Disparities in esophageal cancer care based on race: a National Cancer Database analysis.

Esophageal cancer is one of the most common cancer killers in our country. The effects of racial disparities on care for esophageal cancer patients are incompletely understood. Using the National Cancer Database, we investigated racial disparities in treatment and outcome of esophageal cancer patients. The National Cancer Database was queried from 2004 to 2017. Logistic regression and survival analysis were used to determine racial differences in access, treatment and outcome. A total of 127,098 patients were included. All minority groups were more likely to be diagnosed at advanced stages versus Caucasians after adjusting for covariates (African American OR-1.64 [95% confidence interval 1.53-1.76], Hispanic OR-1.19 [1.08-1.32], Asian OR-1.78 [1.55-2.06]). After adjustment, all minorities were less likely at every stage to receive surgery. Despite these disparities, Hispanics and Asians had improved survival compared with Caucasians. African Americans had worse survival. Racial disparities for receiving surgery were present in both academic and community institutions, and at high-volume and low-volume institutions. Surgery partially mediated the survival difference between African Americans and Caucasians (HR-1.13 [1.10-1.16] and HR-1.04 [1.02-1.07], without and with adjustment of surgery).There are racial disparities in the treatment of esophageal cancer. Despite these disparities, Hispanics and Asians have improved overall survival versus Caucasians. African Americans have the worst overall survival. Racial disparities likely affect outcome in esophageal cancer. But other factors, such as epigenetics and tumor biology, may correlate more strongly with outcome for patients with esophageal cancer.

Subtype-Guided 18 F-FDG PET/CT in Tailoring Axillary Surgery Among Patients with Node-Positive Breast Cancer Treated with Neoadjuvant Chemotherapy: A Feasibility Study.

BACKGROUND: The purpose of this study was to investigate the value of 18 [F]-fluorodeoxyglucose (18 F-FDG) positron emission tomography/computed tomography (PET/CT) in tailoring axillary surgery by predicting nodal response among patients with node-positive breast cancer after neoadjuvant chemotherapy (NAC). METHODS: One hundred thirty-three patients with breast cancer with biopsy-confirmed nodal metastasis were prospectively enrolled. 18 F-FDG PET/CT scan was performed before NAC (a second one after two cycles with baseline maximum standardized uptake value [SUVmax ] ≥2.5), and a subset of patients underwent targeted axillary dissection (TAD). All the patients underwent axillary lymph node dissection (ALND). The accuracy was calculated by a comparison with the final pathologic results. RESULTS: With the cutoff value of 2.5 for baseline SUVmax and 78.4% for change in SUVmax , sequential 18 F-FDG PET/CT scans demonstrated a sensitivity of 79.0% and specificity of 71.4% in predicting axillary pathologic complete response with an area under curve (AUC) of 0.75 (95% confidence interval, 0.65-0.84). Explorative subgroup analyses indicated little value for estrogen receptor (ER)-negative, human epidermal growth factor receptor 2 (HER2)-positive patients (AUC, 0.55; sensitivity, 56.5%; specificity, 50.0%). Application of 18 F-FDG PET/CT could spare 19 patients from supplementary ALNDs and reduce one of three false-negative cases in TAD among the remaining patients without ER-negative/HER2-positive subtype. CONCLUSION: Application of the subtype-guided 18 F-FDG PET/CT could accurately predict nodal response and aid in tailoring axillary surgery among patients with node-positive breast cancer after NAC, which includes identifying candidates appropriate for TAD or directly proceeding to ALND. This approach might help to avoid false-negative events in TAD. IMPLICATIONS FOR PRACTICE: This feasibility study showed that 18 [F]-fluorodeoxyglucose (18 F-FDG) positron emission tomography/computed tomography (PET/CT) could accurately predict nodal response after neoadjuvant chemotherapy (NAC) among patients with breast cancer with initial nodal metastasis except in estrogen receptor-negative, human epidermal growth factor receptor 2-positive subtype. Furthermore, the incorporation of 18 F-FDG PET/CT can tailor subsequent axillary surgery by identifying patients with residual nodal disease, thus sparing those patients supplementary axillary lymph node dissection. Finally, we have proposed a possibly feasible flowchart involving 18 F-FDG PET/CT that might be applied in post-NAC axillary evaluation.

