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Vitamin D and

Breast Cancer
Prevention
Practical
Guidelines
for
Clinicians

Tara Bergren, MS, RD


Roschelle Heuberger, PhD, RD
Vitamin D deficiency has been hypothetically linked to a number of
diseases (Gissel, Rejnmark, Mosekilde, & Vestergaard, 2008), including
cancer (Grant, 2002, 2003), and recent research has shown that adequate
amounts of vitamin D may help prevent breast cancer (Crew et al., 2009).
One theory regarding the protective properties of vitamin D centers on the
biologically active form of the vitamin, 1,25 dihydroxyvitamin D. Vitamin
D is converted to this active form mostly in the kidneys, but also in target
tissues, such as breast tissue (Tangpricha et al., 2001; Zehnder et al., 2001). In
addition, data from clinical studies suggest that the biologically active form of
vitamin D prevents rapid cell growth in breast tissue that could lead to cancer
(Christakos, Ravil-Pandya, Wernyj, & Yang, 1996; Danielsson et al., 1997;
Love-Schimenti, Gibson, Ratnam, & Bikle, 1996). When a woman is deficient
in vitamin D these effects are limited, which may increase her risk of
cancer. The focus of this article is to provide practical guidelines for
clinicians regarding vitamin D deficiency and breast cancer risk.
Vitamin D: tHe BasiCs 2005; Zinser & Welsh, 2004). An animal study conducted in
Vitamin D comprises a group of fat-soluble compounds found 2008 examined whether supplementing a Western diet with
naturally only in a few foods, including fish-liver oils, fatty fish, increased vitamin D and calcium would have an effect on the
mushrooms, egg yolks and liver. The two major physiologi- mammary glands of mice (Kurihara, Fan, Thaler, Yang, & Lip-
cally relevant forms of vitamin D are D2 (ergocalciferol) and kin, 2008). The mice fed the standard Western diet showed an
D3 (cholecalciferol). Vitamin D3 is photosynthesized in the skin accumulation of cells in ducts of the mammary gland and in-
of vertebrates by ultraviolet B (UVB) radiation on a precursor creased duct cell growth (see Box 1). Additional animal studies
(7-dehydrocholesterol); vitamin D2 is produced by UV irradia- provided similar findings (Lipkin & Newmark, 1999).
tion of ergosterol, which occurs in molds, yeast and higher-or- Over the past decade, most of the research on vitamin D
der plants. Vitamin D from either source circulates in the blood and breast cancer has been done using case-control and cohort
for 1 to 2 days, and is then stored in fat cells or metabolized in studies. A recent large, population-based case-control investi-
the liver. In the liver, it is converted to 25-hydroxyvitamin D, gation by Crew et al. (2009) examined the association between
which must be further activated in the kidneys (and to a small levels of 25-hydroxyvitamin D and breast cancer incidence.
extent in the breast and other tissues) to 1,25-dihydroxyvita- The study utilized in-person interviews and blood samples
min D. This is the form thought to be responsible for most, if of 25-hydroxyvitamin D from more than 1,000 breast cancer
not all, of the biologic functions of vitamin D. cases and controls. Women with 25-hydroxyvitamin D levels
Active vitamin D functions as a hormone, and its main above 40 ng/mL were less likely to develop breast cancer than
function is to maintain serum calcium and phosphorus con- women with a vitamin D deficiency, defined as 25-hydroxyvi-
centrations within the normal range by enhancing the efficien- tamin D levels <20 ng/mL—suggesting that optimal levels of
25-hydroxyvitamin D for breast cancer prevention may be ≥40
ng/mL (Crew et al.). Other studies have also provided evidence
Bottom Line of an inverse relationship between active vitamin D levels and
• Recent research suggests breast cancer risk (John, Schwartz, Dreon, & Koo, 1999; Mc-
an inverse association between vitamin D intake Cullough et al., 2005; Nunez, Carbajal, Belmonte, Moreiras, &
and breast cancer risk. Varela, 1996; Shin et al., 2002).
• Current recommendations for vitamin D intake Lin et al. (2007) used a prospective study to evaluate the
are likely too low with regard to chemoprevention. association between calcium and vitamin D relative to breast
cancer occurrence in pre- and postmenopausal women. The
• Strategies for increasing vitamin D intake include
women were at least 45 years old and did not have cancer at
the consumption of fatty fish and fortified foods,
supplementation and sensible exposure to sunlight. the beginning of the study. Food frequency questionnaires were
used to assess dietary intake. The premenopausal women who
consumed more calcium and vitamin D were found to have a
lower risk of premenopausal breast cancer. This inverse rela-
cy of the small intestine to absorb these minerals from the diet. tionship was not seen in the postmenopausal women. Another
While it’s too early to draw any definitive conclusions, the vi- study found that women were less likely to die of breast cancer
tamin that was once best known for building strong bones also if they had 25-hydroxyvitamin D levels ≥25 ng/mL (Garland,
appears to be associated with a number of cancers, as well as Gorham, Baggerly, & Garland, 2008).
cognitive changes, autoimmune diseases and the development
of heart disease (Nagpal, Na, & Rathnachalam, 2005). CUrrent Vitamin D reCommenDations
Recommendations for vitamin D intake are available as Dietary
WHat tHe Data teLL Us aBoUt CanCer Reference Intakes (DRI), published by the Institute of Medicine
Animal research provided initial evidence for the inverse as- of the National Academies (Institute of Medicine [IOM], 1997).
sociation between vitamin D and breast cancer. Removal of the From birth to age 50, the adequate intake (AI) is 200 interna-
vitamin D receptor caused an abnormal increase in breast cells tional units (IU) with no increased need during pregnancy or
in studies conducted on animals (Zinser, Suckow, & Welsh, lactation. The AI increases to 400 IU for adults over age 50 and
to 600 IU for those over 70 years of age. However, recent re-
Tara Bergren, MS, RD, is a clinical dietitian and diabetes educator at search suggests that levels of vitamin D above 400 IU may aid
Mercy Hospital in Cadillac, MI. Roschelle Heuberger, PhD, RD, is a in prevention of breast cancer. A meta-analysis by Gissel et al.
professor at Central Michigan University in Mount Pleasant, MI. The (2008) reviewed studies that contained original data on the as-
authors report no conflicts of interest or relevant financial relationships.
There is no discussion of off-label drug or device use in this article. sociation between vitamin D intake and breast cancer risk. The
Address correspondence to: taraj711@hotmail.com. researchers concluded that although there appears to be a trend
DOI: 10.1111/j.1751-486X.2010.01575.x toward a lower incidence of breast cancer with increased intake

