Caroline Paul Mari, Department
of Biochemistry and Biotechnology, Faculty of Science, Annamalai University,
Chidambaram, Tamil Nadu, India, and Mirunalini Sankaran, Department of
Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Chidambaram,
Tamil Nadu, India. Wrote a research article about Fish Oil and Tamoxifen
Modulate Hormone Receptors in Mammary Cancer. Entitle, Modulation of estrogen
and progesterone receptor expression by fish oil and tamoxifen in 7,12 dimethyl
benz(a) anthracene induced mammary carcinogenesis in female sprague dawely rats.
This research paper published by the Journal of Biodiversity and Environmental Sciences | JBES. an open access scholarly research journal
on Environmental Sciences. under the affiliation of the International
Network For Natural Sciences| INNSpub. an open access multidisciplinary
research journal publisher.
Abstract
Cancer remains a
primary global health challenge characterized by uncontrolled cellular
proliferation and significant mortality. Within this landscape, breast cancer
represents one of the most prevalent and hormone-dependent malignancies,
contributing substantially to cancer-related deaths. While endocrine therapy
with tamoxifen is a standard treatment for estrogen receptor-positive (ER+)
breast cancer, its efficacy is often hampered by dose-associated toxicity and
inconsistent outcomes. This study evaluates the potential of fish oil, rich in
omega-3 polyunsaturated fatty acids, as an adjunct to tamoxifen in modulating
hormonal imbalance and estrogen/progesterone receptor (ER/PR) expression. A
7,12-dimethylbenz(a)anthracene (DMBA)–induced mammary tumor model was
established in female Sprague Dawley rats to assess the effects of fish oil
alone and in combination with low and high-dose tamoxifen. Plasma estradiol and
progesterone levels were quantified via ELISA, while ER/PR expression in
mammary tissues was evaluated by immunohistochemistry. DMBA induction
significantly increased ER and PR expression, indicating hormonal
dysregulation. Fish oil treatment alone produced a moderate reduction in
receptor expression. However, the combination of fish oil with tamoxifen markedly
suppressed ER and PR levels. Notably, the fish oil low-dose tamoxifen
combination produced effects comparable to the high-dose combination,
suggesting that fish oil may enhance tamoxifen efficacy and allow effective
endocrine regulation with a lower drug dose and potentially reduced toxicity.
Fish oil maintained physiological hormone levels in control animals. In
conclusion, fish oil enhances the endocrine-modulating effects of tamoxifen and
may serve as a beneficial supplementary strategy to improve therapeutic
efficacy while potentially minimizing adverse effects.
Introduction
Cancer persists as a
leading cause of mortality worldwide, continuing to limit gains in global life
expectancy. According to GLOBOCAN 2022, approximately 20 million new cancer
cases and 9.7 million cancer-related deaths were reported globally. Female breast
cancer has emerged as the most commonly diagnosed malignancy, accounting for
nearly 2.30 million new cases, followed by lung, colorectal, prostate, and
stomach cancer (Bray et al. 2024 and National Cancer Institute, 2026). Despite
significant advances in breast cancer management including surgery,
radiotherapy, and chemotherapy treatment-related toxicity, high economic
burden, and inconsistent therapeutic responses remain major challenges
contributing to sustained mortality rates.
Breast cancer is a
complex and diverse disease influenced by genetic and environmental factors,
resulting in abnormal cell growth through multiple signalling pathways. Nearly
two-thirds of breast cancers are hormone-dependent, regulated by estrogen and progesterone
via Estrogen Receptors (ER) and Progesterone Receptors (PR) (Freihat et al.,
2025). These hormone signalling mechanisms contribute to cancer initiation,
progression, metastasis, and maintenance of normal breast tissue.
Breast cancer is a
complex and diverse disease influenced by genetic and environmental factors,
resulting in abnormal cell growth through multiple signalling pathways. Nearly
two-thirds of breast cancers are hormone-dependent, regulated by estrogen and
progesterone via Estrogen Receptors (ER) and Progesterone Receptors (PR)
(Freihat et al., 2025). These hormone signalling mechanisms contribute to
cancer initiation, progression, metastasis, and maintenance of normal breast
tissue.
In light of this, there
is increasing interest in identifying alternative and supportive therapeutic
approaches that target hormonal dysregulation with reduced toxicity. Natural
bioactive compounds derived from dietary sources have gained attention for
their potential to enhance treatment efficacy while minimizing adverse effects
(Bidinotto et al., 2012 and Bougnoux et al., 2009). Fish oil, rich in omega-3
polyunsaturated fatty acids (PUFAs) such as Eicosapentaenoic acid (EPA) and
Docosahexaenoic acid (DHA), has demonstrated antioxidant, antiinflammatory, and
antitumor properties. These fatty acids modulate membrane fluidity, reduce
oxidative stress, and suppress pro-inflammatory mediators, thereby influencing
estrogen biosynthesis and hormone-dependent signalling pathways (Fabian et al.,
2015). Additionally, their ability to regulate aromatase activity and improve
antioxidant defences supports their role in modulating endocrine function
during mammary carcinogenesis.
