Nicky Hood

Risk of menopause during the first year after breast cancer diagnosis.

PURPOSE Premenopausal women with breast cancer often enter a premature menopause during initial treatment of their malignancy, with resulting loss of childbearing capacity, onset of menopausal symptoms, and subsequent prolonged exposure to long-term risks of menopause. Adjuvant therapy is believed to contribute to this early menopause. PATIENTS AND METHODS One hundred eighty-three premenopausal women with locoregional breast cancer (tumor-node-metastasis staging system classification, T1-3 N0-1 M0) who had undergone surgical treatment and provided information on menopausal status at diagnosis and 1 year later were enrolled. Systemic adjuvant therapy was recorded. Univariate and multivariate predictors of menopause were examined. RESULTS Age, weight gain, tumor stage, nodal stage, and systemic adjuvant therapy (chemotherapy, tamoxifen) were all significant univariate correlates of menopause. In multivariate analysis, age, chemotherapy, and hormone therapy (tamoxifen) made significant independent contributions to the onset of menopause. CONCLUSION Age and systemic chemotherapy are the strongest predictors of menopause in women with locoregional breast cancer. They independently contribute to menopause. A graphic representation of our multivariate model allows an estimation of risk of menopause according to patient age and planned adjuvant treatment, and it may facilitate clinical decision-making.

Prognostic Effects of 25-Hydroxyvitamin D Levels in Early Breast Cancer

PURPOSE Vitamin D has been linked to breast cancer risk, but prognostic effects are unknown. Such effects are biologically plausible given the presence of vitamin D receptors in breast cancer cells, which act as nuclear transcription factors to regulate gene activity. PATIENTS AND METHODS The study was conducted in a prospective inception cohort of 512 women with early breast cancer diagnosed 1989 to 1996. Vitamin D levels were measured in stored blood. Clinical, pathologic, and dietary data were accessed to examine prognostic effects of vitamin D. RESULTS Mean age was 50.4 years, mean vitamin D was 58.1 +/- 23.4 nmol/L. Vitamin D levels were deficient (< 50 nmol/L) in 37.5% of patients, insufficient (50 to 72 nmol/L) in 38.5% of patients, and sufficient (> 72 nmol/L) in 24.0% of patients. There was little variation in mean vitamin D levels between summer and winter months. Mean follow-up was 11.6 years; 116 women had distant recurrences, and 106 women died. Women with deficient vitamin D levels had an increased risk of distant recurrence (hazard ratio [HR] = 1.94; 95% CI, 1.16 to 3.25) and death (HR = 1.73; 95% CI, 1.05 to 2.86) compared with those with sufficient levels. The association remained after individual adjustment for key tumor and treatment related factors but was attenuated in multivariate analyses (HR = 1.71; 95% CI, 1.02 to 2.86 for distant recurrence; HR = 1.60; 95% CI, 0.96 to 2.64 for death). CONCLUSION Vitamin D deficiency may be associated with poor outcomes in breast cancer.

Adjuvant Treatment and Onset of Menopause Predict Weight Gain After Breast Cancer Diagnosis

PURPOSE Weight gain is common during the first year after breast cancer diagnosis. In this study, we examined clinical factors associated with body size at diagnosis and weight gain during the subsequent year. PATIENTS AND METHODS An inception cohort of 535 women with newly diagnosed locoregional breast cancer underwent anthropometric measurements at baseline and 1 year. Information was collected on tumor- and treatment-related variables, as well as diet and physical activity. RESULTS Mean age was 50.3 years; 57% of women were premenopausal. Mean baseline body mass index (weight [kg] divided by height [m] squared) was 25.5 kg/m2. Overall, 84.1% of the patients gained weight. Mean weight gain was 1.6 kg (95% confidence interval, 1.2 to 1.9 kg), 2.5 kg (95% confidence interval, 1.8 to 3.2 kg) in those receiving chemotherapy, 1.3 kg (95% confidence interval, 0.7 to 1.8 kg) in those receiving tamoxifen only, and 0.6 kg (95% confidence interval, 0.01 to 1.3 kg) in those receiving no adjuvant treatment. Menopausal status at diagnosis (P = .02), change in menopausal status over the subsequent year (P = .002), axillary nodal status (P = .009), and adjuvant treatment (P = .0002) predicted weight gain in univariate analysis. In multivariate analysis, onset of menopause and administration of chemotherapy were independent predictors of weight gain (all P < or = .05). Caloric intake decreased (P < .01) and physical activity increased (P < .05) during the year after diagnosis; these factors did not explain the observed weight gain. CONCLUSION Weight gain is common after breast cancer diagnosis; use of adjuvant chemotherapy and onset of menopause are the strongest clinical predictors of this weight gain.

