Dietary Supplements and Br Ca tx

[Guest guest]

The evidence continues to be unclear as to whether dietary supplements are

helpful or harmful during cancer treatment. Many clinicians recommend that

vitamin supplements — and in particular, high doses of antioxidants — not be

used while therapy is ongoing because of concerns that they might reduce the

efficacy of radiation and chemotherapy.

However, a new study finds no evidence that the use of vitamins during first

6 months after a diagnosis of breast cancer adversely affected outcomes. In

fact, it found quite the opposite: vitamin use appeared to have a beneficial

effect among patients with breast cancer who underwent chemotherapy.

Vitamin use — and the use of vitamins C and E in particular — appeared to be

associated with reduced risk for mortality and recurrence.

The study was published online December 21 in *Cancer Epidemiology,

Biomarkers & Prevention*.

Patients who used antioxidants (vitamin E, vitamin C, multivitamins) had an

18% reduction in their mortality risk (hazard ratio (HR), 0.82; 95%

confidence interval [CI], 0.65 - 1.02), and the risk for recurrence was

decreased by 22% (HR, 0.78; 95% CI, 0.63 - 0.95). This association was

observed whether vitamin use was concurrent or nonconcurrent with

chemotherapy. However, this benefit was only seen in patients who did not

receive radiotherapy.

Although complete information was not available for dosages taken,

approximately 85% of vitamin C users took 400 mg/day or less, and 99% of

vitamin E users took 400 mg/day or less.

*Helpful or Harmful?*

" The recommendation to avoid supplements during cancer treatment is based on

the concern that antioxidant supplements may protect tumor cells during

radiotherapy and chemotherapy, thereby reducing the effectiveness of cancer

treatments and potentially increasing risk of mortality and cancer

recurrence, " said Xiao Ou Shu, MD, MPH, PhD, lead author of the study and a

professor of medicine at Vanderbilt University School of Medicine,

Nashville, Tennessee.

Dr. Shu pointed out that the evidence to support this concern is largely

based on laboratory studies and on 1 randomized controlled clinical trial of

540 patients with head and neck cancer. That randomized trial reported that

risk for all-cause mortality was increased among participants who were given

supplements and who smoked during radiotherapy.

" On the other hand, there is also evidence that antioxidant supplements may

help protect normal cells from oxidative damage that occurs during cancer

treatment, and thereby reduce the short- and long-term harmful effects of

cancer treatment, " Dr. Shu told *Medscape Medical News*.

A number of studies have evaluated the use of antioxidant supplements in the

primary prevention <http://www.medscape.com/viewarticle/586083> of

cancer<http://www.medscape.com/viewarticle/582788>.

As previously reported <http://www.medscape.com/viewarticle/720853> by

*Medscape

Medical News*, 2 studies that examined the use of multivitamins and breast

cancer risk came to very different conclusions: One study found that their

use decreased the risk for breast cancer, and the other study showed that

vitamin supplementation actually increased the risk for breast cancer.

The use of vitamin supplements is common among patients with breast cancer,

but very few studies have investigated the role of vitamin supplement use

during treatment and prognosis. " To our knowledge, our study is the first

large prospective cohort study to investigate whether regular doses of

vitamin supplement during cancer treatment influences breast cancer

prognosis, " Dr. Shu commented. " It should be noted that in our study, most

breast cancer patients took a regular dose of vitamin supplement, while the

above-mentioned head-neck cancer clinical trial investigated megadose

vitamin supplements. "

*Opens Door for Discussion*

This latest study is squarely at the heart of an ongoing controversy in

integrative oncology, commented Hardy, MD, medical director of the

Simms/Mann University of California–Los Angeles Center for Integrative

Oncology. " There are theoretical concerns with antioxidants that they can be

harmful, while this paper says that there are beneficial. But even if you

read this paper conservatively, " she said, " it doesn't appear that

antioxidants interfered with outcomes. "

In an interview, Dr. Hardy noted that the study does have significant

limitations — the primary one being that it is not a randomized trial. The

study was also conducted in a population of women in Shanghai, China, so

there may be issues such as diet, culture, genetics, and so forth that could

affect outcome.

" But the most important aspect of this paper is that it begins to

suggest...what a lot of us in integrative oncology have been saying,...that

the monolithic absolute rejection of all antioxidants is probably not going

to be supported by the literature, " said Dr. Hardy.

The risks have always been theoretical, and many patients with cancer are

using supplements, she explained. " And in many cases, when physicians would

say not to use them, patients would just continue anyway and then not tell

their physician. "

The current study " allows physicians some degree of comfort, or to better

tolerate some things that they may not have been comfortable with, " Dr.