Tamoxifen, a selective
estrogen receptor modulator, remains a cornerstone in the treatment of
hormoneresponsive breast cancer due to its ability to inhibit estrogen binding
and suppress tumor growth. However, its long-term use is often limited by
adverse effects and the development of resistance (Manni et al., 2015).
Emerging evidence indicates that the combination of fish oil and tamoxifen may
enhance therapeutic efficacy through multiple mechanisms, including improved
drug bioavailability, modulation of apoptosis, and reduction of inflammation.
(Subbaramaiah et al. 2019), This combination has been shown to influence
circulating hormone levels and downregulate ER and PR expression in tumor
tissues. Collectively, these findings highlight the potential of fish oil as an
effective adjuvant strategy to improve endocrine regulation and therapeutic outcomes
in hormone-dependent breast cancer.
Reference
Bidinotto LT, de Cicco
RL, Vanegas JE, Santucci-Pereira J, Vanden Heuvel JP, Washington S. 2012. Fish
oil alters tamoxifen-modulated expression of mRNAs that encode genes related to
differentiation, proliferation, metastasis, and immune response in rat mammary
tumors. Nutrition and Cancer 64, 991–999.
Bougnoux P, Hajjaji N,
Ferrasson MN, Giraudeau B, Couet C, Le Floch O. 2009. Improving outcome of
chemotherapy of metastatic breast cancer by docosahexaenoic acid: A phase II
trial. British Journal of Cancer 101, 1978–1985.
Bray F, Laversanne M,
Sung H, Ferlay J, Siegel RL, Soerjomataram I. 2024. Global cancer statistics
2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in
185 countries. CA: A Cancer Journal for Clinicians 74, 229–263.
Cao W, Ma Z, Rasenick
MM, Yeh S, Yu J. 2012. N-3 polyunsaturated fatty acids shift estrogen signaling
to inhibit human breast cancer cell growth. PLoS ONE 7, e52838.
Fabian CJ, Kimler BF,
Hursting SD. 2015. Omega-3 fatty acids for breast cancer prevention and
survivorship. Breast Cancer Research 17, 62.
Freihat O, Sipos D,
Kovacs A. 2025. Global burden and projections of breast cancer incidence and
mortality to 2050: A comprehensive analysis of GLOBOCAN data. Frontiers in
Public Health 13, 1622954.
Manni A, El-Bayoumy K,
Skibinski CG, Thompson HJ, Santucci-Pereira J, Bidinotto LT, et al. 2015. Combination
of antiestrogens and omega-3 fatty acids for breast cancer prevention. BioMed
Research International 2015, 638645.
Manni A, Richie JP Jr,
Xu H, Washington S, Aliaga C, Bruggeman R. 2020. Influence of omega-3 fatty
acids on endocrine signaling and mammary tumor growth in experimental breast
cancer. Breast Cancer Research and Treatment 180, 351–362.
Manni A, Xu H,
Washington S, Aliaga C, Cooper TK, Richie JP Jr. 2010. The impact of fish oil
on the chemopreventive efficacy of tamoxifen against development of
N-methyl-N-nitrosourea-induced rat mammary carcinogenesis. Cancer Prevention
Research 3, 322–330.
National Cancer
Institute. 2026. Low dose tamoxifen with or without omega-3 fatty acids for
breast cancer risk reduction (NCT06195306). ClinicalTrials.gov.
Rengarajan T, Rajendran
P, Nandakumar N, Lokeshkumar B, Rajendran P, Nishigaki I. 2015. Exposure to
polycyclic aromatic hydrocarbons and risk of breast cancer. Environmental
Toxicology and Pharmacology 40, 605–614.
Rodgers KM, Udesky JO,
Rudel RA, Brody JG. 2018. Environmental chemicals and breast cancer: An updated
review of epidemiological literature informed by biological mechanisms.
Environmental Research 160, 152–182.
Subbaramaiah K, Iyengar
NM, Dannenberg AJ. 2019. Targeting the white adipose tissue
inflammation-aromatase axis for breast cancer prevention. Cancer Prevention
Research 12, 721–728.
Yager JD, Davidson NE.
2006. Estrogen carcinogenesis in breast cancer. The New England Journal of
Medicine 354, 270–282.
