Breast Cancer In Population Research Articles

Low clinical utility of global longitudinal strain in a real-world breast cancer population

Abstract Background The 2022 European Society of Cardiology (ESC) Cardio-Oncology guidelines recommend the use of global longitudinal strain (GLS) to detect mild asymptomatic cancer therapy related cardiac dysfunction (ma-CTRCD). However, it remains unknown how to best manage these patients in order to prevent clinically significant CTRCD. Purpose To assess the course and outcomes of breast cancer patients meeting criteria for ma-CTRCD. Methods Echocardiograms and medical records were assessed for breast cancer patients receiving trastuzumab or an anthracycline, who underwent serial echocardiographic monitoring, including routine GLS. CTRCD was defined as an absolute decline in LVEF of >10% to <50%. ma-CTRCD was defined as a relative decline in average GLS of >15%, in the absence of significant LVEF decline. Normal was defined as no significant change in LVEF or GLS during cancer therapy. Clinical and echocardiographic course post ma-CTRCD detection was assessed. Baseline risk factors were compared between the three groups. Results 878 echocardiograms from 258 patients were analysed. GLS analysis was available in 76% of echocardiograms. CTRCD occurred in 23 (9%) and ma-CTRCD in 63 (24%). Only eight ma-CTRCD patients had management altered (cancer therapy withheld/ceased in three and heart failure medication commenced in six). Only two ma-CTRCD patients subsequently developed CTRCD, and GLS improved in 74%. Compared to the normal group (172, 67%), at baseline the ma-CTRCD group had higher average GLS (-21.8 vs -19.4, p<0.0001) and less borderline/abnormal average GLS (4% vs 36%, p<0.004). Conclusion Isolated declines in GLS are common and may have low clinical utility in preventing CTRCD. The findings support ESC guideline recommendations that cancer therapy should not be withheld in these patients. Those with higher baseline GLS may be more prone to clinically insignificant declines in GLS during cancer therapy.

Long term risk of heart failure in adult cancer survivors: a systematic review and meta-analysis

Abstract Background Evaluation of the cardiotoxic effects from cancer is most commonly evaluated at the time of chemotherapy. Although cancer survivorship populations are rapidly expanding, there is a paucity of evidence regarding the frequency and causes of heart failure (HF) >5 years after cardiotoxic therapy. Objectives This systematic review sought to investigate the relationship between cardiotoxic cancer therapies and late-onset HF. Methods We searched the EMBASE and MEDLINE databases for studies reporting HF in adult survivors (≥50 years old), who were ≥5 years post-breast/lymphoma cancer therapy. A random effects model was used to examine the associations of HF. A meta-regression analysis was implemented to determine causes of heterogeneity. Results Thirteen papers were included in the review and meta-analysis (Figure 1), comprising 190,259 participants (mean age 53.5 years, 93% female). The risk of HF was increased (overall log risk-ratio 0.39 (95%CI (0.16-0.62)), (Figure 2). Cardiotoxic treatment, compared with cancer alone, provided a similar risk (log risk ratio of 0.38 [95% CI 0.02-0.77]). In the breast cancer population ratio (11 studies) the overall heart failure log risk was 0.41 [95% CI 0.13-0.69]). Although heterogeneity was significant (I²=77.17), this was explained by differences in patient characteristics; once multivariable analysis accounted for follow up (0.99, 95%CI (0.97-0.99), p=0.047), age (1.14, 95%CI (1.04-1.25), p=0.003) and hypertension (0.95, 95%CI (0.92-0.98), p<0.001), residual heterogeneity was low (I²=28.73). Conclusions HF is increased in adult cancer survivors, associated with cardiotoxic cancer therapy and standard risk factors. Consideration should be given for selective screening for HF in this at-risk population.Fig 1:Literature Search Flow DiagramFig 2:Incident HF in Cancer Survivors

Strong association of single nucleotide polymorphisms in BRCA1, ATM, and CHEK2 with breast cancer susceptibility in a sub-population of Iranian women.

