Kumiko Kida

A prospective feasibility study of sentinel node biopsy by modified Indigocarmine blue dye methods after neoadjuvant chemotherapy for breast cancer.

BACKGROUND Although sentinel lymph node biopsy (SLNB) is a standard staging method for assessing nodal status of breast cancer patients, SLNB after neoadjuvant chemotherapy (NAC) remains controversial. The aim of this study was to validate the practicality and accuracy of SLNB by our modified Indigocarmine blue dye methods following NAC. METHODS One hundred consecutive cases with breast cancers treated by NAC were enrolled in this study. After NAC, all patients underwent SLNB performed by our modified Indigocarmine blue dye methods without radioisotope, followed by back-up axillary lymph node dissection (ALND). RESULTS Sentinel nodes (SNs) were identified in 94 cases (identification rate, 94%); the accuracy was 94.7% (89/94 cases); and the false negative rate (FNR) 13.5% (5/37 cases). For cases with vs. without clinically evident metastatic nodes before NAC, the identification rate was 92.4% (61/66 cases) vs. 97.1% (33/34 cases); the accuracy 91.8% (56/61 cases) vs. 97.0% (32/33 cases) and the FNR 16.1% (5/31 cases) vs. 0% (0/6 case), respectively. There were six patients without identified SNs, three of them had metastatic nodes. False negatives occurred in five cases; in four, fewer than two sentinel nodes had been removed. CONCLUSION Following NAC, the accuracy of SLNB by modified Indigocarmine blue dye methods is adequate compared with other tracers. In patients in whom no SNs have been identified, lymphatic metastasis is likely and therefore ALND is recommended. For patients with cN0 prior to NAC, SLNB by modified Indigocarmine blue dye methods is clinically feasible, though controversial for patients with positive nodes.

Abstract 1767: Analysis of biomarkers and anthracycline benefit for hormone receptor-negative breast cancer: results from a randomized phase 2 neoadjuvant study (KBOG 1101 Study)

AIM: We compared 6 cycles of docetaxel and cyclophosphamide (TC6) with 3 cycles of 5-fluorouracil and epirubicin and cyclophosphamide followed by 3 cycles of docetaxel (FEC-D) as neoadjuvant chemotherapy for patients with hormone receptor (HR)-negative breast cancer (BC) to identify biomarkers requiring anthracycline treatment. Methods: In total, 103 patients with operable HR-negative BC were administered TC6 or FEC-D. Triple-negative BC was subdivided by CK5/6 and EGFR into basal- and non-basal BCs. The primary endpoint was pathological complete response (pCR). Secondary endpoints were safety, breast-conserving surgery ratio, disease-free survival, overall survival, and predictive factors (Ki-67, P-53, ALDH1 and TOP2A by IHC and TOP2A by FISH) for each regimen. Results: Of the 103 patients, 97 completed the study. Overall pCR was higher for patients treated with FEC-D (36%) than for those treated with TC6 (25.5%) (P=0.265). FEC-D was significantly superior to TC6 in basal BC (42.9% vs 13.6%; P=0.033), while no differences in HER2 and non-basal BCs. Aldehyde dehydrogenase 1 (ALDH1) positivity was inversely associated with pCR for both regimens, significantly for FEC-D (FEC-D: p=0.047, TC6: p=0.085). Patients who achieved pCR tended to have longer DFS (P = 0.287) and OS (P = 0.069). Patients with basal and non-basal BC treated with FEC-D had significantly better DFS (P = 0.016) and OS (P = 0.034) than those with TC6. Conclusion: We found TC6 was less effective than FEC-D for HR-negative BC because it was not sufficient to treat basal-BC. This suggests that DNA damaging agents like anthracyclines are required for treating basal-BC. Additionally, ALDH1 could be a marker for resistance to conventional chemotherapy. Citation Format: Takashi Ishikawa, Kazutaka Narui, Mari S. Oba, Akimitsu Yamada, Kumiko Kida, Mikiko Tanabe, Yasushi Ichikawa. Analysis of biomarkers and anthracycline benefit for hormone receptor-negative breast cancer: results from a randomized phase 2 neoadjuvant study (KBOG 1101 Study) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1767. doi:10.1158/1538-7445.AM2017-1767

