Chemotherapy For Early Breast Cancer Research Articles

Abstract PO5-17-12: Impact of HER2-low status on axillary response and surgical management after neoadjuvant chemotherapy in early breast cancer

Abstract Background: Breast cancer (BC) with low expression of HER2 (HER2-low) might constitute a group of tumors with unique clinical and biological characteristics. Little is known about axillary downstaging and nodal surgical outcomes in HER2-low BC after neoadjuvant chemotherapy (NACT). The aim of this study was to evaluate axillary response and surgical management of the axilla in HER2-low BC patients submitted to NACT. Methods: In this cross-sectional single center study, we consecutively included all patients diagnosed with early HER2-negative BC between 2017 to 2021 that were treated with NACT. Patients must have biopsy-confirmed stage II-III BC, submitted to breast surgery after NACT. Clinical and pathological response in the axilla, type of axillary surgery, and surgical outcomes data were collected. HER2-low was defined by IHC score 1+, or 2+ ISH non-amplified; HER2-zero was defined by IHC score 0. Pathological response was determined locally. Results: At diagnosis, 291 patients had clinically involved axillary nodes (cN1: 69.4%; cN2: 25.1%; cN3: 5.5%). Among 136 patients eligible for SLN biopsy after NACT, 77 (26.5%) had pathologically negative SLN. Of those submitted to upfront axillary dissection (n=154), 52 (33.7%) had pN0 disease. In total, 129 (44.3%) patients with clinically involved axillary lymph nodes at diagnosis were converted to cN0 after NACT. There was no difference in the rate of axillary downstaging between HER2-low and HER2-zero tumors, 17.8% vs 26.5%, respectively (p=0.0026). 236 patients were submitted to sentinel lymph node biopsy (SLN), of whom 214 (81.4%) with blue dye-only, 40 (15.2%) with radioactive isotope, and 7 (2.7%) with dual tracer. SLN detection failure were reported for 12 patients (0.046%). Mean number of lymph nodes retrieved were 2.7. Most patients had a negative SLN biopsy (180/263; 68.4%), of whom 91 (50.6%) were HER2-low and 89 (49.4%) were HER2-zero. Positive SLN biopsy were reported in 83 patients (isolated tumor cells: 20,5%; micrometastasis: 24.1%; macrometastasis: 55.4%), with capsular extravasation in 25.3%. A positive SLN biopsy occurred in 61.4% of patients with HER2-low tumors, and in 38.5% of patients with HER2-zero tumors. Among patients with a positive SLN biopsy (n=83), 67 were submitted to axillary dissection, of whom 39 (58.2%) had no additional nodes involved (HER2-low: 61.5%; HER2-zero: 38.4%). Considering N0 tumors at diagnosis, 127 patients were submitted to SNL, and only 18.9% had a positive result (HER2-low: 66.6%; HER2-zero: 33.3%). In the subgroup of initially cN+ disease, 136 (46.7%) underwent SLN biopsy, with 59 (43.4%) with a positive result (HER2-low: 59.3%; HER2-zero: 40.7%). Conclusions: Our results showed that HER2-low BC patients had a statistically significant lower frequency of axillary downstaging after NACT. More than 40% of patients with cN+ at diagnosis were downstaged to cN0 and were submitted to SNL biopsy. Axillary dissection were avoided in roughly 25% of patients with cN+ BC at initial staging. Citation Format: Leonardo Roberto da Silva, Guilherme Sartori, Susana Ramalho, Tomás Reinert, Mahira Lopes Da Rosa, Grazielle Morais Tavares, Higor Mantovani, Vivian Vasconcelos, Ana Elisa Ribeiro Da Silva Cabello, Guilherme Coelho, Jovana Mandelli, Facundo Zaffaroni, Carlos Barrios, Marcia Silveira Graudenz, César Cabello. Impact of HER2-low status on axillary response and surgical management after neoadjuvant chemotherapy in early breast cancer [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 PO5-17-12.

Abstract PO2-12-12: REaCT 5G: A randomized study comparing bone pain after 5 days of filgrastim or one day of pegfilgrastim for primary febrile neutropenia prophylaxis during neo-/adjuvant chemotherapy for early breast cancer

