Population Of Breast Cancer Patients Research Articles

The Association Between Meningioma and Breast Cancer

A potential relationship between meningioma and breast cancer was suggested 70 years ago. However, to date, no conclusive evidence is available on this topic. To provide a comprehensive review of the literature on the association of meningioma with breast cancer, supported by a meta-analysis. A systematic PubMed search was performed up to April 2023 to identify articles on the association of meningioma with breast cancer. The following key words were used strategically: meningioma, breast cancer, breast carcinoma, association, relation. All studies reporting women diagnosed with meningioma and breast cancer were identified. The search strategy was not limited by study design or publication date but only included articles in English. Additional articles were identified via citation searching. Studies reporting a complete population of meningiomas or breast cancer patients throughout a specific study period and a proportion of patients with a second pathology could be used for the meta-analysis. Data extraction was performed by 2 authors in accordance with the Preferred Reporting Items for Systematic Reviews (PRISMA) statement. Meta-analyses regarding both populations were performed using a random-effects model. Risk of bias was assessed. The main measures were whether there was an increased prevalence of breast cancer in female patients with meningioma and whether there was an increased prevalence of meningioma in female patients with breast cancer. A total of 51 retrospective studies (case reports, case series, and cancer registry reports) describing 2238 patients with both diseases were identified; 18 studies qualified for prevalence analyses and meta-analysis. The random-effects meta-analysis (13 studies) revealed a significantly greater prevalence of breast cancer in female patients with meningioma than in the overall population (odds ratio [OR], 9.87; 95% CI, 7.31-13.32). Meningioma incidence in patients with breast cancer (11 studies) was greater than that in the baseline population; however, the difference according to the random-effects model was not statistically significant (OR, 1.41; 95% CI, 0.99-2.02). This large systematic review and the meta-analysis on the association between meningioma and breast cancer found nearly 10-fold higher odds of breast cancer in female patients with meningioma compared with the general female population. These findings suggest that female patients with meningioma should be screened more intensively for breast cancer. Further research is required to identify the factors causing this association.

Using SMS technology to improve quality of life and symptom management in the breast cancer patient population: A feasibility study.

e13619 Background: Cancer patients experience a wide range of negative side effects/symptoms from chemotherapy and radiation including pain, dehydration, nausea/vomiting, and diarrhea/constipation. Symptoms are distressing and decrease the overall quality of life and increase unnecessary hospitalizations and emergency visits. Symptom management and quality of life may be improved by using Short Message System (SMS) texting in cardiac and diabetic patient populations. The technology may also decrease costs for unnecessary emergency department (ED) visits by breast cancer patients. The purpose of this study was to determine if an SMS texting service can improve quality of life by improving symptom management. A secondary purpose was to evaluate if texting decreases emergency visits by breast cancer patients. Methods: This IRB-approved, consented study implemented an SMS texting program for breast cancer patients. Participants received two texts per day during their chemotherapy treatment period (6 months), one text being informational regarding symptom management and the second was one of encouragement and inspiration. Participants were called bi-weekly to complete the Distress Thermometer for Patients (NCCN). ED visits and/or hospital admission rates for the sample were collected. An exit interview measured satisfaction with the program in quantitative measures and theme analysis for qualitative measures. Twenty patients participated in this study, with 13 included in the data analysis. Results: SMS texting provided a change in treatment for symptom management in 40% of patients. Overall satisfaction with the SMS program was at the 89th percentile. Almost all participants felt supported and cared for due to bi-weekly calls by the investigators. Only 10% of the participants visited the emergency department, which is lower than historical averages. Data concerning the distress thermometer proved to be non-informative. Conclusions: SMS texting is feasible and easily integrated into the care of breast cancer patients. Texting technology may provide engagement with the care team leading to changes and improvement in symptom management during chemotherapy treatment. Further study of texting technology providing interactive abilities for patient-reported outcomes is warranted.

Factors associated with oncotype and recurrence among a diverse breast cancer population seeking care at an urban safety-net hospital.

e12537 Background: The landmark trials, TAILORx and RxPONDER have established Oncotype DX (ODX) as a prognostic and predictive tool in the management of estrogen receptor positive (ER+), early-stage breast cancer. However, recent studies have revealed existing racial disparities in the ODX test. These findings call into question whether ODX is generalizable to diverse populations. We evaluated the prognostic value of ODX RS at an urban, academic safety net hospital. Methods: We conducted a single-institution retrospective study of patients diagnosed with invasive breast cancer and had an ODX test performed between January 1, 2010 to December 31, 2021. Demographic, tumor and treatment characteristics were obtained. Chi-square and ANOVA were used to examine associated factors among recurrences and non-recurrences. Results: We identified 315 patients diagnosed with ER+ breast cancer with an ODX test obtained. Racial breakdown was 47% White, 35% Black and 18% Other. 69% of the patients had public or no insurance. 20% of the patients had a low RS (0-10), 62% had intermediate (11-25) and 18% were high (26-100). 264 patients had no evidence of recurrence, 15 patients had a local or distant recurrence and 36 were unknown. Recurrence was significantly associated with younger age (p = 0.04), higher histologic grade (P < 0.001, < 0.001), intermediate oncotype score (p = 0.002) and no receipt of chemotherapy (p = 0.014). Focused analysis of the recurrence cohort demonstrates a significant proportion with an Intermediate ODX RS classification (93.3%, P = 0.001). 53% had distant recurrence, 20% had received adjuvant chemotherapy and 93.3% were adherent to hormonal therapy. Conclusions: In a diverse patient population, recurrences were significantly more likely among younger patients with high grade tumors, intermediate RS and those who did not receive chemotherapy. Further investigation and understanding whether Oncotype DX is generalizable to diverse breast cancer patient populations is needed.

