Jun J. Mao

Symptom Burden Among Cancer Survivors: Impact of Age and Comorbidity

Background: Previous research among specific cancer populations has shown high but variable symptom burden; however, very little is known about its extent and pattern among the entire population of US cancer survivors, which is more clinically relevant to primary care physicians. Methods: To determine the prevalence of ongoing symptom burden among cancer survivors and compare it with the general population without cancer, we analyzed data from the 2002 National Health Interview Survey, which included 1,904 cancer survivors and 29,092 controls. Main outcome measures included self-reported ongoing pain, psychological distress, and insomnia. Multivariate logistic regression models were used to adjust for confounders and test for interactions. Results: The rates of ongoing pain, psychological distress, and insomnia among cancer survivors were 34%, 26%, and 30%, respectively, and were significantly higher (all P < .001) than controls without a history of cancer (18%, 16%, and 17%). Compared with controls in the same age groups, younger survivors (younger than 50) were much more likely to report ongoing symptoms than older survivors (older than 64); adjusted odds ratios were 2.96 and 1.36 for pain in the respective age groups (P < .001). Comorbidities also interact with cancer status and contribute to a marked increase in reports of ongoing symptom burden among cancer survivors, with a greater number of comorbidities leading to greater degree of symptom burden in a dose-dependent manner (P < .001). Conclusions: The symptom burden among cancer survivors on a population level is substantial and can be impacted by other comorbidities. Thus, engaging primary care physicians in the design, testing, and implementation of effective interventions is important to reduce the symptom burden among cancer survivors.

Patterns and Risk Factors Associated with Aromatase Inhibitor Related Arthralgia Among Breast Cancer Survivors

Arthralgia is common in postmenopausal breast cancer survivors (BCS) who are receiving aromatase inhibitors (AIs). The objective of this study was to evaluate the perceived onset, characteristics, and risk factors for AI‐related arthralgia (AIA).

Association of functional polymorphisms in CYP19A1 with aromatase inhibitor associated arthralgia in breast cancer survivors

IntroductionAromatase inhibitor-associated arthralgia (AIAA) is a common and often debilitating symptom in breast cancer survivors. Since joint symptoms have been related to estrogen deprivation through the menopausal transition, we hypothesized that genetic polymorphisms in CYP19A1, the final enzyme in estrogen synthesis, may be associated with the occurrence of AIAA.MethodsWe performed a cross-sectional study of postmenopausal women with stage 0 to III breast cancer receiving adjuvant aromatase inhibitor (AI) therapy. Patient-reported AIAA was the primary outcome. DNA was genotyped for candidate CYP19A1 polymorphisms. Serum estrogen levels were evaluated by radioimmunoassay. Multivariate analyses were performed to examine associations between AIAA and genetic variants controlling for possible confounders.ResultsAmong 390 Caucasian participants, 50.8% reported AIAA. Women carrying at least one 8-repeat allele had lower odds of AIAA (adjusted odds ratio (AOR) 0.41, 95% confidence interval (CI) 0.21 to 0.79, P = 0.008) after adjusting for demographic and clinical covariates. Estradiol and estrone were detectable in 47% and 86% of subjects on AIs, respectively. Although these post-AI levels were associated with multiple genotypes, they were not associated with AIAA. In multivariate analyses, women with more recent transition into menopause (less than five years) were significantly more likely to report AIAA than those greater than ten years post-menopause (AOR 3.31, 95% CI 1.72 to 6.39, P < 0.001).ConclusionsFunctional polymorphism in CYP19A1 and time since menopause are associated with patient-reported AIAA, supporting the hypothesis that the host hormonal environment contributes to the pathophysiology of AAIA. Prospective investigation is needed to further delineate relationships between host genetics, changing estrogen levels and AIAA.

Online discussion of drug side effects and discontinuation among breast cancer survivors

While patients often use the internet as a medium to search for and exchange health‐related information, little is known about the extent to which patients use social media to discuss side effects related to medications. We aim to understand the frequency and content of side effects and associated adherence behaviors discussed by breast cancer patients related to using aromatase inhibitors (AIs), with particular emphasis on AI‐related arthralgia.

