Breast cancer diagnosed at a young age is associated with a poor prognosis. It is possible that inadequate endocrine therapy for the youngest women contributes to their poorer prognosis. Data on ...optimal endocrine therapy selection as well as duration for premenopausal women are crucial. Recently published clinical trials including Australian Breast and Colorectal Cancer Study Group-12 (ABCSG-12), E-3193, and Suppression of Ovarian Function Trial (SOFT)/Tamoxifen and Exemestane Trial (TEXT) have shed light on the role of ovarian function suppression and aromatase inhibitors in premenopausal women. Additionally, optimal duration of endocrine therapy has been addressed in the recent Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) and Adjuvant Tamoxifen—To Offer More? (aTTom) trials.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract Background: The Oncotype DX (ODX) test is a 21-gene expression assay widely used for the prediction of risk recurrence in early-stage breast cancer, but it may be possible to identify ...patients who can forgo testing using only clinicopathologic variables. In 2018, the National Cancer Database (NCDB) began reporting quantitative histologic parameters for estrogen receptor (ER), progesterone receptor (PR), and Ki-67 expression in breast cancer patients. Inclusion of these variables may improve the development of nationally applicable models to predict ODX results using clinicopathologic variables alone. Methods: Using a cohort of patients from the NCDB diagnosed from 2018–2020 with hormone receptor (HR)-positive, HER2-negative, Stage I-III breast cancer, we trained machine learning models to predict high-risk (26-100) ODX score. A subset comprising 80% of patients was used for model training, while the remaining data were set aside for internal validation. An external validation cohort was selected from the University of Chicago Medical Center (UCMC), including patients diagnosed from 2009–2021. Feature selection, model architecture selection, and hyperparameter tuning were performed using 10-fold cross-validation within the NCDB training set. We compared a model with quantitative ER, PR, and Ki-67; a model with only quantitative ER and PR, and a model without quantitative immunohistochemistry – to best reflect the likely data available in a variety of practice patterns. The primary endpoint was the area under the receiver operating characteristic curve (AUROC) for prediction of high-risk ODX results in the UCMC validation cohort. Models were also evaluated as rule-out tests to identify low-risk patients who did not require further ODX testing, using a high (90%) sensitivity threshold, fit in the NCDB training dataset. Results: We identified 53,346 patients from the NCDB cohort meeting the inclusion criteria; 7% had a high risk ODX score, with a median follow-up time of 28 months. The UCMC validation cohort included 896 patients, and was more diverse, with 30% non-Hispanic Black patients (versus 8% in NCDB), more high-risk patients (18% with high ODX), and a longer median follow-up time of 55 months. In the NCDB validation cohort, models incorporating quantitative ER/PR (AUROC 0.78, 95% CI 0.77–0.80) and quantitative ER/PR/Ki-67 (AUROC 0.81, 95% CI 0.80–0.83) both performed better than the non-quantitative model (AUROC 0.70, 95% CI 0.68–0.72). These results were preserved in the external UCMC cohort, where the ER/PR model (AUROC 0.86, 95% CI 0.80–0.92, p = 0.032) and the ER/PR/Ki-67 model (AUROC 0.87, 95% CI 0.81–0.93) outperformed the non-quantitative model (AUROC 0.80, 95% CI 0.73–0.87, p = 0.009). The high sensitivity rule-out threshold of the ER/PR model predicted that 30% of patients in the UCMC cohort would be low ODX, and the ER/PR/Ki-67 model predicted 44% as low risk – negative predictive value was over 96% for prediction of high ODX. Of the patients predicted to be low risk by the quantitative models, none had a documented high ODX score, and recurrence was < 3% at 5 years. The hazard ratio for recurrence free interval, adjusted for age and comorbidity score, of patients predicted to be high risk by this threshold was 2.96 (95% CI 1.02–8.58) for the ER/PR model and 3.84 (95% CI 1.48–9.97) for the ER/PR/Ki-67 model. Conclusions: We present externally validated and nationally applicable models that identify approximately half of HR-positive/HER2-negative breast cancer patients who are unlikely to have high ODX results using widely available quantitative clinicopathologic variables. Patients identified as low risk by these models have excellent long-term outcomes and may be able to forgo adjuvant chemotherapy without further genomic testing. Citation Format: Asim Dhungana, Augustin Vannier, Fangyuan Zhao, Jincong Freeman, Poornima Saha, Megan Sullivan, Katharine Yao, Elbio Flores, Olufunmilayo Olopade, Dezheng Huo, Alexander Pearson, Frederick Howard. Development and Validation of a Breast Cancer Recurrence Model Demonstrates Accurate Identification of Patients with Favorable Long-Term Outcomes abstract. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-01-11.