Assessment of Practice Patterns Following Publication of the SSO-ASTRO Consensus Guideline on Margins for Breast-Conserving Therapy in Stage I and II Invasive Breast Cancer.

BACKGROUND: The recently published SSO-ASTRO consensus guideline on margins concluded "no ink on tumor" is the standard for an adequate margin. This study was conducted to determine how this guideline is aligned with current clinical practice. METHODS: A survey was sent to 3057 members of the American Society of Breast Surgeons. Questions assessed respondents' clinical practice type and duration, familiarity with the guideline, and preferences for margin re-excision. RESULTS: Of those surveyed, 777 (25%) responded. Most (92%) indicated familiarity with the guideline. Of these respondents, the majority (n = 678, or 94.7%) would re-excise all or most of the time when tumor extended to the inked margin. Very few (n = 9, or 1.3%) would re-excise all or most of the time when tumor was within 2 mm of the margin. Over 12 % (n = 90) would re-excise all or most of the time for a triple-negative tumor within 1 mm of the margin, whereas 353 (49.6%) would re-excise all or most of the time when imaging and pathology were discordant, and tumor was within 1 mm of multiple margins. Finally, 330 (45.8%) would re-excise all or most of the time when multiple foci of ductal carcinoma in situ extended to within 1 mm of multiple inked margins. CONCLUSIONS: Surgeons are in agreement to re-excise margins when tumor touches ink and generally not to perform re-excisions when tumor is close to (but not touching) the inked margin. For more complex scenarios, surgeons are utilizing their individual clinical judgment to determine the need for re-excision.

Society of Surgical Oncology-American Society for Radiation Oncology consensus guideline on margins for breast-conserving surgery with whole-breast irradiation in stages I and II invasive breast cancer.

PURPOSE: Controversy exists regarding the optimal margin width in breast-conserving surgery for invasive breast cancer. METHODS: A multidisciplinary consensus panel used a meta-analysis of margin width and ipsilateral breast tumor recurrence (IBTR) from a systematic review of 33 studies including 28,162 patients as the primary evidence base for consensus. RESULTS: Positive margins (ink on invasive carcinoma or ductal carcinoma in situ) are associated with a two-fold increase in the risk of IBTR compared with negative margins. This increased risk is not mitigated by favorable biology, endocrine therapy, or a radiation boost. More widely clear margins than no ink on tumor do not significantly decrease the rate of IBTR compared with no ink on tumor. There is no evidence that more widely clear margins reduce IBTR for young patients or for those with unfavorable biology, lobular cancers, or cancers with an extensive intraductal component. CONCLUSION: The use of no ink on tumor as the standard for an adequate margin in invasive cancer in the era of multidisciplinary therapy is associated with low rates of IBTR and has the potential to decrease re-excision rates, improve cosmetic outcomes, and decrease health care costs.

Racial disparity in colorectal cancer: the role of equal treatment.

BACKGROUND: Racial disparity exists in colorectal cancer outcomes. The reasons for this are multifactorial. OBJECTIVE: The aim of this study was to evaluate the role of equal treatment of blacks and whites in the elimination of racial disparity in colorectal cancer outcomes. DESIGN: A retrospective cohort study of 878 patients with colorectal cancer diagnosed between 1998 and 2008 was done at a University tertiary referral center. Demographic variables including age, sex, and race were abstracted. Tumor-specific variables including American Joint Committee on Cancer stage, anatomic tumor location, vital status, and survival were obtained. Treatment-specific variables including surgery, chemotherapy, radiotherapy, and follow-up were also obtained. Racial differences in these variables were studied and their effect on overall survival was determined by using univariate and multivariate analyses. The findings were then compared with previous data from our institution. SETTING: University tertiary referral center. MAIN OUTCOME MEASURES: The primary outcomes measured were overall survival and cancer-specific mortality. RESULTS: A total of 878 patients met the inclusion criteria, 186 (21.2%) of whom were black. Blacks were significantly younger at diagnosis in comparison with whites, with a median (quartiles) age of 55 years (28-87) compared with 59 years (23-94) (p = 0.0012). Equal proportions of blacks (78.5%) and whites (79.2%) underwent surgery (p = 0.84), similar proportions of blacks (55.4%) and whites (60.8%) received chemotherapy (p = 0.18), and similar proportions of blacks (17.2%) and whites (20.5%) received radiation therapy (p = 0.31). There was no difference in overall survival or cancer-specific mortality between the 2 racial groups. Univariate analysis showed American Joint Committee on Cancer stage and surgery as the only statistically significant factors for overall survival. On multivariate analysis, stage, surgery, and chemotherapy were the only statistically significant factors. Race was not an independent determinant of survival. CONCLUSIONS: There were no differences in overall survival and cancer-related mortality between blacks and whites, and this may have resulted from identical treatment. The previously noted disparities in treatment and overall survival at our institution have disappeared.

