, , Triple negative breast cancer (TNBC) is associated with different ethnic groups in the United States (US), however this has not previously been examined in a population-based study within the United Kingdom (UK).
Electronic pathology reports from the North East London Cancer Network (NELCN) on women diagnosed with breast cancer between 2005 and 2007 were collated. The statuses of oestrogen receptor, progesterone receptor and HER-2 were extracted. Women were classified as having TNBC if all three receptor statuses were negative, and as not having TNBC if at least one receptor was positive or borderline. Logistic regression was used to quantify the association between TNBC and ethnicity, adjusting for age, year of diagnosis and socioeconomic deprivation. Overall survival in different ethnic groups was examined using Cox regression, adjusting as appropriate for age, stage of disease, triple negative status, year of diagnosis, socioeconomic deprivation and recorded treatment.
There were 2417 women resident in NELCN diagnosed with breast cancer between 2005 and 2007, and TNBC status was determined for 1228 (51%) women. Overall, of women who had their TNBC status determined, 128 (10%) were diagnosed with TNBC. Compared with White women, Black (odds ratio [OR] = 2.81, p < 0.001) and South Asian (OR = 1.80, p = 0.044) women with breast cancer were more likely to have TNBC. Black women had a worse age-adjusted survival than White women (hazard ratio [HR] = 2.05,p < 0.001). This was attenuated by further adjustment for stage of disease (1.52, p = 0.032) and triple negative status (1.31, p = 0.175).
Better methods of early detection may need to be developed in addition to more effective systemic treatment in order to improve outcomes for women with TNBC.
Although breast cancer is the most commonly diagnosed cancer in England,1 different subtypes require different treatments and vary in terms of survival outcomes.2, 3, 4 and 5 Triple negative breast cancer (TNBC) is diagnosed when a tumour tests negative for oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) expression, and is associated with a poor prognosis.5,6 and 7 Studies in the United States (US) have shown that among breast cancer patients a higher proportion of Black women than White women are diagnosed with TNBC.8, 9, 10 and 11 In the United Kingdom (UK), one hospital-based study in North East London found that among breast cancer patients aged under 60, Black women were more likely to have TNBC than White women, but this was of borderline statistical significance, possibly due to the small numbers of patients analysed.12
Variation in the survival of breast cancer patients between ethnic groups has been identified in the US13,14 and 15 and the UK.16 and 17 In US work these differences remain after adjusting for breast cancer subtype.13 and 14 In the UK, studies have not been able to examine the combined effect of these variables on survival as data on receptor status and ethnicity have historically not been routinely recorded.
The age-specific incidence of breast cancer in ethnic groups in this South East England population has been reported separately.17 and 18 This study uses new electronic pathology data obtained in recent improvements of routine cancer registration processes to study women with breast cancer in more detail. Its objectives were to determine whether there is any variation in the proportion of women with TNBC among breast cancer patients from different ethnic groups, and to examine survival in these patients.
In the UK, cancer registries record the occurrence of cancer in their resident populations. In the area covered by the Thames Cancer Registry (TCR), registration is initiated by clinical and pathological information received from hospitals and by information about deaths provided by the National Health Service Central Register through the Office for National Statistics. Trained cancer registration officers then extract further information on demographic details, disease stage and treatment in the first six months after diagnosis from individual medical records. Data are quality assured as they are added to the central database.
For this study, electronic pathology reports dated between 2005 and 2007 for patients diagnosed with breast cancer from the North East London Cancer Network (NELCN) were collated. Reports from two of the three hospital trusts that provide pathology reports in this cancer network were available for this period. The ER, PR and HER-2 statuses were reviewed, and combined to create a single record for each patient. If a woman had more than one pathology record, and the receptor statuses were different, information from the TCR and pathology records were examined together. If a date of diagnosis or laterality of the tumour indicated which pathology record was relevant, this record was used. Otherwise, the initial biopsy result was used for the ER and HER-2 results, and the later excision result was used for the PR.19 Women were classified as having TNBC if all three receptor statuses were negative, and as not having TNBC if at least one receptor was positive or borderline. Triple negative status could not be determined if receptor statuses were a combination of negative and not known or were all missing.
These records were matched to data from TCR on women resident in NELCN diagnosed with breast cancer (ICD-10 C50) in the same period. Ethnicity information in the Registry data was combined into the following five broad groups: White (including White British, White Irish and ‘White other’ groups), South Asian (including Indian, Pakistani, Bangladeshi and ‘Asian other’ groups), Black (including Black Caribbean, Black African and ‘Black other’ groups), other (including Mixed, Chinese and any other ethnic groups), and not known (where no information was available). Socioeconomic deprivation was measured using the quintiles of the income domain of the English Indices of Deprivation 2007.20 The staging data available in the Registry rely on what is recorded in the medical records. As this is often not complete, the Registry uses all the information available to classify stage using a simplified system. The five “TCR stage of disease at diagnosis” categories are: 1 – ‘localised’; 2 – ‘extension beyond the organ of origin’; 3 – ‘local lymph node involvement’; 4 – ‘metastases’ and ‘not known’.
