Pesticides and Breast Cancer

doi:10.4236/abcr.2012.13005

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Advances in Breast Cancer Research, 2012, 1, 30-35

http://dx.doi.org/10.4236/abcr.2012.13005 Published Online October 2012 (http://www.SciRP.org/journal/abcr)

Pesticides and Breast Cancer

Roberto Ferro, Arvin Parvathaneni*,

Sachin Patel, Pramil Cheriyath

Pinnacle Health, Harrisburg, USA

Email: *[email protected]

Received June 7, 2012; revised July 15, 2012; accepted July 24, 2012

ABSTRACT

Along with other etiological factors like genetics, family history, age, etc. there is growing scientific evidence that ex-

posure to chemicals, including pesticides is associated with increased incidence of breast cancer among women. Vari-

ous animal studies have demonstrated the carcinogenic effect of pesticides byacting as Xenoestrogen, interacting and

disrupting estrogen receptors or by damaging breast tissue DNA inducing malignancy/catalyzing existing DNA muta-

tion in susceptible individuals. Pesticide’s role as a contributing etiological factor in growing incidence of breast cancer

is of particular concern as pesticides is one of the chemicals to which humans get exposed every day in significant con-

centration. In this review we describe various kinds of pesticides and their respective associations to breast cancer.

Keywords: Breast Cancer; Pesticides

1. Background

Breast cancer is the second most common cancer occur-

ring among American women, after skin cancer [1], with

incidence rate of 124.3 per 100,000 women per year. It is

also the second leading cause of cancer related mortality

in women with high mortality rate of 23.0 per 100,000

women, followed by lung cancer. According toAmerican

Cancer Society (ACS), in the year 2012, 226,870 new

cases of invasive breast cancer will be diagnosed and

39,510 women will die from breast cancer. Incidence rate

has steadily increased from 1 in 20 women in 1961 up to

1 in 8 women in 2010 [1].

Along with other etiological factors like genetics, fam-

ily history, age, etc. there is growing scientific evidence

that exposure to chemicals, including pesticides is asso-

ciated with increased incidence of breast cancer among

women. Various animal studies have demonstrated the

carcinogenic effect of pesticides byacting as Xenoestro-

gen, interacting and disrupting estrogen receptors or by

damaging breast tissue DNA inducing malignancy/cata-

lyzing existing DNA mutation in susceptible individuals.

Pesticide’s role as a contributing etiological factor in

growing incidence of breast cancer is of particular con-

cern as pesticides is one of the chemicals to which hu-

mans get exposed every day in significant concentration.

Most of the exposure to harmful carcinogenic agents is

through food, water, products used to control pests like-

herbicides (weeds), fungicides (fungi), insecticides (in-

sects) and Rodenticide (rodents), cosmetics, plastics,

pharmaceuticals etc. Environmental Protection Agency

(E- PA) is responsible for regulating pesticides under the

Federal Insecticide, Fungicide, and Rodenticide Act

(FIFRA) and the Food Quality Protection Act (FQPA).

EPA provides federal control of pesticide distribution,

sale, and use. However, their regulatory laws are based

on risk benefit ratio, giving more weight to economic

benefits of pest control against health and environmental

hazards posed by them. In this review we describe vari-

ous kinds of pesticides and their respective associations

to breast cancer.

2. Definition of Pesticide

As per Food and Agriculture Organization (FAO); Pesti-

cide is any substance or mixture of substances intended

for preventing, destroying or controlling any pest, in-

cluding vectors of human or animal disease, unwanted

species of plants or animals causing harm during or oth-

erwise interfering with the production, processing, stor-

age, transport or marketing of food, agricultural com-

modities, wood and wood products or animal feedstuffs,

or substances which may be administered to animals for

the control of insects, arachnids or other pests in or on

their bodies, also included are substances intended for

use as a plant growth regulator, defoliant, desiccant or

agent for thinning fruit or preventing the premature fall

of fruit and substances applied to crops either before or

after harvest to protect the commodity from deterioration

during storage and transport.

*Corresponding author.

