Chemotherapy For Early Breast Cancer Research Articles

HELENA: HER2-Low as a prEdictive factor of response to Neoadjuvant chemotherapy in eArly breast cancer

BackgroundHER2 expression has a prognostic and predictive impact in early-stage breast cancer (BC). HER2 positive BC (immunohistochemistry (IHC) score 3 + or 2 + with in situ hybridization (ISH) amplification) are treated with HER2 targeted therapies. The concept of HER2-low BC (IHC score 1 + or 2 + without ISH amplification) is drawing attention as anti-HER2 treatment has recently shown efficacy in this subgroup. We aimed to explore the response to neoadjuvant chemotherapy (NAC) in HER2-low early BC according to the HER2 score (1 + or 2 + without amplification).MethodsWe conducted a retrospective study in two French comprehensive cancer centers. All patients with HER2-low BC treated with NAC from January 2014 to December 2020 were included. The primary objective was to analyze the pathological complete response (pCR) rate to NAC using the Sataloff or RCB system, according to the HER2 score. Secondary objectives were to assess disease free survival (DFS), overall survival (OS) and to explore the immune environment through the Neutrophil-to-Lymphocyte Ratio (NLR), according to HER2 expression. Univariate and multivariate analyses were performed.ResultsWe included 237 tumors for 229 patients. Of these, 160 (67.5%) tumors were HER2 1 + , 77 (32.5%) were HER2 2 + , and 152 (64.1%) were hormone receptor (HR) positive. The median age was 53.9 years. No differences in tumor characteristics were observed between HER2 1 + and HER2 2 + subgroups. pCR was achieved in 38 tumors (17%), without any difference between HER2 1 + and HER2 2 + subgroups (p = 0.77). DFS and OS were significantly different between HER2 1 + and HER2 2 + patients (HR = 0.41,CI95%[0.17;0.97] p = 0.037 and HR = 0.31,CI95%[0.09;1.02] p = 0.042, respectively). HER2 status was still associated with DFS and OS after adjustment for age, HR status and NLR, with better outcomes in favor of HER2 score 2 + (HR = 0.35 [0.15–0.84] and HR = 0.24 [0.07–0.81], respectively). NLR was not associated with worse DFS or OS.ConclusionIn HER2-low early BC, no differences in pCR were observed between HER2 1 + and HER2 2 + tumors, however patients with HER2 2 + tumors had a better DFS and OS than those with HER2 1 + . Further investigations are needed to describe the intrinsic differences in the spectrum of HER2-low BC.

Impact of body mass index on survival in women receiving chemotherapy for early breast cancer

The impact of elevated body mass index (BMI) on overall survival (OS) in patients receiving modern anthracycline-taxane chemotherapy for early breast cancer (EBC) has not yet been well established. The purpose of our study was to examine overall survival (OS) by BMI category in women with EBC receiving either doxorubicin (A), cyclophosphamide (C) + paclitaxel (P) or fluorouracil (F), epirubicin (E), cyclophosphamide (C) + docetaxel (D). This was a retrospective cohort study in patients ≥ 18years with resected stage I-III BC diagnosed between 2007 and 2017 in Ontario, identified through linkage of administrative databases. Patients were classified according to baseline BMI into underweight (< 18.5kg/m2), normal (18.5-24.9kg/m2), overweight (25-29.9kg/m2), and obese (≥ 30kg/m2) World Health Organization (WHO) categories. The primary outcome was OS. Univariable and multivariable analyses were used to examine the association between clinico-pathologic characteristics and OS among BMI categories. Our cohort included 11,601 women, of whom 3890 (33.5%) were normal weight, 3696 (31.9%) overweight, and 3847 (33.1%) obese. Median OS was 7.9years. There were no statistically significant differences in OS according to BMI (p = 0.66) in the overall study cohort or among the BMI categories after adjusting for age, nodal status, stage, grade, ER and HER2 status for either AC-P or FEC-D- treated patients (p = 0.45 and p = 0.97, respectively). Our large population-based retrospective cohort analysis of EBC patients receiving adjuvant anthracycline-taxane chemotherapy found no significant impact of BMI on OS. Further investigation is warranted to confirm these findings in prospective patient cohorts.

