Phase II randomized controlled trial of hypnosis versus progressive muscle relaxation for body image after breast or gynecologic cancer.

BACKGROUND: Sexual dysfunction, fueled by body image stress, is prevalent in women with a history of breast or gynecologic cancer. Preliminary data support that mind-body connections may improve sexual health outcomes through improving body image. OBJECTIVE: This randomized controlled trial compared hypnosis to progressive muscle relaxation (PMR). The primary outcome was body image at week 6 as measured by the Impact of Treatment Scale for women who have or have had breast or gynecologic cancer. INTERVENTIONS/METHODS: Consented participants were randomized 2:1 to hypnosis or PMR. Both arms consisted of three face-to-face sessions delivered by a trained therapist. Sessions were every 2 weeks for 6 weeks; participants practiced at home between sessions using an audio recording. RESULTS: Eighty-seven women were randomized, 59 to hypnosis and 28 to PMR. Both groups reported significant improvements on body image over time (within group effect size Cohen's d = 0.49-0.75) with no significant difference between groups (p = 0.15). Secondary outcomes were not significantly different between groups. The hypnosis group improved more in sexual satisfaction and sexual interest while the PMR group improved more in positive affect. CONCLUSIONS: Interventions facilitating mind-body connections such as hypnosis and PMR may help to improve body image. This study suggests that stress relieving strategies of hypnosis and PMR may contribute to providing a re-connection to one's body, improved positive affect, and overall better sexual health.

Use of Adjuvant Bisphosphonates and Other Bone-Modifying Agents in Breast Cancer: A Cancer Care Ontario and American Society of Clinical Oncology Clinical Practice Guideline.

Purpose To make recommendations regarding the use of bisphosphonates and other bone-modifying agents as adjuvant therapy for patients with breast cancer. Methods Cancer Care Ontario and ASCO convened a Working Group and Expert Panel to develop evidence-based recommendations informed by a systematic review of the literature. Results Adjuvant bisphosphonates were found to reduce bone recurrence and improve survival in postmenopausal patients with nonmetastatic breast cancer. In this guideline, postmenopausal includes patients with natural menopause or that induced by ovarian suppression or ablation. Absolute benefit is greater in patients who are at higher risk of recurrence, and almost all trials were conducted in patients who also received systemic therapy. Most studies evaluated zoledronic acid or clodronate, and data are extremely limited for other bisphosphonates. While denosumab was found to reduce fractures, long-term survival data are still required. Recommendations It is recommended that, if available, zoledronic acid (4 mg intravenously every 6 months) or clodronate (1,600 mg/d orally) be considered as adjuvant therapy for postmenopausal patients with breast cancer who are deemed candidates for adjuvant systemic therapy. Further research comparing different bone-modifying agents, doses, dosing intervals, and durations is required. Risk factors for osteonecrosis of the jaw and renal impairment should be assessed, and any pending dental or oral health problems should be dealt with prior to starting treatment. Data for adjuvant denosumab look promising but are currently insufficient to make any recommendation. Use of these agents to reduce fragility fractures in patients with low bone mineral density is beyond the scope of the guideline. Recommendations are not meant to restrict such use of bone-modifying agents in these situations. Additional information at www.asco.org/breast-cancer-adjuvant-bisphosphonates-guideline , www.asco.org/guidelineswiki , https://www.cancercareontario.ca/guidelines-advice/types-of-cancer/breast .

Periodontal health in breast cancer patients on aromatase inhibitors versus postmenopausal controls: a longitudinal analysis.

AIM: This study was conducted to determine periodontal changes in postmenopausal breast cancer (BCa) survivors using aromatase inhibitors (AI) as compared to postmenopausal women without BCa. METHODS: An 18-month prospective examination of periodontal health in postmenopausal women (29 receiving AI therapy; 29 women without BCa) was conducted at University of Michigan. Comprehensive periodontal examinations including alveolar bone height (ABH) were conducted at baseline, 6, 12, and 18 months. Bisphosphonate, vitamin D, and calcium supplementation were collected via chart review. Linear mixed models were utilized to investigate the relationship between AI and periodontal measures. RESULTS: Aromatase inhibitor users had significantly deeper probing depths, more dental plaque and clinical attachment loss as compared to controls at the 6, 12, and 18 month study visits (p < 0.05). ABH loss was seen over time within the AI group. The linear mixed model showed a significant effect of time as well as an interaction between aromatase inhibitor use and calcium supplement status. AI users taking calcium experienced less ABH loss over the study than AI users not taking calcium (p = 0.005). CONCLUSION: Aromatase inhibitor therapy has a negative impact on the periodontal health of postmenopausal BCa patients. Calcium supplementation appears to mitigate ABH loss in women on AI.

