Intravascular, Interstitial and Intracellular Volume Changes During Short Term Deep Tissue Massage of the Calf: A Case Study.

The following case study demonstrates that the effectiveness of Deep Tissue Massage (DTM) can be monitored in real time with bioimpedance. DTM techniques are used as a medical treatment to help reduce swelling of the calves of congestive heart failure patients. Bioimpedance monitoring shows immediately how fluid is redistributed within the intravascular, interstitial and intracellular fluid compartments, and how long the redistribution lasts. Bioimpedance spectroscopy, as used in this study, is a non-invasive procedure that can be used to monitor compartment fluid volumes and changes during many fluid management procedures.

Segmental Volume and Circulatory Changes that Occur in Humans and Rhesus Monkeys During 4 Hour, -6 Degree Head Down Tilt.

Nonhuman primates are often used to investigate physiologic processes that occur in man during aerospace/cardiovascular orthostatic research. Few studies have compared nonhuman primates and man under identical test conditions to assess the degree of similarity between the two species. Impedance plethysmography was used to measure calf, thigh, pelvic, thoracic, upper arm, and lower arm volume changes in eight rhesus (Macacca Mulatta) monkeys and twelve human subjects during four hour exposures to -6 degree head down tilt (HDT).

Early reflector localization improves the accuracy of localization and excision of a previously positive axillary lymph node following neoadjuvant chemotherapy in patients with breast cancer.

PURPOSE: Clipped axillary lymph node (CALN) localization after neoadjuvant chemotherapy (NAC) for axillary node positive breast cancer can be difficult due to significant shrinkage or disappearance of the CALN after NAC. This study compares wire localization to a radar-based localization system utilizing a reflector that can be placed before or during NAC, in the months before definitive surgery, to facilitate accurate localization and excision of the CALN. METHODS: Between 2016 and 2019, women with T0-4 N1-3 M0 breast cancer who underwent NAC followed by axillary surgery with planned excision of a biopsy positive or clinically suspicious axillary node via wire or reflector localization were identified. A retrospective chart review was performed comparing successful localization and CALN retrieval by each localization technique. RESULTS: Ninety-nine patients met inclusion criteria. Forty-two patients underwent wire localization while 57 patients underwent reflector localization of the CALN. Successful identification of the CALN by wire or reflector was equivalent (83.3% vs 84.2%, respectively). Twenty-two reflectors placed before or during early/mid NAC (early placement) had 100% successful CALN localization and retrieval in the OR. Placement of wire or reflector localization devices within 8 weeks of surgery (late placement) only resulted in 79.2% localization success (p = .02). CONCLUSION: This study suggests a benefit of axillary lymph node reflector placement in the early NAC setting. Early reflector placement allows for more accurate excision of the CALN during axillary surgery after NAC as compared to placement of localization wires or reflectors in the few weeks prior to surgery.

Comparison of two mathematical models for predicted human thermal responses to hot and humid environments.

PURPOSE: We compared the accuracy and design of two thermoregulatory models, the US Army's empirically designed Heat Strain Decision Aid (HSDA) and the rationally based Health Risk Prediction (HRP) for predicting human thermal responses during exercise in hot and humid conditions and wearing chemical protective clothing. METHODS: Accuracy of the HSDA and HRP model predictions of core body and skin temperature (Tc, Ts) were compared to each other and relative to measured outcomes from eight male volunteers (age 24 ± 6 years; height 178 ± 5 cm; body mass 76.6 ± 8.4 kg) during intermittent treadmill marching in an environmental chamber (air temperature 29.3 ± 0.1 °C; relative humidity 56 ± 1%; wind speed 0.4 ± 0.1 m∙s-1) wearing three separate chemical protective ensembles. Model accuracies and precisions were evaluated by the bias, mean absolute error (MAE), and root mean square error (RMSE) compared to observed data mean ± SD and the calculated limits of agreement (LoA). RESULTS: Average predictions of Tc were comparable and acceptable for each method, HSDA (Bias 0.02 °C; MAE 0.18 °C; RMSE 0.21 °C) and HRP (Bias 0.10 °C; MAE 0.25 °C; RMSE 0.34 °C). The HRP averaged predictions for Ts were within an acceptable agreement to observed values (Bias 1.01 °C; MAE 1.01 °C; RMSE 1.11 °C). CONCLUSION: Both HSDA and HRP acceptably predict Tc and HRP acceptably predicts Ts when wearing chemical protective clothing during exercise in hot and humid conditions.

