Laura Petersen

Breast Cancer in Younger Women: Reproductive and Late Health Effects of Treatment

PURPOSE In 1997, we initiated a cohort study to evaluate quality of life (QOL) and reproductive health outcomes in younger female breast cancer survivors. MATERIALS AND METHODS Using listings from two tumor registries, we recruited women with stage 0, I, or II breast cancer who were 50 years or younger at diagnosis and were also disease-free survivors for 2 to 10 years. A mailed survey questionnaire assessed medical and demographic factors, health-related QOL, mood, outlook on life, and reproductive health outcomes. RESULTS We recruited 577 women, who ranged in age from 30 to 61.6 years (mean, 49.5 years) and were surveyed approximately 6 years after diagnosis. Almost three fourths had received some form of adjuvant therapy. Amenorrhea occurred frequently as a result of treatment in women > or = 40 years at diagnosis, and treatment-associated menopause was associated with poorer health perceptions. Across the cohort, physical functioning was quite good, but the youngest women experienced poorer mental health (P =.0002) and less vitality (energy; P =.03). Multiple regression analyses predicting QOL demonstrated better outcomes in African-American women, married or partnered women, and women with better emotional and physical functioning, whereas women who reported greater vulnerability had poorer QOL. CONCLUSION Overall QOL in younger women who survive breast cancer is good, but there is evidence of increased emotional disruption, especially among the youngest women. Factors that may contribute to poorer health perceptions and QOL include experiencing a menopausal transition as part of therapy, and feeling more vulnerable after cancer.

Neurocognitive Performance in Breast Cancer Survivors Exposed to Adjuvant Chemotherapy and Tamoxifen

ABSTRACT The primary aim of the current study was to examine whether neurocognitive functioning among breast cancer survivors (BCS) exposed to systemic adjuvant chemotherapy differs from that seen among BCS who did not receive chemotherapy. The performance of each of these BCS groups was compared to a demographically matched comparison group without history of breast cancer, a group not included in the majority of previous cognitive functioning studies. We also sought to explore whether usage of the anti-estrogen drug tamoxifen, a common component of breast cancer treatment, was related to neurocognitive functioning. Finally, we wished to examine the relationship between subjective report of cognitive functioning and objective performance on neurocognitive measures among BCS. Fifty-three survivors of breast cancer (all between 2–5 years after diagnosis and initial surgical removal of cancerous tissue) and 19 healthy non-BCS comparison subjects were administered a comprehensive neurocognitive battery, and measures of mood, energy level, and self-reported cognitive functioning. Those BCS who received adjuvant chemotherapy performed significantly worse in the domains of verbal learning, visuospatial functioning, and visual memory than BCS treated with surgery only. Those who received both chemotherapy and tamoxifen showed the greatest compromise. Although patients who received chemotherapy (with and without tamoxifen) performed worse than those treated with surgery only on several domains, neither group was significantly different from demographically matched comparison subjects without a history of breast cancer. Finally, we found no relationship between subjective cognitive complaints and objective performance, although cognitive complaints were associated with measures of psychological distress and fatigue. We highlight ways in which these data converge with other recent studies to suggest that systemic chemotherapy, especially in combination with tamoxifen, can have adverse yet subtle effects on cognitive functioning.

Characteristics of women at risk for psychosocial distress in the year after breast cancer.

PURPOSE To provide a detailed description of rehabilitation problems of women, considered to be low risk and at risk for psychosocial morbidity, diagnosed with stage I and II breast cancer 1 month and 1 year after primary treatment. PATIENTS AND METHODS A sample of 227 newly diagnosed breast cancer patients were systematically interviewed by a clinical social worker and classified for risk of psychosocial distress in the year after diagnosis. They completed a battery of standardized instruments to assess quality of life (QL), rehabilitation needs, and psychologic distress. The primary QL instrument, the Cancer Rehabilitation Evaluation System (CARES), provides a detailed listing of rehabilitation needs. Descriptive CARES data are presented with comparisons between the two groups. RESULTS The at-risk women had significantly more problems with greater severity than the low-risk women in all areas (physical, psychosocial, medical interaction, sexual, and marital). While both groups showed improvement over the year following diagnosis, the at-risk group had significantly more problems 1 year later. Many physical problems subside, but problems at the local surgical site, psychologic distress, communication with marital partners, and negative body image are more persistent in the at-risk group 1 year later, while half of both groups continue to have sexual dysfunction. CONCLUSION The detailed listing of problems provided by the CARES may be helpful to clinicians in their interactions with patients. The need for preventive and early intervention for the at-risk patients is underscored.

