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
Received June 7, 2012; revised July 15, 2012; accepted July 24, 2012
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
Breast cancer is the second most common cancer occur-
ring among American women, after skin cancer , 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 .
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.
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R. FERRO ET AL. 31
2.1. Groups of pesticides based on the target
Type of pesticide Target pest group
Algaecides or algaecides Algae
Miticides or acaricides Mites
Herbicides Unwanted plants
2.2. Groups of pesticides based on chemical
organochlorine Atrazine: triazine PCBs
organochlorine 2,4,5 TP: auxin Dioxin
3. Pesticides Associated with Breast Cancer
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-
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 .There is docu-
mented evidence of Atrazine causing dramatic damage to
reproductive structures in frogs, fish and other wildlife
, 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 . 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 . 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 .
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 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 . 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
Copyright © 2012 SciRes. ABCR
R. FERRO ET AL.
cancer when compared to the control group . 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) . 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
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) . 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 . 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 .
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 . 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)
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,
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 . 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 . A study done by Sijin Liue et al.
concluded that PCBs enhance metastatic potential of
breast cancer cells by activating Rho-associated Kinase
(ROCK) . Muscat et al. concluded that high PCB
levels in breast tissue are directly related to breast cancer
occurrence . 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) .
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-
Copyright © 2012 SciRes. ABCR
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 .
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 . 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 .
3.6. Relation of Pesticides with Estrogen
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
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 .
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
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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