370 © 2010, AWHONN http://nwh.awhonn.org


of vitamin D ≥400 IU/day, many of the studies included in the
meta-analysis were of poor quality.
To date, the exact amount of vitamin D needed for chemo-
prevention is still unknown. However, some experts believe that Monitoring vitamin D should
at least 1,000 IU/day is needed by most adults (Holick, 2008).
Currently, the tolerable upper intake levels (ULs) are 1,000 IU become the standard
from birth to 12 months and 2,000 IU for all others. The IOM
defines the UL as “the maximum level of daily nutrient intake
of care among primary
that is likely to pose no risk of adverse effects” (IOM, 1997). care practitioners
WHo’s at risK?
Monitoring vitamin D should become the standard of
care among primary care practitioners. Measurement of GettinG enoUGH Vitamin D
25-hydroxyvitamin D is the best indicator of one’s overall Food Sources
vitamin D status (Moyad, 2009) as it reflects vitamin D levels Helping patients achieve optimal vitamin D status requires that
in the body from all sources, including diet, supplements, and they understand the various sources of vitamin D, starting with
sunlight (Moyad; Rajakumar, Greenspan, Thomas, & Holick, food sources (see Box 2). Very few foods in nature contain vi-
2007). The test should ideally be ordered in the winter when tamin D. The flesh of fish (such as salmon, tuna, and mack-
vitamin D levels are typically lower due to limited sun exposure erel) and fish liver oils are among the best sources, with small
(Moyad). There is currently disagreement about the lower limit amounts of vitamin D found in beef liver and egg yolks.
of optimal vitamin D levels, but most experts believe that levels Fortified foods provide most of the vitamin D in the Ameri-
lower than 20 ng/mL are undesirable and that the lower limit can diet. For example, almost all of the U.S. milk supply is
is likely <30 ng/mL (Weng, Shults, Leonard, Stallings, & Zemel, fortified with 100 IU/cup of vitamin D (50 percent of the AI
2007). Note that the IOM has defined vitamin D deficiency as a level for ages 14-50 years). Other dairy products made from
concentration less than 12 ng/mL (IOM, 1997). milk, such as cheese and ice cream, are generally not fortified.
Those at risk for vitamin D deficiency include older adults, Ready-to-eat breakfast cereals may contain added vitamin D,
those with limited sun exposure, individuals with dark skin, as do some brands of orange juice, yogurt, and margarine. In
people with fat absorption disorders and individuals with a the United States, foods allowed to be fortified with vitamin D
body mass index (BMI) ≥30 (Vilarrasa et al., 2007). In women, include cereal flours and related products, milk and products
the risk for breast cancer should also be taken into account. made from milk, and calcium-fortified fruit juices and drinks.
The Breast Cancer Risk Assessment Tool may also be useful in Maximum levels of added vitamin D are specified by law.
determining current risk for breast cancer. The tool was devel-
oped at the National Cancer Institute as part of the National Sunlight
Surgical Adjuvant Breast and Bowel Project and is useful in de- Sunlight is another source of vitamin D. Known for years as the
termining breast cancer risk (see Get the Facts). “sunshine vitamin,” vitamin D is partially activated when UVB

