Citations

Abstract Background: It has long been known that chemotherapy can result in premature menopause, causing follicular senescence and estrogen depletion with associated hot flashes and mood alterations. What is less well appreciated is whether the stroma of the ovary is equally impacted after chemotherapy, resulting in androgen deprivation. The aim of this pilot study was to evaluate whether androgen levels are adversely affected after chemotherapy and whether this is associated with unwanted symptoms. Methods: Women who were premenopausal, newly diagnosed with breast cancer, and about to undergo adjuvant chemotherapy were followed longitudinally. Women with adrenal insufficiencies, taking steroids, oral contraceptives, or had had previous chemotherapy were excluded. Self report questionnaires regarding sexual function, fatigue, mood, menstrual symptoms; menstrual diaries; and blood were collected at 4 points: before treatment, mid chemotherapy, post chemotherapy and 6 months later. Serum concentrations of dehydroepiandrosterone sulfate (DHEA-S) (adrenal hormone), bioavailable testosterone (bioT), androstenedione (Adione) (stromal hormone), estrone (E1), estradiol (E2) (follicular hormone), sex hormone binding globulin (SHBG), and follicle stimulating hormone (FSH) were evaluated. Descriptive statistics, comparisons of means by two sided t-tests and Pearson correlation coefficients were computed. Six month post treatment data are reported. Results: 24 women were accrued and 21 provided serum and questionnaires through 6 months. All sex steroid hormones decreased during chemotherapy and did not return to baseline by 6 months for the group as a whole. At 6 months, 14 women were postmenopausal per FSH, E2 and menstrual diaries and 7 had resumed menses. There were no significant differences in hormone concentrations at baseline between women who ended up menopausal from those who resumed menses. However, at 6 months, postmenopausal women had significantly lower concentrations than premenopausal women of E2 (289 pg/ml pre- 9 pg/ml post), E1 (132 pg/ml pre- 22 pg/ml post), and Adione (102 ng/dL pre- 56 ng/dL post), but not DHEA-S or bioT (all p < .01). E2 was significantly correlated with Adione (R = .47 p = .03), and E1 (R = .57, p = .007). Low to moderate correlations were found between hormone concentrations and symptoms. The use of tamoxifen was significantly, and negatively correlated with the total score on the Female Sexual Function Index (r = −.572, p = .005), indicating worse sexual function for women on tamoxifen. Conclusion: These data support the hypothesis that the post chemotherapy ovary suffers both follicular and stromal dysfunction, as noted by lower Adione, which is specific to the ovarian stroma. Adione concentrations in the postmenopausal group women are similar to published reports of women post oophorectomy. This is the first longitudinal study we are aware of to evaluate ovarian stromal function in women undergoing chemotherapy. This total hormone depletion may be why women experiencing chemotherapy induced menopause report severe and distressing menopausal symptoms such as hot flashes. Estrogen is often implicated, but androgen deprivation in this population should be taken into consideration when planning interventions to improve health related quality of life. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-11-01.

Abstract Atypical hyperplasia is a high-risk premalignant lesion of the breast, but its biology is poorly understood. Many believe that atypical ductal hyperplasia (ADH) is a direct precursor for low-grade ductal breast cancer, whereas atypical lobular hyperplasia (ALH) serves as a risk indicator. These assumptions underlie current clinical recommendations. We tested these assumptions by studying the characteristics of the breast cancers that develop in women with ADH or ALH. Using the Mayo Benign Breast Disease Cohort, we identified all women with ADH or ALH from 1967 to 2001 and followed them for later breast cancers, characterizing side of breast cancer versus side of atypia; time to breast cancer; type, histology, and grade of breast cancer, looking for patterns consistent with precursors versus risk indicators. A total of 698 women with atypical hyperplasia were followed a mean of 12.5 years; 143 developed breast cancer. For both ADH and ALH, there is a 2:1 ratio of ipsilateral to contralateral breast cancer. The ipsilateral predominance is marked in the first 5 years, consistent with a precursor phenotype for both ADH and ALH. For both, there is a predominance of invasive ductal cancers with 69% of moderate or high grade. Twenty-five percent are node positive. Both ADH and ALH portend risk for ductal carcinoma in situ and invasive breast cancers, predominantly ductal, with two thirds moderate or high grade. The ipsilateral breast is at especially high risk for breast cancer in the first 5 years after atypia, with risk remaining elevated in both breasts long term. ADH and ALH behave similarly in terms of later breast cancer endpoints. Cancer Prev Res; 7(2); 211–7. ©2014 AACR.