Insulin- and Obesity-Related Variables in Early-Stage Breast Cancer: Correlations and Time Course of Prognostic Associations

PURPOSE To investigate patterns of prognostic associations over time of insulin- and obesity-related variables measured at diagnosis of early breast cancer (BC), focusing on whether the prognostic associations with distant recurrence and death changed over time. PATIENTS AND METHODS Five hundred thirty-five nondiabetic women with T1-3, N0-1, M0 invasive BC diagnosed from 1989 to 1996 were included in the study. Insulin-related variables included fasting insulin, Homeostasis Model Assessment, C-peptide, and glucose. Obesity-related variables included weight, body mass index (BMI), waist and hip circumference, and leptin. Correlations were examined using the Pearson correlation coefficient and prognostic associations using the Cox model. RESULTS There was evidence that associations of baseline insulin-related variables with distant recurrence and death were not constant over time; univariable adverse prognostic associations were significant only during the first 5 years (eg, insulin quartile 4 v 1: hazard ratio [HR], 2.32; 95% CI, 1.39 to 3.86; P < .001 for distant disease-free survival [DDFS]; and HR, 2.85; 95% CI, 1.48 to 5.50; P = .002 for overall survival [OS], with little attenuation of this pattern in multivariable analyses). In contrast, obesity-related variables (BMI, weight, leptin) exerted significant adverse univariable associations that were constant over time (eg, BMI quartile 4 v 2: HR, 1.40; 95% CI, 1.07 to 1.82 for DDFS; P = .014; and HR, 1.50; 95% CI, 1.16 to 1.93; P < .001 for OS); prognostic associations of leptin remained significant in multivariable analyses. CONCLUSION Baseline insulin- and obesity-related variables exert different patterns of prognostic associations over time in early BC.

Insulin-like growth factor binding proteins 1 and 3 and breast cancer outcomes

The IGF family of growth factors is believed to play a role in the development and progression of breast cancer. We recently identified an adverse prognostic effect of insulin in breast cancer; we now report prognostic effects of circulating IGFBPs 1 and 3. 512 women with T1-3, N0-1, M0 breast cancer provided fasting blood which was analysed for IGFBPs 1 and 3. Information on body size, diet and traditional prognostic factors and treatment was obtained; women were followed for recurrence and death. IGFBP-1 levels correlated inversely with insulin levels (Spearman r = −0.60, p < 0.0001), reflecting known inhibition of IGFBP-1 gene expression by insulin. Insulin explained 36% of the variance in IGFBP-1 levels. IGFBP-1 levels were also correlated with obesity and diet. Levels of IGFBP-1 significantly predicted distant recurrence and death, hazard ratio (95% CI) for lower versus upper quartile 2.08 (1.20–3.61) and 3.0 (1.45–6.21), respectively. These effects persisted after adjustment for tumor-related variables and treatment but were not independent of insulin levels. High levels of IGFBP-3 predicted distant recurrence (hazard ratio upper v.s. lower quartile 1.8, 95% CI 1.1–3.0) but not death (hazard ratio 1.0, 95% CI 0.5–1.9). The effect on distant recurrence was restricted to postmenopausal women (hazard ratio 3.8, 95% CI 1.6–9.0) and to those with estrogen receptor positive tumors (p = 0.002). Prognostic effects of IGFBP-1 appear related to the known effect of insulin on IGFBP-1 gene expression. The adverse effect of IGFBP-3 on distant recurrence in postmenopausal women with estrogen receptor positive breast cancer should be further investigated.