Abstract P2-06-16: The impact of ALDH1 on chemo-resistance and prognosis according to intrinsic subtype in breast cancers

[Background]Aldehyde dehydrogenase 1 (ALDH1) has been identified as a breast cancer stem cell marker. The clinical significance of ALDH1 as a chemo-resistant and prognostic indicator has been reported recently. However, the analysis according to each intrinsic subtype was not reported. [Aims] To investigate the impact of ALDH1 on chemo-resistance and prognosis according to intrinsic subtypes in invasive breast cancers. [Methods] 1) Patients and tumor specimens; A total of 653 primary breast cancer patients were enrolled in this study from 2004 to 2013 at the Yokohama City University Medical Center in Japan. We performed immunohistochemical analyses using paraffin-embedded core needle biopsy sections prior to the treatment. 2) Correlation of ALDH1 with clinicopathological factors; Analyses were performed to investigate association of ALDH1 expression with other biomarkers and clinicopathological factors in breast cancers. Age, histologic type, tumor size, nodal status, ER/PgR/HER2 status, nuclear grade, Ki67, Topo2, p53, CK5/6 and EGFR were observed. 3) Neoadjuvant patient cohort study 234 breast cancer patients receiving neoadjuvant chemotherapy were enrolled. The correlation between ALDH1 and pathological complete response (pCR) rate was investigated in each intrinsic subtype. 4) Prognostic cohort study We performed a Cox analysis of disease free survival and overall survival of all 653 cases according to each subtype, taking account of clinicopathological factors. [Results] ALDH1 expression in tumor cells was seen in 139 of 653 cases (21.3%). The ALDH1 expression correlated significantly with tumor size, clinical node metastasis, clinical staging, nuclear grade and HER2 status positively, ER and PgR status negatively. ALDH1 expression was significantly seen in HER2-positive cancers and triple negative type. In neoadjuvant study, we analyzed 234 patients treated with neoadjuvant chemotherapy including 63 luminal type, 20 luminal-HER2 type, 45 HER2-enriched type and 106 triple negative type. The pCR rate was significantly lower in patients with ALDH1-positive cases (13.5%vs.30.3%,p=0.003). In multivariate analysis, ALDH1 and ER are correlated with pCR rate significantly. According to the intrinsic subtypes, the correlation between pCR and ALDH1 expression was extremely significant in triple negative type (p=0.003). In HER2 positive type, ALDH1 expression had tendency with low pCR, but with no significance. In luminal type, two patients achieved pCR and both had no ALDH1 expression. In prognostic analysis, patients with ALDH1 expression had significantly poor disease free survival (DFS; p [Conclusions] Breast cancers with ALDH1 expression posse biologically aggressive phenotypes that tend to have a poor prognosis. Chemoresistance was significantly seen in ALDH1-positive triple negative type, on the other hand, impact on prognosis was seen in luminal type more highly than triple negative type. Citation Format: Kumiko Kida, Takashi Ishikawa, Akimitsu Yamada, Kazutaka Narui, Sadataka Sugae, Mikiko Tanabe, Yasushi Ichikawa, Itaru Endo. The impact of ALDH1 on chemo-resistance and prognosis according to intrinsic subtype in breast cancers [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-06-16.