AbstractObjectiveThe aim of this randomized controlled trial for patients with advanced cancer receiving radiation therapy was to determine the effect of a multidisciplinary intervention on spiritual quality of life (QOL) at the end of the intervention (week 4) and at two follow‐up time points (weeks 26 and 52).MethodsOne hundred thirty‐one persons were randomized to either the intervention or control (forms only) groups. The intervention included six 90‐min in‐person sessions based on the physical, emotion, social, and spiritual domains of QOL. Three sessions included the spiritual component. Caregivers were present for four sessions, one which included a spiritual component. Ten follow‐up phone calls were made to the patients in the intervention group during the 6‐month follow‐up period. Patients completed the Functional Assessment of Cancer Therapy: General Scale, the Linear Analog Self‐Assessment which includes an assessment of spiritual QOL, and the Functional Assessment of Chronic Illness Therapy‐Spiritual Well‐Being (FACIT‐Sp) at enrollment, and weeks 4, 27, and 52.ResultsFollowing the intervention, the intervention group demonstrated improved spiritual QOL on the FACIT‐Sp, whereas the spiritual QOL of the control group decreased, resulting in significant mean changes between groups (total score: 1.7 vs. −2.9; p < 0.01; meaning/peace subscale: 1.0 vs. −3.5; p < 0.01; faith subscale: 3.1 vs. −1.7; p = 0.04).ConclusionsThe results indicate that a multidisciplinary intervention which includes a spiritual component can maintain the spiritual QOL of patients with advanced cancer during radiation therapy. Copyright © 2013 John Wiley & Sons, Ltd.

In vivo assessment of ventricular function in rodents has largely been restricted to transthoracic echocardiography (TTE). However 1.5 T cardiac magnetic resonance (CMR) and transoesophageal echocardiography (TOE) have emerged as possible alternatives. Yet, to date, no study has systematically assessed these three imaging modalities in determining ejection fraction (EF) in rats. Twenty rats underwent imaging four weeks after surgically-induced myocardial infarction. CMR was performed on a 1.5 T scanner, TTE was conducted using a 9.2 MHz transducer and TOE was performed with a 10 MHz intracardiac echo catheter. Correlation between the three techniques for EF determination and analysis reproducibility was assessed. Moderate-strong correlation was observed between the three modalities; the greatest between CMR and TOE (intraclass correlation coefficient (ICC) = 0.89), followed by TOE and TTE (ICC = 0.70) and CMR and TTE (ICC = 0.63). Intra- and inter-observer variations were excellent with CMR (ICC = 0.99 and 0.98 respectively), very good with TTE (0.90 and 0.89) and TOE (0.87 and 0.84). Each modality is a viable option for evaluating ventricular function in rats, however the high image quality and excellent reproducibility of CMR offers distinct advantages even at 1.5 T with conventional coils and software.

Fatigue is the problematic symptom identified by patients with cancer. However, fatigue has not been widely examined in caregivers of patients with cancer. In this study, 131 caregivers of patients diagnosed with advanced stage cancer and actively receiving radiotherapy reported experiencing the most difficulties with fatigue (mean 46.9; on a 0-100 scale, with a 10-point difference having clinical meaning) at baseline and at a 6-month follow-up (mean 48.3). This is in sharp contrast to other domains of quality of life and functioning being rated in the 60s, 70s and 80s by the caregivers of patients with cancer. Given the level of fatigue reported by the caregivers of patients with cancer, if confirmed by other investigators in larger and more diverse samples, interventions targeting caregiver fatigue should be explored.

