Breast Cancer and Chlorinated Pesticides. Literature

review and clinical study.

Walter J. Crinnion ND

Abstract

Published studies on adipose and serum levels of chlorinated pesticides in cases of breast cancer are reviewed. Adipose studies of breast tissue consistently show increased levels of chlorinated compounds in breast cancer cases over controls. These studies indicate that chlorinated compounds are concentrated in breast fat in those women who develop breast cancer. Studies of serum levels are conflicting, although mathematical calculations done in the two main studies are inconsistent. A review of non-lipid adjusted pesticide levels in a clinical setting has revealed that breast cancer patients and females with other cancers have twice the level of DDE as non-cancer controls.

Research on OCCs and Breast Cancer

1. From 1973 through 1987, cardiovascular mortality decreased 42% in the age group 0-54 years and decreased 33% in the age group 55to 84 years; concurrently, cancer mortality decreased 17% in the younger group but increased 12% in the older group. By 1987, even though proportionally fewer people in the older age groups died, relatively more of them died of cancer. Men born in the 1940s had twice as much cancer as those born in 1888 through 1897 and more than twice as much cancer not linked to smoking; women born during this period had 50% and 30% more of these same cancers respectively. Rates of smoking-related cancers in recent cohorts of women were five to six times greater than in those born in 1888 through 1897, while rates in men declined. Recent cohorts of women also had more than twice as much breast cancer as those born in 1888 through 1897.

Davis DL, Dinse GE, Hoel DG. Decreasing cardiovascular disease and increasing cancer among whites in the United States from 1973 through 1987, good news and bad news. JAMA 1994;27(6):431-437

2. What happened in Israel?

Prior to 1976 Israel had the highest age-adjusted breast cancer mortality rate per capita fat intake of any nation. Yet, while all the risk factors, including fat intake, continued to increase after 1976, the overall rate of breast cancer mortality decreased between 1976 and 1986. Prior to this drop Israel had a continual rise in age-adjusted breast cancer mortality for the previous 25 years running. This drop in mortality rate was most pronounced in the premenopausal ages with a 34% decline in the 25-34 age group.

Prior to 1976 levels of DDT, HCH (alpha-BHC) and Lindane were present in the Israeli milk supply in excessive levels. After a ban on the use of these compounds in the daily industry the levels of lindane were reduced by 80%, DDT by 43%, and alpha-BHC by 98% (by 1980).

Westin J, Richter E. The Israeli Breast-Cancer anomaly. Ann NY Acad Sci. 1990;609: 269-279.

Westin J. Carcinogens in Israeli milk: a study of regulatory failure. Int J Health Services 1993; 23(3):497-517

3. The level of total DDT and PCBs in malignant breast tissue>adjacent breast tissue>adjacent adipose tissue. In controls without breast cancer the levels of these compounds in breast tissue>adjacent adipose tissue. Between controls and breast cancer patients the levels of total p,p’-DDT in non-malignant breast tissue averaged approximately 50% more than in malignant tissue. But the levels of total o,p’-DDT averaged over six times higher in malignant breast tissue than control healthy breast tissue. Levels of BHC, Dieldrin, and HCH were all higher in malignant tissue than control breast tissue. (9 cases, 5 controls)

Wasserman M, Nogueira D, Tomatis L, et. al. Organochlorine compounds in neoplastic and adjacent apparently normal breast tissue. Bull Env Contam Toxic. 1976;15(4):478-484

4. Adipose study of 44 Finnish breast cancer patients and 33 controls. Approximately the same levels of total DDT (o,p’-DDT or E were not checked for) in cases and controls. However, significantly higher levels of HCH were found in cancer patients. If both parity and age were adjusted, the odds ratio, in persons whose breast adipose tissue contained more than 0.1 mg/kg fat beta-HCH, was 10.51 (95% confidence interval, 2.00-55.36). Adipose tissue from cases were 10-20 gm of breast adipose tissue taken from as near the malignant tissue as possible. Controls were breast tissue taken from autopsy.

Mussalo-Rauhamaa H, Hasanen E, Pyysalo H, et. al. Occurrence of Beta-Hexachlorocyclohexane in breast cancer patients. Cancer 1990;66:2124-2128

5. Adipose sample from 20 malignant cases and 20 non-malignant controls from Hartford, Connecticut (all adipose from biopsy of palpable lump or mammography abnormality) showed the mean concentrations of PCBs and p,p-DDE were 50-60% higher in tissues of women who had breast cancer. Levels of p,p-DDT were also higher in cases. When adjusted for smoking status (not a breast cancer risk!) levels of PCBs remained statistically significant. Their results indicate that a 10ppb increase in tissue level of PCB and DDE corresponded with a 1% increase in breast cancer risk. (10ppb in adipose = .1ppb in serum)

Falck F, Ricci A, Wolff M, Godbold J, Deckers P. Pesticides and polychlorinated biphenyl residues in human breast lipids and their relation to breast cancer. Arch Env Health 1992; 47(2): 143-146

6. Stored serum from 58 women with breast cancer and 171 control the New York University Women’s Health Study were assessed for the presence of DDT, DDE and PCBs. DDE levels were 35% higher and PCBs were 15% higher in cases than in controls. After adjusting for various factors the risk of breast cancer was four times higher with a DDE increase from 2ng/mL (ppb) to 19.1 ng/mL. There was approximately a 9% increased risk for every 1ppb of DDE in the serum. Samples were not adjusted for lipid content in the blood.

Wolff M, Toniolo P, Lee E, Rivera M, Dubin N. Blood levels of organochlorine residues and risk of breast cancer. J Natl Cancer Inst 1993; 85(8):648-652.

