- Vitamin D Deficiency Linked to Poor Outcome for Patients with Early Breast Cancer
- 作者:吴一龙|发布时间:2008-06-16|浏览量:1546次
今年刚结束的ASCO会议报道:早期乳腺癌患者若缺乏维生素D其预后较差, 原文如下:
Vitamin D deficiency is common at breast cancer diagnosis, but it also is associated with poor prognosis, according to a study conducted at three University of Toronto hospitals. Pamela J. Goodwin, MD, of Mount Sinai Hospital, presented the data from the study on behalf of her colleagues on Sunday (Abstract 511).广东省人民医院乳腺科王坤
Previous studies have found vitamin D receptors on normal and malignant breast tissue, and low levels of vitamin D have been associated with increased breast cancer risk. In order to further explore the prognostic associations of vitamin D, Dr. Goodwin and her colleagues studied an existing cohort of 512 patients with newly diagnosed breast cancer who were consecutively enrolled between 1989 and 1996.
In 2007, using frozen blood samples taken at time of diagnosis, the researchers measured 25-hydroxyvitamin D by radioimmunoassay. The liver converts circulating endogenous and exogenous vitamin D into this inactive form that reflects total body stores. Vitamin D levels were categorized by standard definition as deficient, insufficient, sufficient, and toxic. At diagnosis, mean vitamin D level was 58 nmol/L. Only 24% of the patients had sufficient levels of vitamin D; 39% had insufficient levels and 38% were deficient in vitamin D. None of the patients had toxic levels.
Higher mean vitamin D levels were associated with age 50 years and older (p = 0.006), obesity (p = 0.004), and use of vitamin D supplements (p < 0.0001; average dose was less than 400 IU daily). Vitamin D levels correlated with dietary intake or consumption of the following: retinol; vitamins B, C, E; riboflavin; grains and cereals; and alcohol (all p < 0.05). An inverse correlation was found between vitamin D and insulin (p < 0.0004).
Regarding tumor characteristics and treatment, low vitamin D levels were associated only with a higher tumor grade (p = 0.03) and adjuvant chemotherapy (p = 0.02). Tumor size, nodal involvement, and estrogen receptor status were not associated with vitamin D level.
Distant disease-free survival was significantly shorter for patients with deficient (versus sufficient) vitamin D levels (hazard ratio (HR) = 1.94, p = 0.02). Adjustment for patient and tumor characteristics had little effect on the hazard ratio.
Overall 10-year survival rates were 74%, 85%, and 85% for patients with deficient, insufficient, and adequate vitamin D, respectively; the hazard ratio was 1.73 (p = 0.02). As with distant disease-free survival, adjustment for patient and tumor characteristics had little effect on the hazard ratio. ER status was not differentially affected by vitamin D deficiency (contrary to the statement in the abstract).
No difference in survival was detected between patients with sufficient and insufficient vitamin D levels so a smoothed log hazard of death curve was plotted across the range of vitamin D levels. The plot was curvilinear, with the lowest hazard at vitamin D levels between 80 and 110 nmol/L, and a trend for increased risk of death at higher levels. For distant disease-free survival, the smoothed log hazard curve exhibited decreased risk across the vitamin D range. Dr. Goodwin said that the different patterns could not be explained and required further study.
Dr. Goodwin noted that the data must be replicated by additional observational studies. If the work is corroborated, before undertaking any randomized trials of vitamin D supplementation, researchers should conduct a survey to establish whether vitamin D deficiency remains a problem in an era of widespread vitamin supplementation. "I believe it is premature to advise patients with breast cancer to use vitamin D supplements in doses higher than that recommended for bone health," said Dr Goodwin.
In discussing Dr. Goodwin"s presentation, Bruce Trock, PhD, of Johns Hopkins University School of Medicine, commented that future research also should determine whether circulating 25-hydroxyvitamin D is a good surrogate for vitamin D activity in the normal and cancerous breast, whether the enzyme that converts the inactive form of vitamin D to the active form varies in breast cancer according to genetic profiles, and whether there is individual variation in serum 25-hydroxyvitamin D.
