Breast Cancer Review The ASCO Report
Gurdev Parmar, ND, FABNO and Jacob Schor, ND, FABNO
Each year the American Society of Clinical Oncology (ASCO) holds a meeting that few NDs attend. Article co-author Gurdev Parmar, ND, FABNO went to this year’s meeting and gleaned through the many presentations those that are most relevant to our naturopathic practices. This article will summarize what he considers to be the most pertinent developments in treating breast cancer. Dr. Parmar selected five areas:
• Body Mass Index (BMI)
• Vitamin D levels
• 2:16 hydroxyestrone ratio
• Breast imaging for high-risk women
• Circulating tumor cell (CTC) testing
BMI is defined as an individual’s body weight divided by the square of his or her height, and waist-to-hip ratio (WHR) is the ratio of hip-to-waist circumference. People with abdominal obesity are at increased risk for cancers of all types, including breast cancer. Information presented at the ASCO meeting clarifies that breast cancer patients can improve their outcomes, measured as disease-free survival and overall survival, by reducing their BMI. Reducing BMI improves response to cancer treatments and reduces complications. BMI data show that even brisk walking provides a survival benefit for breast cancer patients. All women with breast cancer should be encouraged to eat well and exercise. Here are highlights from the papers presented.
Obesity leads to worse outcomes in breast cancer. Litton and colleagues, writing in the Journal of Clinical Oncology, compared BMI and response to chemotherapy in 1,169 women with breast cancer treated at MD Anderson from 1990 to 2004. Median age was 50 years; 30% of the women were obese, 32% overweight and 38% normal or underweight.
There was no significant difference in pCR (pathologic complete response, i.e., complete tumor shrinkage) for obese compared with normal weight patients. But, normal weight patients were more likely to have tumor shrinkage after chemo than heavier patients. Obese patients also had less hormone-dependent tumors, more Stage III-IV tumors and worse overall survival four years later. The study concluded that higher BMI was associated with worse pCR, progression-free survival and overall survival, and that greater attention should be focused on BMI to optimize the care of breast cancer patients.
BMI is correlated with tumor size, positive lymph nodes, tumor stage and grade. The higher the BMI, the worse each of these is. Jensen et al. made these conclusions when presenting results of a study they conducted in Denmark. They evaluated BMI in 4,917 women diagnosed with breast cancer between 2001 and 2004. Overweight patients had more extensive axillary surgery and more lymph nodes involved. Losing the extra abdominal weight is good for cancer patients.
So is exercise. Irwin presented a study in which he and his colleagues investigated whether walking makes a difference in survival. They observed 933 women with breast cancer who were followed as part of the Health, Eating, Activity and Lifestyle Study. The researchers looked for and found an association between pre- and post-diagnosis physical activity and mortality.
Compared with women who were inactive both before and after diagnosis, women who increased physical activity after diagnosis had a 45% lower risk of death. Women who decreased physical activity after diagnosis had a four-fold greater risk of death. This is information worth sharing with anyone with breast cancer. Do the math: The difference in risk between women who increase their exercise after diagnosis and those who decrease exercise is eightfold.
The evidence that vitamin D deficiency is common in women diagnosed with cancer continues to grow. New information from ASCO suggests that women can use vitamin D supplementation to decrease symptoms associated with treatment while increasing overall survival.
It is already known that low levels of vitamin D are associated with increased breast cancer risk. Goodwin and associates from the University of Toronto presented their work questioning whether vitamin D levels were prognostic for outcome. They examined vitamin D levels and prognostic effects in 512 women with newly diagnosed breast cancer, enrolled between 1989 and 1995 and followed until 2006. Low vitamin D was associated with high BMI, high insulin levels and high tumor grade. Deficient vitamin D levels in women were predictive of a worse prognosis of distant disease-free survival, as well as overall survival. This fact was independent of age, BMI, insulin, tumor stage and grade, node involvement and estrogen receptor status. Vitamin D deficiency is common in breast cancer and is now associated with poor prognosis.
