Chemotherapy For Breast Cancer Research Articles

Predicting pathological response in early-stage triple-negative breast cancer: Exploring the role of BRCA gene mutations—A retrospective single-institution study.

e12656 Background: Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer, constituting approximately 15-20% of all breast cancer cases. While less than 10% of all breast cancer patients harbor BRCA1/2 mutations, ~20% of TNBC patients carry these mutations. Notably, at least one-third of BRCA1 carriers develop TNBC. This study aimed to investigate the association between BRCA mutation status and pathological response (PR) in early-stage TNBC patients, specifically, the impact of BRCA positivity on achieving pathological complete response (pCR), and identify other potential predictors of PR. Methods: We conducted a retrospective cohort study of patients with early-stage (Stage I-III) triple-negative breast cancer diagnosed and treated at our institution between January 2012 and June 2022, following Institutional Review Board (IRB) approval. Patients were identified from our Institutional Cancer Registry based on complete data availability (including other inclusion criteria) excluding patients who did not receive neoadjuvant chemotherapy. Data on demographics, tumor characteristics, treatment regimens, and pathological response (assessed according to [specified criteria]) were extracted from the charts. Results: Out of 228 patients diagnosed with early-stage triple-negative breast cancer, 54.6% had no genetic mutations, while 7.9%, 4.9%, and 8.4% harbored BRCA1, BRCA2, and other mutations, respectively. Notably, 23.4% did not receive genetic counseling or testing at our institution. Patients with BRCA2 mutations had a 100% pathological response rate, of which 57.14% had pCR, compared to 85.7% for BRCA1, of which 71.43% had pCR. Furthermore, 93.8% of patients with other genetic mutations had pathological response, of which 56.25% had pCR, as compared to 68.42% in non-mutated cases of which 26.7% had pCR ( P=0.038). Analysis of other variables revealed no significant impact of age, BMI, performance status, or neoadjuvant chemotherapy regimen on pathological response. Conclusions: This retrospective study suggests a trend towards higher complete pathological responses in early-stage triple-negative breast cancer patients with BRCA and other genetic mutations compared to those without. These findings were statistically significant, indicating a potential clinical trend that specific genetic mutations may be associated with improved response to neoadjuvant chemotherapy in early-stage triple-negative breast cancer. Further research is needed to confirm these findings and guide the development of personalized treatment strategies based on a patient's genetic profile. Additionally, our findings highlight the importance of genetic testing for all patients with early-stage triple-negative breast cancer, regardless of age or family history.

Safety run-in phase of the multi-epitope HER2 peptide vaccine in combination with trastuzumab emtansine in HER2-positive breast cancer with residual disease after neoadjuvant chemotherapy.

550 Background: Residual disease after neoadjuvant chemotherapy (NAC) in HER2-positive breast cancer (BC) confers poor outcomes. Despite additional trastuzumab emtansine (T-DM1) in the adjuvant setting, a significant number of patients with residual disease still develop recurrence. H2NVAC is a multi-epitope T helper cell-activating peptide vaccine that is composed of 4 degenerate HER2-derived HLA-DR epitopes admixed with GM-CSF. Our previous phase I trial showed that this vaccine was safe and generated robust, long-lasting T and B cell immune responses. Methods: Patients with stage II-III HER2+ BC with any amount of residual disease in the breast /axilla after NAC were enrolled in a safety run-in phase of H2NVAC in combination with T-DM1. Patients were treated with H2NVAC and T-DM1 for 6 cycles, followed by 2 boosters at 3 and 12 months. Dose-limiting toxicity (DLT) was defined as any grade (G) ≥ 3 adverse events (AE) occurring within 21 days after the first vaccination. Results: A total of20 patients were enrolled with a median age of 51 years (range 27-69), 80% were White and 15% were Black. Most patients had hormone receptor-positive disease (90%). 40% were premenopausal, 40% were postmenopausal, and 20% were unknown. 14 patients had ypT1, 3 patients ypT2, 3 patients ypT3, 1 patient ypT4, 8 patients ypN0, 9 patients yp N1, 1 patient ypN1mi, and 2 patients ypN2. H2NVAC, in combination with T-DM1, was well tolerated, with no DLT being observed. Only grades 1 and 2 AEs were observed during the DLT period, with fatigue being the most common (G1 60%, G2 5%), followed by peripheral sensory neuropathy (G1 55%, G2 5%) and injection site reaction (G1 50%). Across all treatment cycles, the top 10 most common AEs that were at least possibly related to treatment include injection site reaction (G1 85%, G2 15%), AST increase (G1 65%), ALT increase (G1 45%), fatigue (G1 35%, G2 10%), peripheral sensory neuropathy (G1 35%, G-tube 10%), alk-phos increase (40% G1), nausea (G1 35%, G2 5%), arthralgia (G1 35%), myalgia (G1 25%, G2 5%), and platelet count decrease (G1 30%). There were four patients with G3 AEs at least possibly related to the vaccine observed after the DLT period, including allergic reaction, myositis/skin infection, urticaria, and pruritus/maculopapular rash. Conclusions: H2NVAC, in combination with T-DM1, was safe without DLT observed. The side effect profile was favorable, with the most common AE being the G1 injection site reaction. A multicenter, randomized, placebo-controlled, phase II trial of H2NVAC vs. placebo in combination with trastuzumab emtansine is currently ongoing through the ACCRU consortium. Clinical trial information: NCT04197687 .