Vitamin D deficiency is common at breast cancer diagnosis, but it also is associated with poor prognosis, according to a study conducted at three University of Toronto hospitals. Pamela J. Goodwin, MD, of Mount Sinai Hospital, presented the data from the study on behalf of her colleagues on Sunday (Abstract 511).广东省人民医院乳腺科王坤
Previous studies have found vitamin D receptors on normal and malignant breast tissue, and low levels of vitamin D have been associated with increased breast cancer risk. In order to further explore the prognostic associations of vitamin D, Dr. Goodwin and her colleagues studied an existing cohort of 512 patients with newly diagnosed breast cancer who were consecutively enrolled between 1989 and 1996.
In 2007, using frozen blood samples taken at time of diagnosis, the researchers measured 25-hydroxyvitamin D by radioimmunoassay. The liver converts circulating endogenous and exogenous vitamin D into this inactive form that reflects total body stores. Vitamin D levels were categorized by standard definition as deficient, insufficient, sufficient, and toxic. At diagnosis, mean vitamin D level was 58 nmol/L. Only 24% of the patients had sufficient levels of vitamin D; 39% had insufficient levels and 38% were deficient in vitamin D. None of the patients had toxic levels.
Higher mean vitamin D levels were associated with age 50 years and older (p = 0.006), obesity (p = 0.004), and use of vitamin D supplements (p < 0.0001; average dose was less than 400 IU daily). Vitamin D levels correlated with dietary intake or consumption of the following: retinol; vitamins B, C, E; riboflavin; grains and cereals; and alcohol (all p < 0.05). An inverse correlation was found between vitamin D and insulin (p < 0.0004).
Regarding tumor characteristics and treatment, low vitamin D levels were associated only with a higher tumor grade (p = 0.03) and adjuvant chemotherapy (p = 0.02). Tumor size, nodal involvement, and estrogen receptor status were not associated with vitamin D level.
Distant disease-free survival was significantly shorter for patients with deficient (versus sufficient) vitamin D levels (hazard ratio (HR) = 1.94, p = 0.02). Adjustment for patient and tumor characteristics had little effect on the hazard ratio.
Overall 10-year survival rates were 74%, 85%, and 85% for patients with deficient, insufficient, and adequate vitamin D, respectively; the hazard ratio was 1.73 (p = 0.02). As with distant disease-free survival, adjustment for patient and tumor characteristics had little effect on the hazard ratio. ER status was not differentially affected by vitamin D deficiency (contrary to the statement in the abstract).
No difference in survival was detected between patients with sufficient and insufficient vitamin D levels so a smoothed log hazard of death curve was plotted across the range of vitamin D levels. The plot was curvilinear, with the lowest hazard at vitamin D levels between 80 and 110 nmol/L, and a trend for increased risk of death at higher levels. For distant disease-free survival, the smoothed log hazard curve exhibited decreased risk across the vitamin D range. Dr. Goodwin said that the different patterns could not be explained and required further study.
Dr. Goodwin noted that the data must be replicated by additional observational studies. If the work is corroborated, before undertaking any randomized trials of vitamin D supplementation, researchers should conduct a survey to establish whether vitamin D deficiency remains a problem in an era of widespread vitamin supplementation. "I believe it is premature to advise patients with breast cancer to use vitamin D supplements in doses higher than that recommended for bone health," said Dr Goodwin.
In discussing Dr. Goodwin"s presentation, Bruce Trock, PhD, of Johns Hopkins University School of Medicine, commented that future research also should determine whether circulating 25-hydroxyvitamin D is a good surrogate for vitamin D activity in the normal and cancerous breast, whether the enzyme that converts the inactive form of vitamin D to the active form varies in breast cancer according to genetic profiles, and whether there is individual variation in serum 25-hydroxyvitamin D.