Triple-negative Breast Cancers Are Increased in Black Women Regardless of Age or Body Mass Index

Increased Risk Regardless of Age or Body Mass Index

Lesley A Stead; Timothy L Lash; Jerome E Sobieraj; Dorcas D Chi; Jennifer L Westrup; Marjory Charlot; Rita A Blanchard; John C Lee; Thomas C King; Carol L Rosenberg

Disclosures

Breast Cancer Res 

In This Article

Materials and Methods

Study Population

With Institutional Review Board approval, we established a database of all female patients diagnosed at our institution with invasive breast cancer between March 1998 and November 2006. Informed consent was waived because individual patient information was identified only by investigator-generated code numbers that are not linkable to patient identifiers. For each patient, we identified tumour grade, stage, level of ER, PR and HER2 expression (or gene amplification), patient age, BMI (using standard National Heart, Lung and Blood Institute categories) and self-identified racial group. Recurrent tumours were excluded. (Recurrence was defined by time elapsed since first tumour, interim treatment, immunophenotype, histology, metastases and clinical impression). Ten of 415 tumours (2%) were second primary or synchronous contralateral breast tumours and were included in this study.

Data Collection

We queried electronic medical records (EMR) and performed manual medical record review for all patients to ensure quality control. Tumour histology, grade, stage, ER, PR and HER2 expression were determined from the original pathology reports. Tumours had been diagnosed by experienced pathologists using standard criteria for histology and modified Scarff-Bloom-Richardson criteria for grade. ER and PR expression were determined using immunoperoxidase staining (Dako, Carpinteria, CA, USA) and quantified by image analysis (Biogenex, San Ramon, CA, USA) with values less than 5% categorised as negative. HER2 expression was determined by immunohistochemistry (Dako, Carpinteria, CA, USA). Tumours that showed 2+ Her2/neu immunohistochemistry staining based on HercepTest criteria were definitively assessed by fluorescence in situ hybridisation (FISH) (Vysis, Des Plaines, IL, USA). Tumours were designated as being HER2+ if they showed 3+ Her2/neu immunohistochemistry staining (based on HercepTest criteria) or if they were FISH positive.[27,28] Stage at diagnosis was coded according to the American Joint Commission on Cancer's Cancer Staging Manual.[29]

Patient age at diagnosis was calculated using the dates of birth and diagnosis in the EMR. Patients were categorised as diagnosed at age 50 years or younger, when they are more likely to be premenopausal, or at age over 50 years, when they are more likely to be postmenopausal. BMI was calculated by weight (kg)/height squared (m2) using EMR data. In 97% of cases, weight and height were recorded within six months of diagnosis. If more than one weight or height value was available, we used the values closest to the date of diagnosis. Patients were placed into one of five BMI categories: under/normal weight (BMI < 25), overweight (BMI 25 to < 30), obesity I (BMI 30 to < 35), obesity II (BMI 35 to < 40) or obesity III (BMI ≥ 40).

Racial/ethnic group was determined by patient self-identification at the time of registration. Categories included: white/caucasian, black/African-American, hispanic, Asian/Pacific Islander, Middle Eastern and other. Due to sparse data, patients self-identified as Asian or Middle Eastern were included in the other category. To test the accuracy of the registration data, a manual review of the EMR was performed to determine provider-identified racial/ethnic group. A provider-identified racial/ethnic group was available for 402 of 415 patients and was concordant with the self-identified group in 91% of cases. When groups differed, the self-identified group was used. EMR data often included country of origin.

Because women born in the Caribbean constituted a large subgroup of our black population (n = 56, 27%), we compared this subgroup to the rest of the black population, which comprised patients who were provider-identified as African-American, African or black without further specification. Our Caribbean black patients were from countries with a majority pan-West African origin (Haiti, Jamaica, Trinidad, Tobago, Barbados and Montserrat). Patients from the Caribbean countries with a majority hispanic origin (Dominican Republic, Puerto Rico and Cuba) were classified as hispanic and not included in this black subgroup comparison.

Morphology and Immunohistochemistry

For 56 of the 81 triple-negative tumours, residual paraffin-embedded tumour tissue was available and additional evaluation could be performed. For additional morphological assessment, tumours were classified as grade 2 or grade 3 ductal carcinoma not otherwise specified (NOS), medullary-like carcinoma or other (for example, grade 1 ductal NOS, lobular or micropapillary tumours). Additional immunohistochemistry was performed with antibodies to CK 5/6 (Biocare Medical, Concord, CA, USA), and EGFR (Dako, Carpinteria, CA, USA) using a streptavidin-biotin horseradish peroxidase detection kit (Biogenex, San Ramon, CA, USA). The expression of these markers was graded semi-quantitatively. Allred scoring[30] was used for CK5/6, with a score of 5 or more considered as positive. HercepTest scoring criteria[27] were used to grade EGFR expression, with a score of 2+ or more considered as positive.[31]

Statistical Analysis

Data on patient and tumour characteristics were entered into a Microsoft Excel worksheet (Redmond, WA, USA) and exported into the SAS (Cary, NC, USA) statistical package. We used chi-squares statistics based on contingency tables to test for homogeneity of proportions and multivariate logistic regression to determine associations between patient-tumour characteristics and triple-negative breast cancer. Odds ratios (OR) and 95% confidence intervals (CI) from the multivariate logistic regression analyses were adjusted for race, BMI and age (≤ 50 or > 50). We investigated whether there was an adjusted association between categorical variables (race and BMI group) and triple-negative tumour type by calculating twice the difference in the model log-likelihood with and without the categorical variable. This was distributed as chi-squared with degrees of freedom equal to the number of categories less one. Women with missing data were excluded from these analyses.

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