Health-Related Quality of Life and Psychosocial Status in Breast Cancer Prognosis: Analysis of Multiple Variables

PURPOSE Evidence that psychosocial status and health-related quality of life (HRQOL) are associated with breast cancer (BC) outcomes is weak and inconsistent. We examined prognostic effects of these factors in a prospective cohort study. PATIENTS AND METHODS Three hundred ninety-seven women with surgically resected T1 to T3, N0/N1, M0 BC completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (Core 30 items), Profile of Mood States, Psychosocial Adjustment to Illness Scale, Impact of Events Scale, Mental Adjustment to Cancer Scale, and the Courtauld Emotional Control Scale 2 months after diagnosis and 1 year later. Data on tumor-related factors, treatment, and outcomes were obtained prospectively from medical records, and Cox survival analyses were performed. RESULTS Mean age was 52.0 +/- 9.9 years. Two hundred twenty-five women had T1, 136 women had T2, 16 women had T3, and 20 women had TX tumors; 127 were N1. One hundred thirteen women received adjuvant chemotherapy, 130 received hormone therapy, 45 received both, and 109 received neither. We investigated 140 prognostic associations; four were found to be statistically significant at a P value of </= .05 (three fewer than expected by chance). Two were in the hypothesized direction of effect, and two were in the opposite direction. All arose from measurements 1 year after diagnosis, which were most susceptible to confounding by treatment. There was no evidence of consistency of associations across outcomes or questionnaires. These results are in keeping with chance as the explanation for our statistically significant findings. CONCLUSION HRQOL and psychosocial status at diagnosis and 1 year later are not associated with medical outcome in women with early-stage BC.

Is Leptin a Mediator of Adverse Prognostic Effects of Obesity in Breast Cancer

PURPOSE Leptin, an adipocyte-derived cytokine that is elevated in obesity, has been associated with carcinogenesis, tumor migration and invasion, enhancement of angiogenesis, and increased aromatase activity. It has been suggested that leptin may mediate adverse prognostic effects of obesity in breast cancer. PATIENTS AND METHODS Four hundred seventy-one women with surgically resected T1-3, N0-1, M0 breast cancer were studied. Leptin was assayed in stored fasting blood specimens obtained before adjuvant therapy. Women were followed prospectively for distant disease-free survival (DDFS) and overall survival (OS). RESULTS Patients ranged from 26 to 74 years of age, and staging was as follows: T1 = 262, T2 = 151, T3 = 23, TX = 35, N0 = 323, and N1 = 148. Estrogen receptor was positive in 286 patients, and progesterone receptor was positive in 259 patients. One hundred forty-five patients received adjuvant chemotherapy, 146 received adjuvant tamoxifen, 46 received both, and 134 received neither. Mean leptin was 15.2 +/- 10.1 ng/mL. Univariately, leptin was associated with OS (overall P = .049; P = .014 postmenopausal). Leptin was not associated with DDFS overall or in any menopausal subgroup (P > or = .19). In multivariate Cox modeling, leptin was not significantly associated with DDFS or OS (P = .11 and 0.075, respectively). Adjustment for insulin or body mass index further reduced the association of leptin with outcome. CONCLUSION Although leptin is strongly correlated with obesity and insulin, we could not show that it is independently associated with prognosis in early-stage breast cancer. Because we cannot rule out modest prognostic effects, we recommend additional research to explore this potential association, particularly in postmenopausal women.

Quality of Life in Long-Term Breast Cancer Survivors

PURPOSE There is considerable interest in the quality of life (QOL) of long-term breast cancer (BC) survivors. We studied changes in QOL from time of BC diagnosis to long-term survivorship and compared QOL in long-term survivors to that of age-matched women with no history of BC. PATIENTS AND METHODS In all, 535 women with localized BC (T1-3N0-1M0) were recruited from 1989 to 1996 and followed prospectively, completing QOL questionnaires at diagnosis and 1 year postdiagnosis. Between 2005 and 2007, those alive without distant recurrence were recontacted to participate in a long-term follow-up (LTFU) study. A control group was recruited from women presenting for screening mammograms, and both groups completed LTFU QOL questionnaires. Longitudinal change in BC survivors and differences between BC survivors and controls were assessed in eight broad categories with clinically significant differences set at 5% and 10% of the breadth of each QOL scale. RESULTS A total of 285 patients with BC were included in the study, on average 12.5 years postdiagnosis. Longitudinally, clinically significant improvements were observed in overall QOL by 1 year postdiagnosis with further improvements by LTFU. Some clinically significant improvements over time were seen in all categories. A total of 167 controls were recruited. Deficits were observed in self-reported cognitive functioning (5.3% difference) and financial impact (6.3% difference) in BC survivors at LTFU compared with controls. CONCLUSION Long-term BC survivors show improvement in many domains of QOL over time, and they appear to have similar QOL in most respects to age-matched noncancer controls, although small deficits in cognition and finances were identified.