Thoracic, Peripheral, and Cerebral Volume, Circulatory and Pressure Responses To PEEP During Simulated Hemorrhage in a Pig Model: a Case Study.

Positive end-expiratory pressure (PEEP) is a respiratory/ventilation procedure that is used to maintain or improve breathing in clinical and experimental cases that exhibit impaired lung function. Body fluid shift movement is not monitored during PEEP application in intensive care units (ICU), which would be interesting specifically in hypotensive patients. Brain injured and hypotensive patients are known to have compromised cerebral blood flow (CBF) autoregulation (AR) but currently, there is no non-invasive way to assess the risk of implementing a hypotensive resuscitation strategy and PEEP use in these patients. The advantage of electrical bioimpedance measurement is that it is noninvasive, continuous, and convenient. Since it has good time resolution, it is ideal for monitoring in intensive care units (ICU). The basis of its future use is to establish physiological correlates. In this study, we demonstrate the use of electrical bioimpedance measurement during bleeding and the use of PEEP in pig measurement. In an anesthetized pig, we performed multimodal recording on the torso and head involving electrical bioimpedance spectroscopy (EIS), fixed frequency impedance plethysmography (IPG), and bipolar (rheoencephalography - REG) measurements and processed data offline. Challenges (n=16) were PEEP, bleeding, change of SAP, and CO2 inhalation. The total measurement time was 4.12 hours. Systemic circulatory results: Bleeding caused a continuous decrease of SAP, cardiac output (CO), and increase of heart rate, temperature, shock index (SI), vegetative - Kerdo index (KI). Pulse pressure (PP) decreased only after second bleeding which coincided with loss of CBF AR. Pulmonary arterial pressure (PAP) increased during PEEP challenges as a function of time and bleeding. EIS/IPG results: Body fluid shift change was characterized by EIS-related variables. Electrical Impedance Spectroscopy was used to quantify the intravascular, interstitial, and intracellular volume changes during the application of PEEP and simulated hemorrhage. The intravascular fluid compartment was the primary source of blood during hemorrhage. PEEP produced a large fluid shift out of the intravascular compartment during the first bleeding period and continued to lose more blood following the second and third bleeding. Fixed frequency IPG was used to quantify the circulatory responses of the calf during PEEP and simulated hemorrhage. PEEP reduced the arterial blood flow into the calf and venous outflow from the calf. Head results: CBF AR was evaluated as a function of SAP change. Before bleeding, and after moderate bleeding, intracranial pressure (ICP), REG, and carotid flow pulse amplitudes (CFa) increased. This change reflected vasodilatation and active CBF AR. After additional hemorrhaging during PEEP, SAP, ICP, REG, CFa signal amplitudes decreased, indicating passive CBF AR. 1) The indicators of active AR status by modalities was the following: REG (n=9, 56 %), CFa (n=7, 44 %), and ICP (n=6, 38 %); 2) CBF reactivity was better for REG than ICP; 3) REG and ICP correlation coefficient were high (R2 = 0.81) during CBF AR active status; 4) PRx and REGx reflected active CBF AR status. CBF AR monitoring with REG offers safety for patients by preventing decreased CBF and secondary brain injury. We used different types of bioimpedance instrumentation to identify physiologic responses in the different parts of the body (that have not been discussed before) and how the peripheral responses ultimately lead to decreased cardiac output and changes in the head. These bioimpedance methods can improve ICU monitoring, increase the adequacy of therapy, and decrease mortality and morbidity.

Segmental Volume Changes that Occur in Nonhuman Primates During Short Term Head Up (HUT) and Head Down (HDT) Tilt.

