Adjuvant Treatment Of Breast Cancer Research Articles

Breast Cancer Adjuvant Radiotherapy and Chemotherapy Sequencing: Sequential, Concomitant, or What Else? A Comprehensive Review of the Adjuvant Combinations Journey.

Background: To date, in breast cancer (BC) treatment, adjuvant chemotherapy (A-CT) has preceded adjuvant radiotherapy (A-RT). In the last twenty years, the adjuvant treatment of BC has quickly evolved due to better knowledge of its molecular biology, genetic profile, and α/β ratio of 3/4 Gy for tumor and normal tissue radiosensitivity. Thus, new schedules with hypofractionated radiotherapy have been tested, and a third generation of A-CT has been introduced, raising the question of whether it is time to rethink the sequencing between these two approaches. Methods: In the last 20 years, many attempts have been made worldwide to optimize the best sequencing strategy between these two approaches in terms of sequential CT-RT and RT-CT and concomitant and sandwich modalities using drugs and schedules. This paper presents a comprehensive review of the state of the art, analyzing all the available studies to assess the sequencing between A-CT and A-RT with different generations of chemotherapy schedules. Results: More than 8000 patients from 30 studies treated with adjuvant chemotherapy and whole breast radiotherapy who were enrolled in randomized, retrospective, and prospective studies were analyzed. Sequential, concomitant, and sandwich modalities of chemotherapy with conventional or hypofractionated RT schedules from the most important studies were included. The most used sequence was adjuvant chemotherapy followed by conventional or hypofractionated radiotherapy. In the concomitant approach, i.v. CMF has been the most important adopted schedule, while the concomitant use of anthracyclines and taxanes with conventional or hypofractionated radiotherapy has been found to be more toxic. One study analyzed the benefit in terms of reducing adjuvant treatment time with upfront hypofractionated radiotherapy and third-generation chemotherapy. Conclusions: At present, the best sequencing strategy has not yet been defined. This comprehensive review is a journey among the most important randomized, retrospective, and prospective studies that highlights the past, current, and novel time sequencing proposals between A-CT and A-RT to assess the state of the art and provide useful information for future adjuvant approaches in breast cancer treatment.

Pro-inflammatory cytokines increase temporarily after adjuvant treatment for breast cancer in postmenopausal women: a longitudinal study

BackgroundBreast cancer patients have an increased risk of cardiometabolic disease and for many patients, adjuvant therapy causes an altered lipid profile, insulin resistance and inflammation. Previous follow-up studies are inconclusive regarding the duration of therapy-induced inflammation. We examined the acute and persistent changes of adjuvant chemotherapy on inflammatory and metabolic health markers in breast cancer patients.MethodsPlasma levels of IL-6, IL-8, IL-10, IFN-γ, TNF-α, high-sensitivity C-reactive protein (hsCRP) and metabolic health parameters were analyzed before, shortly after and every six months up to two years after adjuvant chemotherapy treatment in 51 postmenopausal early breast cancer (EBC) patients, as well as in 41 healthy age- and BMI-matched controls. A target-specific multiplex assay was applied for cytokine measurements.ResultsBefore initiation of adjuvant therapy, plasma IL-8 levels were higher in EBC patients (31%, p = 0.0001). Also, a larger proportion of the patients had a hsCRP level above 2 mg/L (41%) compared to the controls (17%, Χ2 = 5.15, p = 0.023). Plasma levels of all five cytokines, but not hsCRP, were significantly increased after compared to before adjuvant chemotherapy (15–48% increase; all p ≤ 0.05). Already six months after ending chemotherapy treatment, all plasma cytokine levels were significantly reduced and close to pre-chemotherapy levels. Adjuvant chemotherapy caused a worsened lipid profile (increased triglycerides, lower HDL levels), insulin resistance and increased plasma insulin levels that remained high during the first year after chemotherapy.ConclusionPostmenopausal women with EBC have temporarily increased plasma levels of pro-inflammatory cytokines after adjuvant chemotherapy. Although transient, the therapy-induced increase in plasma cytokine levels, together with dyslipidemia and insulin resistance, may contribute to cardiometabolic risk in breast cancer patients treated with adjuvant chemotherapy.Trial registration The clinical trial (registration number NCT03784651) was registered on www.clinicaltrials.gov on 24 December 2018.

Targeting STAT3 signaling pathway by curcumin and its analogues for breast cancer: A narrative review.

Breast cancer (BC) continues to be a significant global health issue, with a rising number of cases requiring ongoing research and innovation in treatment strategies. Curcumin (CUR), a natural compound derived from Curcuma longa, and similar compounds have shown potential in targeting the STAT3 signaling pathway, which plays a crucial role in BC progression. The aim of this study was to investigate the effects of curcumin and its analogues on BC based on cellular and molecular mechanisms. The literature search conducted for this study involved utilizing the Scopus, ScienceDirect, PubMed, and Google Scholar databases in order to identify pertinent articles. This narrative review explores the potential of CUR and similar compounds in inhibiting STAT3 activation, thereby suppressing the proliferation of cancer cells, inducing apoptosis, and inhibiting metastasis. The review demonstrates that CUR directly inhibits the phosphorylation of STAT3, preventing its movement into the nucleus and its ability to bind to DNA, thereby hindering the survival and proliferation of cancer cells. CUR also enhances the effectiveness of other therapeutic agents and modulates the tumor microenvironment by affecting tumor-associated macrophages (TAMs). CUR analogues, such as hydrazinocurcumin (HC), FLLL11, FLLL12, and GO-Y030, show improved bioavailability and potency in inhibiting STAT3, resulting in reduced cell proliferation and increased apoptosis. CUR and its analogues hold promise as effective adjuvant treatments for BC by targeting the STAT3 signaling pathway. These compounds provide new insights into the mechanisms of action of CUR and its potential to enhance the effectiveness of BC therapies.

