Introduction

Breast cancer is the most frequently diagnosed cancer in women, impacting about 2.1 million women each year around the world in 2018, and is also the commonest cause of cancer death for women [1, 2]. Diversities in cancer characteristics, treatment and survival between different ethnic groups have been well documented [3,4,5,6,7,8,9]. Compared to European, Hispanic and Asian women in the US, African American women have the higher risk of having triple-negative breast cancer that is associated with a poor outcome [4]. Japanese and Filipino women were found to be less likely to receive breast conserving surgery than white women [3]. Asian women are more likely to have human epidermal growth factor receptor 2 positive (HER2+) than European (10.9% vs 7.0%) [4]. African American women have worse breast cancer-specific survival, and Asian women have better survival than European women [4, 5].

European, Māori, Pacific and Asian are the four main ethnic groups in New Zealand. It has been demonstrated that Māori and Pacific women were more likely to be diagnosed with advanced breast cancer, have disadvantages in access to treatment and have poorer survival compared to European women [6,7,8,9,10,11,12,13,14,15]. Breast cancer in Asian women has rarely been studied in New Zealand, but the above studies suggested that Asian women in New Zealand may have better outcomes that the other groups.

In New Zealand, Asian ethnicity accounts for 11.8% (471,708) of the population in 2013, increasing from 9.2% (354,552) in 2006 [16]. The Asian ethnic group is getting older, with a median age of 28.6 years in 2006 and a median age of 30.6 years in 2013 [16]. The health needs of Asian are changing with the increasing population and the ageing problem. This study aims to examine the differences in characteristics, treatment and survival between Asian and European women diagnosed in stage I–III breast cancer in New Zealand.

Methods

The studied population included European women and Asian women diagnosed with stage I–III breast cancer between June 2000 and May 2013 identified from the combined Waikato and Auckland Breast Cancer Registers [17]. The registers’ data include (1) patient characteristics: age, ethnicity and BMI (body mass index); (2) tumour information: diagnosis date, cancer stage, cancer grade, tumour size and biomarkers including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2); and (3) information on treatment: surgery (including breast conserving surgery (BCS) and mastectomy), chemotherapy, trastuzumab, endocrine therapy and radiation therapy. Ethnicity was self-identified as part of the registers consent process. The classification of New Zealand European women and Asian women followed the Ethnicity New Zealand Standard Classification (2005 V2.0.0) [18].

Information on comorbidities has been obtained by reviewing linked data from the National Minimum dataset (NMDS) by National Health Index number (NHI) and categorising patients using the C3 comorbidity index: [19, 20] (1) less or equal to zero, (2) greater than zero but less or equal to one, and (3) greater than one. BMI were grouped into < 18.5 (underweight), 18.5–25 (normal), 25–30 (overweight) and ≥ 30 (obese). In this study, HER2+ was defined as FISH amplified or IHC 3+ according to the 2013 American Society of Clinical Oncology (ASCO) guideline [21]. Recommended in the 2001 St. Gallen Consensus, ER+ or PR+ was assessed as IHC positive (1+) [22]. Based on the status of the three biomarkers, ER, PR and HER2, five cancer subtype groups were categorised including Luminal A, Luminal B HER2−, Luminal B HER2+ , HER2+ non-luminal and triple negative [9, 23]. Patient and tumour characteristics were compared between Asian and European women. Chi-square test was used to examine the differences between the two ethnic groups.

The PHARMS dataset contains claim and payment information from pharmacists for subsidised dispensing. Adherence to endocrine therapy was investigated in patients diagnosed during 2005–2013, because 2005 was the first year when over 80% of pharmaceutical dispensing records reported NHI in the PHARMS dataset. The quality of PHARMS data has improved, and in 2010, NHI was provided for approximately 97% of pharmaceutical dispensing [24]. An adherence index/medication possession ratio (MPR) for each woman was calculated by dividing the number of days covered by endocrine therapy with the number of days for up to 5 years unless censored by death or the conclusion of the study (31 December 2014). A MPR of 80% or more was considered to be high/optimal level of adherence [25,26,27]. Stepwise logistic regression model was used to estimate the odds ratio of treatment and adherence to endocrine therapy between the two groups.