Breast cancer (BC) is the most prevalent malignancy in females worldwide. Mutations in the DNA repair pathway genes contribute to a significant increase in BC risk. The present study aimed to assess the frequency of polymorphisms in BRCA1, ATM, and CHEK2 genes and their association with BC susceptibility in the Kurdish population from the West of Iran. In the present case-control study, the distribution of single nucleotide polymorphisms (SNPs) in CHEK2 (rs17879961), ATM (rs28904921), and BRCA1 (rs80357906, rs1555576855, rs1555576858, and rs397509247) genes were investigated in 335 BC cases and 354 healthy-matched controls by Taqman allelic discrimination assay. The chi-square goodness-of-fit test was employed for the assessment of Hardy-Weinberg Equation. Relative risk and odds ratios were calculated based on the Koopman asymptotic score and the Baptista-Pike method, respectively. Also, the sensitivity and specificity of each polymorphism were assessed using the Wilson-Brown test and a P-value < 0.05 indicating significant differences between the two groups in all assessments. Data showed there was a strong association between rs397509247 (OR = 7.53, 95% CI 1.88-90.91, p = 0.004), rs1555576858 (OR = 10.53, 95% CI 0.01-0.51, p = 0.0005), and rs80357906 (OR = 6.33, 95% CI 0.05-0.043, p < 0.0001) in BRCA1 gene and rs17879961 (OR = 3.52, 95% CI 0.084-0.946, p = 0.02) in CHEK2 gene, with BC risk in the population of interest. Among these, rs28904921 in ATM gene demonstrated the strongest association (OR = 72.66, 95% CI 0.007-0.214, p < 0.0001). This suggests that these SNPs, particularly rs28904921, are significantly associated with an increased risk of BC in the studied population. Our results indicated that BRCA1, ATM, and CHEK2 polymorphisms have a high frequency in the Iranian breast cancer population, with some mutant allele frequencies being much higher than those reported in other populations. We have also provided a simple, multiplex, rapid, and accurate genotyping assay that is useful in clinical settings.

Effects of Mobile Application-Based Cognitive Behavioral Therapy on Psychological Outcomes in Women Treated for Breast Cancer: A Randomized Controlled Pilot Trial in Germany.

Breast cancer has a strong impact on the mental state of those affected. Cognitive behavioral therapy (CBT) is one effective approach to reduce disease burden. This randomized controlled pilot trial aimed to assess the effect of the digital CBT-based application Living Well on psychological outcomes in a German female breast cancer population. Female breast cancer patients (n=70) with ongoing or finished oncological treatment that is who were receiving or had received any type of oncological treatment were included in the study and randomized to an intervention group (IG, n=32) receiving Living Well in addition to care as usual, and a control group (CG, n=38) receiving care as usual only. Participants completed standardized questionnaires at baseline and after 2, 4, 8, and 12weeks to assess anxiety and depression (HADS) as primary outcomes, distress (DT), health-related quality of life (HRQoL, AQoL-8D), and illness perception (B-IPQ) as secondary outcomes. After 12weeks, significant (p<0.05) higher improvements in the IG could be observed in anxiety levels, HRQoL, and illness perception, when compared to the CG. Age and time since diagnosis were found to be relevant covariates for anxiety levels. In distress levels, the IG showed a clinically relevant and nearly significant reduction compared to the CG (p=0.057). No effects could be observed in depression levels. The results demonstrate the potential of Living Well to improve psychological outcomes of female breast cancer patients and encourage further studies evaluating the effectiveness of the digital application. The trial has been registered in the German Clinical Trials Register (DRKS00029918).

Associations between acupuncture and uses of opioids and neuropsychiatric medication following chemotherapy-induced peripheral neuropathy among patients with breast cancer.

216 Background: Chemotherapy-induced peripheral neuropathy (CIPN) features debilitative neuropathic pain and neurologic deficits, commonly present in breast cancer population exposed to certain chemo-agents. Given suboptimal effects often rendered by limited therapeutic options, CIPN is associated to psychological distress and drug-seeking behaviors, which leads to heightened functional impairment and disease burden. Acupuncture has gained clinical recognitions for alleviating pain and mental distress, but its impact on medication uses for pain or psychiatric disorders in CIPN remains unclear. As such, this study aims to investigate the association between acupuncture and use of these medications among breast cancer patients experiencing CIPN. Methods: This survival analysis utilized data from the TriNetX Network comprising real-time electronic health records from over 60 healthcare organizations across the United States. Breast cancer patients over 18 at the index date within 01/01/1997 (inception of acupuncture practice in US) and 05/10/2023, diagnosed with CIPN after exposure to chemo-agents such as taxane, platinum, vinca alkaloids, thalidomide, or bortezomib, were identified as the baseline cohort. Patients who received at least three acupuncture sessions post CIPN diagnosis were compared to those without any acupuncture record. Endpoints included prescription of sedative/hypnotics, anti-depressants, anti-psychotics, anti-convulsant agents, and opioid analgesics, within a twelve-month follow-up period after index date. Antibiotics use was the negative control outcome. A 1:1 propensity-score-matching (PSM) method was applied for between-group balance of demographics, BMI, cancer treatment history, health comorbidities, and concurrent medications, followed by hazard ratios and 95% CI calculation using Cox regression model. Results: Among 398 PSM pairs, acupuncture group demonstrated significantly lower hazards of sedative/hypnotics (HR= 0.74, 95% CI 0.61-0.9), anti-depressants (HR= 0.75, 95% CI 0.61-0.93), anti-psychotics (HR= 0.74, 95% CI 0.58-0.96), anticonvulsants (HR= 0.48, 95% CI 0.27-0.87), and opioids (HR= 0.78, 95% CI 0.65-0.94) use, whereas antibiotics showed insignificant result (HR= 0.75, 95% CI 0.55-1.02). The significance sustained after sensitivity analyses, excluding patients with concurrent other cancers, and narrowing follow-up period down to the last nine months to concentrate on treatment effects. Conclusions: Our study suggests a decreased need of opioids and neuropsychiatric medication associated with acupuncture treatment among breast cancer patients endorsing CIPN. Rigorous clinical studies are warranted to validate the causal underpinnings.