Complementary and Alternative Medicine and Supportive Care at Leading Cancer Centers: A Systematic Analysis of Websites

BACKGROUND With increasing frequency, patients with cancer and their family members are turning to the Internet to educate themselves about their disease and treatment options, including complementary and alternative medicine (CAM) and supportive care. However, very little is known about how national leading cancer centers represent these therapies via their websites. METHODS Simulating the perspective of an information-seeking patient or family member, we performed a systematic analysis of the websites of 41 National Cancer Institute designated comprehensive cancer centers. Two researchers independently evaluated websites, recorded CAM information, and rated quality of the websites using a 4-item Likert scale (overall, information, presentation, and navigation) with Cronbachs alpha = 0.97. Rating was adequately correlated between the two raters (correlation coefficient 0.8). RESULTS Of 41 centers, 12 (29%) did not have functional websites with regard to information related to CAM. The most common CAM approaches mentioned were: acupuncture (59%), meditation/nutrition/spiritual support/yoga (56% for each), massage therapy (54%), and music therapy (51%). Twenty-three (23; 56%) presented information on support groups, 19 (46%) on patient seminars, 18 (44%) on survivorship effort, and 17 (41%) on symptom management clinics. Twenty-nine (29) (71%) of these websites had a telephone number available, 22 (54%) mentioned at least one ongoing research opportunity, and 19 (46%) provided links to the National Center for Complementary and Alternative Medicine website. Median rating of the quality of websites was 50 of 100, with only 7 (17%) of centers receiving a composite score 80 (excellent) or better. CONCLUSIONS While a growing number of leading cancer centers provide information about CAM and supportive oncology information for patients via their websites, the quality and ease of navigation of these sites remain highly variable. Effective development and redesign of many of the websites is needed to better inform and empower patients and families seeking CAM and supportive care information.

De qi: Chinese acupuncture patients' experiences and beliefs regarding acupuncture needling sensation--an exploratory survey.

Introduction While de qi, the acupuncture needling sensation, has been considered as an important component of acupuncture, little is known of the acupuncture patients experience and beliefs about de qi in clinical settings. The aim of this study was to describe Chinese acupuncture patients’ perceived sensations of, and beliefs about, acupuncture needling. Methods We developed a questionnaire and conducted a survey study at two time periods among 200 subjects at six outpatient acupuncture clinics in Beijing, China. Results Respondents were 55% female and had a mean age of 41 years. The most common types of needling sensations reported by subjects were the terms ‘distended’(94%), ‘sore’(81%), ‘electric’(81%) and ‘numb’ (78%). Eighty-nine percent of subjects reported that the needling sensation travelled away from the puncturing points or travelled among the needling points. Eighty-two percent of subjects believed that the needling sensation was very important for acupuncture treatment, and 68% further indicated that the stronger the needling sensation, the more effective the therapy. Eighty-one percent of subjects found the acupuncture process to be very comfortable and relaxing. Conclusion Chinese acupuncture patients described the common characteristics of de qi and its migratory nature. The sensations were believed to be important in producing clinical efficacy by most patients. Measuring the sensations described as de qi in future prospective studies will help us understand the degree to which this phenomenon has an effect on the physiological outcome and clinical response to acupuncture. There appears to be a limit to the number of sensations that can be discriminated by each individual patient, and further development of the questionnaire is planned.

A randomised trial of electro-acupuncture for arthralgia related to aromatase inhibitor use

BACKGROUND Arthralgia is a common and debilitating side-effect experienced by breast cancer patients receiving aromatase inhibitors (AIs) and often results in premature drug discontinuation. METHODS We conducted a randomised controlled trial of electro-acupuncture (EA) as compared to waitlist control (WLC) and sham acupuncture (SA) in postmenopausal women with breast cancer who self-reported arthralgia attributable to AIs. Acupuncturists performed 10 EA/SA treatments over 8 weeks using a manualised protocol with 2 Hz electro-stimulation delivered by a TENS unit. Acupuncturists administered SA using Streitberger (non-penetrating) needles at non-traditional acupuncture points without electro-stimulation. The primary end-point was pain severity by Brief Pain Inventory (BPI) between EA and WLC at Week 8; durability of response at Week 12 and comparison of EA to SA were secondary aims. FINDINGS Of the 67 randomly assigned patients, mean reduction in pain severity was greater in the EA group than in the WLC group at Week 8 (-2.2 versus -0.2, p=0.0004) and at Week 12 (-2.4 versus -0.2, p<0.0001). Pain-related interference measured by BPI also improved in the EA group compared to the WLC group at both Week 8 (-2.0 versus 0.2, p=0.0006) and Week 12 (-2.1 versus -0.1, p=0.0034). SA produced a magnitude of change in pain severity and pain-related interference at Week 8 (-2.3, -1.5 respectively) and Week 12 (-1.7, -1.3 respectively) similar to that of EA. Participants in both EA and SA groups reported few minor adverse events. INTERPRETATIONS Compared to usual care, EA produced clinically important and durable improvement in arthralgia related to AIs in breast cancer patients, and SA had a similar effect. Both EA and SA were safe.

