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American Journal of Cancer Research logoLink to American Journal of Cancer Research
. 2023 Feb 15;13(2):678–691.

Incidence trends in triple-negative breast cancer among women in the United States from 2010 to 2019 by race/ethnicity, age and tumor stage

Xianglin L Du 1, Zhuoyun Li 1
PMCID: PMC9989620  PMID: 36895969

Abstract

There were substantial ethnic disparities in the incidence rates of triple-negative breast cancer, but few studies were conducted on the incidence trend of triple-negative breast cancer by race/ethnicity. This study aimed to address the longer trends in the incidence of triple-negative breast cancer by race/ethnicity in women from 2010 to 2019, examine the incidence trends by patient age, tumor stage and time periods, and explore the changing proportions of three component receptors over time for triple-negative breast cancer. Our study identified 573,168 women with incident breast cancer at age ≥20 years between 2010 and 2019 in 18 SEER (Surveillance, Epidemiology, and End Results) registries. Of them, 62,623 (10.9%) were incident triple-negative breast cancer and 510,545 were non-triple negative breast cancer cases. The denominator of population included 320,117,009 women aged ≥20 in the same SEER areas. The study found that overall age-adjusted incidence rate of triple-negative breast cancer in women aged ≥20 years was 18.3 cases per 100,000 women. Age-adjusted incidence rate of triple-negative breast cancer was the highest in black women (33.8 cases per 100,000 women), followed by white (17.5), American Indian and Alaska Native (AIAN) (14.7), Hispanic (14.7), and Asian women (12.4). The significantly higher age-adjusted incidence of triple-negative breast cancer in black women as compared to white women appeared to be limited in younger women aged 20-44 only. Annual percentage changes in age-adjusted incidence of triple-negative breast cancer slightly decreased insignificantly in white, black and Asian women aged 20-44 and 45-54 years. There was a statistically significant annual percentage increase in age-adjusted incidence of triple-negative breast cancer in Asian and black women aged ≥55 years. In conclusion, there was a significantly higher incidence of triple-negative breast cancer in black women aged 20-44 years. From 2010 to 2019, there were no significant annual percentage changes in age-adjusted incidence of triple-negative breast cancer in all ethnic groups of women aged <55 years, with the exception of a significant decrease among AIAN women aged 45-54 years. However, there was a statistically significant annual percentage increase in age-adjusted incidence of triple-negative breast cancer in Asian and black women aged ≥55 years.

Keywords: Triple-negative breast cancer, cancer incidence, incidence trend, racial disparities, SEER

Introduction

It has been well documented that breast cancer incidence rates varied significantly by race and ethnicity with a higher risk of breast cancer in non-Hispanic (NH) white and black women and a lower risk in women from Hispanics, Asians and Pacific Islanders, and American Indians and Alaska Natives (AIAN) [1-8]. From 2000 to 2018, there was a slightly increasing trend in overall breast cancer incidence for all ethnic women in the United States, except for NH-white women who experienced a decreasing trend [9]. Over the past decade, there have been an increasing number of investigations on the incidence of an aggressive molecular subtype of breast cancer, i.e., triple-negative breast cancer which refers to the fact that estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) are all negative [10-19]. Triple-negative breast cancer is more aggressive, tends to grow and spread faster, and currently has fewer options of effective treatment, leading to worse outcomes and higher mortality [15,20]. Triple-negative breast cancer accounts for approximately 10%~15% of all breast cancers in women and appears to be more common in black women [10-19]. A number of studies reported racial and ethnic disparities in the incidence rates of triple-negative breast cancer [21-25]. Only one study specifically examined the incidence trends of molecular subtypes of breast cancer by race/ethnicity over multiple years from 2010 to 2016 [25], which concluded that triple-negative breast cancer incidence rates decreased among midlife non-Hispanic white and black women. This current study aims to 1) address the longer trends in the incidence of triple-negative breast cancer by race/ethnicity in women in the SEER areas from 2010 to 2019, 2) examine the incidence trends stratified by patient age, tumor stage and time periods, and 3) explore the changing proportions of three component receptors over time to see if any factor is the main driver for triple-negative breast cancer incidence trend.

Methods

Data sources

The National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Public Use Datasets released in November 2021 were used for this study. Both breast cancer cases (numerator) and population (denominator) from SEER areas from 2010 to 2019 are available for cancer incidence calculation [26]. The year 2010 is the earliest year for triple-negative breast cancer data available in SEER data and the year 2019 is the latest dataset. The SEER program supports 18 population-based tumor registries in 9 areas (San Francisco/Oakland, San Jose-Monterey, Los Angeles, Greater California, Detroit, Seattle, Atlanta, Rural Georgia, and Greater Georgia) and 9 states (Alaska, Connecticut, Iowa, New Mexico, Utah, Hawaii, Louisiana, Kentucky, and New Jersey), accounting for 28% of the U.S. population. The SEER registries ascertain all newly diagnosed (incident) cancer cases from multiple reporting sources. The estimated completeness of cancer case reporting in SEER areas was 97.7% [26]. Cancer-related variables collected in SEER registries include tumor location and size; histologic type and grade of tumor; demographic characteristics such as age, gender, race/ethnicity, and marital status; and type of treatments provided in the first course of therapy after diagnosis. This study was considered exempt for Institutional Review Board (IRB) review because it did not involve any patient contact, only had the analysis of de-identified existing SEER Public Use Data, and had no any health risk to study subjects.

Study population

Our study identified 573,168 women who were diagnosed with incident breast cancer at age ≥20 years between 2010 and 2019 in 18 SEER registries. Of them, 62,623 (10.9%) were incident triple-negative breast cancer and 510,545 (89.1%) were non-triple negative breast cancer cases. Because this study focused on the incidence trend of triple-negative breast cancer [hormone receptor (HR) negative: HR-/HER2-], other three groups of breast cancer (HR+/HER2+, HR+/HER2-, and HR-/HER2+) were considered as non-triple negative breast cancers. The denominator of population data included all 320,117,009 women aged ≥20 years in the same SEER areas that were provided in the SEER*Stat package.

