Breast cancer patients ask me about specific dietary supplements to use during their journey through cancer quite a bit. One of the complaints I hear sometimes is that patients’ physicians are exceedingly vague in rendering nutrition advice, many discourage the use of dietary supplements during chemotherapy, and then there are those who advocate the use of nutritional supplements during chemotherapy. So what is a person to do? Look at the evidence, right?
North American Breast Cancer Group phase III Clinical Trial: SWOG S0221 (Formerly Southwest Oncology Group).
The trial I am going to dissect for you today dealt with just that, nutritional supplements during chemotherapy for breast cancer patients. The principal investigators also looked at the impact of a doctor’s advice on intake of dietary supplements. The long-term goal of the diet, exercise, lifestyle, and cancer prognosis (DELCaP) study aims to investigate whether or not habits and practices before and during chemotherapy will affect treatment outcomes, as well as treatment related toxicities, recurrence and survival (Zirpoli et al., 2013).
- 1,467 women (218 participants dropped from study. Attrition rate 14.9%)
- Confirmed diagnosis of operable Stage II or III invasive breast cancer with known estrogen or progesterone receptor status, High-risk status based on tumor size or nodal involvement,
- A history of modified radical mastectomy or local excision of all tumors plus axillary node dissection or sentinel node resection, and no previous history of chemotherapy or radiation.
- Criteria also included normal blood work,
- age 18+,
- Zubrod performance status of 0–2,
- as well as a medical history free of heart failure, angina, HIV, and previous malignancies.
Principal investigators randomized women into four treatment arms, and each arm utilized the same 3 drugs, but followed a different treatment schedule. Patients received:
- Doxorubicin plus cyclophosphamide every 2 weeks with pegfilgrastim support,
- Weeklyy doxorubicin plus daily cyclophosphamide with filgrastim support.
- Patients then received either 12 cycles of weekly paclitaxel or
- Paclitaxell every 2 weeks with pegfilgrastim support for 6 cycles.
Principal investigators, besides giving the baseline questionnaire also included a 110-item food frequency questionnaire inquiring about specific data on multivitamin use and other nutritional supplements. In the first questionnaire patients were asked if they took dietary supplements before breast cancer diagnosis and/or if they took supplements after diagnosis (Zirpoli et al., 2013).
When chemotherapy is thought to be complete, study participants are then given a second questionnaire asking for updated information on lifestyle factors and dietary supplement use during chemotherapy for breast cancer (Zirpoli et al., 2013).
The second questionnaire included questions pertaining nutritional supplement use during cancer chemotherapy. The second questionnaire also included a section that asked the breast cancer patients about recommendations they might have received from their physician pertaining the use of dietary supplements. Additional questionnaires are then sent annually (Zirpoli et al., 2013).
The answers pertaining physician recommendations on dietary supplement use were categorized into
- Physician made “No Recommendation,”
- Physician made a “Do not use vitamins/and or supplements during treatment” recommendation,
- Physician made a “Use multivitamins only” guidance and the last category,
- Physician recommended “Use vitamins and supplements during and after treatment.”
- The low rate of nutritional supplement use required that the investigators only present data on nutritional supplements with at least 10 % use at any time point (Zirpoli et al., 2013)
Table 1 assesses the quality of this study. Because of the nature of this study, a double-blind, randomized controlled study was out of the question. This study, despite the design limitations, yielded particularly intriguing results. I encourage readers to explore the Institute of Medicine of the National Academies. The report is titled “Need for innovative designs in research on CAM and conventional medicine.” It provides a comprehensive elaboration why double-blind randomized control trials, even though the gold standard in pharmaceutical research, are not always the best vehicle to research complementary and alternative medicine, or mind-body medicine for that matter.
Results – Nutritional Supplement Use:
- Multivitamins were the most frequently used (48% use before diagnosis, 43% during treatment.
- Decrease of nutritional supplement use during treatment were observed in (Zirpoli et al., 2013).
- Vitamin C (20% before diagnosis vs. 12% during treatment)
- Vitamin E (15% before diagnosis vs. 6% during treatment)
- Folic acid (10% before diagnosis vs. 8% during treatment)
- Calcium (34% before diagnosis vs. 28% during treatment)
- Fish oil (22% before diagnosis vs. 12% during treatment)
- Glucosamine (13% before diagnosis vs. 7% during treatment)
Oral intake of vitamin B6 and vitamin D increased during treatment.