R. FERRO ET AL. 31

2.1. Groups of pesticides based on the target

organism

Type of pesticide Target pest group

Algaecides or algaecides Algae

Avicides Birds

Bactericides Bacteria

Fungicides Fungi

Insecticides Insects

Miticides or acaricides Mites

Molluscicides Snails

Nematicides Nematodes

Rodenticide Rodents

Herbicides Unwanted plants

2.2. Groups of pesticides based on chemical

composition

Insecticides Herbicides

Persistent organic

pollutant

Dieldrin/aldrin:

organochlorine Atrazine: triazine PCBs

Heptachlor:

organochlorine 2,4,5 TP: auxin Dioxin

Ddt/dde:

organochlorine DDT/DDE

Malathion:

organophosphates

3. Pesticides Associated with Breast Cancer

3.1. Triazine

Triazine group of chemicals are most widely used herbi-

cidesin the world. This group consists of atrazine, si-

mazine, propazine and cyanazine. Among all triazines,

Atrazine is of particular concern because it is one of the

most widely used herbicides with 76 million pounds of it

applied each year as it is economical and effective. Epi-

demiological studies have shown that it is associated

with Breast cancer in women and other ecological dis-

ruptions. Continuous use of atrazine as the primary her-

bicide for years has resulted into contamination of

ground water and soil with it.

Elevated levels of atrazine have been demonstrated in

water and soil each spring and summer, particularly in

agricultural areas like Midwest where it is primarily used

to control weeds in cornfields. Increasing Atrazine use is

concerning as United States and other countries are

mulling on corn production for ethanol, resulting in con-

current rise in use of Atrazine herbicides and its associ-

ated toxicity.

Atrazine is a known endocrine disruptor. It interferes

with Pituitary-Ovarian axis decreasing Prolactin and lu-

teinizing hormone levels, the changes which contribute

to increase in mammary gland tumor [2].There is docu-

mented evidence of Atrazine causing dramatic damage to

reproductive structures in frogs, fish and other wildlife

[3], however correlational human studies are lacking.

Atrazine also induces increased aromatase enzyme activ-

ity resulting in increased levels of estrogen which is di-

rectly linked with Breast cancer [4]. Studies by Ueda et

al. showed significant acceleration in tumor cell prolif-

eration when experimental rats with existing breast can-

cer were exposed to Atrazine compounds [5]. Studies by

Raynor et al. concluded that Inutero exposure of Atrazine

compounds results in delayed development of mammary

glands, a known risk factor for breast neoplasm [6].

Current standards for drinking water restricts atrazine

to 3 parts per billion in United States, but from studies, it

has been concluded that Atrazine is harmful even at lev-

els of 0.1 parts per billion, which is 30 times lower than

the current drinking water standard in the United States.

Atrazine was banned in European Union in 2005 because

of the persistent ground water contamination caused by it

and studies indicating its carcinogenic potential for

mammary gland, prostate and also its correlation with

ecological disruption. But it is still widely used in USA

as Environmental Protection Agency (EPA) is reluctant

to ban Atrazine as it considers Atrazine’s risk benefit

ratio in favor of its use as an herbicide.

3.2. Di-Chloro Di-Phenyl Trichloro Ethane

(DDT/DDE)

DDT was one of the most widely used insecticide in the

world , successful in eradication of malaria from USA

and other countries, though at an expense of devastating

environmental problems and human health hazards. Mul-

tiple case control studies have shown a correlation be-

tween blood DDT/DDE levels and development of Breast

malignancy. Cohn. BA et al. carried out a prospective,

nested case control study to analyze the relation between

age of exposure to DDT and subsequent breast cancer

occurrence later in their life. In that study 129 cases de-

veloped breast cancer by the age of 50 years as opposed

to 129 controls (p = 0.02). It concluded that women who

are exposed to DDT and its metabolitesin early half of

their adolescence (first 14 years of women’s life) have 5

fold more risk of having breast cancer later in their life

than those women who had same amount of exposure

after first 14 years of their life [7]. Retrospective case

control studies by Charlier et al. indicate that certain

pollutants like DDT and its metabolites are present insig-

nificantly higher concentration in women with breast

R. FERRO ET AL.

cancer when compared to the control group [8]. A case

control study to analyze the relationship between DDT

levels, lactation history and breast cancer occurrence, by

Romieu et al. deduced evidence of dose response rela-

tionship of breast cancer with DDE in serum (highest

compared with lowest quintile OR = 3.81; 95% CI, 1.14 -

12.8) [9]. In a hospital based case control study by

Demers et al. to investigate the relation between blood

DDE levels with staging and grading of tumor, a positive

correlation was found between increased doses of DDE

and its metabolites with aggressive tumors with lymph

node involvement indicating that DDT/DDE might ag-

gravate malignancy of mammary glands, if not initiate it

[10].