Study variables

Race/ethnicity variable was classified into non-Hispanic white (white), non-Hispanic black (black), non-Hispanic Asians/Pacific Islanders (Asian), Hispanic women, and American Indians and Alaska Natives (AIAN), and others or unknown race. Patients with unknown or missing information on race/ethnicity were included for the incidence calculation for overall population and some sup-total stratified groups, but were not presented as a separate race/ethnicity group because the SEER*Stat software did not provide this incidence information for this group. Patient age was divided into 3 broad groups as young (20-44 years), middle-age (45-54) who were recommended to start for regular screening, and older age (≥55) in order to avoid small number of cases in stratified analyses by race/ethnicity, tumor stage, age group, and year of diagnosis. The other covariates included year of diagnosis (2010 to 2019) and geographic areas (18 SEER registries). Tumor factors included triple-negative vs non-triple negative breast cancer, estrogen receptor status, progesterone receptor status, HER2 receptor status, and tumor stage (in-situ or local, regional, distant stage, or unknown/missing).

Statistical analysis

We utilized the SEER*Stat software (version 8.4.0.1) that was provided by the National Cancer Institute together with the SEER data for analyses in cancer incidence rates and trends. Incidence of breast cancer in women is defined as a ratio of the number of women with a new breast cancer at age ≥20 years over the number of total female population at age ≥20 years in the same SEER areas by year, which is presented as the number of breast cancer cases per 100,000 persons. Because age is a significant risk factor for cancer incidence, the incidence rates of breast cancer in all comparison groups by race/ethnicity or time periods that may consist of different age compositions are standardized by age. The incidence rates in this study are adjusted to the year 2000 U.S. population by age available from the SEER*Stat. The age-adjusted incidence rates, 95% confidence intervals for incidence rates, incidence rate ratios (IRR) and their 95% confidence intervals, and annual percentage change (APC) of incidence rates are calculated from the SEER*Stat software. A p value <0.05 is considered statistically significant.

Results

Table 1 presents the number of total female population, number of incident triple-negative breast cancer cases, number of incident non-triple-negative breast cancer cases, unadjusted and age-adjusted breast cancer incidence rates, and incidence rate ratio by race/ethnicity. The overall age-adjusted incidence rate of triple-negative breast cancer in women aged ≥20 years was 18.3 cases per 100,000 women. The age-adjusted incidence rate of triple-negative breast cancer was the highest in black women (33.8 cases per 100,000 women), followed by white (17.5), AIAN (14.7), Hispanic (14.7), and Asian women (12.4). When compared to white women, the incidence rate ratio was statistically significantly higher in black women (incidence rate ratio: 1.93, 95% CI: 1.88-1.97) and significantly lower in AIAN (0.84, 0.75-0.93), Hispanic (0.84, 0.82-0.86), and Asian women (0.71, 0.68-0.73). However, the patterns of age-adjusted incidence rates of non-triple-negative breast cancer cases by race/ethnicity were different. The age-adjusted non-triple-negative breast cancer incidence rate ratio was statistically significantly lower in black women (0.83, 0.83-0.84) and in all other ethnic women as compared to white women (Table 1).

Table 1.

Number of population, number of triple-negative breast cancer cases and non-triple negative breast cancer, and incidence rates of breast cancer in all SEER areas, 2010-2019, by race/ethnicity

Race/Ethnicity Number of population Number of breast cancer cases Unadjusted Incidence rates (N of cases per 100,000) (95% CI) Age-adjusted* incidence rates (N of cases per 100,000) (95% CI) Rate ratio (between age-adjusted incidence rates) (95% CI)
Triple-negative breast cancer
    Non-Hispanic white 178,531,435 36,695 20.6 (20.3-20.8) 17.5 (17.4-17.7) 1.00 (reference)
    Non-Hispanic Asians and Pacific Islanders 37,051,694 4,727 12.8 (12.4-13.1) 12.4 (12.0-12.7) 0.71* (0.68-0.73)
    Non-Hispanic black 2,608,851 12,102 33.9 (33.3-34.5) 33.8 (33.2-34.4) 1.93* (1.88-1.97)
    American Indians and Alaska Natives 2,608,851 371 14.2 (12.8-15.7) 14.7 (13.2-16.3) 0.84* (0.75-0.93)
    Hispanics 66,191,520 8,494 12.8 (12.6-13.1) 14.7 (14.4-15.1) 0.84* (0.82-0.86)
    Sub-Total 320,117,009 62,623 19.6 (19.4-19.7) 18.3 (18.1-18.4) 1.04* (1.03-1.06)
Non-Triple-negative breast cancer
    Non-Hispanic white 178,531,435 349,087 195.5 (194.9-196.2) 159.4 (158.9-160.0) 1.00 (reference)
    Non-Hispanic Asians and Pacific Islanders 37,051,694 48,061 129.7 (128.6-130.9) 125.8 (124.7-127.0) 0.79* (0.78-0.80)
    Non-Hispanic black 2,608,851 47,156 132.0 (130.8-133.2) 133.0 (131.7-134.2) 0.83* (0.83-0.84)
    American Indians and Alaska Natives 2,608,851 3,057 117.2 (113.1-121.4) 116.7 (112.5-121.0) 0.73* (0.71-0.76)
    Hispanics 66,191,520 60,528 91.4 (90.7-92.2) 109.4 (108.5-110.3) 0.69* (0.68-0.69)
    Sub-Total 320,117,009 510,545 159.5 (159-159.9) 145.8 (145.4-146.2) 0.91* (0.91-0.92)
*

Incidence rates were adjusted to the 2000 US population by age.

Breast cancer cases with unknown or missing information on race/ethnicity were included in the total or sub-total incidence calculation.

Figure 1 presents the age-adjusted incidence trends over time from 2010 to 2019 for both triple-negative breast cancer (Figure 1A) and non-triple-negative breast cancer cases (Figure 1B) by race/ethnicity. The age-adjusted incidence rate of triple-negative breast cancer was much higher in black women than other ethnic women and increased slightly over time from 2010 to 2019, whereas the age-adjusted incidence rate of non-triple-negative breast cancer was much higher in white women than other ethnic women and increased more sharply over time.

Figure 1.

Figure 1

Trends in age-adjusted incidence rates of triple-negative (TN) breast cancer versus incidence trends in age-adjusted non-triple-negative (Non-TN) breast cancer (number of breast cancer cases per 100,000 population) among women in SEER areas from 2010 to 2019, by race/ethnicity.