Associations between genetic variants and the effect of letrozole and exemestane on bone mass and bone turnover.

Adjuvant therapy for hormone receptor (HR) positive postmenopausal breast cancer patients includes aromatase inhibitors (AI). While both the non-steroidal AI letrozole and the steroidal AI exemestane decrease serum estrogen concentrations, there is evidence that exemestane may be less detrimental to bone. We hypothesized that single nucleotide polymorphisms (SNP) predict effects of AIs on bone turnover. Early stage HR-positive breast cancer patients were enrolled in a randomized trial of exemestane versus letrozole. Effects of AI on bone mineral density (BMD) and bone turnover markers (BTM), and associations between SNPs in 24 candidate genes and changes in BMD or BTM were determined. Of the 503 enrolled patients, paired BMD data were available for 123 and 101 patients treated with letrozole and exemestane, respectively, and paired BTM data were available for 175 and 173 patients, respectively. The mean change in lumbar spine BMD was significantly greater for letrozole-treated (-3.2 %) compared to exemestane-treated patients (-1.0 %) (p = 0.0016). Urine N-telopeptide was significantly increased in patients treated with exemestane (p = 0.001) but not letrozole. Two SNPs (rs4870061 and rs9322335) in ESR1 and one SNP (rs10140457) in ESR2 were associated with decreased BMD in letrozole-treated patients. In the exemestane-treated patients, SNPs in ESR1 (Rs2813543) and CYP19A1 (Rs6493497) were associated with decreased bone density. Exemestane had a less negative impact on bone density compared to letrozole, and the effects of AI therapy on bone may be impacted by genetic variants in the ER pathway.

Adjuvant Endocrine Therapy and Bone Health in Breast Cancer.

Breast cancer is one of the most common malignancies of women. The majority of breast cancers express estrogen and/or progesterone receptors, permitting anticancer targeting strategies to reduce estrogen signaling in the cancer cells and thereby lowering the risk of breast cancer recurrence. The development of the selective estrogen receptor modulator (SERM) tamoxifen marked a significant milestone in breast cancer care that transcended older estrogen ablative strategies such as oophorectomy and ovarian irradiation. An unintended benefit of tamoxifen in postmenopausal women was bone density preservation. The third generation of aromatase inhibitors (AIs) have demonstrated superior efficacy to tamoxifen in improving disease-free survival in postmenopausal women. However, the AIs significantly increase bone resorption, reduce bone mineral density, and increase the risk of fracture above that of tamoxifen. As a consequence of this, clinical oncologists have assumed a larger role in the screening and treatment of the skeletal complications of breast cancer therapies. The key features of managing bone health in women with early stage breast cancer receiving adjuvant endocrine therapy are reviewed here.

Hypocalcaemia in patients with metastatic bone disease treated with denosumab.

BACKGROUND: This analysis was performed to further characterise treatment-emergent hypocalcaemia in patients with bone metastases receiving denosumab. METHODS: Laboratory abnormalities and adverse events of hypocalcaemia in patients with metastatic bone disease were analysed using data from three identically designed phase 3 trials of subcutaneous denosumab 120 mg (n = 2841) versus intravenous zoledronic acid 4 mg (n = 2836). RESULTS: The overall incidence of laboratory events of hypocalcaemia grade ⩾ 2 was higher with denosumab (12.4%) than with zoledronic acid (5.3%). Hypocalcaemia events were primarily grade 2 in severity and usually occurred within the first 6 months of treatment. Patients who reported taking calcium and/or vitamin D supplements had a lower incidence of hypocalcaemia. Prostate cancer or small-cell lung cancer, reduced creatinine clearance and higher baseline bone turnover markers of urinary N-telopeptide of type I collagen (uNTx; > 50 versus ⩽ 50 nmol/mmol) and bone-specific alkaline phosphatase (BSAP; > 20.77 µg/L [median] versus ⩽ 20.77 µg/L) values were important risk factors for developing hypocalcaemia. The risk associated with increased baseline BSAP levels was greater among patients who had > 2 bone metastases at baseline versus those with ⩽ 2 bone metastases at baseline. CONCLUSION: Hypocalcaemia was more frequent with denosumab versus zoledronic acid, consistent with denosumab's greater antiresorptive effect. Low serum calcium levels and potential vitamin D deficiency should be corrected before initiating treatment with a potent osteoclast inhibitor, and corrected serum calcium levels should be monitored during treatment. Adequate calcium and vitamin D intake appears to substantially reduce the risk of hypocalcaemia.