Acknowledging these ideas, colleagues at Columbia University asked whether taking supplemental vitamin D made a difference. They determined the prevalence of vitamin D deficiency in pre-menopausal women at initial diagnosis of breast cancer and after one year of vitamin D supplementation. The study included 103 pre-menopausal women with invasive breast cancer, median age 43 and median BMI of 25. All subjects received adjuvant chemotherapy, bisphosphonate and vitamin D3 (400IU daily). After one year they found vitamin D deficiency was still common in these women, particularly among African Americans and Hispanics. They concluded that the current recommended daily allowance (RDA) is too low. Most NDs consider the serum level that researchers considered as satisfactory (>30 ng/mL) as still too low, and many suggest levels twice as high. It is imperative that serum 25(OH) D levels be measured and there should be supplementation in all women with breast cancer.
Khan from the University of Kansas looked at vitamin D and the side effects of aromatase inhibitors. This prospective study measured the effect of high-dose vitamin D on joint pain and fatigue in postmenopausal women with invasive breast cancer taking adjuvant letrozole, an aromatase inhibitor. At baseline, all women started 2.5mg/d of letrozole, and moderate doses of calcium (1,200mg/d) and vitamin D (600IU/d). At week four, women with 25(OH)D <40ng/mL were given 50,000IU of vitamin D3 per week for 12 weeks. Highdose vitamin D provided relief from fatigue and joint pain. Standard doses of vitamin D were not adequate to increase blood levels or to provide relief.
Estrogen Metabolite Ratio
The idea that measuring the ratio of 2 hydroxyestrone (2-OHE1) metabolites to 16a-hydroxyestrone (16a-OHE1) metabolites could be used as a risk assessment tool for breast cancer has been kicked around for a decade or more. Researchers at the ASCO meeting presented more information in support of this test.
Researchers from the University of Pittsburgh reported on urinary estrogen metabolites in women at high risk for breast cancer. They examined the idea that the ratio of 2-OHE1 metabolites to 16a-OHE1 metabolites is predictive of breast cancer risk. They looked at estrogen metabolism in high-risk women, defining risk as first-degree family history, breast atypia, fibrocystic breast disease, BRCA1/2 or Ashkenazi Jewish descent. Their results supported what we have long suspected: There is an association between lower urine 2:16 OHE ratios and high risk breast cancer.
Comparing Imaging Techniques
In Canada, there are very few MRI imaging centers. In the U.S., few insurance companies will cover screening MRIs. Yet, it looks as if MRIs should be the preferred screening method for young women at high risk of breast cancer. The lower radiation exposure received by the women tested using MRIs is only part of their advantage, though not insignificant, especially for young women with a strong family history who start getting yearly screens as early as age 30. New studies suggest that MRIs do a better job at finding cancer than mammograms.
Researchers from the University of Bonn in Germany compared the diagnostic imaging technologies in use for women at high risk of breast cancer. Germany’s current national guidelines recommend mammography (Mx), with or without ultrasound (US), and annual MRI starting at age 30 or younger for screening women with increased familial risk. Kuhl compared the contribution of the different imaging modalities, Mx, US and MRI, alone or in different combinations to the early diagnosis of breast cancer. They conducted a prospective study on 687 asymptomatic women who were at high risk. Women were screened yearly using all three techniques. During the study, 27 cases of breast cancer were diagnosed. An incredible 14 of the 27 cases (52%) were diagnosed by MRI alone and missed by a combination of Mx and US. The sensitivity of the various tests was as follows:
• Mx alone (9/27) = 33%
• Mx + US (13/27) = 48%
• MRI alone (25/27) = 93%
• MRI + US (25/27) = 93%
• MRI + Mx (27/27) = 100%
The results showed that breast MRI was significantly more sensitive than both Mx and US combined. One would also have to consider that the advantage of MRI is even larger because mammograms have the penalty of ionizing radiation. We propose a reappraisal of the use of mammograms to screen high-risk women in favor of an annual MRI.