Clinical outcomes of patients with HER2-positive microinvasive breast cancer.

544 Background: Although previous studies have reported that adjuvant trastuzumab with paclitaxel resulted in excellent survival outcomes in small, node-negative HER2-positive breast cancer, the necessity of adjuvant chemotherapy in HER2-positive microinvasive breast cancer (MIBC) remains controversial. Methods: Between January 2000 and January 2020, women with curatively resected pT1mi N0 and/or N1mi in Asan Medical Center were retrospectively identified and their survival outcomes including invasive disease-free survival (IDFS, excluding second primary cancer), distant recurrence-free survival (DRFS), and overall survival (OS) and the effect of adjuvant chemotherapy were analyzed. Results: A total of 833 patients were included. The median age was 51 years, and 51% (n = 426) were premenopausal. Pathologic nodal stage was pN0 in 96% (n = 799) and pN1mi in 0.7% (n = 6), and estrogen receptor (ER) was positive in 30% (n = 247). Adjuvant chemotherapy was administered to 18% (n = 147) of patients, of which 95% were fluorouracil-based. Six patients (0.7%) received adjuvant trastuzumab. With the median follow-up of 118.7 months, the 8-year IDFS and DRFS rates were 90.6% (95% CI, 88.4-92.7), and 97.3% (95% CI, 96.1-98.4), respectively, and the 8-year OS were 98.6% (95% CI, 97.8-99.5). IDFS did not differ by adjuvant chemotherapy, as the 8-year IDFS rates for patients who did and did not receive adjuvant chemotherapy were 91.1% (95% CI, 86.6-95.8) and 90.3% (95% CI, 87.9-92.8), respectively ( p = 0.930). The lack of differences in IDFS by chemotherapy was consistent across subgroups including pre-/postmenopausal patients, grade 1-2/3 tumors, and ER-negative diseases. Conclusions: In HER2-positive MIBC, a clinically meaningful proportion of patients experience IDFS events with long-term follow-up. The role of modern adjuvant chemotherapy regimens, as well as the role of adjuvant trastuzumab, should be further explored in this early-stage patient population.

Association of germline polygenic risk for thyroid autoimmunity with overall survival in the I-SPY2 Trial.

10600 Background: Germline genetic variation influences immune activity and risk of autoimmunity, and has been hypothesized to play a role in response to cancer therapeutics and survival. Prior studies of breast cancer have reported associations between genetic variation in thyroid autoimmunity and overall survival (OS). Here, we aim to investigate the association between a polygenic risk score for hypothyroidism (PRS-H) and response to therapy in women with early-stage breast cancer, and hypothesize that high PRS-H will be associated with better treatment response and survival. Methods: This study includes 1,368 women aged 18 years and above with stage II-III breast cancer of size > 2.5cm by clinical exam, with germline data available. It is an approved biomarker analysis of the I-SPY 2 trial, which is a phase II, adaptive, randomized platform trial across multiple sites studying novel cancer therapeutics across multiple arms for use as neoadjuvant chemotherapy for early-stage breast cancer. The outcome of survival is defined as alive at the most recent follow-up. Using the Cox proportional hazards model, we evaluate the association between a previously published PRS-H and overall survival. Models are adjusted for age at screening, immunotherapy status, and five principal components. Results: Among 1,368 early-stage breast cancer women, 33% (n=447) had pCR, and 85% (n=1,157) were alive at the last follow-up. Additionally, 16% (n=219) of women received immunotherapy. We observe a significant association between PRS-H and OS (HR = 0.78, 95% CI 0.66-0.92, p=0.004). Individuals in the top 10th percentile of the PRS-H (highest genetic risk) have improved survival (log rank p=0.04). Conclusions: Germline genetic variation in thyroid autoimmunity proclivity is associated with improved overall survival in our cohort of women with early-stage breast cancer receiving neoadjuvant chemotherapy. Our findings suggest that the genetic risk for autoimmunity may be important for long-term survival. We will expand this analysis to include the entire I SPY 2 population when all patients have completed genotyping. We plan to further characterize the role of germline autoimmunity profiles and survival. Clinical trial information: NCT01042379 .

Assessing the feasibility and cost-effectiveness of all oral adjuvant chemotherapy (cyclophosphamide, methotrexate, capecitabine) in high-risk hormone receptor positive breast cancer.