Surgical Management and Its Impact on Adjuvant Treatment in Recurrent Ipsilateral Breast Cancer: A Retrospective Cohort Study.

Background: Breast cancer (BC) recurrence, defined as the reappearance of cancer in the ipsilateral breast after primary treatment, poses significant challenges in clinical management. Despite advances in treatment, recurrence rates persist, ranging from 0.6 to 1.5% annually, reaching 10-15% at 20 years. This study aims to analyze the surgical and oncological characteristics of patients with BC recurrence. Methods: This retrospective study includes 56 patients diagnosed with recurrent BC between October 2018 and April 2022. Data were collected from a prospectively maintained surgical database. A descriptive analysis was performed on the initial BC, and the recurrence, including surgical complications, was classified using the Clavien-Dindo system. The success rates of selective sentinel lymph node (SLN) biopsies and aberrant drainages were assessed based on previous surgeries. Results: The cohort included 55 females and 1 male, with a median age of 65.3 years. The mean time to BC recurrence was 11.5 years. Among them, 26.8% underwent breast-conserving surgery, 41.1% had a mastectomy, 21.4% had a mastectomy with reconstruction, and 10.7% had an excision over a previous mastectomy. An SLN biopsy was performed in 78.6% of cases, with higher success rates in those without a previous axillary lymph node dissection (85.7% vs. 63.2%). Aberrant drainage was more frequent in patients with a previous ALND (44.4% vs. 20%). The median follow-up was 41.3 months, with 10.7% experiencing a second recurrence. Conclusions: Repeat breast-conserving surgery with re-irradiation for ipsilateral recurrence is feasible and does not significantly increase complications. SLN biopsy is valuable for restaging and tailoring adjuvant therapies, with ALND not being necessary if re-SLN biopsy shows no drainage. The management of aberrant drainage remains controversial.

Efficacy and safety of nanoparticle albumin‑bound paclitaxel compared with solvent‑based paclitaxel in adjuvant therapy for breast cancer: A retrospective study.

The current evidence for the use of nanoparticle albumin-bound paclitaxel (nab-PTX) for adjuvant breast cancer chemotherapy is insufficient. The present study aimed to assess the efficacy and toxicity of nab-PTX in comparison with solvent-based paclitaxel (sb-PTX) in postoperative adjuvant breast cancer treatment. A total of 345 patients were included in the study and separated into nab-PTX (n=289) and sb-PTX (n=56) groups based on the type of taxane used in the adjuvant chemotherapy regimen. The study evaluated the baseline characteristics in both groups and the risk factors for postoperative recurrence of mammary cancer. Furthermore, data concerning disease-free survival (DFS) and adverse effects were obtained and analyzed, and group confounding variables were addressed using 1:2 propensity score matching (PSM). Comparisons before PSM revealed significant differences in baseline characteristics including age, underlying disease, lymph node involvement, vascular invasion, human epidermal growth factor receptor 2 and axillary surgery (P<0.05). Following PSM, there were 90 patients in the nab-PTX group and 56 in the sb-PTX group, with no significant differences in the baseline differences (P>0.05). Before PSM, the 73-month DFS rate was 97.9% in the nab-PTX group compared with 91.1% in the sb-PTX group. However, there were no significant differences between the groups before or after PSM (P=0.15 and P=0.49, respectively). Additionally, Cox regression analysis demonstrated a significantly lower chance of recurrence in patients aged >45 years [hazard ratio (HR), 0.197; 95% confidence interval (CI), 0.052-0.753; P=0.018], whereas underlying disease (HR, 5.352; 95% CI, 1.310-21.854; P=0.019) and lymph node infiltration (HR, 8.930; 95% CI, 1.121-71.161; P=0.039) significantly increased the risk of recurrence. Regarding safety, the sb-PTX group had a significantly greater incidence of anaphylaxis, whereas the nab-PTX group had significantly increased rates of anemia and peripheral neuropathy (P<0.05). In summary, the 73-month DFS rate of the nab-PTX cohort exceeded that of the sb-PTX cohort, but no significant difference was detected between them. Underlying disease, lymph node metastasis and an age of ≤45 years are significant predictors of postoperative recurrence of breast cancer.

Efficacy of antiobesity medications among breast cancer survivors taking aromatase inhibitors.