Nonhuman primates are often used in biomedical research and to investigate physiologic processes that occur in man. Impedance plethysmography was used to measure calf, thigh, pelvic, abdominal, and thoracic volume changes in ten Rhesus and eight squirrel monkeys during five-minute exposures to HUT and HDT at angles of 5, 10, and 20 degrees. Calf, rump and tail measurements were made in three squirrel monkeys at 10 and 20 degrees of HUT and HDT. Fluid volume changes in all segments of the Rhesus monkeys were found to change during HUT an HDT in direct relation to the angle of tilt used. However, the volume changes that occurred in the squirrel monkeys were found to be quite different. Their calf, thigh, and pelvic segments lost volume during both HUT and HDT while their abdominal and thoracic segments responded similarly to those of the Rhesus monkeys. These results and those of the calf/tail measurements of the squirrel monkeys suggest that they may utilize their tails as a compensatory reservoir during postural changes and therefore, may not be an appropriate animal model for man under some orthostatic test conditions.

Segmental Intracellular, Interstitial, and Intravascular Volume Changes during Simulated Hemorrhage and Resuscitation: A Case Study.

This paper describes a new combined impedance plethysmographic (IPG) and electrical bioimpedance spectroscopic (BIS) instrument and software that will allow noninvasive real-time measurement of segmental blood flow, intracellular, interstitial, and intravascular volume changes during various fluid management procedures. The impedance device can be operated either as a fixed frequency IPG for the quantification of segmental blood flow and hemodynamics or as a multi-frequency BIS for the recording of intracellular and extracellular resistances at 40 discrete input frequencies. The extracellular volume is then deconvoluted to obtain its intravascular and interstitial component volumes as functions of elapsed time. The purpose of this paper is to describe this instrumentation and to demonstrate the information that can be obtained by using it to monitor segmental compartment volume responses of a pig model during simulated hemorrhage and resuscitation. Such information may prove valuable in the diagnosis and management of rapid changes in the body fluid balance and various clinical treatments.

Measurement of Cerebral Blood Flow Autoregulation with Rheoencephalography: A Comparative Pig Study.

Neuromonitoring is performed to prevent further (secondary) brain damage by detecting low brain blood flow following a head injury, stroke or neurosurgery. This comparative neuromonitoring study is part of an ongoing investigation of brain bioimpedance (rheoencephalography-REG) as a measuring modality for use in both civilian and military medical settings, such as patient transport, emergency care and neurosurgery intensive care. In a previous animal study, we validated that REG detects cerebral blood flow autoregulation (CBF AR), the body's physiological mechanism that protects the brain from adverse effects of low brain blood flow (hypoxia/ischemia). In the current descriptive pig study, the primary goal was to compare measurements of CBF AR made with REG to measurements made with other neuromonitoring modalities: laser Doppler flow (LDF); intracranial pressure (ICP); absolute CBF; carotid flow (CF); and systemic arterial pressure (SAP). Challenges administered to anesthetized pigs were severe induced hemorrhage (bleeding) and resuscitation; CO2 inhalation; and positive end expiratory pressure (PEEP). Data were stored on a computer and processed offline. After hemorrhage, the loss of CBF AR was detected by REG, ICP, and CF, all of which passively followed systemic arterial SAP after bleeding. Loss of CBF AR was the earliest indicator of low brain blood flow: loss of CBF AR occurred before a decrease in cardiac output, which is the cardiovascular response to hemorrhage. A secondary goal of this study was to validate the usefulness of new automated data processing software developed to detect the status of CBF AR. Both the new automated software and the traditional (observational) evaluation indicated the status of CBF AR. REG indicates the earliest breakdown of CBF AR; cessation of EEG for 2 seconds and respiration would be used as additional indicators of loss of CBF AR. The clinical significance of this animal study is that REG shows potential for use as a noninvasive, continuous and non-operator dependent neuromonitor of CBF AR in both civilian and military medical settings. Human validation studies of neuromonitoring with REG are currently in progress.

Bioimpedance monitoring of cellular hydration during hemodialysis therapy.

