Hormone-Dependent Tumors and Sexuality in the Neuro-Oncology of Women (N.O.W.): Women's Brain Tumors, Gaps in Sexuality Considerations, and a Need for Evidence-Based Guidelines.

PURPOSE OF REVIEW: While females make up almost 60% of all brain and spinal cord tumors in adults, guidelines that address women's issues in neuro-oncology are lacking. This review sheds light on two common women's issues in neuro-oncology. RECENT FINDINGS: Neuro-oncology providers are often faced with patient questions about fertility and pregnancy maintenance or prevention and typically respond with generic cancer chemotherapy recommendations, based on the paucity of evidence on the use of common neuro-oncology chemotherapies and pregnancy. While these remain important gap issues, there are several other poorly researched issues in the Neuro-Oncology of Women (N.O.W.) including recommendations around endogenous and iatrogenic hormone exposure and female sexuality in cancer. As a significant percentage of cancers are hormone-dependent, it is important to understand how changes in hormone levels impact tumor biology over the course of a woman's lifespan. Furthermore, greater attention should be given to the impact of tumors and tumor treatments on female sexuality. This article is intended to serve as an introduction to these two specific subjects within the vast expanse of N.O.W. subject matter.

Body composition, physical function and quality of life in healthy men and across different stages of prostate cancer.

BACKGROUND: Androgen deprivation therapy (ADT) for prostate cancer (PC) has detrimental effects on physical function and quality of life (QoL), but the addition of androgen receptor signalling inhibitors (ARSI) on these outcomes is unclear. PURPOSE: To compare body composition, physical function, and QoL across progressive stages of PC and non-cancer controls (CON). METHODS: In men with hormone sensitive PC (HSPC, n = 43) or metastatic castration-resistant PC (mCRPC, n = 22) or CON (n = 37), relative and absolute lean and fat mass, physical function (6 m walk, chair stands, timed up and go [TUG], stair climb), and QoL were determined. RESULTS: Relative body composition differed amongst all groups, along with ~39% greater absolute fat mass in mCRPC vs. CON. TUG and chair stands were ~71% and ~33% slower in mCRPC compared to both CON and HSPC, whereas stair climb was ~29% and 6 m walk was ~18% slower in mCRPC vs. CON. Relative body composition was correlated with physical function (r = 0.259-0.385). Clinically relevant differences for mCRPC were observed for overall QoL and several subscales vs. CON, although body composition and physical function did not influence QoL. CONCLUSIONS: PC progression is associated with deteriorations in body composition and physical function. As ADT length was similar between groups, ARSI use for mCRPC likely contributed in part to these changes. Given the difficulties of improving lean mass during ADT, interventions that reduce adiposity may lessen the side effects of hormone therapy.

Tor Vergata University-Hospital in the Beginning of COVID-19-Era: Experience and Recommendation for Breast Cancer Patients.

COVID-19 has been officially declared as a pandemic by the WHO. Italy was the first European country to be strongly affected by this outbreak. All elective and health promotion activities were reduced. Accordingly, Italian Breast Units and breast cancer (BC) screening programs scaled down significantly their activities. The aim of this study was to evaluate measures that could potentially reduce the clinical impact of COVID-19 on BC patients. Temporary recommendations are needed that could assist specialists in preventing COVID-19 infection and optimizing resources for diagnosis and treatment of BC patients.

Understanding Breast Cancer Survivors' Beliefs and Concerns About Adjuvant Hormonal Therapy: Promoting Adherence.