Vitamin B6 consumption increased from 10% before diagnosis to 19% during treatment. The daily dosage of vitamin B6 increased remarkably during therapy (Zirpoli et al., 2013)
Results – Physician Recommendations Pertaining Dietary Supplements:
- 51% (574) breast cancer patients received “No Recommendation” from their physician
- 10% (112) breast cancer patients received a “Do not use vitamins/and or supplements during treatment” guidance from their physician,
- 7% (80) breast cancer patients received a “Use multivitamins only” guidance from their physician and
- 32% (368) breast cancer patients received a “Use vitamins and supplements during and after treatment” recommendation from their physician.
- 115 participant’s information was not classifiable.
The investigators report that “…supplement use was most likely to be stopped when patients were advised by their physicians to discontinue use” (Zirpoli et al., 2013, p. 912). The investigators also write “…patterns of use in this study are impacted greatly by physician recommendations” (Zirpoli et al., 2013, p. 912). For example baseline non-users of vitamin C and E were more likely to initiate use during treatment after receiving a recommendation to use vitamins and supplements compared to those receiving no guidance.
Limitations of this Study for Breast Cancer Patients and Cancer Survivors:
- The investigators were unable to determine whether physicians or patients initiated discussions on nutritional supplements.
- Only general questions regarding vitamin and nutritional supplement use were posed, without asking for specific supplements.
- The researchers did not distinguish between use of high-dose nutritional supplements versus meeting recommended daily requirements.
- Regular vitamin C and E use, both before diagnosis and during treatment, was relatively low when compared to the scientific literature.
- The investigators were unable to compare low rates of use of nutritional supplements in relation to physician recommendations to other published data on antioxidant use among breast cancer patients.
Conclusions and Implications of Key Findings for Breast Cancer Patients and Cancer Survivors:
A major strength of this study is the detailed analysis of multivitamin and supplement use at various time points, specifically before diagnosis, and during breast cancer treatment a number of participants did not discuss supplement use with their doctors.
With adequate follow-up time of patients enrolled in S0221 information upon which to base those recommendations will be available for advising patients on habits during cancer therapy.
As the investigators elaborate, the use of nutritional supplements during chemotherapy is controversial. Only about half of physicians in this study gave their patients a nutritional recommendation. Health care providers communications with patients about nutritional supplement use might be low because health care providers lack confident knowledge in this matter (Kwan, Hirschkorn, & Boon, 2006; Roth, Lin, Kim, & Moody, 2009).
This would suggest that improving patient-physician communication is needed although there are no clear empirical data upon which to base suggestions regarding habits during chemotherapy.
Even the experts seem to contradict:
- Taking dietary supplements containing levels of nutrients with antioxidant properties much greater than the dietary reference intakes is not recommended during chemotherapy (American Institute for Cancer Research, 2000; Norman et al., 2003).
- A 2005 Journal of Clinical Oncology report discloses that their patients are discouraged from taking supplements during cancer treatment (Cassileth, 2004).
- Greenlee, Hershman, & Jacobson, (2008), after conducting a review of 22 studies, concluded that findings did not support any conclusions regarding the effects of individual antioxidant supplements during conventional breast cancer treatment.
However, there are also reports that antioxidants may reduce chemotherapy- induced neurotoxicity and cardiotoxicity.
- Breast cancer patients using vitamin C and vitamin E had fewer recurrences and a reduced risk of mortality, but an increased risk of death with frequent carotenoid use (Greenlee et al., 2012).
- In a prospective study of 1,038 patients with stage III colon cancer enrolled in the NCI- sponsored Cancer and Leukemia Group B, Ng and colleagues found no significant survival benefit to multivitamin use during treatment (Ng et al., 2010).
- Data from the Shanghai Breast Cancer Survival Study showed that use of vitamin E, vitamin C and multivitamins by breast cancer patients was associated with reduced risk of recurrence and survival. Regardless of whether the use was during chemotherapy or not (Nechuta et al., 2010). A word of caution is warranted about this study: Because dietary and lifestyle factors may differ between populations, it is unclear as to whether these findings would apply to a mainly white, U.S. population.
What’s a Breast Cancer Patient to do?
Find the right physician! If considering nutritional supplements during your cancer journey is secondary or not relevant at all, then you probably have no problem with most physicians or oncologists. If optimizing nutrition and nutritional supplements are on your mind during your breast cancer journey, finding an oncologist who shares your beliefs should certainly be one of your priorities.
