Antibiotic Use in Relation to the Risk of Breast Cancer
JAMA, Vol. 291 No.7, February 18, 2004, pp. 827-835
Cristine M. Velicer, PhD; Susan R. Heckbert, MD, PhD; Johanna W. Lampe, PhD, RD; John D. Potter, MD, PhD; Carol A. Robertson, RPh; Stephen H. Taplin, MD, MPH
Context: Use of antibiotics may be associated with risk of breast cancer through effects on immune function, inflammation, and metabolism of estrogen and phytochemicals; however, clinical data on the association between antibiotic use and risk of breast cancer are sparse.
Objective: To examine the association between use of antibiotics and risk of breast cancer.
Design, Setting, and Participants
Case-control study among 2266 women older than 19 years with primary, invasive breast cancer (cases) enrolled in a large, nonprofit health plan for at least 1 year between January 1, 1993, and June 30, 2001, and 7953 randomly selected female health plan members (controls), frequency-matched to cases on age and length of enrollment. Cases were ascertained from the Surveillance, Epidemiology, and End Results cancer registry. Antibiotic use was ascertained from computerized pharmacy records.
Main Outcome Measure: Association between extent of antibiotic use and risk of breast cancer.
Results: Increasing cumulative days of antibiotic use were associated with increased risk of incident breast cancer, adjusted for age and length of enrollment.
Increased risk was observed in all antibiotic classes studied and in a subanalysis having breast cancer fatality as the outcome.
Among women with the highest levels of tetracycline or macrolide use, risk of breast cancer was not elevated in those using these antibiotics exclusively for acne or rosacea (indications that could be risk factors for breast cancer due to altered hormone levels), compared with those using them exclusively for respiratory tract infections, adjusted for age and length of enrollment.
Use of antibiotics is associated with increased risk of incident and fatal breast cancer .
It cannot be determined from this study whether antibiotic use is causally related to breast cancer, or whether indication for use, overall weakened immune function, or otherfactors are pertinent underlying exposures.
Although further studies are needed, these findings reinforce the need for prudent long-term use of antibiotics.
THESE AUTHORS ALSO NOTE:
The hypothesis that use of antibiotics may increase risk of cancer was first proposed in 1981.
[Setchell KD, Lawson AM, Borriello SP,et al. Lignan formation in man-microbial involvement and possible roles in relation to cancer. Lancet. 1981;2:4-7.]
"Use of antibiotics reduces the capacity of intestinal microflora to metabolize phytochemicals into compounds that may protect against cancer."
"Use. of antibiotics may be associated with cancer risk through effects on immune function and inflammation, although little is known about these mechanisms."
"Understanding whether an association between antibiotic use and breast cancer exists is particularly important given the high incidence of breast cancer and widespread antibiotic use in many countries."
Breast cancer is the second leading cause of cancer mortality in US women and the most common cancer in women worldwide, with more than 1 million cases diagnosed each year.
"Antibiotics are used extensively and overused in many countries."
"In the United States, more than 22.6 million antibiotic prescriptions for non bacterial acute respiratory infections were filled in 1995 alone."
[Gonzales R, Malone DC, Maselli JH, Sande MA. Excessive antibiotic use for acute respiratory infections in the United States. Clin Infect Dis. 2001;33:757-762]
[This is crazy! And the medical establishment often has the gall to refer to chiropractors as quacks. This 22.6 million inappropriate prescriptions is likely the "tip of the iceberg," as it does not include antibiotics prescribed for chronic non bacterial respiratory infections, for other nonbacterial infections in the GI or elsewhere, or antibiotics prescribed for self limiting bacterial infections, etc.]
"Although the biological mechanisms through which antibiotics might alter cancer risk may also be relevant to other cancers, we selected breast cancer for this study because it is the topic of the only other epidemiologic study of antibiotic use and cancer risk, and it is an important cancer in women." [WOW! These authors are implying that antibiotic use may be associated with other cancers as well].
These authors selected 2 measures of antibiotic exposure:
1) The cumulative number of days of antibiotic use
2) The total number of antibiotic prescriptions per participant
These authors also conducted a substudy of women to verify that it was antibiotic use, not the indication for antibiotic use, that was related to increased cancer rates.
A total of 110,191 antibiotic prescriptions were dispensed to study participants.
“Cumulative duration of antibiotic use ranged from 0 to 7600 days, and cumulative number of antibiotic prescriptions ranged from 0 to 194."
For all antibiotic classes, increasing cumulative days of use was associated with risk of incident breast cancer.
“The association between cumulative days of antibiotic use and death due to breast cancer was strong for all antibiotic classes, controlling for age, length of enrollment, and ever use of postmenopausal hormones."
COMMENT BY AUTHORS
"In this population-based case-control study, we found that increasing cumulative days of antibiotic use and increasing cumulative number of antibiotic prescriptions were associated with increased risk of incident breast cancer, after controlling for age and length of enrollment."
"Increasing cumulative days of antibiotic use was associated with death due to breast cancer, controlling for age, length of enrollment, and ever use of postmenopausal hormones."
"All classes of antibiotics were associated with increased risk."
"Our findings were robust."
"The hypothesis that some classes of antibiotics may increase risk of breast cancer is plausible; antibiotics have effects on intestinal microflora and on immune and inflammatory responses."
[Velicer eM, Lampe JW, Heckbert SR, Potter JD, Taplin SH. Hypothesis: is antibiotic use associated with breast cancer? Cancer Causes Control. 2003;14:739-747.]
"Antibiotic use may increase risk of breast cancer by decreasing phytochemical metabolism by intestinal microflora."
"Phytochemicals are hypothesized to play an inhibitory role at several points in the carcinogenesis pathway by modulating enzymes involved in carcinogen and steroid hormone metabolism."