Archived Comments for:
Cardiovascular disease competes with breast cancer as the leading cause of death for older females diagnosed with breast cancer: a retrospective cohort study
Vitamin D deficiency may contribute to cause of death for those diagnosed with breast cancer
William B. Grant, Sunlight, Nutrition and Health Research Center
1 July 2011
The paper by Patnaik et al. [1] is quite interesting. The conclusion, “Comorbid conditions contribute importantly to both total mortality and breast cancer-specific mortality among breast cancer survivors. Attention to reducing the risk of cardiovascular disease should be a priority for the long-term care of women following the diagnosis and treatment of breast cancer.” is correct, although other cancers, COPD, and diabetes should also be added to the list of diseases to be concerned about.
Missing from the paper, however, is any mention of how to go about reducing the risk of cardiovascular disease (CVD) or any other disease. A rather simple and straight forward approach is available: increase serum 25-hydroxyvitamin D [25(OH)D] levels. There is excellent evidence from ecological [2,3] and observational studies [4-7] that vitamin D deficiency is an important risk factor for breast cancer and other types of cancer [2,3,6]. The discrepancy between case-control and nested case-control studies of breast cancer incidence with respect to serum 25(OH)D level is due to the decrease of the prognostic value of a single serum 25(OH)D level value with increasing time [7,8].
There is also very good observational evidence that vitamin D deficiency is an important risk factor for CVD incidence [9-11] and death [12]. Vitamin D deficiency has also been implicated in COPD [13,14] and diabetes [9,15].
While admittedly these associations have not been confirmed in randomized controlled trials except for all-cancer incidence [16], and not everyone is convinced of the health benefits of vitamin D [17], if the findings are substantially correct, then increasing serum 25(OH)D levels to above 40-45 ng/ml would be the simplest thing that could increase survival after diagnosis of breast cancer [18]. In fact, an 11.6-year follow-up study of those diagnosed with breast cancer in Toronto found a hazard ratio = 1.73 (95% CI, 1.05 to 2.86) for all-cause mortality rate for those with serum 25(OH)D levels <20 ng/ml compared to >30 ng/ml [19]. The Endocrine Society recently released vitamin D guidelines above those recommended by the Institute of Medicine [20]. While additional evidence may be required to fully assess the role of vitamin D in reducing the burden of disease, waiting to change policies on vitamin D the five plus years it will take for results of such studies as VITAL to be announced [21] will very likely subject many people to needless suffering and premature death, including African-Americans, who are more likely than white-Americans to have vitamin D deficiency [22]. There are very few risks associated with increasing serum 25(OH)D levels to 100 ng/ml [23].
References 1. Patnaik JL, Byers T, DiGuiseppi C, Dabelea D, Denberg TD. Cardiovascular disease competes with breast cancer as the leading cause of death for older females diagnosed with breast cancer: a retrospective cohort study. Breast Cancer Research 2011, 13:R64 (20 June 2011) epub 2. Grant WB, Garland CF. The association of solar ultraviolet B (UVB) with reducing risk of cancer: multifactorial ecologic analysis of geographic variation in age-adjusted cancer mortality rates. Anticancer Res. 2006;26:2687-99. 3. Grant WB. Lower vitamin-D production from solar ultraviolet-B irradiance may explain some differences in cancer survival rates. J Natl Med Assoc. 2006;98:357-64. 4. Abbas S, Linseisen J, Slanger T, Kropp S, Mutschelknauss E, Flesch-Janys D, Chang-Claude J. Serum 25-hydroxyvitamin D and risk of postmenopausal breast cancer - results of a large case-control study. Carcinogenesis. 2008;29:93-9. 5. Abbas S, Chang-Claude J, Linseisen J. Plasma 25-hydroxyvitamin D and premenopausal breast cancer risk in a German case-control study. Int J Cancer. 2009;124:250-5. 6. Gandini S, Boniol M, Haukka J, Byrnes G, Cox B, Sneyd MJ, Mullie P, Autier P. Meta-analysis of observational studies of serum 25-hydroxyvitamin D levels and colorectal, breast and prostate cancer and colorectal adenoma. Int J Cancer. 2011;128:1414-24. 7. Grant WB. Effect of interval between serum draw and follow-up period on relative risk of cancer incidence with respect to 25-hydroxyvitamin D level; implications for meta-analyses and setting vitamin D guidelines, Dermato-Dermatology, 2011 July, Aug Sept.;3(3) epub 8. Robien K, Cutler GJ, Lazovich D. Vitamin D intake and breast cancer risk in postmenopausal women: the Iowa Women's Health Study. Cancer Causes Control. 2007;18:775-82. 9. Parker J, Hashmi O, Dutton D, Mavrodaris A, Stranges S, Kandala NB, Clarke A, Franco OH. Levels of vitamin D and cardiometabolic disorders: systematic review and meta-analysis. Maturitas. 2010;65:225-36. 10. Anderson JL, May HT, Horne BD, Bair TL, Hall NL, Carlquist JF, Lappé DL, Muhlestein JB; Intermountain Heart Collaborative (IHC) Study Group. Relation of vitamin D deficiency to cardiovascular risk factors, disease status, and incident events in a general healthcare population. Am J Cardiol. 