Introduction The aim of this paper is to describe and demonstrate how a new bioimpedance analytical procedure can be used to monitor cellular hydration of End Stage Renal Disease (ESRD) patients during hemodialysis (HD). Methods A tetra-polar bioimpedance spectroscope (BIS), (UFI Inc., Morro Bay, CA), was used to measure the tissue resistance and reactance of the calf of 17 ESRD patients at 40 discrete frequencies once a minute during dialysis treatment. These measurements were then used to derive intracellular, interstitial, and intravascular compartment volume changes during dialysis. Findings The mean (± SD) extracellular resistance increased during dialysis from 92.4 ± 3.5 to 117.7 ± 5.8 Ohms. While the mean intracellular resistance decreased from 413.5 ± 11.7 to 348.5 ± 8.2 Ohms. It was calculated from these data that the mean intravascular volume fell 9.5%; interstitial volume fell 33.4%; and intracellular volume gained 20.3%. Discussion These results suggest that an extensive fluid shift into the cells may take place during HD. The present research may contribute to a better understanding of how factors that influence fluid redistribution may affect an ESRD patient during dialysis. In light of this finding, it is concluded that the rate of vascular refill is jointly determined with the rate of "cellular refill" and the transfer of fluid from the intertitial compartment into the intravascular space.

Antiphospholipid antibodies promote tissue factor-dependent angiogenic switch and tumor progression.

Progression to an angiogenic state is a critical event in tumor development, yet few patient characteristics have been identified that can be mechanistically linked to this transition. Antiphospholipid autoantibodies (aPLs) are prevalent in many human cancers and can elicit proangiogenic expression in several cell types, but their role in tumor biology is unknown. Herein, we observed that the elevation of circulating aPLs among breast cancer patients is specifically associated with invasive-stage tumors. By using multiple in vivo models of breast cancer, we demonstrated that aPL-positive IgG from patients with autoimmune disease rapidly accelerates tumor angiogenesis and consequent tumor progression, particularly in slow-growing avascular tumors. The action of aPLs was local to the tumor site and elicited leukocytic infiltration and tumor invasion. Tumor cells treated with aPL-positive IgG expressed multiple proangiogenic genes, including vascular endothelial growth factor, tissue factor (TF), and colony-stimulating factor 1. Knockdown and neutralization studies demonstrated that the effects of aPLs on tumor angiogenesis and growth were dependent on tumor cell-derived TF. Tumor-derived TF was essential for the development of pericyte coverage of tumor microvessels and aPL-induced tumor cell expression of chemokine ligand 2, a mediator of pericyte recruitment. These findings identify antiphospholipid autoantibodies as a potential patient-specific host factor promoting the transition of indolent tumors to an angiogenic malignant state through a TF-mediated pathogenic mechanism.

A phase I-II study of the histone deacetylase inhibitor vorinostat plus sequential weekly paclitaxel and doxorubicin-cyclophosphamide in locally advanced breast cancer.

Histone deacetylases (HDACs) are a family of enzymes that regulate chromatin remodeling and gene transcription. Vorinostat is a panHDAC inhibitor that sensitizes breast cancer cells to taxanes and trastuzumab by suppressing HDAC6 and Hsp90 client proteins. Fifty-five patients with clinical stage IIA-IIIC breast cancer received 12 weekly doses of paclitaxel (80 mg/m(2)) plus vorinostat (200-300 mg PO BID) on days 1-3 of each paclitaxel dose plus trastuzumab (for Her2/neu positive disease only), followed by doxorubicin/cyclophosphamide (60/600 mg/m(2) every 2 weeks plus pegfilgrastim). The primary study endpoint was pathologic complete response (pCR). pCR occurred in 13 of 24 evaluable patients with Her2-positive disease (54, 95 % confidence intervals [CI] 35-72 %), which met the prespecified study endpoint. pCR occurred in 4 of 15 patients with triple negative disease (27, 95 % CI 11-52 %) and none of 12 patients with ER-positive, Her2/neu negative disease (0, 95 % CI 0-24 %), which did not meet the prespecified endpoint. ER-positive tumors exhibited lower Ki67 and higher Hsp70 expression, and HDAC6, Hsp70, p21, and p27 expression were not predictive of response. Vorinostat increased acetylation of Hsp90 and alpha tubulin, and reduced expression of Hsp90 client proteins and HDAC6 in the primary tumor. Combination of vorinostat with weekly paclitaxel plus trastuzumab followed by doxorubicin-cyclophosphamide is associated with a high pCR rate in locally advanced Her2/neu positive breast cancer. Consistent with cell line and xenograft data, vorinostat increased acetylation of Hsp90 and alpha tubulin, and decreased Hsp90 client protein and HDAC6 expression in human breast cancers in vivo.