TPS616 Background: Women with high-risk HR+/HER2- breast cancer (BCA) receive additional chemotherapy to reduce disease recurrence. Preferred Taxane and Anthracycline based chemotherapy regimens have debilitating side effects such as cardiotoxicity, leukemia, peripheral neuropathy, severe fatigue, alopecia, downtime which are more common in black women thereby necessitating dose reductions. Metronomic cyclophosphamide, methotrexate, 5-fluourouracil (CMF) is an option but less preferred due to frequent dosing and longer therapy duration. Head-to-head comparison of CMF to anthracycline-based chemotherapy conducted 3 decades ago in early-stage BCA showed anthracycline benefit was driven by HER2+ disease with no benefit for HR+/HER2- BCA. Head-to-head comparison trials of CMF and Taxane-based regimen have not been conducted but single institution data suggest similar disease-free and similar overall survival but different toxicity profiles favoring CMF. In our ongoing trial, we converted all three chemotherapy drugs in CMF regimen to an all-oral regimen namely oral Cyclophosphamide, oral Methotrexate, oral Capecitabine (CMC) with the potential benefit of increased patient convenience, decreased costs (oral agents are generic; no chair time; no growth factors), and improved toxicity profile (low rates of grade III neutropenia, no port complications, no alopecia). This trial in progress aims to evaluate the feasibility of oral CMC by measuring the relative dose intensity in addition to the safety and tolerability of oral CMC. We hypothesize that 80% of patients will receive >85% of the intended dose of oral CMC. Methods: This is a Phase II, single arm, non-randomized study enrolling 25 patients with high-risk early-stage HR+ HER2- breast cancer to receive oral CMC regimen based on dose conversion equivalent bioavailability with conventional metronomic CMF chemotherapy. Enrolled patients will receive adjuvant therapy of oral cyclophosphamide 60 mg/m2 PO days 1-21 continuously, Methotrexate 15 mg/m2 PO Day 1, 8, and 15 and Capecitabine 650 mg/m2 PO BID Day 1- 14 to be given every 21 days for 8 cycles. The primary objective is to assess feasibility which is defined as 80% of patients (greater than 20 patients) maintaining a relative dose intensity (RDI) > 85%. The RDI is calculated as the ratio of the actual dose intensity/standard dose intensity; the average RDI for oral CMC regimen is the sum of RDI for each drug divided by 3. This study will be stopped if >25% of patients report Grade 4+ toxicity on oral CMC. The secondary objectives will assess quality of life as reported by the patients and report adverse effects. Clinical trial information: NCT06085742 . [Table: see text]

Fulvestrant with or without the cyclin-dependent kinase 7 (CDK7) inhibitor samuraciclib in advanced hormone receptor positive (HR+) breast cancer after CDK4/6 inhibition: Phase II SUMIT-BC study.

TPS1126 Background: CDK7 enhances oncogene transcription and upregulates anti-apoptotic genes, accelerates the cell cycle via CDK phosphorylation, and activates estrogen receptors (ERs) that can drive resistance to hormonal therapy in cancer. CDK7 inhibition therefore represents a potential anticancer strategy in cancer. Samuraciclib (CT7001) is a small molecule, ATP competitive, selective oral inhibitor of CDK7 that inhibits these key effects of CDK7. Samuraciclib had a favorable safety profile and showed clinical activity when combined with fulvestrant in a phase I study in patients with HR+/HER2− advanced breast cancer (BC) who had previously been treated with a CDK4/6 inhibitor. Patients with no detectable TP53 mutation in ctDNA at baseline and those without baseline liver metastases appeared to have better outcomes. The instant release capsule formulation of samuraciclib used in this study released large amounts of samuraciclib high in the gastrointestinal (GI) tract, which may have contributed to the observed low grade GI adverse events, which were managed with prophylaxis and counselling (1). Methods: A phase 2 open-label randomized study has been designed to evaluate the efficacy, safety, pharmacokinetics (PK), and quality of Life (QoL) of samuraciclib combined with fulvestrant compared to fulvestrant monotherapy (SUMIT-BC; NCT05963984). Eligible patients (n=60) are ≥18 years, have histologically or cytologically confirmed ER+/HER2− advanced or metastatic BC not amenable to resection or radiotherapy of curative intent, have received an aromatase inhibitor combined with a CDK4/6 inhibitor in the adjuvant or advanced setting, are receiving a luteinizing hormone-releasing hormone agonist if pre/perimenopausal, and have RECIST v1.1 evaluable disease. Prior SERD, mTOR inhibition, or chemotherapy for advanced BC are not permitted. All patients undergo baseline Guardant360 ctDNA analysis to establish TP53 and other mutation status. Patients are randomized 1:1:1 to fulvestrant alone (500 mg IM administered on days 1, 15 and 29 and then monthly), fulvestrant and samuraciclib 240 mg QD, or fulvestrant and samuraciclib 360 mg QD. In preparation for phase 3 development, a novel single tablet formulation of samuraciclib is used, which may enhance GI tolerability. Patients undergo RECIST v1.1 evaluation at baseline, every 8 weeks until week 48, and every 12 weeks thereafter. The primary endpoint is clinical benefit response at 24 weeks. Secondary endpoints are tolerability, progression free survival, overall response rate, duration of response, and PK of fulvestrant and samuraciclib. QoL (Functional Assessment of Cancer Therapy - Breast questionnaire [FACT-B]) and correlations between TP53 mutation and efficacy/safety will be assessed. 1. Coombes et al. Nature Comms 2023. Clinical trial information: NCT05963984 .