158P The impact of tumor microenviroment on pathologic complete response after neoadjuvant chemotherapy of early breast cancer

We investigated the impact of baseline tumor infiltrating lymphocytes (TIL) density and TIL composition along with clinicopathological factors on pathologic complete response (pCR) rate in patients treated with standard neoadjuvant chemotherapy ± targeted therapy for early breast cancer.

The influence of body mass index on the tolerability and effectiveness of full-weight-based paclitaxel chemotherapy in women with early-stage breast cancer

PurposeTo investigate the influence of body mass index (BMI) on the tolerability and effectiveness of full-weight-based paclitaxel chemotherapy in early breast cancer patients.MethodsEarly-stage breast cancer patients who received (neo)adjuvant weekly paclitaxel 80 mg/m2 chemotherapy were included in this retrospective study. Patients were divided into three groups based on their BMI: lean, overweight, and obese. Logistic regression was used to assess for association between BMI with administered relative dose intensity (RDI) < 85%. The occurrence of treatment modifications and the pathological response on neoadjuvant chemotherapy were compared between BMI categories.ResultsFour hundred (400) patients were included in this study; 200 (50%) lean, 125 (31%) overweight, and 75 (19%) obese patients. The adjusted odds ratio to receive RDI < 85% for BMI was 1.02 (p value, .263). Treatment modifications occurred in 115 (58%), 82 (66%), and 52 (69%) patients in the respective BMI categories (p value = .132). Peripheral neuropathy was observed in 79 (40%), 58 (46%), and 41 (55%) patients in the lean, overweight, and obese group (p value = .069), whereas hematologic toxicity was observed in 31 (16%), 10 (8%), and 4 (5%) patients (p value = .025). Pathological complete response was observed in 22 (17%), 11 (14%), and 6 (13%) patients in the respective BMI categories (p value = .799).ConclusionBMI did not significantly influence the tolerability and effectiveness of full-weight-based paclitaxel chemotherapy. Therefore, the results of this study align with current guideline recommendations of using full-weight-based paclitaxel chemotherapy in obese patients.

Edmonton Symptom Assessment Scale may reduce medical visits in patients undergoing chemotherapy for breast cancer.

BACKGROUNDAdjuvant chemotherapy is recommended in high-risk breast cancer. However, no universally accepted guidelines exist on pre-chemotherapy assessment. In particular, the number and frequency of medical visits vary according to each institution’s policy. We hypothesised that the Edmonton Symptom Assessment Scale (ESAS) may have a favourable impact on the pre-treatment assessment in candidates for adjuvant chemotherapy.AIMTo investigate whether the ESAS can be used to safely reduce the number of medical visits in women with breast cancer undergoing adjuvant chemotherapy.METHODSIn a retrospectively prospective matched-pair analysis, 100 patients who completed the ESAS questionnaire before administration of adjuvant chemotherapy (ESAS Group) were compared with 100 patients who underwent chemotherapy according to the traditional modality, without ESAS (no-ESAS Group). Patients of the ESAS Group received additional visits before treatment if their ESAS score was > 3. The primary endpoint was the total number of medical visits during the entire duration of the chemotherapy period. The secondary endpoints were the occurrence of severe complications (grade 3-4) and the number of unplanned visits during the chemotherapy period.RESULTSThe study variables did not statistically differ between patients of the ESAS Group and no-ESAS Group (age P = 0.880; breast cancer stage P = 0.56; cancer histology P = 0.415; tumour size P = 0.258; lymph node status P = 0.883; immunohistochemical classification P = 0.754; type of surgery P = 0.157), except for premenopausal status (P = 0.015). The study variables did not statistically differ between patients of the ESAS Group and no-ESAS Group regarding age, cancer stage, histology, tumour size, lymph node status, immunohistochemical classification, and type of surgery. Unplanned visits during the entire duration of chemotherapy were 8 in the ESAS Group and 18 in the no-ESAS Group visits (P = 0.035). Grade 3-4 toxicity did not differ between the study groups (P = 0.652). Forty-eight patients of the ESAS Group received additional visits due to an ESAS score > 3. The mean number of medical visits was 4.38 ± 0.51 in the ESAS Group and 16.18 ± 1.82 in the no-ESAS group (P < 0.001). With multivariate analysis, women of the ESAS group were more likely to undergo additional visits for an ESAS score > 3 if they were aged 60 or older, received a mastectomy, or had tumour stage II/III.CONCLUSIONThe ESAS score may safely reduce the number of medical visits in candidates for adjuvant chemotherapy for early breast cancer. Our results suggest that the ESAS score may be used for selecting a group of breast cancer patients for whom it is safe to reduce the number of medical visits in the setting of adjuvant chemotherapy. This may translate into several advantages, such as a more rational utilization of human resources and a possible reduction of coronavirus pandemic infection risk in oncologic patients.

