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

Results

Patient Characteristics

The demographic features of the 415 patients in our database are presented in Table 1. Some features are consistent with averages for the USA, but our population is unusual compared with most other reported cohorts because of its marked ethnic and racial diversity (Figure 1). In the present analysis, we grouped patients into four racial/ethnic categories: white (36%), black (43%), hispanic (10%) and other (11%). Within these broad categories, our patient population contained diverse subcategories. The median age at diagnosis of invasive breast cancer in our patients was 58 years, which is slightly younger than the US average age of 61 years, as reported in the National Cancer Institute's SEER Cancer Statistics Review.[32] Of our patients, 29% were 50 years or younger and 71% were older than 50 years at diagnosis. These proportions are generally consistent with US averages.[33] Notable in our population was the frequency of elevated BMI (only 23% of women fell into the under/normal weight category, while 30% were overweight, 27% were classified as obesity I, 13% as obesity II and 7% as obesity III).

Figure 1.

Distribution of breast cancer patients by race/ethnicity. The chart depicts the proportion of patients by race/ethnicity, classifying them by region of origin. NOS, not otherwise specified.

Tumour Characteristics

Tumour characteristics are presented in Table 1. Of the 415 invasive breast cancers in our database, 81 (20%) were triple negative, 297 (72%) were ER and/or PR positive and 53 (13%) were HER2 positive. Overall, our patients had fewer HER2-positive tumours and more triple-negative tumours than in some series, although our proportions are consistent with those in racially/ethnically heterogeneous cohorts.[34,35,36] In addition, our patients presented at a somewhat later stage than average for the USA: 47% of our tumours were lymph node-positive; the USA average is 39%.[32] However, the presence of 96 tumours with unconfirmed node status may have affected these proportions.

We characterised all available triple-negative tumours (56 of 81 (69%)) with additional morphological classification and immunohistochemical staining for CK5/6 and EGFR to determine what proportion of the triple-negative tumours had the basal-like phenotype. We found that 19 of 56 (34%) tumours were medullary-like, 14 of 56 (25%) were grade 2 and 18 of 56 (32%) were grade 3 ductal carcinoma NOS and 5 of 56 (9%) were of other histologies. Of 56 tumours, 38 (68%) were CK5/6 and/or EGFR positive. There was a significant association between CK5/6 expression and EGFR expression with a Spearman correlation coefficient of 0.34 (p = 0.01). Taken together, these studies suggest that our triple-negative tumours include a high proportion of basal-like tumours.

Patient-tumour Associations

We examined associations between race, BMI, age (and presumed menopausal status), tumour grade, ER expression, PR expression, HER2 expression and nodal involvement. We confirmed previously noted associations between patient and tumour variables, for example, positive associations between markers of poor prognosis (e.g., grade and stage). Of particular relevance, we found in bivariate analyses that obesity was associated with race (p = 0.01)[15,37] and that triple-negative status was associated with race (p = 0.0002).[6,34,35,36,38,39]

Table 1 shows the associations of race/ethnicity with tumour prognostic markers and other clinicopathological features. We noted two associations pertinent to triple-negative tumours and BMI. First, 30% of tumours in black women were triple negative, compared with 11 to 13% of tumours in other women. Second, 55% of black women were obese, compared with 36 to 45% of other women. There was no substantial dependence on race/ethnicity categories other than black (Table 1): the results of our analyses did not substantially depend on more finely-divided race categories, as determined by visual examination of the associations and their intervals with the reference category limited to whites versus the reference category defined as non-blacks. Therefore, we combined white, hispanic and other race/ethnicity categories into a single category 'non-black', which serves as our reference group, to address two questions.

Black women were both more likely than other women to be obese and to have triple-negative tumours, so we asked whether obese black women had a higher proportion of triple-negative tumours than other obese women. As shown in Table 2, stratifying the dataset to black vs. non-black women, we found that 29% of obese black women had triple-negative tumours compared with 8.6% of obese non-black women (OR = 4.3: 95 CI = 1.8 to 10; p = 0.0004). (Using whites as the reference category, the OR = 4.2 and 95% CI = 1.6 to 13). Similarly, 31% of non-obese black women had triple-negative tumours compared with 15% of non-obese non-black women (OR = 2.7, 95% CI = 1.4 to 5.3; p = 0.003). (Using whites as the reference category, the OR = 2.5 and 95% CI = 1.2 to 5.4). These two ORs were not significantly different from one another (p = 0.41), suggesting that among black women, BMI does not appear to be associated with triple-negative status.

Next, we examined associations of age at diagnosis with tumour characteristics within black and non-black women (Table 3). In contrast to previous reports,[6,40] we did not find a strong association between triple-negative tumour status and younger age when we considered all patients (24% triple-negative tumours in women aged ≤ 50 years compared with 18% triple-negative women aged > 50 years; p = 0.22). Adjustment for more finely divided age categories made no difference in the estimates of association. We next considered black vs. non-black women. We found that the proportions of triple-negative tumours were similar in younger and older black women: 31% of black women aged 50 years or younger and 29% of black women aged over 50 years had triple-negative tumours (p = 0.76). In contrast, we found a marginal association between triple-negative tumours and age in non-black women: 17% of non-black women aged 50 years or younger had triple-negative tumours, compared with 10% of non-black women aged over 50 years (p = 0.11).

To further characterise the possible relations between race/ethnicity, BMI and triple-negative breast cancer, we performed multiple logistic regression analyses. Table 4 shows the adjusted OR and 95% CI from the multiple logistic regression analyses for patient characteristics of triple-negative breast cancers compared with other types of breast cancer. The odds of having a triple-negative tumour were three-fold higher (95% CI = 1.6 to 5.4) in black women as compared with white women. Mutually adjusting for race/ethnicity, BMI and age (age ≤ 50 years vs. > 50 years, as a surrogate for menopausal status), there remained a strong association between race/ethnicity and triple-negative tumours (p = 0.0001). After adjusting for race/ethnicity and age, we noted decreasing proportions of triple-negative tumours with increasing category of BMI (p = 0.08).

Because women of Caribbean origin constituted a large proportion of our black population (n = 56, 27%), we compared this subgroup to the rest of the black population. Controlling for age (≤ 50 years vs > 50 years), no significant differences were seen between Caribbean black women and other black women in the proportion of triple-negative tumours, BMI, grade or node involvement (see Additional Data File 1).

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