Diurnal cortisol rhythm and fatigue in breast cancer survivors.

Approximately 30% of breast cancer survivors report persistent fatigue of unknown origin. We have previously shown that cancer-related fatigue is associated with alterations in immunological parameters and serum cortisol levels in breast cancer survivors. The current study examined the diurnal rhythm of salivary cortisol in fatigued and non-fatigued breast cancer survivors. Salivary cortisol measures were obtained from breast cancer survivors with persistent fatigue (n=13) and a control group of non-fatigued survivors (n=16). Participants collected saliva samples upon awakening and at 1200, 1700, and 2200 h on two consecutive days. Diurnal cortisol slope for each day was determined by linear regression of log-transformed cortisol values on collection time and analyzed using multi-level modeling. Fatigued breast cancer survivors had a significantly flatter cortisol slope than non-fatigued survivors, with a less rapid decline in cortisol levels in the evening hours. At the individual patient level, survivors who reported the highest levels of fatigue also had the flattest cortisol slopes. Group differences remained significant in analyses controlling for demographic and medical factors, daily health behaviors, and other potential confounds (e.g. depressed mood, body mass index). Results suggest a subtle dysregulation in hypothalamic-pituitary-adrenal axis functioning in breast cancer survivors with persistent fatigue.

Quality of life in the first year after breast cancer surgery: rehabilitation needs and patterns of recovery.

Background. Although mortality rates from breast cancer are declining, many breast cancer survivors will experience physical and psychological sequelae that affect their everyday lives. Few prospective studies have examined the rehabilitation needs of newly diagnosed breast cancer patients, and little is known about the predictors of health‐related quality of life (QOL) in this population.Methods. Between 1987 and 1990, 227 women with early stage breast cancer participated in a prospective longitudinal study in which detailed information was collected through interviews, standardized measures of QOL and psychological distress, and clinical evaluation. Comparisons of physical and treatment‐related problems were made according to type of surgical treatment. Multivariate regression analysis was performed to examine the predictors of QOL at one year after surgery.Results. Physical and treatment‐related problems were reported frequently one month after breast cancer surgery, and occurred with equal frequency in women receiving modified radical mastectomy or breast conservation treatment. There were no significant differences in problems reported at one year by type of surgery; however, frequently reported problems include ‘numbness in the chest wall or axilla,’ ‘tightness, pulling or stretching in the arm or axilla,’ ‘less energy or fatigue,’ ‘difficulty in sleeping,’ and ‘hot flashes’. There was no relationship between the type of surgery and mood or QOL. Poorer QOL one year after surgery was significantly associated with greater mood disturbance and body image discomfort one month after surgery, as well as positive lymph node involvement. Although the majority of patients experienced substantial disruptions in the physical and psychosocial dimensions of QOL post‐operatively, most women recovered during the year after surgery, with only a minority (<10%) significantly worsening during that time.Conclusions. At one year after surgery, most women report high levels of functioning and QOL, with no relationship between the type of surgery and QOL. Women who reported lower levels of QOL at one year after diagnosis had greater mood disturbance and poorer body image one month after surgery, as well as lower income and positive axillary nodes.