Periodontal Health in Women With Early-Stage Postmenopausal Breast Cancer Newly on Aromatase Inhibitors: A Pilot Study.

BACKGROUND: Aromatase inhibitor (AI) use results in low estrogen levels, which in turn affect bone mineral density (BMD). Periodontitis, alveolar bone loss, and tooth loss are associated with low BMD. The goal of this study is to assess the prevalence of periodontitis and perceived oral health and evaluate salivary biomarkers in postmenopausal women who are survivors of early-stage (I to IIIA) breast cancer (BCa) and receive adjuvant AI therapy. METHODS: Participants included 58 postmenopausal women: 29 with BCa on AIs and 29 controls without BCa diagnoses. Baseline periodontal status was assessed with: 1) periodontal probing depth (PD); 2) bleeding on probing (BOP); and 3) attachment loss (AL). Demographic and dental utilization information was gathered by questionnaire. Linear regression modeling was used to analyze the outcomes. RESULTS: No differences were found in mean PD or number of teeth. The AI group had significantly more sites with BOP (27.8 versus 16.7; P = 0.02), higher worst-site AL (5.2 versus 4.0 mm; P <0.01), and more sites with dental calculus (18.2 versus 6.4; P <0.001) than controls. Linear regression adjusted for income, tobacco use, dental insurance, and previous radiation and chemotherapy exposure demonstrated that AI use increased AL by >2 mm (95% confidence interval, 0.46 to 3.92). Median salivary osteocalcin and tumor necrosis factor-α levels were significantly higher in the AI group than the control group. CONCLUSION: This first investigation of the periodontal status of women initiating adjuvant AI therapy identifies this population as having an increased risk for periodontitis.

NCCN Task Force Report: Bone Health In Cancer Care.

Bone health and maintenance of bone integrity are important components of comprehensive cancer care. Many patients with cancer are at risk for therapy-induced bone loss, with resultant osteoporotic fractures, or skeletal metastases, which may result in pathologic fractures, hypercalcemia, bone pain, and decline in motility and performance status. Effective screening and timely interventions are essential for reducing bone-related morbidity. Management of long-term bone health requires a broad knowledge base. A multidisciplinary health care team may be needed for optimal assessment and treatment of bone-related issues in patients with cancer. Since publication of the previous NCCN Task Force Report: Bone Health in Cancer Care in 2009, new data have emerged on bone health and treatment, prompting NCCN to convene this multidisciplinary task force to discuss the progress made in optimizing bone health in patients with cancer. In December 2012, the panel members provided didactic presentations on various topics, integrating expert judgment with a review of the key literature. This report summarizes issues surrounding bone health in cancer care presented and discussed during this NCCN Bone Health in Cancer Care Task Force meeting.

Managing bone mineral density with oral bisphosphonate therapy in women with breast cancer receiving adjuvant aromatase inhibition.

The use of adjuvant aromatase inhibitors is associated with an increased risk of osteoporosis and fractures. The oral bisphosphonate, risedronate--dosed as the US Food and Drug Administration approved for the treatment or prevention of postmenopausal osteoporosis--appears to mitigate bone loss associated with 2 years of adjuvant anastrozole in women with early-stage breast cancer.

Prevention of aromatase inhibitor-induced bone loss using risedronate: the SABRE trial.

PURPOSE To investigate the management of bone health in women with early breast cancer (EBC) who were scheduled to receive anastrozole. PATIENTS AND METHODS Postmenopausal women with hormone receptor-positive EBC were assigned to one of three strata by risk of fragility fracture. Patients with the highest risk (H) received anastrozole 1 mg/d plus risedronate 35 mg/wk orally. Patients with moderate-risk (M) were randomly assigned in a double-blind manner to anastrozole and risedronate (A + R) or to anastrozole and placebo (A + P). Patients with lower-risk (L) received anastrozole (A) alone. Calcium and vitamin D were recommended for all patients. Lumbar spine and total hip bone mineral density (BMD) were assessed at baseline, 12 months, and 24 months. Results At 24 months, in the M group, treatment with A + R resulted in a significant increase in lumbar spine and total hip BMD compared with A + P treatment (2.2% v -1.8%; treatment ratio, 1.04; P < .0001; and 1.8% v -1.1%; treatment ratio, 1.03; P < .0001, respectively). In the H stratum, lumbar spine and total hip BMD increased significantly (3.0%; P = .0006; and 2.0%; P = .0104, respectively). Patients in the L stratum showed a significant decrease in lumbar spine BMD (-2.1%; P = .0109) and a numerical decrease in total hip BMD (-0.4%; P = .5988). Safety profiles for anastrozole and risedronate were similar to those already established. CONCLUSION In postmenopausal women at risk of fragility fracture who were receiving adjuvant anastrozole for EBC, the addition of risedronate at doses established for preventing and treating osteoporosis resulted in favorable effects in BMD during 24 months.

