Antihistamine use and breast cancer risk

Abstract

Antihistamines are structurally similar to DPPE, a tamoxifen derivative known to promote tumor growth, and to antidepressants. Animal experiments have linked certain antihistamines and antidepressants with enhanced tumor growth in mice. The few epidemiologic studies examining antihistamine use have not indicated an increased risk. In light of suggestive animal data, structural similarities between antihistamines and DPPE, the widespread use of antihistamines, and the lack of epidemiologic investigation into their use and breast cancer risk, it is important to examine this issue. Antihistamines are available as both prescription and nonprescription medications, and are commonly used for the treatment of allergic symptoms (e.g., for relief from hayfever), for cold symptoms or for insomnia. Both antihistamines and tricyclic antidepressants are structurally similar to DPPE [N,N-diethyl-2-(4-(phenylmethyl)phenoxy) ethanamine HC1], a tamoxifen derivative known to promote tumor growth by binding to intracellular histamine receptors. This structural similarity to DPPE led to 2 widely cited rodent studies led by Brandes, 1,2 which suggested that both antihistamines and antidepressants promote accelerated tumor growth. 1,2 . One study found that inoculated fibrosarcomas and melanomas, and carcinogen (DMBA) induced mammary tumors were promoted by the administration of the antidepressants fluoxetine and amitriptyline. 1 The other study found that mice injected with melanoma or fibrosarcoma cells experienced accelerated tumor growth with the administration of human equivalent doses of the antihistamines loratidine and astemizole (for melanoma and fibrosarcoma), and hydroxyzine (for melanoma). 2 Animal data are suggestive of the effect that these medications might have on humans. As a result, following the publication of these results, epidemiologic studies have used human populations to explore the hypothesis that there may be a relationship between cancer risk and the use of antidepressants, and, to a lesser degree, antihistamines. Although not consistent, these studies have shown that the use of some antidepressants may be associated with an increased risk for a number of cancers, including breast. 3,4 Conversely, antihistamine use has not been associated with an increased cancer risk for breast, colon or all cancers, cancer recurrence (of melanoma, breast, or colon cancers) or for second primary cancers. 5-7 These reassuring results regarding antihistamines are not definitive, however, as the number of studies examining this relationship is small; one was limited to an examination of prescription antihistamine use, and another considered only cancer recurrence and second primary cancers. 6,7 To our knowledge, there are no other epidemiologic studies examining the relationship between nonprescription antihistamine use and the risk of cancer.Given the high incidence of breast cancer, widespread use of antihistamines, lack of epidemiologic investigation into the association, suggestive animal data and its structural similari...

An overview of the association between allergy and cancer

“…Early birth order and reduced sidship size (as possible indicators of environmental exposures such as reduced exposure to infectious agents or exposures in the intrauterine environment) have been positively associated with allergy occurrence167, 168, 169 and inversely associated with risks of NHL,62 AML,170 and HD in children,171 but positively associated with ALL170 and HD in young adults 171, 172. There is a possibility that asthma and allergy medications are related to cancer; however, there exists little evidence to date 54, 67, 76, 90, 91, 92, 94, 95, 97, 102, 105, 173, 174, 175, 176, 177, 178. Those with a history of asthma and allergy may also tend to avoid other exposures related to cancer due to their allergy symptoms such as certain occupational exposures or exhibit different dietary or lifestyle preferences 179, 180, 181, 182…”

Clinical outcomes and adverse effect monitoring in allergic rhinitis

“…Large epidemiological studies of the longterm safety of H 1 -antihistamines have not raised any concerns about their potential tumor-promoting effects, [141][142][143] and case reports of tumor promotion in this population are extremely rare. In mice, some H 1 -antihistamines injected by the intraperitoneal route were reported to promote the growth of B16F10 melanoma cells or C-3 fibrosarcoma cells injected subcutaneously 144 ; however, these findings have not been replicated, and regulatory agencies have not recommended any change in H 1 -antihistamine usage on the basis of them.…”

Antihistamine use and immunoglobulin E levels in glioma risk and prognosis

“…In addition to their immunomodulatory capabilities, another reason for suspecting the potential involvement of common antihistamines in carcinogenic processes is their structural similarity to N,N-diethyl-2-[4-(phenylmethyl)phe- noxy]ethanamine • HCl (DPPE), which is an intracellular histamine antagonist related to tamoxifen that has been shown to promote tumor growth [26]. Also of concern, particularly with regard to brain tumor etiology, is that antihistamines, many of which are capable of crossing the blood-brain barrier, may induce nitrosatable exposures in the brain [11, 25].…”