Adjuvant hormonal therapy is recommended for women with hormone receptor (HR)-positive breast cancer. Though critical, many patients are non-adherent to this therapy. Few scales have been developed to specifically address beliefs about adjuvant hormonal therapy. This study explores the clarity and relevance of the Beliefs about Medicine Questionnaire (BMQ) in the context of adherence behaviors to hormonal therapy in Black and White breast cancer survivors. We recruited women diagnosed with HR-positive cancer from the Washington, DC, area. An interviewer administered a standardized survey and conducted a cognitive interview. Participants rated the BMQ across three areas: relevance, difficulty, and clarity. We coded whether the comments identified item level issues: limited applicability, unclear reference, unclear perspective, or wording or tone. In-depth interviews were conducted with women who prematurely discontinued hormone therapy. The sample (n = 30) was equally split between Black and White survivors. On average, women were 57.9 years old (SD = 9.0). Overall 77% rated scale as relevant. Cognitive interviews revealed areas of perceived limited acceptability such as the notion of becoming too dependent or the notion of becoming worse if not taking the medication. Women who discontinued hormonal therapy (n = 2) felt ambivalent towards hormonal therapy as they reported having both positive and negative beliefs about the medication. Our study findings suggest new areas for further research and instrument development to accurately measure self-reported beliefs about hormonal therapy by HR-positive breast cancer survivors.

Optimizing Quality of Life in Patients with Hormone Receptor-Positive Metastatic Breast Cancer: Treatment Options and Considerations.

The treatment landscape for hormone receptor-positive metastatic breast cancer continues to evolve as the molecular mechanisms of this heterogeneous disease are better understood and targeted treatment strategies are developed. Patients are now living for extended periods of time with this disease as they progress through sequential lines of treatment. With a rapidly expanding therapeutic armamentarium, the prevalence of metastatic breast cancer patients with prolonged survival is expected to increase, as is the duration of survival. Practice guidelines recommend endocrine therapy alone as first-line therapy for the majority of patients with metastatic hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. The approval of new agents and expanded combination options has extended their use beyond first line, but endocrine therapy is not used as widely in clinical practice as recommended. As all treatments are palliative, even as survival is prolonged, optimizing and maintaining patient quality of life is crucial. This article surveys data relevant to the use of endocrine therapy in the setting of hormone receptor-positive metastatic breast cancer, including key clinical evidence regarding approved therapies and the impact of these therapies on patient quality of life.

What do women with breast cancer expect from their treatment? Correlates of negative treatment expectations about endocrine therapy.

OBJECTIVES: Patients' negative treatment expectations can lead to nocebo-related side effects and non-initiation of treatment. This study aims to identify correlates of treatment expectations in patients with breast cancer before the start of endocrine therapy. METHODS: Expectations were assessed in a cross-sectional sample of 166 patients with breast cancer after receiving treatment information. Side effect expectations (one item) and treatment necessity-concern balance (Beliefs about Medicines Questionnaire) were assessed. Correlates were analyzed using regression analyses. The structure of treatment expectations was investigated using a network analysis. RESULTS: About 25% of patients expressed negative expectations. Higher side effect expectations were associated with lower treatment efficacy expectations (ß = -0.20, p = 0.01), higher medication overuse beliefs (ß = 0.17, p = 0.01), and a negative treatment appraisal before study treatment information (ß = -0.17, p = 0.02). A negative necessity-concern balance was associated with lower treatment efficacy expectations (ß = 0.36, p < 0.001), lower adherence intention (ß = 0.21, p < 0.001), and no knowledge of tumor's receptor status (ß = 0.21, p < 0.001); furthermore, it was associated with higher medication harmfulness beliefs (ß = -0.16, p = 0.02), negative treatment pre-appraisal (ß = 0.15, p = 0.01), higher somatosensory amplification (ß = -0.14, p = 0.02), and higher education (ß = -0.12, p = 0.02). The most important network node was the concern that endocrine therapy disrupts life. CONCLUSION: Negative treatment expectations before treatment start are mainly associated with psychological variables. These results are relevant for patient education in clinical settings. To improve expectations, clinicians might emphasize treatment efficacy and discuss general and specific medication concerns. Improving treatment knowledge could also be beneficial. Copyright © 2016 John Wiley & Sons, Ltd.

Exercise preferences among men with prostate cancer receiving androgen-deprivation therapy.