An epigenome-wide analysis of socioeconomic position and tumor DNA methylation in breast cancer patients

BackgroundDisadvantaged socioeconomic position (SEP), including lower educational attainment and household income, may influence cancer risk and outcomes. We hypothesized that DNA methylation could function as an intermediary epigenetic mechanism that internalizes and reflects the biological impact of SEP.MethodsBased on tumor DNA methylation data from the Illumina 450 K array from 694 breast cancer patients in the Women’s Circle of Health Study, we conducted an epigenome-wide analysis in relation to educational attainment and household income. Functional impact of the identified CpG sites was explored in silico using data from publicly available databases.ResultsWe identified 25 CpG sites associated with household income at an array-wide significance level, but none with educational attainment. Two of the top CpG sites, cg00452016 and cg01667837, were in promoter regions of NNT and GPR37, respectively, with multiple epigenetic regulatory features identified in each region. NNT is involved in β-adrenergic stress signaling and inflammatory responses, whereas GPR37 is involved in neurological and immune responses. For both loci, gene expression was inversely correlated to the levels of DNA methylation. The associations were consistent between Black and White women and did not differ by tumor estrogen receptor (ER) status.ConclusionsIn a large breast cancer patient population, we discovered evidence of the significant biological impact of household income on the tumor DNA methylome, including genes in the β-adrenergic stress and immune response pathways. Our findings support biological effects of socioeconomic status on tumor tissues, which might be relevant to cancer development and progression.

Breast Cancer and Obesity: a Qualitative Analysis of a Diverse Population of Breast Cancer Patients' Perspectives on Weight Management.

Obesity and weight gain in breast cancer survivors leads to a greater risk of recurrence and a decreased chance of survival. A paucity of data exists regarding strengths, weaknesses, and barriers for implementing culturally sensitive, patient-centered interventions for weight management among minority communities. The objective of this study was to evaluate breast cancer patients' experience and perspectives regarding weight management in a racially diverse population. Semi-structured qualitative interviews were conducted with breast cancer patients with a body mass index ≥ 25kg/m2 regarding their experience with weight management. Interviews were transcribed verbatim, and a thematic analysis was conducted. Participants (n = 17) most commonly self-identified as non-Hispanic Black (70.6%). Nearly all participants felt comfortable being approached about weight management, yet less than half (41.2%) reported that they knew about the link between breast cancer and body weight prior to the interview. Four themes emerged: (1) lack of knowledge regarding the link between body weight and breast cancer risk, (2) barriers to weight management including family stressors, high cost, mental health issues, and chronic medical conditions, (3) previous attempts at weight loss including bariatric surgery, and (4) best practices for approaching weight management including discussion of weight management prior to survivorship. There is a need for a multidisciplinary, patient-centered weight management program for minority breast cancer patients that improves awareness of the link between weight and breast cancer risk. Weight management should be introduced early on as an element of the treatment plan for breast cancer.

P016 Patient Characteristics, Treatment and Long-term Outcomes from a Real-World Population of Early Breast Cancer Patients at High risk of Recurrence in Scotland

P016 Patient Characteristics, Treatment and Long-term Outcomes from a Real-World Population of Early Breast Cancer Patients at High risk of Recurrence in Scotland

Abstract P5-03-12: DNA repair genes are more frequently mutated in non-white populations of metastatic breast cancer (MBC) patients