Clinicopathological characteristics, treatment patterns and outcomes in patients with HER2-positive breast cancer based on hormone receptor status: a retrospective study

BackgroundDifferent hormone receptor (HR) expression patterns have significant biological and therapeutic implications in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, the distinction between HR-positive /HER2-positive (HR+/HER2+) and HR-negative/HER2-positive (HR-/HER2+) subtypes remains unclear.MethodsThis retrospective study analyzed 828 patients with HER2-positive breast cancer at the First Affiliated Hospital of Xi’an Jiaotong University from 2012 to 2022. Baseline characteristics were compared by chi-square test. Survival outcomes were estimated by Kaplan-Meier method.ResultsIn total, 56.3% (n = 466) had HR-positive and 43.7% (n = 362) had HR-negative disease. Comparatively, HR+/HER2 + breast cancers presented favorable clinicopathological features. At a median follow-up of 49 months, 199 disease-free survival (DFS) events and 99 deaths were observed. HR+/HER2 + patients had significantly better survival outcomes than HR-/HER2 + patients. HR-positive status was an independent protective factor for overall survival (OS) [P = 0.032; hazard ratio, 0.61; 95% confidence interval (CI), 0.39–0.96] and DFS (P = 0.001; hazard ratio, 0.61; 95% CI, 0.46–0.81). HR+/HER2 + patients were significantly less sensitive to neoadjuvant therapy than HR-/HER2 + patients. In the first-line treatment for HR+/HER2 + advanced breast cancer, receiving endocrine therapy significantly improved advanced-OS (P < 0.001; hazard ratio, 0.33; 95% CI, 0.18–0.59) and progression-free survival (PFS) (P < 0.001; hazard ratio, 0.38; 95% CI, 0.25–0.58) compared with not receiving endocrine therapy. Moreover, maintenance endocrine therapy after HER2-targeted therapy and chemotherapy is associated with significant advanced-OS and PFS benefits compared with no maintenance endocrine therapy (advanced-OS: P < 0.001; hazard ratio, 0.05; 95% CI, 0.03–0.12; PFS: P < 0.001; hazard ratio, 0.35; 95% CI, 0.21–0.57).ConclusionsThis study reveals the high heterogeneity of HER2-positive breast cancer related to HR status in clinicopathological features, metastasis patterns, and outcomes. Large randomized controlled trials are warranted to optimize treatment strategies for the HER2-positive breast cancer population.

Abstract B006: Reduced survival outcomes in lower income quintile groups for women with breast cancer treated with chemotherapy in Ontario, Canada