Aromatase inhibitors (AI) block estrogen synthesis and are used as long-term adjuvant treatment for breast cancer in postmenopausal women. AI use can be associated with weight gain that can lead to increased cardiometabolic risk. The response to anti-obesity medications (AOM) in patients using AI has yet to be studied. We sought to investigate weight loss outcomes of AOM in patients taking AI for breast cancer treatment. This is a matched retrospective cohort study of breast cancer survivors on AI using AOM (AOM/AI group). We compared their weight loss outcomes with a group of female patients with obesity, without a history of breast cancer or AI use, on AOM (AOM group). The primary endpoint was total body weight loss percentage (TBWL %) at the last follow-up. We performed mixed linear regression models, including diabetes status at baseline, to assess associations between use of AOM with/without AI with total body weight loss percentage (TBWL%). We included 124 patients: 62 in the AOM/AI group (63.6 ± 10years, body mass index [BMI] 34.3 ± 7.1kg/m2) and 62 in the AOM group (62.8 ± 9.9years, BMI 34.6 ± 6.5kg/m2). The mean time of follow up was 9.3 ± 3.5months, with no differences among the two groups. The AOM/AI group had a lower TBWL% compared to the AOM group at the last follow-up -5.3 ± 5.0 vs. -8.2 ± 6.3 (p = 0.005). The results remained significant after adjusting for diabetes status (p = 0.0002). At 12months, the AOM/AI group had a lower TBWL% compared to the AOM group 6.4 ± 0.8% vs. 9.8 ± 0.9% (p = 0.04). The percentage of patients achieving ≥ 5%, ≥ 10%, and ≥ 15% of weight loss at 12months was greater in the AOM compared to the AOM/AI group. Although the weight loss response was suboptimal, patients in the AOM/AI group had improvement in fasting glucose, glycated hemoglobin, systolic blood pressure, and low-density lipoprotein cholesterol. The use of AI in breast cancer survivors is associated with less weight loss response to AOM compared to patients without breast cancer history and who do not take AI. Studies are needed to assess the mechanisms behind the differential weight loss response to AOM in women taking AI.

Cost-effectiveness of Pembrolizumab in Combination with Chemotherapy as Neoadjuvant Treatment and Continued as a Single Agent Adjuvant Treatment for High-Risk Early-Stage Triple-Negative Breast Cancer in Hong Kong.

The phaseIII randomized KEYNOTE-522 trial demonstrated that pembrolizumab in combination with chemotherapy as neoadjuvant treatment followed by adjuvant pembrolizumab (pembrolizumab + chemotherapy) provided significant improvements in event-free survival (EFS) and overall survival (OS) for patients with high-risk early-stage triple-negative breast cancer (eTNBC). The objective was to assess the cost-effectiveness of pembrolizumab + chemotherapy compared to neoadjuvant chemotherapy alone (chemotherapy) in patients with high-risk eTNBC from a Hong Kong third-party payer perspective. A multistate transition model with four health states (event-free), locoregional recurrence, distant metastases, and death) was developed to assess the lifetime medical costs and health outcomes (3% annual discount), along with incremental cost-effectiveness ratios (ICERs) using efficacy and safety data from the KEYNOTE-522 trial. The health state utilities were derived from KEYNOTE-522 Euro-QoL-five-dimension five-level questionnaire (EQ-5D-5L) data. Costs were expressed in 2022 Hong Kong dollars (HKD).Scenario and sensitivity analyses were performed to assess the robustness of results. Over a 32-year time horizon, base case results showed that pembrolizumab + chemotherapy was associated with a 3.42year longer EFS and expected gains of 3.05 lifeyears (LYs) and 2.45 quality-adjusted lifeyears (QALYs) compared to chemotherapy. The resultant ICERs were HKD135,200 per QALY gained and HKD108,463 per LY gained, which were lower than the World Health Organization (WHO) cost-effectiveness threshold of three times gross domestic product (GDP) per capita for Hong Kong of HKD1,171,308 per QALY. The one-way sensitivity analyses (OWSA) and probabilistic sensitivity analysis (PSA) showed the results were robust across various inputs and alternative scenarios. On the basis of the analysis conducted for a 56-year-old cohort with high-risk eTNBC and assumptions in the model, pembrolizumab + chemotherapy represents a cost-effective proposition (as the ICER is approximately 35% of the GDP per capita in Hong Kong) for patients with high-risk eTNBC in Hong Kong.

Prognostic impact of selection criteria of current adjuvant endocrine therapy trials NATALEE and monarchE in postmenopausal HRpos/HER2neg breast cancer patients treated with upfront letrozole