Abstract Background: Although improvements in detection, therapeutic development and molecular profiling have decreased MBC mortality over the last twenty years, clinical outcomes are not being equally realized among all patients. Representation and enrollment into clinical trials are often not reflective of the general MBC population in terms of race and ethnicity, with Black and Hispanic patients being largely and often underrepresented. Not only does this imbalance translate into overall access to novel agents, but the lack of understanding of therapeutic efficacy in minority populations and tumor-based molecular differences reduce the use of truly personalized treatments for these groups. There is an opportunity to improve clinical outcomes for all patients with MBC, starting with a better understanding of the degree of any potential differences in underlying tumor molecular biology between racial groups. Methods: We utilized data from two cohorts of patients whose tumors underwent molecular profiling to examine differences in the frequency of genetic mutations across racial groups with MBC. The first cohort included 856 MBCs whose genomic profiles were retrieved from the AACR Genomics Evidence Neoplasia Information Exchange (GENIE) publicly available database. The second cohort included a separate set of 91 patients with MBC from an ongoing precision medicine program sponsored by the Side-Out Foundation (SOF). While the GENIE data were collected at 19 large academic cancer centers, the SOF data are derived from patients treated in the community setting. We compared the relative distributions of age and reported ethnicity between datasets, and compared the 20 most frequently mutated genes in each racial group across datasets. The analysis across races included 73 genes that were examined for differences in mutation frequency using Fisher’s Exact test and Pearson Chi-Square test (p< 0.05 uncorrected). Results: Although the GENIE set was significantly larger, race distribution was not statistically significant across the two populations. The combined populations included 831 white patients (88.4%), 43 Black patients (4.6%), 30 Asian patients (3.2%), and 35 Hispanic patients (3.7%). The age of initial (59.61) and metastatic (61.19) diagnosis was older in the SOF population compared to the GENIE population (48.81, 53.14; p < 0.001). Hispanic patients (46.92) were diagnosed with MBC at a younger age compared to White patients (53.78; p < 0.001). Of the 73 genes analyzed, 11 genes were found less frequently mutated in whites compared to non-whites including, NTRK1, SDHA, MSH6, TCF3, FANCC, GNAS, COP1, RECQL4, WRN, BCL6, and U2AF1. When the same 73 genes were examined for differences across racial groups, alterations of 22 genes reached statistical significance. The gene(s) with the largest difference compared to white patients were RECQL4 in black patients (13.95% vs 5.29%; p = 0.019), WRN in Asian patients (16.63% vs 2.53%; p < 0.001), and RECQL4 and ERBB2 in Hispanic patients (16.13% vs 5.29%; p = 0.019, p = 0.020). Of the 22 genes that were more frequently altered in the non-white population, 6 have roles in DNA repair including RECQL4, WRN, ERCC2, BLM, MSH6, FANCC. 4/22 are receptor tyrosine kinases (RTKs), including NTRK2, RET, ERBB3, and ERBB2, and 3/22 have roles in immune function, including BCL6, CIITA, and TLR4. Conclusion: Analysis of genomic alterations derived from 2 independent real-world molecular profiling-based cohorts identified in non-whites MBC patients a set of candidate “actionable” genes involved in DNA damage repair, RTK expression, and immune function. Although these results require further validation, considering the relatively small samples sizes of the non-white populations, these findings may provide actionable targets for non-white patients with MBC that could be utilized in future trials. Citation Format: Sydney Hilley, Rick Dunetz, Edik Blais, Mariaelena Pierobon, Emanuel F. Petricoin, Elisa Baldelli. DNA repair genes are more frequently mutated in non-white populations of metastatic breast cancer (MBC) patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-03-12.

Abstract P6-05-27: FEASIBILITY, SAFETY AND EFFICACY OF A COMBINED SUPERVISED PHYSICAL EXERCISE AND NUTRITIONAL PROGRAM IN A SELECTED POPULATION OF LUMINAL METASTATIC BREAST CANCER PATIENTS: ONCARE-01 PILOT STUDY

Abstract Background: Supervised exercise programs (SEP) have demonstrated an improvement in quality of life (QoL), cardiovascular health, treatment tolerance and disease outcomes in early breast cancer patients. In metastatic breast cancer (MBC), previous data suggest SEP are safe but no impact on QoL and a low adherence to programs were shown. These studies included a heterogenous population in terms of type of treatments received, numbers of previous lines or comorbidities. From our perspective, MBC profile that could benefit most from SEP needs to be explored. Thus, we conducted a pilot study to assess adherence, safety and impact on QoL of a combined SEP and nutritional program (NP) in a selected population of MBC of patients treated with cyclin-dependent kinase 4/6 inhibitors (iCDK 4/6). Methods: This is a prospective, single center, single arm pilot study. SEP consisted in a 12-week intervention with twice a week in-person resistance exercise session. Patients also completed weekly aerobic exercise goals in self-managed sessions monitored with activity trackers. SEP was conducted by registered Physical Activity and Sports Science instructors that followed American College of Sports Medicine guidelines. In addition, participants had an initial nutritional assessment and personalized counselling by a qualified nutritionist. Adherence to treatment, biological variables and QoL assessments (FACIT-Fatigue and QLQ-C30 questionnaires) were collected at baseline (B) and week-12 (w12). Primary endpoint was global adherence (≥70% of attended sessions relative to scheduled sessions). Secondary endpoints included safety, changes in biological variables and QoL. Paired samples t-tests (Wilcoxon) were used to assess biological changes and QoL. Results: Patients (n=26) were recruited from October 2020 to November 2021. Median age was 47,5 years (45-55); 84,6% of patients were ECOG 0. 42,3% of patients were receiving Abemaciclib; 34,6% Ribociclib and 23,1% Palbociclib in first (73,1%) or second (26,9%) line treatment. Patients had bone (69,2%); visceral metastasis (57,7%) or both (30,8%). 2 patients did not start the intervention and additional 7 patients discontinued the program prematurely, the majority of them due to COVID-related concerns. Considering all patients who at least attended one session, global adherence was 66% (39-77,5%) and 45,8% of patients achieved an adherence of ≥ 70%. Patients reported an improvement in QoL [B global QLQ-C30 66,6 (50-75), w12 75 (66,6-83,3); p 0,0121] and fatigue [B FACIT-Fatigue 37 (30-44), w12 42 (38-48); p 0,0017]. Sit-to-stand repetitions in 30-second period also improved [(B 15 (12-17), 19 (15-23); p 0,0002]. Same benefits were seen in patients with adherence ≥ 70%. No statistically significant changes were seen in body fat or muscular composition and handgrip scores. Importantly, no safety issues related to study intervention were reported. Conclusions: Even though the study was conducted during COVID-19 pandemic, global adherence was 66%. For the first time in MBC, SEP and NP combined program demonstrated to be safe and improved QoL in patients with first or second line MBC treated with iCDK4/6. Further research is needed to identify strategies that improve QoL in MBC. Citation Format: Alfonso Cortés, Alejandro Riquelme, Gemma Ferrero, Federico Longo, Manuel Garví, Lisandro Lamas, Ángela Morales, Lidia García, Patricia Cortez-Castedo, Maria Gión, Cristina Saavedra, Noelia Martínez-Jáñez, María Fernández-Abad. FEASIBILITY, SAFETY AND EFFICACY OF A COMBINED SUPERVISED PHYSICAL EXERCISE AND NUTRITIONAL PROGRAM IN A SELECTED POPULATION OF LUMINAL METASTATIC BREAST CANCER PATIENTS: ONCARE-01 PILOT STUDY [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-05-27.

