Breast cancer is a serious illness that affects a large number of women in the Western world, a majority of whom are beyond the age of menopause. Psychosocial distress is common at points along the illness trajectory. For some, the distress can initiate disabling psychological symptoms; it can also exacerbate underlying mental illness. Depression, anxiety, and cognitive impairments can be serious consequences of the illness and its treatments. The interactions between distress, cancer, and psychiatric illness need to be understood and addressed within the context of the physical and psychosocial challenges inherent to the illness experience.

In the United States alone, more than 250,000 new cases of breast cancer were diagnosed in 2004 (+1). Overall, one in seven women will develop breast cancer. Only lung cancer causes more cancer deaths in women. The risk of breast cancer increases markedly with age, with approximately half of all breast cancers occurring after the age of 65 years and a quarter occurring after the age of 75 years (+2).

Emotional stress is a common difficulty for women with breast cancer. Prevalence rates of specific psychiatric diagnoses among patients with breast cancer vary widely; for example, the prevalence of significant depression ranges from 1.5 percent (+3) to 57 percent (+4). This large variation is likely due to differences in study populations—for example, age range, socioeconomic status, stage of cancer, definitions of depression, and assessment instruments used—which can all have an impact on prevalence estimates. Although some recent studies have attempted to better define cohorts and diagnostic criteria (+5), many studies of patients with breast cancer measure distress in terms of quality of life, which can yield an indirect assessment of depression and other psychological symptoms. Anxiety symptoms also are relatively common. For example, an estimated 20 percent of women with breast cancer have anxiety symptoms from unresolved distressing cancer-related experiences (+6). Moreover, treatments for breast cancer can directly affect psychological and cognitive functioning, as discussed below.

Menopause is a normal part of the life cycle for women, usually occurring some time in mid to later life. Given the age demographics of breast cancer, a majority of women with the diagnosis are also postmenopausal (+7). In addition, an estrogen deficiency or a premature menopause state can be induced among patients with breast cancer by antiestrogen treatments, which include tamoxifen, raloxifene, and letrozole. In the general population, increased depression associated with estrogen-reduced states, such as menopause, has been reported, and there have been clinical observations that depression can be an adverse side effect of tamoxifen treatment. Attention to this topic was ignited a few years ago by a small, uncontrolled study of 21 patients who were likely to become acutely estrogen deficient during treatment for breast cancer, some because of tamoxifen treatment (+8). Thirty-eight percent of the women reportedly developed major depressive disorder. However, larger, controlled studies have not found an association between tamoxifen treatment and depression. For example, the National Surgical Adjuvant Breast and Bowel Project (NSABP) Breast Cancer Prevention Trial followed 11,064 women who were given tamoxifen or placebo for three years and found no significant differences in depression levels between the two groups (+9).

Although women with breast cancer may be menopausal or taking tamoxifen, another issue to consider is whether or not they have physical side effects from being in an estrogen-deficient state. Symptoms of menopause, such as hot flashes, sweats, vaginal dryness, and dyspareunia, can have a direct impact on quality of life and psychological well-being (+7). Menopausal symptoms have been shown to trigger or intensify depression among women with coexisting stressors, a previous history of depression, or a negative attitude toward menopause (+7).

Consistent with these findings, depression in postmenopausal women with breast cancer has been shown in other studies to be closely associated with a high level of health complaints (+10). Such complaints may be related to the illness burden of cancer or may result from cancer treatments. For example, breast irradiation can cause progressive fatigue, resulting in delayed return to usual activities, which may increase vulnerability to depression. Likewise, patients with breast cancer who receive high-dose chemotherapy may be at risk of severe fatigue, which has been associated with depression, pain, and sleep disturbances (+11). The pain from chemotherapy-induced neuropathies also may worsen symptoms.

There has been abundant concern in the literature regarding the psychological effects of mastectomy. Debates have centered on whether or not breast-conserving therapies, such as lumpectomy, are associated with fewer psychological symptoms. Several studies suggest that lumpectomy patients judge their body image and sexual attractiveness more positively than mastectomy patients; however, when the psychological adjustment of mastectomy patients and that of lumpectomy patients are compared, most studies have found little to no difference in depression and anxiety levels (+11). This issue also was studied specifically in postmenopausal patients, and no significant differences were found in depressive symptoms between the mastectomy and lumpectomy groups (+10).

Another important consideration of the illness experience for some women is the potential negative effects of chemotherapy on cognitive function. Most studies have shown various short-term cognitive deficits associated with standard systemic chemotherapy agents for breast cancer, although long-term effects have been questionable (+12). A recent study by Ahles and coworkers (+13) compared the cognitive function of 70 long-term breast cancer survivors and 58 patients with lymphoma who received either standard systemic chemotherapy or local therapy alone. Patients in the chemotherapy group scored significantly worse on neuropsychiatric testing of verbal memory and psychomotor functioning. Tamoxifen was administered to some patients with breast cancer, but with no effect on neuropsychological outcome.

