Aspirin use and mortality in women with stage I-III breast cancer: A population-based study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 521-521
Author(s):  
Thomas Ian Barron ◽  
Linda Sharp ◽  
Kathleen Bennett ◽  
Kala Visvanathan
Keyword(s):  
Breast Cancer ◽  
Exposure Duration ◽  
Proportional Hazards ◽  
Early Stage ◽  
Cox Proportional Hazards ◽  
Stage I ◽  
Response Analysis ◽  
Limited Information ◽  
Specific Mortality

521 Background: Recent observational studies have associated aspirin (ASP) use with large reductions in breast cancer (BC) mortality. However, these studies have provided limited information on dose or duration of ASP use, key issues relevant to translation of the results into clinical practice. Methods: Linked National Cancer Registry Ireland and prescription refill data (General Medical Services Ireland, GMS) were used to identify women aged 50-80 with incident stage I-III BC (2001-2006). ASP use was defined as high or low by the median number of ASP days’ supply (85 days) in the 90 days pre-diagnosis. Full capture of ASP use is expected as the GMS provides all medications, including ASP, without charge. Hazard ratios (HR) with 95% confidence intervals (CI) for ASP use and (i) all-cause and (ii) BC-specific mortality were estimated using Cox proportional hazards models adjusted for age, stage, grade, ER, PR, HER-2 status, comorbidity and other drug exposures. Analyses were stratified by tumor stage and nodal status. Results: 2714 women with stage I-III BC were identified (median follow-up = 3.3 years), of whom 642 (23.7%) used ASP in the 90 days pre diagnosis. High and low ASP exposure groups were strongly predictive of post-diagnosis ASP exposure levels (High: mean post diagnosis exposure duration – 83% of follow-up; dose – 75mg/day in 91% of women. Low: mean post-diagnosis exposure duration – 58% of follow-up; dose – 75mg/day in 80% of women). Women with any ASP use had a non-significant reduction in all-cause (HR 0.85 95%CI 0.68, 1.06) and BC-specific (HR 0.86 95%CI 0.65, 1.15) mortality, compared to ASP unexposed women. However, in the dose response analysis high ASP exposure was associated with a significant reduction in all-cause (HR 0.70 95% CI 0.51, 0.95) and BC-specific (HR 0.63 95% CI 0.42, 0.96) mortality. No reduction was observed for low ASP exposure. The benefits of ASP exposure were greater in early stage, node negative disease. Conclusions: Only high ASP exposure was associated with a significant reduction in all cause and BC-specific mortality. These findings may explain inconsistent results from previous studies. Our findings can inform future clinical trials.

Effects of metformin and sulfonylureas on overall and colorectal cancer-specific mortality.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2599-2599
Author(s):  
Susan Spillane ◽  
Kathleen Bennett ◽  
Linda Sharp ◽  
Thomas Ian Barron
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Proportional Hazards ◽  
Early Stage ◽  
Population Based ◽  
Cox Proportional Hazards ◽  
Stage I ◽  
Early Stage Disease ◽  
All Cause Mortality ◽  
Specific Mortality

2599 Background: Preclinical studies have suggested a role for metformin in the treatment of colorectal cancer (CRC). Associations between metformin versus sulfonylurea exposure and mortality (all-cause and colorectal cancer specific) are assessed in this population-based study of patients with a diagnosis of stage I-IV CRC. Methods: National Cancer Registry Ireland records were linked to prescription claims data and used to identify a cohort of patients with incident TNM stage I-IV CRC diagnosed 2001-2006. From this cohort, 2 patient groups were identified and compared for outcomes - those who received a prescription for metformin +/- a sulfonylurea (MET) or a prescription for sulfonylurea alone (SUL) in the 90 days pre CRC diagnosis. Adjusted hazard ratios (HR) with 95% confidence intervals (CI) were estimated using Cox proportional hazards models adjusted for age, sex, stage, grade, site, comorbidities, year of diagnosis, and insulin, aspirin or statin exposure. Analyses were repeated stratifying by stage and site. Results: 5,617 patients with stage I-IV CRC were identified, of whom 369 received a prescription for metformin or a sulfonylurea in the 90 days pre diagnosis (median follow-up 1.6 years; MET: n=257; SUL: n=112). In adjusted analyses metformin exposure was associated with a 28% lower risk of all-cause mortality relative to sulfonylurea exposure (HR 0.72, 95% CI 0.53-0.98) and a non-significant 24% reduction in CRC-specific mortality (HR 0.76, 95% CI 0.52-1.13). In analyses stratified by site, in colon cancer, metformin exposure was associated with a significant one-third reduction in all-cause mortality (HR 0.66, 95% CI 0.46-0.95) and a non-significant reduction in site-specific mortality (HR 0.64, 95% CI 0.40-1.02). No mortality benefit was observed for rectal cancer. The association between metformin exposure and reduced mortality was strongest for stage I/II disease (all-cause mortality: HR 0.56, 95% CI 0.32-0.98; CRC-specific mortality: HR 0.48, 95% CI 0.21-1.11). Conclusions: Pre-diagnosis metformin exposure in CRC patients was associated with a significant reduction in mortality relative to sulfonylurea exposure. This benefit was greatest in patients with colon cancer and early stage disease.