Day to day treatment variations of accelerated partial breast brachytherapy using a multi-lumen balloon.

PURPOSE: To evaluate the variations of multi-lumen balloon (MLB)-based brachytherapy from simulation day to treatment day and their dosimetric impacts during accelerated partial breast irradiation (APBI). MATERIAL AND METHODS: A total of 42 CT images scanned from seven patients were evaluated with regards to daily variation due to of: 1) internal uncertainty: size and shape of balloon, seroma volume; 2) geometrical uncertainty-random: length of each catheter was measured for each fraction (total 70); 3) geometrical uncertainty-systematic: virtual systematic errors were tested by offsetting dwell positions. The original plans (as group A) had a mean value of 96.8% on V95 of the PTV_Eval. Plans were rerun (as group B) such that the mean value of the V95 was relaxed to 90.4%. By applying the reference plan to each daily CT image, variations of target coverage under different sources of error were evaluated. RESULTS: Shape and size of the balloon had means of < 1 mm decreased in diameter and < 0.4 cm(3) decreased in volume; the mean seroma volume increased by 0.2 cm(3). This internal variation has a mean of < 1% difference for both V90 and V95. The geometrical uncertainty made a mean deviation of 2.7 mm per root of sum of square. It caused the degradations of V90 and V95 by mean values of 1.0% and 1.2%, respectively. A systematic error of 3 mm and 4 mm would degrade both of V90 and V95 by 4% and 6%, respectively. The degradations on target coverage of the plans in group A were statistically the same as those in group B. CONCLUSIONS: Overall, APBI treatments with MLB based brachytherapy are precise from day to day. However, minor variation due to daily treatment uncertainties can still degrade tumor bed coverage to an unacceptable coverage when V95 of the original plan is close to 90%.

Monitoring intracellular, interstitial, and intravascular volume changes during fluid management procedures.

The bioimpedance spectroscopic (BIS) analytical algorithm described in this report allows for the non-invasive measurement of intravascular, interstitial, and intracellular volume changes during various fluid management procedures. The purpose of this study was to test clinical use feasibility and to demonstrate the validity of the BIS algorithm in computing compartmental volume shifts in human subjects undergoing fluid management treatment. Validation was performed using volume changes recorded from 20 end stage renal disease patients. The validation procedure involved mathematically deriving post hoc hematocrit profiles from the BIS data-generated fluid redistribution time profiles. These derived hematocrit profiles were then compared to serial hematocrit values measured simultaneously by a CritLine(®) monitor during 60 routine hemodialysis sessions. Regression and Bland-Altman analyses confirm that the BIS algorithm can be used to reliably derive the continuous and real-time rates of change of the compartmental fluid volumes. Regression results yielded a R (2) > 0.99 between the two measures of hematocrit at different times during dialysis. The slopes of the regression equations at the different times were nearly identical, demonstrating an almost one-to-one correspondence between the BIS and CritLine(®) hematocrits. Bland-Altman analysis show that the BIS algorithm can be used interchangeably with the CritLine(®) monitor for the measurement of hematocrit. The present study demonstrates for the first time that BIS can provide real-time continuous measurements of compartmental intravascular, interstitial and intracellular fluid volume changes during fluid management procedures when used in conjunction with this new algorithm.

Muscle and tendon heating rates with therapeutic ultrasound in horses.

