Genotype Frequencies of Selected Drug Metabolizing Enzymes and ABC Drug Transporters among Breast Cancer Patients on FAC Chemotherapy

PURPOSE Adjuvant chemotherapy for breast cancer has been the routine practice in the past decade. A number of studies have observed an increased incidence of treatment-related leukemias following chemotherapy with alkylating agents and/or topoisomerase II inhibitors. We evaluated the incidence of treatment-related leukemias in breast cancer patients treated in four adjuvant and two neoadjuvant chemotherapy trials at The University of Texas M.D. Anderson Cancer Center. PATIENTS AND METHODS Between 1974 and 1989, 1,474 patients with stage II or III breast cancer were treated in six prospective trials of adjuvant (n = 4) or neoadjuvant (n = 2) chemotherapy with fluorouracil, doxorubicin, and cyclophosphamide (CTX) (FAC) with or without other drugs. The median observation time was 97 months. In 1,107 patients, FAC chemotherapy was given postoperatively; 367 patients received induction chemotherapy, as well as postoperative chemotherapy. Eight hundred ten patients had surgery followed by radiotherapy and chemotherapy; 664 patients had surgery and chemotherapy only. Patients in two adjuvant and one neoadjuvant study received higher cumulative doses of CTX compared with those in the other studies. RESULTS Fourteen cases of leukemia were observed. Twelve of these patients had received radiotherapy and chemotherapy, and two had received chemotherapy only. Six of the reported patients with leukemia were treated with a cumulative CTX dose of greater than 6 g/ m2. Five of these patients had received both radiotherapy and chemotherapy. The median latency period in the 14 patients was 66 months (range, 22 to 113). Six of 10 patients with adequate cytogenetic analyses had abnormalities that involved chromosomes 5 and/or 7. The rest of the patients had nonspecific cytogenetic abnormalities or lacked cytogenetic information. The 10-year estimated leukemia rate was 1.5% (95% confidence interval [CI], 0.7% to 2.9%) for all patients treated, 2.5% (95% CI, 1.0% to 5.1%) for the radiotherapy-plus-chemotherapy group, and 0.5% (95% CI, 0.1% to 2.4%) for the chemotherapy-only group; this difference was statistically significant (P = .01). The 10-year estimated leukemia risk for the higher-dose (> 6 g/m2) CTX group was 2% (95% CI, 0.5% to 5.0%) compared with 1.3% (95% CI, 0.4% to 3.0%) for the lower-dose group, a difference that was not statistically significant (P = .53). CONCLUSION These data illustrate that patients treated with adjuvant FAC chemotherapy plus radiotherapy have a slightly increased risk of leukemia. This information needs to be considered in the treatment plans for patients with breast cancer. However, for most patients, the benefits of adjuvant therapy exceed the risk of treatment-related leukemia.

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The effect of prophylactic carvedilol on subclinical left ventricular dysfunction after 1 cycle FAC chemotherapy in breast cancer patients

IJC Heart & Vasculature ◽

10.1016/j.ijcha.2020.100575 ◽

2020 ◽

Vol 29 ◽

pp. 100575

Author(s):

Januar Wibawa Martha ◽

Dery A. Soedarsono ◽

Mohammad Iqbal ◽

Astri Astuti ◽

Erwan Martanto ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Left Ventricular Dysfunction ◽

Ventricular Dysfunction ◽

Left Ventricular ◽

Breast Cancer Patients ◽

Fac Chemotherapy

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Tumoral expression of drug and xenobiotic metabolizing enzymes in breast cancer patients of different ethnicities with implications to personalized medicine

Scientific Reports ◽

10.1038/s41598-017-04250-2 ◽

2017 ◽

Vol 7 (1) ◽

Cited By ~ 22

Author(s):

Yan Li ◽

Albert Steppi ◽

Yidong Zhou ◽

Feng Mao ◽

Philip Craig Miller ◽

...

Keyword(s):

Breast Cancer ◽

Personalized Medicine ◽

Cancer Patients ◽

Breast Cancer Patients ◽

Metabolizing Enzymes ◽

Xenobiotic Metabolizing Enzymes

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Abstract C073: The association between 27-hydroxycholesterol metabolizing enzymes, CYP27A1 and CYP7B1, expression and mortality in a multiethnic U.S. population of breast cancer patients

10.1158/1538-7755.disp19-c073 ◽

2020 ◽

Author(s):

Lenora WM Loo ◽

Yurii B Shvetsov ◽

Iona Cheng ◽

Brenda Y Hernandez

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Breast Cancer Patients ◽

Metabolizing Enzymes

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Evaluation of Ile655Val HER2 polymorphism associated with cardiac toxicity following the administration of trastuzumab in women with breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.634 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 634-634

Author(s):

Caroline Diorio ◽

Julie Lemieux ◽

Marc-Andre Cote ◽

Louise Provencher ◽

Corinne Nadeau-Larochelle ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Cancer Patients ◽