Prevention of Adjuvant Treatment Induced Cardiotoxicity in Egyptian Breast Cancer (BC) Patients: A Randomized Prospective Study

Background: Adjuvant Anthracyclines Chemotherapy (ANTC) and trastuzumab have been documented to prolong survival in patients with breast cancer (BC). However, these drugs are also well known to induce left ventricular systolic dysfunction (LVSD). Multiple studies have shown that angiotensin converting enzyme inhibitors (ACEIs) and beta blockers (BBs) can prevent LVSD among women with BC.&#x0D; Objectives: We aimed to prospectively evaluate the efficacy of enalapril (ACEI) and carvedilol (BB) in preventing the ANTC ± trastuzumab induced LVSD, in patients with non-metastatic BC.&#x0D; Patients and Methods: We randomized 126 patients with non-metastatic (M0) BC, who were scheduled to be treated with ANTC ± trastuzumab into the intervention group (group 1; n = 63), which received enalapril and carvedilol or the control group (group 2; n = 63), which did not receive enalapril or carvedilol. To evaluate left ventricular (LV) systolic and diastolic functions the conventional echocardiography (ECHO) and cardiac magnetic resonance imaging (CMR) were performed at baseline, after 3 therapy cycles, and at 1-year follow-up. The secondary endpoint was designed to detect the incidence of a decrease in left ventricular ejection fraction (LVEF) ≥ 10%, heart failure (HF), LVSD (defined as LVEF&lt;45%) or deterioration in LV diastolic function.&#x0D; Results: In the intervention group, 58 patients had 3 cycles ANTC, 6 patients received 6 cycles ANTC, and 12 patients received trastuzumab. In the control group, 47 patients had 3 cycles ANTC, 16 patients were given 6 cycles ANTC and 18 patients received trastuzumab (as per the guidelines issued by breast clinic in the department of clinical oncology, faculty of medicine, Ain Shams University) for adjuvant and neoadjuvant chemotherapy in early breast cancer).&#x0D; After 3 ANTC cycles, LVEF did not change in the intervention group, but decreased by M-mode in the control group (p-value: 0.03), which was associated with statistically significant deterioration of LV diastolic function. At 1 year follow-up, while no change was observed in LVEF in group 1, there was a decrease in LVEF by CMR in group 2 (65.78% at baseline, 61.48% at 1 year; p-value: 0.04 8).&#x0D; Conclusion: Combined prophylaxis with enalapril and carvedilol may prevent LVSD in patients with non-metastatic BC treated with anthracycline-containing chemotherapy ± trastuzumab. However, the clinical relevance of this strategy should be confirmed in the future, large-scale randomized studies.

Current practice and surgical outcomes of neoadjuvant chemotherapy for early breast cancer: UK NeST study.

Current practice and surgical outcomes of neoadjuvant chemotherapy for early breast cancer: UK NeST study.

104P HELENA: Study of HER2-low as a prEdictive factor of response to Neoadjuvant chemotherapy in eArly breast cancer

HER2 expression has a prognostic and predictive impact in early breast cancer (BC). HER2-positive BC (score 3+ or 2+ with in situ hybridization (ISH) amplification) are treated with anti-HER2 therapies. HER2-low BC (score 1+ or 2+ without ISH amplification) are less defined and until now, no specific treatment has been provided for this subgroup. We tried to explore the response of HER2-low early BC to neoadjuvant chemotherapy (NAC) according to the HER2 score (1+ or 2+).