Abstract P6-05-03: Post-Mastectomy Implant Complications in a Hispanic Breast Cancer Patient Population

Abstract Introduction: Breast cancer is the most common cancer diagnosed in women in the United States with primary treatment consisting of a combination of surgery, systemic therapy, and radiation. Breast reconstruction has been shown to improve quality of life in women and utilization is increasing with time. There is a large amount of evidence demonstrating the complications of radiation therapy on implant-based breast reconstruction including but not limited to, capsular contracture, infection, and reoperation. However, the majority of these studies have examined populations consisting primarily of non-Hispanic white patients with breast cancer. In general, hispanic populations are not well represented in research studies or Phase II/III clinical trials. Therefore, the goal of this study was to analyze the impact of radiation therapy on post mastectomy implant-based breast reconstruction complications in self-identified Hispanic patients. Methods: We retrospectively reviewed patients who underwent mastectomy with implant reconstruction between January 1, 2017 and December 1, 2019. The inclusion criteria included female patients 18 years or older who self-reported as Hispanic or Latino. Exclusion criterias included patients who did not undergo mastectomy, did not undergo tissue-expander or implant reconstruction, or did not self identify as Hispanic descent. Outcomes infection needing antibiotics, capsular contracture Baker grade II-IV, and implant loss. Statistical analysis was performed using Chi-squared analysis. Results: A total of 258 patients of Hispanic or Latino women were included in the study. This included 343 total number of breasts, with 228 breasts that underwent mastectomy with reconstruction due to breast cancer and 115 breasts that underwent prophylactic mastectomy with reconstruction. The median age at time of initial mastectomy was 49 years (range 19-86). 46 total breasts received adjuvant postoperative radiation and 296 breasts did not receive radiation. Median radiation dose to the chest wall was 50 Gy (range 42.56 - 60) in 2Gy (range 1.8 - 2.66) fractions. All patients who received postoperative radiation had at least 1 complication. The rate of complications and comparison between radiated breast compared to non-radiated breasts is demonstrated in table 1. Conclusion: The goal of this study was to analyze the impact of radiation therapy complications on post-mastectomy implant-based breast reconstruction surgeries in patients of Hispanic descent. We demonstrate that the rate of capsular contracture is significantly higher after radiation therapy and the rate of overall complication after radiation therapy is higher (even though non statistically significant) compared with patients who do not undergo radiation. While these results are comparable to similar studies done in non-Hispanic groups, this is the first study to our knowledge that has looked at post-mastectomy complications focusing specifically on a Hispanic population. Mastectomy and subsequent implant reconstruction, radiation, and complications can have negative psychological effects on patients and can manifest differently with varying cultural backgrounds. It is imperative to understand the complications associated with race to better allow practitioners to cater treatment and support for a diverse patient population with breast cancer. Table 1. Complications. Citation Format: Brianna Conte, Caroline Shermoen, Danielle Cerbon, Susan Kesmodel, Caroline Fiser, sophia liu, Cristiane Takita, Jessica Meshman, John Oeltjen, Lora Wang. Post-Mastectomy Implant Complications in a Hispanic Breast Cancer Patient Population [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-05-03.

Abstract P6-05-34: Depression and Psychological Distress in Breast Cancer Patients

Abstract Introduction: Patients with breast cancer are at increased risk for depression and suicide compared to the general population. Breast cancer is unique among other cancers in that some treatments aim to decrease levels of estrogen, a hormone that is intricately linked to mood regulation. The trauma of diagnosis, invasive treatments, and hormone dysregulation all possibly contribute to poor mental health outcomes. Understanding risk factors associated with depression and distress are important for timely interventions. Methods: We performed a retrospective chart review of breast cancer patients seen at Froedtert & MCW Cancer Center Breast Care Clinic between 2019 and 2020. The present study had two aims. The primary aim was to identify breast cancer patient populations at increased risk of depression and psychological distress. Patient populations were distinguished by tumor pathology, patient demographics, and types of treatment interventions. The secondary aim was to identify demographic and clinical variables associated with changes in self-reported distress and depression. Univariate and multivariate analysis of demographic and clinical variables was performed in relation to Patient Health Questionnaire (PHQ) and The National Comprehensive Cancer Network (NCCN) Distress Thermometer scores. Results: Data from 197 patients was analyzed. Patients with a history of depression scored significantly higher on distress screening (mean= 4.4  3.0, p=0.004) versus patients without psychiatric history (mean 2.8  2.9). Patients under 50 years old reported higher levels of distress than patients over 70 years old (p=0.031, beta= -1.0). Self-reported distress declined significantly with increased time from initial diagnosis (p=0.043; p=0.006 at 2 years). Distress was significantly higher prior to initiation of radiation versus during and immediately following therapy (p=0.028). A history of depression, younger age, passage of time, and temporal relationship to radiation treatment were not associated with significant differences in self-reported depression on multivariate analysis. Distress and depression screening scores were not significantly impacted by surgery or chemotherapy (p=0.5; p=0.11 respectively). Conclusion: Patients with a known history of depression and age less than 50 reported significantly higher levels of distress but not depression associated with diagnosis of breast cancer. Distress exhibited a greater downward trend than depression following initiation of oncologic intervention. The results of this study indicate that breast cancer patients are susceptible to significant fluctuations in psychological distress. In contrast, clinically relevant depression screening scores were less frequent and less subject to deviation. Table 1. Multivariate analysis. Citation Format: Kelly R. Cotchett, Adam H. Kelly, Aniko Szabo, Yee Chung Cheng, Sailaja Kamaraju, Christopher Chitambar, Lyndsey Wallace, Lubna N. Chaudhary, John Burfeind. Depression and Psychological Distress in Breast Cancer Patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-05-34.