Can patient reported outcomes help identify the optimal outcome in palliative surgery?

BACKGROUND: The purpose of this pilot study was to determine whether an open-ended questionnaire captures severe symptoms in cancer patients undergoing palliative surgical consultation that a structured, validated quality-of-life assessment does not capture. METHODS: We prospectively used the Functional Assessment of Cancer Therapy-General (FACT-G) and an open-ended questionnaire to assess the symptoms of patients with incurable malignancies who underwent palliative surgical consultation at our institution between January 2011 and September 2012. RESULTS: Of the 69 patients enrolled, the most common indications for consultation were bowel obstruction (54%), jaundice (13%), wound problems (10%), and gastrointestinal bleeding (7%). Of the severe symptoms patients reported, 76% were identified with the FACT-G alone, 22% were identified with the open-ended questionnaire alone, and 2% were duplicate responses captured with both the FACT-G and open-ended questionnaire. The open-ended questionnaire captured 68 instances of severe symptoms in 47 patients that the FACT-G did not capture; of these symptoms, 52 were considered to be highly relevant to surgery and potential outcome measures. CONCLUSIONS: An open-ended questionnaire can identify severe symptoms that a global quality of life survey cannot capture and could be used in conjunction with a global survey to reassess symptoms after palliative surgical consultation.

Cross-sectional study to assess the association of population density with predicted breast cancer risk.

The Gail and CARE models estimate breast cancer risk for white and African-American (AA) women, respectively. The aims of this study were to compare metropolitan and nonmetropolitan women with respect to predicted breast cancer risks based on known risk factors, and to determine if population density was an independent risk factor for breast cancer risk. A cross-sectional survey was completed by 15,582 women between 35 and 85 years of age with no history of breast cancer. Metropolitan and nonmetropolitan women were compared with respect to risk factors, and breast cancer risk estimates, using general linear models adjusted for age. For both white and AA women, tisk factors used to estimate breast cancer risk included age at menarche, history of breast biopsies, and family history. For white women, age at first childbirth was an additional risk factor. In comparison to their nonmetropolitan counterparts, metropolitan white women were more likely to report having a breast biopsy, have family history of breast cancer, and delay childbirth. Among white metropolitan and nonmetropolitan women, mean estimated 5-year risks were 1.44% and 1.32% (p < 0.001), and lifetime risks of breast cancer were 10.81% and 10.01% (p < 0.001), respectively. AA metropolitan residents were more likely than those from nonmetropolitan areas to have had a breast biopsy. Among AA metropolitan and nonmetropolitan women, mean estimated 5-year risks were 1.16% and 1.12% (p = 0.039) and lifetime risks were 8.94%, and 8.85% (p = 0.344). Metropolitan residence was associated with higher predicted breast cancer risks for white women. Among AA women, metropolitan residence was associated with a higher predicted breast cancer risk at 5 years, but not over a lifetime. Population density was not an independent risk factor for breast cancer.

Racial disparity in colorectal cancer: the role of ABO blood group.

