Often a breast cancer patient will come into our office for secondary or supportive care to the primary cancer treatment they are receiving. One of the first things their loved ones will usually say in our initial meeting is, “I wish they told us about these side effects so we could have been prepared better.” Among the side effects and health concerns are cognitive function, memory impairment, and depressive cycles in their loved one.
“Cognitive deficits are common complications of breast cancer survivors treated with chemotherapy.”
Researchers writing in the journal BioMed Central cancer, (1) echoed the concerns of family members and patients, they write: “Cognitive deficits are common complications of breast cancer survivors treated with chemotherapy. The most frequently observed disorders involve executive function and memory impairment. With improvements in tumor intervention and the consequent increase in the number of cancer survivors, the quality of life of patients has become an important issue.”
We are going to return to this research, but first let’s explore the well known effect of chemotherapy, “chemo brain.” This is a “brain fog sensation,” a loss of memory and cognitive function during and after chemotherapy or radiotherapy treatments.
Alterations in the brain does occur with chemotherapy
A December 2019 study (2) tested the best methods of taking a brain MRI to assess the possible damage caused by chemotherapy treatments. Here is what the researchers wrote and the type of damage the researchers were hoping to isolate on film:
“Chemotherapy related cognitive impairments are common in breast cancer patients undergoing chemotherapy. These cognitive dysfunctions are mainly attributable to chemotherapy related brain structural and functional alterations. Multimodality magnetic resonance imaging (MRI) can reveal brain gray matter volume loss, white matter microstructural disruption, reduced gray matter density, impaired cerebral blood flow and brain structural and functional connection networks at both local and global levels.”
This is significant damage to the brain, however most research reports that these are temporary conditions. Symptoms should be treated with various methods including memory and brain exercises when needed. Also included in the treatment methods are certain Alzheimer medications and those medications for attention-deficit disorder. However, new research is suggesting doctors look at how to manage post chemo and radiation therapy inflammation for possible answers.
Researchers noted cognitive problems for up to three years post chemo
Initially it was thought that the side effects of chemotherapy were solely responsible for “chemo brain.” This limitation to chemotherapy causing effects was challenged by a research team from the Moffitt Cancer Center and Research Institute working with associates from the University of South Florida and the University of Kentucky.
In a study they published in the medical journal Cancer, (3) changes in cognitive functioning over time were compared in:
(1) breast cancer survivors treated with chemotherapy plus radiotherapy,
(2) breast cancer survivors treated with radiotherapy only, and
(3) women with no history of cancer.
The researchers noted cognitive problems for up to three years post chemo. What they also found in test subjects was that not only did chemotherapy lead to what is commonly referred to as “Chemo Brain,” but radiotherapy did as well.
Referring back to the study we referenced at the beginning of this article, the researchers of that study suggested that the impact of chemotherapy on brain function in breast cancer survivors who were given chemotherapy: “provide further evidence that adjuvant chemotherapy (chemotherapy provided after initial treatment to address secondary cancers) is associated with demyelination of white matter (damage to the protective myelin sheath covering that surrounds nerve fibers in your brain.)” In addition, adjuvant chemotherapy affected the integrity of white matter (the nerves and myelin sheath of the “deep brain,” resulted in poor cognitive performance.”
The researchers concluded that the brain network integration of breast cancer survivors became worse. That their study demonstrated alterations in the structural brain networks of breast cancer survivors.
But what impact does “alterations in the structural brain networks of breast cancer survivors,” have beyond cognitive function? Mental health issues.
As cancer survivors and their families are aware, side effects of chemotherapy are usually not limited to one or two problems, they propagate and expand into other concerns. In the case of some breast cancer patients, concerns of cognitive dysfunction and memory may expand into mental health issues.
Cognitive dysfunction and memory impairment may only be the tip of the same iceberg that includes depression, anxiety, and other challanges.
Another study in the Journal of the National Cancer Institute (4) noted: “There is compelling evidence of an increased risk of anxiety, depression and suicide, and neurocognitive and sexual dysfunctions in breast cancer survivors compared with women with no prior cancer.”
Adjuvant hormone therapy is a psychosocial issue
Now let’s look at a December 2019 study (5) from France. Here researchers suggested:
“Despite proven survival benefits after breast cancer, long-term compliance with adjuvant hormone therapy remains a major issue, partly due to the side effects of treatment. In young women treated for breast cancer, these treatments include tamoxifen, anti-aromatase and LH-RH analogues, with even more side effects when these treatments are combined, especially for younger patients with more aggressive disease.
The management of the potential side effects requires first of all detailed and precise information at initiation of treatment, and preventive measures including patient education. Once the treatment has been initiated, clinicians should be able to propose to their patients appropriate measures to alleviate the potential of the side effects, which can be of various types: biological (dyslipidemia), physical (weight gain, hot flushes, vaginal dryness, sexual disorders with low libido, musculoskeletal symptoms…) or psychosocial (anxio-depressive disorders, poor body image, difficulties of professional reintegration).
