Tracey O'Connor

Pretreatment Serum Concentrations of 25-Hydroxyvitamin D and Breast Cancer Prognostic Characteristics: A Case-Control and a Case-Series Study

Background Results from epidemiologic studies on the relationship between vitamin D and breast cancer risk are inconclusive. It is possible that vitamin D may be effective in reducing risk only of specific subtypes due to disease heterogeneity. Methods and Findings In case-control and case-series analyses, we examined serum concentrations of 25-hydroxyvitamin D (25OHD) in relation to breast cancer prognostic characteristics, including histologic grade, estrogen receptor (ER), and molecular subtypes defined by ER, progesterone receptor (PR) and HER2, among 579 women with incident breast cancer and 574 controls matched on age and time of blood draw enrolled in the Roswell Park Cancer Institute from 2003 to 2008. We found that breast cancer cases had significantly lower 25OHD concentrations than controls (adjusted mean, 22.8 versus 26.2 ng/mL, p<0.001). Among premenopausal women, 25OHD concentrations were lower in those with high- versus low-grade tumors, and ER negative versus ER positive tumors (p≤0.03). Levels were lowest among women with triple-negative cancer (17.5 ng/mL), significantly different from those with luminal A cancer (24.5 ng/mL, p = 0.002). In case-control analyses, premenopausal women with 25OHD concentrations above the median had significantly lower odds of having triple-negative cancer (OR = 0.21, 95% CI = 0.08–0.53) than those with levels below the median; and every 10 ng/mL increase in serum 25OHD concentrations was associated with a 64% lower odds of having triple-negative cancer (OR = 0.36, 95% CI = 0.22–0.56). The differential associations by tumor subtypes among premenopausal women were confirmed in case-series analyses. Conclusion In our analyses, higher serum levels of 25OHD were associated with reduced risk of breast cancer, with associations strongest for high grade, ER negative or triple negative cancers in premenopausal women. With further confirmation in large prospective studies, these findings could warrant vitamin D supplementation for reducing breast cancer risk, particularly those with poor prognostic characteristics among premenopausal women.

Impact of Body Mass Index on Clinical Outcomes in Triple-Negative Breast Cancer

Obesity is associated with poorer outcomes in patients with hormone receptor‐positive breast cancers. This association is not well established for women with triple‐negative breast cancers (TNBC). In this study, the prognostic effects of body mass index on clinical outcome were evaluated in patients with TNBC.

Effect of longer-interval vs standard dosing of zoledronic acid on skeletal events in patients with bone metastases: A randomized clinical trial

Importance Zoledronic acid, a third-generation aminobisphosphonate, reduces the incidence of skeletal-related events and pain in patients with bone metastases. The optimal dosing interval for zoledronic acid is uncertain. Objective To determine whether zoledronic acid administered every 12 weeks is noninferior to zoledronic acid administered every 4 weeks. Design, Setting, Participants Randomized, open-label clinical trial conducted at 269 academic and community sites in the United States. Patients (n = 1822) with metastatic breast cancer, metastatic prostate cancer, or multiple myeloma who had at least 1 site of bone involvement were enrolled between May 2009 and April 2012; follow-up concluded in April 2014. Interventions Patients were randomized to receive zoledronic acid administered intravenously every 4 weeks (n = 911) vs every 12 weeks (n = 911) for 2 years. Main Outcomes and Measures The primary end point was the proportion of patients having at least 1 skeletal-related event (defined as clinical fracture, spinal cord compression, radiation to bone, or surgery involving bone) within 2 years after randomization and a between-group absolute difference of 7% as the noninferiority margin. Secondary end points included the proportion of patients with at least 1 skeletal-related event by disease type, pain as assessed by the Brief Pain Inventory (range, 0-10; higher scores indicate worse pain), Eastern Cooperative Oncology Group performance status (range, 0-4; higher scores indicate worse disability), incidence of osteonecrosis of the jaw, kidney dysfunction, skeletal morbidity rate (mean number of skeletal-related events per year), and, in a subset of 553 patients, suppression of bone turnover (assessed by C-terminal telopeptide levels). Results Among 1822 patients who were randomized (median age, 65 years; 980 [53.8%] women; 855 with breast cancer, 689 with prostate cancer, and 278 with multiple myeloma), 795 completed the study at 2 years. A total of 260 patients (29.5%) in the zoledronic acid every 4-week dosing group and 253 patients (28.6%) in the every 12-week dosing group experienced at least 1 skeletal-related event within 2 years of randomization (risk difference of −0.3% [1-sided 95% CI, −4% to ∞]; P < .001 for noninferiority). The proportions of skeletal-related events did not differ significantly between the every 4-week dosing group vs the every 12-week dosing group for patients with breast cancer, prostate cancer, or multiple myeloma. Pain scores, performance status scores, incidence of jaw osteonecrosis, and kidney dysfunction did not differ significantly between the treatment groups. Skeletal morbidity rates were numerically identical in both groups, but bone turnover was greater (C-terminal telopeptide levels were higher) among patients who received zoledronic acid every 12 weeks. Conclusions and Relevance Among patients with bone metastases due to breast cancer, prostate cancer, or multiple myeloma, the use of zoledronic acid every 12 weeks compared with the standard dosing interval of every 4 weeks did not result in an increased risk of skeletal events over 2 years. This longer interval may be an acceptable treatment option. Trial Registration clinicaltrials.gov Identifier: NCT00869206

