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BackgroundBehavioral symptoms in breast cancer (BC) survivors have been attributed to cancer treatment and resulting inflammation. However, studies linking behavioral symptoms to BC treatment have observed patients only after some treatment. Our prospective study with pre-treatment baseline investigates post-treatment changes in inflammation-related biomarkers and whether those changes correlate with changes in symptoms.MethodsParticipants were postmenopausal women, newly-diagnosed with stage 0-3 BC before any treatment (n = 173 "patients"), and age-matched women without cancer (n = 77 "controls"), who were assessed on plasma markers [soluble tumor necrosis factor receptor type 2 (sTNF-RII), interleukin (IL)-6, IL-1 receptor antagonist (IL-1RA), C-reactive protein (CRP)]) and symptoms (Physical Functioning, Pain, Attention/concentration, Perceived Cognitive Problems, Fatigue, Sleep Insufficiency, Depression). Participants were assessed again 1 month, 1 year, and 2 years after completing primary treatment or similar interval in controls. Generalized linear mixed models tested 4 treatments (surgery alone or with chemotherapy, radiation, or both) for association with change per marker. Joint models tested change per marker for association with change per symptom. Models considered demographic, socioeconomic, and clinical covariates. False Discovery Rate method controlled risk of error from multiple hypotheses.ResultsAt one month post-completion of treatment, sTNF-RII and IL-6 were elevated by all BC treatments, as were IL-1RA and CRP after surgery alone (all, p

BackgroundThrombocytopenia is a common adverse event on HER2-targeted therapies, fam-trastuzumab deruxtecan (T-DXd) and ado-trastuzumab emtansine (T-DM1). A reported association of Asian ancestry with this event merits investigation to rule out potential confounding.MethodsSubjects in this retrospective cohort were female patients with HER2 positive breast cancer, of Asian or non-Hispanic White ancestry, who initiated T-DM1 or T-DXd from January 2017 through October 2021. Follow-up closed in January 2022. Primary endpoint was dose adjustment for thrombocytopenia. Competing endpoints were discontinuation of drug for other toxicity, disease progression, or for completion of prescribed cycles. The association between Asian ancestry and thrombocytopenia-related dose adjustment was tested at p

BackgroundHyperglycemia is recognized as a common adverse event for patients receiving alpelisib but has been little studied outside of clinical trials. We report the frequency of alpelisib-associated hyperglycemia in a real-world setting and evaluate proposed risk factors.Patients and methodsWe retrospectively identified patients with PIK3CA-mutated, hormone receptor-positive, metastatic breast cancer who initiated treatment with alpelisib plus fulvestrant between August 2019 and December 2021. Ordinal logistic regression evaluated 5 characteristics (diabetes, prediabetes, body mass index [BMI], age, and Asian ancestry) as independent risk factors for ALP-associated hyperglycemia grades 2-4. Risk of error from multiple hypothesis testing was controlled using the false discovery rate method.ResultsThe study included n = 92 subjects, all but 1 female, mean age 59.9 (+11.9) years with 50% non-Hispanic White, 15% Hispanic/Latino, 13% Asian, 9% African/Black, and 13% other/unknown. In total 34% of patients had diabetes, 10% had pre-diabetes, and 56% had normoglycemia. Thirty-six percent were obese, 32% were overweight, 25% were normal weight, and 7% were lean. Frequency of grades 1-4 hyperglycemia in current subjects (64.1%) was similar to hyperglycemia reported in the SOLAR-1 trial (63.7%). Our subjects' risk of grades 2-4 hyperglycemia was independently increased by pre-existing diabetes (Odds ratio 3.75, 95% CI, 1.40-10.01), pre-diabetes (6.22, 1.12-34.47), Asian ancestry (7.10, 1.75-28.84), and each unit of BMI above 20 (1.17, 1.07-1.28).ConclusionWhile receiving alpelisib, patients of Asian ancestry, as well as patients with pre-existing hyperglycemia and/or BMI above 20, should be closely monitored for hyperglycemia. The mechanism underlying the current association of alpelisib-associated hyperglycemia with Asian ancestry is independent of BMI and merits further study. The high incidence of hyperglycemia resulted in a change in practice to include consultation with a diabetes nurse educator or endocrinologist at the start of alpelisib.

