Breast cancer affected 1.7 million women worldwide in 2012 [1]. In low-income countries such as Vietnam, breast cancer was traditionally found to have a low incidence rate (less than 20 per 100,000 women) compared with Westernized populations [2], but recently reported increases demand attention. For example, in 2012 over 10,000 cases of female breast cancer were diagnosed in Vietnam, which is a 30% increase compared with 10 years ago [3]. At the time of writing, breast cancer was the most common cancer amongst women in Vietnam.

In response to this increase in breast cancer incidence, the Vietnamese government is promoting breast self-examination as a method of breast cancer screening. However, focused primary prevention is significantly hindered by limited data pertaining to risk factors associated with the disease. While demographic, reproductive and lifestyle factors linked to breast cancer are reasonably well understood in developed countries [4], the relevance of these parameters to Vietnamese women is much less understood. Two previous studies relating to breast cancer in Vietnam exist. The first, which focused only on BRCA mutations, found an insignificant association between genetic profiles and breast cancer due to low BRCA positivity in Vietnam [5]. The second investigation did not find any association of breast cancer with body mass index (BMI), age of menarche, total months of lactation, and family history of breast cancer [6]; however, this sample included only premenopausal women in Vietnam and China, which limited its scope in general and specifically its relevance to Vietnam. Other potentially important agents such as breast density and lifestyle parameters have been under-explored. Therefore, this study was conducted to explore the association of breast density, demographic, reproductive and lifestyle factors with female breast cancer in Vietnam.

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Ethical approval was obtained from the Research Ethics Board of the University of Sydney, the Biomedical Research Board of Ethics at the University of Medicine and Pharmacy in Ho Chi Minh City and site permission from two hospitals involved in this study.

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The distribution of cases and controls for all women, premenopausal and postmenopausal women are presented in Tables 1-3. The average age was 49.2 for cancer cases and 48.8 for controls (p=0.37). Premenopausal cancer women had an average age of 43.3 years old, while postmenopausal women diagnosed with breast cancer had a mean age of 55.2 years old. There were no significant differences in ages between cases and controls in either premenopausal (p=0.72) or postmenopausal women (p=0.65).

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To the best of our knowledge, this is the first study to investigate a wide range of breast cancer risk factors in Vietnam. Similar to the results of previous studies conducted in other countries, we found an increased risk of breast cancer associated with high breast density, early age at first menarche, low number of pregnancies, few live births, postmenopausal status, hormone use, and lack of engagement in physical activities, although there are differences in the distribution of risk factors when the analyses are stratified by menopausal status. Additionally, while use of external hormones and no physical activities were associated with breast cancer in premenopausal women, these associations were not found in postmenopausal women whose cancer risks were more influenced by high breast density and low number of pregnancies. Other risk factors reported in Westernized countries, such as BMI, family history of breast cancer, age at first giving birth, and breastfeeding duration were not significant in our study, which might be reflective of the different populations enrolled. Accurate identification of relevant risks helps to frame policies around the most effective strategies to maximize the prevention of breast cancer.

Consistent with case-control studies in other populations, an increased risk of developing breast cancer was observed among women with a breast density > 75% (as reported using BI-RADS scoring) compared to those with less dense breast, although the risk in Vietnam (OR, 1.7) was found to be lower than that reported for westernized countries (OR, 3-5) [14-16]. Moreover, high breast density was more frequent in Vietnamese women than low breast density (BI-RADS 1%-8.3%, BI-RADS 2%-19.9%, BI-RADS 3%-43.2%, BI-RADS 4%-28.6%). This could be explained by the fact that Asian women’s breasts are known to be more dense than those of westernized women [17]; therefore, there can be a high degree of density even in non-cancer women when compared with normalized figures from other countries, and the difference between the number of cancer and normal cases in high breast density groups might not be as substantial as in a Caucasian population. Another possible reason is that the cases in this study were retrieved from both screening and diagnostic populations in oncology hospitals, while other studies have often obtained their data from mammographic screening services. Although we would have preferred to have worked with a screening system, the absence of a nationally recognized screening service in Vietnam prevented this.

