Antibiotic Use and the Risk of Breast Cancer - Literature review Example

REVIEW: ANTIBIOTIC USE AND RISK OF BREAST CANCER INTRODUCTION: According to the recent studies there found a positive association between the antibiotics and risk of breast cancer. The more antibiotics the women in the study had used, the higher their risk of breast cancer. These study results do not mean that antibiotics cause cancer. These results only show that there is an association between the two. More research is necessary to learn if there is a direct cause-and-effect relationship. Factors such as age, reproductive and menstrual history, lifestyle factors, use of hormone therapy, and high breast density, among other factors, can affect breast cancer risk. The authors describe an association between antibiotic use and increased breast cancer risk that persisted after adjustment for factors known to be associated with breast cancer. The question remains as to whether antibiotic use is causally related to breast cancer or whether there are common mediators of antibiotic use and breast cancer. For example, some women may have underlying immune or inflammatory disorders that might predispose them to neoplasia or infections. In that case, antibiotic use would only be a marker for such a predisposition. If this hypothesis were true, one would also expect an increased frequency of other types of malignancies to be associated with antibiotic use. Although there are a number of interesting proposed mechanisms related to interference with intestinal microflora and estrogen production that suggest a potential causal relation between antibiotic use and breast cancer, these hypotheses remain unproven . It is also possible that the underlying conditions that led to the antibiotics prescriptions caused the increased risk, or that a weakened immune system - either alone, or in combination with the use of antibiotics - is the cause of this association. Summary of five studies: Authors Characteristics Methods Results Discussion Knekt et al(2000) Low lignan status has been reported to be related to an elevated risk of Breast cancer. Since lignan status is reduced by antibacterial medications it is possible to hypnotise that repeated use of antibiotics may also be a risk factor for breast Cancer. During the follow up in 1973-1991, 157 women reported previous or present medication for urinary tract infection of elevated breast cancer risk in comparison with other women. The association was concentrate-d to women under 50 years of age. Information during the follow up was obtained by linking data in the nation wide Finnish cancer registry to the data of study population. The cox poxial model was used to estimate the association between treatment for urinary tract infection and incidence of breast cancer. The results are still inconclusive and the hypothesis needs to be tested by other studies. A total of 9461 women were at risk after exclusion of persons who has diagnosed cancer before or during the baseline examination. Association between history of antibacterial treatment and breast cancer varied considerably among age groups. The RR (history of antibacterial treatment positive vs negative) for the age groups < 40 years, 40-49 years, 50-59 years, and 60-69 years were 1.92, 1.46, 1.25 and 0.87 respectively. With few exceptions only weak associations between the history of antibacterial treatment for urinary tract infection and known potential risk factors of breast cancer. The results of present study suggest that premenopausal treatment for bacteriuria have an elevated risk of developing breast cancer. A 74%excess risk was observed among women under 50 years of age; where as no excess risk was noted among older women. In the present study the history of antibacterial medication was based on questions. In accordance with the findings from several studies it was found that there is an elevated risk of breast cancer among women living in urban or industrial areas having a higher level of education with low parity, low body mass index, and high stature and among women who consume alcohol. Velicer, Heckbert, Lampe et al. (2004) Antibiotics affect the immune and inflammatory function. Antibiotics inhibit cytokine production. Antibiotics may have varied effects on prosglandin function. Antibiotics inhibit T-lymphocyte proliferation. Antibiotics inhibit matrix metalloproteinase production. Antibiotics inhibit oestrogen decongugation. Antibiotics effect intestinal microflora and inhibit phytochemical metabolism. Few ecologic and epidemiologic data have been explored to test this hypothesis. Only epidemiologic study of antibiotic use and cancer risk was a cohort study in Finland; the researchers found that women under 50 years old who reported previous and /or present antibiotic use of urinary tract infections had a Elevated levels of breast cancer risk. Overall the evidence suggest that ,depending on antibiotic class, some antibiotics may act on mechanisms that increase breast cancer risk, while others may decrease risk or may have varied effects. Antibiotic use can alter breast cancer risk through effects on immune function and inflammation response and metabolism of phytochemicals and oestrogen. Sorensen et al(2004) Breast cancer is the most commonly occurring cancer in women. It has been hypnotized that antibiotics may effect the ability of intestinal microflora to metabolize phytochemicals from edible plants into the compounds that may protect against cancer. Since antibiotics are commonly used and breast cancer is common, any increased risk has Major public health potential. The national health service in each Danish country provides health care for all residents, with free access to general practitioners and hospitals, and also refunding a variable proportion of the costs of prescribed drugs. To further evaluate this case control study of breast cancer was conducted in Denmark, a country with of the highest incidents of breast cancer worldwide. Risk of breast cancer according to number of prescriptions for antibiotics was summarized for 2728-27280 controls. Mean age was 62 years for both cases and controls. Almost all risk estimates was close to 1.0. The odd