Abstract Background: Despite the comparably comprehensive healthcare system in Canada, health inequities are widespread, and this holds true for breast cancer patients in Ontario. It is thus essential to learn if socio-demographic disparities continue after diagnosis of breast cancer, and if these contribute to higher mortality rates in the lower income quintile groups. Methods: We conducted a real-word population-based study using a provincial health administrative dataset from Ontario, Canada. We included patients diagnosed with HER2-negative breast cancer, treated with surgery and adjuvant chemotherapy, between 2009 to 2017. We used log-rank test and Kaplan Meier curves to compare overall survival (OS) between breast cancer populations among income quintile groups, and Cox regression to evaluate risk factors, using hazard ratio (HR) and 95% confidence intervals (CI). Results: We analysed 10,634 women diagnosed with stage I-III breast cancer. At diagnosis, in the Q1 group, there were 248 (15.8%) women with stage I, 997 (63.7%) with stage II, and 320 (20.45%) with stage III. In the Q5 group, there were 568 (22.15%), with stage I, 1,532 (59.75%) with stage II and 464 (18%) with stage III. Comparison between those in the lowest versus highest income quintile groups, and lymph node (LN) status at diagnosis, showed that in Q1, 534 (34%) women had LN 0 and 897 (57.3%) had LN+. In Q5, there were 954 (37.2%) women with LN 0 and 1,379 (53.8%) with LN+. Similarly, comparing tumor size (TS) at diagnosis, we found that in Q1, there were 463 (32.2%) women with TS≤ 2 cm and 974 (67.8%) with TS &amp;gt; 2 cm. In Q5, 915 (39%) women had TS≤ 2 cm and 1,426 (61%) had TS &amp;gt; 2 cm. In the Q1 group, there were 325 (20.7%) patients who received non- anthracycline and 1,240 (79.3%) treated with anthracycline-taxane chemotherapy. In Q5, there were 673 (26.2%) women treated with non-anthracycline and 1,891 (73.8%) who received anthracycline-taxane chemotherapy. The OS analysis based on the household income group compared to Q5 showed a substantial difference in the Q1 (HR 1.52, 1.2–1.9, p = 0.0002) and Q2 (HR 1.34, 1.1–1.7, p = 0.006) groups. In Cox regression models, Q5 group and endocrine receptor (ER) positive were significantly associated with reduced mortality risk. There was a significant correlation between increased risk of death and the following: receipt of non- anthracycline chemotherapy, TS &amp;gt; 2 cm, LN+ and grade 3 histology. Conclusion: Our study found an uneven distribution of breast cancer patients between the lowest and highest income quintile groups. Women with HER2-negative breast cancer who were part of the lower income quintile groups, thereby likely with a socioeconomic disadvantage, had the lowest OS. At diagnosis, these women were more likely to have more advanced breast cancer staging, including larger tumors, LN+, and receive anthracycline-based chemotherapy as compared to those with higher household income. Further research is warranted to identify the key social determinants that are systematically associated with disparities in equitable access to care. Citation Format: Danilo Giffoni M. M. Mata, Rossanna C. Pezo, Kelvin K.W. Chan, Ines Menjak, Andrea Eisen, Maureen Trudeau. Reduced survival outcomes in lower income quintile groups for women with breast cancer treated with chemotherapy in Ontario, Canada [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B006.

Abstract C050: Breast cancer in Ghana: assessment of multidrug-resistant genes among breast cancer patients

Abstract Breast cancer (BC) is the most frequently diagnosed cancer among women globally and chemotherapy plays a crucial role in its management in sub-Saharan Africa. The long-term BC survival rate remains poor due to chemoresistance. Over 80% of currently used chemotherapy drugs are substrates of ABC transporter genes, ABCB1, ABCC1 and ABCG2. Possessing the wild-type genotype and alleles of these genes reduces intracellular drug accumulation and leads to poorer treatment outcomes due to the upregulation of efflux function. This study therefore determined the allelic and genotype frequencies of three variant alleles, rs1045642, rs28706727 and rs2231142 in these transporter genes, and assessed the association between the variant statuses and BC recurrence or metastasis in the Ghanaian BC population. A quantitative, observational, case-control study was conducted using a purposive and convenience sampling method. Sociodemographic and clinical data were collected from study participants using questionnaires and a review of medical records. Extracted blood DNA from participants was used to determine the gene variants in ABCB1, ABCC1 and ABCG2 genes using the TaqMan Allelic Discrimination assays. A significantly high frequency (p ≤ 0.001) of the homozygous wild-type genotypes and alleles (ABCB1 had 77.3%/88% for CC/C, ABCC1 had 95.3%/97.7% for GG/G and ABCG2 had 100%/100% for CC/C) was found in both case and control groups. The wild-type genotypes and alleles of ABCB1, ABCC1 and ABCG2 may contribute to poor BC treatment outcomes among Ghanaian BC patients receiving chemotherapy. Citation Format: Gloria Agyekum Boaitey, Rachel Martini, Nourddine Dean Djeddar, Brian Stonaker, Stevens M. Patino, Jason White, Ernest Osei Bonsu, Yaw Agyekum Boaitey, Christian Obirikorang, Melissa B. Davis, Linda Ahenkorah Fondjo. Breast cancer in Ghana: assessment of multidrug-resistant genes among breast cancer patients [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C050.

Long-term risk of heart failure in adult cancer survivors: a systematic review and meta-analysis

BackgroundCancer survivors are at increased risk of heart failure (HF). While cardiotoxicity is commonly sought at the time of cancer chemotherapy, HF develops as a result of multiple ‘hits’ over...

Double-negative T cells with a distinct transcriptomic profile are abundant in the peripheral blood of patients with breast cancer.