Surgical decision-making after neoadjuvant chemotherapy for breast cancer.

e23282 Background: Following neoadjuvant chemotherapy (NAC), a significant subset of breast cancer patients become candidates for breast conserving surgery (BCS) after tumor downstaging. Studies have shown there is no survival advantage between BCS and mastectomy after NAC and that patient prognosis is largely predicted by the pathologic response to treatment. While the literature highlights many aspects of surgical decision-making in breast cancer, there is little analysis of patient choice after NAC. The goal of this study is to investigate clinical and demographic factors that may associate with patients’ surgical decision-making after receiving NAC as well as related outcomes. Methods: A retrospective chart review was conducted on breast cancer patients at our institution who became BCS candidates after receiving NAC from 1/1/2010 to 9/30/2020. Patient demographics, clinical characteristics, choice of mastectomy versus BCS, and outcomes were compared. Exclusion criteria included inflammatory, recurrent, and bilateral breast cancers, and patients with genetic predisposition. T-tests and chi-squared tests of association were used for continuous and categorical variables respectively. Survival outcomes were reported using the log-rank test. The p-value threshold for significance was p < 0.05. Statistical analysis was performed using R software version 4.2.3. Results: In this analysis, 244 patients met study criteria, of which 181 (74.2%) patients chose BCS and 63 (25.8%) patients elected mastectomy. Patients who chose mastectomy were younger at time of diagnosis than those who chose BCS: median age 48 years in mastectomy group versus 53 years in BCS group (p = 0.003). Regarding physical exam findings, while palpability of the primary breast tumor was not associated with choice of surgery (p = 0.271), presence of axillary lymphadenopathy was associated with a higher likelihood of choosing mastectomy (44.4% in mastectomy subgroup versus 29.3% in BCS subgroup, p = 0.041). Patient race, pre-treatment clinical stage, and doxorubicin-based chemotherapy were not associated with patients’ decisions for type of surgery. With respect to outcomes, follow-up time was similar between both groups with overall median of 5 years, and there was no significant difference in local or distant recurrence, and overall mortality (log-rank p = 0.3). Conclusions: The majority of breast cancer patients elect BCS after downstaging from NAC. Factors that are associated with choosing mastectomy include younger age at diagnosis and pre-treatment palpable axillary lymphadenopathy, which may be perceived as more advanced stage, despite no difference in stage between both groups. Regardless of surgical choice, both recurrence and mortality rates did not significantly differ between patients who chose BCS versus mastectomy, which is consistent with the literature.

Integrating 4 Methods (In4M) to evaluate physical function in patients with cancer: Results of a comprehensive digital health study.

1564 Background: Physical function (PF) is a core outcome in cancer trials that can inform treatment tolerability. PF can be assessed across modalities including by patient (pt) report, clinician (clin) report, performance tests and digital sensors. The optimal approach for PF measurement has not been defined. Methods: In4M is a prospective observational study evaluating PF in pts initiating chemotherapy for breast cancer or lymphoma followed over 9 months. We used an electronic platform (Hugo) to aggregate serially assessed pt-reported PF, clin- and pt-reported ECOG performance status (PS), 6-minute walk test (6MWT) and wearable (Fitbit) data. We evaluated feasibility in all pts; associations among PF measures and the ability of PF measures to detect change were evaluated in pts with both baseline (BL) and 3-month (3M) data. We used Pearson correlations to assess the relationship of average daily steps with measures of PF. To assess change, we compared each PF measure from BL to 3M using a 2-sided α=.05 paired t-test. Results: Of the208 pts enrolled, 193 (93%) and 159 (76%) completed surveys, and 121 (58%) and 124 (60%) provided wearable data (evaluable: ≥1 day data) at BL and 3M, respectively. When requiring a stringent BL with 4+ days of data with ≥1 weekend day to be evaluable, 88 (42%) and 120 (58%) provided wearable data at BL and 3M. At both BL and 3M, pt-reported PF was generally more highly correlated with wearable-derived daily steps than clin-reported PF and 6MWT were (Table). Significant declines in PF were observed for pt- and clin-reported PF (all p<0.05), but not other modalities. Conclusions: Longitudinalassessment of multi-modal PF data including pragmatic wearable data collection was feasible in pts receiving chemotherapy. Pt-reported PF was the only modality that was both correlated with step count and able to detect change. Additional wearable metrics, correlations among PF measurements and outcomes, and clinically meaningful change scores will be reported. Optimal PF measurement may improve future reporting of treatment tolerability. Clinical trial information: NCT05214144 . [Table: see text]

Patient factors associated with chemotherapy modifications: Results from the Optimal Breast Cancer Chemotherapy Dosing (OBCD) study.