Circulating tumor cell status and benefit of radiotherapy in stage I breast cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11524-11524
Author(s):  
Chelain Rae Goodman ◽  
Brandon-Luke L Seagle ◽  
Eric Donald Donnelly ◽  
Jonathan Blake Strauss ◽  
Shohreh Shahabi
Keyword(s):  
Breast Cancer ◽  
Tumor Cell ◽  
Proportional Hazards ◽  
Early Stage ◽  
Cohort Analysis ◽  
Metastatic Breast ◽  
Circulating Tumor Cell ◽  
Cox Proportional Hazards ◽  
Stage I ◽  
Matched Cohort

11524 Background: Circulating tumor cell (CTC) status has been shown to be prognostic of decreased survival in non-metastatic breast cancer. While up to 20-30% of patients with early breast cancer have detectable CTCs, less is known regarding the role of CTC-status in guiding clinical management. Methods: An observational cohort study was performed on women with stage I breast cancer evaluated for CTCs from the 2004-2014 National Cancer Database. Logistic regression was used to explore clinicopathological associations with CTC-status. Kaplan-Meier and multivariable Cox proportional-hazards survival analyses were used to estimate associations of CTC-status with overall survival using a propensity score-adjusted and inverse probability-weighted matched cohort. Results: Of the stage I breast cancer women evaluated for CTCs, 23.1% (325/1,407) were CTC-positive. Age, histology, receptor status, and nodal stage were associated with CTC-status. CTC-status was an effect modifier of the radiotherapy-survival association: CTC-positive women who did not receive radiotherapy had an increased hazard of death compared to CTC-negative women who also did not receive radiotherapy (four-year survival: 85.7% vs. 93.3%, HR = 2.92, CI = 1.43-5.98, P = 0.003). CTC-positive patients treated with radiotherapy did not have decreased survival compared to CTC-negative patients not treated with radiotherapy (HR = 0.67, CI = 0.28-1.65, P = 0.40). From the matched cohort analysis, CTC-positive women who did not receive radiation had a 4.82-fold increased hazard of death compared to CTC-positive women treated with radiotherapy (four-year survival: 83.2% vs. 96.6%; CI = 2.62-8.85, P < 0.001). Conclusions: Treatment with adjuvant radiotherapy was associated with improved survival in CTC-positive women with stage I breast cancer. If prospectively validated, CTC-status may be valuable as a predictor of benefit of radiotherapy in early stage breast cancer.

Adjuvant endocrine monotherapy (ET) versus adjuvant breast radiation (RT) alone in healthy older women with stage I, estrogen receptor-positive (ER+) breast cancer: An analysis of the National Cancer Database (NCDB).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 519-519
Author(s):  
Anthony H. Bui ◽  
Manjeet Chadha ◽  
Theresa H. Shao ◽  
Naamit K. Gerber ◽  
Sarah P. Cate ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Older Women ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Stage I ◽  
Nccn Guidelines ◽  
Treatment Groups ◽  
Distant Relapse ◽  
Demographic Covariates

