Patient-reported treatment toxicity and adverse events in Black and White women receiving chemotherapy for early breast cancer.

PURPOSE: It is not known whether chemotherapy-related symptom experiences differ between Black and White women with early breast cancer (Stage I-III) receiving current chemotherapy regimens and, in turn, influences dose delay, dose reduction, early treatment discontinuation, or hospitalization. METHODS: Patients self-reported their race and provided symptom reports for 17 major side effects throughout chemotherapy. Toxicity and adverse events were analyzed separately for anthracycline and non-anthracycline regimens. Fisher's exact tests and two-sample t-tests compared baseline patient characteristics. Modified Poisson regression estimated relative risks of moderate, severe, or very severe (MSVS) symptom severity, and chemotherapy-related adverse events.Please check and confirm that the authors and their respective affiliations have been correctly identified and amend if necessary.no changes RESULTS: In 294 patients accrued between 2014 and 2020, mean age was 58 (SD13) and 23% were Black. For anthracycline-based regimens, the only significant difference in MSVS symptoms was in lymphedema (41% Black vs 20% White, p = .04) after controlling for axillary surgery. For non-anthracycline regimens, the only significant difference was MSVS peripheral neuropathy (41% Blacks vs. 23% White) after controlling for taxane type (p = .05) and diabetes (p = .05). For all other symptoms, severity scores were similar. Dose reduction differed significantly for non-anthracycline regimens (49% Black vs. 25% White, p = .01), but not for anthracycline regimens or in dose delay, early treatment discontinuation, or hospitalization for either regimen. CONCLUSION: Except for lymphedema and peripheral neuropathy, Black and White patients reported similar symptom severity during adjuvant chemotherapy. Dose reductions in Black patients were more common for non-anthracycline regimens. In this sample, there were minimal differences in patient-reported symptoms and other adverse outcomes in Black versus White patients.

Correction to: Measuring and understanding adherence in a home-based exercise intervention during chemotherapy for early breast cancer.

In the original publication, the sixth author name was published incorrectly as A. Wood. The correct author name should read as W. A. Wood.

Measuring and understanding adherence in a home-based exercise intervention during chemotherapy for early breast cancer.

PURPOSE: Ensuring and measuring adherence to prescribed exercise regimens are fundamental challenges in intervention studies to promote exercise in adults with cancer. This study reports exercise adherence in women who were asked to walk 150 min/week throughout chemotherapy treatment for early breast cancer. Participants were asked to wear a FitbitTM throughout their waking hours, and Fitbit steps were uploaded directly into study computers. METHODS: Descriptive statistics are reported, and both unadjusted and multivariable linear regression models were used to assess associations between participant characteristics, breast cancer diagnosis, treatment, chemotherapy toxicities, and patient-reported symptoms with average Fitbit steps/week. RESULTS: Of 127 women consented to the study, 100 had analyzable Fitbit data (79%); mean age was 48 and 31% were non-white. Mean walking steps were 3956 per day. Nineteen percent were fully adherent with the target of 6686 steps/day and an additional 24% were moderately adherent. In unadjusted analysis, baseline variables associated with fewer Fitbit steps were: non-white race (p = 0.012), high school education or less (p = 0.0005), higher body mass index (p = 0.0024), and never/almost never drinking alcohol (p = 0.0048). Physical activity variables associated with greater Fitbit steps were: pre-chemotherapy history of vigorous physical activity (p = 0.0091) and higher self-reported walking minutes/week (p < 0.001), and higher outcome expectations from exercise (p = 0.014). Higher baseline anxiety (p = 0.03) and higher number of chemotherapy-related symptoms rates "severe/very severe" (p = 0.012) were associated with fewer steps. In multivariable analysis, white race was associated with 12,146 greater Fitbit steps per week (p = 0.004), as was self-reported walking minutes prior to start of chemotherapy (p < 0.0001). CONCLUSIONS: Inexpensive commercial-grade activity trackers, with data uploaded directly into research computers, enable objective monitoring of home-based exercise interventions in adults diagnosed with cancer. Analysis of the association of walking steps with participant characteristics at baseline and toxicities during chemotherapy can identify reasons for low/non-adherence with prescribed exercise regimens.