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Background: Glucocorticoid receptor (GR) activity inhibits chemotherapy-induced apoptosis, and GR antagonism with m enhances chemotherapy sensitivity in GR+ breast (B) and ovarian ...cancer (OC) cells. C+G is a commonly used regimen for B and OC. We report the results of a phase I trial of the GR antagonist m plus C+G in patients with advanced B and OC. Methods: A standard “3+3” dose escalation phase I study was performed. Objectives were to assess the safety and tolerability of the regimen, and to determine the recommended phase 2 (RP2D) dose of M+C+G. C+G was administered on days 1 and 8 of a 21 day cycle, and m was administered the day prior to and the day of chemotherapy. The starting dose level (DL) was 1, with additional DLs as follows in the table. Results: 31 patients (pts) with a median age of 54 years (range 32-76) were enrolled. 18 pts had BC (3 ER+, 15 triple-negative), and 13 had high grade serous OC (11 platinum-sensitive, 2 platinum-resistant). The median number of prior therapies for advanced BC was 1 (range 0-5) and for OC was 2 (range 1-3). Dose de-escalation was necessary due to the DLT of neutropenia. After DL -3, prophylactic G-CSF (PGF) was instituted. The RP2D was C AUC 2, G 600 mg/m2, m 300 mg with PGF administered on day 9. Of the BC pts, 2 had a complete response (CR), 2 had a partial response (PR), 8 had stable disease (SD), 4 had progressive disease (PD). Of the OC pts, there was 1 CR (CR2 lasted > 27 mos; CR1 lasted only 8 mos), 1 PR, 6 SD, and 3 PD. 4 pts were inevaluable for response. Conclusions: These data suggest that M+C+G is safe and tolerable, and the most common DLT is neutropenia. This was easily managed with the institution of PGF. Studies correlating tumor GR expression with response are ongoing, and may help identify patients who are most likely to benefit from this combination. Clinical trial information: NCT02046421. Table: see text
Purpose
Glucocorticoid receptor (GR) overexpression is associated with poor prognosis ER-negative breast cancer. GR antagonism with mifepristone increases chemotherapy-induced breast cancer cell ...death, therefore we conducted a phase I clinical trial of mifepristone and nab-paclitaxel in advanced breast cancer.
Methods
A novel randomized phase I design was used to assess the effect of mifepristone on nab-paclitaxel pharmacokinetics and toxicity. Patients were randomized to placebo or mifepristone for the first cycle; mifepristone was given to all for subsequent cycles.
Results
Nine patients were enrolled. All were found to have a twofold or greater increase in serum cortisol after mifepristone administration, reflecting effective GR inhibition. Neutropenia occurred at both nab-paclitaxel dose levels studied (100 and 80 mg/m
2
), and was easily managed with dose reduction and/or growth factor administration. Pharmacokinetic data suggest an interaction between nab-paclitaxel and mifepristone in some patients. Two patients had complete responses (CR), three partial responses (PR), one stable disease (SD), and three progressive disease (PD). Immunohistochemical staining for GR found six of nine tumors were GR-positive. All six GR-positive tumors were triple-negative at the time of recurrence. Of these six patients, two had CRs, two PRs, one SD, and one PD.
Conclusions
GR appears to be a promising target in TNBC, and GR inhibition plus chemotherapy produces manageable toxicity. While neutropenia was observed in some, a nab-paclitaxel dose of 100 mg/m
2
plus mifepristone 300 mg was found to be tolerable, and a randomized phase II trial of nab-paclitaxel with/without mifepristone is planned in GR-positive advanced TNBC.
Chronic pain and mood disorders share common neuroanatomical substrates involving disruption of the reward system. Although increase in negative affect (NA) and decrease in positive affect (PA) are ...well-known factors complicating the clinical presentation of chronic pain patients, our understanding of the mechanisms underlying the interaction between pain and PA/NA remains limited. Here, we used a validated task probing behavioral and neural responses to monetary rewards and losses in conjunction with functional magnetic resonance imaging (fMRI) to test the hypothesis that dysfunction of the striatum, a key mesolimbic structure involved in the encoding of motivational salience, relates to mood alterations comorbid with chronic pain.
Twenty-eight chronic musculoskeletal pain patients (chronic low back pain, n=15; fibromyalgia, n=13) and 18 healthy controls underwent fMRI while performing the Monetary Incentive Delay (MID) task. Behavioral and neural responses were compared across groups and correlated against measures of depression (Beck Depression Inventory) and hedonic capacity (Snaith-Hamilton Pleasure Scale).