Patient outcomes include breast cancer-specific survival and all-cause survival. These mortality data were derived from the New Zealand National Mortality Collection. For all-cause survival analyses, patients without a documented record of death were considered to be censored on the last updated date for Mortality Collection which was 31 December 2014. For cancer-specific analyses, deaths from other causes were censored on the date of death. Kaplan–Meier method was used to examine the survival between Asian and European women, as well as the survival between Asian subgroups (Chinese, Southeast Asian, Indian and other Asian). We used Cox proportional hazards model to estimate the hazard ratio (HR) of breast cancer-specific mortality and all-cause mortality between Asian and European women after adjustment for characteristics and treatments. All data analyses were performed in IBM SPSS statistics 25 (New York, United States).

Results

The studied cohort included 8608 European women and 949 Asian women (317 Chinese, 225 Indian, 94 Southeast Asian and 313 other Asian). The number of Asian women diagnosed with stage I–III breast cancer has been increasing rapidly, from 148 in 2000–2003 to 331 in 2010–2013 (Table 1). Asian women who were diagnosed with stage I–III breast cancer were generally younger (average age: 53 years vs 60 years) and had less comorbidities than European women. Compared to 78.7% of European women, 86.7% of Asian women had no severe comorbidities. BMI data was only available in 28.0% of patients. Among those with BMI information, 30.2% of European women were obese (BMI ≥ 30) compared to 15.4% of Asian women. A higher proportion of Asian women were diagnosed with grade 3 breast cancer than European women (36.6% vs 27.3%), as well as HER2+ breast cancer (16.0% vs 11.8%). The tumour size for Asian women was larger than that for European women.

Table 1 Characteristics of NZ European women and Asian women diagnosed with stage I–III breast cancer
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Asian women were more likely to receive mastectomy rather than BCS compared to European women (Table 2). The odds ratio of Asian women having BCS compared to European was 0.63 (95% confidence interval (CI) 0.54–0.74) after adjustment for age, year, register, screen detection, public/private treatment, cancer stage, grade, tumour size and subtype. Among the 532 Asian women diagnosed with T1 breast cancer, 41.0% (218) had mastectomy and 59.0% (314) had BCS. The respective percentage was 28.5% and 70.7% for European women diagnosed with T1 breast cancer. Asian women were also less likely to have reconstruction after mastectomy (adjusted odds ratio: 0.34), less likely to have chemotherapy (adjusted odds ratio: 0.73), and less likely to be treated with trastuzumab if tested HER2+ (adjusted odds ratio: 0.43). Use of radiotherapy and endocrine therapy for ER/PR positive cancer were similar between the two ethnic groups. Asian women had better adherence to endocrine therapy with an adjusted odds ratio of 1.54 (95% CI 1.22–1.93, p value < 0.001).

Table 2 Difference in treatments between European and Asian women with breast cancer
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Asian women had better breast cancer-specific survival and all-cause survival than European women (Figs. 1, 2). The crude HR of breast cancer mortality for Asian women compared to European women was 0.60 (95% CI 0.47–0.78), and the crude HR of all-cause mortality was 0.66 (95% CI 0.53–0.81). The respective HR was 0.64 (95% CI 0.49–0.82) and 0.68 (95% CI 0.55–0.84) after adjustment for characteristics and treatments (Table 3). Better breast cancer-specific survival and all-cause survival were associated with fewer comorbidities, younger age, diagnosed in recent years, earlier cancer stage, lower cancer grade, smaller tumour size, less aggressive subtypes, having surgery, chemotherapy, radiotherapy and good adherence to endocrine therapy. The Kaplan–Meier method showed that Chinese, Indian and other Asian women had similar breast cancer-specific survival, but Southeast Asian women had worse survival than other Asian subgroups (Fig. 3. log-rank test p value = 0.016). The adjusted hazard ratio of breast cancer-specific mortality for Southeast Asian women compared to other Asian subgroups was 2.90 (95% CI 1.42–5.51).

Fig. 1
figure 1

Breast cancer-specific survival between European and Asian women with breast cancer

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Fig. 2
figure 2

All-cause survival between European and Asian women with breast cancer

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Table 3 Hazard ratios of breast cancer-specific mortality and all-cause mortality
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Fig. 3
figure 3

Breast cancer-specific survival between the Asian subgroups

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Discussion

This study shows that Asian women with stage I–III breast cancer have better survival than European women. This is consistent with two American studies [4, 5] demonstrating a lower HR of mortality in Asian women compared to European women. However, in these two studies, the Asian group includes Pacific islanders who were found to have the worst survival of breast cancer compared to other ethnic groups in New Zealand [28, 29]. If Pacific women were not included in the Asian group, the HR of death in Asian women would likely have been even lower. Among the Asian subgroups, Southeast Asian women had the worst survival, as found in another American study compared to Chinese and Japanese [30]. However, the numbers of Asian subgroups were small, and therefore, the Asian subgroup findings were prone to great uncertainty. The definition of Southeast Asian [30,31,32] was different in other studies, and therefore the comparison with other studies is difficult. In New Zealand, Southeast Asian includes Filipino, Cambodian, Vietnamese, Indonesian, etc. [18], but Filipino and Vietnamese were not included in the Southeast Asian group in some American studies [32].

