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Breast Cancer – Cardiotoxicity

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Flaxseed Oil did not interfere with Trastuzumab in breast cancer but rather enhanced its tumor-reducing effects and combined Flaxseed Oil and low dose Trastuzumab was as effective as high dose TRAS treatment.

I was diagnosed with multiple myeloma in early 1994. I underwent aggressive conventional therapies including several cardiotoxic chemotherapy regimens including adriamycin, cytoxan, busulphan and melphalan. I developed chemotherapy-induced cardiomyopathy (CIC) in late 2010.

A common breast cancer side effect is chemotherapy-induced cardiomyopathy. According to the research below, Trastuzumab can do the same thing to HER breast cancer patients undergoing chemotherapy.

I wish I knew then what I know now…If you are a breast cancer patient undergoing Trastuzumab, what do you do? The answer is to include evidence-based integrative therapies.

According to the study linked below, flaxseed oil can enhance the BC killing effect of Trastuzumab while it protects the heart from the cardio toxicity of Trastuzumab.

I am both a CIC survivor and cardiac rehab coach. Meaning, I’ve taken my years managing my own CIC and work with fellow cancer survivors manage their own heart health.

I often encourage cancer patients to add integrative therapies to their conventional chemotherapy and radiation. Research has repeatedly shown that the efficacy of chemo can be enhanced with many different integrative therapies. Flaxseed oil is one of those integrative therapies.

Flaxseed oil (FO), according to the study linked below, enhances the efficacy of Trastuzumab (TRAS) while FO protects the heart from TRAS’s cardio toxicity.  In fact, there are a number of evidence-based supplements that work with conventional chemotherapies to both enhance efficacy while reducing toxicity.

To learn more about interactive therapies for breast cancer, scroll down the page, post a question or comment and I will reply ASAP.

If you worry about CIC as a breast cancer side effect and you’d like to learn more about heart healthy nutrition, supplementation and lifestyle therapies, scroll down the page, post a question or a comment and I will get back to you too. 

Thank you,

David Emerson

  • Cancer Survivor
  • Cancer Coach
  • Director PeopleBeatingCancer

Recommended Reading:

Trastuzumab-mediated cardiotoxicity: current understanding, challenges, and frontiers

“Trastuzumab, an epidermal growth factor receptor 2 (HER2) targeting humanized monoclonal antibody, has been approved for the treatment HER2-positive breast cancer and HER2-positve metastatic gastric cancer.

However, cardiotoxicity associated with its clinical application poses challenges for clinicians and patients, mechanisms of which are still evolving.

This review will summarize the current mechanistic understanding of trastuzumab-mediated cardiotoxicity, discuss the novel role of DNA topoisomerase IIB as a shared target for enhanced cardiotoxicity induced by trastuzumab and anthracyclines-based combination regimens, and speculate the potential impact of trastuzumab intervention in immune checkpoint inhibitors-based therapies…”

Flaxseed oil-trastuzumab interaction in breast cancer.

“Flaxseed oil (FO), which is rich in n-3 fatty acid, is commonly consumed by breast cancer patients because of its potential anti-cancer effects. Trastuzumab (TRAS) is the primary drug for epidermal growth factor receptor 2 (HER2) positive breast cancer.

We investigated in athymic mice whether combining dietary FO (8%) with TRAS treatment (2.5 or 5mg/kg body weight) can cause better or adverse effect on established human breast tumors overexpressing HER2 (BT-474). Control tumors significantly grew 187%, TRAS2.5 treated tumors did not change, while TRAS5, FO+TRAS2.5 and FO+TRAS5 treated tumors significantly regressed 75%, 89% and 84%, respectively, after 4weeks treatment.

Two weeks after stopping TRAS treatment while continuing on same diet, tumor size in FO+TRAS2.5 group was 87% lower than in TRAS2.5 group and was not different from TRAS5 group with or without FO. Combined TRAS2.5 treatment with FO caused a significantly lower tumor cell proliferation and higher apoptosis compared to TRAS2.5 treatment alone and showed similar effect to TRAS5 treatment with or without FO.

Hence, FO did not interfere with TRAS but rather enhanced its tumor-reducing effects and combined FO and low dose TRAS was as effective as high dose TRAS treatment.”

