Abstract & Commentary
Source: Velicer CM, et al. JAMA. 2004;291:827-835.
Synopsis: Use of antibiotics is associated with increased risk of breast cancer and death from breast cancer in a dose-dependent way.
The study population was drawn from members of Group Health Cooperative (GHC), a large nonprofit health plan in Washington State. Cases were 2266 women with primary invasive breast cancer who had been enrolled in the plan for at least 1 year. Controls were 7953 age-matched women who were also drawn from the GHC plan. Data on antibiotic use came from the GHC pharmacy. Information about other breast cancer risk factors came from GHC breast cancer surveillance questionnaires and other sources. Women who had used either tetracycline or a macrolide for at least 50 days for acne or rosacea were compared to those who had used these antibiotics for respiratory tract infections, to determine if underlying hormonal conditions (present in acne) could contribute to increased risk
There was an association between antibiotic use and the risks both of breast cancer and of breast cancer deaths in a dose-dependent way. Compared with women who had never taken antibiotics, the adjusted Relative Risks (RR) and confidence intervals for breast cancer increased with the number of days of lifetime antibiotic use as follows: 0 days, RR, 1; 1-50 days, RR, 1.45 (1.24-1.69); 51-100 days, RR, 1.53 (1.28-1.83);. 101-500 days, RR, 1.68 (1.42-2.00); 501-1000 days, RR, 2.14 (1.6-2.88). > 1000 days, RR 2.07 (RR, 1.48-2.89). This was highly statistically significant, of course. This increased risk was observed for all antibiotic classes, and was not substantially changed by controlling for other risk factors. When the analysis was restricted to women who had filled at least 1 antibiotic prescription, an increased risk was still present. However, in the sub study of 136 women who took at least 50 days’ worth of tetracycline or a macrolide for acne or for rosacea, compared with 65 women who took these antibiotics for respiratory tract infections, there was no increased risk of breast cancer for those who took it for "dermatologic" reasons, compared with those who took it for respiratory tract infections.
There were some other interesting differences between cases and controls in this study: patients with breast cancer tended to be educated beyond high school, to have more health care visits, to be premenopausal, and to have used either oral contraceptives or more than 26 hormone replacement prescriptions. They also were more likely to have had menarche before age 11, to have had their first birth after the age of 30, to have a higher body mass index, to have a first degree family relative with breast cancer, and to have a higher mammography breast density.
Comment by Barbara A. Phillips, MD, MSPH
If you need a compelling argument to use the next time a patient requests unwarranted antibiotics, this is it! This article received some attention in the lay press, and many of your patients will have heard about it and will be looking to you for reinforcement. Of course, heart disease is the leading cause of death in post-adolescent people in this country. But patients tend to focus more on cancer. If you are a woman and you don’t smoke, the cancer you are most likely to get is breast cancer. While we have made great strides in early detection and reduced mortality from breast cancer, our female patients appropriately still fear it. In this study, any antibiotic use increased the risk of breast cancer.
The accompanying editorial1 elaborates on a couple of possible mechanisms suggested by Velicer and colleagues. These are that antibiotics might reduce the ability of gut microbes to metabolize phytochemicals and that antibiotics might stimulate production of prostaglandin E2, which is implicated in breast cancer.2 It is also possible that some of the increased risk of breast cancer could have resulted from the increased likelihood of upper respiratory tract infections in women who smoked. Smoking is a well-established risk factor for breast cancer,3 and it is possible that cigarette smokers were more likely to receive antibiotics in this study. I did not find any evidence that controlled for smoking in this study.
The bottom line for us and for our patients is that this study is one more piece of evidence for the increasingly compelling case against unwarranted antibiotics.
Dr. Phillips, Professor of Medicine, University of Kentucky; Director, Sleep Disorders Center, Samaritan Hospital, Lexington, KY, is Associate Editor of Internal Medicine Alert.
1. Ness RB, Cauley JA. JAMA. 2004. 291:880-881.
2. Hwang D, et al. J Natl Cancer Inst. 1998;90: 455-460.
3. Reynolds P, et al Natl Cancer Inst. 2004;96:29-37.