The data from this study showed that 39% of physician and or oncologists seem to be prepared to discuss this issue with their patients. I am going to leave you with another article to consider. The article is titled “Impact of Antioxidant Supplementation on Chemotherapeutic Efficacy: A Systematic Review of the Evidence from Randomized Controlled Trials.”
The authors of this review concluded “None of the trials reported evidence of significant decreases in efficacy from antioxidant supplementation during chemotherapy.” To the contrary, the data shows that nutritional supplementation resulted in either increased survival times, increased tumor responses, or both, as well as fewer toxicities than controls; however, lack of sufficient statistical power was a consistent limitation (Block et al., 2007).
The Bottom Line?
Large, well-designed studies of nutritional supplementation concurrent with chemotherapy are warranted. In the meantime, it is beneficial to find a healthcare provider who can work with you to address your needs to see you through your cancer journey, whether they include nutritional supplementation or not.
American Institute for Cancer Research. (2000). Nutrition of the cancer patient. Washington, D.C.
Block, K. I., Koch, A. C., Mead, M. N., Tothy, P. K., Newman, R. A., & Gyllenhaal, C. (2007). Impact of antioxidant supplementation on chemotherapeutic efficacy: A systematic review of the evidence from randomized controlled trials. Cancer Treatment Reviews, 33(5), 407–418. doi:10.1016/j.ctrv.2007.01.005
Cassileth, B. R. (2004). High Prevalence of Complementary and Alternative Medicine Use Among Cancer Patients: Implications for Research and Clinical Care. Journal of Clinical Oncology, 23(12), 2590–2592. doi:10.1200/JCO.2005.11.922
Greenlee, H., Hershman, D. L., & Jacobson, J. S. (2008). Use of antioxidant supplements during breast cancer treatment: a comprehensive review. Breast Cancer Research and Treatment, 115(3), 437–452. doi:10.1007/s10549-008-0193-0
Greenlee, H., Kwan, M. L., Kushi, L. H., Song, J., Castillo, A., Weltzien, E., … Caan, B. J. (2012). Antioxidant supplement use after breast cancer diagnosis and mortality in the Life After Cancer Epidemiology (LACE) cohort. Cancer, 118(8), 2048–2058. doi:10.1002/cncr.26526
Kwan, D., Hirschkorn, K., & Boon, H. (2006). U.S. and Canadian pharmacists’ attitudes, knowledge, and professional practice behaviors toward dietary supplements: a systematic review. BMC complementary and alternative medicine, 6, 31. doi:10.1186/1472-6882-6-31
Nechuta, S., Lu, W., Chen, Z., Zheng, Y., Gu, K., Cai, H., … Shu, X. O. (2010). Vitamin Supplement Use During Breast Cancer Treatment and Survival: A Prospective Cohort Study. Cancer Epidemiology Biomarkers & Prevention, 20(2), 262–271. doi:10.1158/1055-9965.EPI-10-1072
Ng, K., Meyerhardt, J. A., Chan, J. A., Niedzwiecki, D., Hollis, D. R., Saltz, L. B., … Fuchs, C. S. (2010). Multivitamin Use Is Not Associated With Cancer Recurrence or Survival in Patients With Stage III Colon Cancer: Findings From CALGB 89803. Journal of Clinical Oncology, 28(28), 4354–4363. doi:10.1200/JCO.2010.28.0362
Norman, H. A., Butrum, R. R., Feldman, E., Heber, D., Nixon, D., Picciano, M. F., … Zeisel, S. H. (2003). The role of dietary supplements during cancer therapy. The Journal of nutrition, 133(11 Suppl 1), 3794S–3799S.
Roth, M., Lin, J., Kim, M., & Moody, K. (2009). Pediatric Oncologistsʼ Views Toward the Use of Complementary and Alternative Medicine in Children With Cancer. Journal of Pediatric Hematology/Oncology, 31(3), 177–182. doi:10.1097/MPH.0b013e3181984f5a
Zirpoli, G. R., Brennan, P. M., Hong, C.-C., McCann, S. E., Ciupak, G., Davis, W., … Ambrosone, C. B. (2013). Supplement use during an intergroup clinical trial for breast cancer (S0221). Breast Cancer Research and Treatment, 137(3), 903–913. doi:10.1007/s10549-012-2400-2