PURPOSE/OBJECTIVES: To investigate acceptability of and preferences for physical activity participation in men receiving androgen-deprivation therapy (ADT) for prostate cancer, to identify influencing clinical and demographic factors, and to determine the percentage meeting national exercise guidelines. DESIGN: Cross-sectional, descriptive. SETTING: Ambulatory care clinic of a large medical center. SAMPLE: 135 men receiving ADT. METHODS: A structured interview with a systematic procedure was used to elicit preferences for physical activity. MAIN RESEARCH VARIABLES: Exercise preferences and acceptability; evidence-based exercise intervention. FINDINGS: Participants expressed high levels of acceptability of and willingness to participate in aerobic (64% and 79%) and muscle-strengthening (79% and 81%) programs. Preferences were expressed for muscle-strengthening activities performed at home, either alone or in the company of a family member. Flexible, spontaneous, and self-paced programs were preferred. Significant associations were identified for distance, age, obesity, duration of ADT, and meeting American College of Sports Medicine (ACSM) and American Heart Association (AHA) guidelines. Nineteen percent of the study population met the guidelines for weekly physical activity. CONCLUSIONS: High levels of expressed acceptance of and willingness to participate in physical activity programs as well as the small number of participants meeting ACSM and AHA guidelines suggest feasibility of and support the need for the development of exercise programs in this population. IMPLICATIONS FOR NURSING: Incorporating patient preferences and evidence-based practice is integral to providing high-quality patient-centered care and is the foundation for appropriate intervention programs. Insight from this study will facilitate the design of programs that better reflect actual preferences of prostate cancer survivors. KNOWLEDGE TRANSLATION: ADT-induced changes in body composition are believed to contribute to a reduction in insulin sensitivity and dyslipidemia that contribute to increased cardiovascular risk profile. Exercise has the potential to mitigate the harmful effects of ADT.

[Innovative individualized rehabilitation concepts in oncology]. / Innovative individualisierte Rehabilitationskonzepte in der Onkologie.

Die onkologische Rehabilitation zielt auf die Verbesserung der körperlichen, psychischen und sozialen Fähigkeiten und Unterstützung bei der Bewältigung der Krankheit ("Coping") ab. Ein wichtiges Ziel ist dabei neben der psycho-onkologischen Therapie die Steigerung der körperlichen Aktivität zur Prävention und Therapie chronischer Krankheiten, insbesondere auch der mit steigender Überlebensrate an Bedeutung zunehmenden Folge- und Begleiterkrankungen. Immer mehr Beobachtungsstudien weisen außerdem darauf, dass körperliche Aktivität auch die Prognose der Krebserkrankung günstig beeinflussen kann. Die beste Evidenz besteht dabei bislang für das (Hormonrezeptor-positive) postmenopausale Mamma-Karzinom. Eine nachhaltige Lebensstilmodifikation ist bislang oft nur schwer erreichbar. Langfristig angelegte, interdisziplinäre Rehabilitationskonzepte, deren Ziel eine intensive und nachhaltige Steigerung der körperlichen Aktivität ist, scheinen bei Brustkrebspatientinnen ein erfolgversprechender Ansatz zu sein und werden durch das hier vorgestellte Studienkonzept exemplarisch erläutert.

Health-related quality of life, psychological distress, and adverse events in postmenopausal women with breast cancer who receive tamoxifen, exemestane, or anastrozole as adjuvant endocrine therapy: National Surgical Adjuvant Study of Breast Cancer 04 (N-SAS BC 04).

Health-related quality of life (HRQOL), symptoms of depression, and adverse events (AEs) were compared between Japanese postmenopausal patients with hormone-sensitive breast cancer (BC) who received adjuvant tamoxifen, exemestane, or anastrozole in an open-labeled, randomized, multicenter trial designated as the National Surgical Adjuvant Study of Breast Cancer (N-SAS BC) 04 substudy of the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial. During the first year of treatment, HRQOL and symptoms of depression were analyzed using the Functional Assessment of Cancer Therapy-Breast (FACT-B) and its Endocrine Symptom Subscale (ES), and the Center for Epidemiologic Studies Depression Scale (CES-D), respectively. In addition, predefined AEs were analyzed. A total of 166 eligible patients were randomly assigned to receive adjuvant tamoxifen, exemestane, or anastrozole. FACT-B scores increased after treatment began and remained significantly higher in the tamoxifen group than in the exemestane group or anastrozole group during the first year (P = 0.045). FACT-B scores were similar in the exemestane group and anastrozole group. ES scores and CES-D scores were similar in all treatment groups. Arthralgia and fatigue were less frequent, but vaginal discharge was more frequent in the tamoxifen group than in the exemestane group or anastrozole group. HRQOL was better in Japanese postmenopausal women treated with tamoxifen than those treated with exemestane or anastrozole. HRQOL and AEs were similar with exemestane and anastrozole. Given the results of the TEAM trial, upfront use of tamoxifen followed by an aromatase inhibitor (AI) may be an important option for adjuvant endocrine therapy in Japanese postmenopausal women.