2010;106:963-8. 11. Lee JH, Gadi R, Spertus JA, Tang F, O'Keefe JH. Prevalence of vitamin d deficiency in patients with acute myocardial infarction. Am J Cardiol. 2011;107:1636-8. 12. Fiscella K, Franks P. Vitamin D, race, and cardiovascular mortality: findings from a national US sample. Ann Fam Med. 2010;8:11-8. 13. Franco CB, Paz-Filho G, Gomes PE, Nascimento VB, Kulak CA, Boguszewski CL, Borba VZ. Chronic obstructive pulmonary disease is associated with osteoporosis and low levels of vitamin D. Osteoporos Int. 2009;20:1881-7. 14. Janssens W, Mathieu C, Boonen S, Decramer M. Vitamin D deficiency and chronic obstructive pulmonary disease: a vicious circle. Vitam Horm. 2011;86:379-99. 15. Boucher BJ. Vitamin D insufficiency and diabetes risks. Curr Drug Targets. 2011;12:61-87. 16. Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr. 2007;85:1586-91. 17. Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, Durazo-Arvizu RA, Gallagher JC, Gallo RL, Jones G, Kovacs CS, Mayne ST, Rosen CJ, Shapses SA. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011;96:53-8. 18. Grant WB. In defense of the sun: An estimate of changes in mortality rates in the United States if mean serum 25-hydroxyvitamin D levels were raised to 45 ng/mL by solar ultraviolet-B irradiance. Dermato-Endocrinology, 2009;1:207-14. 19. Goodwin PJ, Ennis M, Pritchard KI, Koo J, Hood N. Prognostic effects of 25-hydroxyvitamin D levels in early breast cancer. J Clin Oncol. 2009;27:3757-63. 20, Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM. Evaluation, Treatment, and Prevention of Vitamin D Deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab, July 2011, Jun 6. [Epub ahead of print] 21. Manson JE. Vitamin D and the heart: why we need large-scale clinical trials. Cleve Clin J Med. 2010;77:903-10. 22. Grant WB. Peiris AN. Possible role of serum 25-hydroxyvitamin D in Black–White health disparities in the United States. J Am Med Directors Assoc. 2010;11:617-28. 23. Hathcock JN, Shao A, Vieth R, Heaney R. Risk assessment for vitamin D. Am J Clin Nutr. 2007;85:6-18.
Competing interests
Disclosure I receive or have received funding from the UV Foundation (McLean, VA), the Sunlight Research Forum (Veldhoven), Bio-Tech-Pharmacal (Fayetteville, AR), and the Vitamin D Council (San Luis Obispo, CA).
Vitamin D deficiency may contribute to cause of death for those diagnosed with breast cancer
1 July 2011
The paper by Patnaik et al. [1] is quite interesting. The conclusion, “Comorbid conditions contribute importantly to both total mortality and breast cancer-specific mortality among breast cancer survivors. Attention to reducing the risk of cardiovascular disease should be a priority for the long-term care of women following the diagnosis and treatment of breast cancer.” is correct, although other cancers, COPD, and diabetes should also be added to the list of diseases to be concerned about.
Missing from the paper, however, is any mention of how to go about reducing the risk of cardiovascular disease (CVD) or any other disease. A rather simple and straight forward approach is available: increase serum 25-hydroxyvitamin D [25(OH)D] levels. There is excellent evidence from ecological [2,3] and observational studies [4-7] that vitamin D deficiency is an important risk factor for breast cancer and other types of cancer [2,3,6]. The discrepancy between case-control and nested case-control studies of breast cancer incidence with respect to serum 25(OH)D level is due to the decrease of the prognostic value of a single serum 25(OH)D level value with increasing time [7,8].
There is also very good observational evidence that vitamin D deficiency is an important risk factor for CVD incidence [9-11] and death [12]. Vitamin D deficiency has also been implicated in COPD [13,14] and diabetes [9,15].
While admittedly these associations have not been confirmed in randomized controlled trials except for all-cancer incidence [16], and not everyone is convinced of the health benefits of vitamin D [17], if the findings are substantially correct, then increasing serum 25(OH)D levels to above 40-45 ng/ml would be the simplest thing that could increase survival after diagnosis of breast cancer [18]. In fact, an 11.6-year follow-up study of those diagnosed with breast cancer in Toronto found a hazard ratio = 1.73 (95% CI, 1.05 to 2.86) for all-cause mortality rate for those with serum 25(OH)D levels <20 ng/ml compared to >30 ng/ml [19]. The Endocrine Society recently released vitamin D guidelines above those recommended by the Institute of Medicine [20]. While additional evidence may be required to fully assess the role of vitamin D in reducing the burden of disease, waiting to change policies on vitamin D the five plus years it will take for results of such studies as VITAL to be announced [21] will very likely subject many people to needless suffering and premature death, including African-Americans, who are more likely than white-Americans to have vitamin D deficiency [22]. There are very few risks associated with increasing serum 25(OH)D levels to 100 ng/ml [23].