Logistic regression was used to quantify the associations between TNBC and ethnicity, adjusting for age, year of diagnosis and socioeconomic deprivation. Cox regression analysis was used to assess survival in different ethnic groups, with women followed up until 31st December 2010. Results were adjusted as appropriate for age, stage of disease at diagnosis, triple negative disease status, socioeconomic deprivation, year of diagnosis and recorded treatment.
There were 2417 women resident in NELCN diagnosed with breast cancer between 2005 and 2007. Pathology reports were found and matched for 1538 (64%) women, and the TNBC status was determined for 1228 (51%) women. Of the patients who had a matching pathology report but their TNBC status could not be determined, the majority (266/310, 86%) had no ER, PR or HER-2 status information contained in the pathology report. Of those who did have a matching pathology report, HER-2 status was more likely to be unknown (43%) than ER (18%) or PR (18%). The age and socioeconomic deprivation distributions were similar in the groups defined by whether TNBC was determined. Median age was 61 years in those who had their TNBC status determined, and 60 years in those who had not. Of those who had TNBC status determined, 70% were resident in the two most deprived quintiles, compared with 71% of those whose TNBC status could not be determined. White (53%), South Asian (51%) and Black (53%) breast cancer patients were more likely to have their TNBC status determined than the other (45%) and not known (38%) ethnic groups. Overall, of women who had their TNBC status determined, 128 (10%) were diagnosed with TNBC.
The characteristics of the 1228 women with TNBC status determined are shown in Table 1. Women younger than 40 years old were more likely to have TNBC than older women. In the ethnic groups examined, the highest proportion of women with TNBC was in Black breast cancer patients (25%), followed by South Asian (19%), other (14%), White (8%) and those where ethnicity was not known (6%). Triple negative disease was more common in women who lived in more socioeconomically deprived areas. Women who were diagnosed with metastatic disease (TCR stage 4) also had a higher proportion of TNBC. There was no real difference in the proportion of patients with TNBC diagnosed each year.
Table 1. Total number of women with breast cancer resident in North East London Cancer Network diagnosed with breast cancer between 2005 and 2007 with triple receptor status determined, and number and percentage of women with triple negative breast cancer (TNBC). Chi squared tests (χ2) for triple negative and non-triple negative cases.
Table 2 shows the odds ratio of having TNBC in each of the ethnic groups studied. In the unadjusted analysis, Black (OR = 3.95, p < 0.001) and South Asian (2.67, p < 0.001) women were more likely to have TNBC. These differences were reduced, but still high, when adjusting for age (3.21, p < 0.001 and 2.13,p = 0.007 for Black and South Asian women, respectively). Further adjustment for year of diagnosis and socioeconomic deprivation attenuated the results further, but the odds ratios remained high for both Black (2.81, p < 0.001) and South Asian (1.80, p = 0.044) women. A strong trend was seen over the age groups, with older women less likely to have TNBC (trend p < 0.001).
Table 2. Odds ratios (OR), 95% confidence intervals (95% CI) and p values of having triple negative disease in female breast cancer patients from North East London Cancer Network, diagnosed 2005–2007.
Baseline group.
Results from the survival analyses are shown in Table 3. Black women with breast cancer had worse age-adjusted survival compared with White women (HR = 2.05, p < 0.001). Further adjustment for stage of disease at diagnosis attenuated this estimate, but survival was still significantly worse in Black women (1.52, p = 0.032). However, there was no statistically significant association when TNBC status was also adjusted for (1.31, p = 0.175). There was little material difference between estimates when year of diagnosis, socioeconomic deprivation and recorded treatment were additionally adjusted for (1.39, p = 0.105). While South Asian women had slightly worse survival estimates than White women, and women from the other ethnic group had better survival estimates, none were statistically significant in any of the models. Women with TNBC had worse survival than other women in all of the survival models examined (fully adjusted HR = 1.70, p = 0.004). Age and stage had very strong associations with survival (fully adjusted trendp < 0.001 for both variables).
Table 3. Hazard ratios (HR), 95% confidence intervals (95% CI) and p values for overall survival in female breast cancer patients from North East London Cancer Network, diagnosed 2005–2007.
Ethnic group, age, stage of disease, triple negative status, year, socioeconomic deprivation and treatment.
Baseline group.
This study of a population of London women with breast cancer found that TNBC makes up a higher proportion in Black women, and is also more common in South Asian than White women. The worse survival in Black women is partially explained by TNBC status, but is also due to differences in stage of disease at diagnosis.