BACKGROUND: We tested the hypothesis that racial differences that exist in the distribution of ABO blood type would partially explain the racial disparity in overall survival seen in colorectal cancer. METHODS: retrospective analysis of the cancer registry of a university hospital for patients treated for colorectal cancer between 1996 and 2008. Demographic, tumor-specific, and treatment-specific variables were abstracted. We also obtained ABO blood group data. The primary end point was overall survival. We divided patients into two groups based on where they underwent surgery: the University of Arkansas for Medical Sciences (UAMS) or outside facilities. RESULTS: Of 833 patients, 182 (21.8%) were black. There was no difference in overall survival between blacks and whites for the entire group (P = 0.61). There was a statistically significant difference in overall survival between patients at the UAMS and outside facilities (P < 0.0001). For the outside facilities group, there was a statistically significant difference in overall survival between blacks and whites (hazard ratio, CI: 1.48 [1.06-2.00]; P = 0.012); no race difference existed for the UAMS group. The ABO blood group had no effect on overall survival. On stage-stratified univariate and multivariate analyses, chemotherapy and surgery were the only statistically significant determinants of survival. CONCLUSIONS: In this study, racial differences in ABO blood group distribution had no effect on overall survival.

Comprehensive geriatric assessment of risk factors associated with adverse outcomes and resource utilization in cancer patients undergoing abdominal surgery.

BACKGROUND: The purpose of this prospective study was to identify risk factors for adverse outcomes or increased resource utilization after abdominal cancer surgery in geriatric patients. METHODS: Baseline clinical and geriatric assessment variables including functional status, nutritional status, comorbidity index, mental status, depression scale score, fatigue inventory scale, and polypharmacy scale were prospectively recorded for patients age ≥65 undergoing intra-abdominal oncologic surgery. Outcome variables included morbidity, mortality, discharge to nursing facility, prolonged hospital stay, and readmission. RESULTS: Of 111 patients, surgery type was colorectal in 40%, hepatopancreatobiliary in 30%, and gastric/duodenal in 14%. Variables associated with discharge to a nursing facility on multivariate analysis included weight loss ≥10% (OR 6.52 [95% CI: 1.43-29.76], P = 0.02), ASA score ≥2 (OR 5.08 [1.13-22.77], P = 0.03), and ECOG score ≥2 (OR 4.51 [1.03-19.71], P = 0.04). Variables independently associated with prolonged hospital stay included weight loss ≥10% (OR 4.03 [1.13-14.43], P = 0.03), the presence of polypharmacy (OR 2.45 [1.09-5.48], P = 0.03), and distant disease (OR 0.37 [0.15-0.91], P = 0.03). No variables were associated with morbidity or readmission. CONCLUSIONS: Pre-operative clinical and geriatric assessment tools can help predict the need for discharge to a nursing facility or increased length of stay. Future studies will be required to identify patients suitable for interventions to decrease hospital and post-discharge resource utilization.

The prevention and treatment of breast cancer- related lymphedema: A review.

Background: Breast cancer- related lymphedema (BCRL) affects about 3 to 5 million patients worldwide, with about 20,000 per year in the United States. As breast cancer mortality is declining due to improved diagnostics and treatments, the long-term effects of treatment for BCRL need to be addressed. Methods: The American Society of Breast Surgeons Lymphatic Surgery Working Group conducted a large review of the literature in order to develop guidelines on BCRL prevention and treatment. This was a comprehensive but not systematic review of the literature. This was inclusive of recent randomized controlled trials, meta-analyses, and reviews evaluating the prevention and treatment of BCRL. There were 25 randomized clinical trials, 13 systemic reviews and meta-analyses, and 87 observational studies included. Results: The findings of our review are detailed in the paper, with each guideline being analyzed with the most recent data that the group found evidence of to suggest these recommendations. Conclusions: Prevention and treatment of BCRL involve a multidisciplinary team. Early detection, before clinically apparent, is crucial to prevent irreversible lymphedema. Awareness of risk factors and appropriate practice adjustments to reduce the risk aids are crucial to decrease the progression of lymphedema. The treatment can be costly, time- consuming, and not always effective, and therefore, the overall goal should be prevention.

A 10-miRNA risk score-based prediction model for pathological complete response to neoadjuvant chemotherapy in hormone receptor-positive breast cancer.