Many of the same researchers from Bonn took part in another study. This study investigated the sensitivity of mammography vs. contrast-enhanced breast MRI for identifying and delineating intraductal components around invasive cancers. Between 2002 and 2007, a total of 139 patients, mean age 54 years, received the final surgical pathology diagnosis of invasive breast cancer with additional intraductal components. Mammograms identified 51 of the 139 (37%) of the intraductal components, vs. 118 of the 139 (85%) identified by MRI. Thus, MRI provided a more accurate road map for breast conserving surgery than mammography alone.
There was a buzz at ASCO this year about CTCs. These are tumor cells that can be measured in the peripheral blood of patients with metastatic breast cancer. In localized breast cancer with no spread into the blood, lymph or other tissue, CTC levels are low, <5CTC/7.5ml of blood. Once tumor cells start circulating through the blood, they will be found in significant numbers (>5CTC/7.5ml blood). Several ASCO papers suggest that CTCs are reliable measures of prognosis and efficacy of treatment, and a good determination of whether patients should continue with a course of treatment.
Liu and colleagues in Washington, DC tested CTCs to predict whether treatment had worked. Current evidence suggests that a CTC of >5/7.5ml blood is associated with worse progression-free survival and overall survival in metastatic breast cancer. Persistence of >5CTC/7.5ml appears to predict treatment failure. In this study, the researcher collected serial CTC levels in patients starting a new systemic regimen for progressive, radiographically measurable metastatic breast cancer. Disease progression occurred in 29% of cases with low CTC and 69% of cases with high CTC (>5CTC/7.5ml). Correlating CTC and radiographic assessments from the same patient, >5 CTC/7.5 mL is associated with a 5.32-fold higher risk of disease progression.
Pachmann and colleagues reported on their study, in which they measured CTCs before each new therapy cycle and before and after surgery from 70 patients treated with primary systemic chemotherapy. They made the same measurements on 150 patients treated with adjuvant chemotherapy until three weeks after the end of chemotherapy. CTC response to therapy was correlated to outcome, and the CTC number also correlated with tumor size. During primary systemic therapy, the decrease in cell numbers highly correlated with the final tumor size reduction and also predicted for relapse-free survival. During 4.5 years of follow-up, no patient with a good response had relapsed (<5CTC/7.5ml).
The researchers concluded that monitoring CTC will not only provide the earliest and most reliable indicator of successful neoadjuvant treatment, but will also spare patients unnecessary treatment.
In simple words, this test may tell us whether treatment has worked.
There were other exciting papers on CTCs.
For example, Rack and colleagues presented another study demonstrating the usefulness of assessing CTC levels. The presence of CTCs in early breast cancer predicts an increased risk for relapse, making this a good method to be used as an early marker for treatment efficacy and risk for recurrence. In this German study, called the SUCCESS trial, researchers analyzed peripheral blood from 1,500 node-positive and high-risk node-negative breast cancer patients before and after taxane chemotherapy. While the presence of CTCs did not correlate with tumor size, grading, hormonal status or HER2/neu status of the primary tumor, it did correlate with the presence of lymph node metastases.
Persistence of CTCs after chemotherapy was a significant predictor for both reduced disease-free survival and overall survival. Abstracts of all papers presented at ASCO meetings can be viewed at www.asco.org/ASCO/Abstracts+%26+Virtual+Meeting/Abstracts.
The Oncology Association of Naturopathic Physicians (OncANP) was founded in 2004 to enhance the quality of life of people living with cancer through both increasing the collaboration between NDs working with patients with cancer and integrating naturopathic practice into medical oncology care. Withits co-organization, the American Board of Naturopathic Oncology (ABNO), the OncANP has set standards, instituted testing and now credentials Fellows in naturopathic oncology.
The OncANP welcomes all NDs interested in improving their knowledge and ability to work with oncology patients. For more information see www.OncANP.org.