Current clinical practice and outcome of neoadjuvant chemotherapy for early breast cancer: analysis of individual data from 94,638 patients treated in 55 breast cancer centers

Neoadjuvant chemotherapy (NACT) is frequently used in patients with early breast cancer. Randomized controlled trials have demonstrated similar survival after NACT or adjuvant chemotherapy (ACT). However, certain subtypes may benefit more when NACT contains regimes leading to high rates of pathologic complete response (pCR) rates. In this study we analyzed data using the OncoBox research from 94,638 patients treated in 55 breast cancer centers to describe the current clinical practice of and outcomes after NACT under routine conditions. These data were compared to patients treated with ACT. 40% of all patients received chemotherapy. The use of NACT increased over time from 5% in 2007 up to 17.3% in 2016. The proportion of patients receiving NACT varied by subtype. It was low in patients with HR-positive/HER2-negative breast cancer (5.8%). However, 31.8% of patients with triple-negative, 31.9% with HR-negative/HER2-positive, and 26.5% with HR-positive/HER2-positive breast cancer received NACT. The rates of pCR were higher in patients with HR-positive/HER2-positive, HR-negative/HER2-positive and triple-negative tumors (36, 53 and 38%) compared to HR-positive/HER2-negative tumors (12%). PCR was achieved more often in HER2-positive and triple-negative tumors over time.This is the largest study on use and effects of NACT in German breast cancer centers. It demonstrates the increased use of NACT based on recommendations in current clinical guidelines. An improvement of pCR was shown in particular in HER2-positive and triple-negative breast cancer, which is consistent with data from randomized controlled trails.

Real World Responses to Neoadjuvant Chemotherapy for Early Breast Cancer

Purpose: Neoadjuvant chemotherapy (NACT) for early breast cancer (EBC) is indicated for downstaging tumours to allow for breast conserving surgery (BCS). Furthermore, pCR is a surrogate marker for outcome which allows for tailoring of adjuvant treatment to optimise outcomes, especially for Her2(+) and triple negative. This retrospective review aims to provide real world data, regarding downstaging rates, pCR rates and correlation between pCR rates and post-NACT MRI.

Use of Dose-dense EC Chemotherapy in Early Breast Cancer – Experience from Two London Hospitals

Purpose: Dose-dense (dd) chemotherapy regimens reduce breast cancer recurrence and mortality with no significant increase in non-cancer related mortality [1]. However, uptake is poor, probably due to concerns regarding toxicity. We aimed to quantify rates of toxicity and dose reduction in patients receiving dd epirubicin and cyclophosphamide (EC), and to identify any associated patient factors.

Impact of Human Epidermal Growth Factor Receptor 2 (HER2) Low Status in Response to Neoadjuvant Chemotherapy in Early Breast Cancer.

