Randomised controlled trial comparing hypnotherapy versus gabapentin for the treatment of hot flashes in breast cancer survivors: a pilot study

Objectives: To compare the efficacy of hypnotherapy versus gabapentin for the treatment of hot flashes in breast cancer survivors, and to evaluate the feasibility of conducting a clinical trial comparing a drug with a complementary or alternative method (CAM). Design: Prospective randomised trial. Setting: Breast health centre of a tertiary care centre. Participants: 15 women with a personal history of breast cancer or an increased risk of breast cancer who reported at least one daily hot flash. Interventions Gabapentin 900 mg daily in three divided doses (control) compared with standardised hypnotherapy. Participation lasted 8 weeks. Outcome measures The primary endpoints were the number of daily hot flashes and hot flash severity score (HFSS). The secondary endpoint was the Hot Flash Related Daily Interference Scale (HFRDIS). Results: 27 women were randomised and 15 (56%) were considered evaluable for the primary endpoint (n=8 gabapentin, n=7 hypnotherapy). The median number of daily hot flashes at enrolment was 4.5 in the gabapentin arm and 5 in the hypnotherapy arm. HFSS scores were 7.5 in the gabapentin arm and 10 in the hypnotherapy arm. After 8 weeks, the median number of daily hot flashes was reduced by 33.3% in the gabapentin arm and by 80% in the hypnotherapy arm. The median HFSS was reduced by 33.3% in the gabapentin arm and by 85% in the hypnotherapy arm. HFRDIS scores improved by 51.6% in the gabapentin group and by 55.2% in the hypnotherapy group. There were no statistically significant differences between groups. Conclusions: Hypnotherapy and gabapentin demonstrate efficacy in improving hot flashes. A definitive trial evaluating traditional interventions against CAM methods is feasible, but not without challenges. Further studies aimed at defining evidence-based recommendations for CAM are necessary. Trial registration clinicaltrials.gov (NCT00711529)

Identification of ovarian cancer metastatic miRNAs

Serous epithelial ovarian cancer (EOC) patients often succumb to aggressive metastatic disease, yet little is known about the behavior and genetics of ovarian cancer metastasis. Here, we aim to understand how omental metastases differ from primary tumors and how these differences may influence chemotherapy. We analyzed the miRNA expression profiles of primary EOC tumors and their respective omental metastases from 9 patients using miRNA Taqman qPCR arrays. We find 17 miRNAs with differential expression in omental lesions compared to primary tumors. miR-21, miR-150, and miR-146a have low expression in most primary tumors with significantly increased expression in omental lesions, with concomitant decreased expression of predicted mRNA targets based on mRNA expression. We find that miR-150 and miR-146a mediate spheroid size. Both miR-146a and miR-150 increase the number of residual surviving cells by 2–4 fold when challenged with lethal cisplatin concentrations. These observations suggest that at least two of the miRNAs, miR-146a and miR-150, up-regulated in omental lesions, stimulate survival and increase drug tolerance. Our observations suggest that cancer cells in omental tumors express key miRNAs differently than primary tumors, and that at least some of these microRNAs may be critical regulators of the emergence of drug resistant disease.<br/

Expression profiling of primary and metastatic ovarian tumors reveals differences indicative of aggressive disease

The behavior and genetics of serous epithelial ovarian cancer (EOC) metastasis, the form of the disease lethal to patients, is poorly understood. The unique properties of metastases are critical to understand to improve treatments of the disease that remains in patients after debulking surgery. We sought to identify the genetic and phenotypic landscape of metastatic progression of EOC to understand how metastases compare to primary tumors. DNA copy number and mRNA expression differences between matched primary human tumors and omental metastases, collected at the same time during debulking surgery before chemotherapy, were measured using microarrays. qPCR and immunohistochemistry validated findings. Pathway analysis of mRNA expression revealed metastatic cancer cells are more proliferative and less apoptotic than primary tumors, perhaps explaining the aggressive nature of these lesions. Most cases had copy number aberrations (CNAs) that differed between primary and metastatic tumors, but we did not detect CNAs that are recurrent across cases. A six gene expression signature distinguishes primary from metastatic tumors and predicts overall survival in independent datasets. The genetic differences between primary and metastatic tumors, yet common expression changes, suggest that the major clone in metastases is not the same as in primary tumors, but the cancer cells adapt to the omentum similarly. Together, these data highlight how ovarian tumors develop into a distinct, more aggressive metastatic state that should be considered for therapy development

Abstract P6-12-13: Developing a non-hormonal treatment for vaginal dryness for breast cancer survivors: A pilot study of a therapeutic ultrasound device