Patients with hormone receptor (HR)-positive tumors breast cancer usually experience a relatively low pathological complete response (pCR) to neoadjuvant chemotherapy (NAC). Here, we derived a 10-microRNA risk score (10-miRNA RS)-based model with better performance in the prediction of pCR and validated its relation with the disease-free survival (DFS) in 755 HR-positive breast cancer patients (273, 265, and 217 in the training, internal, and external validation sets, respectively). This model, presented as a nomogram, included four parameters: the 10-miRNA RS found in our previous study, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) status, and volume transfer constant (Ktrans). Favorable calibration and discrimination of 10-miRNA RS-based model with areas under the curve (AUC) of 0.865, 0.811, and 0.804 were shown in the training, internal, and external validation sets, respectively. Patients who have higher nomogram score (>92.2) with NAC treatment would have longer DFS (hazard ratio=0.57; 95%CI: 0.39-0.83; P=0.004). In summary, our data showed the 10-miRNA RS-based model could precisely identify more patients who can attain pCR to NAC, which may help clinicians formulate the personalized initial treatment strategy and consequently achieves better clinical prognosis for patients with HR-positive breast cancer.

Lower extremity glandography (LEG): a new concept to identify and enhance lymphatic preservation.

BACKGROUND: Lower extremity edema remains a major postoperative complication after inguinal lymphadenectomy for vulvar cancer. This study documents the lymphatic drainage of the vulva versus the lymphatic drainage of the lower extremity coming through the femoral triangle. METHODS: Seven patients underwent either unilateral or bilateral inguinal lymphadenectomy in conjunction with a radical vulvar resection. Preoperatively, patients had technetium-99 injected into the vulvar cancer. Isosulfan blue was injected into the medioanterior thigh 10 cm below the inguinal ligament. The femoral triangle was opened, and a neoprobe was used to locate the "hot" node bearing the technetium-99. Gentle dissection located the blue lymphatic channel and any blue lymph nodes. The blue and hot nodes were resected and submitted separately. The patients then underwent a complete inguinal lymphadenectomy. RESULTS: A total of 11 groin dissections were performed. In 9 of the 11 groins, the hot node was identified, and in 8 of the 11 groins, blue node or lymphatic channel was identified. The hot nodes were uniformly located on the superior medial aspect of the femoral triangle. The blue nodes were uniformly located on the lateral aspect of the femoral triangle just anterior to the femoral artery or vein. Three patients had hot lymph nodes containing cancer. Of those 3 patients, one had an additional node positive. None of the blue lymph nodes contained cancer. CONCLUSIONS: This procedure demonstrates the alternative lymphatic drainage of the leg versus the vulva. Larger studies are necessary to document the exclusivity of these 2 drainage systems. Preservation of the lymphatic drainage of the leg may result in decreased lymphedema.

Establishment of a southern breast cancer cohort.

Breast cancer continues to be among the most common cancers affecting women in the United States. Researchers investigating the area are turning their attention to novel prevention, detection, and treatment options. Recent molecular epidemiology research has highlighted the effects of both genetic and environmental exposures on an individual's risk of developing breast cancer and predicted response to treatment. Cohort designs are a potentially powerful tool that researchers can utilize to investigate the genetic and environmental factors affecting breast cancer risk and treatment options. This paper describes the recruitment of a community-based cohort of women in a southern state. The Spit for the Cure Cohort (SFCC), being developed by researchers at the University of Arkansas for Medical Sciences (Little Rock, AR), is designed to be representative of the female population of the state with oversampling of women with a history of breast cancer and women of color. To date, the SFCC includes more than 14,000 women recruited from all 75 counties of Arkansas and six neighboring states. Methods used to recruit and maintain the cohort and collect both questionnaire data and genetic material are described, as are the demographic characteristics of the cohort as it currently exists. The recruitment methods utilized for the SFCC are rapidly building a breast cancer cohort and providing a large biorepository for molecular epidemiology research.

Immune response proteins as predictive biomarkers of doxorubicin-induced cardiotoxicity in breast cancer patients.