Double-negative T (DNT) cells comprise a distinct subset of T lymphocytes that have been implicated in immune responses. The aim of this study was to characterize the peripheral DNT population in breast cancer (BC) patients. DNT cells were isolated from the peripheral blood samples of BC patients and healthy controls by flow cytometry. The sorted DNT cells were analyzed by the Smart-seq2 for single-cell full-length transcriptome profiling. The differentially expressed genes (DEGs) between the BC and control groups were screened and functionally annotated by Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses using R. The protein-protein interaction (PPI) network of the DEGs was constructed using the CytoHubba and MCODE plug-in of Cytoscape software to identify the core genes. Survival status, DNA methylation level, immune infiltration and immune checkpoint expression were analyzed using Kaplan-Meier Plotter, UALCAN, MethSeuvr, TIMER, and TISIDB respectively. The sequencing results were verified by RT-qPCR. The percentage of DNT cells was higher in the BC patients compared to healthy controls. We identified 289 DEGs between the DNT populations of both groups. GO and KEGG pathway analyses revealed that the DEGs were mainly related to immunoglobulin mediated immune response, complement activation, and B cell receptor signaling. The PPI networks of the common DEGs were constructed using Cytoscape, and 10 core genes were identified, including TMEM176B, C1QB, C1QC, RASD2, and IFIT3. The expression levels of these genes correlated with the prognosis and immune infiltration in BC patients, and were validated by RT-qPCR (P < 0.05). DNT cells are abundant in patients with BC, and might exert anti-tumor immune responses by regulating genes such as TMEM176B and EGR1.

Psychometric properties of the Depression Anxiety Stress Scales (DASS-21) in women with breast cancer

Breast cancer impacts the psychological well-being of women, leaving them at risk of developing depression, anxiety, and other stress-related disorders. The Depression Anxiety Stress Scales (DASS-21) is a widely used measure, although empirical evidence regarding its psychometric properties in the breast cancer population is limited. The purpose of this study was to conduct an exhaustive analysis of the psychometric properties of the DASS-21 in a sample of Spanish women diagnosed with breast cancer. Participants were 289 breast cancer patients who completed the DASS-21 and other questionnaires measuring life satisfaction, positive and negative affect, flourishing, perceived stress, and breast cancer-specific stressors. In terms of validity evidence based on the internal structure of the DASS-21, adequate fit indices were obtained for the model based on three first-order factors (depression, anxiety, stress) and one second-order factor (general psychological distress). Reliability coefficients (McDonald’s omega) ranged from .84 to .95. Validity evidence based on relationships with other variables was also provided by moderate and strong correlations with well-being indicators and stress measures. The results support the use of the DASS-21 for measuring general psychological distress in the breast cancer context, where it may provide useful information for the design of psychological interventions with patients.

1625: Sleep disturbance amongst the breast cancer population - a single-centre prospective experience

1625: Sleep disturbance amongst the breast cancer population - a single-centre prospective experience

The Comparison of Newly Diagnosed Invasive Breast Patient Cohorts in Genomics Evidence Neoplasia Information Exchange Biopharma Collaborative (GENIE-BPC) and Other Real-World Databases.

Oncology databases that integrate genomic and clinical data have become valuable resources for precision medicine. However, the generalizability of these databases has not been comprehensively assessed. To describe the demographics, clinical characteristics, treatments, and overall survival of breast cancer cohorts in GENIE-BPC and three other databases. This study utilized GENIE-BPC, SEER, SEER-Medicare, and Merative MarketScan Research Databases. Women with invasive breast cancer were identified through EHR, cancer registries or ICD-9/10-CM codes. The ages were 18+ years or per database requirement. Treatments were based on EHR or HCPCS/NDC codes in claims. Overall survival was estimated as time from diagnosis to death. Of female breast cancer patients in GENIE-BPC (n = 775), SEER (n = 548 336), SEER-Medicare (n = 68 914), and Marketscan (n = 109 499) databases, the median ages at initial diagnosis were 44, 62, 74, and 57 years, respectively. A greater proportion of patients in GENIE-BPC, compared to SEER/SEER-Medicare, had higher nuclear grades (%III-%IV: 57% vs. 26%/24%), advanced disease stage (%IV: 25.3% vs. 5%/3.6%), percent of triple negative breast cancer (19.7% vs. 10.2%/8.5%), and receipt of chemotherapy (85.0% vs. NA/22.3%). The 1-, 3-, and 5-year overall survival rates were lower in GENIE-BPC (78.5%, 60.5%, 55.5%) than in SEER (95.8%, 89.5%, 85.5%) and SEER-Medicare (91.6%, 81.4%, 75.0%). Breast cancer patients in GENIE-BPC were younger, had more advanced disease, had a higher proportion of triple negative breast cancer and recipients of chemotherapy, and had poorer overall survival. Researchers must use statistical adjustment when extrapolating results (e.g., biomarker prevalence) from GENIE-BPC to the larger breast cancer population.

Sociodemographic Disparities in HER2+ Breast Cancer Trastuzumab Receipt: An English Population-Based Study.

