Increased IGF1R gene copy number and IGF1R protein overexpression was found in numerous SCLC patients, but did not affect prognosis. These findings support potential role of targeting IGF1 signaling pathway in SCLC and warrant further investigations in this field. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ventana Medical system, Ventana Medical Systems AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb/ImClone, GlaxoSmithKline, Lilly, Merck Serono, OSI/Genenetech/Roche, Pfizer, Syndax Ventana Medical Systems AstraZeneca, Biogen Idec, Genentech, Genmab, Merck, OSI, Roche, Syndax, Ventana Medical Systems, Ventana-Roche Abbott Laboratories

Abstract Abstract #1078 Background: Particular molecular subtypes of breast cancer (BC) have been shown to manifest various clinical behaviors. In a large consecutive series of pts we compared treatment outcomes of four major BC subtypes, with particular focus on the risk of second malignancies. Materials and methods: Triple negative breast cancer (TNBC) was characterized by negativity of hormone receptors (HR) and HER2 (0-2+ by immunohistochemistry). Other subtypes included HR+/HER2-, HR+ /HER2+ and HR-/HER2+. All pts underwent curative surgery from January 2003 to December 2007, followed by radiation and/or systemic therapy according to current standards. Univariate risks of relapse and death were estimated using Kaplan-Meier survival curves and compared with log-rank test, and the multivariate analysis used stratified Cox model. Results: Of the 783 tumors, 520, 50, 48 and 165 were classified as HR+/HER2-, HR+ /HER2+, HR-/HER2+ and TNBC, respectively. The TNBC and HR-/HER2+ subtypes were associated with a higher tumor grade (p<0.001), higher T stage (p<0.001) and higher proportion of medullary type (p<0.001) compared to other two subgroups. Other characteristics, such as age and menopausal status showed no difference. The probability of relapse-free survival (RFS) and overall survival (OS) in TNBC and HR-/HER2+ groups were similar, and lower than in other two types (TNBC vs. HR+/HER2- and HR+ /HER2+; p=0.002 and 0.03 for RFS and OS). Impaired prognosis of TNBC and HR-/HER2+ pts remained significant after correction by T and N stage. TNBC was associated with almost doubled risk of second malignancy (12.7 vs. 6.5%) compared to all other types (p=0.008). This risk was significantly increased for contralateral BC and endometrial cancer (p=0.002 and 0.024, respectively). Conclusion: TNBC and HR-/HER2+ subtypes are associated with worse prognosis. Additionally, TNBC carries an increased risk of second malignancies, most likely due to higher proportion of hereditary BC. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1078.

e22057 Background: In a large, consecutive series of early BC patients (pts) we investigated clinical behavior of four major molecular subtypes, with particular focus on pattern of relapse and the risk of second malignancies. Methods: BC cases were divided into four phenotypes: triple negative BC (TNBC), characterized by negativity of hormone receptors (HR) and HER2 (0–2+ by immunohistochemistry), HR+/HER2-, HR+ /HER2+ and HR-/HER2+. All pts underwent curative surgery between January 2003 and December 2007, followed by radiation and/or systemic therapy according to current standards. Univariate risks of relapse and death were estimated using Kaplan-Meier survival curves and compared with log-rank test, and the multivariate analysis used stratified Cox model. Results: Of the 783 tumors, 520, 50, 48 and 165 were classified as HR+/HER2-, HR+/HER2+, HR-/HER2+ and TNBC, respectively. The TNBC and HR-/HER2+ subtypes were associated with higher tumor grade (p<0.001), higher T stage (p<0.001), and higher proportion of medullary type (p<0.001) compared to other two subtypes. After a median follow-up of 30 months, the risk of relapse in HR+/HER2-, HR+/HER2+, HR-/HER2+ and TNBC was 5.0%, 10.0%, 12.5% and 12.1%, respectively (p=0.007). Inferior prognosis of TNBC and HR-/HER2+ types remained significant after correction by T and N stage. Of the 57 relapses, 12 were locoregional, 37 distant and 8 concomitantly locoregional and distant. In TNBC isolated locoregional relapse constituted 45% of all relapses, compared to 8.1% in three other subtypes combined (p=0.001). TNBC was associated with almost doubled risk of second malignancy compared to all other types combined (12.7% vs. 6.5%, respectively; p=0.008). This risk was significantly increased for contralateral BC and endometrial cancer (p=0.002 and 0.024, respectively). Conclusions: Poor prognosis of TNBC is related to increased occurrence of both locoregional and distant relapses. Additionally, this subtype carries increased risk of second malignancies, most likely due to higher proportion of hereditary BC. No significant financial relationships to disclose.

Conformal radiotherapy constitutes the standard management of pelvic malignancies, yet its role in thin patients remains debatable. This study compares dose distribution for 2D and 3D treatment techniques for cobalt (60Co) and high energy photons from linear accelerator (LA) in cervical and endometrial cancer patients with antero-posterior diameter of less than 20 cm. CT-based 3D treatment planning and 2D simulation were performed in 10 patients. Particular techniques were compared in terms of treatment portal areas, coverage of planning target volume (PTV) and sparing of critical organs. For 60Co beams, PTV was not covered adequately with 2D fields in nine patients and with conformal fields in seven. For LA, PTV was not adequately covered with 2D two-field and 2D four-field ("box") technique in three and one patients, respectively. Mean bladder dose was comparable for all plans. Both 2D "box" and 3D "box" technique spared additional portion of the rectum volume included in 95% isodose, compared to two-field plan. 3D treatment planning better protected the small intestine. Use of multiple field techniques and 3D planning allows for some improvement of PTV coverage and normal tissue sparing, although the magnitude of this benefit must be weighted against savings of time and labour related to use of simpler treatment techniques.