520 Background: Understanding patient factors associated with an increased likelihood of receiving chemotherapy modifications is important for treatment planning and anticipating which patient groups might require extra support through the course of treatment. Methods: We have evaluated patient and tumor factors associated with chemotherapy modifications in a cohort of 9700 women receiving adjuvant chemotherapy for breast cancer at Kaiser Permanente Northern California (KPNC) and Kaiser Permanente Washington (KPWA) in the Optimal Breast Cancer Chemotherapy Dosing (OBCD) Study diagnosed between 2005-2019. The outcome variable, receipt of a ‘chemotherapy modification’ is defined as a composite representing any of the following deviations from the intended regimen: dose reduction >10% (first cycle or overall), extensive delay (any single delay >14 days), regimen change, or receipt of fewer cycles of any given drug than intended in the original chemotherapy plan. Multivariable-adjusted prevalence ratios (PR) and corresponding 95% confidence intervals (95% CI) were calculated using generalized linear models of the Poisson family with a log link-function and robust standard errors. Results: Several factors were associated with chemotherapy modifications. Notably, older age was associated with an increased likelihood of modifications (p-trend<0.001), with adults aged 80+ years at diagnosis 1.93-fold more likely to experience modification than adults 18-39 years (95% CI: 1.50-2.50). Increased comorbidity and BMI were also associated with increased likelihood of modification (p-trend for both:<0.001), with patients with a Charlson Comorbidity Index of 3+ (vs 0) having an PR of 1.33 (95% CI: 1.19-1.48) and those with a BMI of 35+ kg/m2 (vs <25 kg/m2) having an PR of 1.53 (95% CI: 1.41-1.65). HER2+ status (PR HER2+ vs HER2-: 1.99 95% CI: 1.89-2.10) and higher stage of disease (PR IIIA vs I:1.24; 95% CI: 1.13-1.35; p-trend<0.001) were associated with increased likelihood of chemotherapy modification, while hormone receptor positivity was associated with lower likelihood of modification (PR ER+ and/or PR+ vs ER-/PR-: 0.93; 95% CI: 0.88-0.99). Diagnosis in more recent years was also associated with decreased likelihood of modification (PR 2015-2019 vs 2004-2009: 0.70; 95% CI: 0.66-0.75), as was higher neighborhood income (PR Q4 vs Q1: 0.78; 95% CI: 0.72-0.84). Conclusions: Several patient-level and clinical factors were associated with chemotherapy modifications, including age, comorbidity, BMI, and ER/PR/HER2 status. Future research might focus on the groups noted to have increased risk of treatment modification to better understand the factors underlying these changes, as well as the impact on patient outcomes.

Trends and outcomes in patients receiving neoadjuvant chemotherapy for breast cancer in Ontario: A population-based study.

e12664 Background: Modern neoadjuvant chemotherapy (NAC) regimens in breast cancer offer higher rates of pathologic complete response, an ability to guide further adjuvant treatment, and may de-escalate surgery. However, the utilization of NAC has been heterogeneous in Ontario. This study aimed to describe trends in NAC use in Ontario, report survival outcomes, and explore factors associated with overall survival in these patients. Methods: This was a population-based cohort study using linked health administrative data in Ontario, Canada. From the Ontario Cancer Registry, we identified women ≥18 years who underwent neoadjuvant chemotherapy followed by surgery for operable (cT1N1, cT2-3N0, or cT2-3N1) breast cancer between 2012 and 2020. Patients were divided by receptor subtype (triple negative breast cancer [TNBC], ER+/HER2-, ER+/HER2+, ER-/HER2+) and characteristics were compared using standardized mean differences (SMDs). Five-year overall survival (OS) and breast cancer-specific survival (BCSS) were determined and reported for each subtype. Associations with OS and BCSS were calculated for patient and disease characteristics using univariate and multivariable Cox proportional hazards models and Fine and Gray models, respectively. Results: 3,804 women underwent NAC for cT1N1, cT2-3N0, or cT2-3N1 breast cancer in Ontario between 2012 and 2020. The largest contributing subtype was ER+/HER2- patients (39.3%) followed by those with HER2+ disease (ER-/HER2+ 13.8%, ER+/HER2+ 23.4%), and TNBC (23.5%). The median age was 50 years (IQR 42-59 years). Most patients were clinically node-positive (2,736; 71.9%), and underwent mastectomy (2,397; 63.0%). There was a significant increase in the number of patients receiving NAC in Ontario, from 217 in 2012 to 667 in 2019 ( p<0.001), with a greater increase among patients with TNBC or HER2+ disease. Compared to those with ER+/HER2- disease, TNBC patients were treated for smaller tumours (28.6% T3 vs. 39.8%; SMD = 0.24), and were more likely to be node-negative (39.1% N0 vs. 22.1%; SMD = 0.38). Similar trends for nodal status were found for patients with ER-/HER2+ (26.7% N0) and ER+/HER2+ cancer (27.9% N0). 5-year OS for the entire cohort was 88.1% (95% CI 87.1 – 89.2%). Survival was highest for ER+/HER2+ patients (94.2%, 95% CI 92.6 – 95.8%) and lowest for TNBC patients (80.1%, 95% CI 77.5 – 82.8%). Similar patterns were seen for BCSS. Factors associated with OS in a multivariable model included older age (increase in 5 years HR 1.1, 95% CI 1.07 – 1.14), N1 status (HR 1.99, 95% CI 1.61 – 2.47), larger tumour size (T3 HR 1.83, 95% CI 1.34 – 2.5), mastectomy (HR 1.45, 95% CI 1.2 – 1.75), and TNBC (versus ER+/HER2- HR 1.9, 95% CI 1.56 – 2.32). Conclusions: The use of NAC has increased in Ontario, particularly among TNBC and HER2+ patients. Women with TNBC have worse outcomes compared to those with ER+/HER2- disease, despite being treated for less advanced disease.