519 Background: The NCCN guidelines state that breast RT may be omitted in patients > 70 years of age with ER+, clinically node-negative, T1 breast cancer (BC) who receive adjuvant ET. Available data on older patients notes that local relapses are the most frequent site of failure, and distant relapse rates are low. The side effects of ET are not inconsequential and negatively affect QOL. The objectives of this study are to examine clinical outcomes including overall survival (OS) in women ≥70 years of age treated by lumpectomy(L)+ET and L+RT in the NCDB. Methods: The 2004-2013 NCDB includes 76,431 women ≥70 years with ER+ stage I BC who underwent L, and had a minimum one year follow up. Women who received no adjuvant therapy, both ET+RT, or any chemotherapy were excluded. To limit the analysis to healthy women, we excluded subjects with a Charlson comorbidity index > 0. We identified 24,572 patients who received either adjuvant ET monotherapy or adjuvant RT alone. Among these, 46% (11,313) received ET and 54% (13,259) breast RT. Overall median follow up was 57 months (range: 12-143 months). Analysis of OS between the 2 treatment groups was performed using Kaplan-Meier statistics and Cox proportional hazards regression; propensity weighting was used to balance covariates across the 2 treatment groups. Results: After propensity weighting, demographic covariates including age, race, insurance, and facility type were balanced between the 2 treatment groups. The median OS for ET was 125.9 months (95% CI 120.1-131.8), and 127.2 months for RT (95% CI 124.5-131.7) (p < 0.0001). The weighted hazard of death was 11.7% less in women receiving RT compared to ET (HR 0.883, 95% CI 0.834-0.936, p < 0.0001). Conclusions: To our knowledge, this is the first large study comparing RT and ET monotherapy in healthy older women with stage I, ER+ BC. The OS with RT alone is not inferior to ET alone, and in this study population is noted to be better. While this analysis has various limitations not dissimilar from other NCDB database studies, our observations are encouraging and warrant further research with prospective studies.

scholarly journals Association between overall diet quality and postmenopausal breast cancer risk in five Finnish cohort studies

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Satu Männistö ◽  
Kennet Harald ◽  
Tommi Härkänen ◽  
Mirkka Maukonen ◽  
Johan G. Eriksson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Diet Quality ◽  
Proportional Hazards ◽  
Postmenopausal Breast Cancer ◽  
Healthy Eating Index ◽  
Cox Proportional Hazards ◽  
Healthy Diet ◽  
Food Culture ◽  
Alternative Healthy Eating Index

AbstractThere is limited evidence for any dietary factor, except alcohol, in breast cancer (BC) risk. Therefore, studies on a whole diet, using diet quality indices, can broaden our insight. We examined associations of the Nordic Diet (mNDI), Mediterranean diet (mMEDI) and Alternative Healthy Eating Index (mAHEI) with postmenopausal BC risk. Five Finnish cohorts were combined including 6374 postmenopausal women with dietary information. In all, 8–9 dietary components were aggregated in each index, higher total score indicating higher adherence to a healthy diet. Cox proportional hazards regression was used to estimate the combined hazard ratio (HR) and 95% confidence interval (CI) for BC risk. During an average 10-year follow-up period, 274 incident postmenopausal BC cases were diagnosed. In multivariable models, the HR for highest vs. lowest quintile of index was 0.67 (95 %CI 0.48–1.01) for mNDI, 0.88 (0.59–1.30) for mMEDI and 0.89 (0.60–1.32) for mAHEI. In this combined dataset, a borderline preventive finding of high adherence to mNDI on postmenopausal BC risk was found. Of the indices, mNDI was more based on the local food culture than the others. Although a healthy diet has beneficially been related to several chronic diseases, the link with the etiology of postmenopausal BC does not seem to be that obvious.

Effect of Pregnancy on Overall Survival After the Diagnosis of Early-Stage Breast Cancer

2001 ◽  
Vol 19 (6) ◽  
pp. 1671-1675 ◽  
Author(s):  
Shari Gelber ◽  
Alan S. Coates ◽  
Aron Goldhirsch ◽  
Monica Castiglione-Gertsch ◽  
Gianluigi Marini ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Proportional Hazards ◽  
Comparison Group ◽  
Early Stage ◽  
Pregnant Patient ◽  
Subsequent Pregnancy ◽  
Cox Proportional Hazards ◽  
Early Stage Breast Cancer ◽  
Study Group ◽  
The Impact