Abstract Objectives: Breast cancer survivors need a non-hormonal treatment for vaginal dryness, as estrogen replacement therapy is often contraindicated or undesired. Therapeutic ultrasound applied to the vaginal introitus is safe and was shown to increase vaginal temperature and blood flow in our phase I study. We now report results from a twelve-week trial of daily, self-applied therapeutic ultrasound to the vaginal introitus. Methods: Breast cancer survivors and post-menopausal women with symptomatic vaginal atrophy were enrolled. A gynecologic oncologist supervised participants in application of a gel-pad equipped ultrasound head (Intelect TranSport, Chattanooga Group) to the vaginal introitus at an enrollment visit, and instructed women on self-application. Daily, 8-minute treatment applications for 12 weeks were planned, and dose was titrated as needed for comfort. Vaginal Maturation Index (VMI) specimens were collected and Vaginal Health Index (VHI) was recorded at study visits. Patient-reported outcomes for vaginal dryness and personal lubrication were recorded on a Likert-type scale (0-3). Student's t-test was used to analyze ordinal and continuous variables in an intent-to-treat analysis. Results: From December 2015 to January 2017, 20 women were enrolled, including 7 breast cancer survivors. Mean VMI for the study population was 25.1 (median 25) at baseline, and 21.4 (median 6) after 12 weeks of treatment (p&amp;gt;0.05). Similarly, there were no significant changes seen in mean VHI, which was 12.8 (median 13) at baseline and 14.1 (median 14) at 12 weeks (p&amp;gt;0.05). Statistically significant improvements were seen in both vaginal dryness and lubrication as reported by patients' scores. The mean vaginal dryness score for the population was 1.9 (median 2) at baseline and 1 (median 1) at 12 weeks (p&amp;lt;0.05). The effect was more pronounced in a subset of women (n=6) who did not use ultrasound jelly with their device (mean baseline score of 2.3 reduced to 1 at 12 weeks). Baseline vaginal lubrication scores (mean 0.6, median 1) for the population also improved after 12 weeks (mean 1.4, median 1, p&amp;lt;0.05), though the scores remained in the “mild” range. The six women who used the ultrasound device without jelly reported essentially no lubrication at the start of the study (mean 0.17, median 0), and had notably improved symptoms, reporting moderate lubrication after 12 weeks (mean and median score 1.5). Of the 15 women who completed the treatment according to protocol, 93% reported an improvement in at least one of their symptoms. Conclusions: Self-application of therapeutic ultrasound to the vaginal introitus decreased symptoms of vaginal atrophy in the majority of users. While no detectable changes in tissue physiology were noted with the VMI or VHI tools, the notable improvement in patient-reported outcomes warrants further study. A phase III clinical trial with a customized device is planned. Citation Format: MacLaughlan David S, Rockweiler H, Krone R, Middelton S, Blayney D. Developing a non-hormonal treatment for vaginal dryness for breast cancer survivors: A pilot study of a therapeutic ultrasound device [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-12-13.</jats:p

Abstract A091: Mediation of racial/ethnic inequities in the diagnosis of early-stage cervical cancer by insurance status

Abstract Background: Black and Latina/Hispanic women are more likely to be diagnosed with and die from cervical cancer than White women in the US. Having adequate health insurance, a social and structural determinant of health, may be associated with an earlier stage cervical cancer diagnosis and improved prognosis for racial/ethnic minorities. Objective: To determine whether insurance status among racial/ethnic groups is associated with earlier diagnosis of cervical cancer among a large and diverse population of US women with cervical cancer. Methods: A retrospective, cross-sectional population-based study utilizing data from the Surveillance, Epidemiology, and End Results Census Tract-Level Socioeconomic Status and Rurality Database on 24,945 women aged 21-64 years who were diagnosed with a histologically confirmed invasive cervical cancer between January 1, 2007, to December 31, 2016. The primary outcome was the risk of having a more advanced cervical cancer diagnosis (regional or distant versus localized). Causal mediation analyses were performed using a series of multivariable logistic regression models to determine the association of race/ethnicity with cervical cancer stage and the potential mediator, health insurance status (private insurance versus Medicaid coverage or no insurance). Adjusted odds ratios (OR) and 95% confidence intervals were calculated, and estimates of direct and indirect effects of race/ethnicity and cervical cancer stage were used to calculate the proportion mediated (PM) by health insurance status. Results: 24,945 women (median [IQR] age, 45 [37-54] years) were included in the study. 52% of women were identified as Non-Hispanic (NH) White, 13% as NH Black, and 24% as Hispanic/Latina. Overall, 14,271 women had private insurance, 9,765 women were uninsured or received Medicaid, and 909 women had no documented insurance status. A larger proportion of women who were uninsured or received Medicaid were diagnosed with more advanced stage cancer (regional/distant) compared to women with private health insurance (53.5% versus 42.0%). In models adjusted for age, year of diagnosis and histology type: NH Black (OR 1.38, 95% CI 1.27-1.50), and Hispanic/Latina (OR 1.13, 95% CI 1.06-1.21) women had higher odds of being diagnosed with regional/distant cancer compared to NH White women. After adjustment for insurance status and accounting for co-mediation by area-level socioeconomic status, the association with regional/distant cervical cancer was attenuated toward the null (Black: OR 1.18, 95% CI 1.08-1.29; Hispanic/Latina: OR 0.93, 95% CI 0.87-1.00). Our mediation analysis found that over half (PM 51% to 56%) of the inequities in cervical cancer diagnosis were mediated by health insurance across all racial/ethnic groups. Conclusion: In this population-based sample of US women, insurance status was major mediator of over half the racial/ethnic inequities in late-stage cervical cancer diagnoses. Focused policies making robust health coverage accessible may mitigate the known inequities in cervical cancer diagnosis and outcomes. Citation Format: Hunter K. Holt, Caryn Peterson, Shannon MacLaughlan, George F. Sawaya, Gregory S. Calip. Mediation of racial/ethnic inequities in the diagnosis of early-stage cervical cancer by insurance status [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A091.</jats:p