Application of multidisciplinary team model based on full-course management in health promotion of patients with breast cancer.

e13546 Background: To explore the application effectiveness of the multidisciplinary team model based on full-course management, in advancing the health promotion of breast cancer patients. Methods: This research involved a cohort of 84 breast cancer patients, recruited from the First Affiliated Hospital of Nanjing Medical University, spanning December 2022 and June 2023. These participants were divided into a control group and an intervention group using a convenience sampling method. The control group accepted routine nursing care, while the intervention group was treated with the multidisciplinary team approaches based on full-course management. These approaches included informal pre-admission interventions and multi-dimensional improvements to peri-operative patient comfort, integrated regimens combining Chinese and Western medicine to alleviate chemotherapy complications, diversified and extended nursing care focused on improving patients' quality of life, and facilitating physical and psychological rehabilitation. The two groups of patients were evaluated in satisfaction, comfort, quality of life, psychological state and other aspects. The results were evaluated by self-made satisfaction scale, breast cancer complications during chemotherapy questionnaire, Kolcaba Comfort Scale, Quality of Life Scale (QLQ-C30), self-rating Anxiety Scale (SAS) and self-rating Depression Scale (SDS). Patient outcomes were assessed in terms of satisfaction, comfort, quality of life, and psychological state. The results were evaluated by the self-made satisfaction scale, the breast cancer chemotherapy complications questionnaire, the Kolcaba Comfort Scale, the Quality of Life Scale (QLQ-C30), the Self-Rating Anxiety Scale (SAS), and the Self-Rating Depression Scale (SDS). Results: The intervention group showed statistically significant improvements in patient satisfaction, comfort and quality of life scores compared to the control group (P<0.05). Additionally, they exhibited a lower incidence of chemotherapy complications, severe anxiety and depression during the extended care period (P<0.05). Conclusions: The multi-disciplinary team model based on the full-course management demonstrated significant clinical benefits in the application of the full-course management of breast cancer patients. It effectively reduced chemotherapy-related complications, improved peri-operative comfort, decreased the incidence of severe anxiety and depression during the period of extended care, improved the physical and mental well-being of patients, leading to greater satisfaction and an enhanced quality of life.

Relationship between Tumor Infiltrating Lymphocytes and Neoadjuvant Chemoterapy Responsiveness: A Cross-Sectional Study on Breast Cancer Patients

Breast cancer is still a significant health problem in the world, with chemotherapy as an essential component in its management. Limited research on tumor- infiltrating lymphocytes (TIL) as a biomarker for the effectiveness of breast cancer treatment was conducted and is still contradictory. This study aims to investigate the relationship between TILs and the clinical response to neoadjuvant chemotherapy in breast cancer. The research used a cross-sectional study on eligible breast cancer patients in Wahidin Sudirohusodo Hospital in Makassar. TIL levels were grouped based on the histopathological examination results of breast tissue samples into three categories: low (0% to 10%), medium 15% to 50% and high (55% to 100%). Responsiveness was assessed based on changes in tumor size after neoadjuvant chemotherapy. The Chi-Square test is the primary analysis in this study. Results of 40 participants, the sample had a median age of 40 (27-73 years), mainly in the clinical stage III (40.0%), had moderate TIL concentration (47.5%), and was responsive to the neoadjuvant chemotherapy (87.5%). There was no significant association between TIL concentration and chemotherapy responsiveness (p > 0.05). However, in post-chemotherapy conditions, the median value of tumor size in the group with the high TIL category was significantly lower than in the low and medium TIL groups (p=0.034). There was no association between TIL levels and the clinical response to neoadjuvant chemotherapy in breast cancer patients. Further research is needed to confirm these findings.

Emulation and evaluation of tumor cell combined chemotherapy in isotropic/anisotropic collagen fiber microenvironments.

The rapid emergence of anisotropic collagen fibers in the tissue microenvironment is a critical transition point in late-stage breast cancer. Specifically, the fiber orientation facilitates the likelihood of high-speed tumor cell invasion and metastasis, which pose lethal threats to patients. Thus, based on this transition point, one key issue is how to determine and evaluate efficient combination chemotherapy treatments in late-stage cancer. In this study, we designed a collagen microarray chip containing 241 high-throughput microchambers with embedded metastatic breast cancer cell MDA-MB-231-RFP. By utilizing collagen's unique structure and hydromechanical properties, the chip constructed three-dimensional isotropic and anisotropic collagen fiber structures to emulate the tumor cell microenvironment at early and late stages. We injected different chemotherapeutic drugs into its four channels and obtained composite biochemical concentration profiles. Our results demonstrate that anisotropic collagen fibers promote cell proliferation and migration more than isotropic collagen fibers, suggesting that the geometric arrangement of fibers plays an important role in regulating cell behavior. Moreover, the presence of anisotropic collagen fibers may be a potential factor leading to the poor efficacy of combined chemotherapy in late-stage breast cancer. We investigated the efficacy of various chemotherapy drugs using cell proliferation inhibitors paclitaxel and gemcitabine and tumor cell migration inhibitors 7rh and PP2. To ensure the validity of our findings, we followed a systematic approach that involved testing the inhibitory effects of these drugs. According to our results, the drug combinations' effectiveness could be ordered as follows: paclitaxel + gemcitabine > gemcitabine + 7rh > PP2 + paclitaxel > 7rh + PP2. This study shows that the biomimetic chip system not only facilitates the creation of a realistic in vitro model for examining the cell migration mechanism in late-stage breast cancer but also has the potential to function as an effective tool for future chemotherapy assessment and personalized medicine.