BackgroundThe monarchE and NATALEE trials demonstrated the benefit of CDK4/6 inhibitor (CDK4/6i) therapy in adjuvant breast cancer (BC) treatment. Patient selection, based on clinical characteristics, delineated those at high (monarchE) and high/intermediate recurrence risk (NATALEE). This study employed a historical patient cohort to describe the proportion and prognosis of patients eligible for adjuvant CDK4/6i trials. MethodsBetween 2009 and 2011, 3529 patients were enrolled in the adjuvant PreFace clinical trial (NCT01908556). Eligibility criteria included postmenopausal patients with hormone receptor-positive (HRpos) BC for whom a five-year upfront therapy with letrozole was indicated. Patients were categorized into prognostic groups according to monarchE and NATALEE inclusion criteria, and their invasive disease-free survival (iDFS) and overall survival (OS) were assessed. ResultsAmong 2891 HRpos patients, 384 (13.3 %) met the primary monarchE inclusion criteria. The majority (n = 261) qualified due to having ≥ 4 positive lymph nodes. For NATALEE, 915 out of 2886 patients (31.7 %) met the eligibility criteria, with 126 patients (13.7 %) being node-negative. Patients from monarchE with ≥ 4 positive lymph nodes and NATALEE with stage III BC exhibited the poorest prognosis (3-year iDFS rate 0.87). Patients ineligible for the trials demonstrated prognoses similar to the most favorable patient groups within the eligibility criteria. ConclusionPatient populations eligible for monarchE and NATALEE trials differed. Nearly a third of the postmenopausal HRpos population, previously under upfront letrozole treatment, met the NATALEE prognostic eligibility criteria. As certain eligible groups had a prognosis similar to non-eligible patients, it might be interesting to explore additional patient groups for CDK4/6i therapy.

Apple polyphenol phloretin inhibits type II glucose transporter and enhances anti-HER2 antibody drug binding as an adjuvant treatment for HER2-positive breast cancer

Apple polyphenol phloretin inhibits type II glucose transporter and enhances anti-HER2 antibody drug binding as an adjuvant treatment for HER2-positive breast cancer

Aromatase inhibitors evoke periorbital allodynia in mice via calcitonin gene-related peptide and its receptors in Schwann cells

Background: Treatment with the currently recommended aromatase inhibitors (AIs) for adjuvant endocrine treatment of estrogen receptorpositive breast cancer is associated with debilitating musculoskeletal pain symptoms (AIMS) and headache. Recent evidence suggests that the proalgesic channel transient receptor potential ankyrin 1 (TRPA1) is implicated in AIMS. Here, we investigated the cellular and molecular mechanisms, including TRPA1, implicated in periorbital mechanical allodynia (PMA), a surrogate of headache-like pain, evoked by AIs in mice. Methods: C57BL6/J mice were treated with intragastric letrozole (0.05-0.5 mg/kg), exemestane (1-5 mg/kg) or anastrozole (0.02-0.2 mg/kg) and were evaluated by applying von Frey filaments to the periorbital region over the rostral portion of the eye. Some mice were pretreated (subcutaneous in the periorbital area) with receptor, channel, or enzyme inhibitors. PMA was also investigated in mice with selective silencing of Trpa1 and receptor activity modifying protein 1 [Ramp1, the component of calcitonin gene related peptide (CGRP) receptor required for its functioning] in Schwann cells (Plp-Cre+-Trpa1fl/fl and Plp-Cre+-Ramp1fl/fl mice, respectively) or trigeminal neurons (Adv-Cre+- Trpa1fl/fl and Adv- Cre+- Ramp1fl/fl mice, respectively). Results: Letrozole dose-dependently produced PMA that was attenuated by a TRPA1 antagonist (A967079) or a CGRP receptor antagonist (olcegepant), whereas indomethacin was ineffective. Selective silencing of Trpa1 in both Schwann cells and trigeminal neurons reduced letrozole- evoked PMA. Silencing of Ramp1 in Schwann cells, but not in trigeminal neurons, attenuated PMA. Inhibition of the intracellular pathway known to promote PMA by CGRP action in Schwann cells, including adenylyl cyclase (SQ-22536), nitric oxide synthase (L-NG-Nitro arginine methyl ester), and oxidative stress (N-tert-butyl-a-phenylnitrone) inhibitors reduced letrozole-evoked PMA. PMA evoked by exemestane (1, 5, 10 mg/kg i.g.) or anastrozole (0.02, 0.1, 0.2 mg/kg i.g.) Was also markedly reduced in mice with selective silencing of TRPA1 in Schwann cells and nociceptors. Conclusions: Data indicate that letrozole, targeting TRPA1 in peptidergic nerve terminals, releases CGRP that engages its receptor in adjacent Schwann cells to trigger a complex intracellular pathway that results in TRPA1 activation and the ensuing ROS release to sustain PMA. Should these mechanisms be present in patients, their inhibition may ameliorate cephalic mechanical allodynia associated with aromatase inhibitors-induced headaches.

Real-World Study of Adjuvant Biosimilar Trastuzumab-dkst for HER2-Positive Breast Cancer Treatment in a Brazilian Population.