Cancer treatment with doxorubicin (DOX) can induce cumulative dose-dependent cardiotoxicity. Currently, there are no specific biomarkers that can identify patients at risk during the initial doses of chemotherapy. The aim of this study was to examine plasma cytokines/chemokines and potential cardiovascular biomarkers for the prediction of DOX-induced cardiotoxicity. Plasma samples were collected before (T0), and after the first (T1) and the second (T2) cycles of DOX-based chemotherapy of 27 breast cancer patients, including five patients who presented with >10% decline of left ventricular ejection fraction (LVEF), five patients with LVEF decline of 5-10%, and 17 patients who maintained normal LVEF at the end of chemotherapy (240 mg/m2 cumulative dose of DOX from four cycles of treatment). Multiplex immunoassays were used to screen plasma samples for 40 distinct chemokines, nine matrix metalloproteinases, 33 potential markers of cardiovascular diseases, and the fourth-generation cardiac troponin T assay. The results showed that the patients with abnormal decline of LVEF (>10%) had lower levels of CXCL6 and sICAM-1 and higher levels of CCL23 and CCL27 at T0; higher levels of CCL23 and lower levels of CXCL5, CCL26, CXCL6, GM-CSF, CXCL1, IFN-γ, IL-2, IL-8, CXCL11, CXCL9, CCL17, and CCL25 at T1; and higher levels of MIF and CCL23 at T2 than the patients who maintained normal LVEF. Patients with LVEF decline of 5-10% had lower plasma levels of CXCL1, CCL3, GDF-15, and haptoglobin at T0; lower levels of IL-16, FABP3, and myoglobin at T1; and lower levels of myoglobin and CCL23 at T2 as compared to the patients who maintained normal LVEF. This pilot study identified potential biomarkers that may help predict which patients are vulnerable to DOX-induced cardiotoxicity although further validation is needed in a larger cohort of patients. Impact statement Drug-induced cardiotoxicity is one of the major concerns in drug development and clinical practice. It is critical to detect potential cardiotoxicity early before onset of symptomatic cardiac dysfunction or heart failure. Currently there are no qualified clinical biomarkers for the prediction of cardiotoxicity caused by cancer treatment such as doxorubicin (DOX). By using multiplex immunoassays, we identified proteins with significantly changed plasma levels in a group of breast cancer patients who were treated with DOX-based chemotherapy and produced cardiotoxicity. These proteins were associated with immune response and were identified before DOX treatment or at early doses of treatment, thus they could be potential predictive biomarkers of cardiotoxicity although further validation is required to warrant their clinical values.

Conductive interstitial thermal therapy (CITT) device evaluation in VX2 rabbit model.

We have developed a conductive interstitial thermal therapy (CITT) device to precisely and reliably deliver controlled thermal doses to the surgical margins at the cavity site following tumor resection, intraoperatively. The temperature field created by CITT ablation of a perfused tissue was modeled with a finite element package Femlab. The modeling suggested that a maximum probe temperature of 120 degrees C and an ablation time of 20 minutes were required to ablate highly perfused tissue such as the VX2 carcinoma. Deployable pins enable faster and more reliable thermal ablation. The model predictions were tested by thermal ablation of VX2 carcinoma tumors implanted in adult New Zealand rabbits. The size of the ablated region was confirmed with a viability stain, triphenyltetrazolium chloride (TTC). Histopathological examination revealed 3 regions in the ablated area: a carbonized region (1-3 mm); a region that contained thermally fixed cells; and an area of coagulated necrosis cells. Cells in the thermally fixed region stained for PCNA (proliferating cell nuclear antigen) and were bounded by the carbonized layer at the cavity wall, and by necrotic cells that exhibit nuclear fragmentation and cell dissociation, 5 to 10 mm away from the CITT probe. Adjacent tissue outside the target region was spared with a clear demarcation between ablated and normal viable tissue. It is suggested that the CITT device can be used, clinically, to inhibit local recurrence by creating negative surgical margins following the resection of a primary tumor in non-metastatic early staged tumors.