IntroductionIn clinical practice, there is a binary distinction between human epidermal growth factor receptor 2 (HER2)-positive and HER2-negative (HER2−) breast cancer (BC). However, within HER2− disease, there is significant heterogeneity. Particularly, HER2− tumors that express some level of HER2 by immunohistochemistry (IHC) score 1+ or 2+/in situ hybridization (ISH) non-amplified are currently defined as HER2-low. This subgroup has shown distinct biological features compared to HER2-zero (HER2-0) BC and additionally novel antibody-drug conjugate therapies have demonstrated a potential and promising activity in HER2-low BC population. This study aims to evaluate the impact of HER2-low status in response to neoadjuvant chemotherapy (NACT) in HER2− BC being HER2-low and HER2-0 status.Materials and methodsIn a single institution, we retrospectively reviewed clinical and pathological data of HER2 early-stage BC patients treated with NACT following definitive surgery from January 2015 to December 2020. Tumors with HER2 IHC 0 were classified as HER2-0 and IHC score 1+ and 2+/ISH non-amplified as HER2-low. The primary objective was to evaluate the rate of pathological complete response (pCR) using the definition of ypT0/Tis ypN0 according to HER2-low and HER2-0 subgroups. Secondary objectives were to evaluate biological features between the two subgroups, disease-free survival (DFS), and overall survival (OS). Pearson chi-square, Fisher’s exact, and Mann-Whitney tests were performed. The Kaplan-Meier method was used to plot DFS and OS curves. A p-value of <0.05 was considered statistically significant.ResultsA total of 72 patients with HER2 BC were included with a median age at diagnosis of 52.5 years and a median follow-up time of 35.5 months. Of patients, 56.9% had HER2-low disease and 43.1% had HER2-0 disease. Significant differences between the two subgroups were detected regarding hormonal receptor status and proliferation grade (Ki67). In the HER2-low subgroup, 70% of tumors were luminal-like and 64.5% of HER2-0 patients had triple-negative BC (p = 0.03). There were statistically significant differences regarding estrogen (p = 0.00) and progesterone (p = 0.02) receptors. The median Ki67 rate was higher in the HER2-0 subset (mean rank = 43.9) compared to HER2-low (mean rank = 30.9) and this difference was statistically significant (p = 0.00). HER2-low patients presented more stage III tumors (65.9%) and HER2-0 patients were mainly stage II (61.3%), and this was statistically relevant (p = 0.03). The prevalence of other clinical and pathological features was comparable between both groups. HER2-low subgroup achieved lower pCR rates (14.6% vs. 29.0%) but this difference was not statistically significant (p = 0.15). Similarly, there was no difference between the two subgroups regarding DFS (p = 0.97) and OS (p = 0.35), although the data were immature.ConclusionAs in prior studies, this study did not support a significant impact of HER2-low status on response to NACT in HER2− patients with early-stage BC. HER2-low patients had a lower pCR, which may suggest a worse response to classic chemotherapy regimen and may have clinical implications that should be further exploited. The prevalence of hormonal receptors in HER2-low tumors was consistent with previous data in the literature. Although retrospective, the data suggest that HER2-low tumors should be regarded as a distinct biological subtype and more research is warranted.

Abstract P2-12-08: Impact of summation dose intensity product on pathologic response in patients receiving neoadjuvant chemotherapy for early breast cancer