Reference values of EORTC QLQ-C30, EORTC QLQ-BR23, and EQ-5D-5L for women with non-metastatic breast cancer at diagnosis and 2 years after

PurposeTo obtain reference norms of EORTC QLQ-C30, EORTC QLQ-BR23, and EQ-5D-5L, based on a population of Spanish non-metastatic breast cancer patients at diagnosis and 2 years after, according to relevant demographic and clinical characteristics.MethodsMulticentric prospective cohort study including consecutive women aged ≥ 18 years with a diagnosis of incident non-metastatic breast cancer from April 2013 to May 2015. Health-related quality of life (HRQoL) questionnaires were administered between diagnosis and beginning the therapy, and 2 years after. HRQoL differences according to age, comorbidity and stage were tested with ANOVA or Chi Square test and multivariate linear regression models.Results1276 patients were included, with a mean age of 58 years. Multivariate models of EORTC QLQ-C30 summary score and EQ-5D-5L index at diagnosis and at 2-year follow-up show the independent association of comorbidity and tumor stage with HRQoL. The standardized multivariate regression coefficient of EORTC QLQ-C30 summary score was lower (poorer HRQoL) for women with stage II and III than for those with stage 0 at diagnosis (− 0.11 and − 0.07, p < 0.05) and follow-up (− 0.15 and − 0.10, p < 0.01). The EQ-5D-5L index indicated poorer HRQoL for women with Charlson comorbidity index ≥ 2 than comorbidity 0 both at diagnosis (− 0.13, p < 0.001) and follow-up (− 0.18, p < 0.001). Therefore, we provided the reference norms at diagnosis and at the 2-year follow-up, stratified by age, comorbidity index, and tumor stage.ConclusionThese HRQoL reference norms can be useful to interpret the scores of women with non-metastatic breast cancer, comparing them with country-specific reference values for this population.

Inherited Cancer Knowledge Among Black Females with Breast Cancer Before and After Viewing a Web-Based Educational Video.

Purpose: Scalable solutions are needed to make pre-test genetic education about inherited cancer risk accessible across diverse and underserved populations. We evaluated an automated strategy to deliver genetic education through a web-based video among young Black females with breast cancer. Methods: 96 participants were recruited through state cancer registries in Florida and Tennesee. All participants viewed a 12 min video and completed a ten question quiz on inherited cancer knowledge before and after viewing the video. Median pre- and postvideo knowledge scores were categorized as <60% versus ≥60% and compared across demographic and clinical characteristics using binary logistic regression. Results: Of the 96 participants, mean age was 51, over 50% had income <$50 K, over 40% did not graduate college or have private insurance, and over 70% had previous genetic testing. Median knowledge scores significantly increased after viewing the video (p < 001), with no significant differences in those with or without prior testing. A higher post-video knowledge score was associated with an income ≥$50 K, a college degree, and private insurance (all p < .05). Conclusion: Among a population of young Black breast cancer patients, the educational video significantly increased knowledge. Findings support the use of automated pre-test educational tools as a scalable solution to make these services more accessible across populations.

The impact of adverse drug reactions on medication adherence and outpatient treatment outcomes in female breast cancer: A review protocol.

Discover the impact of adverse drug reactions of hormonal and chemotherapy on medication adherence and outpatient treatment outcomes in the breast cancer patient population. A systematic review following the reporting guidance from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) guided by the Joanna Briggs Institute methodology will be conducted. A literature search will be conducted using the following databases: PubMed, CINAHL, Web of Science, Medline and Scopus. Studies published in English before 2022 that report adverse drug reactions with medication adherence and outpatient treatment outcomes as primary outcome measures, following the initiation of one or more oral hormonal, endocrine and chemotherapy agents in female patients with diagnoses of breast cancer will be identified. Observational studies will be included for review, and two reviewers will independently screen study titles, abstracts and full text for inclusion. The quality assessment will be conducted using the Joanna Briggs Institute tools. A meta-analysis will be conducted where sufficient data are available. This is a systematic review study protocol, and results are not available at the time of the submission. All results will be reported on the completion of this study. This systematic review will highlight the impact of medication non-adherence on the breast cancer patient population, support determining strategies to address this issue and identify areas for further research. This protocol article will identify the impact of adverse drug reactions on medication non-adherence and treatment outcomes in the female breast cancer patient population. A unique contribution of our study is to support determining strategies to address this ongoing public health issue and identify areas for further research. This protocol has been registered with the International Prospective Register of Systematic Reviews (PROSPERO) database (registration number CRD 42021291364).