7. Stored serum from 150 breast cancer cases and 150 controls from 57,040 women from the San Francisco Bay Area, 50 from 3 ethnic groups (white, black and Asian). Initial fasting sampling was in the 1960s, the final samples in 1990. Matched analysis showed no difference in DDE or PCBs between cases and controls, but they did find ethnic differences. This was taken at a time when DDT was still used in homes and agriculturally in the US. There was no adjusting for lipid status.

Krieger N, Wolff M, Hiatt R, et. al. Breast cancer and serum organochlorines: a prospective study among white, black, and Asian women. J Natl Cancer Inst 1994; 86(8):589-599

Savitz took the published information from the above study and reanalyzed the data. His results showed that the odds ratio for white women with DDE levels were 1.0 (referent), 1.9 (95% CI = 0.6-6.0), and 2.4 (95% CI = 0.5-10.6). For black women they were 1.0 (referent), 2.3 (95% CI = 0.6-8.4), and 3.9 (95% CI = 0.9-16.1)

Savitz DA. Re: Breast cancer and serum organochlorines: a prospective study among white, black, and Asian women. J Natl Cancer Inst 1994; 86(16) 1255-1256

8. Canadian study looking at both adipose and serum showed significantly higher levels of DDE in estrogen receptor positive breast cancer cases compared to controls. 1.2ppb of DDE gave a risk of 1.0 (referent), 3.8 ppb gave a risk of 3.0, and 6.5 ppb gave a risk of 8.9. 0.2-1.0gm of breast adipose tissue was taken with fasting serum samples. Elevated HCH also found. Adipose tissue levels of OCCs were lower in ER negative cases than in controls. “These results suggest that women with hormone-responsive breast cancer, but not those with hormone-nonresponsive breast cancer, have a higher DDE body burden than women with benign breast diseases.”

Dewailly E, Dodin S, Verreault R, Ayotte P, Sauve L, Morin J. High organochlorine body burden in women with estrogen receptor positive breast cancer. J Natl Cancer Inst 1994; 86:232-234

9. Multicenter trial (Germany, Netherlands, Northern Ireland, Switzerland, and Spain) 265 women with breast cancer and 341 controls. All gave a single adipose sample from the buttocks. Mean DDE concentration was 1.35 ug/g among cases and 1.51 ug/g among controls. Hormone receptor positive status not taken into account.

van’t Veer P, Lobbezoo I, Martin-Moreno J, Guallar E, et al. DDT (dicophane) and postmenopausal breast cancer in Europe:case-control study BMJ 1997;315:81-5

10. 236 nurses with breast cancer and 230 nurse controls showed slightly lower mean DDE for cases (4.71 –cholesterol adjusted) than control (5.35-cholesterol adjusted). Non-lipid adjusted means were 5.07 for cases and 5.59 for controls. Blood was taken 1989 or 1990 and cancers showed up by 1992. Among 48 premenopausal cases the avg DDE was 3.72 ppb and controls was 3.30ppb. Positive association was found between DDE levels and body mass. Hormone receptor status not looked at. Quintiles of DDE levels increased with age. Pesticide levels given as linear regression analysis of log transformed DDE and PCB to adjust for cholesterol levels. A different method than Wolff used in JNCI article.

Hunter D, Hankinson S, Laden F, Colditz G, Manson J, Willett W, Speizer F, Wolff M. Plasma organochlorine levels and the risk of breast cancer. NEJM 1997;337:1253-8.

11. Adipose levels of DDE positively associated with ER positive breast cancers.

Mussalo-Rauhamaa, H. Selenium and DDE in breast fat of breast cancer patients: Their relationship to hormone receptors in breast tissue. JNCI 1993, 85(23): 1964,5

12. Adipose samples from two small groups showed no difference.

Unger M, Kiaer H, Blichert-toft M, Olsen J, Clausen J. Organochlorine compounds in human breast fat from deceased with and without breast cancer and in a biopsy material for newly diagnosed patients undergoing breast surgery. Env. Res. 1984, 34: 24-26

Testing of OCCs

13. For adipose sample to be most accurate. Three sites should be taken and combined into one sample for testing.

Rea, W. Personal Communication. Dallas Tx, February 1995.

14. Serum testing: non-fasting samples have 22-29% higher mean concent4rations than fasting of PCB, HCB, DDE. Total serum lipids were 20% higher in non-fasting than fasting samples. When the OCC levels were adjusted for lipid content the difference between feeding and fasting were non-significant.

Phillips D, Pirkle J, Burse V, Bernert J, Henderson L, Needham L. Chlorinated Hydrocarbon levels in human serum: effects of fasting and feeding. Arch Environ Contam Toxicol 1989, 18:495-500.

15. Serum testing in breast cancer patients who have had surgery/chemo/ and radiation had .15% increase of DDE. Those with surgery alone has 1.5% decrease in serum levels of DDE.

Gammon M, Wolff M, Neufut A, Terry M, Britton J, Greenebaum E, Hibshoosh H, Levin B, Wang Q, Santella R. Treatment for breast cancer and blood levels of chlorinated hydrocarbons. Canc Epidem BioMark Prev. 1996, 5:467-471.

16. Serum levels of pesticides higher with age, residing on a farm, being male and having greater exposure risk. Some differences were also seen with the particular area of the country (Midwest was the lowest, south and west were usually the highest), poverty level also had higher levels.

Stehr-Green P, Demographic and seasonal influences on human serum pesticide residue levels. J Toxicol Environ Health 1989, 27;405-421.

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