Abstract Background: Pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) is associated with beneficial long-term outcome in early breast cancer (EBC). pCR is defined as ypT0/is, ypN0. It is well known that pCR rates depend on tumor subtype. However, the impact of different therapy regimens, dose delays and dose reductions on pCR rates is still unclear. This retrospective study analyzed the therapy dose of patients with pCR and non-pCR after NACT for EBC using referenced and delivered summation dose intensity product (SDIP) and relative dose intensity (RDI) calculations. Methods: SDIP of different therapy regimens were calculated by defining a unit dose intensity (UDI) for each therapy (Hryniuk et al. JCO 1998). The UDI is defined as the dose in mg/m2/week that produces a 30% complete or partial remission rate as a single agent in first-line therapy for metastatic breast cancer. For each regimen, the planned dose intensities (PDI) were divided by the UDI for every single drug. The summation dose intensity (SDI) is the addition of the resulting decimal fractions. Multiplying the SDI by the treatment intervals and number of cycles gives the SDIP. SDIP can be divided into referenced SDIP (rSDIP) and delivered SDIP (dSDIP). RDI is the ratio of dSDIP in comparison to rSDIP. Therapy dose calculations were performed for patients who received NACT for EBC at the National Center for Tumor Diseases (NCT) Heidelberg, Germany, between 01/2015 and 08/2019. Results: 590 patients (median age 51 years) were included, median follow up was 38 months, 225 patients (38.1%) achieved pCR. 65 patients (11.0%) were hormone receptor positive HER2 negative (HR+HER2-), 164 (27.8%) were HR-HER2-, 133 (22.5%) were HR+HER2+, 97 (16.4%) were HR-HER2+. Significant difference between the pCR and non-pCR group was observed for HR-status (p&amp;lt;0.001), HER2-status (p&amp;lt;0.001), tumor grading (p&amp;lt;0.001) and Ki-67 (p&amp;lt;0.001). Age of diagnosis (p=0.611), menopause-status (p=0.769), tumor size (p=0.183) and nodal status (p=0.163) did not significantly vary between patients with pCR versus non-pCR. Patients with pCR had significantly higher rates of anemia II° (p=0.006). No significant difference was seen for anemia ≥III°, neutropenia ≥II°, deviation of liver enzymes ≥II°, nephrotoxicity ≥II°, polyneuropathy ≥II° or the administration of red cell and platelet concentrate as well as the use of Granulocyte-Colony Stimulating Factor (G-CSF). 3 year overall survival (OS), metastasis-free survival (MFS) and recurrence-free survival (RFS) were found to be significantly better in patients with pCR (OS: 98.0% vs. 90.2%, p&amp;lt;0.001; MFS: 94.5% vs. 84.6%, p&amp;lt;0.001; RFS: 97.7% vs. 94.0 %, p=0.029). Patients with pCR had a significantly higher mean rSDIP (69.8 vs. 58.9, p=0.001) and dSDIP (59.5 vs. 49.1, p=0.001). Mean RDI did not significantly vary between pCR and non-pCR (0.853 vs. 0.840, p=0.350). Mean rSDIP and dSDIP significantly vary between the tumor subtypes HR+HER2-, HR-HER2-, HR+HER2+, and HR-HER2+ (rSDIP: 47.4, 54.5, 74.3, 76.7; p&amp;lt;0.001; dSDIP: 39.5, 43.3, 62.0, 67.0; p&amp;lt;0.001). Mean rSDIP and dSDIP did not significantly vary between patients with pCR and non-pCR within the tumor subtypes. Conclusion: Outcomes for NACT are consistent with published data concerning pCR rates. It is notable that the pCR group had significantly higher rSDIP and dSDIP than the non-pCR group whereas RDI and toxicity did not significantly vary between the two groups. rSDIP and dSDIP were mainly depending on the tumor subtype. This data confirms that the tumor subtype has a major impact on pCR rate. Whilst this retrospective analysis must be interpreted with caution, the results show that SDIP is an integral parameter for assessing the efficacy and adequate application of combination therapy and is associated with pCR rate and overall survival. Citation Format: Thomas M Deutsch, Michelle Kobel, Manuel Feisst, Fabian Riedel, Katharina Smetanay, Carlo Fremd, Laura Michel, Michael Golatta, Joerg Heil, Markus Wallwiener, Andreas Schneeweiss. Impact of summation dose intensity product on pathologic response in patients receiving neoadjuvant chemotherapy for early breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-12-08.

Patient-reported treatment toxicity and adverse events in Black and White women receiving chemotherapy for early breast cancer

Patient-reported treatment toxicity and adverse events in Black and White women receiving chemotherapy for early breast cancer

Randomised controlled trial of intermittent vs continuous energy restriction during chemotherapy for early breast cancer

BackgroundExcess adiposity at diagnosis and weight gain during chemotherapy is associated with tumour recurrence and chemotherapy toxicity. We assessed the efficacy of intermittent energy restriction (IER) vs continuous energy restriction (CER) for weight control and toxicity reduction during chemotherapy.MethodsOne hundred and seventy-two women were randomised to follow IER or CER throughout adjuvant/neoadjuvant chemotherapy. Primary endpoints were weight and body fat change. Secondary endpoints included chemotherapy toxicity, cardiovascular risk markers, and correlative markers of metabolism, inflammation and oxidative stress.ResultsPrimary analyses showed non-significant reductions in weight (−1.1 (−2.4 to +0.2) kg, p = 0.11) and body fat (−1.0 (−2.1 to +0.1) kg, p = 0.086) in IER compared with CER. Predefined secondary analyses adjusted for body water showed significantly greater reductions in weight (−1.4 (−2.5 to −0.2) kg, p = 0.024) and body fat (−1.1 (−2.1 to −0.2) kg, p = 0.046) in IER compared with CER. Incidence of grade 3/4 toxicities were comparable overall (IER 31.0 vs CER 36.5%, p = 0.45) with a trend to fewer grade 3/4 toxicities with IER (18%) vs CER (31%) during cycles 4–6 of primarily taxane therapy (p = 0.063).ConclusionsIER is feasible during chemotherapy. The potential efficacy for weight control and reducing toxicity needs to be tested in future larger trials.Clinical trial registrationISRCTN04156504.