“Both basic and clinical research indicates that peripheral inflammation leads to central inflammation and behavioral changes.”
We have now, with the help of research, demonstrated the problems that doctors tackle in helping breast cancer survivors during and post-treatment. Now we will examine some possible answers to addressing these concerns. One possible answer is in managing chronic inflammation. To help us understand this concept, let’s look at a June 2018 study in the journal Frontiers in immunology. (6) The study opens with this:
“Behavioral comorbidities (depression, anxiety, fatigue, cognitive disturbances, and neuropathic pain) are prevalent in cancer patients and survivors. These mental and neurological health issues reduce quality-of-life, which is a significant societal concern given the increasing rates of long-term survival after various cancers. Hypothesized causes of behavioral comorbidities with cancer include tumor biology, stress associated with the cancer experience, and cancer treatments. A relatively recent leading mechanism by which these causes contribute to changes in neurobiology that underlie behavior is inflammation. Indeed, both basic and clinical research indicates that peripheral inflammation leads to central inflammation and behavioral changes in other illness contexts.“
Inflammation is used to treat cancer tumors:
In the cancer journal Oncotarget, (7) researchers noted cancer patients often report behavioral and cognitive changes following cancer treatment. That treatments combining radiotherapy and immunotherapy demonstrated remarkable efficacy with respect to tumor outcomes by enhancing the pro-inflammatory environment in the tumor. (Immunotherapy enhances the immune response to invading cells like cancer, flu or cold, by increasing inflammation).
However, a pro-inflammatory environment in the brain causes and induces cognitive impairments and may affect brain function in cancer patients receiving these treatments.
The research team from Oregon Health and Science University behind this research concluded that, “Although combined treatment achieved tumor growth control, it affected the brain and induced changes in measures of anxiety, cognitive impairments, and neuroinflammation.”
Inflammation opens a door for neurotoxicity and cognitive dysfunction
The focus of this section will be on cytokines – a small protein that communicates with immune cells to get them to the site of injury, infection, and inflammation. The thinking is that cytokines are somehow opening a doorway in “blood-brain barrier” the blood filtering mechanism that carries blood to the brain while blocking many harmful substances. It is through that it is through this doorway that “unfiltered” chemicals are getting through into the brain.
In research from the International Journal of Cancer, (8) doctors looked at the neurotoxicity side effect of chemotherapy treatment. Here is what they wrote:
Clinical studies suggest that the most frequent neurotoxic adverse events affect memory and learning, attention, concentration, processing speeds and executive function.
Emerging pre-clinical research points toward direct cellular toxicity and induction of neuroinflammation as key drivers of neurotoxicity and subsequent cognitive impairment. (The research suggests that the chemicals used in chemotherapy are somehow bypassing the blood – brain barrier., as we mentioned above.)
Emerging data now show detectable levels of some chemotherapeutic agents within the central nervous system, indicating potential disruption of blood brain barrier integrity.
Blood brain barrier disruption is a key aspect of many neurocognitive disorders, particularly those characterized by a pro-inflammatory state.
Research from doctors in the Czech Republic (9) reported that cognitive impairment (impairment of memory, attention, or concentration) is documented in 17-75% of patients with various malignancies treated with chemotherapeutic agents that worsen quality of life.
Changes occur mainly in the ability to learn and remember, in the speed of reactions, and in attention and executive functions.
Although Chemo-related cognitive impairment’s complexities are not yet fully understood, the involvement of neurotoxicity, such as that induced by treatment, anemia, higher levels of oxidative stress and inflammatory responses, genetic factors, and reduced brain connectivity should be discussed.
What can help?
As you know, this is a complex problem and simple recommendations does not encompass all the challenges a patient may face. We will present some information on what may help the patient but these suggestions are only that, suggestions and introductions to treatments that may help. Your should discuss your options with your doctors.
Omega 3 and sugar reduction can help with inflammation
Research suggests dietary changes may offer some benefit. Here we will feature on two aspects of diet, omega-3 supplementation and sugar reduction.
In the medical journal Breast cancer research and treatment, (10) a paper entitled, “Clearing the fog: a review of the effects of dietary omega-3 fatty acids and added sugars on chemotherapy-induced cognitive deficits,”doctors from Ohio State University suggested that:
Dietary approaches that modify inflammation and neurogenesis (growth of nervous system tissue) are promising strategies for reducing chemotherapy-induced cognitive deficits in breast cancer survivors.
Omega-3 fatty acids administered concurrently with doxorubicin chemotherapy have been shown to prevent depressive-like behaviors and reduce neuroinflammation, oxidative stress, and neural apoptosis (nerve cell death) in animal studies.