Annual percentage change (APC) in age-adjusted incidence of triple-negative breast cancer in the total population aged ≥20 years from 2010 to 2019 slightly increased in Hispanic, black, and Asian women, and slightly decreased in white and AIAN women, but none of these trends was statistically significant (Table 2). In the stratified analyses by the 3 age groups (20-44, 45-54, and ≥55), annual percentage changes in age-adjusted incidence of triple-negative breast cancer slightly decreased but not significantly in white, black and Asian women aged 20-44 and 45-54 years. In AIAN and Hispanic women, there were no significant annual percentage changes in age-adjusted incidence of triple-negative breast cancer except a significant decrease in AIAN women aged 45-54 years. Interestingly, there was a statistically significant annual percentage increase in age-adjusted incidence of triple-negative breast cancer in Asian and black women aged 55 years or older. However, annual percentage change in age-adjusted incidence of non-triple-negative breast cancer from 2010 to 2019 increased significantly in all ethnic women except in AIAN and black women aged 45-54 years.

Table 2.

Annual percentage change (APC) in age-adjusted incidence rates (number of breast cancer cases per 100,000 population) in women in 2010-2019 by triple-negative breast cancer status, race/ethnicity and age groups

Race/Ethnicity Triple-negative breast cancer Non-Triple-negative breast cancer Total breast cancer (triple-negative and non-triple-negative breast cancer)



N. Cases Incidence rate (95% CI) APC (95% CI) from 2010 to 2019 P value N. Cases Incidence rate (95% CI) APC (95% CI) from 2010 to 2019 P value N. Cases Incidence rate (95% CI) APC (95% CI) from 2010 to 2019 P value
All breast cancer cases aged 20 or older
    Non-Hispanic white 36,695 17.5 (17.4-17.7) -0.7 (-1.5-0.1) 0.1 349,087 159.4 (158.9-160.0) 1.2 (1.0-1.5) <0.001 385,782 176.9 (176.4-177.5) 1.1 (0.8-1.3) <0.001
    Non-Hispanic Asians and Pacific Islanders 4,727 12.4 (12.0-12.7) 0.6 (-0.6-1.9) 0.3 48,061 125.8 (124.7-127.0) 2.3 (1.8-2.8) <0.001 52,788 138.2 (137.0-139.4) 2.1 (1.6-2.6) <0.001
    Non-Hispanic black 12,102 33.8 (33.2-34.4) 0.3 (-0.5-1.1) 0.4 47,156 133.0 (131.7-134.2) 1.4 (0.8-1.9) <0.001 59,258 166.7 (165.4-168.1) 1.2 (0.8-1.5) <0.001
    American Indians and Alaska Natives 371 14.7 (13.2-16.3) -0.7 (-4-2.7) 0.7 3,057 116.7 (112.5-121.0) 1.7 (-0.1-3.5) 0.1 3,428 131.4 (126.9-136.0) 1.4 (-0.3-3.1) 0.1
    Hispanics 8,494 14.7 (14.4-15.1) 1.0 (-0.2-2.2) 0.1 60,528 109.4 (108.5-110.3) 1.7 (0.9-2.5) <0.001 69,022 124.2 (123.2-125.1) 1.7 (1.0-2.3) <0.001
    Total 62,623 18.3 (18.1-18.4) -0.2 (-1-0.6) 0.5 510,545 145.8 (145.4-146.2) 1.3 (1.0-1.6) <0.001 573,168 164.1 (163.7-164.5) 1.1 (0.8-1.4) <0.001
Breast cancer cases aged 20-44 years
    Non-Hispanic white 4,590 7.3 (7.1-7.5) -0.7 (-3.0-1.7) 0.2 26,465 42.5 (42.0-43.0) 1.7 (0.7-2.7) <0.001 31,055 49.8 (49.2-50.3) 1.3 (0.2-2.5) <0.001
    Non-Hispanic Asians and Pacific Islanders 855 4.9 (4.6-5.2) -1.3 (-7.5-5.3) 0.3 7,214 42.1 (41.2-43.1) 2.4 (0.2-4.7) <0.001 8,069 47.0 (46.0-48.1) 2.0 (-0.2-4.3) <0.001
    Non-Hispanic black 1,904 12.3 (11.8-12.9) -0.7 (-6.0-4.9) 0.5 6,045 39.3 (38.3-40.3) 1.5 (-0.3-3.4) <0.001 7,949 51.7 (50.5-52.8) 1.0 (-0.6-2.6) <0.001
    American Indians and Alaska Natives 80 7.4 (5.9-9.3) 1.7 (-14.4-20.8) 0.6 373 35.7 (32.1-39.5) 4.5 (-4.1-13.8) <0.001 453 43.1 (39.2-47.3) 4.1 (-3.5-12.3) <0.001
    Hispanics 2,239 6.6 (6.3-6.9) 1.1 (-1.9-4.1) 0.1 10,110 30.4 (29.8-31.0) 2.9 (0.1-5.8) <0.001 12,349 37.0 (36.3-37.7) 2.6 (0.3-4.9) <0.001
    Sub-Total 9,710 7.4 (7.3-7.6) -0.4 (-2.1-1.4) 0.3 50,548 39.2 (38.8-39.5) 2.0 (1.1-2.9) <0.001 60,258 46.6 (46.2-47.0) 1.6 (0.7-2.6) <0.001
Breast cancer cases aged 45-54 years
    Non-Hispanic white 7,060 21.7 (21.2-22.2) -0.7 (-2.4-1.1) 0.1 61,500 189.2 (187.7-190.7) 1.7 (0.7-2.7) <0.001 68,560 210.9 (209.3-212.5) 1.4 (0.5-2.4) <0.001
    Non-Hispanic Asians and Pacific Islanders 1,033 15.3 (14.4-16.3) -0.4 (-8.0-7.7) 0.8 12,143 180.4 (177.2-183.6) 2.7 (1.4-4.0) <0.001 13,176 195.7 (192.4-199.1) 2.5 (0.8-4.1) <0.001
    Non-Hispanic black 3,100 45.5 (43.9-47.1) -0.2 (-4.0-3.8) 0.8 10,175 149.8 (146.9-152.8) 1.2 (-1.6-4.1) 0.1 13,275 195.4 (192-198.7) 0.9 (-1.4-3.2) 0.1
    American Indians and Alaska Natives 89 18.1 (14.5-22.3) -6.0 (-16.7-6.0) <0.001 642 130.6 (120.6-141.2) 2.7 (-6.8-13.2) 0.2 731 148.7 (138-159.9) 1.5 (-6.4-10.1) 0.4
    Hispanics 2,338 19.8 (19.0-20.6) -0.5 (-5.7-5.0) 0.7 15,762 133.5 (131.4-135.6) 1.8 (-0.6-4.2) <0.001 18,100 153.3 (151.1-155.6) 1.5 (-0.6-3.6) <0.001
    Sub-Total 13,688 23.4 (23.0-23.8) -0.6 (-3.1-2.0) 0.3 100,804 172.7 (171.7-173.8) 1.6 (0.6-2.6) <0.001 114,492 196.2 (195-197.3) 1.3 (0.4-2.3) <0.001
Breast cancer cases aged 55 years or older
    Non-Hispanic white 25,045 32.4 (32.0-32.9) -0.7 (-2.8-1.6) 0.2 261,122 340.2 (338.9-341.5) 1.0 (0.4-1.6) <0.001 286,167 372.6 (371.3-374) 0.9 (0.3-1.4) <0.001
    Non-Hispanic Asians and Pacific Islanders 2,839 23.3 (22.4-24.1) 1.7 (-1.7-5.2) <0.001 28,704 234.3 (231.6-237.1) 2.0 (0.5-3.5) <0.001 31,543 257.6 (254.7-260.5) 2.0 (0.7-3.3) <0.001
    Non-Hispanic black 7,098 62.9 (61.4-64.5) 0.8 (-0.1-1.8) <0.001 30,936 282.1 (278.9-285.4) 1.4 (0.1-2.7) <0.001 38,034 345.1 (341.5-348.7) 1.3 (0.3-2.3) <0.001
    American Indians and Alaska Natives 202 25.0 (21.6-28.9) 0.6 (-8.8-10.9) 0.8 2,042 246.2 (235.2-257.5) 0.6 (-5.3-6.7) 0.7 2,244 271.2 (259.7-283.1) 0.6 (-5.2-6.7) 0.6
    Hispanics 3,917 25.5 (24.7-26.3) 1.7 (-2.2-5.8) 0.1 34,656 229.1 (226.6-231.6) 1.5 (-0.1-3.1) <0.001 38,573 254.6 (252-257.2) 1.5 (0.2-2.8) <0.001
    Sub-Total 39,225 33.6 (33.3-34.0) 0.0 (-1.7-1.8) 0.9 359,193 310.8 (309.8-311.9) 1.0 (0.4-1.6) <0.001 398,418 344.5 (343.4-345.5) 0.9 (0.4-1.5) <0.001