Abstract P3-06-27: BRCAness is important to identify TNBC subtype resistant to taxanes

BACKGROUND: Triple negative breast cancer (TNBC) is heterogeneous and consists of tumors associated with basal like, BRCA related and cancer stem cell (CSC) phenotypes. Although anti-cancer agents are substantial for treating TNBC, existing ones do not work in some subpopulation in TNBC at all. However, it has not been reported that subdivision of TNBC is useful for choosing ant-cancer agents. AIM: To examine whether subdividing TNBC is beneficial for tailored chemotherapy and to identify predictive factors for existing anti-cancer agents in TNBC. METHODS: Sixty-six TNBC cases from a randomized phase II trial comparing TCx6 (TC6) with FEC followed by docetaxel (FEC-D) as neoadjuvant chemotherapy for hormone receptor-negative breast cancer (Kanagawa Breast Oncology Group 1101 Study). TNBC was subdivided by 1) IHC of CK 5/6 and EGFR into basal- and non-basal subtypes, and 2) MLPA of BRCA1 into BRCA1 and non-BRCA1 subtypes. The pCR rates were examined according to each regimen and subtype. 3) The association of grade 3 pCR was examined with Ki-67, p53, aldehyde dehydrogenase (ALDH) 1 and topoisomerase 2A (topoIIα) by IHC and TOP2A by FISH for each regimen. RESULTS: 1) In basal subtype, the pCR rate was significantly higher for FEC-D (42.9%) compared with TC6 (13.6%) (p=0.033), but it was equivalent in non-basal subtype (FEC-D vs TC: 25.0% vs 36.4%, p=0.554). 2) In BRCA1 subtype, it was more significant (FEC-D vs TC: 53.8 % vs 13.3%, p=0.022). 3) An association between pCR and low ALDH1 expression was found in both FEC-D and TC6 (OR: 3.75 and 2.73). High topo IIα protein expression was associated with pCR in FEC-D (OR: 3.5). DISCUSSION: TC6 was less effective than FEC-D in basal subtype and BRCA1 subtype, showing that taxanes cannot exert their anticancer role in tumors with BRCA1 dysfunction. Although basal subtype may contain more BRCA1-defective tumors than non-basal subtype, MLPA of BRCA1 was better to identify subtype resistant to taxanes than CK5/6 and EGFR. ALDH1 predicted treatment efficacy, and could therefore represent a marker of resistance to conventional chemotherapy. Citation Format: Takashi Ishikawa, Kazutaka Narui, Kazuhiro Shimada, Kumiko Kida, Mari S Oba, Mikiko Tanabe, Yasushi Ichikawa, Sadatoshi Sugae, Itaru Endo. BRCAness is important to identify TNBC subtype resistant to taxanes [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-06-27.

Abstract 4247: BRCAness by MLPA is clinically useful for tailored treatment in triple-negative breast cancer

BACKGROUBD: Cytotoxic anticancer drugs are the only clinically available agents for treating triple-negative breast cancer (TNBC). Recent gene expression analysis revealed that TNBC shows considerable overlap with basal-like tumors characterized by a potential loss of BRCA1 function. Further subdivision of TNBC represents an important clinical topic for treatments. We therefore subdivided TNBC into basal-like (BL) and non-BL subtypes defined by EGFR and/or CK5/6 positive in our previous neoadjuvant chemotherapy (NAC) study (KBOG1101 study). We reported that BL subtype were resistant to taxane regimen at AACR2013. AIM: To examine impaired BRCA1 function “BRCAness” is beneficial for tailored chemotherapy in TNBC. METHODS: Sixty-six TNBC cases from a randomized phase II trial comparing Docetaxel and cyclophosphamide x 6 (TC6) with 5-fluorouracil, epirubucin and cyclophosphamide followed by docetaxel (FEC-D) as NAC for hormone receptor-negative breast cancer (Kanagawa Breast Oncology Group 1101 Study). TNBC was subdivided by 1) Immunohistochemistry (IHC) of CK 5/6 and EGFR into BL and non-BL subtypes, and 2) Multiplex Ligation-dependent Probe Amplification (MLPA) of BRCAness into BRCAness and non-BRCAness subtypes. The pCR rates were examined according to each regimen and subtype. 3) The association of grade 3 pCR was examined with Ki-67, p53, aldehyde dehydrogenase (ALDH) 1 and topoisomerase 2A (topoIIα) by IHC and TOP2A by FISH for each regimen. RESULTS: 1) The pCR rates of FEC-D and TC were 37% vs 18.5% in BL(n = 54), while 40.4% and 16.7% in non-BL (n = 11), respectively. FEC-D was superior in both subtypes without statistical significance. 2) In BRCAness (n = 34), FEC-D was significantly superior to TC6 (FEC-D vs TC: 56.3% vs 16.7%, p = 0.030), while not different in non-BRCAness (20.0% vs 16.7%). 3) No factors were associated with pCR. DISCUSSION: TC6 was less effective than FEC-D in TNBC with BRCAness, showing that taxane cannot exert their anticancer role in tumors with BRCA1 dysfunction. Although BL may contain more BRCA1-defective tumors than non-BL, MLPA of BRCAness was better to identify subtype resistant to taxane than BL defined by IHC. BRCAness by MLPA method is practically useful for treatment selection in TNBC. Citation Format: Takashi Ishikawa, Kazutaka Narui, Akimitsu Yamada, Sadatishi Sugae, Yasushi Ichikawa, Mari S. Oba, Saeko Teraoka, Kumiko Kida, Hidetaka Shima, Itaru Endo. BRCAness by MLPA is clinically useful for tailored treatment in triple-negative breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4247. doi:10.1158/1538-7445.AM2015-4247