A Randomized Trial Comparing 3- versus 4-Monthly Cardiac Monitoring in Patients Receiving Trastuzumab-Based Chemotherapy for Early Breast Cancer.

Purpose: The optimal frequency for cardiac monitoring of left ventricular ejection fraction (LVEF) in patients receiving trastuzumab-based therapy for early breast cancer (EBC) is unknown. We conducted a randomized controlled trial comparing 3- versus 4-monthly cardiac monitoring. Patients and Method: Patients scheduled to receive trastuzumab-containing cancer therapy for EBC with normal (>53%) baseline LVEF were randomized to undergo LVEF assessments every 3 or 4 months. The primary outcome was the change in LVEF from baseline. Secondary outcomes included the rate of cardiac dysfunction (defined as a decrease in the LVEF of ≥10 percentage points, to a value <53%), delays in or discontinuation of trastuzumab therapy, and cardiology referral. Results: Of the 200 eligible and enrolled patients, 100 (50%) were randomized to 3-monthly and 100 (50%) to 4-monthly cardiac monitoring. Of these patients, 98 and 97 respectively underwent at least one cardiac scan. The estimated mean difference in LVEF from baseline was −0.94% (one-sided 95% lower bound: −2.14), which exceeded the pre-defined non-inferiority margin of −4%. There were also no significant differences between the two study arms for any of the secondary endpoints. The rate of detection of cardiac dysfunction was 16.3% (16/98) and 12.4% (12/97) in the 3- and 4-monthly arms, respectively (95% CI: 4.0 [−5.9, 13.8]). Conclusions: Cardiac monitoring every 4 months was deemed non-inferior to that every 3 months in patients with HER2-positive EBC being treated with trastuzumab-based therapy. Given its costs and inconvenience, cardiac monitoring every 4 months should be considered standard practice. Registration: NCT02696707, 18 February 2016.

Survival and Time to Initiation of Adjuvant Chemotherapy Among Breast Cancer Patients in Uruguay.

IntroductionIncreases in disease-free survival and overall survival (OS) with the use of adjuvant chemotherapy in early breast cancer (BC) are widely known; however, the optimal time to initiate treatment with adjuvant chemotherapy remains controversial.ObjectiveTo evaluate the time elapsed between surgery and the initiation of adjuvant chemotherapy and its possible impact on OS in patients diagnosed with BC stages I–III.Materials and MethodsThis retrospective study included 112 patients diagnosed with BC stages I–III who received adjuvant chemotherapy at the Mastology Unit of the Hospital de Clínicas in Uruguay from 2009 to 2019. OS was estimated using the Kaplan–Meier method, and a Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals.ResultsNo statistically significant association was found between the time from surgery to the initiation of chemotherapy and the described variables. OS was worse for patients initiating chemotherapy more than 90 days after breast surgery (n = 19) (HR 7.63; p = 0.004) and between 61 and 90 days after surgery (n = 46) (HR 4.58; p = 0.040) compared to those who started before 30 days (n = 23). Controlling by type of surgery and stage, the prognosis of patients who started chemotherapy between 61 and 90 days after surgery was similar to that of patients who underwent chemotherapy within the first 30 days, controlling for surgery (HR 4.10; p = 0.056) and controlling for stage (HR 3.76; p = 0.075). Prognosis was worse for patients with stage III disease (p = 0.022) who underwent a mastectomy and/or axillary lymph node dissection (p = 0.025).ConclusionPatients who started chemotherapy more than 90 days following surgery and those with stage III disease or underwent mastectomy and/or axillary lymph node dissection who initiated it between 61 and 90 days had a worse OS. Multiple factors are involved in the time between surgery and the initiation of chemotherapy, and further studies are needed to evaluate which of these factors influence the delay of chemotherapy in order to design strategies to avoid such delays and their negative impact on survival.