Comprehensive analysis of plasma methylome reveals distinct patterns of methylation changes between responders and non-responders to neoadjuvant chemotherapy in breast cancer

The potential of cell-free DNA (cfDNA) methylation profiling in oncology is increasingly recognized for its ability to offer a comprehensive assessment of tumor biology. In this report, we explore the plasma methylome dynamics in patients with early breast cancer (BC) undergoing neoadjuvant chemotherapy (NACT) using an agnostic genome-wide approach with cell-free DNA immunoprecipitation and sequencing (cfMeDIP-seq). Our cohort comprised seven women with triple-positive BC, assessed for cfDNA methylation changes at multiple time points during their treatment course. Genome-wide analysis revealed distinctive patterns of differential methylation in patients achieving pathological complete response (pCR), with no significant epigenomic modifications in patients with residual disease (RD). Gene set enrichment analysis highlighted dynamic variations in functional pathways associated with therapy response, including metabolism, immune response, and response to xenobiotics, with a notable reversibility post-treatment. Principal component analysis of the differentially methylated regions demonstrated a clear distinction between pCR and RD patients, indicating the potential of cfMeDIP-seq for the non-invasive assessment of therapy response. Such findings suggest that cfMeDIP-seq could complement ctDNA offering broader insights into the global modifications induced by chemotherapy. Although future research is needed to validate and expand on our findings, we offer a proof-of-principle of the potential utility of cfMeDIP-seq in the personalized management of BC.

Delayed onset skin toxicity reaction after peripherally inserted central catheter rupture in lower extremities combined with chemotherapy.

Herein, we present a patient who was undergoing chemotherapy for bilateral breast cancer and experienced delayed-onset skin toxicity reactions after rupture of a peripherally inserted central catheter (PICC) in the lower extremities. The objective of this case report is to provide the necessary nursing assessment for the risk awareness of the PICC internal rupture and the occurrence of central venous catheter extravasation, as well as to strengthen the judgment of delayed skin toxicity of chemotherapeutic drugs. Rupture of the PICC in the lower extremities was primarily attributed to the use of a silicone catheter and an excessive puncture angle. The nature of docetaxel and partial catheter rupture caused drug extravasation, leading to delayed skin toxicity. The use of a polyurethane catheter reduces the incidence of catheter rupture; hence, silicon catheters should be avoided. The central venous catheter is also at risk for the extravasation of chemotherapeutic agents. Moreover, docetaxel-induced delayed skin toxicity, which has a high incidence, should be treated as expected. Nurses and clinicians should be aware of PICC internal rupture and central venous catheter extravasation to strengthen the judgment of delayed skin toxicity of chemotherapeutic drugs.

Telehealth cognitive behaviour therapy for the management of sleep disturbance in women with early breast cancer receiving chemotherapy: a feasibility study

PurposeSleep quality commonly deteriorates in people receiving chemotherapy for breast cancer (BC). We aimed to determine feasibility and acceptability of telehealth-delivered cognitive behaviour therapy for insomnia (CBT-I) in people with early BC receiving (neo)adjuvant chemotherapy.MethodsMulti-centre, single arm, phase 2 feasibility trial. People with stage I-III BC received 4 sessions of telehealth CBT-I over 8 weeks, during chemotherapy. Participants completed Pittsburgh Sleep Quality Index (PSQI) and other Patient Reported Outcome Measures (PROMs) at baseline, post-program (week 9) and post-chemotherapy (week 24); and an Acceptability Questionnaire at week 9. Primary endpoint was proportion completing 4 sessions of telehealth CBT-I.ResultsIn total, 41 participants were recruited: mean age 51 years (range 31–73). All 4 CBT-I sessions were completed by 35 (85%) participants. Acceptability of the program was high and 71% reported ‘the program was useful’. There was no significant difference in the number of poor sleepers (PSQI score ≥ 5) at baseline 29/40 (73%) and week 24 17/25 (68%); or in the mean PSQI score at baseline (7.43, SD 4.06) and week 24 (7.48, SD 4.41). From baseline to week 24, 7/25 (28%) participants had a ≥ 3 point improvement in sleep quality on PSQI, and 5/25 (20%) had a ≥ 3 point deterioration. There was no significant difference in mean PROM scores.ConclusionIt is feasible to deliver telehealth CBT-I to people with early BC receiving chemotherapy. Contrary to literature predictions, sleep quality did not deteriorate. Telehealth CBT-I has a potential role in preventing and managing sleep disturbance during chemotherapy.Australian New Zealand Clinical Trials Registry (ANZCTR) registration number: ACTRN12620001379909 and date 22/12/2020.