Abstract 1890: Activated SphK1 and export of S1P via ABCC1 shorten disease free survival in breast cancer

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA ATP-binding cassette (ABC) transporters are known to be multidrug resistance proteins that efflux various compounds out of cells including chemotherapeutic agents. A number of clinical trials have been conducted targeting ABCB1: however, none showed beneficial effects. The pleiotropic bioactive lipid mediator sphingosine-1-phosphate (S1P), which is generated by sphingosine kinase 1 (SphK1) inside breast cancer cells and exerts its functions by binding to its specific cell surface G-protein coupled receptors (S1PR1-5) after being exported, is now known as a key regulatory molecule in breast cancer progression. We have previously demonstrated that ABCC1 and ABCG2, but not ABCB1 export S1P out of MCF7 human breast cancer cells. We hypothesized that ABCC1 expression in the presence of S1P produced by activated SphK1 in human breast cancer is associated with poor prognosis. We demonstrate the role of ABCC1 and SphK1/ S1P axis in breast cancer progression utilizing ABC transporter transduced breast cancer cell lines for in vitro and in vivo study. For clinical study, we analyze the expression of ABC transporters and S1P signaling factors utilizing a tissue microarray constructed from 276 breast cancer samples. Overexpression of ABCC1 in breast cancer cell lines export more S1P. ABCC1 overexpression but not ABCB1 enhance proliferation and cell migration, and promote angiogenesis (AG) and lymph angiogenesis (LAG). MK571 which is inhibitor of ABCC1 suppress them. Overexpression of ABCC1 also aggravate tumor grow and contribute poor survival in syngeneic and xenograft mice model. In the clinical study, ABCC1 expression was associated with significantly shorter disease free survival (DFS) while ABCB1 was not. pSphK1 high expression group had significantly shorter DFS. Most of the patients expressed S1PR1; however, there were no significant differences in prognosis. Patients with tumors expressing both pSphK1 and ABCC1 had significantly shorter DFS, while patients expressing both ABCB1 and pSphK1 did not. These translational findings suggest that inside-out signaling of S1P via ABCC1 may play a significant role in the course of human breast cancer progression. This work was supported by grants from the National Institute of Health (R01CA160688 to K.T and R01CA61774 to S.S). M.N. is a Japan Society for the Promotion of Science Postdoctoral Fellow. Citation Format: Akimitsu Yamada, Masayuki Nagahashi, Tomoyoshi Aoyagi, Wei C. Huang, Krista P. Terracina, Jeremy C. Allegood, Santiago Lima, Sheldon Milstien, Sarah Spiegel, Kumiko Kida, Takashi Ishikawa, Itaru Endo, Kazuaki Takabe. Activated SphK1 and export of S1P via ABCC1 shorten disease free survival in breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1890. doi:10.1158/1538-7445.AM2014-1890