Biological monoclonal antibodies play a pivotal role in cancer treatment, with biosimilars significantly enhancing their accessibility. In Brazil's ethnically diverse setting, real-world evidence is crucial for assessing the effectiveness and applicability of these therapies in routine clinical practice. We performed a multicentric, observational, prospective real-world study on biosimilar trastuzumab-dkst for adjuvant treatment of early HER2-positive breast cancer in Brazilian patients. Data were collected using a case-report form. Of the 176 recruited, we present data from the first 59 patients (mean age 51.7 ± 12.9years) who had completed treatment with trastuzumab-dkst. The mean time from diagnosis to the first adjuvant treatment with trastuzumab-dkst was 5.5 ± 2.7months. Of the patients, 59% of patients achieved at least a 30-month follow-up. The 31.7-month invasive disease-free survival rate (IDFS) was 94.5% (95% CI 83.9-98.2%) and median IDFS was not achieved, since only three patients had invasive disease recurrence. The overall survival rate was 100% until the last assessment. The observed adverse events were similar to those presented by other studies using biosimilar or reference trastuzumab. Four serious adverse events (8.5%) were observed. A reduction in left ventricular ejection fraction of at least 10% was observed in 16.9% of participants. There was no treatment interruption, and three participants (5.1%) had their trastuzumab-dkst dose reduced. Our study reinforces the existing pivotal data, underscoring the real-world efficacy and safety of biosimilar trastuzumab-dkst in the adjuvant treatment for early HER2-positive breast cancer. The preliminary long-term effectiveness and safety data we present further validate trastuzumab-dkst's role as a cost-saving alternative in oncological care. These findings have important implications for improving patient access to crucial treatments and for the more efficient use of healthcare resources. NCT03892655.

Efficacy and safety of concurrent capecitabine and radiotherapy as adjuvant treatment in triple negative breast cancer.

e12534 Background: Triple-negative breast cancer remains a very aggressive disease with few treatments option. Neoadjuvant dose dense chemotherapy, adjuvant therapy with capecitabine for residual disease and radiotherapy are standard treatments. The aims of this study were to evaluate the efficacy and safety of capecitabine concurrent with radiotherapy in initially clinical stage III patients with triple negative breast cancer in order to improve locoregional control and survival of these patients. Methods: We prospectively analyzed 24 patients with triple negative breast cancer with residual disease after dose dense neoadjuvant chemotherapy with Epirubicin and Cyclophosphamide and Docetaxel (in some cases with carboplatin) who received concurrent Capecitabine and radiotherapy in adjuvant setting. External beam radiotherapy to the hole breast was administered at a dose of 45–50.4 Gy in 25–28 fractions, concurrent with Capecitabine 825 mg/m2, 5 days/week. Results: Median age at diagnostic was 47.1±7.4. Stage distribution was as followed: 45.8% stage IIIA, 25% stage IIIB and 29.2% stage IIIC. Median follow-up was 31 months. Median Disease-Free Survival (DFS) was 48 months, with 76%, 68%, and 46% of patients without recurrence at 24, 36 and 48 months respectively. All patients presented with distant relapses. Median overall survival (OS) was not reached, and 3 years survival rate was 88%. Most common toxicities of concurrent radiotherapy and capecitabine were radiation dermatitis all grades in 100% of patients, grade 3 in 37.5% and grade 4 in 4.1%. Other side effects were neutropenia grade 4 in 8.3% and lymphopenia grade 4 in 45.8% of patients. Conclusions: Capecitabine concurrent with radiotherapy appears to be very efficacious and safe in the adjuvant treatment of breast cancer, especially in preventing local recurrence.

A single-center retrospective review of the impact of cryotherapy on peripheral neuropathy scores in patients with breast cancer who received chemotherapy with a taxane-based treatment regimen.

e24106 Background: Taxanes are a class of chemotherapy frequently used for neoadjuvant and adjuvant treatment of breast cancer. While effective, taxane use is not without adverse effects, the most well-known being chemotherapy-induced peripheral neuropathy (CIPN). As CIPN is dose-related, it can lead to dose reductions and interruptions in therapy that may be detrimental to the patient. Cryotherapy has been used as a prevention strategy, but its efficacy remains unclear. Methods: We performed a retrospective review of the cryotherapy program in our center. Included patients had breast cancer of any stage treated with a taxane in the neoadjuvant or adjuvant setting. All patients were offered cryotherapy at the time of their treatment and were separated into cohorts whether they opted in or out (“cryotherapy” and “non cryotherapy,” respectively). Neuropathy scores were collected by nursing staff via survey and scaled from 0-4. Patient demographics and neuropathy scoring were compared between the “cryotherapy” and “non cryotherapy” cohorts. Results: In total, 41 patients were included. Nearly half of patients in each cohort experienced neuropathy, 10 patients (41.7%) treated with cryotherapy and 8 patients (47.1%) without cryotherapy use. Younger age (46.5 years vs 57 years, p = 0.060), and patients using Medicaid (35.3% vs 75.0%, when compared to all other insurance types, p = 0.023) predicted cryotherapy use. Use of paclitaxel also predicted cryotherapy used when compared to docetaxel (76.0% and 31.2%, respectively, p = 0.009). There was not a significant difference in predicted neuropathy score between the cohorts (Adjusted Multiplicative Effect = .81, 95% CI = .34-1.96, p = .645). Conclusions: Our data did not suggest that the use of cryotherapy could predict lower neuropathy scores, but our study suffered from small sample size and short-duration of follow-up. Additional large, randomized trials with standard neuropathy scoring scales are needed to better evaluate the efficacy of cryotherapy in prevention of CIPN for breast cancer patients receiving taxane-based therapy.