Novel 2,6,9-Trisubstituted Purines as Potent CDK Inhibitors Alleviating Trastuzumab-Resistance of HER2-Positive Breast Cancers.

HER2-positive (HER2+) breast cancer is defined by HER2 oncogene amplification on chromosome 17q12 and accounts for 15–20% population of breast-cancer patients. Therapeutic anti-HER2 antibody such as trastuzumab is used as the first-line therapy for HER2-positive breast cancers. However, more than 50% of the patients respond poorly to trastuzumab, illustrating that novel therapy is warranted to overcome the resistance. We previously reported that in the majority of HER2+ breast-cancer patients, CDK12 is co-amplified on 17q12 and involved in developing tumors and trastuzumab resistance, proposing CDK12 as a potential drug target for HER2+ breast cancers. Here, we designed and synthesized novel 2,6,9-trisubstituted purines as potent CDK12 inhibitors showing strong, equipotent antiproliferative activity against trastuzumab-sensitive HER2+ SK-Br3 cells and trastuzumab-resistant HER2+ HCC1954 cells (GI50 values < 50 nM) both of which express a high level of CDK12. Two potent analogue 30d and 30e at 40, 200 nM greatly downregulated the levels of cyclinK and Pol II p-CTD (Ser2), as well as the expression of CDK12 downstream genes (IRS1 and WNT1) in a dose-dependent manner. We also observed structure-property relationship for a subset of potent analogues, and found that 30e is highly stable in liver microsomes with lack of CYP inhibition. In addition, 30d exhibited a synergy with trastuzumab in the both cells, suggesting that our inhibitors could be applied to alleviate trastuzumab-resistance of HER2+ breast cancers and escalate the efficacy of trastuzumab as well. Our study may provide insight into developing a novel therapy for HER2+ breast cancers.

PI3K/AKT/mTOR-Targeted Therapy for Breast Cancer.

Phosphatidylinositol 3-kinase (PI3K), protein kinase B (PKB/AKT) and mechanistic target of rapamycin (mTOR) (PAM) pathways play important roles in breast tumorigenesis and confer worse prognosis in breast cancer patients. The inhibitors targeting three key nodes of these pathways, PI3K, AKT and mTOR, are continuously developed. For breast cancer patients to truly benefit from PAM pathway inhibitors, it is necessary to clarify the frequency and mechanism of abnormal alterations in the PAM pathway in different breast cancer subtypes, and further explore reliable biomarkers to identify the appropriate population for precision therapy. Some PI3K and mTOR inhibitors have been approved by regulatory authorities for the treatment of specific breast cancer patient populations, and many new-generation PI3K/mTOR inhibitors and AKT isoform inhibitors have also been shown to have good prospects for cancer therapy. This review summarizes the changes in the PAM signaling pathway in different subtypes of breast cancer, and the latest research progress about the biomarkers and clinical application of PAM-targeted inhibitors.

Final results of a phase 1 evaluation of niraparib and everolimus in advanced ovarian and metastatic breast cancer (303)