Sociodemographic disparities in traditional breast cancer treatment receipt in nonpublicly funded healthcare systems are well documented. This study investigated trastuzumab receipt by sociodemographic factors within a female, HER2+ breast cancer population in England's publicly funded National Health Service. The English national population-based cancer registry and linked Systemic Anti-Cancer Therapy database identified 36,985 women with HER2+ invasive breast cancer diagnosed between January 1, 2012 and December 31, 2017. Multivariable logistic regression determined the likelihood of trastuzumab receipt in early and metastatic disease by the deprivation category of area of residence and other sociodemographic characteristics. Early-stage trastuzumab receipt followed a socioeconomic gradient. Women residing in the most deprived areas were 10% less likely to receive trastuzumab [multivariable OR 0.90; 95% confidence interval (CI), 0.83-0.98] compared with women residing in the least deprived areas. In both early and metastatic disease, trastuzumab receipt was less likely in older women with more comorbidities, estrogen receptor-positive disease, and who were not discussed at a multidisciplinary team meeting. Despite the provision of free care at the point of delivery in England, sociodemographic disparities in early-stage HER2+ trastuzumab receipt occur. Further research determining how inequities contribute to disparities in outcomes is warranted to ensure optimized trastuzumab use for all. Fair access to novel cancer treatments regardless of place of residence, sociodemographic characteristics, and/or cancer stage requires prioritization in future cancer improvement policies. See related In the Spotlight, p. 1259.

Oncoplastic Surgery Outcomes in the Older Breast Cancer Population: A Matched-Cohort Comparison Study.

Oncoplastic breast surgery (OBS) is a form of breast conservation surgery (BCS) that involves a partial mastectomy followed by immediate volume displacement or volume replacement surgical techniques. To date, there are few studies evaluating OBS in older patients. Therefore, we sought to determine if outcomes differed between patients 65 years and older versus younger patients who underwent oncoplastic surgical procedures. A retrospective chart review was performed for all oncoplastic breast operations within a single health system from 2015 to 2021. Patients were stratified by age, with patients 65 years and older (OBS65+) identified and then matched with younger patients (OBS <65) based on BMI. Primary outcomes were positive margin rates and overall complication rates; secondary outcomes were locoregional recurrence (LR), distant recurrence (DR), disease-free survival (DFS), overall survival (OS), and long-term breast asymmetry. A total of 217 patients underwent OBS over the 6-year period, with 22% being OBS65+. Preoperatively, older patients experienced higher American Anesthesia (ASA) scores, Charlson Co-morbidity index (CCI) scores, and higher rates of diabetes mellitus, hypertension, and grade 3 breast ptosis. Despite this, no significant differences were found between primary or secondary outcomes compared to younger patients undergoing the same procedures. Oncoplastic breast reconstruction is a safe option in patients 65 years and older, with overall similar recurrence rates, positive margin rates, and survival when compared to younger patients. Although the older cohort of patients had greater preoperative risk, there was no difference in overall surgical complication rates or outcomes. Supporting the argument that all oncoplastic breast reconstruction techniques should be offered to eligible patients, irrespective of age.

Metabolomics in Radiotherapy-Induced Early Adverse Skin Reactions of Breast Cancer Patients.

Early adverse skin reactions (EASRs) are common side effects of radiotherapy (RT) that impact the quality of life of breast cancer patients. This study used global metabolomics profiles of breast cancer populations to identify metabolic pathways and biomarkers significantly associated with RT-induced EASRs to identify potential targets for precision interventions. We used a frequency-matched study design to identify pre-RT urine samples from 60 female breast cancer patients (30 with high and 30 with low EASRs) for metabolomic analysis by Metabolon Inc. using UPLC-MS/MS and GC-MS. Using MetaboAnalyst, we performed metabolomic data analysis and visualization on 84 candidate metabolites from 478 total compounds. We used the Oncology Nursing Society (ONS) Skin Toxicity Criteria (0-6) for EASRs assessment. Seven metabolic pathways were significantly associated with RT-induced EASRs, including alanine, aspartate, and glutamate metabolism (p = 0.0028), caffeine metabolism (p = 0.0360), pentose and glucuronate interconversions (p = 0.0028), glycine, serine, and threonine metabolism (p = 0.0360), beta-alanine metabolism (p = 0.0210), pantothenate and CoA biosynthesis (p = 0.0028), and glutathione metabolism (p = 0.0490). The alanine, aspartate, and glutamate metabolic pathway had the lowest false discovery rate (FDR)-adjusted p-value and the highest impact value of 0.60. Thirteen metabolite biomarkers were significantly associated with RT-induced EASRs. Our data show that the alanine, aspartate, and glutamate metabolism pathways had the highest impact value on RT-induced EASRs. Future larger studies are warranted to validate our findings and facilitate targeted interventions for preventing or mitigating RT-induced EASRs, offering a promising direction for further research and clinical applications.