Hardy told *Medscape Medical News*. " Patients really don't like absolutes,

and this allows doctors to have a much more nuanced discussion about the

subject. "

However, it remains a complicated issue, and this study does not settle the

question, she added.

Dr. Shu agrees. " Results from single observational study are not adequate to

change the guidelines of vitamin use during cancer treatment, " she said.

" However, our study calls for more studies on this particular question,

particularly in different settings and populations. "

*Lower Risk for Mortality and Recurrence*

In this study, Dr. Shu and colleagues evaluated the associations of total

mortality and breast cancer recurrence with vitamin supplement use in a

population-based prospective cohort study of 4877 women diagnosed with

invasive breast cancer. The study was conducted in Shanghai, China, between

March 2002 and April 2006, and patients were interviewed approximately 6

months after their diagnosis.

At an average of 4.1 years of follow-up (range, 0.5 - 6.2 years), 444 women

had died (389 from breast cancer, 55 from other causes). A total of 4325

patients remained disease free during the follow-up period, and 532

experienced a disease recurrence.

Of the breast cancer survivors, approximately 36.4% ever used any type of

vitamin supplement after their diagnosis. Vitamin C was the most commonly

used (17.5%), followed by B vitamins (16.3%), vitamin E (7.6%), vitamin A

(1.7%), and vitamin D (0.4%). In addition, about 11% reported using

multivitamins.

Vitamin users tended to have higher levels of education, income, daily

intake of cruciferous vegetables, and soy protein and were more likely to

have a lower body mass index. They were also more likely to be nonsmokers

and to report consumption of tea and regular exercise.

The use of vitamins also did not significantly vary as far as age at

diagnosis, joint estrogen receptor and progesterone receptor tumor status,

TNM stage, type of cancer treatment (chemotherapy, radiotherapy, tamoxifen

use), number of pregnancies, family history of breast cancer, alcohol

intake, or meat intake.

Overall, use of vitamins within the first 6 months of cancer diagnosis

(including any vitamins, multivitamins, vitamin E alone, vitamin C alone,

and any antioxidants) was associated with a lower risk for total mortality

and breast cancer recurrence, with the largest risk reduction observed in

patients who used vitamins C or E for a longer duration after diagnosis.

More specifically, the authors note, women who used vitamin C for more than

3 months had a 44% decrease in risk for mortality (adjusted HR, 0.56; 95%

CI, 0.37 - 0.87) and a 38% decrease in risk for disease recurrence (adjusted

HR, 0.62; 95% CI, 0.43 - 0.90).

On a similar note, women who used vitamin E for more than 3 months had a

reduced risk for both mortality (adjusted HR, 0.52; 95% CI, 0.27 - 1.01) and

recurrence (adjusted HR, 0.57; 95% CI, 0.32 - 1.01), although point

estimates were of marginal statistical significance.

*Associations With Radiotherapy*

The researchers also investigated the effect of radiotherapy (which was used

in about one third of women) on the outcomes seen with vitamin use.

Among the women who did not receive radiotherapy (n = 3280), vitamin use was

associated with a lower risk for both mortality and recurrence. This

association was the strongest observed for use of any antioxidant (adjusted

HR for mortality, 0.65; 95% CI, 0.47 - 0.92; adjusted HR for recurrence,

0.63; 95% CI, 0.46 - 0.86).

Patients who used vitamins and did not receive radiotherapy were at reduced

risk for mortality (adjusted HR, 0.67; 95% CI, 0.48 - 0.94) and recurrence

(adjusted HR, 0.66; 95% CI, 0.49 - 0.89) compared with those who did not

receive radiotherapy or use vitamins.

Women who did undergo radiotherapy (n = 1597) showed slightly worse

outcomes, but the results were not statistically significant. Women who

underwent radiotherapy and who did not take antioxidant vitamins were at

nonsignificant increased risk for mortality (adjusted HR, 1.26; 95% CI, 0.92

- 1.72) and recurrence (adjusted HR, 1.26; 95% CI, 1.00 - 1.57).

Similarly, patients treated with radiotherapy and who used antioxidant

vitamins also had nonsignificant increased risk for mortality (adjusted HR,

1.27; 95% CI, 0.99 - 1.64) and recurrence (adjusted HR, 1.17; 95% CI, 0.88 -

1.54).

*The study was funded by grants from the Department of Defense Breast Cancer

Research Program and the National Cancer Institute. The authors have

disclosed no relevant financial relationships.*

*Cancer Epidemiol Biomarkers Prev*. Published online December 21, 2010.

www.medscape.com (free registration required)

--

Ortiz, MS, RD

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