Osteonecrosis of The Jaw: Dental Outcomes in Metastatic Breast Cancer Patients Treated With Bisphosphonates With/Without Bevacizumab

The etiology, optimal management, and outcome of osteonecrosis of the jaw (ONJ) are not well understood. Because healing after mucosal trauma requires revascularization, theoretically, the combination of bevacizumab (bev) and a bisphosphonate (BP) could affect the time to development of ONJ and/or the response to dental therapy. We reviewed all cases of ONJ in metastatic breast cancer patients treated at our institution with bev+BPs and BPs alone between October 2002 and April 2010. We identified 27 ONJ patients with a median age of 57 years (range, 40 to 68 years). Seven patients received bev+BPs; 20 patients received BPs alone. Patients received intravenous zolendronate (95%), pamidronate (20%), or both (15%). Patients were treated with antibiotics (93%), alveoplasty/debridement (67%), and chlorhexidine scrub (81%). There was no difference in dental treatment between the groups or by the year of diagnosis (before 2007 versus 2007-2010). Complete resolution (CR) was achieved in 24% of all patients; 33% treated with bev+BPs, and 21% treated with BPs alone. Rates of CR improved from 15% to 33% after 2007. The median time to response was 5.6 months (range, 1.3 to 67.5 months). The addition of bev to BPs did not appear to alter the time to development of ONJ (32.6 months versus 34.6 months, respectively). The number of BP treatments administered before the diagnosis of ONJ between bev+BPs and BPs (32 doses versus 36.5 doses) was similar. However, our sample size was too small to characterize the difference statistically. Because dental management of ONJ has not changed over time at our institute, early recognition and screening may account for the improvement in dental outcomes.

Older adult oncology, version 2.2016: Featured updates to the NCCN guidelines

Cancer is the leading cause of death in older adults aged 60 to 79 years. Older patients with good performance status are able to tolerate commonly used treatment modalities as well as younger patients, particularly when adequate supportive care is provided. For older patients who are able to tolerate curative treatment, options include surgery, radiation therapy (RT), chemotherapy, and targeted therapies. RT can be highly effective and well tolerated in carefully selected patients, and advanced age alone should not preclude the use of RT in older patients with cancer. Judicious application of advanced RT techniques that facilitate normal tissue sparing and reduce RT doses to organs at risk are important for all patients, and may help to assuage concerns about the risks of RT in older adults. These NCCN Guidelines Insights focus on the recent updates to the 2016 NCCN Guidelines for Older Adult Oncology specific to the use of RT in the management of older adults with cancer.

Exercise intervention in breast cancer patients with aromatase inhibitor-associated arthralgia: a pilot study

Aromatase inhibitors (AIs) block estrogen synthesis and are commonly used as adjuvant treatments for breast cancer patients. A common side effect is joint pain. This was a pilot study to examine implementation of an exercise program in reducing joint pain and improving quality of life (QoL) and functional performance in breast cancer patients treated with AIs. Twenty-six participants completed an 8-week, home-based program that combined upper and lower body resistance exercises with self-selected aerobic exercises. We measured: (1) anthropometry (2) functional performance (grip strength, biceps curl to exhaustion, and sit-to-stand and cardiovascular endurance (3-min step test). Joint pain and QoL were assessed using self-administered surveys. Participants reported a significantly lower number of painful joints, an improvement in QoL and a reduction in depressive symptoms. Significant improvements in grip strength, biceps curl, and sit-to-stand (by 14%, 51% and 15% respectively) were also observed. However, we found no significant changes in cardiovascular endurance or in anthropometric measures. An 8-week, home-based exercise program may provide potential benefit to the breast cancer patients undergoing AI treatment by reducing joint pain, improving functional performance and QoL, and reducing depressive symptoms. Further studies are needed to confirm these results.