Impact of racial disparities in adjuvant treatment of triple negative breast cancer (TNBC) among American Indians/Alaskan Natives (AI/AN) and non-Hispanic Whites (NHW) on overall survival (OS).

e13736 Background: There are significant differences in patient and tumor characteristics among AI/AN and NHW breast cancers (BC) which adversely impact overall survival in AI/AN. Prior studies have also shown higher Mortality: Incidence ratio for BCs in AI/AN as compared to NHW. The aims of this study are to 1) investigate disparities in adjuvant treatment of TNBC between the two races adjusting for age, stage, and year of diagnosis; and 2) Assess differences in OS. Methods: This was a hospital based, retrospective cohort study using the National Cancer Database. AI/AN and NHW women with TNBC, greater than or equal to 18 years of age, diagnosed with BC between the years 2010 through 2019, stages I, II, and III were included. Propensity score matching in a 1:3 ratio was used for age, year, and analytical stage at diagnosis. Primary endpoint was time to first treatment and compliance with recommended treatment. Secondary endpoint was OS. Results: A total of 489 AI/AN and 1465 matched NHW women with TNBC were identified. AI/AN women traveled longer distances for cancer care (p&lt;.01), resided in lower median income zip codes at the time of diagnosis (p&lt;.001), had a higher Charlson-Deyo (CD) comorbidity score (p&lt;.001), and were less likely to have private insurance (p&lt;.001). There was no difference in the rates of chemotherapy, surgery, and radiation therapies that were recommended and received by the two races. Time to first treatment was significantly longer for AI/AN as compared to NHW women (Mean ± SD: 35 ± 27 days vs. 39 ±27 days; p=.005). Multivariable analysis revealed that longer time to first treatment was associated with only higher CD score (p=.013) and non-private insurance (p=.027), but no longer associated with race (p=.324). Compliance with recommended treatment was similar between AI/AN and NHW women (93.5% vs 92.9%, p=.096). Compliance was significantly associated with only insurance status (p &lt; .001) with Medicare/Medicaid having the lowest compliance. OS did not differ by race (p=.299, HR=1.132; 95% CI: 0.90-1.43). Cancer stage, CD score, insurance status, and treatment compliance were associated with worse OS. Conclusions: In patients with TNBC, there was no difference in time to treatment, compliance with recommended treatment or OS among AI/AN in comparison to White women when matched for age, stage, and year of diagnosis. Medicare/Medicaid insurance was associated with prolonged time to treatment, lower compliance with recommended treatment and decreased survival when compared with other insurances. Higher comorbidities adversely impacted time to treatment and overall survival. In order to improve BC mortality, it is important to manage comorbid conditions and improve detection of cancer at earlier stages. Prospective studies comparing outcomes by race are needed to confirm these findings.

Pathological and clinical outcomes following neoadjuvant dual HER2 therapy for early-stage breast cancer: An Australian institutional real-world experience.

There has been significant progress made in developing novel targeted therapies in the neoadjuvant setting for non-metastatic HER2-positive breast cancer, which may be used in combination with conventional chemotherapy to optimise pathological responses at surgery. However, these therapies, particularly the chemotherapeutic components, may portend significant and long-lasting toxicity. Hence, de-escalation of treatment intensity has been an area of interest and was evaluated in the phase II NeoSphere study. Herein, we report the real-world pathological and survival outcomes from neoadjuvant taxane and dual HER2 blockade recorded at our centre. This was a retrospective cohort study of patients receiving neoadjuvant pertuzumab, trastuzumab and taxane chemotherapy for non-metastatic HER2-positive breast cancer at a single centre in Sydney, Australia. We collected data pertaining to baseline demographic characteristics, pathological response rates, post-surgical prescribing patterns and also undertook survival analyses for invasive disease-free survival (iDFS) as well as exploratory analyses for correlations between pre-specified clinicopathologic factors and pathological response at surgery. Our population was largely similar at baseline to the NeoSphere study. 71 patients were included in the final analysis. 61% achieved a pathological complete response (pCR). Three patients received conventional chemotherapy in the adjuvant setting. 92% of included patients were alive and disease-free at 3 years of follow-up. Only 3 events of recurrence or death were recorded at a median follow-up of 32 months. No significant difference in iDFS was noted between patients achieving pCR and those with residual disease at surgery. This study demonstrates that de-escalated adjuvant treatment for HER2-positive early breast cancer achieved favourable pathological and long-term outcomes comparable to large trials, some utilising more intensive chemotherapeutic components.

Statins inhibit paclitaxel-induced PD-L1 expression and increase CD8+ T cytotoxicity for better prognosis in breast cancer.