BOX 1
Measurements of Epithelial Cells in Ducts
Western Diet With Increased
Western Diet With Increased Calcium and Vitamin D as
Calcium and Vitamin D in Dried Elemental Calcium Carbonate
Diet group Western Diet—Mean Yogurt Powder—Mean and Vitamin D3—Mean
Small 13.6 10.6 11.1
Medium 28.8 24.6 25.0
Large 95.4 80.0 78.4
Average 33.2 27.4 27.8

Source: Kurihara et al. (2008).

October November 2010 Nursing for Women’s Health 371


radiation from sunlight hits cholesterol compounds in the skin, Past studies have shown that some sun exposure may be a
converting them to vitamin D precursors. These precursors beneficial approach to preventing breast cancer. An inverse re-
travel to the liver and kidneys, where they are converted to the lationship has been found between sunlight exposure and death
active form of vitamin D. The total amount of vitamin D synthe- from breast cancer (Garland, Garland, Gorham, & Young,
sized depends not only on sun exposure, but also on the season 1990). Another study showed that breast cancer incidence de-
(winter is less desirable than summer), skin color (darker tones creased as sun exposure increased (Gorham, Garland, & Gar-
absorb less UVB) and residence (the farther from the equator, land, 1990). Recent research shows similar findings. Data from
the less UVB is available). In fact, North Americans who live the Women’s Health Initiative Observational Study (WHIOS)
north of 42 degrees latitude—which would include residents of showed that women who reported limited sun exposure were
Boston, Milwaukee and Seattle—don’t get enough UVB from 20 percent more likely to have breast cancer compared with
roughly mid-October to mid-March, regardless of how much those who spent much time outside each day (Millen et al.,
time they spend outdoors (Looker, Dawson-Hughes, Calvo, 2009).
Gunter, & Sayhoun, 2002). Another recent study looking at large groups of people
According to Moyad (2009), a 21-year-old who spends 15 to found an inverse relationship between high levels of UVB
20 minutes exposed to summer UVB rays will produce 10,000 rays and age-standardized breast cancer rates in 107 countries
IU of vitamin D; continued exposure beyond 20 minutes will (Mohr, Garland, Gorham, Grant, & Garland, 2008). These re-
not produce additional vitamin D. This assumes that the sun search conclusions are supported by others as well, who agree
exposure occurs without sunscreen, as even low levels of sun that the minimum requirement to maintain a circulating level
protection factor in sunscreen may block the synthesis of vi- of 25-hyroxyvitamin D of more than 20 ng/mL is 1,000 IU/
tamin D. Other factors that affect the skin’s ability to produce day, a level that is difficult to achieve from diet alone (Holick,
vitamin D include age, skin color, latitude, time of day, season, 2008). But even this level is well below the >40 ng/mL thought
and cloud/pollution cover (Litchford, 2009). to be necessary for chemoprevention. While 15 to 20 minutes

BOX 2
Selected Food Sources of Vitamin D
Food IU per serving Food IU per serving
Cod liver oil, 1 tablespoon 1,360 Sardines, canned in oil, drained, 46
Salmon (sockeye), cooked, 3oz 794 2 sardines