NCCN Task Force Report: Bone Health in Cancer Care.

Bone health and maintenance of bone integrity are important components of comprehensive cancer care in both early and late stages of disease. Risk factors for osteoporosis are increased in patients with cancer, including women with chemotherapy-induced ovarian failure, those treated with aromatase inhibitors for breast cancer, men receiving androgen-deprivation therapy for prostate cancer, and patients undergoing glucocorticoid therapy. The skeleton is a common site of metastatic cancer recurrence, and skeletal-related events are the cause of significant morbidity. The National Comprehensive Cancer Network (NCCN) convened a multidisciplinary task force on Bone Health in Cancer Care to discuss the progress made in identifying effective screening and therapeutic options for management of treatment-related bone loss; understanding the factors that result in bone metastases; managing skeletal metastases; and evolving strategies to reduce bone recurrences. This report summarizes presentations made at the meeting.

NCCN Task Force Report: Bone Health and Cancer Care.

Higher incidences of osteoporosis and osteopenia are found in cancer patients, particularly in women receiving aromatase inhibitors or with chemotherapy-induced ovarian failure, or in men with prostate cancer and androgen deprivation therapy. Therefore, management of long-term bone health is emerging as an important aspect of comprehensive cancer care. Patients with cancer typically have a number of additional risk factors for osteoporosis that should prompt screening, regardless of patient age or sex. Maintaining bone health requires a broad knowledge base, including understanding underlying bone metabolism and how it is affected by both cancer itself and the drugs used to treat cancer, the effect of chemotherapy-induced menopause on bone health, bone markers and imaging techniques used to assess bone health, therapeutic strategies to maintain bone health, and treatment of bone metastases, including surgery for pathologic fractures. Multiple members of the healthcare team may need to be involved in education and care of the patient. This report summarizes discussion of these and other issues regarding bone health and cancer care from the NCCN Bone Health and Cancer Care Task Force meeting in early 2006.

Baseline bone mineral density of the total lumbar spine may predict for chemotherapy-induced ovarian failure.

Age at treatment and the total cumulative dose of cyclophosphamide are established predictors of chemotherapy-induced ovarian failure in premenopausal women with breast cancer. In a prospective trial of 49 women receiving adjuvant chemotherapy, we sought to identify whether other factors including family history of osteoporosis, lifestyle factors, reproductive hormones, bone turnover markers, or bone mineral density (BMD) of the hip or total spine measured before (baseline) and 6 months after chemotherapy increased the risk of ovarian failure. Univariate logistic regression analyses were used to identify the variables related to the risk of ovarian failure, and a multivariate logistic regression model was used to find the best of predictors of ovarian failure among the variables. In the multivariate model a higher total spine BMD at baseline (OR=6.0, p=0.02, 95% CI 1.4-27.3), and a 10% change in estradiol (E2) from baseline to six months (OR=0.80, p=0.02, 95% CI 0.67-0.97) were predictive of ovarian failure adjusted for age. In particular, as total spine BMD at baseline increases by 0.1 g/cm2 the odds of developing chemotherapy-induced ovarian failure increases by 6-fold. The multivariate model provides a good fit to the data (GOF p-value=0.8852), and provides excellent discrimination between those women who will and will not develop ovarian failure (Area under ROC=0.9487). If confirmed in larger data sets, using baseline spinal BMD to identify women who are at higher risk of developing ovarian failure independent of their age would be of value.

The use of bisphosphonates in patients with breast cancer.

BACKGROUND: Bone is the most common site of breast cancer metastases. Skeletal metastases may be associated with harmful and painful events such as fractures, spinal cord compression, and hypercalcemia. By inhibiting osteoclasts and bone resorption, bisphosphonates can interrupt the process of bone destruction and decrease the risk of skeletal complications. METHODS: A review of the literature was undertaken regarding the use of bisphosphonates in breast cancer management, with particular attention to prospective, randomized clinical trials that have influenced the treatment of bone metastases. RESULTS: Large prospective, randomized trials have demonstrated that bisphosphonates are effective in reducing skeletal-related complications from metastatic breast cancer. CONCLUSIONS: For many patients with osseous lesions from breast cancer, bisphosphonate therapy is a useful intervention in managing their disease. Bisphosphonates are the treatment of choice for hypercalcemia of malignancy and bisphosphonates reduce the risk of pathologic fractures, spinal cord compromise, the need for radiation or surgery to bone, and bone pain.