OBJECTIVE: To (1) determine the temperature change in equine tendon and muscle during therapeutic ultrasound and (2) develop guidelines for treating horses for muscular or tendinous injury using therapeutic ultrasound. STUDY DESIGN: Experimental, in vivo study. ANIMALS: Adult horses (n = 10). METHODS: Thermistors were inserted in the superficial and deep digital flexor tendons (SDFT and DDFT) of the thoracic limbs of 10 adult horses. On the left, 3.3 MHz therapeutic continuous ultrasound was done for 10 minutes at an intensity of 1.0 W/cm(2) and for the right thoracic limb at 1.5 W/cm(2). Thermistors were placed at 1 cm, 4 cm, and 8 cm depths in the epaxial muscles of the same 10 horses, for a 20-minute treatment at a frequency of 3.3 MHz and intensity of 1.5 W/cm(2). Temperature was recorded before, during, and after treatment. Data were statistically analyzed. RESULTS: Mean temperature rise was 3.5°C in the SDFT and 2.5°C in the DDFT at the end of the 1.0 W/cm(2) treatment (P = .94) and 5.2°C in the SDFT and 3.0°C in the DDFT at the end of the 1.5-W/cm(2) treatment (P = .48). Mean temperature rise in epaxial musculature was 1.3°C at a depth of 1.0 cm, 0.7°C at 4.0 cm, and 0.7°C at 8 cm. CONCLUSIONS: The SDFT and DDFT are heated to a therapeutic temperature using a frequency of 3.3 MHz and intensity of 1.0 W/cm(2). The epaxial muscles are not heated to a therapeutic temperature using a frequency of 3.3 MHz and an intensity of 1.5 W/cm(2).

Pathologic complete response predicts recurrence-free survival more effectively by cancer subset: results from the I-SPY 1 TRIAL--CALGB 150007/150012, ACRIN 6657.

PURPOSE: Neoadjuvant chemotherapy for breast cancer provides critical information about tumor response; how best to leverage this for predicting recurrence-free survival (RFS) is not established. The I-SPY 1 TRIAL (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis) was a multicenter breast cancer study integrating clinical, imaging, and genomic data to evaluate pathologic response, RFS, and their relationship and predictability based on tumor biomarkers. PATIENTS AND METHODS: Eligible patients had tumors ≥ 3 cm and received neoadjuvant chemotherapy. We determined associations between pathologic complete response (pCR; defined as the absence of invasive cancer in breast and nodes) and RFS, overall and within receptor subsets. RESULTS: In 221 evaluable patients (median tumor size, 6.0 cm; median age, 49 years; 91% classified as poor risk on the basis of the 70-gene prognosis profile), 41% were hormone receptor (HR) negative, and 31% were human epidermal growth factor receptor 2 (HER2) positive. For 190 patients treated without neoadjuvant trastuzumab, pCR was highest for HR-negative/HER2-positive patients (45%) and lowest for HR-positive/HER2-negative patients (9%). Achieving pCR predicted favorable RFS. For 172 patients treated without trastuzumab, the hazard ratio for RFS of pCR versus no pCR was 0.29 (95% CI, 0.07 to 0.82). pCR was more predictive of RFS by multivariate analysis when subtype was taken into account, and point estimates of hazard ratios within the HR-positive/HER2-negative (hazard ratio, 0.00; 95% CI, 0.00 to 0.93), HR-negative/HER2-negative (hazard ratio, 0.25; 95% CI, 0.04 to 0.97), and HER2-positive (hazard ratio, 0.14; 95% CI, 0.01 to 1.0) subtypes are lower. Ki67 further improved the prediction of pCR within subsets. CONCLUSION: In this biologically high-risk group, pCR differs by receptor subset. pCR is more highly predictive of RFS within every established receptor subset than overall, demonstrating that the extent of outcome advantage conferred by pCR is specific to tumor biology.

A case report: lobular carcinoma in situ in a male patient with subsequent invasive ductal carcinoma identified on screening breast MRI.

Lobular carcinoma in situ is a form of in situ neoplasia that develops within the terminal lobules of the breast. It is an extremely rare finding in males due to the lack of lobular development in the male breast. The authors herein report an unusual case of incidentally discovered lobular carcinoma in situ in a male patient with recurrent bilateral gynecomastia who was subsequently diagnosed with invasive ductal carcinoma of the left breast. The pathology of lobular carcinoma in situ in a male as well as screening MRI surveillance of male patients at high risk for breast cancer are discussed, emphasizing the importance of screening and imaging follow up in men who are at high risk for breast cancer.

Locally advanced breast cancers are more likely to present as Interval Cancers: results from the I-SPY 1 TRIAL (CALGB 150007/150012, ACRIN 6657, InterSPORE Trial).