These results replicate the findings in the US that TNBC is more common in Black breast cancer patients than in White patients.8, 9, 10 and 11 A study in California also examined the differences in breast cancer tumour subtypes in several ethnic groups.21 Results were similar to the present study, with 12% of White, 18% of South Asian and 26% of Black women having TNBC. After adjusting for age, stage, tumour grade, socioeconomic status, year of diagnosis, place of birth and hospital ownership status, Black and South Asian women were more likely to have TNBC than White women. Other studies from India have found higher proportions of breast cancer patients with TNBC than in the present study (25%22 and 30%23). Women with breast cancer who were resident in more deprived areas were more likely to have TNBC, although this result was of borderline statistical significance, possibly due to the small numbers in some of the groups analysed. Previous studies in the US have also found this association for ER and PR negative24 and ER negative25cancers, although in another analysis of ER status the association varied depending on whether education or income was analysed.26
Several studies have shown worse survival in TNBC patients compared with other breast cancer subtypes.7,8 and 27 Bauer et al.8 stratified their analysis by stage group and found that five-year relative survival was worse in women with TNBC than other breast cancer types within each ethnic group examined. However, there was less variation in survival between the ethnic groups within each breast cancer type. This is similar to the present study where in the full model women with TNBC had worse survival, while there were smaller and not statistically significant differences between the ethnic groups. This is likely to be because of high risks of micrometastatic dissemination coupled with lack of efficacy, and therefore use, of adjuvant endocrine therapy or trastuzumab in comparison to ER positive or HER-2 positive forms of breast cancer.
There were some limitations to this study. Triple negative status was determined for only 51% of women resident in NELCN who were diagnosed with breast cancer in the period examined. This was mostly due to the availability and content of pathology reports. During the study period, two of the three hospital trusts in the network that provide this information supplied usable pathology data. There were also 310 patients with pathology records matched to their cancer registration whose triple negative status could not be determined. It is therefore possible that additional pathology reports containing receptor status information were missing. Another disparity between the data sources is that cancer registration data are defined based on a person’s place of residence, while pathology reports are provided for all tests from a hospital’s laboratory. Residents of a particular cancer network may therefore have had pathology tests performed by a hospital in another area, and such information was not available for the present study. By coding reports with a borderline ER, PR or HER-2 as not TNBC, some cases could have been misclassified. However, there were only a small number of patients where reclassifying borderline results may have led to a TNBC definition, and this was less than 3% in each ethnic group examined. The age and socioeconomic deprivation distribution of the group whose TNBC status could not be determined was similar to patients who did have enough information to determine TNBC status.
Black and South Asian women in the UK have lower breast cancer incidence rates than White women.17 and 28 It is possible that TNBC has similar absolute incidence rates in all ethnic groups, but the smaller number of non-triple negative cases in Black and South Asian women leads to TNBC contributing a higher proportion in these breast cancer patients.11 While it was not possible to calculate incidence rates for the different types of breast cancer in this study, due to the lack of completeness of receptor data, several studies in the US have done this. These population-based studies found higher absolute incidence rates of TNBC in Black than in White women,10 and 11 suggesting a genuine increased risk in Black women.
The ability to adjust for several factors in this analysis of survival in different ethnic groups has shown that TNBC and stage of disease are both essential in explaining differences between ethnic groups, and once these have been accounted for, the further contributions of socioeconomic deprivation and recorded treatment are relatively minor.
Differences in breast cancer incidence have been shown to vary within broad ethnic groups commonly used in the UK.17 As a sensitivity analysis, the more detailed Indian, Pakistani, Bangladeshi, Black Caribbean and Black African ethnic groups were also compared with the White group. Although there were small numbers of women in these different groups (between 21 Pakistani and 48 Black Caribbean women), Bangladeshi, Black Caribbean and Black African breast cancer patients were statistically significantly more likely to have TNBC (data not shown). Indian and Pakistani breast cancer patients were also more likely to have a diagnosis of TNBC than White breast cancer patients, but there was no statistically significant difference. Using these more detailed ethnic groups, Black African women consistently had worse survival estimates than White women, which was not explained by adjusting for age, TNBC status, stage of disease, year of diagnosis, socioeconomic deprivation or treatment. Larger studies will be able to investigate in more detail the possible differences between the detailed ethnic groups.
In this study, 39% of women with TNBC were aged under 50 compared with 22% of women with other types of breast cancer. While the different age profiles and the aggressive nature of TNBC may seem to suggest that breast cancer screening should be extended to younger women, it remains uncertain whether mammographic screening of young women in fact reduces the breast cancer death rate.29 A study in Canada examined the method of detection in TNBC and other breast cancer patients in women aged 50 or over.7Women with TNBC were less likely to have had their tumour diagnosed through mammography or ultrasound, despite breast screening mammography being routinely recommended for women in this area and age group. Also, in the present study, women whose breast cancer was screen detected were less likely to have TNBC, but this adjustment made little material difference to the ethnicity results (data not shown). Other methods of detection or more effective treatments may need to be developed in order to improve outcomes for women with TNBC, which disproportionately affects Black, South Asian and younger women, as well as those living in more deprived areas.
None declared.
This work was carried out by the Thames Cancer Registry, King’s College London, which receives funding from the Department of Health. The research was supported by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s and St. Thomas’ NHS Foundation Trust and King’s College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.
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