Association of young age and chemotherapy with psychosocial distress and health-related quality of life (HRQOL) during the first year after breast cancer (BC)

8014 Background: Psychosocial distress and HRQOL after BC diagnosis may be related to a variety of factors, including age and treatment. METHODS We investigated these attributes in 397 women with newly diagnosed T1-3, N0-1, M0 BC. Women completed the Profile of Mood States (POMS), Impact of Event Scale (IES), Psychosocial Adjustment to Illness Scale (PAIS), Mental Adjustment to Cancer Scale (MAC) and EORTC QLQ-C30 questionnaires shortly after diagnosis (9.7±5.2 weeks) and one year post diagnosis (57.4±7.7 weeks). The impact of age and adjuvant chemotherapy was analysed with t-tests and regression analysis. Mean age was 52.0±9.9 years. 47.6% were postmenopausal, 68.0% had ER/PgR positive tumors, 39.8% received CXT, 44.0% tamoxifen. RESULTS At baseline, young age was significantly associated with greater distress (POMS all scales, total score), greater adverse impact on adjustment (PAIS 4 subscales, total), greater anxious-preoccupied and reduced fatalistic coping (MAC), and reduced emotional and cognitive functioning (EORTC QLQ-C30) (all p≤0.05); most of these effects were attenuated at one year, reflecting improvement over time. At 1 year, anxiety, anger and total mood disturbance (POMS), psychological distress and total score (PAIS), poor emotional functioning (EORTC QLQ-C30), and greater anxious-preoccupied coping and fatalistic coping (MAC) remained significantly associated with young age (p≤0.05). Physical functioning (EORTC QLQ-C30) was worse in older women at both timepoints. Adjusting for age, women who received chemotherapy reported greater adverse impact on vocational and social functioning (PAIS); role, social functioning and QOL (EORTC QLQ-C30) at baseline (p≤0.05). At one year, greater adverse impact of chemotherapy was seen for most PAIS scales and for physical, role and social functioning (EORTC QLQ-C30) (p≤0.05). CONCLUSIONS Age is an important determinant of psychosocial distress and HRQOL in newly diagnosed BC; women who receive CXT report greater adverse impact on adjustment, role, social and vocational functioning which persisted at one year. No significant financial relationships to disclose.

Prospective change in 25-OH vitamin D levels over long-term follow-up and health outcomes in breast cancer survivors.

6111 Background: 25 OH vitamin D (VitD) deficiency, common at breast cancer (BC) diagnosis, is associated with poor BC outcomes. Change in VitD after diagnosis of BC and associations with other health outcomes are unknown. Methods: 535 patients with T1-3,N0-1,M0 newly diagnosed BC enrolled in a prospective cohort study (1989-1996) were candidates for a long-term follow-up (LTFU) study (2004-2007). 123 had died, 75 were ineligible (33 distant recurrence, 28 other invasive cancer, 14 moved > 1 hour away). Of the remaining 337, 29 (9%) refused participation, 23 (7%) could not be contacted, 285 were enrolled. Women reported medical status, diet and exercise, allowed anthropometric measurements, and completed questionnaires (EORTC QLQ C-30, SF36, POMS, Key Everyday Problems, and Ladder of Life). Fasting blood was analyzed for VitD (nmol/L) by radioimmunoassay (DIASORIN, Stillwater, MN). Associations of VitD with health outcomes were examined in 231 women with VitD levels at baseline and LTFU using standard sta...