Self-renewal of CD133(hi) cells by IL6/Notch3 signalling regulates endocrine resistance in metastatic breast cancer.

The mechanisms of metastatic progression from hormonal therapy (HT) are largely unknown in luminal breast cancer. Here we demonstrate the enrichment of CD133hi/ERlo cancer cells in clinical specimens following neoadjuvant endocrine therapy and in HT refractory metastatic disease. We develop experimental models of metastatic luminal breast cancer and demonstrate that HT can promote the generation of HT-resistant, self-renewing CD133hi/ERlo/IL6hi cancer stem cells (CSCs). HT initially abrogates oxidative phosphorylation (OXPHOS) generating self-renewal-deficient cancer cells, CD133hi/ERlo/OXPHOSlo. These cells exit metabolic dormancy via an IL6-driven feed-forward ERlo-IL6hi-Notchhi loop, activating OXPHOS, in the absence of ER activity. The inhibition of IL6R/IL6-Notch pathways switches the self-renewal of CD133hi CSCs, from an IL6/Notch-dependent one to an ER-dependent one, through the re-expression of ER. Thus, HT induces an OXPHOS metabolic editing of luminal breast cancers, paradoxically establishing HT-driven self-renewal of dormant CD133hi/ERlo cells mediating metastatic progression, which is sensitive to dual targeted therapy.

Impact of Chemotherapy-Induced Peripheral Neuropathy on Treatment Delivery in Nonmetastatic Breast Cancer

PURPOSE To determine the incidence of dose-limiting (DL) chemotherapy-induced peripheral neuropathy (CIPN) events in clinical practice. PATIENTS AND METHODS This retrospective cohort study included 488 women who received docetaxel or paclitaxel. The primary outcome was a DL event (dose delay, dose reduction, or treatment discontinuation) attributed to CIPN (DL CIPN). The paired t test was used to test the difference in received cumulative dose and planned cumulative dose by dose reduction and treatment discontinuation status. RESULTS A total of 150 unique DL events occurred in 120 women (24.6%). More than one third (37.3%; n=56) of the events were attributed to CIPN. The 56 DL CIPN events occurred in 50 women (10.2%). DL CIPN incidence differed significantly by agent (docetaxel, 2.4%; n=five of 209; paclitaxel, 16.1%; n=45 of 279; P<.001). DL CIPN occurred in 24.5% and 14.4% of women who received paclitaxel 80 mg/m2 weekly for 12 cycles and 175 mg/m2 biweekly for four cycles, respectively (adjusted odds ratio, 2.11; 95% CI, 0.97 to 4.60; P=.06). The cumulative dose actually received was significantly lower than the planned cumulative dose among women who had a dose reduction or treatment termination attributed to CIPN (9.4% less; P<.001 and 28.4% less; P<.001, respectively). CONCLUSION Oncologists limited the dosing of chemotherapy because of CIPN in a significant proportion of paclitaxel recipients, most frequently in those who received a weekly regimen. Patients who had their dose reduced or discontinued received significantly less cumulative chemotherapy than planned. The implications of these DL CIPN events on treatment outcomes must be investigated.

Electroacupuncture for fatigue, sleep, and psychological distress in breast cancer patients with aromatase inhibitor‐related arthralgia: A randomized trial

Although fatigue, sleep disturbance, depression, and anxiety are associated with pain in breast cancer patients, it is unknown whether acupuncture can decrease these comorbid symptoms in cancer patients with pain. The objective of this study was to evaluate the effect of electroacupuncture (EA) on fatigue, sleep, and psychological distress in breast cancer survivors who experience joint pain related to aromatase inhibitors (AIs).