Table 3 presents the age-adjusted incidence of triple-negative breast cancer and non-triple-negative breast cancer by 3 time periods (2010-2013, 2014-2016, and 2017-2019) and race/ethnicity. The age-adjusted incidence of triple-negative breast cancer marginally increased during these time periods among Hispanic, black and Asian women. For example, the age-adjusted incidence of triple-negative breast cancer in black women was 33.3 cases per 100,000 women for 2010-2013, 33.5 cases for 2014-2016, and 34.5 cases for 2017-2019. The age-adjusted incidence of non-triple-negative breast cancer increased in white, black, Asian and Hispanic women by these 3 time periods, while the age-adjusted incidence of non-triple-negative breast cancer among AIAN women was lower in 2014-2016 than in 2010-2013 but was higher in 2017-2019.

Table 3.

Annual percentage change (APC) in age-adjusted incidence rates* of triple-negative breast cancer (number of breast cancer cases per 100,000 population) in women by time period and race/ethnicity

Race/Ethnicity 2010-2013 2014-2016 2017-2019 APC (95% CI) P value



N. Population N. Cases Incidence rate (95% CI) N. Population N. Cases Incidence rate (95% CI) N. Population N. Cases Incidence rate (95% CI)
Triple-negative breast cancer
    NH-white 71,255,586 14,871 18.1 (17.8-18.4) 53,725,401 10,615 16.9 (16.5-17.2) 53,550,448 11,209 17.5 (17.2-17.9) -0.7 (-1.5-0.1) 0.1
    NH-Asians and P. Islanders 13,667,498 1,696 12.4 (11.8-13.0) 11,287,880 1,387 11.8 (11.2-12.4) 12,096,316 1,644 12.8 (12.2-13.5) 0.6 (-0.6-1.9) 0.3
    NH-black 13,649,493 4,502 33.3 (32.3-34.3) 10,818,753 3,637 33.5 (32.4-34.6) 11,265,263 3,963 34.5 (33.4-35.6) 0.3 (-0.5-1.1) 0.4
    American Indians and AN 1,008,653 149 15.7 (13.2-18.5) 789,737 108 14.1 (11.5-17.1) 810,461 114 14.0 (11.5-17.0) -0.7 (-4-2.7) 0.7
    Hispanics 24,791,947 2,997 14.2 (13.7-14.7) 20,108,413 2,574 14.7 (14.1-15.3) 21,291,160 2,923 15.3 (14.8-15.9) 1.0 (-0.2-2.2) 0.1
    Total 124,373,177 24,283 18.5 (18.3-18.8) 96,730,184 18,387 17.7 (17.5-18.0) 99,013,648 19,953 18.5 (18.2-18.8) -0.2 (-1-0.6) 0.5
Non-Triple-negative breast cancer
    NH-white 71,255,586 131,546 153.8 (152.9-154.6) 53,725,401 106,100 160.4 (159.4-161.4) 53,550,448 111,441 165.9 (164.9-167.0) 1.2 (1-1.5) <0.001
    NH-Asians and P. Islanders 13,667,498 16,194 117.4 (115.6-119.2) 11,287,880 14,640 125.5 (123.4-127.5) 12,096,316 17,227 135.5 (133.4-137.5) 2.3 (1.8-2.8) <0.001
    NH-black 13,649,493 16,773 127.2 (125.2-129.1) 10,818,753 14,531 134.9 (132.6-137.1) 11,265,263 15,852 137.7 (135.5-139.9) 1.4 (0.8-1.9) <0.001
    American Indians and AN 1,008,653 1,108 113.5 (106.7-120.6) 789,737 892 111.6 (104.2-119.4) 810,461 1,057 126.6 (118.8-134.8) 1.7 (-0.1-3.5) 0.1
    Hispanics 24,791,947 20,567 104.0 (102.6-105.5) 20,108,413 18,607 110.0 (108.4-111.7) 21,291,160 21,354 114.7 (113.1-116.3) 1.7 (0.9-2.5) <0.001
    Total 124,373,177 186,874 140.4 (139.8-141.1) 96,730,184 155,540 146.6 (145.8-147.3) 99,013,648 168,131 151.7 (151.0-152.5) 1.3 (1.0-1.6) <0.001
*

Incidence rates were age adjusted to the 2000 US population.

