Total hemoglobin reduction in the tumor volume correlates with response to breast cancer neoadjuvant chemotherapy within two weeks of treatment

Optical imaging techniques have emerged as a possible alternative to predict pathological complete response (pCR) in breast cancer patients undergoing neoadjuvant chemotherapy (NAC). Our team developed a so-called diffuse optical tomographic breast imaging system (DOTBIS) which does not require the use of contrast agents or compression, and enables imaging of the whole breast volume using low intensity near infrared light capable to measure tissue concentration of oxy-hemoglobin (ctO2Hb), deoxy-hemoglobin (ctHHb) and water percentage. In this retrospective study, ctTHb changes in the tumor region of 16 breast cancer patients were analyzed across NAC. Both breasts of all patients have been scanned simultaneously with our DOTBIS system, Figure 1, which employs four wavelengths and gathers data from a total of 64 sources and 128 detectors per breast. A PDE-constrained multispectral image reconstruction code creates 3D image maps of total hemoglobin (ctHbT = ctO2Hb+ ctHHb). Tumor volume is selected by entering radiologic information such as tumor side, clock position and distance from the nipple (FN). An automated code was designed to select the highest value from the distance FN and the quadrant referent to the clock position. Subsequently, a region-based image segmentation method is implemented to examine neighboring pixels of the highest value point considering a mask of 90%. After tumor volume segmentation, we calculate the mean ctHbT extracted from the region of interest. An independent-samples t-test was run to determine if there were differences in ctTHb reduction in the tumor region before the third cycle of taxane between responders (n=4) and non-responders (n=12). ctTHb reduction was greater to pCR (45.71 ± 25.16 mM) than non-pCR tumors (-9.67 ± 25.65 mM), a statistically significant difference of 55.38 mM (95% CI, 23.74 to 87), t(14) = 3.755, p = .002, in Figure 2 we can see an example. From the ROC plot results, we can observe that ctTHb reduction in the tumor region after 2 cycles of Taxane is a good indicator to anticipate pCR status. With an area under the curve of 0.958, the best cut-off that maximizes sensitivity and specificity is 16.86mM. At this reduction level, the sensitivity is 100% and specificity is 91.7%. In conclusion, our findings indicate that DOTBIS-measured total hemoglobin in the tumor region may be a strong and independent predictor of treatment response to NAC. Please click Additional Files below to see the full abstract

Study protocol: a cluster randomized controlled trial of web-based decision support tools for increasing BRCA1/2 genetic counseling referral in primary care

Background BRCA1 and BRCA2 mutations confer a substantial breast risk of developing breast cancer to those who carry them. For this reason, the United States Preventative Services Task Force (USPSTF) has recommended that all women be screened in the primary care setting for a family history indicative of a mutation, and women with strong family histories of breast or ovarian cancer be referred to genetic counseling. However, few high-risk women are being routinely screened and fewer are referred to genetic counseling. To address this need we have developed two decision support tools that are integrated into clinical care. Method This study is a cluster randomized controlled trial of high-risk patients and their health care providers. Patient-provider dyads will be randomized to receive either standard education that is supplemented with the patient-facing decision aid, RealRisks, and the provider-facing Breast Cancer Risk Navigation Toolbox (BNAV) or standard education alone. We will assess these tools’ effectiveness in promoting genetic counseling uptake and informed and shared decision making about genetic testing. Discussion If found to be effective, these tools can help integrate genomic risk assessment into primary care and, ultimately, help expand access to risk-appropriate breast cancer prevention options to a broader population of high-risk women. Trial registration This trial is retrospectively registered with ClinicalTrials.gov Identifier: NCT03470402 : 20 March 2018

Use of a Urine Anastrozole Assay to Determine Treatment Discontinuation Among Women With Hormone-Sensitive Breast Cancer: A Pilot Study