Ten percent of Asian women diagnosed with breast cancer were 70 years or older compared to 24.6% of European women. This is a reflection in the make-up of the Asian and European populations in New Zealand. Five percent of Asian women in New Zealand are 70 years or older compared to 14% of European women [33].

Asian women have shown better survival from breast cancer, in spite of the fact that they are more likely to be diagnosed with HER2+ breast cancer—a factor that is associated with worse outcomes [11]. Sixteen percent of Asian women had HER2+ breast cancer compared to 11.8% of European women. This has also been found in other studies, but the proportions of HER2+ breast cancers were slightly different [4, 32, 34]. The reported percentages of HER2+ breast cancer ranged from 20.6% to 36% for Asian women and 16.8% to 19% for European women [4, 32, 34].

The better breast cancer outcome in Asian women was partly due to the better adherence to endocrine therapy (odds ratio: 1.54). In the Cox proportional hazards model, high adherence to endocrine therapy was associated with a decreased risk of breast cancer-specific mortality and all-cause mortality (respective hazard ratio: 0.41, 0.57). Previous studies have also shown that suboptimal adherence to adjuvant endocrine therapy increased the risk of breast cancer recurrence and mortality [27, 35, 36].

Fewer comorbidities and younger age have a significant impact on both breast cancer-specific and all cause survival. Compared to European women, Asian women were younger and were less likely to have comorbidities [37, 38]. Comorbidities in patients with breast cancer can lead to dose reduction in chemotherapy and radiotherapy [37, 38], and consistent underdosing of chemotherapy, and dose reductions in radiation therapy limit treatment efficacy and disease outcome [37,38,39].

In Seneviratne’s paper [15], the survival difference between Māori women and European diagnosed with breast cancer disappeared after adjustment for patient characteristics and treatment, but the HR in our study did not change substantially after adjustment. That means there are some unknown factors contributing to the survival difference between Asian and European women. The breast cancer outcome in Asian women may be also associated with their health status and life style. The available BMI data show that Asian women were half as likely to be obese compared to European women (15.4% vs 30.2%). This is consistent with the data reported in the New Zealand Health Survey 2017/18: 15.1% of Asian and 30.7% of New Zealand European were obese [40]. Obesity is associated with a higher risk of developing breast cancer, especially in postmenopausal women, and with worse disease outcome for women of all ages [38]. Exercise and weight loss can reduce breast cancer risk and improve outcomes [38].

The New Zealand Health Survey 2017/18 also showed that only 6.5% of Asian people are hazardous drinkers, but 21.2% of European women are hazardous drinkers. Alcohol consumption has an adverse impact on survival for women with breast cancer. Drinking ≥ 6 g/d of alcohol compared with no drinking after a breast cancer diagnosis increase risk of breast cancer recurrence (HR, 1.35; 95% CI, 1.00 to 1.83), especially among postmenopausal (HR, 1.51; 95% CI, 1.05 to 2.19) and overweight/obese women (HR, 1.60; 95% CI, 1.08 to 2.38) [41].

The difference in diets between Asian and European women may have an impact on the incidence and outcome of breast cancer. An American study found that low intake of meat/starches and high intake of legumes is associated with a reduced risk of breast cancer in Asian Americans [42]. A meta-analysis also show that a Mediterranean diet including fresh produce, whole grains, and legumes, as well as some healthful fats and fish, can reduce the risk of breast cancer [43].

The strength of this study is that it comprises a relatively large population based database with comprehensive data on patient characteristics, patient treatment as well as outcomes. One weakness is that we do not have good data on BMI, exercise, drinking and diet that may explain the survival difference between Asian and New Zealand European women. Therefore, we used the New Zealand Health Survey data for discussion of possible explanations. It has been found that survival after breast cancer is different between immigrant Asian women and locally born Asian women [44, 45]. The Breast Cancer Registers do not record immigrant status and therefore we cannot compare the survival between immigrant Asian women and New Zealand born Asian women.

Conclusion

Asian women are more likely to have high grade, larger and HER2+ breast cancers than New Zealand European women. In spite of this, they had better breast cancer outcomes. Possible explanations include the differences in adherence to endocrine therapy, age, BMI and comorbidities.