Table 4 presents the age-adjusted incidence of triple-negative breast cancer and incidence rate ratio by age groups (20-44, 45-54, and ≥55), 3 time periods (2010-2013, 2014-2016, and 2017-2019) and race/ethnicity. The significantly higher age-adjusted incidence of triple-negative breast cancer in black women as compared to white women appeared to be limited in younger women aged 20-44 only (incidence rate ratio: 1.04, 95% CI: 1.00-1.08 for 2010-2013; 1.03, 1.00-1.09 for 2014-2016, and 1.03, 0.98-1.07 for 2017-2019). There were significantly lower age-adjusted incidence rates of triple-negative breast cancer in black women than in white women in other 2 age groups (44-54 and 55 or older). The age-adjusted incidence rates of triple-negative breast cancer were generally lower in the 3 age groups among Asian, AIAN and Hispanic women than white women.

Table 4.

Age-adjusted incidence rates of triple-negative breast cancer (number of breast cancer cases per 100,000 women) by age groups, race/ethnicity, and time period

Race/Ethnicity Age 20-44 yrs Age 45-54 yrs Age ≥55 yrs



N. Population N. Cases Incidence rate* (95% CI) Rate ratio (95% CI) N. Population N. Cases Incidence rate* (95% CI) Rate ratio (95% CI) N. Population N. Cases Incidence rate* (95% CI) Rate ratio (95% CI)
2010-2013
    NH-white 27,673,809 12,411 47.9 (47.1-48.8) 1.00 (ref) 13,849,991 28,442 203.6 (201.2-205.9) 1.00 (ref) 29,731,786 105,564 363.3 (361.1-365.6) 1.00 (ref)
    NH-Asians and P. Islanders 6,822,173 2,875 44.3 (42.7-46.0) 0.92 (0.89-0.96) 2,550,269 4,667 182.4 (177.2-187.7) 0.90 (0.87-0.92) 4,295,056 10,348 242.4 (237.7-247.2) 0.67 (0.65-0.68)
    NH-black 6,865,584 3,040 49.9 (48.2-51.7) 1.04 (1.00-1.08) 2,736,798 5,212 189.5 (184.3-194.7) 0.93 (0.90-0.96) 4,047,111 13,023 330.9 (325.1-336.8) 0.91 (0.89-0.93)
    American Indians and AN 501,604 163 38.6 (32.9-45.0) 0.81 (0.69-0.94) 206,716 290 139.1 (123.5-156.1) 0.68 (0.61-0.77) 300,333 804 277.6 (257.9-298.4) 0.76 (0.71-0.82)
    Hispanics 15,051,841 4,442 34.3 (33.3-35.3) 0.72 (0.69-0.74) 4,408,238 6,460 146.7 (143.1-150.3) 0.72 (0.70-0.74) 5,331,868 12,662 243.5 (239.1-247.9) 0.67 (0.66-0.68)
    Sub-Total (2010-2013) 56,915,011 23,044 44.5 (43.9-45.1) 23,752,012 45,266 189.3 (187.6-191.1) 43,706,154 142,847 335.2 (333.4-336.9)
2014-2016
    NH-white 20,443,406 9,217 50.1 (49.0-51.1) 1.00 (ref) 9,587,313 20,423 210.5 (207.6-213.4) 1.00 (ref) 23,694,682 87,075 373.4 (370.9-376) 1.00 (ref)
    NH-Asians and P. Islanders 5,491,452 2,452 46.9 (45.0-48.8) 0.94 (0.9-0.98) 2,027,709 3,953 194.5 (188.5-200.7) 0.92 (0.89-0.96) 3,768,719 9,622 255.4 (250.3-260.7) 0.68 (0.67-0.70)
    NH-black 5,333,868 2,387 52.2 (50.1-54.3) 1.04 (1.00-1.09) 2,025,818 4,084 199.3 (193.2-205.5) 0.95 (0.92-0.98) 3,459,067 11,697 347.1 (340.6-353.6) 0.93 (0.91-0.95)
    American Indians and AN 384,892 130 41.3 (34.4-49.0) 0.83 (0.69-0.98) 145,382 218 149.1 (129.8-170.5) 0.71 (0.62-0.81) 259,463 652 254.9 (235-276.1) 0.68 (0.63-0.74)
    Hispanics 11,764,741 3,811 37.7 (36.5-38.9) 0.75 (0.73-0.78) 3,596,453 5,541 154.0 (149.9-158.1) 0.73 (0.71-0.75) 4,747,219 11,829 254.9 (250.2-259.7) 0.68 (0.67-0.70)
    Sub-Total (2014-2016) 43,418,359 18,108 46.9 (46.2-47.6) 17,382,675 34,411 196.2 (194.1-198.3) 35,929,150 121,408 344.6 (342.7-346.6)
2017-2019
    NH-white 20,200,529 9,427 52.1 (51.0-53.2) 1.00 (ref) 8,766,150 19,695 222.9 (219.7-226) 1.00 (ref) 24,583,769 93,528 382.7 (380.3-385.2) 1.00 (ref)
    NH-Asians and P. Islanders 5,732,601 2,742 50.5 (48.6-52.4) 0.97 (0.93-1.01) 2,144,483 4,556 212.4 (206.3-218.7) 0.95 (0.92-0.98) 4,219,232 11,573 274.9 (269.9-280.1) 0.72 (0.70-0.73)
    NH-black 5,470,780 2,522 53.5 (51.4-55.6) 1.03 (0.98-1.07) 1,980,094 3,979 199.4 (193.2-205.7) 0.89 (0.86-0.93) 3,814,389 13,314 357.7 (351.5-364) 0.93 (0.92-0.95)
    American Indians and AN 389,128 160 51.2 (43.5-59.8) 0.98 (0.83-1.15) 134,852 223 163.1 (142.3-186.1) 0.73 (0.64-0.84) 286,481 788 279.1 (259.4-299.9) 0.73 (0.68-0.78)
    Hispanics 12,067,250 4,096 39.7 (38.5-40.9) 0.76 (0.73-0.79) 3,801,546 6,099 160.4 (156.4-164.4) 0.72 (0.70-0.74) 5,422,364 14,082 265.1 (260.6-269.6) 0.69 (0.68-0.71)
    Sub-Total (2017-2019) 43,860,288 19,106 49.2 (48.5-49.9) 16,827,125 34,815 205.7 (203.6-207.9) 38,326,235 134,163 354.5 (352.6-356.4)
    Total (2010-2019) 144,193,65 60,258 46.6 (46.2-47.0) 57,961,812 114,492 196.2 (195.0-197.3) 117,961,539 398,418 344.5 (343.4-345.5)
*