The cardioprotective role of flaxseed in the prevention of anthracycline and trastuzumab mediated cardiotoxicity

“Background: Cardio-Oncology focuses on the detection, prevention, and treatment of cardiovascular complications in individuals receiving cancer therapy. While the combination of Doxorubicin (DOX) and Trastuzumab (TRZ) reduces the progression and recurrence of breast cancer, these anti-cancer drugs are associated with significant cardiotoxic side effects. Little is known on the potential cardioprotective role of flaxseed (FLX) in the prevention of DOX+TRZ mediated cardiotoxicity…

Results: In our chronic in vivo model of DOX and TRZ induced cardiotoxicity, prophylactic treatment with FLX, ALA, or SDG prevented the development of left ventricular systolic dysfunction (LVSD)…

The echocardiographic findings revealed that in RC+DOX treated mice, left ventricular ejection fraction (LVEF) decreased from 75±2% to 49±2% at week-6. Prophylactic administration of FLX, ALA, or SDG partially preserved LVEF with values of 66±3%, 63±3% and 65±4%, respectively…

Conclusion: In a chronic in vivo female murine model of DOX+TRZ mediated cardiotoxicity, FLX, ALA, and SDG partially prevented adverse cardiovascular remodeling by attenuating the degree of inflammation, apoptosis, and mitochondrial dysfunction.”

Breast Cancer Side Effects- Preventing Cardiotoxicity-

According to the research below, Omega-3’s, Curcumin, Vitamin E, and vitamin C all can reduce the risk of heart damage from the breast cancer side effects caused by adriamycin-

Hello David- I was diagnosed with stage 3C HER2+ oestrogen and progesterone + receptors (breast cancer). I am 54 years old. I have had one course of “red devil” – (Adrianycin and cytoxian). I have been able to begin swimming and in my 3rd week after my 1st round am able to swim 40 lengths of a 12 meter pool. It takes me about 20 minutes. Please advice on how to avoid breast cancer side effects of this chemotherapy and protect my heart from the toxins I will be getting.

I am not one for exercise usually, but do walk a lot during my working day. I am 5.5 feet tall and weigh 67 kg.

Any assistance will be appreciated.  Thanks    Carol

Hi Carol-

I am sorry to read of your BC diagnosis. You are off to a great start however, in reducing your risk of heart damage from breast cancer side effects. The cardio toxicity of both adriamycin and cytoxan are well documented. Regular exercise (swimming, walking, etc.) stimulates your heart muscle and has been shown to reduce your risk of heart failure from BC chemotherapy. Excellent start.

I will link other studies about therapies to reduce your risk of heart disease and enhance your heart health below.

Regarding the info below, two issues to keep in mind. First, my experience and belief is that anecdotal info is useless without studies to support them. Secondly, I have broadened my definition of “evidence-based practice” to include research such as in-vivo and in-vitro studies. In other words, I look beyond FDA approved research…

Doxorubicin is the same as adriamycin- feel free to ask any and all questions.

Recommended Reading:

Protective Effects of ω-3 PUFA in Anthracycline-Induced Cardiotoxicity: A Critical Review

” ω-3 PUFA have also been shown to prevent harmful side-effects (including cardiotoxicity and heart failure) induced by conventional and innovative anti-cancer drugs in both animals and patients…

Potential Adjuvant Role of ω-3 PUFA in Combination with Antineoplastic Drugs

The ability of these fatty acids to reduce the toxic side-effects of these drugs has been largely proven [,,], and several results have also concurred to demonstrate their chemosensitizing effects, as well as their ability to prevent drug-resistance [,,]…

Can Anthracyclines (ATC)-Induced Cardiotoxicity Be Prevented by ω-3 PUFA?

ω-3 PUFA appear as ideal candidates in preventing the development of cardiac events induced by ATC chemotherapy, since these fatty acids are known to induce benefits at a cardiovascular level by positively modulating some of the cellular processes and molecular pathways that, conversely, are harmfully altered by ATC and other chemotherapeutic agents…”

Curcumin attenuates doxorubicin-induced cardiotoxicity via suppressing oxidative stress and preventing mitochondrial dysfunction mediated by 14-3-3γ.