Objectives: To evaluate the safety and efficacy of the combination of niraparib and everolimus in a heavily pretreated PARP naïve population of advanced ovarian and metastatic breast cancer patients. Methods: An open-label, Phase I cohort study with a standard 3+3 design with four planned cohorts. All patients were PARP naïve. The planned schema was as follows: · Cohort 1 – Niraparib 100mg daily and everolimus 5mg MWF · Cohort 2 – Niraparib 200mg daily and everolimus 5mg MWF · Cohort 3 – Niraparib 200mg daily and everolimus 1mg daily · Cohort 4 – Niraparib 200mg daily and everolimus 5mg daily After two DLTs were experienced in cohort 2, four additional patients were enrolled at cohort 1 dose levels to confirm the safety of the combination at this dose and schedule. Results: Fourteen patients were enrolled in this study, and the safety evaluation has been completed. Three patients were not evaluable due to not completing the first cycle of treatment; two patients experienced DLTs, and one patient had rapid disease progression during the first week of cycle 1. Twelve patients had high-grade serous ovarian cancer, one patient had clear cell ovarian cancer, and one patient had breast cancer. Two dose-limiting toxicities (thrombocytopenia and hypertension) occurred in cohort 2. Of the 11 evaluable patients who received at least one complete cycle of treatment, the response rate was 18%, and the clinical benefit rate was 45%. One patient achieved a PR, and three patients had stable disease. The median progression-free survival for patients deriving clinical benefit was six months. There were 154 attributed adverse events; of these, 17 were grade 3 or grade 4 events (11%). The most common toxicities requiring intervention were thrombocytopenia (9.7%), hypertension (7.1%), nausea (4.6%), and stomatitis (3.9%). No new toxicities with this combination were evident. All patients had comprehensive molecular profiling prior to enrollment. Patient-reported outcomes were collected using the Treatment-Related Symptom Checklist (TRSC) and HRQOL-LASA and will be presented separately. Conclusions: The combination of niraparib and everolimus appears to provide some support for efficacy at the lowest doses. However, based on the DLTs experienced in cohort 2, the treatment proved to be too toxic to explore further at higher doses than niraparib 100mg daily and everolimus 5mg MWF. Objectives: To evaluate the safety and efficacy of the combination of niraparib and everolimus in a heavily pretreated PARP naïve population of advanced ovarian and metastatic breast cancer patients. Methods: An open-label, Phase I cohort study with a standard 3+3 design with four planned cohorts. All patients were PARP naïve. The planned schema was as follows: · Cohort 1 – Niraparib 100mg daily and everolimus 5mg MWF · Cohort 2 – Niraparib 200mg daily and everolimus 5mg MWF · Cohort 3 – Niraparib 200mg daily and everolimus 1mg daily · Cohort 4 – Niraparib 200mg daily and everolimus 5mg daily After two DLTs were experienced in cohort 2, four additional patients were enrolled at cohort 1 dose levels to confirm the safety of the combination at this dose and schedule. Results: Fourteen patients were enrolled in this study, and the safety evaluation has been completed. Three patients were not evaluable due to not completing the first cycle of treatment; two patients experienced DLTs, and one patient had rapid disease progression during the first week of cycle 1. Twelve patients had high-grade serous ovarian cancer, one patient had clear cell ovarian cancer, and one patient had breast cancer. Two dose-limiting toxicities (thrombocytopenia and hypertension) occurred in cohort 2. Of the 11 evaluable patients who received at least one complete cycle of treatment, the response rate was 18%, and the clinical benefit rate was 45%. One patient achieved a PR, and three patients had stable disease. The median progression-free survival for patients deriving clinical benefit was six months. There were 154 attributed adverse events; of these, 17 were grade 3 or grade 4 events (11%). The most common toxicities requiring intervention were thrombocytopenia (9.7%), hypertension (7.1%), nausea (4.6%), and stomatitis (3.9%). No new toxicities with this combination were evident. All patients had comprehensive molecular profiling prior to enrollment. Patient-reported outcomes were collected using the Treatment-Related Symptom Checklist (TRSC) and HRQOL-LASA and will be presented separately. Conclusions: The combination of niraparib and everolimus appears to provide some support for efficacy at the lowest doses. However, based on the DLTs experienced in cohort 2, the treatment proved to be too toxic to explore further at higher doses than niraparib 100mg daily and everolimus 5mg MWF.

Targeting Cell Cycle Progression in HER2+ Breast Cancer: An Emerging Treatment Opportunity.

Layman summaryHER2 is an oncogenic driver in a subset of breast cancer. Despite the fact that there are the options of several anti-HER2 targeted therapies, most patients with metastatic HER2+ breast cancer die from the disease. Therapies to overcome treatment resistance in the metastatic settings (including brain metastasis) are actively being pursued. Recently, cell cycle inhibitors (CDK 4/6 inhibitors) have been approved to manage hormone receptor-positive breast cancer, and have encountered tremendous success. The cell cycle signaling proteins, Cyclin D-CDK4/6, are downstream of HER2 and play a key role in cellular proliferation. Moreover, cell cycle inhibitors have the capacity to cross the blood–brain barrier. Here, we review the published literature with regard to the rationale for CDK4/6-directed therapies in HER2+ breast cancer.The development of HER2-targeted therapies has dramatically improved patient survival and patient management and increased the quality of life in the HER2+ breast cancer patient population. Due to the activation of compensatory pathways, patients eventually suffer from resistance to HER2-directed therapies and develop a more aggressive disease phenotype. One of these mechanisms is the crosstalk between ER and HER2 signaling, especially the CDK4/6-Cyclin D-Rb signaling axis that is commonly active and has received attention for its potential role in regulating tumor progression. CDK 4/6 inhibitors interfere with the binding of cell-cycle-dependent kinases (CDKs) with their cognate partner cyclins, and forestall the progression of the cell cycle by preventing Rb phosphorylation and E2F release that consequentially leads to cancer cell senescence. CDK 4/6 inhibitors, namely, palbociclib, ribociclib, and abemaciclib, in combination with anti-estrogen therapies, have shown impressive outcomes in hormonal receptor-positive (HR+) disease and have received approval for this disease context. As an extension of this concept, preclinical/clinical studies incorporating CDK 4/6 inhibitors with HER2-targeted drugs have been evaluated and have shown potency in limiting tumor progression, restoring therapeutic sensitivity, and may improving the management of the disease. Currently, several clinical trials are examining the synergistic effects of CDK 4/6 inhibitors with optimized HER2-directed therapies for the (ER+/-) HER2+ population in the metastatic setting. In this review, we aim to interrogate the burden of HER2+ disease in light of recent treatment progress in the field and examine the clinical benefit of CDK 4/6 inhibitors as a replacement for traditional chemotherapy to improve outcomes in HER2+ breast cancer.