Incidence rates were age adjusted to the 2000 US population in each of the 3 age groups.

Table 5 presents the annual percentage change in age-adjusted incidence of triple-negative breast cancer and non-triple-negative breast cancer by tumor stage (in-situ/local, regional, distant stage, or unknown stage) and race/ethnicity. Among patients with local stage breast cancer, annual percentage change in age-adjusted incidence of triple-negative breast cancer from 2010 to 2019 slightly decreased in white women but increased in Hispanic, black, Asian, and AIAN women (P>0.05). Among patients with regional stage breast cancer, annual percentage change in age-adjusted incidence of triple-negative breast cancer from 2010 to 2019 decreased in all ethnic women but only statistically significantly decreased in white women. In contrast, annual percentage change in age-adjusted incidence of triple-negative breast cancer from 2010 to 2019 increased significantly in white and Hispanic women with distant stage and in white women with unknown stage breast cancer, but not significantly increased in black and Asian women. Annual percentage change in age-adjusted incidence of non-triple-negative breast cancer from 2010 to 2019 increased significantly in almost all ethnic women with local or distant stage breast cancer and slightly increased in those with regional stage breast cancer. In those with unknown stage breast cancer, annual percentage change in age-adjusted incidence of non-triple-negative breast cancer from 2010 to 2019 increased for white, Asian and Hispanic women, but decreased for black and AIAN women.

Table 5.

Annual percentage change (APC) in age-adjusted incidence rates (number of breast cancer cases per 100,000 population) in women in 2010-2019 by tumor stage, triple-negative breast cancer status and race/ethnicity

Race/Ethnicity Triple-negative breast cancer Non-Triple-negative breast cancer Total breast cancer (triple-negative and non-triple-negative breast cancer)