Association of breast cancer and its therapy with menopause-related symptoms

Objective:To study the relationship between current menopause status, occurrence of menopause transition during cancer treatment, and prevalence and severity of possible menopause-related symptoms. Design:Data from the Cancer and Menopause Study (CAMS), a tumor-registry-based cohort of breast cancer survivors (BCS) diagnosed before age 50, were used. Using a standardized symptom checklist, women reported whether they were not at all, slightly, moderately, quite, or extremely bothered in the past 4 weeks by hot flashes, night sweats, vaginal dryness, pain with intercourse, breast sensitivity, joint pains, frequent mood changes, restless sleep, weight gain, forgetfulness, and difficulty concentrating. Current menopause status (by standard categories based on menstruation) and whether a persistent menopause transition occurred during cancer treatment were the main exposures. Linear (symptom severity as continuous outcome) and logistic (symptom present vs absent) regression models were adjusted for age, ethnicity, current smoking, alcohol use, chemotherapy, tamoxifen, body mass index, and depression scores. Results:Mean age of the participants was 50 years. The prevalence of symptoms was high. Hot flashes occurred in 17%, 51%, and 71% of pre-, peri-, and postmenopausal BCS, respectively. Hot flashes, vaginal dryness, and pain with intercourse were more severe in postmenopausal compared with perimenopausal BCS. Having had a transition during breast cancer treatment was associated with worse hot flash severity, independent of current menopause status. Conclusions:Menopause-related symptoms are common in BCS. Effective treatment options are needed. Having a treatment-related transition confers a persistent effect on hot flash severity. Clinicians should include this information when counseling women on potential outcomes of their cancer therapy.

Factors related to sexual function in postmenopausal women with a history of breast cancer.

Background The normal life expectancy of survivors of early-stage breast cancer (BCS) underscores the need to address long-term quality of life issues in these women. Sexual dysfunction persists after breast cancer treatment, despite recovery in other domains. Objective To examine associations between a broad array of characteristics and sexuality in BCS. Participants Sixty-one postmenopausal BCS who were participants in a randomized, controlled trial of nonhormonal interventions for menopause symptoms and who had a partnered, intimate relationship. Methods Cross-sectional analysis of baseline trial data. Outcomes were standardized scales of sexual interest, dysfunction, and satisfaction. Candidate predictors included demographic, anatomical, medical, psychological, sociocultural, and hormonal characteristics. Forward, stepwise regression was used. Results Relationship quality, vaginal discomfort, education, and hot flashes were each associated with two of the three domains of sexuality assessed. Ten other factors entered predictive models: age, time since diagnosis, breast conservation, comorbidity, urinary incontinence, perceived health, body image, bioavailable testosterone, luteinizing hormone, and sex hormone binding globulin. Each of these 10 factors was associated with only one sexuality domain. Conclusions In this small sample of BCS, we found multiple correlates of sexuality. Most seem to impact uniquely on individual domains of sexual function. Several characteristics are modifiable and could be targets for intervention.

Assessing the needs and quality of life of patients with HIV infection: development of theHIVOverview ofProblems-EvaluationSystem (HOPES)

Objective: To develop and evaluate the psychometric properties (reliability, validity etc.) of a comprehensive Quality of Life (QOL) tool, for patients infected with the human immunodeficiency virus (HIV), that was adapted from a previously validated cancer tool. Design: Cross-sectional, patient completed written surveys and interviews. Setting: The Medical Centers serving HIV infected patients in the Los Angeles community including UCLA, community physicians, Veterans Affairs Medical Centers, and a County hospital: and additional data contributed from Johns Hopkins University Medical Center CMV Retinitis Clinic. Patients: Patients (n=318) with HIV infection including asymptomatic (37%), ARC (20%), AIDS (25%) and AIDS with Cancer (18%) receiving health services at one of the above sites. Measurements: The patients self-administered the newly developed instrument, the HOPES (HIVOverview ofProblems-EvaluationSystem), other QOL related tools including the Medical Outcomes Study instrument adapted for HIV (MOS-HIV) the Profile of Mood States (POMS), the Perceived Adjustment to Chronic Illness Scale (PACIS), and the Physical Activity Scale (PAS). Brief interview to assess the Karnofsky Performance Status Score (KPS). Measured sociodemographic characteristics included age, sex, race, HIV risk factor, education etc. Assessed medical history, current medications, HIV clinical classification. Main results: The sociodemographic and medical characteristics of the sample resemble those of the general population with HIV infection in this geographic area: 96% male, 28% nonwhite, 84% homosexual contact as risk factor, 75% receiving antiretroviral therapy. The adaptation of the cancer QOL instrument to HIV appears to have face and content validity according to patients and health professionals who care for HIV infected patients. Analyses of the psychometric properties found that the HOPES has a similar structure to its parent instrument following factor analyses which results in five summary scales representing the Physical, Psychosocial, Medical Interaction, Sexual and Significant Other/Partners domains in addition to a Global Score. Internal consistency of 35 subscales is high with a mean alpha coefficient of 0.82. Correlations of the HOPES summary scales with other QOL instruments are in the predicted directions. Comparing patients within the HIV clinical diagnostic categories on the HOPES Global, Physical, and Psychosocial Summary Scales indicates that Asymptomatic Patients have better QOL than symptomatic patients. This finding is also found in the other QOL instruments which provides evidence of construct validity. Conclusions: The HOPES is an excellent tool for identifying the problems and needs of patients with HIV infection and for assessing their quality of life. It is reliable, valid and acceptable to patients. The tool may be especially useful in developing a normative data base.