Tamoxifen use and potential effects on liver parenchyma: A long‐term prospective transient elastographic evaluation

Tamoxifen is a commonly prescribed drug in both early and metastatic breast cancer. Prospective studies in Asian populations demonstrated that tamoxifen‐related liver steatosis occurred in more than 30% of the patients within 2 years after start of treatment. No well‐designed prospective studies on potential tamoxifen‐related liver steatosis have been conducted in Caucasian patients so far. Therefore, our prospective study aimed to assess the incidence of tamoxifen‐related liver steatosis for a period of 2 years in a population of Caucasian breast cancer patients treated with tamoxifen. Patients with an indication for adjuvant treatment with tamoxifen were included in this study. Data were collected at 3 months (T1) and at 2 years (T2) after start of tamoxifen treatment (follow‐up period of 21 months). For the quantification of liver steatosis, patients underwent liver stiffness measurement by transient elastography with simultaneous controlled attenuation parameter (CAP) determination using the FibroScan. A total of 95 Caucasian breast cancer patients were included in this evaluation. Liver steatosis was observed in 46 of 95 (48%) and 48 of 95 (51%) of the patients at T1 and T2, respectively. No clinically relevant increase in liver steatosis was observed during the treatment period of 2 years with tamoxifen (median CAP = 243 ± 49 dB/m (T1) and 253 ± 55 dB/m (T2), respectively; p = 0.038). Conclusion: In this prospective longitudinal study in Caucasian breast cancer patients, no clinically relevant alterations in liver steatosis in terms of CAP values and liver/lipid parameters were observed after 2 years of tamoxifen treatment. This study therefore demonstrates an absence of tamoxifen‐related adverse events such as steatosis and (early) development of fibrosis or cirrhosis during a treatment period of at least 2 years.

Representativeness of trial participants: linking the EORTC boost-no boost trial to the Netherlands cancer registry

Background and ObjectivesTo evaluate the representativeness of Dutch patients participating in the European Organization for Research and Treatment of Cancer EORTC boost-no-boost trial to the target breast cancer patient population. MethodsAll female breast cancer patients diagnosed between 1989 and 1996, aged ≤70 years, treated with breast-conserving surgery and radiation therapy, were selected from the Netherlands Cancer Registry (NCR) and linked to the EORTC trial database. Baseline characteristics were compared between trial and non-trial participants, for the Dutch population and according to seven participating institutions. Kaplan-Meier curves and multivariable Cox regression were used to explore potential heterogeneity in overall survival between low, medium and high-volume institutes. ResultsOverall, 20,880 patients were identified from the NCR: 2,445 of 2,602 (94%) trial participants could be linked, and 18,435 were treated outside the trial. Trial participants had similar age, morphology, topography, laterality and socioeconomic status as non-trial participants, but more often stage I (62.7% vs. 56.4%) tumours and less often adjuvant treatment (22.9% vs. 26.5%). Crude 20-year survival ranged from 52.5% to 57.4%, without significant differences in multivariable analyses. ConclusionThis case study showed that participants in the boost-no-boost trial well represented the Dutch target population. Data linkage comes with challenges, but can close the gap between research and clinical practice.

Sexual Health Screening for Gynecologic and Breast Cancer Survivors: A Review and Critical Analysis of Validated Screening Tools.

IntroductionStudies have shown that the sexual health concerns of gynecologic and breast cancer survivors are not adequately being addressed by clinicians.AimTo provide a comprehensive narrative review of validated sexual health screening tools and aid clinicians in choosing a screening tool that will allow them to best address their patients' sexual health concernsMethodsA review of PubMed and Google Scholar databases was conducted, using search terms “sexual health”, “screening”, “tools”, “cancer”, and “survivors” to identify sexual health screening tools meeting the following inclusion criteria: 1) published in a peer-reviewed journal, 2) were written in English, 3) included breast and/or gynecological cancer patient population, 4) included self-reported measure of sexual health and function, and 5) underwent psychometric validation.Main Outcome MeasureCriteria used to evaluate identified screening tools included ability to assess desire, arousal, satisfaction, orgasm, dyspareunia, solo sexual expression, relationship with partner, body image, distress over changes in sexual function, and support systems. Pre and post- treatment comparisons, differentiation between lack of sexual desire and inability, heterosexual bias, diversity in patient population, and ease of scoring were also evaluated.ResultsBased upon the inclusion criteria, the following 10 sexual health screening tools were identified and reviewed: Female Sexual Function Index, European Organization for Research and Treatment of Cancer Quality of Life Questionnaires for both Cervical and Endometrial Cancer, Sexual Adjustment and Body Image Scale, Sexual Adjustment and Body Image Scale- Gynecologic Cancer, Sexual Function and Vaginal Changes Questionnaire, Gynaecologic Leiden Questionnaire, Information on Sexual Health: Your Needs after Cancer, Sexual Satisfaction Questionnaire, and Sexual Activity Questionnaire. Most tools assessed satisfaction (n=10), desire (n=9), and dyspareunia (n=8). Fewer addressed objective arousal (n=7), body image/femininity (n=7), partner relationship (n=7), orgasm (n=5), pre/post treatment considerations (n=5), distress (n=4), and solo-sexual expression (n=2). Heterosexual bias (n=3) and failure to differentiate between lack of desire and inability (n=2) were encountered.ConclusionUnderstanding the strengths and limitations of sexual health screening tools can help clinicians more effectively address cancer survivors' sexual health concerns, which is essential in providing comprehensive care and improving quality of life. Screening tools have room for improvement, such as eliminating heterosexual bias and including cancer and treatment-specific questions. Clinicians can use this guide to select the most appropriate screening tool for their patients and begin bridging the gap in sexual healthcare.Tounkel I, Nalubola S, Schulz A, et al. Sexual Health Screening for Gynecologic and Breast Cancer Survivors: A Review and Critical Analysis of Validated Screening Tools. Sex Med 2022;10:100498.