Abstract Benign breast disease (BBD) is an established risk factor for breast cancer among Caucasian women but less is known about BBD in African American women. As African American women suffer from disproportionate mortality due to breast cancer, special focus on pathologic characteristics that may influence disease risk is warranted. Benign breast biopsies from African American women were identified by the University Pathology Group (Detroit, MI). African American women of ages 20 to 84 years, who underwent a breast biopsy from 1997 to 2000, were eligible for the study. Subsequent breast cancers were identified through a linkage with the Detroit Surveillance Epidemiology and End Results (SEER) program. The first biopsy was reviewed by the pathologist, and lesions were classified following Dupont and Page criteria along with involution and other histologic features. Logistic regression was used to estimate the risk of developing a subsequent breast cancer with the histologic characteristics of BBD. A total of 1,406 BBD biopsies from African American women were included in this study with a median follow-up of 10.1 years. The majority (68%) showed nonproliferative disease, 29% had proliferative disease without atypia, and 3% had proliferative disease with atypia. Subsequent incident breast cancers occurred in 55 women (3.9%). Women whose biopsies showed proliferative disease with atypia were more than three-fold more likely to develop breast cancer as compared with women who had nonproliferative disease [relative risk (RR) 3.29, 95% confidence interval (CI) 1.21–8.93]. Better characterization of the risk of breast cancer among women with BBD, considering both ethnicity and detailed molecular findings, can lead to better surveillance, earlier diagnosis, and potentially improved survival. Cancer Prev Res; 5(12); 1375–80. ©2012 AACR.

Abstract Background: Women with hereditary breast cancer risk, who develop breast cancer, face complex surgical decisions related to their breast cancer and risk to their contralateral breast. The aim of this study was to prospectively evaluate the factors influencing decision making in these women and degree of decision conflict before and after consultation with breast specialized physicians (BSP). Methods: Women with hereditary breast cancer risk and recently diagnosed with unilateral breast cancer were enrolled in a prospective decision making questionnaire study. Questionnaires were completed prior to their initial breast clinic visit and after consultation with a breast clinic physician, nurse educator and a breast surgeon. Results: 68 women completed both questionnaires. Mean age was 52 (range 27–84). Prior to meeting with BSP, 10 (15%) women reported having made a decision for the cancer side and 18 (26%) reported being close to deciding. Of the 20 who expressed a surgical preference prior to consultation, 5 (25%) changed their decision after meeting with the BSP [1 to mastectomy (MTX), 4 to breast conservation (BC)]. After consultation with BSP, 65 (96%) reported having made a decision (BC in 29 (45%), MTX in 35 (54%), unspecified in one). The most commonly cited reasons influencing surgical choice were doctor's advice (79%), family history of breast cancer (74%) and worrisome findings on biopsy (50%). Prior to meeting with BSP, 9 (13%) women reported having made a decision regarding screening and/or risk-reducing options for the contralateral breast and another 11 (16%) reported being close to a decision. The choices in these 20 women were screening only in 10 (50%), contralateral prophylactic MTX (CPM) in 3 (15%), CPM and oophorectomy in 2 (10%), other combinations of options in 4, and unspecified in 1. After meeting with the BSP, 49 (72%) reported having made a decision regarding the contralateral breast; this decision was for screening only in 21 (43%), CPM only in 9 (18%), screening plus tamoxifen in 7 (14%), CPM and oophorectomy in 2 (4%), other combinations of options in 8, and unspecified in 2. The most commonly cited reasons for choices on the contralateral side were: family history (81%), doctor's advice (78%), and worrisome findings on biopsy (43%); only 25% cited psychological or emotional reasons. For both the cancer and contralateral sides, decisional conflict was significantly lower after meeting with BSP than prior to meeting with BSP. Decision-conflict scale total scores (possible range 0–100; higher scores indicate more decisional conflict) summarized for each side and compared between timepoints Conclusion: The BSP consult and family history have the greatest influence on decision making among women with hereditary risk diagnosed with breast cancer. After consultation most women felt they had made decisions for both the cancer and contralateral sides and reported significantly lower decision conflict compared to prior to the consultation. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-15-05.