Most of our other results were also concordant with those of previous observations of reproductive risk factors in westernized and Southeast/East Asian countries [18]. For example, women having their first menstrual period at earlier than 14 years of age were more likely to have breast cancer (OR, 1.7-2.6), while women being pregnant more than two times or having more than one child had a 30%-50% lesser risk of developing breast cancer (although it should be acknowledged that number of babies born was no longer found to be a risk predictor when multivariate logistic regression was used). We also found that women having their first child at 30 years old or older had an increased risk developing breast cancer (OR, 1.5) compared with those who were 23 years old or younger. Although this relationship was not significant (p=0.08), it is relatively similar to a large cohort study in Denmark that showed that women who postpone their first child to after 30 years of age had double the risk of developing breast cancer compared with those who had their first child before they were 20 years old [19]. A number of our findings did not align with those of studies from other countries such as family history of breast cancer or breast feeding duration, neither of which were significantly related to breast cancer in our study. However, the results of breast cancer family history were consistent with those of a previous Hanoi-based investigation [5].

With regard to diet, despite insignificant results (p > 0.05), there was a relationship between breast cancer and consuming one or more cups of coffee per day (OR, 1.5), which is in line with a prospective study in Singapore showing that drinking two or more cups of coffee per day increased the risk of being diagnosed with advanced breast cancer (OR, 2.3) [20]. Similarly, there was no significant relationship between soy intake and breast cancer observed in the present study, which may have been because of the low quantity of soy milk uptake among Vietnamese women; specifically, only 14% of subjects reported that they drank at least one cup of soy milk per day. It seems that the benefit associated with soy milk only occurs in Asian countries in which women begin consuming soy products from early life and in greater amounts [21]. Similar to soy, we did not find any connection between vegetable intake and breast cancer, even though a breast-cancer protective effect of vegetable consumption through antioxidant and fiber content has been reported [22]. Our findings, while consistent with those of a previous U.S. study [23], are at odds with the dose-dependent, decreasing breast cancer trend found to be associated with large quantities of vegetables in postmenopausal Singaporean and Chinese women [22].

Population studies have consistently shown that Western lifestyle patterns such as smoking and drinking alcohol are associated with increased risk of breast cancer; however, no statistical significance was observed in our study. This could be explained by the fact that less than 5% of women in both the control and cancer groups had a history of smoking, and less than 1% consumed alcohol. Whilst in agreement with neighboring countries such as China [11] and Thailand [24], this is in contrast to data from Australia and Japan [25,26].

In this study, a variation of the risk factors for premenopausal and postmenopausal breast cancer was recorded. Having dense breast tissue was a predominant risk factor among all participants, although it had a greater impact on postmenopausal women than premenopausal women as indicated by a higher OR (2.0 vs. 1.6), which was in line with the results of a Korean study [27]. This could be explained by the finding that young women with growing mammary glands often have denser breasts than older women, which make malignant nodules less likely to be detected on mammograms. While having fewer pregnancies was a common risk in both premenopausal and postmenopausal participants, women within menstrual periods were reported to have a higher risk of developing breast cancer (OR, 2.6) than those whose periods had stopped (OR, 2.3). Hormone use and inactivity were only associated with breast cancer in premenopausal women, which illustrate differences in lifestyle between age groups in Vietnam. Premenopausal women tend to have less pregnancies, use more hormone replacements, and participate less in physical activities than postmenopausal women, which makes the risk factors of breast cancer in younger Vietnamese women more similar to those observed in westernized countries [18] where no physical activity is associated with a modest (15%-20%) increased risk [28] and women who have a history of using hormone replacement therapy or regular oral contraceptive pills have an increased risk of breast cancer of 17%-35% [29].

It should be noted that the current study was an exploratory study with several limitations. First, we collected data in a specific period of time; therefore, this study did not allow for changes in behavior over time to be incorporated. Accordingly, a longitudinal study might be needed to confirm these findings. Second, because data were collected through hospital-based systems, participants could not be allocated to a screening or diagnostic route. The inability to consider individually screened and symptomatic women highlights the need for better population-based disease surveillance systems in Vietnam. Nonetheless, this study is the first to investigate key demographic, reproductive and lifestyle factors relating to breast cancer in Vietnam. The findings presented here were similar to and different from those reported elsewhere. Overall, the results of this study will facilitate development of breast cancer prevention strategies specific for the 45 million women who live in Vietnam.

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