Intermittent docetaxel therapy with estramustine for hormone-refractory prostate cancer in Japanese patients.

BACKGROUND: We evaluated the efficacy and toxicity of intermittent docetaxel (DCT) with estramustine (EM) for hormone-refractory prostate cancer (HRPC). METHODS: Fifteen patients were enrolled. They received injected DCT (70 mg/m2 body surface) on day 1 in association with oral EM 560 mg/day (days 1-5). Treatments were repeated every 3 weeks. Serum prostate-specific antigen (PSA) levels were categorized based on the first three courses. Patients exhibiting either a response or stable disease (SD) could have a holiday from treatment (intermittent schedule). The holiday continued until elevation of the PSA level from the nadir baseline level occurred three times. All patients were evaluated for toxicity and quality of life (QOL). Survival curves were established using Kaplan-Meier graphs. RESULTS: The median number of courses of DCT/EM therapy was five (range, 3-12 courses). The response rate of the first cycle was 53%: 3 patients with complete response (CR), 5 patients with partial response (PR), 4 patients with SD, and 3 patients with disease progression. Eight patients were able to begin the second re-entry cycle. No patients showed a CR, 2 patients exhibited PR, 4 patients had SD, and the overall response rate was 25%. The survival rates were 93% at 1 year, and 26.1% at 2 years Grade 3-4 anemia was observed in 2 patients (13.3%), neutropenia in 11 (73.3%), and thrombocytopenia in 2 (13.3%). The QOL scale showed good QOL after 6 months, with improvement in the score for nausea and vomiting. CONCLUSION: Intermittent DCT/EM therapy was well tolerated, and has the potential to prolong survival, with a high QOL, in patients with HRPC.

Cognitive effects of hormonal therapy in early stage breast cancer patients: a prospective study.

OBJECTIVE: The primary purpose of this study was to evaluate the cognitive effects of adjuvant hormonal therapies in breast cancer patients. PARTICIPANTS AND METHODS: Post-menopausal breast cancer patients scheduled to receive tamoxifen (n=31) or anastrozole (n=14) completed neuropsychological testing around the time of commencement of treatment (T1), and again 5-6 months later (T2). A sample of healthy female volunteers (n=28) was tested at comparable intervals. A standardized regression-based approach was used to assess cognitive change. This method uses test/retest scores of the healthy control group to generate an equation that predicts T2 scores from T1 scores. The difference between the predicted and obtained T2 scores divided by the standard error of the estimate produces a deviation score that reflects the discrepancy from the T1-T2 difference scores that would be expected on the basis of practice and error alone. RESULTS: Analysis of individual deviation scores revealed that both the patients taking tamoxifen and those taking anastrozole were more likely than healthy controls to show reliable cognitive decline from T1 to T2 (39, 64, and 7%, respectively). Processing speed and verbal memory were the cognitive domains most affected. CONCLUSION: These data suggest that hormonal therapies exert a subtle negative influence on cognition in breast cancer patients. Further analyses indicated that this effect was not fully accounted for by demographic factors or fatigue. Methodological limitations of the current study are addressed, along with recommendations for future studies in this area.

Psychosocial correlates of progesterone receptors in breast cancer.