ratios for breast cancer associated with more than 10 prescriptions for antibiotics was there were no substantial differences in finding various classes of antibiotics. In women less than 70 years of age, the adjusted odd ratio for breast cancer was 1.11 for women with more than 10 prescriptions. Relative risks did not vary substantially between parous and nulliparous women. In large population based case control study, there found no increased risk of Breast cancer in association with antibiotic use. The main strengths of this study are its large size, the population based design based on Danish health care system, and the use of exposure data collected before hospitalization for breast cancer. In conclusion the present data showed no increased breast cancer risk among antibiotic users in a population characterized by one of the highest breast cancer incidence rates world wide, although further study would be useful. Garcia Rodriguez and Gonzalez-Perez (2005) A recent nested case control study found that increasing use of antibiotics was associated with a significantly elevated risk of breast cancer. Women aged 30- 79 years who were registered in the data base between January 1995 and December 2001 comprised the study cohort. A total of 3,708 women with incident cases of breast cancer and 20,000 frequency matched controls were entered into nested case control analysis. On the basis of these results, antibiotic use does not appear to be a major determinant of breast cancer risk. Antibiotic medications have effects on immune function and inflammation and reduce the ability of intestinal micro flora to metabolize photochemicals. In a recent study from group health cooperative of Puget sound, it was found that cumulative exposure of antibiotics of more than 500 days was associated with a relative risk of breast cancer greater than two-fold. The general practice research contains computerized medical information entered by general practitioners in the United Kingdom. Data on over 2 million patients are systematically recorded and sent anonymously to the medicines and health products regulatory agency, which collects and organizes this information for use in research projects. An additional requirement for participating practices is the recording of indications for new courses of therapy. All females aged 30-79 were identified between January 1995 and December 2001. All study participants were followed from the starting date to the occurrence of one of the following end points: a recorded diagnosis of breast cancer, age 80 years, death, or the end of the study period and 4,005 patients were identified with a recorded code of breast cancer. In the end 3,708 patients were considered to have incident cases of breast cancer. The incidence rate of breast cancer was 156 per 100,000 person-years, which is well in line with other reports from the United Kingdom. The prevalence of ever use of antibiotics among controls in our study was similar to the prevalence observed by velicer et al. Use of antibiotics was not associated with increased risk of breast cancer. How ever, use of antibiotics to treat skin disorders was associated with increased risk of breast cancer in comparison with use of antibiotics to treat respiratory diseases. They could not find clear association between breast cancer and antibiotic use, either overall or when they performed sub analysis according to treatment duration or prescription indication. The results of this study contrast with those of two previous reports. Knekt et al found that young women exposed to antibiotics for treatment of urinary infection had an elevated risk of breast cancer. Finally the findings of small increased risk among users of antibiotics for skin disorders warrants further investigation. Kaye and Jick (2005) Several studies have linked antibiotic use to the risk of breast cancer. Knekt et al found an increased risk of breast cancer during 18 years of follow-up among women younger than 50 years who reported current or past use of antibiotics for urinary tract infections at study entry. Velicer et al noted that intestinal micro flora have the ability to metabolize phytochemicals from edible plants in to the compounds that may protect against the cancer and a reduced concentration of these compounds in the intestinal lumen as a result of antibiotic use might increase the risk of breast cancer and other types of cancer. The study found increased relative risks of breast cancer in relation to 6 to 8 classes of antibiotics analyzed. To further investigate the relation between the antibiotic use and breast cancer, case-control study was undertaken using information from the U.K. General Practice Research database. Computerized medical record information from 270 General Practices in the United Kingdom that contribute data to the general practice research database was used. General practitioners enter demographic and diagnostic data by using computer software. The study protocol was approved by the scientific and ethical advisory group of the general practice research database. They assessed prescriptions for 8 classes of antibiotics. They also used conditional logistic regression to estimate odd ratios and confidence intervals for the association between cumulative days of antibiotics and the risk of breast cancer. 