Purpose: Multiple studies have shown that adherence to adjuvant hormonal therapy in women with breast cancer is suboptimal. Measurements of compliance with self-report, pill counts, and/or pharmacy records are susceptible to bias. We assessed the feasibility of using a urine anastrozole assay as an objective biomarker of nonadherence to anastrozole treatment. Patients and Methods: We recruited consecutive postmenopausal women, age ≥ 18 years, with hormone-sensitive nonmetastatic breast cancer who were prescribed anastrozole at least 3 months before enrollment. Each completed a short survey to gather information on demographics, anastrozole compliance history, and self-reported medication history, tumor characteristics, and treatment received. A single, random 15-mL urine sample was collected and tested for the presence of anastrozole using a previously validated assay. Patients were told they were part of a study to determine if anastrozole could be detected in the urine. Results: Among 96 participants, mean age was 63.7 years (range, 51 to 70 years). The population was diverse, with 56.5% white, 57.6% US born, 59.8% unemployed, and 56.6% college educated. Prior treatment included chemotherapy (50%) and/or radiotherapy (58.7%). Mean duration of anastrozole treatment was 2.2 years (standard deviation, 1.6). Four participants reported nonadherence and declined to submit urine samples, and two had no detectable level of anastrozole (six of 96; 6.3%). Detectable levels among adherent women ranged from 49.3 to 632.8 ng/mL. Conclusion: We demonstrated that collection of urine to measure anastrozole levels is feasible and reliable. Identifying biomarkers to measure adherence is critical for studies investigating interventions to improve hormonal therapy compliance

Methods to Standardize a Multicenter Acupuncture Trial Protocol to Reduce Aromatase Inhibitor-related Joint Symptoms in Breast Cancer Patients

AbstractRobust methods are needed to efficiently conduct large, multisite, randomized, controlled clinical trials of acupuncture protocols. The Southwest Oncology Group (SWOG) S1200 trial is a randomized, controlled (i.e., sham-controlled and waitlist-controlled) trial of a standardized acupuncture protocol for treating aromatase inhibitor (AI)-associated arthralgias in early-stage breast cancer patients (n = 228). The primary objective of this study was to determine whether true acupuncture administered twice weekly for 6 weeks, as compared to sham acupuncture or a waitlist control, reduced AI-associated joint pain at 6 weeks as assessed by patient reports. The study was conducted at 11 institutions across the United States. The true acupuncture protocol was developed using a consensus-based process. The true acupuncture and the sham acupuncture protocols each consisted of 12 sessions administered for 6 weeks, followed by one weekly session for 6 weeks. The true acupuncture protocol used standardized protocol points, and the standardized acupoints were tailored to a patient's joint symptoms. The similarly standardized sham acupuncture protocol utilized superficial needling of nonacupoints. Standardized methods were developed to train and monitor acupuncturists and included online and in-person training, study manuals, monthly phone calls, and remote quality assurance monitoring throughout the study period. The research staff similarly received online and in-person training and monthly phone calls

Association between body mass index and response to duloxetine for aromatase inhibitor‐associated musculoskeletal symptoms in SWOG S1202

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149517/1/cncr32024.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149517/2/cncr32024_am.pd

Mammographic density and serum 25-hydroxyvitamin D levels

Background: Vitamin D, which influences cellular proliferation and breast tissue characteristics, has been inversely correlated with breast cancer risk. Dietary vitamin D intake has been associated with lower mammographic density (MD), a strong intermediate marker of breast cancer risk. Findings: We examined the relationship between MD and serum 25-hydroxyvitamin D [25(OH)D], an integrated measure of vitamin D status from dietary sources and sunlight exposure, in a multi-ethnic cohort of women undergoing screening mammography. We recruited women age 40–60 years without a history of breast cancer at the time of their routine screening mammogram, and conducted in-person interviews and collected blood specimens. We enrolled 195 women from 2007–2008, 120 gave blood, and 114 were evaluable, including 25% white, 41% African American, 18% African Caribbean, and 16% Hispanic. We digitized mammograms and calculated percent density, dense area, and non-dense area on cranial-caudal images. We measured serum 25(OH)D in batched, archived specimens. Median serum 25(OH)D was 22 ng/ml (range, 8–66 ng/ml). In univariable analysis, higher serum 25(OH)D was associated with white race, higher educational level, ever breast feeding, and blood draw during the summer. After adjusting for body mass index and other confounders, we found no association between serum 25(OH)D and different measures of MD. However, when stratified by season, 25(OH)D was inversely associated with dense area during July-December (p = 0.034). Conclusions: Overall, our findings suggest that circulating vitamin D, a potentially modifiable breast cancer risk factor, is not associated with MD; the seasonal effects we observed need to be replicated in larger cohorts

Vitamin D-related gene polymorphisms, plasma 25-hydroxyvitamin D, and breast cancer risk

Studies of vitamin D pathway genetic variants in relation to cancer risk have been inconsistent. We examined associations between vitamin D-related genetic polymorphisms, plasma 25-hydroxyvitamin D [25(OH)D], and breast cancer risk