BACKGROUND: The diagnosis of cancer may lead to psychological distress with anxiety and depression as the most prevalent symptoms. Several investigators have found a correlation between psychosocial factors and tumor levels of estrogen receptors and progesterone receptors (PRs) while others have not. The aim of this study was to investigate demographic characteristics and severity of depression and anxiety as expressed by the Hospital Anxiety and Depression (HAD) scale of patients with high or low PR expression in breast cancers. METHODS: Two hundred and seventy-eight patients with primary breast cancer were divided into two subgroups according to PRs expressed in breast cancers. RESULTS: The subgroup of patients with PR-negative breast cancers expressed depression, as measured by the HAD scale, to a smaller degree (4.7+/-4.1) than the subgroup of patients with PR-positive breast cancers (5.8+/-4.1). The difference was rather small but still statistically significant (t=2.1, df=236.7, P<.05). In contrast, we did not observe any correlation between anxiety and PR status. Differences between the subgroups according to family history of mental disorders were observed (chi(2)=4.7, df=1, P<.05). In the subgroup of patients with PR-negative breast cancers; 13% of patients had a family history of mental disorders compared with 23% of patients with PR-positive breast cancers. CONCLUSIONS: Depression expressed by patients with primary breast cancers could be influenced by the PR status of the tumors; however, other factors such as cancer treatment and family history of mental disorders could also be important.

Intermittent androgen suppression for locally advanced and metastatic prostate cancer: preliminary report of a prospective multicenter study.

OBJECTIVES: To clarify the effect of intermittent androgen suppression on the time to androgen-independent progression and changes in quality of life (QOL). METHODS: Patients with locally advanced or metastatic prostate cancer were treated with a combination of leuprolide acetate and flutamide for 36 weeks. When the serum prostate-specific antigen (PSA) levels at 24 and 32 weeks were less than 4.0 ng/mL, treatment was withheld until the PSA level reached 15 ng/mL or the pretreatment level. This cycle of on-treatment and off-treatment was repeated until PSA failure (three consecutive increases in PSA level greater than 4.0 ng/mL during the on-treatment period) or symptomatic progression was observed. Changes in QOL were assessed by a self-assessment questionnaire. RESULTS: Forty-nine patients (26 with T3N0M0, 8 with T2-T3N1M0, 2 with T4N0M0, and 13 with T2-T3N0M1) were enrolled. The mean follow-up period was 136.5 weeks. Thirty-one patients finished cycle 1, six finished cycle 2, and three finished cycle 3. The mean off-treatment duration in cycles 1, 2, and 3 was 46.1, 36.9, and 23.3 weeks, respectively. In the off-treatment period, statistically significant improvements in the QOL score were observed in the categories of potency (11.4 versus 2.4) and social/family well-being (20.3 versus 16.1) compared with those in the on-treatment period. PSA failure occurred in 6 patients (3 with T3N0M0 and 3 with T2-T3N1M0), and all patients were alive at last follow-up. CONCLUSIONS: Our interim analysis indicated that QOL is remarkably improved during the off-treatment period. Intermittent androgen suppression would be a viable option for treatment of advanced prostate cancer, although a randomized controlled study is required to determine whether intermittent androgen suppression prolongs the time to androgen-independent cancer. We will continue follow-up in this study to a minimum of 3 years.

Effects of social housing condition on the response of the Shionogi mouse mammary carcinoma (SC115) to chemotherapy.

In the present study, we demonstrate that social housing conditions significantly alter the response of the transplantable androgen-responsive Shionogi mouse mammary tumor (SC115) to chemotherapy. Mice were reared either in groups (G) or as individuals (I). Immediately following tumor cell or vehicle injection, mice were rehoused from group to individual (GI) or from individual to group (IG) conditions. A combination of Adriamycin (4 mg/kg) and cyclophosphamide (61.5 mg/kg), in a series of three i.p. injections 7 days apart, was initiated when mean tumor weights of mice within a housing condition (GI or IG) reached 1 g. Survival probability was significantly greater in mice in the IG housing condition compared to those in the GI housing condition (47% versus 19%, respectively). Additionally, the median survival time following the initiation of chemotherapy was greater for mice in the IG than for mice in the GI condition (24.5 days versus 15.0 days, respectively). These findings suggest that a psychosocial stressor, social housing condition, can significantly influence chemotherapeutic efficacy.