Association of childhood trauma with choice of bilateral mastectomy for the treatment of unilateral breast cancer.

e24096 Background: Patients are increasingly choosing bilateral mastectomy (BMX) for the treatment of primary breast cancer (BC) despite minimal survival benefits and potential for adverse medical and psychosocial consequences. Exposure to childhood trauma is associated with dysregulation of stress response systems, threat perception alterations, increased risk-taking behaviors, and body dissatisfaction. We examined childhood trauma in relation to treatment decision-making in adulthood within a sample of breast cancer patients undergoing either BMX or more conservative BC treatment. Methods: Secondary analyses of a case-control study of the neurobiological and affective determinants of BMX choice were conducted. Cross-sectional data from the baseline survey were analyzed. Participants were recruited via institutional clinic practices, social media, and patient advocacy groups. Patients completed a medical status questionnaire and the Childhood Trauma Questionnaire (CTQ). Chi-square and Mann-Whitney U tests examined differences in treatment decision-making by childhood trauma exposure and type. Results: The sample included 137 patients with unilateral stages 0-III BC (mean age 49.2; SD = 11.2; 76.6% White; 10.9% Hispanic/Latina; 68.6% married). Seven tested positive for a BRCA gene mutation. Patients were divided between BMX (n = 66) and non-BMX (n = 71) treatment groups. On average, patients in the non-BMX group reported higher levels of childhood trauma severity (Median = 7; IQR = 0-12.5) compared to patients in the BMX group (Median = 4; IQR = 0-11.75; Mann Whitney U = 4728; small effect size; SRD = -0.11; p = .26). Patients who reported a major parental upheaval (e.g., divorce, separation) were significantly more likely to pursue non-BMX compared to BMX (small effect size; SRD = -.16; p = .047). Patients who reported any uncategorized major upheaval were more likely to choose non-BMX than BMX (small effect size; SRD = -.14), but group differences did not reach significance (p = .093) . No other statistically significant relationships were observed. Conclusions: Contrary to hypotheses, preliminary results suggest BC patients who were exposed to traumatic events in childhood may be more likely to elect conservative BC surgical treatments. Trauma-related hypervigilance to threats may cause patients to exercise more caution regarding treatment choice. More research exploring the effects of adverse childhood experiences in the BC population is warranted. [Table: see text]

Examining a genomic test in predicting extended endocrine benefit and recurrence risk in a diverse breast cancer population.

e12526 Background: Extending adjuvant endocrine therapy (EET) beyond five years for early-stage hormone receptor-positive (HR+) breast cancer reduces late distant recurrence risk. The genomic test, Breast Cancer Index (BCI), has prognostic value and predicts the benefits of prolonged therapy, yet no studies have explored this testing in a diverse population. This study assesses late distant recurrence risk and predictive benefits of EET to better understand its relevance in a diverse early-stage HR+ breast cancer population. Methods: We analyzed patient demographics, clinical and pathologic characteristics, and BCI scores of 150 women in Hawaii with early-stage HR+ breast cancer, self-identifying as White, Filipino, Japanese, Native Hawaiian, or other. Tumor characteristics examined include size, grade, histology, lymph node, and ER/PR/HER2 receptor status. Logistic regression analyses used race, distant recurrence risk, and tumor features as predictor variables. BCI prediction of benefit and distant recurrence risk served as outcome variables. Results: Japanese patients had significantly lower odds of having a high risk for distant recurrence (OR = 0.02, p &lt; 0.0001) compared to White. Other Asian PIs also showed reduced odds of high distant recurrence risk (OR = 0.07, p = 0.02), albeit to a lesser extent than Japanese. Patients with high distant recurrence risk had significantly greater odds of a score predicting benefit than those with low risk (OR = 5.03, p = 0.009). Racial or ethnic differences in predicting benefit with EET were not statistically significant. Conclusions: Results show no racial or ethnic differences in predicting the benefit of EET, strengthening BCI’s universal applicability in diverse women with early-stage HR+ breast cancer. Patients with higher distant recurrence risk were predicted to benefit from EET. This suggests potential variations in tumor features or other factors affecting distant recurrence risk among racial groups. Limitations include a relatively small sample size and lack of data from patients representing other racial groups. Future studies should expand the sample size and adjust for known breast cancer risk factors to better understand the racial and ethnic implications of BCI.

