What You Do Not Know Could Hurt You: What Women Wish Their Doctors Had Told Them About Chemotherapy Side Effects on Memory and Response to Alcohol

INTRODUCTION

Cancer affects an estimated 12 million women of every race and ethnicity around the world with a significant impact on their health and overall well-being.^1–3 Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer death for women in the United States (US), with a total of 246,660 new invasive breast cancer patients and 40,890 breast cancer deaths expected in 2016.³ How­ever, the frequencies of different types of cancer vary based on race, ethnicity, and geographical location. Hispanics within US mainland have lower rates of the most common cancers (breast, prostate, lung, and colorectal) and higher rates of cancers related to infectious agents (liver, stomach, and uterine cervix).⁴ In Puerto Rico (PR), breast cancer has the highest incidence and death rate among women.^4,5 Statistics from the Division of Epidemiology, Department of Health, Puerto Rico, indicate that approximately 1540 women are diagnosed with breast cancer annually with a survival rate of 76.4%.^6,7 This means one out of every eight women in PR can expect to have breast cancer at some point in her life.^7,8 The differences among ethnic groups may arise from the prevalence of cultur­ally associated risk factors for cancer, such as obesity, alcohol use, tobacco use, and lack of exercise.⁶

After a diagnosis of cancer, women can react in various ways, because this condition can affect their life holistically— the impact they suffered after having diagnosis and the side effects they encountered when having chemotherapy treat­ment. Evidence from preclinical model system research suggests that most chemotherapy drugs affect healthy cells, including neurons, progenitor cells, and neurotransmit­ters by crossing the blood–brain barrier leading to neuro­nal adaptations.^9–12 Specifically, long-term neurological side effects have been seen with methotrexate and 5-flourouracil, the most common chemotherapy drugs used to treat gyne­cological cancers.^9,12,13 Even a single intravenous injection of methotrexate resulted in a sustained reduction in hippocampal cell proliferation.¹⁴ Another study suggests that the size of gray and white matters in the parahippocampal gyrus and prefrontal regions was reduced following a year-long course of chemotherapy treatment.^14,15 The most commonly affected regions are involved in attention and memory processes and correlate with neurocognitive impairments reported by the patients.

Reviews of self-report studies that include neurocogni­tive assessments summarize the evidence that chemotherapy causes long-term (effects lasting more than three to five years) cognitive dysfunction in 20%–60% of patients reducing the survivor’s working memory, spatial ability, and capacity to recall memories.^{12,13,16–19} Different types of chemotherapy drugs and duration of treatments result in damage to differ­ent areas of the brain.^12,20,21 Patient’s experience of impaired working memory and spatial ability is shown to correlate with an individual’s coping strategies that suggest the potential utility of therapeutic approaches that facilitate an improved cognitive performance.^13,22 Indeed, cognitive therapy proto­cols exist that reduce the acute effects of chemotherapy treat­ment on verbal memory, attention, and processing speed when initiated immediately after patients are stabilized.^{12,13,16–19} However, patients cannot request a preventative or post­chemotherapy treatment if that they do not know whether it exists or that it might be necessary that underscores the essen­tial importance of educating patients about the possibility of memory loss due to chemotherapy.¹³

Though alcohol intake differs among cultures and gen­der, the relation between alcohol intake and higher risk of breast cancer appears to be universal. In a 2007 publica­tion, the World Cancer Research Fund and the American Institute for Cancer Research reported that the association between an increased risk of breast cancer and an increased alcohol intake is one of the steadiest findings among the many hypothesized relationships between dietary factors and risk for breast cancer. A number of studies have demonstrated a monotonic increase in the risk of breast and ovarian can­cers with an increased alcohol consumption,^23–26 supporting the claim that the risk of breast cancer increases with alco­hol intake. According to the Center for Disease Control’s Behavioral Risk Factor Surveillance System survey, Hispan­ics self-report frequent alcohol consumption (three or more drinks per week) at lower rates than non-Hispanic whites.²⁷ Hispanic women are less likely to report frequent alcohol consumption than Hispanic men (5% of women vs 21% of men).²⁸ The lower incidence of frequent alcohol consumption among Hispanic women is a possible factor in their lower incidence of cancer.

Independent of its role as a risk factor, consump­tion of a small amount of alcohol is associated with lower reports of chemotherapy side effects in patients with head and neck cancers.29 Cancer patients who reported drinking at least once a week also had improved physical health and ability to function overall with reduced fatigue, pain, dry mouth, swelling, and loss of appetite.²⁹ Evidence suggests that a priming dose of alcohol increases an individual’s appe­tite.³⁰ The Study of Epidemiology and Risk Factors in Can­cer Heredity, which examined 4529 breast cancer patients, found that increasing alcohol consumption by 2% improved survival and prognosis.³¹ However, excessive drinking (.13 g/d) has adverse effects on survival for female cancer patients, and in patients with tumors, excessive drinking is associated with poor prognosis.³² The potentially helpful consequences of low or moderate doses of alcohol are not well known by members of the general public and should be included in research studies to help us understand the potential benefits.³³

Alcohol intake and chemotherapy treatment exist in the culture of both the continental US and PR. The pur­pose of this study was to explore the incidence of alcohol and memory-related side effects of chemotherapy in female cancer patients in US and PR. Additionally to determine whether patients were informed, prior to treatment, of poten­tial side effects of chemotherapy. Survey results show that many patients did report changes in memory function and alcohol responses, and a majority reported that they did not receive such information prior to treatment but would have liked to have known about potential side effects of chemo­therapy before undergoing treatment. For clinicians, the pri­mary concern is treatment of the cancer, and the side effects may often be accepted as the unpleasant but inevitable result of treating a deadly disease. However, the overall quality of life for the patient, as a potential survivor, should not be overlooked, especially when a small change in the delivery of care can reduce the impact of unavoidable side effects on the quality of life. We highlight the need for medical providers to make their patients aware of the potential for side effects and adverse reactions associated with chemotherapy, such as memory loss and changes in alcohol response, before the beginning of treatment.

METHODS

Research design and participants. The conducted research design is a quantitative, nonexperimental, cross-sectional study. The sample consists of 79 women between 21 and 85 years old that had been diagnosed with cancer, 46 women in PR and 32 women in the continental US. The participants were recruited upon receiving a diagnosis of breast and/or gynecological cancers, undergoing che­motherapy treatment, or receiving care following chemo­therapy for this condition. Within PR, participants were recruited at cancer walks or support groups by senior-level graduate psychology students and asked to complete a paper version of the survey. Additionally, email invitations to com­plete a web-based survey (http://freeonlinesurveys.com/s.asp?sid=evhmi7s0o2kxggb136235) were sent to individu­als who posted blogs on breast cancer survivorship and to patients in the breast cancer cohort study database.

Survey of female cancer treatments, alcohol aware­ness, and effects on way-finding. This survey, developed by Dr. Summer Acevedo in consultation with cancer survi­vors, neuropsychologists, and medical doctors, is a 42-item questionnaire designed to gather information about patterns of treatment for female cancers that can be used to inform the delivery of health care. The questionnaire consists of 42 questions related to side effects of treatment including memory loss and changes in response to alcohol with response options presented as yes/no answers with additional ques­tions on the quality of alcohol consumption. In order for the questionnaire to be used for English- and Spanish-speaking participants, the questionnaire was back translated using a normative method by two different qualified bilingual clinical psychologists.³⁴ This was done to help guarantee conceptu­ally equivalent versions of a measure when two languages are needed for cross-cultural research.³⁵