Quality of life in patients with prostatic carcinoma: a review and results of a study in N+ disease. Prostate-specific antigen as predictor of quality of life.

Clinical evaluation in oncology has typically focused on outcome indicators, while less attention has been paid to how treatment affects quality of life (QOL) of the patient. In this article some general aspects of quality of life are discussed, a short review of published data on QOL in patients with prostate cancer is given and results of a QOL study executed by the authors on patients with lymph node positive prostatic cancer are presented. The purpose of the study was to examine the impact of immediate or delayed treatment (after objective progression) in patients with prostatic carcinoma (T1-3 N1-3 M0) on quality of life parameters. To this end an extended questionnaire was constructed. Fifty-five patients participated. Assessment was performed twice, in 1994 and 1995. The comparison between patients with and patients without treatment showed in 1994 as well as in 1995 significant differences for hormonal treatment side effects such as sexual functioning and hot flushes, all of which were experienced more frequently by treated patients. In 1994 the treated patients experienced more psychological distress while in 1995 they showed worse physical function, less energy and more fatigue when compared to patients under surveillance. The premise that active treatment would improve the psychological quality of life was not sustained. In addition global health status and quality of life were identified as independent factors for progression in untreated patients with lymph node positive prostate cancer. Finally, an increase in prostate-specific antigen (PSA) in hormonally treated patients not only indicated hormonal escape but also a decrease in QOL.

A histological study of the Shionogi adenocarcinoma 115 grown in male and female mice.

We have previously demonstrated that growth rate and morphology differ between androgen-responsive Shionogi mouse mammary tumours maintained in male and female mice. Furthermore, we can modulate the growth rate of these tumours in male mice by exposing the mice to psychosocial stressors. In the present study, we were interested in determining if tumours in male mice with a comparable growth rate to that in females, also had a morphology similar to that in females. SC115 tumours were examined using histochemical and immunohistochemical techniques. Tumours in male mice were easily distinguishable from tumours in female mice regardless of growth rate. Tumours maintained in female mice contained osteoid-like regions which stained positive for sialic acid and sulphate moieties. No such regions were observed in any of the tumours from male mice. In addition, although all tumours contained MSA (muscle specific actin)-positive and S100 protein-positive cells, these regions were more extensive in the tumours of female mice. This study suggests that tumour growth rate and morphology are independently regulated by the host environment.

Perceived social support and tumor estrogen/progesterone receptor status as predictors of natural killer cell activity in breast cancer patients.

This report is concerned with the prediction of natural killer (NK) cell activity in 61 Stage I and II breast cancer patients, between the ages of 25 and 70, who were accrued to this project. All baseline interview and testing data were obtained either just before patients were discharged from the hospital, or at their first outpatient visit, within two weeks of discharge. A major interest of this project is the predictive value of perceived social support, as a potential "stress" buffer, related to NK activity. In the main model reported here, we found that a significant amount of NK activity variance could be explained by five variables. Higher NK activity could be predicted by the perception of high quality emotional support from a spouse or intimate other, perceived social support from the patient's physician, estrogen receptor-negative tumor status, having an excisional biopsy as surgical treatment, and actively seeking social support as a major coping strategy (R2 = 0.33, F(5,55) = 5.5, p less than 0.0004). Findings are discussed in terms of host interaction with tumor endocrine status, and the role that social support might play in modulating such activity.

The assessment of subjective response in prostatic cancer clinical research.

This paper reviews a range of issues related to the assessment of subjective response and quality of life in prostate cancer clinical research. With regard to subjective response criteria, the Karnofsky performance status scale and the subjective components of the World Health Organization acute and subacute toxicity scales appear to hold certain advantages over competing measurement systems. Nevertheless, the available evidence suggests that further developmental work is needed to improve the precision of these instruments. In the area of quality of life assessment, there does not appear to be a clear choice among the array of available measures. Although there are several promising instruments, none has undergone sufficient field testing to justify widespread adoption in clinical research settings. A number of suggestions are offered to facilitate further development in quality of life instrumentation and research implementation.