Motivated by a preclinical study in a mouse model of breast cancer, we suggest a joint modeling framework for outcomes of mixed type and measurement structures (longitudinal versus single time/time-invariant). We present an approach based on the time-varying copula models, which is used to jointly model longitudinal outcomes of mixed types via a time-varying copula, and extend the scope of these models to handle outcomes with mixed measurement structures. Our framework allows the parameters corresponding to the longitudinal outcome to be time varying and thereby enabling researchers to investigate how the response-predictor relationships change with time. We investigate the finite sample performance of this new approach via a Monte Carlo simulation study and illustrate its usefulness by an empirical analysis of the motivating preclinical study, comparing the effect of various treatments on tumor volume (longitudinal continuous response) and the number of days until tumor volume triples (time-invariant count response). Through the real-life application and the simulation study, we demonstrate that, compared with marginal modeling, the joint modeling framework offers more precision in the estimation of model parameters.

Background: Objective, treatment-independent markers of cancer-related fatigue are needed to advance clinical trials. In the current study, the authors evaluated physical, neurocognitive, and serologic markers for correlation with self-reported fatigue before and after (neo)adjuvant chemotherapy for patients with early-stage breast cancer.Methods: Women with AJCC TNM Stage I-III breast cancer consented to assessment before and after the completion of 4 cycles of dose-dense doxorubicin and cyclophosphamide. Assessment included self-reported fatigue (using the Brief Fatigue Inventory), depression (using the Center for Epidemiologic Studies-Depression Scale [CES-D]), Pittsburgh Sleep Quality Index, and 28 objective measures (grip strength in dominant and nondominant hands, 6-minute walk, daily total energy expenditure, 14 neurocognitive tests, and 10 serologic markers). Generalized linear regression models of fatigue were constructed (1 model per marker), and adjusted for depression, timing before/after chemotherapy, menopausal status, obesity, and educational level. P values were adjusted to control the False Discovery Rate.Results: Of 28 subjects, 3 withdrew without completing baseline assessments. Prechemotherapy and postchemotherapy data were available for the evaluation of physical measures (25 subjects aged 50.6 ± 9.5 years), neurocognitive tests (22 subjects), and serologic markers (10 subjects). On covariate-adjusted analysis, interleukin (IL)-12 was found to be associated with fatigue at both assessments (P<.01). Serum eotaxin (P < .01), IL-1RA (P < .01), monocyte chemoattractant protein 1 (MCP-1) (P<.01), and performance on 2 neurocognitive (Trail Making) tests (P<.01 and P = .02, respectively) were found to be inversely associated with fatigue before chemotherapy but not afterward, whereas daily energy expenditure, serum MCP-1, and serum macrophage inflammatory protein 1a (MIP-1a) were found to be associated with fatigue after receipt of chemotherapy but not before (P<.01 for each). The association between energy expenditure and fatigue was detectable only if an actively athletic subject with outlier values of energy expenditure was excluded.Conclusions: Serum IL-12 merits confirmatory testing as an objective, treatment-independent measure of fatigue in patients with early-stage breast cancer. Cancer 2017;123:1810-1816. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. [ABSTRACT FROM AUTHOR]

Abstract: Despite 2 randomized trials reporting no reduction in operations or local recurrence at 1 year, preoperative magnetic resonance imaging (MRI) is increasingly used in diagnostic workup of breast cancer. We evaluated 5 utilization criteria recently proposed by experts. Of women (n = 340) newly diagnosed with unilateral breast cancer who underwent bilateral MRI, most (69.4%) met at least 1 criterion before MRI: mammographic density (44.4%), under consideration for partial breast irradiation (PBI) (19.7%), genetic-familial risk (12.9%), invasive lobular carcinoma (11.8%), and multifocal/multicentric disease (10.6%). MRI detected occult malignant lesion or extension of index lesion in 21.2% of index, 3.3% of contralateral, breasts. No expert criterion was associated with MRI-detected malignant lesion, which associated instead with pre-MRI plan of lumpectomy without PBI (48.2% of subjects): Odds Ratio 3.05, 95% CI 1.57–5.91 (p adjusted for multiple hypothesis testing = 0.007, adjusted for index-vs-contralateral breast and covariates). The expert guidelines were not confirmed by clinical evidence. [Copyright &y& Elsevier]