11076 Background: The treatment results of patients with locally advanced breast cancer still remain far from satisfactory. Both lack of locoregional control and distant metastases remain the most common pattern of failuire. The aim of this study was to evaluate whether achieving locoregional control decreases the subsequent risk of distant metastases a large series of consecutive locally advanced breast cancer patients managed with radiotherapy as the primary locoregional treatment. Methods: The records of 261 primarily inoperable locally advanced breast cancer patients treated between 1991 and 1997 at two institutions: Medical University of Gdansk, Poland and Velindre NHS Trust, Cardiff, UK were analysed. All patients received megavoltage radiotherapy to the breast with two tangential fields, and the adjacent lymph node areas were irradiated using customised fields. In 241 patients radiotherapy constituted the only local treatment and the remaining 20 patients were subsequently subjected to mastectomy. Most patients received chemotherapy and/or endocrine therapy prior or after radiation therapy. Results: Follow-up ranged from 6 to 133 months (median 37 months). Five- year overall survival was 36% (95%CI: 28–43%) and 5-year loco-regional relapse-free survival was 48% (95%CI: 40–57%). Recurrence occurred in 167 patients (67%), including local recurence in 30 patients (12%), distant metastases - in 72 patients (27%) and both distant and local recurrence - in 65 patients (26%). Median time to distant metastases was significantly shorter among a subgroup of patients who presented locoregional failuire - 33 months as compared to patients who were free of locoregional recurrence or progression before presenting distant metastases-43 months (p<0.05) Conclusions: This study demonstrated that treatment results in patients with locally advanced breast cancer are still far from satisfactory. However it confirmed the importance of putting much effort in achieving locoregional control in that group of patients as it significantly reduces the risk of subsequent distant metastases. No significant financial relationships to disclose.

18189 Background: Bax and Bcl2 proteins are members of Bcl-2 family which plays a critical role in the regulation of apoptosis. There are few data on the occurrence and clinical relevance of these proteins in SCLC. Methods: We have analyzed expression of Bax and Bcl2 in 86 SCLC patients. All patients had limited disease and were treated with surgery followed by chemotherapy between 1982 and 2001 (median follow up 2 years). In all cases the diagnosis of SCLC was established only after the examination of surgical specimen. This series included 59 males and 22 females, 11 T1, 46 T2, 13 T3 and 11 T4 tumors, 41 N0, 15 N1, 24 N2 and 1 N3. Expression of both proteins was evaluated by immunohistochemistry and scored, taking into account proportion of cells with positive staining and staining intensity. H-score was calculated as a proportion of positive cells times staining intensity. Continues data on H-score were used to assess relationships with clinical data. Results: Median H-scores for Bax and Bcl2 were 70 (range 0–300) and 90 (range 0–300) respectively. The positive immunostaining rates (cut-off point of 10%) for Bax and Bcl-2 in the entire group were 81% and 79% respectively. Bax and Bcl-2 expression did not correlate with any clinicopathological parameters such as age, tumor size, lymph node involvement and stage of the disease. Survival was not influenced by expression of Bax (p=0.6) or Bcl2 (p=0.86). There was a significant positive correlation between Bax and Bcl2 expression rates (p=0.018, regression coefficient 0.23). Conclusions: Bax an Bcl2 proteins are commonly overexpressed in SCLC, with tendency for co-expression. Clinical relevance of these markers is questionable in this patient cohort. No significant financial relationships to disclose.

Transmembrane receptor tyrosine kinases have been shown to play an important role in the modulation of growth factor signaling and regulation of key cellular processes. The erbB receptor family is part of the receptor tyrosine kinase superfamily and consists of four members, erbB-1, erbB-2, erbB-3, and erbB-4. A majority of solid tumors express one or more members of this receptor family, and coexpression of multiple erbB receptors leads to an enhanced transforming potential and worsened prognosis. The erbB receptor family has been shown to play an important role in both the development of the normal breast and in the pathogenesis and progression of breast cancer. Receptor overexpression has also been shown to be a negative prognostic indicator and to correlate with both tumor invasiveness and a lack of responsiveness to standard treatment. Clinically, blockade of the erbB-2 receptor has recently been shown to provide benefit in a subset of chemotherapy-resistant breast cancer patients. CI-1033 is an orally available pan-erbB receptor tyrosine kinase inhibitor that, unlike the majority of receptor inhibitors, effectively blocks signal transduction through all four members of the erbB family. In addition, it blocks the highly tumorigenic, constitutively activated variant of erbB-1, EGFRvIII, and inhibits downstream signaling through both the Ras/MAP kinase, and PI-3 kinase/AKT pathways. CI-1033 is also unique in that it is an irreversible inhibitor, thereby providing prolonged suppression of erbB receptor-mediated signaling. Preclinical data have shown CI-1033 to be efficacious against a variety of human tumors in mouse xenograft models, including breast carcinomas. In a phase I study, CI-1033 has been shown to have an acceptable side effect profile at potentially therapeutic dose levels and demonstrates evidence of target biomarker modulation. Antitumor activity has also been observed in this study, including one partial clinical response and stable disease in over 30% of patients, including one patient with heavily pretreated breast cancer. By virtue of its pan-erbB receptor inhibition and potent interruption of downstream mitogenic signaling pathways, CI-1033 may have clinical activity for solid tumors that overexpress one erbB family member, coexpress multiple members of the erbB family, or express a constitutively activated, mutated form of these receptors. Given the important role of the erbB receptor family in the pathogenesis and progression of breast cancer, an irreversible pan-erbB inhibitor like CI-1033 could have an important role to play in the future treatment of breast cancer. Semin Oncol 29 (suppl 11):11-21. Copyright 2002, Elsevier Science (USA). All rights reserved.