PURPOSE: To evaluate the impact of subsequent pregnancy on the prognosis of patients with early breast cancer. PATIENTS AND METHODS: One hundred eight patients who became pregnant after diagnosis of early-stage breast cancer were identified in institutions participating in International Breast Cancer Study Group (IBCSG) studies. Fourteen had relapse of breast cancer before their first subsequent pregnancy. The remaining 94 patients (including eight who relapsed during pregnancy) formed the study group reported here. A comparison group of 188 was obtained by randomly selecting two patients, matched for nodal status, tumor size, age, and year of diagnosis from the IBCSG database, who were free of relapse for at least as long as the time between breast cancer diagnosis and completion of pregnancy for each pregnant patient. Survival comparison used Cox proportional hazards regression models. RESULTS: Overall 5- and 10-year survival percentages (± SE) measured from the diagnosis of early-stage breast cancer among the 94 study group patients were 92% ± 3% and 86% ± 4%, respectively. For the matched comparison group survival was 85% ± 3% at 5 years and 74% ± 4% at 10 years (risk ratio, 0.44; 95% confidence interval, 0.21 to 0.96; P = .04). CONCLUSION: Subsequent pregnancy does not adversely affect the prognosis of early-stage breast cancer. The superior survival seen in this and other controlled series may merely reflect a healthy patient selection bias, but is also consistent with an antitumor effect of the pregnancy.

Utility and factors associated with imaging early-stage breast cancer: Are we choosing wisely?

2018 ◽  
Vol 36 (30_suppl) ◽  
pp. 52-52
Author(s):  
Ana I. Velazquez Manana ◽  
Nina Nguyen ◽  
Carlos Rodriguez Bonilla ◽  
Theresa Shao
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Early Stage ◽  
Positive Lymph Node ◽  
Young Age ◽  
Stage I ◽  
Choosing Wisely ◽  
Factors Associated ◽  
Routine Imaging

52 Background: Breast cancer (BC) is the most common malignancy in women with estimated care costs of $20.50 billion/year by 2020. In 2012, ASCO released the Choosing Wisely Initiative which recommended against the use of routine imaging in patients with newly diagnosed early stage BC. We examined the adherence rate and factors associated with non-adherence in patients with early stage BC treated within a large health care system. Methods: We identified all women with stage I-II BC diagnosed between January 1, 2014 and December 31, 2015 from the Cancer Registry of Mount Sinai Health System. Demographic, clinical and treatment related factors were collected. Medical records were reviewed to identify patients who had routine staging scan. Data of initial and follow-up imaging over 1-year period were collected. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from logistic regression models. Results: Among 733 BC patients, the median age at diagnosis was 58 (range 26-98). One hundred thirty nine patients (19%) had routine imaging with a mean number of initial scans of 1.53 and 59 (42%) patients had at least 1 subsequent scan in the 1-year follow up (range 1-4 scans/year). PET/CT was the most frequent modality, followed by CT. Medical oncologist was the ordering provider in 52% of the cases and surgical oncologist in 44.6%. Routine scan identified no cases of metastatic disease. False-positive findings were identified in 43% and incidental findings in 8% of cases. Total cost of imaging in this group was $4480/patient. Young age ( < 50), TN disease, tumor size > 2cm and positive lymph node were associated with increased staging scan on univariate and multivariate analysis. Conclusions: Our study highlights the prevalence of unnecessary scan in up to 19% of patients with stage I-II BC. Routine imaging resulted in increased radiation exposure and additional cost of $4480/patient. The presence of T2 tumor, positive lymph node, TN disease and young age were associated with increased staging scan. Further educational efforts are needed to avoid unnecessary scans in patients with early stage BC. [Table: see text]

Use of surgery and stereotactic body radiotherapy (SBRT) in very elderly patients with early-stage non-small cell lung cancer (NSCLC): A national cancer database (NCDB) analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20058-e20058
Author(s):  
Michael Kharouta ◽  
William Grubb ◽  
Tarun Kanti Podder ◽  
Tithi Biswas
Keyword(s):  
Elderly Patients ◽  
Median Survival ◽  
Early Stage ◽  
Clinical Stage ◽  
Cox Proportional Hazards ◽  
Stage I ◽  
Limited Information ◽  
Very Elderly ◽  
Large Hospital ◽  
Early Stage Nsclc

