associated with breast cancer.
Whether these patients
can be considered to have suffered from vitamin D toxic-
ity is a matter of some contention. It could be argued that
neither patient developed treatment toxicity, as treatment
simply exposed a pre-existing condition rather causing
direct toxicity. However, in view of the increased preva-
lence of hyperparathyroidism among breast cancer
this limitation in the administration of high-
dose vitamin D needs to be highlighted, despite it having
been described previously.
Furthermore, although the
results of this study do not support high-dose supplemen-
tation, many patients choose to supplement with signifi-
cant doses of vitamin D on their own accord. Patients
considering supplementation above currently recom-
mended levels should be made aware of the possible toxic-
ities of treatment with vitamin D, and baseline calcium
and PTH should be ascertained. Clinicians should also be
aware of described toxicities from high doses of vitamin
D. These have been comprehensively described in the lit-
erature and include hypercalcemia, hypercalciuria, neph-
rocalcinosis, and even renal impairment.
In summary, although this study did not meet its
primary endpoint of demonstrating significant changes in
pain or bone turnover markers, the effects of high physio-
logic doses of vitamin D did show some indication of clin-
ical benefit, as manifested by a reduction in the number of
sites of pain. Furthermore, this therapy helped unmask
underlying endocrinopathy, specifically primary hyper-
parathyroidism. Interestingly, there was also an apparent
correction of the presumed secondary hyperparathyroid-
ism in this heavily bisphosphonate-pretreated population,
and the role of higher doses of vitamin D for this purpose
warrants further investigation. The results of this study
therefore lend some support to the notion that there is an
overall need for higher-dose vitamin D supplementation
in metastatic breast cancer with bone metastases. Further
trials will help clarify the optimal dose of supplementation
in this population, but should screen and follow diligently
for masked hyperparathyroid states.
CONFLICT OF INTEREST DISCLOSURES
This study was funded in part by a grant from the Vitamin D
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