Patient-reported treatment toxicity and adverse events in Black and White women receiving chemotherapy for early breast cancer.

It is not known whether chemotherapy-related symptom experiences differ between Black and White women with early breast cancer (Stage I-III) receiving current chemotherapy regimens and, in turn, influences dose delay, dose reduction, early treatment discontinuation, or hospitalization. Patients self-reported their race and provided symptom reports for 17 major side effects throughout chemotherapy. Toxicity and adverse events were analyzed separately for anthracycline and non-anthracycline regimens. Fisher's exact tests and two-sample t-tests compared baseline patient characteristics. Modified Poisson regression estimated relative risks of moderate, severe, or very severe (MSVS) symptom severity, and chemotherapy-related adverse events.Please check and confirm that the authors and their respective affiliations have been correctly identified and amend if necessary.no changes RESULTS: In 294 patients accrued between 2014 and 2020, mean age was 58 (SD13) and 23% were Black. For anthracycline-based regimens, the only significant difference in MSVS symptoms was in lymphedema (41% Black vs 20% White, p = .04) after controlling for axillary surgery. For non-anthracycline regimens, the only significant difference was MSVS peripheral neuropathy (41% Blacks vs. 23% White) after controlling for taxane type (p = .05) and diabetes (p = .05). For all other symptoms, severity scores were similar. Dose reduction differed significantly for non-anthracycline regimens (49% Black vs. 25% White, p = .01), but not for anthracycline regimens or in dose delay, early treatment discontinuation, or hospitalization for either regimen. Except for lymphedema and peripheral neuropathy, Black and White patients reported similar symptom severity during adjuvant chemotherapy. Dose reductions in Black patients were more common for non-anthracycline regimens. In this sample, there were minimal differences in patient-reported symptoms and other adverse outcomes in Black versus White patients.

Activation of a cGAS-STING-mediated immune response predicts response to neoadjuvant chemotherapy in early breast cancer

BackgroundThe DNA-damage immune-response (DDIR) signature is an immune-driven gene expression signature retrospectively validated as predicting response to anthracycline-based therapy. This feasibility study prospectively evaluates the use of this assay to predict neoadjuvant chemotherapy response in early breast cancer.MethodsThis feasibility study assessed the integration of a novel biomarker into clinical workflows. Tumour samples were collected from patients receiving standard of care neoadjuvant chemotherapy (FEC + /−taxane and anti-HER2 therapy as appropriate) at baseline, mid- and post-chemotherapy. Baseline DDIR signature scores were correlated with pathological treatment response. RNA sequencing was used to assess chemotherapy/response-related changes in biologically linked gene signatures.ResultsDDIR signature reports were available within 14 days for 97.8% of 46 patients (13 TNBC, 16 HER2 + ve, 27 ER + HER2-ve). Positive scores predicted response to treatment (odds ratio 4.67 for RCB 0-1 disease (95% CI 1.13–15.09, P = 0.032)). DDIR positivity correlated with immune infiltration and upregulated immune-checkpoint gene expression.ConclusionsThis study validates the DDIR signature as predictive of response to neoadjuvant chemotherapy which can be integrated into clinical workflows, potentially identifying a subgroup with high sensitivity to anthracycline chemotherapy. Transcriptomic data suggest induction with anthracycline-containing regimens in immune restricted, “cold” tumours may be effective for immune priming.Trial registrationNot applicable (non-interventional study). CRUK Internal Database Number 14232.

198P Complications associated with prolonged GCSF with dose-dense EC chemotherapy for early breast cancer patients

Primary granulocyte-colony stimulating factor (GSCF) prophylaxis with dose-dense chemotherapy for early stage breast cancer is routine practice to prevent febrile neutropenia (FN). Our current practice administers 7 days of GCSF, which reduces the FN risk but is associated with extra toxicity and costs. We reviewed the rates of FN, neutropenia, hospital admissions and GCSF-related toxicity in early stage breast cancer patients receiving 7 days of GCSF with dose-dense epirubicin and cyclophosphamide (EC).