Role of progesterone and estrogen in development of uterine tone in mares.

In two experiments (30 mares/experiment), the uterus was recorded as having flaccid tone characteristic of estrus or seasonal anestrus (tone score 1), intermediate tone characteristic of diestrus (tone score 2), or increased or maximal tone characteristic of early pregnancy (tone score 3 or 4). In Experiment I (five mares/group), uterine tone in seasonally anovulatory mares was not altered significantly from the flaccid state by daily administration of 100 mg progesterone plus 1 mg estradiol 17beta or 1 mg estradiol 17beta alone. Uterine tone in seasonally anovulatory mares receiving 100 mg progesterone alone increased to intermediate level (score 2; P<0.05) and remained there throughout the treatment period. Tone scores in the group receiving a 14-d progesterone priming period followed by progesterone plus estradiol were higher (P<0.02) on Days 16 to 28 than scores in the group receiving progesterone alone throughout the treatment period. In Experiment II, (five mares/group), steroid treatments were begun on Day 10 postovulation. The combination of 1 mg exogenous estradiol plus progesterone produced greater uterine tone than exogenous progesterone alone. There were no significant differences between the pregnant control group and the group receiving progesterone plus 1 mg estradiol. There were no significant differences between the group receiving progesterone alone and the group receiving progesterone plus 5 mg estradiol. Results supported the hypothesis that the maximum uterine tone of early pregnancy is caused by progesterone priming followed by exposure to low levels of estradiol plus continued exposure to progesterone.

Effects of estrous cycle and season on ultrasonic uterine anatomy in mares.

The morphological changes in ultrasound images of the uterus at various times of the year were characterized in nonbred mares, using a linear-array scanner. The uterus was recorded as having an ultrasonic morphology characteristic of diestrus (uterine score 1, endometrial folds not visible), estrus (score 3, distinct endometrial folds), or an intermediate stage (score 2). In Experiment I, uterine scores for the first ovulatory period of the year were compared to scores for the second period in 23 pony mares. More mares (P<0.05) showed endometrial folding prior to the second ovulation of the year (14 23 ) than prior to the first (5 23 ). Mean uterine scores were higher (P<0.05) on Day -10 (ovulation = Day 0) and tended to be higher (P<0.1) on Days -14, -13, and -11 of the first ovulatory period than on the corresponding days of the second period. Uterine scores for the first ovulatory period were lower (P<0.05) on Days -5, -4, -3, -2, -1, and 0 and tended to be lower (P<0.01) on Day -6. In addition, the pattern of change in uterine scores paralleled the pattern of change in the intensity of estrous behavior. In Experiment II, in 20 horse mares, the curve for uterine scores during interovulatory intervals in May-June, but not in September-October, was bimodal due to a small rise (P<0.05) and subsequent return to baseline between Days +3 and +6. The mean uterine scores for both May-June and September-October began to increase on Day -7 or -8, reached maximum on Day -3, declined between Days -2 and 0, continued to decline after Day 0, and reached a value characteristic of diestrus by Day +2. Results indicated that the ultrasonic characteristics of the uterus may provide an instant indicator of estrogen exposure and may have practical value in judging the optimal time to breed.

Evaluation of an anesthetic regimen for retroorbital blood collection from mice.

Many Institutional Animal Care and Use Committees require anesthetization of mice for retroorbital blood collection procedures. Optimal anesthetic regimens should provide chemical restraint and adequate analgesia for a sufficient but otherwise minimal duration. This study was conducted to evaluate the effectiveness, safety, and practical utility of the general anesthetic combination of ketamine and medetomidine with and without the topical anesthetic proparacaine. In addition, we sought to evaluate the reversal of general anesthesia with atipamezole. The findings suggest that the combination of ketamine, medetomidine, proparacaine, and atipamezole is a safe and humane anesthetic regimen for retroorbital collection of blood samples from mice.