N. Cases Incidence rate (95% CI) APC (95% CI) from 2010 to 2019 N. Cases Incidence rate (95% CI) APC (95% CI) from 2010 to 2019 N. Cases Incidence rate (95% CI) APC (95% CI) from 2010 to 2019
Local stage Breast Cancer
    Non-Hispanic white 11.0 (10.9-11.2) -0.5 (-2.5-1.5) 238,689 107 (106.6-107.4) 1.8*** (1.0-2.5) 262,038 118.0 (117.6-118.5) 1.5*** (0.8-2.3)
    Non-Hispanic Asians and Pacific Islanders 2,893 7.5 (7.3-7.8) 1.1 (-2.4-4.7) 31,778 83.0 (82-83.9) 2.4*** (1.3-3.5) 34,671 90.5 (89.5-91.5) 2.3*** (1.2-3.3)
    Non-Hispanic black 6,689 18.6 (18.1-19.1) 0.4 (-1.7-2.6) 27,340 77.2 (76.3-78.2) 2.1*** (0.4-3.8) 34,029 95.8 (94.8-96.9) 1.7*** (0.3-3.2)
    American Indians and Alaska Natives 215 8.4 (7.3-9.6) 0.5 (-10.8-13.3) 1,909 72.4 (69.1-75.8) 1.9 (-3.4-7.4) 2,124 80.8 (77.3-84.4) 1.7 (-3.7-7.5)
    Hispanics 4,739 8.3 (8.1-8.5) 1 (-3-5.1) 36,253 66.8 (66.1-67.5) 2.4*** (0.6-4.3) 40,992 75.1 (74.4-75.9) 2.3*** (0.8-3.8)
    Sub-Total 38,016 11.0 (10.9-11.1) -0.2 (-2.1-1.8) 337,626 95.4 (95.1-95.8) 1.7*** (1.0-2.5) 375,642 106.5 (106.1-106.8) 1.5*** (0.8-2.3)
Regional Stage Breast Cancer
    Non-Hispanic white 10,616 5.2 (5.1-5.4) -1.8** (-4.3-0.7) 91,171 43.7 (43.4-44.0) -0.2 (-0.9-0.6) 101,787 48.9 (48.6-49.3) -0.4 (-1.0-0.2)
    Non-Hispanic Asians and Pacific Islanders 1,504 4.0 (3.8-4.2) -0.7 (-6.0-5.0) 13,706 36.2 (35.6-36.8) 1.7* (-0.5-3.9) 15,210 40.1 (39.5-40.8) 1.5* (-0.8-3.8)
    Non-Hispanic black 4,310 12.1 (11.7-12.5) -0.1 (-3.1-3.0) 15,763 44.4 (43.7-45.1) 0.4 (-1.2-2.1) 20,073 56.5 (55.7-57.3) 0.3 (-1.2-1.8)
    American Indians and Alaska Natives 119 4.9 (4.1-5.9) -2.1 (-18.9-18) 944 36.2 (33.9-38.7) 0.0 (-5.9-6.2) 1,063 41.1 (38.6-43.8) -0.3 (-5.5-5.1)
    Hispanics 3,058 5.2 (5-5.4) 0.0 (-2.8-3.0) 20,575 35.9 (35.4-36.4) 0.3 (-1.6-2.3) 23,633 41.1 (40.6-41.7) 0.3 (-1.2-1.8)
    Sub-Total 19,678 5.9 (5.8-5.9) -1.0* (-2.8-0.8) 142,801 41.8 (41.6-42) 0.1 (-0.7-1.0) 162,479 47.6 (47.4-47.9) 0.0 (-0.8-0.8)
Distant Stage Breast Cancer
    Non-Hispanic white 2,458 1.1 (1.1-1.2) 2.0** (-0.8-5) 17,047 7.8 (7.7-7.9) 1.9** (0.0-3.8) 19,505 8.9 (8.8-9.0) 1.9*** (0.3-3.5)
    Non-Hispanic Asians and Pacific Islanders 277 0.7 (0.6-0.8) 1.7 (-10.7-15.8) 2,224 5.8 (5.6-6.0) 3.6** (-0.4-7.8) 2,501 6.5 (6.3-6.8) 3.4*** (0.3-6.7)
    Non-Hispanic black 1,004 2.8 (2.6-3.0) 0.8 (-3.2-4.9) 3,677 10.3 (10.0-10.6) 0.7 (-1.9-3.4) 4,681 13.1 (12.7-13.5) 0.7 (-1.5-3.1)
    American Indians and Alaska Natives 32 1.2 (0.8-1.7) -8.5 (-29.9-19.4) 179 7.0 (5.9-8.1) 8.1*** (1.5-15.2) 211 8.2 (7.1-9.4) 5.4 (-3.8-15.4)
    Hispanics 593 1.1 (1.0-1.2) 5.4** (0.1-11.0) 3,205 5.7 (5.5-5.9) 2.1* (-1.1-5.3) 3,798 6.8 (6.0.6-7) 2.6** (-0.1-5.3)
    Sub-Total 4,371 1.3 (1.2-1.3) 2.1 (-1.4-5.7) 26,421 7.6 (7.5-7.6) 1.8*** (0.4-3.1) 30,792 8.8 (8.7-8.9) 1.8*** (0.7-2.9)
Unknown stage or missing/not coded
    Non-Hispanic white 272 0.1 (0.1-0.1) 10.0* (-5.3-27.7) 2,180 0.9 (0.9-1.0) 4.9* (-5.0-15.9) 2,452 1.1 (1.0-1.1) 5.5* (-4.7-16.8)
    Non-Hispanic Asians and Pacific Islanders 53 0.1 (0.1-0.2) 3.3 (-19.2-32.1) 353 0.9 (0.0.8-1.0) 3.8 (-11.1-21.3) 406 1.1 (1-1.2) 4.1 (-10.6-21.2)
    Non-Hispanic black 99 0.3 (0.2-0.3) 1.9 (-16.6-24.6) 376 1.1 (1.0-1.2) -0.4 (-8.0-7.8) 475 1.4 (1.2-1.5) 0.2 (-8.0-9.0)
    American Indians and Alaska Natives 104 0.2 (0.1-0.5) ~ (~-~)$ 25 1.1 (0.7-1.7) -0.1 (-25.4-33.9) 30 1.3 (0.9-1.9) 1.9 (-19.3-28.6)
    Hispanics 5 0.2 (0.1-0.2) 7.7 (-22.2-48.9) 495 0.9 (0.8-1.0) 6.1 (-16.0-34.1) 599 1.1 (1.0-1.2) 6.2 (-16.5-35.1)
    Sub-Total 558 0.2 (0.1-0.2) 7.7* (-7.2-25.1) 3,697 1.0 (1.0-1.1) 4.9 (-6.5-17.7) 4,255 1.2 (1.2-1.2) 5.3 (-6.4-18.5)
*

P<0.05, indicating the incidence rate other ethnic groups is significantly different than the rate for Non-Hispanic White;

**

P<0.01, indicating the incidence rate other ethnic groups is significantly different than the rate for Non-Hispanic White;

***

P<0.001, indicating the incidence rate other ethnic groups is significantly different than the rate for Non-Hispanic White.

$

APC was not obtainable from the SEER*Stat.

Table 6 presents the changes in the proportion of estrogen receptor, progesterone receptor and HER2 receptor status from 2010 to 2019 to determine if the changing trends in the incidence of triple-negative breast cancer was affected more or less by the changing proportions of the 3 individual receptors over time. Of all incident (triple-negative and non-triple-negative) breast cancer cases in 2010-2019, the proportion of patients with estrogen receptor negative slightly decreased from 17.7% in 2010 to 15.3% in 2019; the proportion of patients with progesterone receptor negative also slightly decreased from 29.2% in 2010 to 26.0% in 2019; and the proportion of patients with HER2 receptor negative slightly increased from 85.1% to 86.7%.

Table 6.

Proportion of breast cancer cases having hormone-receptor negative and HER2-negative tumors by year

Year Total N Number by estrogen receptor status negative Row % by estrogen receptor status negative Number by progesterone receptor status negative Row % by progesterone receptor negative Number by HER2-receptor status negative Row % by HER2-receptor negative
2010 49,404 8,740 17.70% 14,410 29.20% 42,036 85.10%
2011 52,452 9,131 17.40% 14,845 28.30% 44,894 85.60%
2012 53,808 9,099 16.90% 14,919 27.70% 45,877 85.30%
2013 55,493 9,001 16.20% 14,785 26.60% 47,335 85.30%
2014 56,482 9,342 16.50% 15,084 26.70% 47,538 84.20%
2015 58,491 9,583 16.40% 15,714 26.90% 49,071 83.90%
2016 58,954 9,241 15.70% 15,704 26.60% 49,594 84.10%
2017 60,770 9,810 16.10% 16,077 26.50% 51,379 84.50%
2018 62,709 9,731 15.50% 16,517 26.30% 53,865 85.90%
2019 64,605 9,870 15.30% 16,769 26.00% 55,999 86.70%
Total 573,168 93,548 16.30% 154,824 27.00% 487,588 85.10%