In recent years, the widespread use of lipid-lowering drugs, especially statins, has attracted people's attention. Statin use may be potentially associated with a reduced risk of breast cancer. To explore the relationship between statin use and cancer risk. And further explore the potential role of statins in the adjuvant treatment of breast cancer. Data for the Mendelian randomization portion of the study were obtained from genome-wide association studies of common cancers in the UK Biobank and FinnGen studies and from the Global Lipid Genetics Consortium's low density lipoprotein (LDL). In addition, the impacts of statins and chemotherapy drugs on breast cancer were examined using both in vitro and in vivo models, with particular attention to the expression levels of the immune checkpoint protein PD-L1 and its potential to suppress tumor growth. Data from about 3.8 million cancer patients and ~1.3 million LDL-measuring individuals were analyzed. Genetically proxied HMGCR inhibition (statins) was associated with breast cancer risk reduction (P=0.0005). In vitro experiments showed that lovastatin significantly inhibited paclitaxel-induced PD-L1 expression and assisted paclitaxel in suppressing tumor cell growth. Furthermore, the combination therapy involving lovastatin and paclitaxel amplified CD8+ T-cell infiltration, bolstering their tumor-killing capacity and enhancing in vivo efficacy. The utilization of statins is correlated with improved prognoses for breast cancer patients and may play a role in facilitating the transition from cold to hot tumors. Combination therapy with lovastatin and paclitaxel enhances CD8+ T-cell activity and leads to better prognostic characteristics.

Nutritional support in the complex of medical rehabilitation at the stage of adjuvant radiation therapy of breast cancer

BACKGROUND: Currently it is known that there exists the need for complex medical rehabilitation at the stage of adjuvant radiation treatment of breast cancer. However, data on the combined use of nutritional support and physical factors at this stage of oncological treatment are not available. AIM: Evaluation of the effectiveness of specialized therapeutic and preventive nutrition in patients with malignant breast diseases and a history of polychemotherapy at the stage of adjuvant radiation therapy in complex medical rehabilitation using low-temperature plasma and general magnetic therapy. MATERIALS AND METHODS: A prospective simple randomized study was conducted, which involved 60 patients at the stage of adjuvant radiation therapy for breast cancer. The main group (n=30) received a course of medical rehabilitation with the inclusion of nutritional support using specialized therapeutic and preventive nutrition LEOVIT ONCO®, as well as exposure to low-temperature plasma and general magnetotherapy. In the comparison group (n=30), the rehabilitation course included general magnetic therapy without therapeutic and preventive nutrition. All patients underwent individual physiotherapy exercises, and sessions with a medical psychologist. The results obtained were recorded using clinical and functional, laboratory, instrumental studies. RESULTS: It has been established that the use of specialized dietary products LEOVIT ONCO and physical factors is an effective method of rehabilitation. The use of nutritional support demonstrates the maintenance of the patient’s protein status, reduces intoxication, and reduces the negative impact of oxidative stress factors in the body at the stage of adjuvant radiation treatment. The inclusion of low-temperature plasma and general magnetic therapy in the rehabilitation program has a beneficial effect on hemomicrocirculation in the area of ionizing radiation exposure. CONCLUSION: The use of nutritional support and physical factors, as a component of complex medical rehabilitation, helps to maintain the optimal nutritional status of the patient, reduces the manifestations of skin radiation reactions, improves the psycho-emotional state of patients and the quality of life of patient.

Abstract PO5-12-11: Characterizing Symptom Alerts in Different Breast Cancer Regimens: A Remote Symptom Monitoring Study

Abstract Introduction: Remote symptom monitoring is becoming more common in the management of patients on active cancer treatments. The patterns of symptoms and subsequent alerts for specific types of treatment administered as part of standard of care remains unknown. This study aims to characterize the frequencies and types of symptom alerts among breast cancer patients receiving neoadjuvant and adjuvant therapy. Methods: This secondary analysis used data from a hybrid type 2 randomized controlled trial testing the implementation of remote symptom monitoring. For our analysis, we included women with breast cancer receiving (neo)adjuvant therapy. Enrolled patients received remote symptom monitoring surveys within 30 days of treatment initiation at the University of Alabama at Birmingham from 06/2021 to 05/2023. Self-reported symptoms were recorded via weekly electronic surveys for six months. The weekly survey used the PRO-CTCAE measurement tool and patients report frequency, intensity, and interference of the following symptoms: constipation, decreased appetite, diarrhea, cough, insomnia, nausea/vomiting, neuropathy, pain, urinary problems. Symptom alert severity is categorized as either moderate or severe. Self-reported race and treatment regimen (within the first 60 days) were abstracted from the electronic medical record. Regimens were grouped into three categories 1) trastuzumab-containing, 2) any regimen with pembrolizumab, 3) chemotherapy without trastuzumab or pembrolizumab. Descriptive statistics were calculated using frequencies and percentages for categorical variables and medians and interquartile ranges (IQR) for categorical variables. Results: A total of 108 women with breast cancer were included in our analysis. Overall, 54% were of White race, 36.1% were of Black or African American race, and 1.85% were of Asian race. The median age was 54 years (IQR 41-65). Fifty-one percent were prescribed a chemotherapy regimen, 33% trastuzumab-based regimen, and 15% pembrolizumab-based regimen. Symptom alerts were addressed supportively or escalated with nursing and treating oncologist via direct communication with patients. A total of 1438 symptom alerts were triggered with 55% of surveys generating an alert. The most reported symptom alert was pain, accounting for 30% of all alerts. Additionally, of all symptom alerts, 70% were moderate and 30% severe, with similar distributions across regimens. Patients receiving pembrolizumab regimen most often reported moderate pain compared to the other two regimens (35% vs 22% vs 23%). However, severe pain was most often reported by those receiving chemotherapy at 46%, trastuzumab-based regimen at 40%, and pembrolizumab-based regimen at 31%. Furthermore, patients on trastuzumab-based regimens reported severe diarrhea most frequently (11%) compared to 3% &amp; 2% for the other two regimens. Discussion: Symptoms experienced during receipt of (neo)adjuvant breast cancer treatment are common, with the majority being moderate in nature. Differences in symptom profiles were observed across different treatment modalities, consistent with known side effect profiles. The higher prevalence of pain in patients receiving chemotherapy alone may be attributed to the use of growth factors in these regimens. Further exploration is warranted to investigate the use of supportive medications in managing these symptoms. Further evaluations are underway to evaluate how symptom alerts could potentially increase treatment adherence and decrease hospitalizations. Citation Format: Katia Khoury, Nicole Caston, Megan Patterson, Nancy Holmes, Jena Seward, Erica Stringer-Reasor, Nusrat Jahan, Gabrielle Rocque. Characterizing Symptom Alerts in Different Breast Cancer Regimens: A Remote Symptom Monitoring Study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-12-11.