3.3. Dieldrin and A ld ri n

Dieldrin and Aldrin were commonly used insecticides in

corn fields till late 1980’s when they were banned in

United States in 1987 due to concerns posed to environ-

ment and human health. Dieldrin mainly acts as a Xeno-

estrogen and also disrupts Androgenic pathways. Addi-

tion of Dieldrin into MCF-7 (Michigan Cancer Founda-

tion-7) human breast cancer cell in vitro lead to cells

accelerated growth and proliferation. (Andersen, 2002;

Soto, 1994) [11]. Exposing experimental rats, prenatally

and neonatally with environmentally relevant doses of

Dieldrin resulted in increased incidence of breast cancer

among them, likely mechanism of it may be Dieldrin

mediated changes in cellular expression of BNDF and

cell signal receptors Heroin breast tissue [12]. In 1998 a

cohort study conducted by Copenhagen Center for pro-

spective studies concluded that Dieldrin is associated

with increased incidence, incidence of aggressive tumor

and higher mortality in breast cancer. The result from the

study showed a dose-related increase in risk of breast

cancer (adjusted odds ratio of 2.05). This study also con-

cluded that tumor grading and staging is directly propor-

tional to blood Dieldrin levels [13].

3.4. Heptachlor (HE)

Heptachlor is a well-known carcinogenic insecticide

which was widely used before 1980. Its commercial use

was banned in 1988 except for controlling the fire ants in

underground structures like buried pad-mounted electric

power transformers, and in underground cable television

and telephone cable boxes. Heptachlor has long half-life

in environment and its residues can be found 14 years

after its intended use.

Heptachlor Epoxide, metabolite of heptachlor gets ac-

cumulated in adipose tissues including mammary gland.

HE (Heptachlor Epoxide) alters the hepatocytes inducing

hepatocellular carcinoma. In a study by Classidy et al.

using sparing extraction coupled with gas chromatogra-

phy to determine the levels of HE, OC, and DDE in adi-

pose tissue within breast biopsies in a series of 34

women evaluated for breast abnormality, only HE show-

ed positive correlation with prevalence of breast cancer

in the biopsies [14]. HE is a xenoestrogenic compound,

combined with HE’s ability to interact with NO induces

an inverted-U increase in intracellular oxidants causing

DNA damage and subsequent malignancy. Heptachlor

also activated kinase signaling pathways resulting in ac-

celerated proliferation of cancer cells (Cassidy, 2005)

[15].

3.5. Persistent Organic Pollutants

Persistent organic pollutants (POP) are organic com-

pounds which are resistant to environmental degradation

and lipophilic (Brody, Moysich, et al. 2007), resulting in

bio accumulation in human tissues causing endocrine,

immune and reproductive system dysfunctions and ma-

lignancy including breast cancer. This group includes

Poly Chlorinated Biphenyls, Chlorinated dioxins, furans,

DDT etc.

3.5.1. Polychlorinated Biph enyl s (PCB)

Though PCBs were banned in USA in 1977, as they are

Persistent organic pollutant, they bio accumulate in hu-

man fat tissue over a period of time and also secreted in

breast milk (Brody, Moysich, et al., 2007). A pilot study

carried out by Falck Jr. F. et al. to measure and compare

PCB levels in breast adipose tissue in women with ma-

lignant and benign neoplasm showed significant higher

levels of PCBs in women with malignant neoplasm

compared to benign counterpart [16]. Many studies con-

cluded that genetic polymorphism plays a vital role in the

association between PCBs and breast cancer risk. They

also concluded that women with CYP1A1-m2 genetic

variant, also referred to as the exon 7 variant (present in

10 - 15 % of white women and higher percentage of Af-

rican American women) (Li, Millikan, et al., 2005) are

far more susceptible to PCB induced malignant changes

in breast tissues [17]. A study done by Sijin Liue et al.

concluded that PCBs enhance metastatic potential of

breast cancer cells by activating Rho-associated Kinase

(ROCK) [18]. Muscat et al. concluded that high PCB

levels in breast tissue are directly related to breast cancer

occurrence [19]. Hoyer et al. reported strong association

between higher PCB values and mortality among women

with Estrogen receptor positive tumors (OR = 2.5; 95%

CI, 1.1 - 5.7) [20].