Abstract 263: Identification of subgroup of triple negative breast cancer by cancer stem cell markers.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC [Background] Anti-cancer agents are essential for treating triple negative breast cancer (TNBC). The cases resistant to them showed unfavorable clinical courses and thus may require novel agents. It is crucial to predict the efficacy of existing agents in TNBC. Recently, cancer stem cell (CSC) theory has drawn an attention in relation to TNBC and chemoresistance. Aldehyde dehydrogenase 1 (ALDH1) is a biomarker of breast cancer stem cell. [Aims] In order to subdivide TNBC and finally find subgroup resistant to existing anti-cancer agents and better markers for stem cell phenotype. [Methods] 1)The expression of ALDH1 was examined immunohistochemically in each subtype of 447 breast cancer patients. 2)The expression of ALDH1 and its association with Ki-67,P53, CK5/6 or EGFR were examined in TNBC. 3)Correlation between ALDH1 and pathological response by neoadjuvant chemotherapy was examined. 4)ALDH1 positive and negative cells were collected by microdissection from 5 ALDH1 positive breast cancer cases. The expression profile was assessed by Affymetrix cDNA microarray. The difference of profile between ALDH-1 positive and negative cells was assessed. [Results] 1)The expression rate of ALDH1 was 4.5% in Luminal type, 11.1% in Luminal-HER2 type, 23.8% in HER2-enriched type and 33.6% in triple negative type. ALDH1 was expressed highly in TNBC. 2)In 79 TNBC with neoadjuvant chemotherapy, 29 cases(36.7%) was positive for ALDH1.The averages of NG, Ki67 and p53 were 2.7, 37.8% and 37.7% respectively in ALDH1 positive TNBC. 80% of them were positive for CK5/6 or EGFR. There was no significant correlation between ALDH1 and these pathological markers. 3) Poorly responsiveness to NAC (0-1b) was found in 17 cases (21.5%). Only ALDH1 was associated with chemoresistance to NAC (P=0.033), suggesting ALDH1 positive TNBC were resistant to anticancer agents. 4)63 and 41 genes were up- and down-regulated respectively in ALDH1 positive cells. These potential related genes are now under investigation. [Conclusions] ALDH1 could be a marker for chemoresistance in TNBC. As ALDH1 identifies some specific subpopulation of breast cancer, further studies will provide important information on subdividing TNBC and individualizing treatment of this intractable subtype. Citation Format: Kumiko Kida, Takashi Ishikawa, Akimitsu Yamada, Kazuhiro Shimada, Kazutaka Narui, Sadatoshi Sugae, Daisuke Shimizu, Mikiko Tanabe, Takeshi Sasaki, Yasushi Ichikawa, Itaru Endo. Identification of subgroup of triple negative breast cancer by cancer stem cell markers. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 263. doi:10.1158/1538-7445.AM2013-263

Abstract P3-14-08: A randomized phase II trial comparing docetaxel plus cyclophosphamide with epirubicin plus cyclophosphamide followed by docetaxel as neoadjuvant chemotherapy for hormone receptor-negative breast cancer. Kanagawa breast oncology group (KBOG) 1101 study