References
1. Patnaik JL, Byers T, DiGuiseppi C, Dabelea D, Denberg TD. Cardiovascular disease competes with breast cancer as the leading cause of death for older females diagnosed with breast cancer: a retrospective cohort study. Breast Cancer Research 2011, 13:R64 (20 June 2011) epub
2. Grant WB, Garland CF. The association of solar ultraviolet B (UVB) with reducing risk of cancer: multifactorial ecologic analysis of geographic variation in age-adjusted cancer mortality rates. Anticancer Res. 2006;26:2687-99.
3. Grant WB. Lower vitamin-D production from solar ultraviolet-B irradiance may explain some differences in cancer survival rates. J Natl Med Assoc. 2006;98:357-64.
4. Abbas S, Linseisen J, Slanger T, Kropp S, Mutschelknauss E, Flesch-Janys D, Chang-Claude J. Serum 25-hydroxyvitamin D and risk of postmenopausal breast cancer - results of a large case-control study. Carcinogenesis. 2008;29:93-9.
5. Abbas S, Chang-Claude J, Linseisen J. Plasma 25-hydroxyvitamin D and premenopausal breast cancer risk in a German case-control study. Int J Cancer. 2009;124:250-5.
6. Gandini S, Boniol M, Haukka J, Byrnes G, Cox B, Sneyd MJ, Mullie P, Autier P. Meta-analysis of observational studies of serum 25-hydroxyvitamin D levels and colorectal, breast and prostate cancer and colorectal adenoma. Int J Cancer. 2011;128:1414-24.
7. Grant WB. Effect of interval between serum draw and follow-up period on relative risk of cancer incidence with respect to 25-hydroxyvitamin D level; implications for meta-analyses and setting vitamin D guidelines, Dermato-Dermatology, 2011 July, Aug Sept.;3(3) epub
8. Robien K, Cutler GJ, Lazovich D. Vitamin D intake and breast cancer risk in postmenopausal women: the Iowa Women's Health Study. Cancer Causes Control. 2007;18:775-82.
9. Parker J, Hashmi O, Dutton D, Mavrodaris A, Stranges S, Kandala NB, Clarke A, Franco OH. Levels of vitamin D and cardiometabolic disorders: systematic review and meta-analysis. Maturitas. 2010;65:225-36.
10. Anderson JL, May HT, Horne BD, Bair TL, Hall NL, Carlquist JF, Lappé DL, Muhlestein JB; Intermountain Heart Collaborative (IHC) Study Group. Relation of vitamin D deficiency to cardiovascular risk factors, disease status, and incident events in a general healthcare population. Am J Cardiol. 2010;106:963-8.
11. Lee JH, Gadi R, Spertus JA, Tang F, O'Keefe JH. Prevalence of vitamin d deficiency in patients with acute myocardial infarction. Am J Cardiol. 2011;107:1636-8.
12. Fiscella K, Franks P. Vitamin D, race, and cardiovascular mortality: findings from a national US sample. Ann Fam Med. 2010;8:11-8.
13. Franco CB, Paz-Filho G, Gomes PE, Nascimento VB, Kulak CA, Boguszewski CL, Borba VZ. Chronic obstructive pulmonary disease is associated with osteoporosis and low levels of vitamin D. Osteoporos Int. 2009;20:1881-7.
14. Janssens W, Mathieu C, Boonen S, Decramer M. Vitamin D deficiency and chronic obstructive pulmonary disease: a vicious circle. Vitam Horm. 2011;86:379-99.
15. Boucher BJ. Vitamin D insufficiency and diabetes risks. Curr Drug Targets. 2011;12:61-87.
16. Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr. 2007;85:1586-91.
17. Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, Durazo-Arvizu RA, Gallagher JC, Gallo RL, Jones G, Kovacs CS, Mayne ST, Rosen CJ, Shapses SA. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011;96:53-8.
18. Grant WB. In defense of the sun: An estimate of changes in mortality rates in the United States if mean serum 25-hydroxyvitamin D levels were raised to 45 ng/mL by solar ultraviolet-B irradiance. Dermato-Endocrinology, 2009;1:207-14.
19. Goodwin PJ, Ennis M, Pritchard KI, Koo J, Hood N. Prognostic effects of 25-hydroxyvitamin D levels in early breast cancer. J Clin Oncol. 2009;27:3757-63.
20, Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM. Evaluation, Treatment, and Prevention of Vitamin D Deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab, July 2011, Jun 6. [Epub ahead of print]
21. Manson JE. Vitamin D and the heart: why we need large-scale clinical trials. Cleve Clin J Med. 2010;77:903-10.
22. Grant WB. Peiris AN. Possible role of serum 25-hydroxyvitamin D in Black–White health disparities in the United States. J Am Med Directors Assoc. 2010;11:617-28.
23. Hathcock JN, Shao A, Vieth R, Heaney R. Risk assessment for vitamin D. Am J Clin Nutr. 2007;85:6-18.
Competing interests
Disclosure
I receive or have received funding from the UV Foundation (McLean, VA), the Sunlight Research Forum (Veldhoven), Bio-Tech-Pharmacal (Fayetteville, AR), and the Vitamin D Council (San Luis Obispo, CA).