Aspirin vs Placebo as Adjuvant Therapy for Breast Cancer

Observational studies of survivors of breast cancer and prospective trials of aspirin for cardiovascular disease suggest improved breast cancer survival among aspirin users, but prospective studies of aspirin to prevent breast cancer recurrence are lacking. To determine whether aspirin decreases the risk of invasive cancer events among survivors of breast cancer. A011502, a phase 3, randomized, placebo-controlled, double-blind trial conducted in the United States and Canada with 3020 participants who had high-risk nonmetastatic breast cancer, enrolled participants from 534 sites from January 6, 2017, through December 4, 2020, with follow-up to March 4, 2023. Participants were randomized (stratified for hormone receptor status [positive vs negative], body mass index [≤30 vs >30], stage II vs III, and time since diagnosis [<18 vs ≥18 months]) to receive 300 mg of aspirin (n = 1510) or placebo once daily (n = 1510) for 5 years. The primary outcome was invasive disease-free survival. Overall survival was a key secondary outcome. A total of 3020 participants were randomized when the data and safety monitoring committee recommended suspending the study at the first interim analysis because the hazard ratio had crossed the prespecified futility bound. By median follow-up of 33.8 months (range, 0.1-72.6 months), 253 invasive disease-free survival events were observed (141 in the aspirin group and 112 in the placebo group), yielding a hazard ratio of 1.27 (95% CI, 0.99-1.63; P = .06). All invasive disease-free survival events, including death, invasive progression (both distant and locoregional), and new primary events, were numerically higher in the aspirin group, although the differences were not statistically significant. There was no difference in overall survival (hazard ratio, 1.19; 95% CI, 0.82-1.72). Rates of grades 3 and 4 adverse events were similar in both groups. Among participants with high-risk nonmetastatic breast cancer, daily aspirin therapy did not improve risk of breast cancer recurrence or survival in early follow-up. Despite its promise and wide availability, aspirin should not be recommended as an adjuvant breast cancer treatment. ClinicalTrials.gov Identifier: NCT02927249.

Adverse effects of tamoxifen treatment on bone mineral density in premenopausal patients with breast cancer: a systematic review and meta-analysis.

It is well known that adjuvant tamoxifen treatment for breast cancer in postmenopausal women decreased bone loss. However, the effects of adjuvant tamoxifen therapy on bone mineral density (BMD) in premenopausal patients with breast cancer remains uncertain. Tamoxifen would have a potential impact of premenopausal BMD on health. The aim of this meta-analysis was to assess this in premenopausal women with primary breast cancer. Through April 2020, studies reporting BMD changes of lumbar spine or hip in premenopausal women with primary breast cancer treated with adjuvant tamoxifen and tamoxifen plus chemotherapy or ovarian function suppression (OFS) were collected from EMBASE and PubMed. The meta-analysis was performed using random effects model of the standardized mean difference (SMD) of BMD in patients. A total of 1432 premenopausal patients were enrolled in eight studies, involving 198 patients treated with tamoxifen alone in three studies. After a 3-year median follow-up, adjuvant tamoxifen decreased the lumbar spinal and hip BMD by as much as an SMD of -1.17 [95% confidence interval (CI); -1.58 to -0.76)] and -0.66 (95% CI, -1.55 to 0.23), respectively. In subgroup analysis in patients treated adjuvant tamoxifen and tamoxifen plus chemotherapy or OFS according to follow-up duration, the bone change of < 3years follow-up group was -0.03 SMD (95% CI, -0.47 to 0.41) and that of ≥ 3years follow-up group was -1.06 SMD (95% CI, -1.48 to -0.64). Compared with patients who received tamoxifen alone, patients who received combination therapy with chemotherapy or OFS showed lesser bone loss at the lumbar spine. Our meta-analysis demonstrated that adjuvant tamoxifen therapy in premenopausal patients caused bone loss after 3years of follow-up, especially at the lumbar spines. For a definite evaluation of the adverse effects of tamoxifen on bone, it is necessary to accumulate more relevant studies.