Background: Taxane-based regimens have been developed and used widely to treat breast cancer. It has therefore become important to identify subgroups of patients in which anthracyclines are indispensable. Pathological response to neoadjuvant chemotherapy (NAC) predicts prognosis in hormone-negative subtypes. We therefore initiated a randomized phase II NAC study to compare a taxane with and without an anthracycline in these breast-cancer subtypes. Aim: To determine the safety and activity of six cycles of docetaxel and cyclophosphamide (TC6) compared with 5-fluorouracil, epirubicin, and cyclophosphamide followed by docetaxel (FEC-D), and to examine the predictive factors for each regimen. Methods: Eligibility criteria were operable hormone-receptor-negative breast cancer, age younger than 75 years and ECOG PS0-1. According to HER2 status, patients were randomly assigned to TC (75/600 mg/m2) every 3 weeks X 6 or FEC (500/100/500 mg/m2) every 3 weeks X 3 followed by D (100 mg/m2) every 3 weeks X 3. The primary endpoint was the rate of pathological complete response (pCR; grade 3). Triple-negative (TN) breast cancer was subdivided by cytokeratin 5/6 and epidermal growth factor receptor into basal- and non-basal subtypes. Secondary endpoints were safety, breast-conserving surgery, disease-free survival, overall survival, and predictive factors: Ki-67, p53, aldehyde dehydrogenase (ALDH) 1 and topoisomerase 2A by both immunohistochemistry and fluorescence in situ hybridization for each regimen. Results: Ninety-seven of 103 patients were analyzed successfully (50 for FEC-D and 47 for TC6). Significantly more severe adverse events (grade 2) were observed in FEC-D-treated patients (poor appetite, nausea and vomiting: p = 0.001; febrile neutropenia: p = 0.016). The pCR rate tended to be higher in FEC-D-treated patients compared with TC6-treated patients (pCR: 36.0 vs. 25.5%, n.s.). FEC-D treatment was significantly more effective than TC6 in basal-type (p = 0.033) but not in non-basal and HER2 subtypes. ALDH1 was associated with resistance to both regimens (FEC-D: p = 0.047, TC6: p = 0.085) Conclusions: TC6 was safer, but not more effective than FEC-D. TC6 was significantly less active than FEC-D in basal subtype, and equivalent to FEC-D in HER2 and non-basal subtypes. Concurrent use of trastuzumab with TC could thus represent a reasonable option for NAC in HER2-subtype patients. ALDH1 could provide a marker for novel strategies such as stem cell-based therapies for breast cancer. Analyses on pathological factors in surgical specimens after NAC will be presented at the meeting. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-14-08.

Abstract 5350: Aldehyde dehydrogenase 1 is useful for identifying some subtypes of non-basal triple negative breast cancer

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL BACKGROUND Triple negative breast cancer (TNBC) is heterogeneous and consists of tumors associated with basal-type and cancer stem cell (CSC) phenotypes. Identifying these specific phenotypes is important for treating TNBC. The expression of aldehyde dehydrogenase 1 (ALDH-1), a biomarker of CSC phenotype, is observed more frequently in TNBC than non-TNBC and is associated with biologically aggressive features. AIM In order to categorize types of breast cancer, especially TNBC, ALDH-1 was examined in terms of 1) its association with pathological factors and 2) the genes significantly expressed in ALDH-1 positive cells. METHODS 1) The expression of ALDH-1 and its association with the other pathological factors of ER, PgR, HER2, p53, Ki-67, CK5/6, EGFR were examined immunohistochemically in 87 breast cancer samples. Histological grade was assigned to each of the samples.2) ALDH-1 positive and negative cells were collected by microdissection from formalin-fixed paraffin- embedded samples of 5 ALDH-1 positive breast cancer cases. mRNA was extracted and the expression profile of approximately 5,000 genes was assessed by cDNA microarray (Affymetrix GeneChip®, Human Genome U133 Plus 2.0 Array). By comparing gene expressions of ALDH-1 positive and negative cells in the same sample, characteristic genes related to CSC were identified. RESULTS 1) ALDH-1 was inversely correlated with ER (p=0.0006) and PgR (p=0.0054), while positively correlated with Ki67 (p=0.0023) and TopoII (p=0.0014). No association was found between ALDH-1 with CK5/6 or with EGFR. 2) Approximately 800 annotated genes were significantly up- or down- regulated. Several characteristic genes related to ALDH-1 have been presently confirmed by other methodologies. CONCLUSION CK5/6 and EGFR are currently used to identify basal-type TNBC. Because ALDH-1 was not associated with CK5/6 or EGFR, ALDH-1 and related genes may be helpful in identifying some non-basal types of TNBC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5350. doi:1538-7445.AM2012-5350