Hospice Utilization and End-of-Life Care in Metastatic Breast Cancer Patients at a Comprehensive Cancer Center

BACKGROUND Metastatic breast cancer patients have many options for therapy and may be at risk for late or absent hospice referrals, which make meaningful improvements in symptoms and quality of life difficult to achieve. OBJECTIVE We aimed to examine hospice utilization, status of patients on admission, and quality of care of patients treated for metastatic breast cancer from 1999 to 2010 at a National Cancer Institute (NCI)-designated comprehensive cancer center located in Western New York. METHODS We conducted a retrospective database review that identified 182 patients with deaths resulting from breast cancer who were eligible for services through a local not-for-profit hospice. Patients with metastatic breast cancer were matched to the hospice database for information on hospice utilization and quality measures. Date of last chemotherapy, medication use, documentation of advance directive and palliative care discussions, and place of death were collected through chart abstraction. RESULTS One-third (33%) of metastatic breast cancer patients treated at the cancer institute during the study period died without a hospice referral. Only 7% of patients who died without a hospice referral had a documented discussion of palliative care as an option by the oncology team (p < 0.001). Those patients referred to hospice were significantly more likely to have an advance directive and to die at home. Patients with a longer duration of metastatic cancer were at risk for late referral. CONCLUSIONS Efforts to enhance end-of-life (EOL) discussions and earlier referral to palliative care and hospice for patients with metastatic breast cancer are critical to improved patient care.

Delayed Seizure Associated with Paclitaxel‐Cremophor EL in a Patient with Early‐Stage Breast Cancer

Paclitaxel, a microtubule stabilizer, is an effective agent for treating cancer of the breast, ovary, head and neck, and lung. Because paclitaxel is insoluble in water, it is formulated with the micelle‐forming Cremophor EL. Neurologic toxicity is well described with both the drug and this carrier, with most toxicities manifesting as peripheral neuropathy, motor neuropathy, autonomic neuropathy, and myopathy. Toxic effects on the central nervous system, such as seizures or encephalopathy, have been rarely reported; however, the seizures reported were closely related to the time of infusion. We describe a 41‐year‐old woman with no history of seizures who was treated with paclitaxel for breast cancer. Four days after the drug was infused, she developed a generalized tonic‐clonic seizure that could not be attributed to other causes. The patient was treated with phenytoin and was able to complete her adjuvant chemotherapy with nab‐paclitaxel without further events. Her condition was neurologically stable without phenytoin for the next 6 months. Use of the Naranjo adverse drug reaction probability scale indicated a possible association (score of 3) between the delayed seizure and paclitaxel or its solvent, Cremophor EL. Clinicians should be aware of the potential for seizure activity in patients who receive paclitaxel formulated with Cremophor EL.

Survivorship, Version 2.2017: Clinical practice guidelines in oncology

Many cancer survivors experience menopausal symptoms, including female survivors taking aromatase inhibitors or with a history of oophorectomy or chemotherapy, and male survivors who received or are receiving androgen-ablative therapies. Sexual dysfunction is also common in cancer survivors. Sexual dysfunction and menopause-related symptoms can increase distress and have a significant negative impact on quality of life. This portion of the NCCN Guidelines for Survivorship provide recommendations for screening, evaluation, and treatment of sexual dysfunction and menopausal symptoms to help healthcare professionals who work with survivors of adult-onset cancer in the posttreatment period.

Survivorship: Fatigue, version 1.2014 - Clinical practice guidelines in oncology

Many posttreatment cancer survivors experience chronic pain, often leading to psychological distress; decreased activity, motivation, and personal interactions; and an overall poor quality of life. This section of the NCCN Guidelines for Survivorship provides screening and management recommendations for pain in survivors. A multidisciplinary approach is recommended, with a combination of pharmacologic treatments, psychosocial and behavioral interventions, physical therapy and exercise, and interventional procedures.