3.5.2. Polybrom i n ated Diph eny l Ethers (PBDE)

These compounds are structurally and functionally simi-

lar to PCBs and were widely used after PCBs were

banned. A recent study done by Zhi-Hua Li et al. in

china found out that PBDEs, especially PBDE-209 en-

hance proliferation of tumor cell lines in a dose depend-

R. FERRO ET AL. 33

ent manner by altering cell growth cycle inducing S

phase between G2 and M phase. PBDE-209 is also

known to partially inhibit the cell apoptosis in breast

cancer cells (MCF-7) and also suppresses Gö6976- and

PD98059- induced apoptosis in all cell lines. Zhi-Hua Li

et al. Concluded that PBDE induces proliferative effect

on normal as well as cancer cell lines in breast and

women’s reproductive system, warranting further studies

to confirm the role of BDEs in Breast cancer and other

neoplasm of reproductive system among women [21].

3.5.3. Other Pe sti c i des

Among other pesticides Chlordane, Malathion were as-

sociated with increased risk of breast cancer, specifically

in young women or who had early onset of cancer. In a

registry-based case-control study of breast cancer in farm

labor union members in California, Mills PK, Yang R

investigated new diagnosed 128 breast cancer patients

and 640 cancer free controls which revealed this associa-

tion [22]. Another large prospective cohort study under-

taken by Lawrence et al. to evaluate the association be-

tween pesticides and occurrence of breast cancer among

women whose husbands work in agricultural fields, re-

vealed an increased incidence of breast cancer in women

exposed to 2, 4, 5-triclorophenoxypropionic acid [23].

3.6. Relation of Pesticides with Estrogen

Receptor Status

Most of the pesticides have xenoestrogenic properties,

they interact with estrogen receptor acting as a weak es-

trogen, and hence their effect on Estrogen receptor posi-

tive breast cancer cells is worse when compared with

estrogen receptor negative breast cancer. Epidemiologi-

cal study conducted by Sophie St-Hilaire et al. to find out

Estrogen receptor positive breast cancers and their asso-

ciation with environmental factors concluded that ER+

breast cancer develops aggressively when exposed to

pesticides having xenoestrogenic effect than ER− breast

cancer [24].

4. Conclusions

Despite efforts by environmental regulatory authorities to

monitor the health effects of exposure to pesticides nu-

merous people get exposed to these harmful chemicals

each year. With the alarming rise of unsafe practices in

agriculture the rate of this exposure is also escalating

each year. There has been increasing evidence of asso-

ciation between pesticide use and occurrence of breast

cancer across the world. The economic burden due to

breast cancer in USA alone was 13.886 billion dollars in

year 2006, which accounts to about 12.5 percent of total

cancer care cost for all type of cancers in USA [25].

There is growing scientific evidence of association be-

tween exposure to pesticide and increased occurrence of

breast cancer. Many studies have identified the carcino-

genic potential of pesticides like Atrazine, DDT, DDE,

Dieldrin, Aldrin, Heptachlor, Polychlorinated biphenyls

(PCB), Polybrominated diphenyl ethers (PBDE) and few

others. They have been found to have positive correlation

with incidence and aggressiveness of breast cancer. In-

terestingly, increase in incidence of breast cancer has

paralleled the escalating consumption of pesticide in

western countriespost-World War 2, and the trend is rep-

licating in developing countries following increase in

agriculture and concurrent increase in use of pesticides.

There are certain measures which if followed, signifi-

cantly decrease the pesticide exposure and subsequent

effect on breast tissue. Most common household meas-

ures includes taking precautionary measures while using

pesticide sources like buying organic produce, buying

produce from local farmers than from large store, Wash-

ing fruits and vegetables before use preferably with

commercially available Commercial vegetable and fruit

washes, identify the produce which has high pesticide

content and avoid it, Using nontoxic methods for con-

trolling insects like diatomaceous earth, which will kill a

broad range of common indoor insects without posing

any hazard to your family or pets, replacing all of house

cleaning chemicals with nontoxic , environment friendly

counterparts, etc.

Measures on larger scale includes enforcing tough

regulations for pesticides suspected of having carcino-

genic potential, development of effective methods to

achieve optimum pest control with minimum use of pes-

ticides, minimizing pollution of surrounding water and

soil in communities, providing technical assistance to

farmers for more effective and judicious use of pesticides

and funding more research to develop pest resistant crops

and environment friendly pesticides.

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