Germline Genetic Variants in TEK, ANGPT1, ANGPT2, MMP9, FGF2 and VEGFA Are Associated with Pathologic Complete Response to Bevacizumab in Breast Cancer Patients.

BACKGROUND: We previously reported improved pathologic complete response (pCR) in a prospective phase II study using neoadjuvant bevacizumab in combination with chemotherapy compared to chemotherapy alone in breast cancer patients (41% vs. 25%, p = 0.0291). In this study, we queried germline single-nucleotide polymorphisms (SNPs) in angiogenesis-related genes for their impact on pCR and overall survival (OS). METHODS: DNA for genotyping was available from 34 subjects who received bevacizumab in addition to chemotherapy and 29 subjects who did not. Using Illumina® technology, we queried 504 SNPs with a minor allele frequency (MAF) of at least 5%, located in 10 angiogenesis-related genes, for their effect on pCR via logistic regression with an additive-inheritance model while adjusting for race and bevacizumab treatment. SNPs that showed significant associations with pCR were selected for additional characterization. RESULTS: After adjusting for race and tumor type, patients who had bevacizumab added to their neoadjuvant therapy were found to experience a significantly improved rate of pCR compared to patients who did not (adjusted OR 8.40, 95% CI 1.90-37.1). When patients were analyzed for SNP effects via logistic regression with race and bevacizumab treatment included as covariates, two SNPs in angiopoietin 1 (ANGPT1), six in ANGPT2, three in fibroblast growth factor 2 (FGF2), four in matrix metalloproteinase 9 (MMP9), three in tyrosine kinase, endothelial (TEK) and two in vascular endothelial growth factor A (VEGFA) were associated with pCR (P<0.05). However, when overall survival was considered, there was no difference between treatment groups or between genotypes. CONCLUSION: Genetic variability in TEK, ANGPT1, ANGPT2, FGF2, MMP9 and VEGFA is associated with pCR in bevacizumab-treated patients. Consistent with other studies, adding bevacizumab to standard chemotherapy did not impact OS, likely due to other factors and thus, while SNPs in TEK, ANGPT1, ANGPT2, FGF2, MMP9 and VEGFA were associated with pCR, they were not predictive of OS in this patient population. TRIAL REGISTRATION: ClinicalTrials.gov NCT00203502.

High-circulating Tie2 Is Associated With Pathologic Complete Response to Chemotherapy and Antiangiogenic Therapy in Breast Cancer.

INTRODUCTION: Vascular endothelial growth factor (VEGF) is a central mediator of angiogenesis in breast cancer. Research in antiangiogenic cancer treatment has been marked by the development of the monoclonal antibody bevacizumab, which targets VEGF in many solid tumors. As patients do not equally benefit from bevacizumab, it has become necessary to define the profile of patients who will benefit from the drug. MATERIALS AND METHODS: We have conducted a prospective phase II study in 39 patients using bevacizumab in breast cancer in the neoadjuvant setting, and found improved pathologic complete response (pCR) when bevacizumab was added to chemotherapy in patients with hormone receptor negative and invasive ductal carcinoma. Blood samples were collected at baseline and serially while patients were on treatment. Circulating angiogenesis-related proteins angiopoietin (ANG)1, ANG2, basic fibroblast growth factor, IL-1a, matrix metalloproteinase 9, platelet derived growth factor - BB, platelet endothelial cell adhesion molecule -1, Tie2, VEGF, and vascular endothelial growth factor receptor 2 were measured at baseline and during treatment. This correlative study was conducted to identify specific serum angiogenic factor profiles that might be associated with pCR in the neoadjuvant setting in breast cancer patients receiving bevacizumab and chemotherapy. RESULTS: Elevated baseline serum Tie2 and basic fibroblast growth factor were associated with pCR in response to this combination. Changes in serum levels of these proteins were seen during treatment but were not significantly different between the pCR and non-pCR groups. CONCLUSIONS: Baseline-circulating Tie2 levels may help distinguish patients who will have pCR from those who will not and may form the basis for future development of antiangiogenic therapy in breast cancer. Larger studies are needed to validate these findings. ClinicalTrials.gov Identifier: NCT00203502.