It is known that vitamin D deficiency is associated with long-term mortality especially in hospitalized, malnourished patients [14]. Furthermore, some studies suggest that higher vitamin D levels might reduce the risk of developing breast cancer [15–18]. Animal studies have also shown that vitamin D deficiency might play a role in primary tumor growth and development of metastases in breast cancer cells [19]. Similarly, there is an ongoing discussion on the potential role of selenium deficiency in tumor genesis and outcome [9].
In the present study we show that almost two thirds of newly diagnosed German breast cancer patients suffer from vitamin D deficiency. The median vitamin D serum concentration was below the recommended minimum value (median vitamin D level of 24 µg/l; vitamin D reference for standard values: 30–100 µg/l) [3]. As expected, patients who consumed supplements had higher vitamin D levels in average. However, despite supplementation, seven out of 17 patients had still mild vitamin D deficiency. None of the patients was above recommended reference values. This supports that vitamin D intoxication and subsequent hypercalcemia and hyperphosphatemia are extremely rare [3]. Vitamin D deficiency was slightly higher in the present study (64.8%) compared to the healthy, cancer free German population, where almost 60% suffer from vitamin D deficiency [2]. A definite connection between breast cancer development and vitamin D levels has not yet been proven [20] and the slightly higher proportion of vitamin D deficiency in the present study seems negligible. Nevertheless, breast cancer patients might be particularly susceptible to suffer complications of vitamin D deficiency such as bone fractures due to additional risk factors caused by the disease itself and by cancer therapy. For example, disease associated immobilization, chemotherapy, endocrine therapy, radiotherapy, and metastases may further increase bone loss and the risk of fractures. Thus, in breast cancer patients, special attention should be paid to achieve and maintain vitamin D levels within the reference range regardless of the potential influence of vitamin D on the cancer cells [20].
We observed higher vitamin D levels in summer than in other seasons. Furthermore, patients who stated that they stayed longer in the sun had higher vitamin D levels. Even if this did not reach statistical significance due to the limited patient number, our observations are in agreement with previous population based publications that describe seasonal variations of vitamin D levels due to varying sun light exposure [21–23]. Sufficient vitamin D values at the end of summer do not prevent vitamin D deficiency in winter [23]. This illustrates the need of vitamin D monitoring and supplementation in clinical routine- especially in highly vulnerable cancer patients [1].
Although exposure to sunlight is the main factor influencing vitamin D levels in human [21], there are some natural sources like fish (e.g. mackerel, salmon or tuna) and fortified foods (e.g. milk, yogurt, butter, margarine, cheese) that contain high amounts of vitamin D [3]. For this reason, patients in the present study were asked about their eating habits. It remains unclear why in our study, increased consumption of cream / gouda and butter was associated with a minimal decrease in serum vitamin D values. However, this effect was negligible, as it was associated only with a reduction of -0.36 µg/l vitamin D in a total range of 30–100 µg/l. Possibly, these patients increased their consumption of foods rich in vitamin D to counteract a known or presumed vitamin D deficiency. This suggests that in our cohort the diet had only little effect on vitamin D levels compared to sunlight exposure and intake of supplemental vitamin D.
Previous publications link particularly aggressive and triple negative carcinomas with reduced vitamin D levels [18, 24]. In a systematic review with 13,135 breast cancer patients, low vitamin D levels were also associated with triple negative breast cancer [25]. This contrasts with the present study, where triple negative patients had higher vitamin D serum levels compared to other tumor subtypes (Luminal A / Luminal B / Her2 positive). As patients with vitamin D supplementation were excluded from analysis, a possible explanation for higher vitamin D levels in triple negative patients might be coincidentally increased sun exposure. Further studies with larger sample sizes are needed to investigate this connection.
There is an ongoing controversial discussion on the potential influence of selenium concentration on cancer development and the course of the disease as well as therapy side effects (e.g., toxicity of chemo- and radiotherapy) [1, 9]. For example, Szwiec et al. described an influence of selenium levels on 10-year survival of breast cancer patients [26]. Lopez-Saez et al. examined selenium serum concentrations of patients suffering from breast cancer and healthy women [9]. They found a statistically significant difference (81.1 µg/l in breast cancer patients and 98.5 µg/l in women with non-tumoral disease; p < 0.001) [9]. Considering the reference range for selenium level of 50–120 µg/l [13], the clinical relevance of this difference is questionable. In a recent systematic review, beneficial effects of selenium supplements on carcinogenesis could not be proven [27]. Furthermore, a prospective cohort study from Sweden also could not prove an influence of increased selenium intake and serum levels on the risk for breast cancer [28]. In the healthy German population median selenium levels range between 70 and 80 µg/l [13]. In the present study, the median selenium level of breast cancer patients was 81 µg/l with 96.2% of patients being within the recommended reference range. Five patients took selenium supplements - none of them had a deficiency, but one patient was slightly above the recommended reference range (> 120 µg/l). Thus, our study does not support the hypothesis that the risk for breast cancer would be associated with lower serum selenium levels.
Surprisingly, we observed lower selenium levels in autumn compared to determination of selenium levels in summer in the current study. As seafood, organic meats, cereals and grains are typical food sources of selenium [8], the seasonal difference of selenium levels might be due to coincidentally changes of nutritional selenium intake. Furthermore, in harmony with previous studies, we found a positive correlation between selenium levels and alcohol consumption [29, 30]. In the third National Examination Survey of 7,517 American women, those who drank alcohol had significantly higher selenium levels compared to non-drinkers [30].
Limitations of the study are the limited number of patients and the fact that nutritional habits and sun exposure were retrospectively reported by the patients themselves. Nevertheless, these results give important insights into the serum vitamin D and selenium levels of newly diagnosed breast cancer patients which has been rarely studied.