Discussion

This study examined the age-adjusted incidence rates and trends by race/ethnicity for both triple-negative breast cancer and non-triple-negative breast cancer. The age-adjusted incidence rate of triple-negative breast cancer was the highest in black women, followed by white, AIAN, Hispanic, and Asian women. The incidence rate ratio was statistically significantly higher in black women and significantly lower in AIAN, Hispanic, and Asian women as compared to white women. The significantly higher age-adjusted incidence of triple-negative breast cancer in black women as compared to white women appeared to be limited in younger women aged 20-44 only. There was no significant difference in age-adjusted incidence of triple-negative breast cancer among women aged 44-54 and ≥55 years. The study found that there were no significant annual percentage changes in age-adjusted incidence of triple-negative breast cancer from 2010 to 2019 in all ethnic groups of women aged 20-44 and 45-54 years, with the exception of a significant decrease in AIAN women aged 45-54 years. However, there was a statistically significant annual percentage increase in age-adjusted incidence of triple-negative breast cancer in Asian and black women aged ≥55 years. All ethnic women, with the exception of AIAN women, experienced a significant annual percentage increase in age-adjusted incidence of non-triple-negative breast cancer from 2010 to 2019. The trends in age-adjusted incidences of triple-negative breast cancer were not affected by dramatical changes in proportions in any of the 3 receptors.

Several previous studies examined the incidence rates of triple-negative breast cancer by race/ethnicity [21-25], of which only one study examined the incidence trends of triple-negative breast cancer among various racial and ethnic women [25]. Clarke and colleagues examined a large cohort of women with invasive breast cancer in California in 2006-2009 and found that black women had statistically significantly higher incidence rates of triple-negative breast cancer than white women at all ages [21]. Howlader and colleagues examined the incidence of triple-negative breast cancer in 2010, which was the first year for HER2-receptor status to be available in the complete SEER data [22]. They found that non-Hispanic black women had the highest incidence rates of triple-negative breast cancer across all age groups and non-Hispanic black women were much more likely to be diagnosed with this subtype of breast cancer than were the three other racial/ethnic groups [22]. Kohler and colleagues specifically examined the incidence of triple-negative breast cancer in 2011 by race/ethnicity in SEER areas and found that the incidence rate of triple-negative breast cancer was highest among non-Hispanic black women with an aged-adjusted rate of 27.2 cases per 100,000 women, as compared with all other racial/ethnic women [23]. Acheampong and colleagues reported the trends in triple-negative breast cancer incidence rates from 2010 to 2016 in SEER areas and found that triple-negative breast cancer incidence decreased in non-Hispanic white women aged 40-54 and 55-69 years as well as in non-Hispanic Black women aged 55-69 years [25]. Our study examined the incidence trends in more recent years from 2010 to 2019 and also addressed the incidence rates and trends among various racial/ethnic women, stratified by age groups and tumor stage. Our study found that there were no significant annual percentage changes in age-adjusted incidence of triple-negative breast cancer in all ethnic women aged 20-44 and 45-54 years except a significant decrease in AIAN women aged 45-54 years. However, there was a statistically significant annual percentage increase in age-adjusted incidence of triple-negative breast cancer from 2010 to 2019 in Asian and black women aged ≥55 years. Some of these findings appeared to differ from a previous study reporting breast cancer cases in 2010-2016 [25]. These differences in age-adjusted incidence rates of triple-negative breast cancer for some older ethnic women may have been resulted from more breast cancer cases in recent years (2017-2019).

Because triple-negative breast cancer is a more aggressive subtype of cancer, spreads much faster than other subtypes of cancer, and has limited effective treatment options, patients with triple-negative breast cancer often have much poorer clinical outcomes and lower survival [10-20]. A higher risk of developing triple-negative breast cancer in black women with limited treatment choices may be one of the reasons why black women with breast cancer were reported to have a significantly higher risk of mortality [10-20]. Apparent racial and ethnic disparities in triple-negative breast cancer incidence and outcomes could be explained by a number of factors according to previous studies [10-20]. These include both biologic factors (such as genetic factors, early menarche, high parity, lack of breastfeeding, and obesity in promoting this subtype of disease biology) and non-biologic factors (such as unsafe neighborhoods, poverty, unmarried household, social stress, and toxic-waste dumping) [12-17,27-34]. Once triple-negative breast cancer can be detectable clinically, it would be critical to have access to medical care in order to improve outcomes. Health insurance, transportation, timely treatment, compliance, and regular follow-up care are some of the factors that have been shown to have an impact on racial/ethnic disparities in breast cancer outcomes [35-40].

There are several limitations in this study. First, because triple-negative breast cancer was based on the coding of estrogen receptor, progesterone receptor, and HER2 receptor status, there were some concerns about completeness and accuracy of information on these receptors and about the number of breast cancer cases with missing or unknown status on these receptors, which could significantly affect the estimates of incidence of triple-negative breast cancer. Second, women aged ≥20 years in SEER areas as dynamic populations and denominators for the incidence rates may change over time due to migration, hence affecting the incidence rates. Third, women were grouped into broader categories of non-Hispanic whites, blacks, Asians, and Hispanics. Variations by sub-Saharan African women, subgroups of Hispanic population (Cuban or Mexico), and subgroups of Asian and Pacific Islanders were not considered in the analyses. Therefore, it should require a caution at interpreting and generalizing the study findings to sub-groups of various racial/ethnic populations.

In conclusion, age-adjusted incidence rates of triple-negative breast cancer was statistically significantly higher in black women and significantly lower in AIAN, Hispanic, and Asian women as compared to white women. The significantly higher age-adjusted incidence of triple-negative breast cancer in black women than white women were observed only in younger women aged 20-44. There were no significant annual percentage changes in age-adjusted incidence of triple-negative breast cancer from 2010 to 2019 in all ethnic women age 20-44 and 45-54 years except a significant decrease in AIAN aged 45-54 years. However, there was a statistically significant annual percentage increase in age-adjusted incidence of triple-negative breast cancer in Asian and black women aged ≥55 years. More research may be needed to explore why there is a significantly higher incidence of triple-negative breast cancer only in younger women aged 20-44 years and why there is significant annual percentage increase in age-adjusted incidence of triple-negative breast cancer in Asian and black women aged ≥55 years.

Acknowledgements

Research reported in this publication was supported in part by the National Institute on Aging of the National Institutes of Health under Award Number R01AG058971 and R01AG067498. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Disclosure of conflict of interest

None.

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