Compared to controls, patients demonstrated higher anhedonia and depression scores, and a dampening of striatal activation and incentive-related behavioral facilitation (reduction in reaction times) during reward and loss trials of the MID task (ps < 0.05). In all participants, lower activation of the right striatum during reward trials was correlated with lower incentive-related behavioral facilitation and higher anhedonia scores (ps < 0.05). Finally, among patients, lower bilateral striatal activation during loss trials was correlated with higher depression scores (ps < 0.05).
In chronic pain, PA reduction and NA increase are accompanied by striatal hypofunction as measured by the MID task.
•Striatal hypofunction accompanies mood alteration in low back pain and fibromyalgia.•Pain patients show dampened behavioral and neural response to reward and punishment.•Striatal hypofunction relates to higher depression and anhedonia scores in patients.•The monetary incentive delay task can probe striatal activity in chronic pain.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Splenic B-cell lymphoma/leukemia with prominent nucleoli (SBLPN) aka hairy cell leukemia variant (HCL-v) is a rare B-cell chronic lymphoproliferative disorder. The main diagnostic challenge is to ...differentiate SBLPN from Classical hairy cell leukemia (HCL-c), as the former faces inferior responses to therapies and a poor prognosis.
The aim is to discuss the clinic-hematological and immunophenotyping findings of three cases of SBLPN.
This is a retrospective observational study.
From the year 2011 to 2021, flow cytometry of all the cases with HCL diagnosis was reviewed, and three cases with negative or dim CD25 and hematological presentation matching with SBLPN were picked up.
Descriptive statistics is used.
All the cases were male. The age ranges from 43 to 64 years. Median hemoglobin concentration, total leucocyte count, and platelet count were 8.6 g/dL, 6.9 × 109/L, and 53 × 109/L, respectively. The atypical cells were medium to large. All three showed prominent nucleoli. Bone marrow biopsies showed an interstitial pattern of infiltration in all the cases. The hairy cells were positive for CD20, CD11c, and CD103. CD25 was dim positive in one case. Annexin A1 was negative in all three cases. BRAF V600E mutation analysis was done in one case and turned out negative for the mutation.
SBLPN is a rare entity, usually on-flow cytometry CD25 negative. However, in dim CD25-positive cases, BRAFV600E mutational analysis helps in discerning SBLPN diagnosis and differentiating it from HCL-c.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Non-suicidal self-injury (NSSI) typically begins during adolescence and the process of treatment and recovery can be challenging. We examine NSSI through the lens of the Transtheoretical Model of ...Change, a framework that views the process of change as five stages, with differing degrees of readiness to change.
Thirty participants, both adolescents and young adults (14 to 35 years), were recruited from a tertiary care neuropsychiatric hospital. The participants were predominantly female and had self-injured at least once in the last year. They completed the Inventory of Statements about Self Injury, the University of Rhode Island Change Assessment and the Reasons to Stop Self-Injury Questionnaire.
Seventy-three percent were in the contemplation stage with respect to their readiness to change, while the rest were in the pre-contemplation stage. Participants endorsed a range of vulnerability and resilience related reasons to stop injuring; reasons related to self-efficacy, the addictive nature of NSSI, self-efficacy and impact on interpersonal relationships were prominent levers for the recovery process. Preliminary trends indicated that participants in the contemplation stage endorsed reasons to stop self-injuring more strongly than those in pre-contemplation.
The findings carry implications for assessment, the amplification of reasons for recovery and individualized interventions to support the recovery process with individuals who engage in NSSI.
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CEKLJ, IZUM, KILJ, NUK, PILJ, SAZU, UL, UM, UPUK
In health care, the rapid proliferation of health information on the internet has resulted in more patients turning to the digital media as their first source of health information and acquiring ...knowledge. The present study was conducted to assess use of the digital medium as a medical information resource in health-related states and to determine their experience and perceptions about the quality and reliability of the information available among the participants.
The study was done in an urban settlement of Delhi among adults who use any digital media. A sample of 321 were selected though convenient sampling. The information was collected through a semi-structured, self-administered, pre-tested questionnaire which contained questions on socio-demographic profile, internet usage and awareness about Digital India. Bivariate analysis was done to determine the association between various socio-demographic variables associated with internet usage for health information.
In the present study, 88.2% (283/321) were using the internet for health information through digital media. This study found out that younger age group (18-30 years), literate and higher socioeconomic group (upper middle and above) population were more likely to access health information via digital media which was found out to be statistically significant.
Access to health information through digitization can improve health literacy among the population and help in promoting a preventive aspect to health problems and disease. They can be the building blocks to build "Swasth Bharat (Healthy India)".
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