e20058 Background: SBRT treatment for very elderly ( > 80 years) patients with early stage NSCLC has been reported to be well tolerated with good short term efficacy. Using a large hospital based registry, we report a comparison of patterns of practice, outcomes, and prognostic factors for very elderly patients undergoing any treatment for early-stage NSCLC. Methods: The NCDB was queried for patients with clinical Stage I-IIA NSCLC with age ≥ 80 years diagnosed from 2001-2015 treated with surgery or SBRT alone. Patients were excluded if they received chemotherapy /immunotherapy or non-standard SBRT doses (i.e. > 5 fractions of RT, < 30 Gy or > 70 Gy total dose). Survival analyses were performed with propensity-matching, Kaplan-Meier estimates, Cox proportional hazards regression, and log rank testing. Results: 26039 patients met search criteria, median age 83 (80-90) years. 17141 (65.8%) patients underwent surgery, and 8898 (34.2%) underwent SBRT. Median follow up was 31 months. Median survival was 52 and 35 months for surgery and SBRT. Of patients receiving SBRT, 2044 (23%) had a contraindication to primary surgery due to patient risk factors. Age, clinical stage, tumor size, surgery type, CDCC score, BED, bronchial involvement, and type of treatment facility were predictive of median survival. BED > 154 Gy was associated with greater median survival (p < 0.01). Lobectomy was associated with greater median survival vs sub-lobar resection/pneumonectomy (p < 0.0001). For stage I tumors, surgery was associated with better median survival (56 vs. 35 months, p < 0.0001), but for stage IIA patients both modalities had similar median survival (30 vs 29 months, p = 0.04). Conclusions: Surgery remains the predominant treatment modality for early stage NSCLC in this very elderly population, and is associated with good outcomes for patients with stage I tumors. For elderly patients who are poor surgical candidates due to medical co-morbidities SBRT is associated with reasonable median survival. With limited information on patient comorbidities, more robust studies are needed to determine the effects of patient selection on treatment outcomes in this population.

Race as an independent factor for survival in breast cancer patients according to analysis of the National Cancer Database (NCDB).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e18155-e18155 ◽  
Author(s):  
Drew Carl Drennan Murray ◽  
Shruti Bhandari ◽  
Phuong Ngo ◽  
Sarah Mudra ◽  
Rachana Shirish Lele ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Proportional Hazards ◽  
Early Stage ◽  
Tumor Biology ◽  
Multivariable Analysis ◽  
Cox Proportional Hazards ◽  
Independent Factor ◽  
Breast Cancer Patients ◽  
Delayed Treatment

e18155 Background: Black (B) women after early stage of diagnosis have been shown to have double the risk of white (W) women for failing to receive adjuvant chemotherapy. Despite lower incidence of breast cancer in B patients, they are more likely to die of the disease. Worse outcomes in B populations have been related to clinical and socioeconomic factors. However, the determination of improved access and its effects on survival in black patients remains uncertain. Methods: 1042844 patients diagnosed between 2004 and 2014 with stage I-III breast cancer were identified in the NCDB. Only W and B races were analyzed with established risk factors of age, stage, comorbidity score, and insurance status. Data was analyzed using univariable and multivariable logistic and Cox proportional hazards regression models. Odds Ratio (OR) for binary outcome, Hazard Ratio (HR) for time-to-event (survival) outcome along with 95% confidence interval (95% CI) are reported. Results: Among the total population 85.5% were W, 10.6% B, and 3.9% other. B were more likely to be uninsured (OR: 1.66; 95% CI: 1.59 - 1.72; p < 0.0001), or have Medicaid (OR: 2.01; 95% CI: 1.96 - 2.07; p < 0.0001). B were also diagnosed at later stage (stage 3 OR: 1.59; 95% CI: 1.57 - 1.63; p < 0.0001) with higher co-morbidities (OR: 2.49; 95% CI: 2.34 - 2.67; p < 0.0001) consistent with prior studies. B were more likely to experience delayed treatment (OR: 2.15; 95% CI: 2.10 - 2.20; p < 0.0001). B race remained an independent factor associated with higher likelihood of death compared to W patients (HR: 1.32; 95% CI: 1.3 - 1.34; p < 0.0001) in multivariable analysis. Conclusions: This large database study demonstrates that even when controlling for established risk factors such lack of insurance or Medicaid, higher comorbidities, and later stage at diagnosis, B patients were more likely to experience delays in treatment initiation and worse overall survival. This suggests race remains an independent risk factor for poor outcome even when clinical factors are matched. Further analysis including tumor biology should be examined to better understand this persistent disparity.