In contrast, diets high in added sugars may interact with the Omega-3s to diminish their anti-inflammatory activity. The sugars may also act independently to increase neuroinflammation and promote cognitive deficits.
A diet rich in long-chain, marine-derived omega-3 fatty acids (fish oils) and low in added sugars may be an ideal pattern for preventing or alleviating neuroinflammation and oxidative stress, thereby protecting neurons from the toxic effects of chemotherapy.
Research testing this hypothesis could lead to the identification of modifiable dietary choices to reduce the long-term impact of chemotherapy on the cognitive functions that are important to quality of life in breast cancer survivors.
At the Magaziner Center for Wellness, our treatments are focused on reducing inflammation, enhancing the cellular immune response, and inactivating cancer stem cells since these are the cells that cause cancer recurrences and are much more harmful than the actual tumor cells—all with the goal of improving quality of life, strength and vigor, and extending life span. We place particular emphasis on an anti-inflammatory diet and lifestyle, and biologic agents that quiet the inflammatory pathways since inflammation has been found to foster the growth of cancer cells.
Most of our patients have already been through the rigors of conventional treatments but either experienced untoward side effects or unsatisfactory outcomes as the cancer continued to grow. The sooner we begin treatment, the better, since there is usually less damage to the immune system and to the vital organs. Your body then has a better chance to recover.
Our program emphasizes the concept of Thriving While Surviving. We strive to transform cancer from an acute disease into more of a chronic illness, one that can be lived with for many months or even years. Some of our patients have greatly outlived their life expectancy by even two or three-fold. Furthermore, most are able to continue with a productive and fulfilling life.
If you would like to explore more information, please contact our office so we can start a conversation with you.
Related articles:
Surviving the Long-Term Effects of Breast Cancer Treatment
Stress Management in Breast Cancer Patients
Inflammation Makes Breast Cancer – Anti-inflammatory Programs Can Stop It
References
1 Li TY, Chen VC, Yeh DC, Huang SL, Chen CN, Chai JW, Chen CC, Weng JC. Investigation of chemotherapy-induced brain structural alterations in breast cancer patients with generalized q-sampling MRI and graph theoretical analysis. BMC cancer. 2018 Dec;18(1):1211.
2 Feng Y, Zhang XD, Zheng G, Zhang LJ. Chemotherapy-induced brain changes in breast cancer survivors: evaluation with multimodality magnetic resonance imaging. Brain Imaging Behav. 2019;13(6):1799–1814. doi:10.1007/s11682-019-00074-y
3 Cognitive functioning after cancer treatment: A three-year longitudinal comparison of breast cancer survivors treated with chemotherapy or radiation and non-cancer controls.” Phillips KM, Jim HS, Small BJ, et al. CANCER; Published Online: December 12, 2011.
4 Carreira H, Williams R, Müller M, Harewood R, Stanway S, Bhaskaran K. Associations Between Breast Cancer Survivorship and Adverse Mental Health Outcomes: A Systematic Review. JNCI: Journal of the National Cancer Institute. 2018 Nov 7;110(12):1311-27.
5 Saghatchian M, Lesur A. Management of side effects related to adjuvant hormone therapy in young women with breast cancer. Bulletin du cancer. 2019 Dec;106(12S1):S37.
6 Dos Santos JC, Pyter LM. Neuroimmunology of behavioral comorbidities associated with cancer and cancer treatments. Frontiers in immunology. 2018;9:1195.
7 McGinnis GJ, Friedman D, Young KH, et al. Neuroinflammatory and cognitive consequences of combined radiation and immunotherapy in a novel preclinical model. Oncotarget. 2017;8(6):9155-9173. doi:10.18632/oncotarget.13551.
8 Wardill HR, Mander KA, Van Sebille YZ, Gibson RJ, Logan RM, Bowen JM, Sonis ST. Cytokine-mediated blood brain barrier disruption as a conduit for cancer/chemotherapy-associated neurotoxicity and cognitive dysfunction. Int JCancer. 2016
9 Fayette D, Gahérová Ľ, Móciková H, Marková J, Kozák T, Horáček J. Chemotherapy-related Cognitive Impairment in Patients with Hodgkin Lymphoma-Pathophysiology and Risk Factors. Klinicka onkologie: casopis Ceske a Slovenske onkologicke spolecnosti. 2017;30(2):93-9.
10 Orchard TS, Gaudier-Diaz MM, Weinhold KR, DeVries AC. Clearing the fog: a review of the effects of dietary omega-3 fatty acids and added sugars on chemotherapy-induced cognitive deficits. Breast cancer research and treatment. 2017;161(3):391-398. doi:10.1007/s10549-016-4073-8.
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