Cardiac Toxicity ◽

Statistical Significance ◽

Metastatic Breast ◽

Fisher Exact Test ◽

Breast Cancer Patients ◽

Her2 Positive ◽

Genotype Frequencies

634 Background: Trastuzumab is well tolerated without major side effects except for cardiac toxicity. Although a number of clinical parameters have been associated with trastuzumab-associated cardiac toxicity (TACT), there is some indication that genetic variation of the HER2 gene may play a toxic role in a population of metastatic breast cancer patients. However, this finding needs confirmation and we looked at a population of non-metastatic breast cancer. This study aimed to evaluate the association between cardiac toxicity and HER2 [Ile655Val] polymorphism in non-metastatic breast cancer patients treated with trastuzumab. Methods: The Ile655Val HER2 polymorphism was assessed in 73 women using TaqMan technology. For this study, the genotyping was performed using DNA extracted from normal breast tissue located at more than 1 cm of any other lesions. Charts review was used to collect information on TACT which was defined as any decline in LVEF > 10 % from the baseline to < 55 % or a decline in LVEF > 5 % to < 50 % (lower limit of normal). The Fisher exact test was used to evaluate the association between cardiac toxicity and HER2 polymorphism. Results: No deviation from the Hardy-Weinberg equilibrium has been observed for the allele and genotype frequencies. The distribution of HER2 polymorphism was 3 Val/Val (4%), 18 Ile/Val (25%) and 52 Ile/Ile (71%). In this population, 19% (14/73) developed a cardiac toxicity. We found that 29% (6/21) of Ile/Val or Val/Val carriers compared to 15% (8/52) of Ile/Ile carriers showed TACT, but this association did not reach statistical significance (P = 0.21). Conclusions: HER2 Ile655Val polymorphism may be an efficient marker of TACT considering this tendency with this small cohort of patients. Larger sample is needed to strengthen this conclusion, since this result may influence on prescribing decision for adjuvant chemotherapy and anti-HER2 therapy in HER2 positive patients.

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False Positive Tumor Markers: Elevation in Patients with Breast Cancer on FAC-type Chemotherapy and Correlation with the Development of Hand-foot Syndrome

The International Journal of Biological Markers ◽

10.1177/172460089601100404 ◽

1996 ◽

Vol 11 (4) ◽

pp. 203-206 ◽

Cited By ~ 4

Author(s):

L.B. Tyshler ◽

G.M. Longton ◽

G.K. Ellis ◽

R.B. Livingston

Keyword(s):

Breast Cancer ◽

Tumor Marker ◽

Cancer Patients ◽

Tumor Markers ◽

False Positive ◽

False Positive Rate ◽

Breast Cancer Patients ◽

Hand Foot Syndrome ◽

Positive Rate ◽

Fac Chemotherapy

Breast cancer patients on dose-intensive chemotherapy often have elevated tumor markers during the course of treatment. Our objective was to estimate the incidence of a “false positive” tumor marker screen and to determine whether hand-foot epithelial damage was correlated. Data from 53 patients with high risk primary breast cancer who had undergone adjuvant or neoadjuvant 5FU-containing chemotherapy (FAC or FAC plus G-CSF) for 3 to 12 months were reviewed. The relationship between tumor marker elevation and disease recur- rence, regimen intensity, and the occurrence of hand-foot syndrome was examined. Thirty-three of the 53 patients had elevated tumor markers in the absence of recurrent disease. The false positive rate was higher in patients who underwent FAC plus G-CSF chemotherapy than in patients who underwent FAC chemotherapy (92% vs 55%, p = .01). A false positive marker screen was associated with the occurrence of hand-foot syndrome even when the effect of regimen was accounted for by stratification (p=.01). Tumor marker screening of breast cancer patients on this type of adjuvant chemotherapy has poor specificity for recurrent malignancy. These data suggest tumor marker elevation may be an indicator of epithelial toxicity during chemotherapy, manifested clinically as hand-foot syndrome.

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Association of CYP19A1 gene variants with differences in disease progression in breast cancer patients from different racial/ethnic backgrounds.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.1558 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 1558-1558

Author(s):

Reina Villareal ◽

Angela W. Meisner ◽

Lina Aguirre ◽

Vibhati Kulkarny ◽

Vallabh Shah ◽

...

Keyword(s):

Breast Cancer ◽

Disease Progression ◽

Cancer Patients ◽

Racial Differences ◽

Cancer Progression ◽

Allele Frequencies ◽

Response To Treatment ◽

Gene Variants ◽

Breast Cancer Patients ◽

Genotype Frequencies

1558 Background: Polymorphisms in the aromatase (CYP19A1) gene result in differences in the risk for breast cancer and response to treatment. We hypothesize that allele frequencies in the CYP19A1 gene vary according to race and may result in differences in progression of breast cancer among women from different racial backgrounds. The objectives of this study are: 1) to determine the allele/genotype frequencies in the CYP19A1 gene among women with breast cancer from different racial backgrounds, and, 2) to determine the association between disease progression and CYP19A1 gene variants. Methods: Clinical data and stored DNA from 327 patients participating in the Expanded Breast Cancer Registry (EBCR) program at the University of New Mexico were analyzed. These patients were followed-up for a period of 1 to 6 years. Comprehensive genotyping for CYP19A1 gene single nucleotide polymorphisms (SNPs) was performed using microarray (Illumina). Results: Data from 164 non-Hispanic white and 119 Hispanic women were analyzed. Four SNPs (rs1259269, rs17703883, rs16964211, rs28757101) were associated with differences in genotype/allele frequencies between the 2 racial groups. Furthermore, 3 SNPs (rs4646, rs17647478, and rs6493486) were associated with differences in disease progression. The rare allele (G) for the rs17647478 (G/T) is associated with poor progression compared those without the allele (41.7% vs. 17.1%, p=0.04). Similarly the minor (A) allele for the rs4646 (A/C) and the rs6493486 (A/G) is also associated with a greater chance of worsening disease (23.2% vs. 12.4%, p=0.02 and 23.4% vs. 12.4%, p=0.02, respectively). A significant percentage of women carrying the A allele for both rs4646 and rs6493486 and the T allele for the rs17647478 have more advanced disease at the time of presentation. None of the SNPs analyzed result in racial differences in breast cancer progression. Conclusions: Polymorphisms in the CYP19A1 gene influence overall disease progression in breast cancer patients but have no impact on the racial differences of disease behavior. Women carrying the risk alleles present at a more advanced stage and are also at greater risk of progression.

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