Linking the companion diagnostic function of cancer genome profiling to therapy: Investigation of TMB-high predictors.

e13033 Background: Based on the companion diagnostic function of the Comprehensive Cancer Genome Profiling (CGP) test in Japan, pembrolizumab is the standard treatment for patients with Tumor Mutational Burden (TMB)-high (H) solid tumors. In this report, we attempted to extract predictive factors of TMB-H from CGP test results. Methods: We carried out a retrospective cohort study of 42 patients with malignant breast tumors (excluding circulating tumor DNA in the blood) who underwent CGP testing between June 1, 2019, and November 30, 2023, at our hospital and affiliated institutions. We analyzed the association between clinicopathological factors, the number of analyzed cancer-related gene mutations (SNV, InDel), and TMB-H using univariate and multivariate statistical analysis. Results: Of the 42 cases (27 positive and 15 negative for estrogen receptor (ER), respectively), seven (16.7%) were TMB-H. Samples significantly associated with TMB-H according to univariate analysis were submitted as pathology specimens (non-primary (16.7%) vs. primary (0%), p = 0.011), ER (positive (16.7%) vs. negative (0%), p = 0.044), letrozole (LET) (yes (11.9%) vs. no (4.8%), p = 0.008), and previous treatment (after 6th line (14.3%) vs. before (2.4%), p = 0.041). Multivariate analysis showed that LET had a significant effect on TMB-H in Aromatase inhibitor agents (LET + Anastrozole + Exemestane) (LET: OR, 19.9; 95% CI, 2.2–183.5; p = 0.008) and the number of cancer-related gene mutations (PIK3CA+TP53) were significantly affected (PIK3CA: OR, 3.8; 95% CI, 1.1–13.2; p = 0.032. TP53: OR, 0.08; 95% CI, 0.01–0.66; p = 0.015). Single regression analysis showed a significant association between the number of PIK3CA mutations and LET. (β, 0.31; SE, 0.11; p = 0.008). Conclusions: ER positivity, history of LET use, prior therapy after the 6th line, and submission of pathology specimens from non-primary tumors to CGP testing are predictive factors for TMB-H. In multivariate analysis, the history of LET use and the number of PIK3CA mutations were significantly associated with TMB-H. Research shows that PIK3CA mutations are most frequent in patients who have undergone preoperative endocrine therapy with LET (Breast Cancer Res Treat. 2020 Nov;184(1):123–133.), suggesting that an increased number of PIK3CA mutations due to LET contributed to TMB-H. Although immune checkpoint inhibitors (ICIs) are not indicated for ER-positive breast cancer, TMB-H may be a predictor of ICI efficacy in such cases. The limitations of our research were the small sample size, and the study population only included Japanese. For the next steps needed to continue in this research, clinical trials should take place to test whether TMB-H is a predictor of ICIs in a wider population of ER-positive breast cancer.

Optimal neoadjuvant treatment and prognostic factors in patients with HR-positive/HER2-positive early or locally advanced breast cancer: A national real-world study in China.

e12514 Background: Few data have been reported regarding breast cancer (BC) population characterized by HR+/HER2+ especially in a real-world setting in China. This analysis aimed at identifying differences in short-term treatment outcomes of different neoadjuvant therapy (NAT) regimens, effects of the demographics and clinical features on short-term outcomes of NAT, and further understanding the prognostic factors related to those outcomes in HR+/HER2+ early (EBC) or locally advanced BC (LABC) pts by using dataset from National Cancer Information Database (NCID) in China. Methods: This retrospective, multicenter, real-world study used electronic medical record data from NCID. We analyzed HR+/HER2+ EBC or LABC Chinese pts who were initially diagnosed between Jan 1, 2019 and May 31, 2022 and received NAT followed by surgery during study period. Primary endpoints included total pathological complete response (tpCR) and breast pCR (bpCR). Secondary endpoints included disease-free survival (DFS) and event-free survival (EFS). Results: 3792 pts from NCID covering 51 hospitals, 26 provinces met inclusion criteria and were included. After controlling for age and post-surgery N staging, 1-, 2- and 3-yr DFS was similar between trastuzumab (T) and T+pertuzumab (P) NAT subgroup (92.79%, 87.20% and 83.32% vs 94.83%, 88.82% and 87.88%; p=0.1120). 1-, 2- and 3-yr EFS was higher in T+P subgroup (T vs T+P: 85.24%, 82.35%, 77.01% vs 90.86%, 89.65%, 82.78%; p = 0.0003). Logistic regression multivariate analysis showed improved tpCR and bpCR was independently positively associated with receiving T+P NAT (vs T: both p &lt; 0.0001), platinum NAT (vs anthracycline: p = 0.0071 and 0.0122, resp.), while negatively associated with receiving no targeted therapy (vs T: p = 0.0002 and &lt; 0.0001, resp.), ≥ 65 yrs (vs &gt; 40 yrs, &lt; 64 yrs: p = 0.0116 and 0.0290, resp.), or post-surgery ER positive (vs negative: both p &lt; 0.0001). Conclusions: HR+/HER2+ EBC or LABC gained short- and long-term benefit from HER2 dual-blockade therapy in clinical practice. Prognostic factors for improved tpCR and bpCR included T+P and platinum NAT, whereas ≥ 65 yrs and post-surgery ER+ were predictive of decreased tpCR and bpCR. [Table: see text]