Gurdev Parmar, ND FABNO co-founded Integrated Health Clinic in 2000, one of the largest integrated health care facilities in Canada. Dr. Parmar focuses on the treatment of cancer with a fellowship with the ABNO. He is a member of ASCO and OncANP. He lectures regularly for the Canadian Cancer Society and other cancer-related organizations. Dr. Parmar founded The HELP Foundation, which, after the tsunami of 2004 built an Integrated Health Clinic on the island of Kho Khao, Thailand (www.thehelpfoundation.ca). He is licensed in both British Columbia and Arizona. He serves as co-chair of the Advisory Committee on Disaster and Pandemic Preparedness for the province of B.C. In his spare time, Dr. Parmar is a competitive tennis player and
enthusiastic Canuck fan. His wife and clinic partner, Karen, and his two sons, Seth and Devan, keep his life balanced and whole. Jacob Schor, ND, FABNO is a 1991 graduate of NCNM and has practiced in Denver for the past 17 years. He served as president of the CANP from 1992 to 1999. He has served on the board of directors of the OncANP since 2006 and currently acts as secretary to the board. He is a Fellow of the ABNO. He was utterly shocked and humbled at the 2008 convention of the AANP to be presented with the Vis Award, an honor bestowed in the memory of William Mitchell. He is incredibly lucky to practice with his wife, Rena Bloom, ND. Dr. Schor writes newsletters for his patients that are popular with doctors and students alike in our profession. Sign up and receive them free at www.DenverNaturopathic.com. Contact him at Jacob@DenverNaturopathic.com.
Crew KD et al: High prevalence of vitamin D deficiency in a multi-ethnic cohort of premenopausal breast cancer patients, J Clin Oncol (ASCO Meeting Abstracts) 26:9583, 2008.
Goodwin PJ et al: Frequency of vitamin D (vit D) deficiency at breast cancer (BC) diagnosis and association with risk of distant recurrence and death in a prospective cohort study of T1-3, N0-1, M0 B, J Clin Oncol (ASCO Meeting Abstracts) 26:511, 2008.
Im A et al: Urinary estrogen metabolites in patients at high risk for breast cancer, J Clin Oncol, (ASCO Meeting Abstracts) 26:1520, 2008.
Irwin ML et al: Influence of pre- and postdiagnosis physical activity on mortality in breast cancer survivors: the health, eating, activity, and lifestyle study, J Clin Oncol (ASCO Meeting Abstracts) 26(24):3958-3964, 2008.
Jensen AR et al: The relation between body mass index, comorbidity, choice of surgery, and prognostic factors in early breast cancer: Data from a nation-wide Danish cohort, J Clin Oncol (ASCO Meeting Abstracts) 26:11110, 2008.
Khan QJ et al: Effect of high-dose vitamin D on joint pain and fatigue from adjuvant letrozole, J Clin Oncol (ASCO Meeting Abstracts) 26:9618, 2008.
Kuhl CK et al: Management recommendations for women at increased familial risk for breast cancer: Results of a prospective national multi-modality cohort study, J Clin Oncol (ASCO Meeting Abstracts) 26:1500, 2008.
Litton JK et al: Relationship between obesity and pathologic response to neoadjuvant chemotherapy among women with operable breast cancer, J Clin Oncol (ASCO Meeting Abstracts) 26:4072-4077, 2008.
Liu MC et al: Circulating tumor cells (CTC): A reliable predictor of treatment efficacy in metastatic breast cancer (MBC), J Clin Oncol (ASCO Meeting Abstracts) 26:11018, 2008.
Pachmann K et al: The impact of systemic chemotherapy on circulating epithelial tumor cells (CETC) in breast cancer, J Clin Oncol (ASCO Meeting Abstracts) 26:11001, 2008.
Rack et al: Prognostic relevance of circulating tumour cells (CTCs) in peripheral blood of breast cancer patients before and after adjuvant chemotherapy: The German SUCCESS-Trial, J Clin Oncol 25(No 15S):S503, 2008.
Schrading S et al: Magnetic resonance imaging versus mammography for diagnosing ductal carcinoma in-situ (DCIS) around invasive breast cancer, J Clin Oncol (ASCO Meeting Abstracts) 26:1507, 2008.