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.

scholarly journals Clinical CYP2D6 Genotyping to Personalize Adjuvant Tamoxifen Treatment in ER-Positive Breast Cancer Patients: Current Status of a Controversy

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 771
Author(s):  
Tessa A. M. Mulder ◽  
Mirjam de With ◽  
Marzia del Re ◽  
Romano Danesi ◽  
Ron H. J. Mathijssen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Outcome ◽  
Cancer Patients ◽  
Plasma Concentrations ◽  
Tamoxifen Treatment ◽  
Current Status ◽  
Endocrine Treatment ◽  
Breast Cancer Patients ◽  
Er Positive ◽  
Positive Breast Cancer

Tamoxifen is a major option for adjuvant endocrine treatment in estrogen receptor (ER) positive breast cancer patients. The conversion of the prodrug tamoxifen into the most active metabolite endoxifen is mainly catalyzed by the enzyme cytochrome P450 2D6 (CYP2D6). Genetic variation in the CYP2D6 gene leads to altered enzyme activity, which influences endoxifen formation and thereby potentially therapy outcome. The association between genetically compromised CYP2D6 activity and low endoxifen plasma concentrations is generally accepted, and it was shown that tamoxifen dose increments in compromised patients resulted in higher endoxifen concentrations. However, the correlation between CYP2D6 genotype and clinical outcome is still under debate. This has led to genotype-based tamoxifen dosing recommendations by the Clinical Pharmacogenetic Implementation Consortium (CPIC) in 2018, whereas in 2019, the European Society of Medical Oncology (ESMO) discouraged the use of CYP2D6 genotyping in clinical practice for tamoxifen therapy. This paper describes the latest developments on CYP2D6 genotyping in relation to endoxifen plasma concentrations and tamoxifen-related clinical outcome. Therefore, we focused on Pharmacogenetic publications from 2018 (CPIC publication) to 2021 in order to shed a light on the current status of this debate.

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.

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