An evaluation of analgesic regimens for abdominal surgery in mice.

This study was designed to evaluate the efficacy of several analgesic regimens for use after intraperitoneal implantation of telemetry transmitters in mice. The lengths of time required for postoperative recovery of food and water intake, locomotor activity, and core temperature of mice that did not receive postsurgical analgesic medication were compared to those of mice that were given either an analgesic in the drinking water or buprenorphine injections. Many measured variables were not substantially altered by analgesic medications. However, ibuprofen-treated mice demonstrated significantly greater locomotor activity on days 2 through 5 after surgery and a more rapid return to stable postsurgical levels of activity and water intake as compared to those in untreated mice. These changes are consistent with potential analgesic efficacy of the ibuprofen treatment regimen. Buprenorphine injections elicited hyperactivity, hyperthermia, and reduced food and water intake during both the immediate postsurgical recovery period and after apparent recuperation from surgery, as compared to effects observed in saline-treated mice. Evaluating the effect of analgesic regimens on postsurgical changes in physiologic and behavioral variables can be useful in assessing the efficacy of analgesic treatments, but some changes may indicate pharmacologic effects that do not reflect pain relief.

Ableson kinases negatively regulate invadopodia function and invasion in head and neck squamous cell carcinoma by inhibiting an HB-EGF autocrine loop.

Head and neck squamous cell carcinoma (HNSCC) has a proclivity for locoregional invasion. HNSCC mediates invasion in part through invadopodia-based proteolysis of the extracellular matrix (ECM). Activation of Src, Erk1/2, Abl and Arg downstream of epidermal growth factor receptor (EGFR) modulates invadopodia activity through phosphorylation of the actin regulatory protein cortactin. In MDA-MB-231 breast cancer cells, Abl and Arg function downstream of Src to phosphorylate cortactin, promoting invadopodia ECM degradation activity and thus assigning a pro-invasive role for Ableson kinases. We report that Abl kinases have an opposite, negative regulatory role in HNSCC where they suppress invadopodia and tumor invasion. Impairment of Abl expression or Abl kinase activity with imatinib mesylate enhanced HNSCC matrix degradation and 3D collagen invasion, functions that were impaired in MDA-MB-231. HNSCC lines with elevated EGFR and Src activation did not contain increased Abl or Arg kinase activity, suggesting that Src could bypass Abl/Arg to phosphorylate cortactin and promote invadopodia ECM degradation. Src-transformed Abl(-/-)/Arg(-/-) fibroblasts produced ECM degrading invadopodia containing pY421 cortactin, indicating that Abl/Arg are dispensable for invadopodia function in this system. Imatinib-treated HNSCC cells had increased EGFR, Erk1/2 and Src activation, enhancing cortactin pY421 and pS405/418 required for invadopodia function. Imatinib stimulated shedding of the EGFR ligand heparin-binding EGF-like growth factor (HB-EGF) from HNSCC cells, where soluble HB-EGF enhanced invadopodia ECM degradation in HNSCC but not in MDA-MB-231. HNSCC cells treated with inhibitors of the EGFR-invadopodia pathway indicated that EGFR and Src are required for invadopodia function. Collectively, our results indicate that Abl kinases negatively regulate HNSCC invasive processes through suppression of an HB-EGF autocrine loop responsible for activating a EGFR-Src-cortactin cascade, in contrast to the invasion promoting functions of Abl kinases in breast and other cancer types. Our results provide mechanistic support for recent failed HNSCC clinical trials utilizing imatinib.

Ovarian teratoma and granulosa cell tumor in two mares.

Simultaneous and successive occurrence of ovarian teratoma and granulosa cell tumor is reported in 2 mares. Simultaneous occurrence of the tumors may obscure clinical diagnosis. Whereas size, unilaterality, and the cystic nature of each may be similar, differentiating features include the potentially palpable presence of bone, cartilage, or teeth in teratoma, and the hormone-induced behavioral and reproductive effects of granulosa cell tumors. Thorough examination of surgical specimens may reveal the existence of a neoplastic process, previously obscured by the more obvious presence of another.