Interval cancers (ICs), defined as cancers detected between regular screening mammograms, have been shown to be of higher grade, larger size, and associated with lower survival, compared with screen-detected cancers (SDCs) and comprise 17% of cancers from population-based screening programs. We sought to determine the frequency of ICs in a study of locally advanced breast cancers, the I-SPY 1 TRIAL. Screening was defined as having a mammogram with 2 years, and the proportion of ICs at 1 and 2 years was calculated for screened patients. Differences in clinical characteristics for ICs versus SDCs and screened versus non-screened cancers were assessed. For the 219 evaluable women, mean tumor size was 6.8 cm. Overall, 80% of women were over 40 and eligible for screening; however, only 31% were getting screened. Among women screened, 85% were ICs, with 68% diagnosed within 1 year of a previously normal mammogram. ICs were of higher grade (49% vs. 10%) than SDCs. Among non-screened women, 28% (43/152) were younger than the recommended screening age of 40. Of the entire cohort, 12% of cancers were mammographically occult (MO); the frequency of MO cancers did not differ between screened (11%) and non-screened (15%). ICs were common in the I-SPY 1 TRIAL suggesting the potential need for new approaches beyond traditional screening to reduce mortality in women who present with larger palpable cancers.

Chemotherapy response and recurrence-free survival in neoadjuvant breast cancer depends on biomarker profiles: results from the I-SPY 1 TRIAL (CALGB 150007/150012; ACRIN 6657).

Neoadjuvant chemotherapy for breast cancer allows individual tumor response to be assessed depending on molecular subtype, and to judge the impact of response to therapy on recurrence-free survival (RFS). The multicenter I-SPY 1 TRIAL evaluated patients with ≥ 3 cm tumors by using early imaging and molecular signatures, with outcomes of pathologic complete response (pCR) and RFS. The current analysis was performed using data from patients who had molecular profiles and did not receive trastuzumab. The various molecular classifiers tested were highly correlated. Categorization of breast cancer by molecular signatures enhanced the ability of pCR to predict improvement in RFS compared to the population as a whole. In multivariate analysis, the molecular signatures that added to the ability of HR and HER2 receptors, clinical stage, and pCR in predicting RFS included 70-gene signature, wound healing signature, p53 mutation signature, and PAM50 risk of recurrence. The low risk signatures were associated with significantly better prognosis, and also identified additional patients with a good prognosis within the no pCR group, primarily in the hormone receptor positive, HER-2 negative subgroup. The I-SPY 1 population is enriched for tumors with a poor prognosis but is still heterogeneous in terms of rates of pCR and RFS. The ability of pCR to predict RFS is better by subset than it is for the whole group. Molecular markers improve prediction of RFS by identifying additional patients with excellent prognosis within the no pCR group.

Segmental blood flow and hemodynamic state of lymphedematous and nonlymphedematous arms.

BACKGROUND: Findings regarding the influence hemodynamic factors, such as increased arterial blood flow or venous abnormalities, on breast cancer treatment-related lymphedema are mixed. The purpose of this study was to compare segmental arterial blood flow, venous blood return, and blood volumes between breast cancer survivors with treatment-related lymphedema and healthy normal individuals without lymphedema. METHODS AND RESULTS: A Tetrapolar High Resolution Impedance Monitor and Cardiotachometer were used to compare segmental arterial blood flow, venous blood return, and blood volumes between breast cancer survivors with treatment-related lymphedema and healthy normal volunteers. Average arterial blood flow in lymphedema-affected arms was higher than that in arms of healthy normal volunteers or in contralateral nonlymphedema affected arms. Time of venous outflow period of blood flow pulse was lower in lymphedema-affected arms than in healthy normal or lymphedema nonaffected arms. Amplitude of the venous component of blood flow pulse signal was lower in lymphedema-affected arms than in healthy or lymphedema nonaffected arms. Index of venular tone was also lower in lymphedema-affected arms than healthy or lymphedema nonaffected arms. CONCLUSIONS: Both arterial and venous components may be altered in the lymphedema-affected arms when compared to healthy normal arms and contralateral arms in the breast cancer survivors.