As mentioned above, obesity portends a poor prognosis for patients with breast cancer owing to the secretion of various hormones and cytokines, thereby causing chronic inflammatory conditions [5–10]. However, obesity was found not to be a poor prognosis factor in our study; in fact, OB patients with TNBC had improved prognoses. One explanation is that this study was performed at a single institution in East Asia; while the BMI distribution of our subjects was not markedly different from those in other studies from this part of the continent, OB patients are fewer in proportion than in Europe and the United States. Over 30% of patients with breast cancer are classified as OB in Europe and New Zealand [4, 11, 13, 35], compared to approximately 5% in East Asia [36–38]. One of the reasons that obesity is associated with poor prognosis among patients with breast cancer is suggested to be the lower rate of chemotherapy; for example, one study found that 20% of patients with breast cancer who had BMIs greater than 30 kg/m2 received reduced doses of chemotherapy . It was also reported that OB patients with breast cancer have improved pCR rates and more favorable progression-free survival when they receive full (uncapped) doses of neoadjuvant chemotherapy . Another study found that obesity was associated with a better prognosis among patients with hormone receptor-negative breast cancer but with a worse prognosis among those with HRBC . These data support our own findings.
Conversely, being UW was associated with a poor prognosis among patients with TNBC. A number of studies from Europe and the United States investigated the relationship between UW and the prognosis of patients with breast cancer, although UW and NW were commonly considered a single group because of the relatively scarcity of the former [12–14]. The proportions of subjects with breast cancer in those geographic areas who were UW were 1–2% [11, 35]. However, UW patients with breast cancer are frequently found in Asia, and their clinicopathological features have been explored [37, 42–44]. These studies did not confirm the existence of associations between UW and prognosis owing to some inconsistencies between them. Depending on the study, UW patients were found to be younger [37, 43], have smaller tumors [37, 42, 43], rarely have lymph node metastases [37, 42], and have lower histologic grades ; one study showed them to have more frequent HER2 positivity , another found them to have more frequent hormone receptor positivity , and two others found them to be more frequently hormone receptor-negative [42, 43]. Regarding prognosis, a number of studies, including one pooled analysis, demonstrated poor survival outcomes not only in OB patients with breast cancer but also in UW patients [11, 37–39, 43–50]. However, there were difference in each subtype; some studies found that UW patients with HRBC had poorer prognoses [47–49] and that those with HER2BC or TNBC did not [47, 49]. One study found that UW patients with HER2BC had poor prognoses . In contrast, our study found that UW was associated with a poor prognosis only in patients with TNBC.
The cause of poor prognosis among UW patients with breast cancer has been speculated on for some time. For example, one group found that UW is associated with a higher frequency of tumor progression ; however, such progression was not marked in other studies (including ours). Another study found that chemotherapy was frequently incomplete in UW patients , but our data suggested that this did not cause poorer prognosis because there were only a few patients who were unable to complete chemotherapy in our study. Some investigators cited the more aggressive breast cancer characteristics among younger patients, who comprised a large proportion of UW subjects, as a reason for poor prognosis [37, 43, 46, 47]; however, this was also not supported by our data. Others posited that the immune system is dysfunctional in UW individuals owing to chronic malnutrition and micronutrient deficiency [43, 51, 52]. Additionally, the effects of inflammatory reactions accompanied by cytokine expression and systemic immune reactions were considered [37, 48]; however, such studies did not identify the causal relationship between poor prognoses of patients with breast cancer and UW. Our study was able to demonstrate that the tumor microenvironment in UW patients may be more tumor-permissive owing to the low TIL density.
The largest limitation in our study was the small number of OB and UW patients with breast cancer. Post-diagnosis weight gain is also known to increase the risk of breast cancer recurrence [1, 53, 54], but we did not examine changes in body weight over time. Additionally, there may have been some BMI-associated confounding factors such as age, given that the frequency of UW patients with breast cancer was high among younger subjects [37, 43]. It has been reported that TILs are lower among the elderly than among younger individuals ; therefore, the composition of the immune microenvironment may change with age. No correlation was found between BMI and age in this study, although this should be considered with caution. Comorbidities, smoking, alcohol, and physical activity can also influence BMI, but these factors were not investigated in our study.