Chemotherapy and Cardiotoxicity in Older Breast Cancer Patients: A Population-Based Study

2005 ◽  
Vol 23 (34) ◽  
pp. 8597-8605 ◽  
Author(s):  
John J. Doyle ◽  
Alfred I. Neugut ◽  
Judith S. Jacobson ◽  
Victor R. Grann ◽  
Dawn L. Hershman
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Proportional Hazards ◽  
Population Based ◽  
Cox Proportional Hazards ◽  
Stage I ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Increased Risk

Purpose Adjuvant chemotherapy, especially with anthracyclines, is known to cause acute and chronic cardiotoxicity in breast cancer patients. We studied the cardiac effects of chemotherapy in a population-based sample of breast cancer patients aged ≥ 65 years with long-term follow-up. Patients and Methods In the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we analyzed treatments and outcomes among women ≥ 65 years of age who were diagnosed with stage I to III breast cancer from January 1, 1992 to December 31, 1999. Propensity scores were used to control for baseline heart disease (HD) and other known predictors of chemotherapy, and Cox proportional hazards models were used to estimate the risk of cardiomyopathy (CM), congestive heart failure (CHF), and HD after chemotherapy. Results Of 31,748 women with stage I to III breast cancer, 5,575 (18%) received chemotherapy. Chemotherapy was associated with younger age, fewer comorbidities, hormone receptor negativity, multiple primary tumors, and advanced disease. Patients who received chemotherapy were less likely than other patients to have pre-existing HD (45% v 55%, respectively; P < .001). The hazard ratios for CM, CHF, and HD for patients treated with doxorubicin (DOX) compared with patients who received no chemotherapy were 2.48 (95% CI, 2.10 to 2.93), 1.38 (95% CI, 1.25 to 1.52), and 1.35 (95% CI, 1.26 to 1.44), respectively. The relative risk of cardiotoxicity among patients who received DOX compared with untreated patients remained elevated 5 years after diagnosis. Conclusion When baseline HD was taken into account, chemotherapy, especially with anthracyclines, was associated with a substantially increased risk of CM. As the number of long-term survivors grows, identifying and minimizing the late effects of treatment will become increasingly important.

The HOXB13:IL17BR Expression Index Is a Prognostic Factor in Early-Stage Breast Cancer

2006 ◽  
Vol 24 (28) ◽  
pp. 4611-4619 ◽  
Author(s):  
Xiao-Jun Ma ◽  
Susan G. Hilsenbeck ◽  
Wilson Wang ◽  
Li Ding ◽  
Dennis C. Sgroi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Factor ◽  
Clinical Outcome ◽  
Cancer Patients ◽  
Proportional Hazards ◽  
Early Stage ◽  
Cox Proportional Hazards ◽  
Tamoxifen Treatment ◽  
Breast Cancer Patients ◽  
Node Negative

Purpose We previously identified three genes, HOXB13, IL17BR and CHDH, and the HOXB13:IL17BR ratio index in particular, that strongly predicted clinical outcome in breast cancer patients receiving tamoxifen monotherapy. Confirmation in larger independent patient cohorts was needed to fully validate their clinical utility. Patients and Methods Expression of HOXB13, IL17BR, CHDH, estrogen receptor (ER) and progesterone receptor (PR) were quantified by real-time polymerase chain reaction in 852 formalin-fixed, paraffin-embedded primary breast cancers from 566 untreated and 286 tamoxifen-treated breast cancer patients. Gene expression and clinical variables were analyzed for association with relapse-free survival (RFS) by Cox proportional hazards regression models. Results ER and PR mRNA measurements were in close agreement with immunohistochemistry. In the entire cohort, expression of HOXB13 was associated with shorter RFS (P = .008), and expression of IL17BR and CHDH was associated with longer RFS (P < .0001 for IL17BR and P = .0002 for CHDH). In ER+ patients, the HOXB13:IL17BR index predicted clinical outcome independently of treatment, but more strongly in node-negative patients. In multivariate analysis of the ER+ node-negative subgroup including age, PR status, tumor size, S phase fraction, and tamoxifen treatment, the two-gene index remained a significant predictor of RFS (hazard ratio = 3.9; 95% CI, 1.5 to 10.3; P = .007). Conclusion This tumor bank study demonstrated HOXB13:IL17BR index is a strong independent prognostic factor for ER+ node-negative patients irrespective of tamoxifen therapy.

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