“Doxorubicin (Dox) induces cardiotoxicity, thereby limiting its clinical application for chemotherapy of cancer. The mechanism of cardiotoxicity includes the production of excess intracellular ROS. 14-3-3s have been found to protect the myocardium against various types of injury…

Curcumin (Cur) is a polyphenolic compound that is derived from turmeric and has multiple bioactivities, including anti-oxidative and radical-scavenging activities that exert cytoprotection…

Our results showed that Dox-induced injury to the myocardium was decreased by Cur treatment via upregulating the protein expression of 14-3-3γ in total protein and Bcl-2 expression on mitochondria, activating Bad (S112) phosphorylation, reducing the heart rate and ST segment, and reducing LDH and CK activities in the serum, thereby causing a reduction in caspase-3 activity, the apoptosis rate, and histopathological changes of the myocardium (in vivo)…

In conclusion, this is the first study to demonstrate that Cur protected the myocardium against Dox-induced injury via upregulating 14-3-3γ expression, thereby promoting the translocation of Bcl-2 to mitochondria, suppressing oxidative stress, and improving mitochondrial function…”

Dietary vitamin E decreases doxorubicin-induced oxidative stress without preventing mitochondrial dysfunction.

“Doxorubicin (DOX) is a widely prescribed antineoplastic and although the precise mechanism(s) have yet to be identified, DOX-induced oxidative stress to mitochondrial membranes is implicated in the pathogenic process…

Treatment with a cumulative dose of 14 mg/kg DOX caused mitochondrial cardiomyopathy as evidenced by histology, accumulation of oxidized cardiac proteins, and a significant decrease in mitochondrial calcium loading capacity.

Maintaining rats on the alpha-tocopherol supplemented diet resulted in a significant (two- to four-fold) enrichment of cardiac mitochondrial membranes with alpha-tocopherol and diminished the content of oxidized cardiac proteins associated with DOX treatment.

However, dietary alpha-tocopherol succinate failed to protect against mitochondrial dysfunction and cardiac histopathology.

From this we conclude that although dietary vitamin E supplementation enriches cardiac mitochondrial membranes with alpha-tocopherol, either (1) this tocopherol enrichment is not sufficient to protect cardiac mitochondrial membranes from DOX toxicity or (2) oxidative stress alone is not responsible for the persistent mitochondrial cardiomyopathy caused by long-term DOX therapy.”

Vitamin C mitigates oxidative/nitrosative stress and inflammation in doxorubicin-induced cardiomyopathy.

“Increase in oxidative/nitrosative stress is one of the mechanisms associated with the development of cardiotoxicity due to doxorubicin (Dox), a potent chemotherapy drug.

In the present in vivo study in rats, we investigated the effect of prophylactic treatment with Vit C on Dox-induced apoptosis, inflammation, oxidative/nitrosative stress, cardiac dysfunction, and Vit C transporter proteins.

Dox (cumulative dose: 15 mg/kg) in rats reduced systolic and diastolic cardiac function and caused structural damage. These changes were associated with a myocardial increase in reactive oxygen species, reduction in antioxidant enzyme activities, increased expression of apoptotic proteins, and inflammation.

These results suggest a cardioprotective role of Vit C in Dox-induced cardiomyopathy by reducing oxidative/nitrosative stress, inflammation, and apoptosis, as well as improving Vit C transporter proteins.

NEW & NOTEWORTHY This in vivo study provides novel data that vitamin C improves cardiac structure and function in doxorubicin-induced cardiomyopathy by reducing oxidative/nitrosative stress, apoptosis, and inflammation along with upregulation of cardiac vitamin C transporter proteins. The latter may have a crucial role in improving antioxidant status in this cardiomyopathy.”

Leave a Comment:

Cardiotoxicity of Doxorubicin - PeopleBeatingCancer says 9 months ago

[…] Breast Cancer – Cardiotoxicity  […]

Lynette Erasmus says 4 years ago

Can flaxseed oil be taken before and while busy with chemo ….. Pls advise thank you!

    David Emerson says 4 years ago

    Hi Lynette-

    I can’t make one blanket statement for ALL chemotherapy regimens but according to the study linked in that blog post, flaxseed oil synergies with that chemotherapy-

    “Hence, FO did not interfere with TRAS but rather enhanced its tumor-reducing effects and combined FO and low dose TRAS was as effective as high dose TRAS treatment.”

    David Emerson

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