Describing the health-related quality of life impact of HIV infection: Findings from a study using the HIV Overview of Problems—Evaluation System (HOPES)

This study aimed to describe the results of findings from data collected with an HIV-specific health-related quality of life tool, and to examine the relationship between clinical and biological factors and health-related quality of life (HRQL). Data were collected as a cross-sectional, patient-completed assessment of health-related quality of life. Laboratory data were abstracted from the medical chart. Patients (n=318) with HIV infection including asymptomatic (37%), ARC (20%), AIDS (25%), and AIDS with cancer (18%) were receiving health services at one of the medical centres serving HIV-infected patients in the Los Angeles community, including UCLA, community physicians, Veterans Affairs Medical Centers, and a county hospital. Additional data were contributed by the Johns Hopkins University Medical Center CMV Retinitis Clinic. Symptomatic patients and patients with the lowest CD4 counts reported poorer HRQL than asymptomatic patients and patients with higher CD4 counts. However, medical and demographic variables explained only 35% of the variability of HRQL ratings in this sample of HIV-infected patients. While clinical status and Karnofsky performance status may be used to estimate the impact of HIV infection on HRQL, they are not a substitute for independent assessment of HRQL by the patient.

Refinement and Psychometric Evaluation of the Impact of Cancer Scale

BACKGROUND Instruments are needed to measure the influence of cancer on quality of life in the expanding population of long-term cancer survivors. We conducted refinement and psychometric evaluation of the Impact of Cancer (IOC) scale by use of data from a large sample of long-term breast cancer survivors and developed an instrument, the Impact of Cancer version 2 (IOCv2), to measure quality of life outcomes. METHODS Questionnaires including 81 potential IOC scale items, the Center for Epidemiologic Studies-Depression (CES-D) scale, and the Breast Cancer Prevention Trial (BCPT) symptom scales, as well as demographic, treatment, and medical information, were completed by 1188 disease-free breast cancer survivors 5-10 years after diagnosis. We used exploratory factor analysis to identify scales and assessed reproducibility by split-sample cross-validation. Higher-order scales were extracted and all scales were evaluated for internal consistency and construct and concurrent validity. RESULTS The analysis yielded a factor structure relating IOC items to psychosocial impact domains that exhibited high factor loadings (factor-item correlations of 0.59-0.94), high internal consistency (Cronbachs alpha statistics of 0.76-0.89), and a total congruence of 0.98 across the split samples. The Impact of Cancer version 2 (IOCv2) scales consist of a Positive Impact Summary scale with four subscales (Altruism and Empathy, Health Awareness, Meaning of Cancer, and Positive Self-Evaluation), a Negative Impact Summary scale with four subscales (Appearance Concerns, Body Change Concerns, Life Interferences, and Worry), and subscales for Employment and Relationship Concerns. Patterns of association between IOCv2 scale scores and CES-D and BCPT scores indicated good concurrent validity. Patterns of associations between IOCv2 scale scores and demographic, medical, and treatment characteristics indicated good construct validity. CONCLUSION The IOCv2 scales provide a validated tool for measuring the impact of cancer on quality of life in long-term cancer survivors.