1268 cases were identified of incident breast cancer among women aged 40-79 years and matched them to 6291 controls. High body mass index, use of hormone replacement therapy, frequency of mammograms and frequency of visits to general practice were independently associated with an increased risk of breast cancer. In a separate analysis of number of antibiotic prescriptions recorded, there found no evidence for an association between antibiotic use and risk of breast cancer. Risk estimates for specific antibiotic classes were estimable because of small numbers. The risk of breast cancer was highest for macrolide use for 101-500 days but this estimate is based on only 10 cases and 8 controls. The case control study of velicer et al which found an increased risk of breast cancer associated with exposure to several commonly used classes of antibiotics, created renewed interest in the hypothesis that various antibiotics might alter women’s risk of developing breast cancer. The previous study did not provide an evidence in the risk of breast cancer in relation to the antibiotic use because the study evaluated only self-reported current or past use of antibiotics to treat infections at one point in time. The data that was presented do not support the hypothesis that antibiotic use is associated with an increased risk of breast cancer. Although we cannot routinely distinguish noninvasive from invasive breast cancers in the General practice research database, noninvasive lesions account for a minority of breast cancers in the U.K. as in the United States. METHODOLOGICAL STRENGTHS AND WEAKNESSES:- According to Knekt (2000) with few exceptions, only weak associations existed between the histories of antibacterial treatment for urinary tract infection and known potential risk factors of breast cancer, i.e. regional type educational level, Marital status, body mass index, height, parity and alcohol use the strongest association was observed with parity, with a considerable low prevalence of antibacterial treatment among nulliparous women. According to Velicer (2003) it is unclear how pertinent antibiotic effects in the humans and the association between antibiotic use and breast cancer warrants further considerations. According to Velicer (2004) increasing cumulative number of antibiotic prescriptions were associated with increasing risk of incident breast cancer and all classes of antibiotics are associated with increased risk. According to Sornson(2004) they found no substantial differences between the classes of antibiotics and relative risk did not vary between parous and nulliparous women. According to Kaye (2005), general current data base do not provide evidence in support of the hypothesis that several classes of commonly used antibiotics increase the risk of breast cancer. Some reasons in my opinion may be responsible for these contradictory results are Some research suggests an increased risk of breast cancer among women with conditions likely to require long-term antibiotic use (e.g., acne, recurrent urinary-tract infections, UTI). However, this hypothesis has not been verified and the possible biological mechanisms are not entirely clear. 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 sub-analysis having breast cancer fatality as the outcome. 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. Therefore 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 other factors are pertinent to underlying exposures. CONCLUSION: 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 and risk of breast cancer are sparse. 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 other factors are pertinent underlying exposures. Although further studies are needed, these findings reinforce the need for prudent long-term use of antibiotics. It is not simply just that antibiotics cause cancer, but it seems that immune insult by the pathogen, inflammation, severity of disease, length of therapy and hormonal status influence the risk of breast cancer. Lacking in the study were the reasons patients were on antibiotics and what type of breast carcinoma was present, for example, estrogen receptor positive versus receptor negative. These factors are important since they would give us a better understanding of the effects of antibiotics on hormones and it would the oncologist to appropriately determine therapy. Additionally, there is no mention of family history of breast cancer, a key risk factor for breast cancer. All in all, women who use long term antibiotics usually are older, menopausal, on hormone replacement therapy, and therefore at higher risk for breast carcinoma. Inflammation (by oxidative free radicals) hasbeen linked to carcinogenesis, therefore the longer the inflammation caused by the pathogen is present the longer the use of antibiotics; and therefore an increased risk linked to inflammation. The real answer may be multifactorial, and no one cause will be the culprit. Whatever the underlying mechanism, several conclusions can be drawn from this study. First, stay away from antibiotics and you will reduce your risk of breast cancer. Second, pursue alternatives to antibiotics for infections. Other effective methods for treating infections include nutritional approaches, homeopathic treatment, and herbal medicines. Third, if you are prone to frequent infections, pursue treatments that will bolster the immune system and prevent future infections. Again, many methods can accomplish this. Seek out a qualified practitioner of classical homeopathy, a licensed acupuncturist who prescribes herbal treatments, a naturopathic physician, or a holistic doctor or nutritionist. BIBLIOGRAPHY Breast Cancer. Cancer Topics. National Cancer Institute. Page retrieved on October 02, 2006 from: http://www.cancer.gov/cancerinfo/types/breast Study Shows Link Between Antibiotic Use and Increased Risk of Breast Cancer. . National Cancer Institute (2004). Page retrieved on October 02, 2006 from: http://www.nci.nih.gov/newscenter/pressreleases/antibiotics Velicer CM, Heckberg SR, Lampe JW, Potter JD, Robertson CA, Taplin SH. Hypothesis: is antibiotic use associated with breast cancer? Cancer Causes and Control (2003). Christine M. Velicer,Susan R. Heckbert,Johanna W. Lampe, John D. Potter, Carol A. Robertson and Stephen H. Taplin. Antibiotic Use in Relation to the Risk of Breast Cancer. American Medical Association. JAMA, February 18, 2004—Vol 291, No. 7. HT Sorensen,MV Skriver, S Friis, JK McLaughlin, WJ Blot and JA Baron. Use of antibiotics and risk of breast cancer: a population-based case–control study.British Journal of Cancer (2004). P Knekt, H Adlercreutz, H Rissanen, A Aromaa , L Teppo and M Heliövaara. Does antibacterial treatment for urinary tract infection contribute to the risk of breast cancer? British Journal of Cancer (2000) 82(5), 1107–1110. L.A.Garcıa Rodrıguez, A.Gonza lez-Perez. Use of Antibiotics and Risk of Breast Cancer. American Journal of Epidemiology. Vol.161,No.7 (2005). James A. Kaye and Hershel Jick. Antibiotics and the Risk of Breast Cancer. Epidemiology. Volume 16.Number 5 (2005). Read More