The role of resilience and coping strategies as predictors of well-being in breast cancer patients

PurposeThis study investigated the role of resilience and coping strategies on breast cancer patients' well-being using a structural equation model. To achieve this objective, a model previously developed by Mayordomo's group was partially replicated using a longitudinal study design in an oncological sample. MethodsThe study was a longitudinal observational survey. Patients with breast cancer were recruited (N = 166). Resilience was measured with the Mexican Resilience Measurement Scale, coping strategies with the Forms of Coping and Dimensions Scale and perception of the psychological well-being with a short-form of Ryff's Scales of Psychological Well-Being at the start and end of adjuvant chemotherapy (T1 and T2 respectively). ResultsThe results showed stability in the variables over time and revealed differences with respect to Mayordomo's model. The best predictor of well-being at T2 was well-being at T1. In addition, the model indicated that resilience had a direct impact on well-being through problem-focused coping. Indeed, resilience and problem-focused coping best explained well-being at T2. ConclusionsBoth at the start and end of adjuvant chemotherapy for breast cancer, problem-focused coping positively predicted resilience, which in turn was a positive predictor of well-being. On the other hand, emotion-focused coping showed no association with resilience or well-being. As part of the multidisciplinary cancer team, oncology nurses have a key role to play in promoting resilience and problem-focused coping as an important goal of psychosocial interventions in breast cancer patients.

Malignant proliferating trichilemmal tumor post-chemotherapy: A case report

The malignant proliferating trichilemmal tumor (MPTT) is an exceptional adnexal neoplasm of the skin, primarily observed in the scalp of elderly women, often precipitated by local trauma or chronic inflammation. Notably, MPTT exhibits a propensity for local aggressiveness, frequently leading to diagnostic challenges reminiscent of squamous cell carcinoma. The primary treatment modality entails surgical excision with adequate margins, yielding a relatively low local recurrence rate. Herein, we present the case of a 50-year-old woman diagnosed with MPTT of the scalp several years subsequent to undergoing chemotherapy for breast cancer, initially misdiagnosed as squamous cell carcinoma upon biopsy. This case marks only the third reported instance associating MPTT with chemotherapy following breast cancer treatment. We aim to draw attention to this particularly aggressive tumor and its potential origination from benign trichilemmal cysts due to chemotherapy.

Alteration of PD-L1 (SP142) status after neoadjuvant chemotherapy and its clinical significance in triple-negative breast cancer.

The tumor immune microenvironment can change after neoadjuvant chemotherapy (NAC) for triple-negative breast cancer (TNBC). We aimed to investigate the effects of NAC on PD-L1 (SP142) status and its clinical significance in TNBC. Paired samples of biopsy and resection specimens were collected from 182 patients with TNBC before and after NAC. PD-L1 (SP142) expression in immune cells in pre- and post-NAC breast cancer samples and the changes between them were analyzed, along with their relationships with the clinicopathological features and clinical outcomes of the patients. Of the 182 patients, 61 (33.5%) achieved pathologic complete response (pCR) after NAC. PD-L1 (SP142) positivity, defined as immune cell staining in ≥ 1% of tumor area, was a predictor for pCR. PD-L1-positive immune cells significantly increased after NAC (2.8% to 5.2% on average) in 109 patients with measurable residual disease. Alteration of PD-L1 status was observed in 24 (22.0%) of the 109 patients with measurable residual tumors after NAC, and all PD-L1 status-converted patients, except one, revealed negative-to-positive conversion. Regarding chemotherapeutic agents, the use of platinum agents was associated with a significant increase in PD-L1-positive immune cells after NAC. In survival analyses, a positive PD-L1 status after NAC and increase of PD-L1-positive immune cells after NAC were associated with better recurrence-free survival of the patients. PD-L1 (SP142) status changes after NAC, mostly as a positive conversion. As PD-L1 (SP142) status can convey prognostic and predictive information, it needs to be tested before and after NAC.

T7 peptide-mediated co-delivery platform overcoming multidrug-resistant breast cancer: In vitro and in vivo evaluation

P-glycoprotein (P-gp) overexpressed mutidrug resistance (MDR) is currently a key factor limiting the effectiveness of breast cancer chemotherapy. Systemic administration based on P-gp-associated mechanism leads to severe toxic side effects. Here, we designed a T7 peptide-modified mixed liposome (T7-MLP@DTX/SchB) that, by active targeting co-delivering chemotherapeutic agents and P-gp inhibitors, harnessed synergistic effects to improve the treatment of MDR breast cancer. This study established drug-resistant cell models and animal models. Subsequently, comprehensive evaluations involving cell uptake, cell apoptosis, cellular toxicity assays, in vivo tumor-targeting capability, and anti-tumor activity assays were conducted to assess the drug resistance reversal effects of T7-MLP@DTX/SchB. Additionally, a systematic assessment of the biosafety profile of T7-MLP@DTX/SchB was executed, including blood profiles, biochemical markers, and histopathological examination. It was found that this co-delivery strategy successfully exerted the synergistic effects, since there was a significant tumor growth inhibitory effect on multidrug-resistant breast cancer. Targeted modification with T7 peptide enhanced the therapeutic efficacy remarkably, while vastly ameliorating the biocompatibility compared to free drugs. The intriguing results supported the promising potential use of T7-MLP@DTX/SchB in overcoming MDR breast cancer treatment.