Abstract Invasive breast carcinoma in African American (AA) women differs significantly from their Caucasian (CA) counterparts in its incidence, morphology and outcome. These tumors are more likely to be high grade, hormone receptor negative, present at a younger age and at a higher stage. Evaluation and a better understanding of precursor lesions may help delineate the mechanisms underlying the development of breast cancer in these two groups. Atypical hyperplasia (AH) in the breast has been associated with an increased risk of developing cancer (relative risk∼4.0). Risk stratification of these women by identification of predictive biomarkers would be beneficial for optimal patient care. In our study we evaluated the expression of the following prognostic biomarkers: estrogen receptor (ER), Cyclooxygenase-2 (COX-2) enzyme and Ki-67 in AH in a cohort of AA women with benign breast biopsies. AA women with benign breast biopsies from years 1997–2000 were retrieved from our departmental database. Clinical and follow up data was obtained from the SEER database. The hematoxylin and eosin (H & E) slides for these cases were reviewed by 2 pathologists, who were blinded to the outcome, and those with atypia were included in this study. Paraffin blocks were retrieved for immunohistochemical (IHC) analysis and standardized scoring methods applied. A total of 1608 AA women had benign breast biopsies during the study period. We performed IHC analysis on 37 (2.3%) who were diagnosed with atypia (25 cases of atypical ductal hyperplasia (ADH) and 12 cases of atypical lobular hyperplasia (ALH)). Increased COX-2 expression was seen in 19 of 28 (67.8%) cases with AH. Of these, 13 of 19 cases (68.4%) were of ADH and 6 of 9 cases (66.7%) were of ALH. Twenty of 25 cases had a high expression of ER overall. Of these, 15 of17 (88.2%) of the positive cases was in the ADH category and 3 of 7 (42.8%) was in the ALH group. Of 32 cases, only 3 cases showed a proliferation rate of &gt; 2% (9.4%) with Ki-67 IHC stain. All of these cases belonged to the ADH (21) category. In summary, the majority of AH cases showed increased COX-2 expression, although no differences were observed between lobular and ductal lesions. In contrast, ADH lesions appeared to exhibit increased reactivity for ER compared to ALH. Similarly, although rare, more ADH cases showed an increased proliferation rate compared to ALH. From our data, COX-2 and ER might be of prognostic significance in AA patients with AH. Larger studies with follow up are needed to understand this disease further. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-11-07.

Abstract African American (AA) women have higher mortality rates from breast cancer (BrCa) and are diagnosed at younger ages than their Caucasian counterparts. Women who have had a benign breast biopsy are at increased risk of the disease, although less is known about the risk of BrCa associated with benign breast disease in AA women. We examined 1428 breast biopsies from AA women which occurred from 1997–2000 and assessed various pathologic markers including: apocrine metaplasia, ductal hyperplasia including atypia, evidence of cysts, duct ectasia, fibrosis, intra-ductal papilloma, sclerosing adenosis, columnar alteration, and involution (atrophy). These women were followed for later BrCa through the Metropolitan Detroit Cancer Surveillance System, part of the Surveillance, Epidemiology and End Results (SEER) program through 2008. Women who developed BrCa were compared to those in the cohort who did not, and to other AA women with BrCa in the SEER registry. AA women in our study were also compared to Caucasian women in the Mayo Clinic cohort. Differences in variables were assessed by chi-squared tests and 95% confidence intervals. Of the 1428 biopsies, 52 (3.6%) subsequent incident breast cancers were reported in SEER. The mean age at diagnosis was 59, and the mean time from biopsy to BrCa diagnosis was 6.1 years. Individuals with atypical ductal hyperplasia at biopsy (n=37, 2.6%) were more likely to develop breast cancer (n=7, 13.5%, p&lt;0.01). No other pathologic variables were associated with increased risk. Women in our cohort with breast cancer did not differ from AA in the SEER database with respect to age at diagnosis, stage at diagnosis, or receptor positivity. Compared to the Caucasian women in the Mayo Clinic BBD cohort, AA women in our study were younger at biopsy (p&lt;0.01), but had similar percentages of involution and atypia (p=0.50 and 0.15, respectively). Our preliminary findings among a relatively small group of AA women with prior benign breast biopsies and incident breast cancers suggest that results from the Mayo Cohort study are likely to apply to AA populations. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-08-16.