The document summarizes two studies on the relationship between calcium, vitamin D, and breast cancer risk. The first study found that higher intakes of calcium and vitamin D were associated with lower breast cancer risk in premenopausal women but not postmenopausal women. The second study examined long-term dietary calcium intake in a cohort of Swedish women and found that higher calcium intake was associated with a 34% lower risk of developing estrogen receptor-negative and progesterone receptor-negative breast cancer. Both studies provide evidence that calcium and vitamin D may reduce breast cancer risk, particularly for hormone receptor-negative breast cancers, though more research is still needed.
2. Breast Cancer
Breast cancer refers to a malignant tumor that has
developed from cells in the breast
Cells of the lobules
Milk producing glands
Ducts
Passages that drain milk from the lobules to the nipple
Less commonly:
Stromal tissues, which include the fatty and fibrous connective
tissues of the breast.
3. What are the symptoms?
Swelling of all or part of the breast
Skin irritation or dimpling
Breast pain
Nipple pain or the nipple turning inward
Redness, scaliness, or thickening of the
nipple or breast skin
Nipple discharge other than breast milk
Lump in the underarm area
4. Overview of Vitamin D
Role in serum calcium homeostasis – acts to
increase or decrease serum calcium levels
Also aids in calcium homeostasis in other
areas such as bone, kidney, intestine, etc.
Helps to maintain/control normal cell
growth, differentiation, and proliferation
5. Overview of Calcium
Calcium plays a regulatory role in cell proliferation,
differentiation, and apoptosis
Experimental studies show that Calcium intake is
related to:
An inverse relationship with mammographic breast density
Decreased fat-induced epithelial hyperproliferation of the
mammary gland and chemically-induced mammary
carcinogenesis in rodents
Reduced amount of breast cancer precursors in epidemiologic
studies
6. Study 1: Intakes of Calcium and Vitamin
D and Breast Cancer Risk in Women
Background
Increasing Calcium and Vitamin D intake in female mice led
to regression in mammary tumors.
Evaluation of Calcium and Vitamin D intake
Subjects were divided into groups
10,578
Premenopausal women
20,909 Post menopausal women
45 years or older
7. Dietary Assessment
Food frequency questionnaire
Average
use of food and beverages past 12
months
Calcium and Vitamin D intakes included
sources from both Diets and Supplements
8. Ascertainment of Breast Cancer Cases
Follow up questionnaires on whether breast cancer
was diagnosed
Every 6 months for first year
Annually after first year
Medical records attained to confirm
diagnosis/death
Average 10 year follow-up of incident invasive
breast cancer
276 premenopausal women diagnosed
743 post menopausal women diagnosed
10. Results
Relation to function:
Premenopausal
women
Higher intakes of total Calcium & Vitamin D
were associated with lower risk of breast cancer
Postmenopausal women
No association between calcium/Vitamin D
levels and risk of breast cancer
Possible explanation: relationship between
Calcium, Vitamin D, and IGFs
11. Discussion
Calcium, Vitamin D, and IGFs:
Suggestion
that Calcium & Vitamin D have
anti-cancer effects on breast cancer cells
expressing high levels of IGF-1 & IGF
binding protein 3
Promote growth inhibition
IGF levels decline with age
12. Discussion
Strengths
Weaknesses
Large sample size
Possible confound
Prospective design
Nutrient intake only
Long duration
assessed once
Vitamin D intake from
sunlight exposure
High follow-up rates
13. Study 2: Long-term dietary calcium intake
and breast cancer risk in a prospective cohort of women
To examine the potential association
between Calcium intake and breast
cancer risk and whether this
association varies by ER/PR status of
the breast tumor
14. Subjects and Methods
Swedish Mammography Cohort
Population-based cohort of 61,433 women cancer-
free at baseline
Enrollment: 1987-1990
Two questionnaires:
Baseline
1997
Case ascertainment for ER/PR status
Pathology labs, Clinical databases
15. Results
17.4 year follow up on average 4.81% developed
invasive breast cancer
Of these cases:
62.4% ER+/PR+
20.2% ER+/PR 12.9% ER-/PR 4.5% ER-/PR+
Adjustments made for:
Dietary Vitamin D
Conjugated Linoleic Acid intake
17. Results
Highest Calcium Intake
34% less likely to develop ER-/PR- breast cancer
Overall Calcium Intake
Decreased receptor-negative species of breast cancer
However, association was not statistically significant
18. Discussion
Strengths
Weakness
Prospective and
Dietary intake was self-
population based
design
Large sample size
Detailed info on diet
Info on hormone
receptor status
administered FFQ
Confounding variables
19. Conclusion
Nutrient Mechanisms:
Calcium absorption is positively correlated with vitamin D
intake
Vitamin D works inversely with estrogen receptors (ERs) and
progesterone receptors (PRs), and actually has its own
receptors (VDRs) in mammary glands/tissue
Apart from its role in aiding calcium absorption, the
receptors for vitamin D found here could indicate a bigger
part in preventing cancer
This facet needs further research for conclusive evidence
20. Cohort: designed to show incidence; best for predicting risk
factors in research, based on exposure or no exposure
Pros
Cons
Easier to administer
Hard to identify
Cheaper than
controls
Blinding is difficult
Recall &/or volunteer
bias
conducting a
Randomized Control
Study (RCT)