Mushrooms that have been 400 Liver, beef, cooked, 3.5oz 46


exposed to ultraviolet light to Ready-to-eat cereal, fortified 40
increase vitamin D, 3oz with 10% of the DV for vitamin D,
(not yet commonly available) 0.75 to 1 cup (more heavily
Mackerel, cooked, 3oz 388 fortified cereals might provide
more of the DV)
Tuna fish, canned in water, 154
drained, 3oz Egg, 1 whole (vitamin D is found 25
in yolk)
Milk, nonfat, reduced fat, and 115 to 124
whole, vitamin D-fortified, 1 cup
Orange juice fortified with 100
vitamin D, 1 cup (check product
labels, as amount of added
vitamin D varies)
Yogurt, fortified with 20% of 80
the DV for vitamin D, 6oz
(more heavily fortified yogurts
provide more of the DV)
IU = International Units DV = Daily Value
Margarine, fortified, 1 tablespoon 60
Source: U.S. Department of Agriculture,
Agricultural Research Service (2010).

372 Nursing for Women’s Health Volume 14 Issue 5


Patients should be advised that a circulating level of 40 ng/
Fortified foods mL 25-hydroxyvitamin D may be required to prevent diseases
such as breast cancer. You should explain the importance of sun
provide most of the exposure to the patient, including information about the fact
vitamin D in the that 15 to 20 minutes of sun exposure (without sunscreen) is
desirable. This exposure should be in direct sunlight and in-
American diet clude exposure to the face and arms. It is also important to ex-
plain that vitamin D production should not extend beyond 20
minutes and that lengthy sun exposure may increase the risk of
skin cancer.
If sun exposure is not possible, vitamin D intake from diet
and supplementation will be required. It might be necessary to
prescribe levels as high as 50,000 IU once per week for 6 to
8 weeks if a mild to moderate deficiency (8-12 ng/mL) is ob-
served. The prescription may be increased to twice per week for
a severe deficiency (<8 ng/mL) (Litchford, 2009). When pre-
scription strength vitamin D is taken for any period of time, the
patient should be monitored for signs of toxicity (Joshi, 2009)
(see Box 3). Signs and symptoms of vitamin D toxicity are listed
in Box 4. Follow-up blood tests should be obtained to monitor
vitamin D status and further recommendations made accord-
ingly. Once an individual reaches the desired level, a mainte-
nance dose of 800 to 1,400 IU may be given (Shils, et al., 2005).
This can come from a multivitamin with 400 IU plus 400 to
of daily sun exposure may be of benefit, it is important not to 1,000 IU from an additional vitamin D supplement.
forget other issues such as the risk of skin cancer. It’s important
to balance the risks versus the benefits and consider all factors. ConCLUsion
Much of the research currently supports vitamin D deficiency
Supplementation as a risk factor for breast cancer. However, more tightly control-
When considering supplementation, the amount of vitamin led randomized clinical trials are needed to substantiate this as-
D obtained from other sources such as diet and sun exposure sociation. Areas for further research include investigation into
should be taken into account. While both vitamin D2 and D3 the amount of vitamin D needed to have a protective benefit
are available as over-the-counter supplements, D3 is the pre- against breast cancer, differential protective effects by source
ferred form for supplementation as it is better able to bind the of vitamin D and alterations in risk stemming from chemical
receptors in human tissue and is more effective at elevating and isoforms of vitamin D. As this is a public health concern, the
maintaining blood levels (Moyad, 2009). Of note is that vita-
min D2 is the only form available by prescription in the United
States (Holick, 2007). BOX 3
Dietary Reference Intake
Patient reCommenDations for Vitamin D
The IOM is currently conducting a review of the DRIs for vi-
tamin D and calcium. Until then, clinicians should use their Age Group (Years) Adequate Intake
judgment about prescribing supplements based on the patient’s
medical history, current 25-hydroxyvitamin D level, and cur- 0 to 1 200 IU or 5 mcg
rent disease state (i.e., people with conditions that interfere 2 to 50 200 IU or 5 mcg
with fat absorption may have higher needs). Risk for cancer 51 to 70 400 IU or 10 mcg
and the tolerable UL for vitamin D should also be considered > 70 600 IU or 15 mcg
when making any recommendations. If a patient is tested and
1 mcg = 40 IU.
found to be vitamin D deficient, then a health care practitioner
might prescribe a dose well above the UL, monitor the patient Source: Institute of Medicine of the National Academies (2010).
for signs of toxicity, check blood levels and adjust the dose as
needed (see Box 3).

October November 2010 Nursing for Women’s Health 373


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