Given the age distribution of women affected by breast cancer, long-term and survival issues are especially relevant for the older, postmenopausal patient. For example, overall survival for early-stage breast cancer is excellent, which is why so much effort and focus is on primary treatment decisions and the delivery of initial cancer care. Although this approach helps ensure disease-free survival and early optimal quality of life, psychosocial problems that occur later in the illness trajectory may get overlooked. Studies have suggested that long-term breast cancer survivors may have late psychosocial problems, especially in the realms of role functioning—for example, as wife, mother, grandmother, and widow—and problems with social adaptation, cognitive function, and sexuality, all of which can contribute to distress levels, depressed mood, and lower quality of life (+11). Many women feel that the window of opportunity to be heard and supported through feelings of emotional distress is relatively short, and these women continue to experience these feelings in secret indefinitely (+14).

Sometimes breast cancer recurs, which can be particularly challenging given that such an event may be experienced as a failure by the patient and her treatment team. In fact, many women blame themselves for their disease or its recurrence (+15). In addition, the clinical symptoms of recurrence may trigger the emotions that had been present at the time of diagnosis, particularly with respect to depressive symptoms. These factors can profoundly affect distress levels, as underscored by a recent study that found significant impairments in physical, functional, and emotional well-being among women with recurrent breast cancer (+16). Family members in that study also reported significant impairments in emotional well-being.

When a true depressive disorder exists, the physician should consider the value of using pharmacologic agents. The choice of antidepressant for breast cancer patients with a depressive disorder requires consideration of the symptom pattern, potential adverse effects, and potential drug interactions, especially when treating older, postmenopausal women who might have additional health issues. There is a paucity of antidepressant clinical trials for major depressive disorder among women with breast cancer, and the few existing studies do not delineate treatment effects by age. In an eight-week, multicenter, randomized clinical trial with 179 women with breast cancer and depression, both paroxetine and amitriptyline were associated with significant improvement in both depression and quality of life, and the outcomes with either drug were not significantly different (+17). However, there was no placebo group in this study.

Of particular relevance for postmenopausal woman is the off-label use of antidepressants, such as venlafaxine, to treat vasovagal symptoms such as hot flashes. Antidepressants have been used in this way among patients with breast cancer even in the absence of depressive symptoms (+18). Such treatment could exert a dual therapeutic effect among depressed postmenopausal women with a history of breast cancer. Given the poorer quality of life associated with hot flashes, additional treatment options have been preliminarily explored in this population, including vitamin E, omega-3 fatty acids, and the progestational agent megestrol acetate (+18).

Although individual psychotherapy may be a useful component of cancer care, much of the data over the past 25 years on psychosocial interventions for cancer patients come from group psychotherapy programs targeted at specific cancer populations. Such programs were derived from traditional psychiatric group therapies and tailored to the needs of cancer patients, with particular emphasis on group support and self-expression. The measured outcomes most commonly targeted for these interventions have been psychological distress and health-related quality of life.

One of the best-known initial (1989) studies on the effects of group treatment for patients with breast cancer demonstrated psychosocial and health benefits, including longer survival time, from a semistructured supportive-expressive group program (+19). A recent multicenter trial of supportive-expressive group therapy with 235 women again demonstrated improved mood and perception of pain, although longevity of survival was not affected (+20). Mindfulness-based stress reduction has recently emerged as a complementary group approach for addressing psychosocial distress among patients with breast cancer, with initial studies demonstrating improved mood, improved immune profiles, and overall lower stress levels (+21). Our team's modification of this program to incorporate creative expression through artwork was recently explored in a heterogeneous group of cancer patients, showing significant improvements in quality of life and stress levels, compared with a control group (+22).

Breast cancer is a relatively common and serious illness for women in the Western world. The numerous physical and psychosocial stressors inherent in the cancer process can contribute to states of depression, anxiety, and cognitive decline, which interfere with overall function and quality of life. The physical status of a patient with breast cancer has a direct impact on perceived distress and psychological symptoms. Physical discomfort, such as pain, meno-pausal symptoms, and fatigue, must be considered in the overall treatment plan, which can include a range of pharmacologic and nonpharmacologic approaches.

Dr. Monti is director of the Jefferson-Myrna Brind Center for Integrative Medicine at Thomas Jefferson University, 111 South 11th Street, Suite 6215, Gibbon Building, Philadelphia, Pennsylvania 19107 (e-mail, monti1@pol.net). Dr. Mago is assistant professor of psychiatry and human behavior and Dr. Shakin Kunkel is professor of psychiatry and human behavior at Jefferson Medical College at the university. Marion Zucker Goldstein, M.D., and Olivera J. Bogunovic, M.D., are editors of this column.