Abstract Background: Granulocyte colony stimulating factor (G-CSF) such as filgrastim (FIL) or pegfilgrastim (PEG) significantly reduces the risk of febrile neutropenia (FN) and treatment-related hospitalization in patients with early breast cancer receiving chemotherapy. However, patients receiving G-CSF can experience clinically significant bone pain. Previous studies examining post-GCSF bone pain were mostly based on physician pain assessment and compared mixed doses (30/60/100 μg/kg) of PEG vs. FIL (5μg/kg/day or 300 μg/day) given for 7 to 14 days. Based on a randomized non-inferiority study, 5 days of FIL is considered non-inferior to 10 days of FIL to prevent FN and hospitalizations and is frequently used in patients receiving chemotherapy for breast cancer. Patient-reported bone pain after 5 days of FIL vs. single dose of PEG has never been compared in a prospective randomized study and has important implications for patient and physician treatment preferences. Methods: In this multicenter, open-label trial, patients receiving neo-/adjuvant chemotherapy for early-stage breast cancer requiring primary FN prophylaxis with G-CSF were randomized 1:1 to either 5 days of FIL (300 μg or 480μg if ≥ 90 kg) or 1 day of PEG (6 mg) with each cycle of chemotherapy. The primary endpoint was bone pain using area under the curve (AUC) of the daily pain score from days 1-5 (AUC score 0 to 40) during cycle 1. We used linear regression adjusting for stratification factors [cancer center (2 centers) and chemotherapy regimen (taxane (TAX) or anthracycline (ANTH)-based during cycle 1] and prespecified baseline covariates: age, pain, and use of pain medications pre-chemotherapy. Supportive analysis of bone pain across cycles 1 to 4 was conducted using repeated linear regression. Key secondary endpoints included incidence of FN, hospitalizations, chemotherapy delay, dose-reduction or discontinuation, and chemotherapy-related deaths. Results: From June 2021 to March 2023, 233 patients were enrolled, with 217 patients (108 FIL/109 PEG) in the intention-to-treat analysis; 16 (7.4%) patients were excluded because of incomplete follow-up. Participants were mean age 55.6 years; almost exclusively female (99.1%), on chemotherapy regimen TAX 57% vs. ANTH 43%, had mean baseline pain score 1.12, and prevalence of pain medication use pre-chemotherapy was acetaminophen 14.7%, non-steroidal anti-inflammatory drugs (NSAIDs) 6.0% and opioids 3.2%. Characteristics were balanced between arms (Table 1). After repeated measures linear regression adjusted for age, chemotherapy regimen, baseline pain, and use of pain medications pre-chemotherapy, mean AUC for bone pain at cycle 1 was 10.94 for FIL and 10.12 for PEG (mean difference 0.82; 95% CI: -1.59, 3.23; p = 0.516). There was no significant difference between arms across treatment cycles (interaction p = 0.785; mean time-averaged difference 0.28; 95% CI: -1.75, 2.32). Across cycles 1 to 4, mean peak pain over 5 days post-GCSF was 3.27 vs. 3.41 (p=0.700); frequency of bone pain during first 8 days (pain score > 0) was 52.5% vs. 51.3%; p=0.358, and mean frequency of severe pain (pain score ≥ 5) was 17.5% vs. 15.2%; p=0.014 for FIL vs. PEG, respectively. The incidence of FN [4.6% vs. 0%, absolute difference 4.6% (95% CI: -0.3%, 9.5%; p=0.069)] and hospitalization [FN and non-FN related: 10.2% vs. 1.8%, absolute difference of 8.4% (95% CI: 1.2%, 15.5%; p=0.021)] was higher in the FIL group. There were no significant differences in chemotherapy delay (13% vs. 11%; p=0.815), dose reduction (14.8% vs. 14.7%; p=0.999), early discontinuation (8.3% vs. 5.5%; p=0.580), or chemotherapy-related death (0.9% vs. 0%; p=0.996) in the FIL vs. PEG groups, respectively. Conclusion: There was no difference in patient-reported bone pain after 5 days of FIL or PEG, even after controlling for important clinical factors. Importantly, the study observed higher rates of FN and hospitalizations in patients receiving FIL for 5 days only. Table 1 Baseline Characteristics Citation Format: Terry Ng, Yuxin Zhang, Carol Stober, Jennifer Shamess, Natalie Mills, Stuart Nicholls, Mohammed Ibrahim, Daniel Davoudpour, Christopher Armiento, Marie-France Savard, Moira Rushton, Arif Awan, Sandeep Sehdev, John Hilton, Xinni Song, Rakesh Goel, Fiona Macdonald, Kelly Daigle, Lisa Vandermeer, Monica Taljaard, Mark Clemons. REaCT 5G: A randomized study comparing bone pain after 5 days of filgrastim or one day of pegfilgrastim for primary febrile neutropenia prophylaxis during neo-/adjuvant chemotherapy for early breast cancer [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 PO2-12-12.

Imaging responses in different biology during neoadjuvant chemotherapy in early breast cancer and correlation with oncoplastic surgery planning

Imaging responses in different biology during neoadjuvant chemotherapy in early breast cancer and correlation with oncoplastic surgery planning

Patient-reported outcomes and symptom clusters pattern of chemotherapy-induced toxicity in patients with early breast cancer.

This study aims to characterize patient-reported chemotherapy-induced toxicity in patients with breast cancer, determine its association with treatment regimens and patient characteristics, identify toxicity symptom clusters within a specific chemotherapy timeframe and analyze the correlation between symptom clusters within and between the timeframe to understand the changes and influences across chemotherapy. Forty-six patient-reported toxicities during neoadjuvant/adjuvant chemotherapy for breast cancer were evaluated using adapted CTCAE version 4.0. Chi-Square/Fisher's Exact test was performed to analyze the difference in the incidence of toxicity symptoms by chemotherapy regimens. Poisson regression performed to assess factors associated with patient's total chemotherapy toxicity. Exploratory factor analysis (EFA) conducted to identify symptom clusters at T1 (first half) and T2 (second half of planned cycle). Factor scores were generated and Spearman correlation performed to explore the factor scores correlation between symptom clusters. A total of 142 patients with stage I-III breast cancer were included. The incidence of several toxicities differed significantly among three chemotherapy regimens. Subjects age ≥51 years are associated with lower number of reported toxicity (IRR/incidence rate ratio = 0.94, 95% confidence interval/CI 0.88 to 0.99, p = 0.042). Receiving more chemotherapy cycles are associated with higher number of reported toxicity (IRR = 1.06, 95% CI 1.03 to 1.10, p<0.001). Two symptom clusters identified at T1 (psychoneurological-pain/PNP-T1 and gastrointestinal-psychological/GIP-T1 cluster) and three at T2 (psychoneurological-pain/PNP-T2, epithelial/EPI-T2, and gastrointestinal cluster/GI-T2), with moderate-strong positive correlation between PNP-T1 and GIP-T2 (p<0.001), PNP-T1 and PNP-T2 (p<0.001), and GIP-T1 and PNP-T2 (p<0.001). This study investigated 46 patient-reported toxicities prospectively during adjuvant/neoadjuvant chemotherapy for early breast cancer. Anthracycline-taxane combination regimen had higher proportions of toxicity incidence. Subject's age and number of chemotherapy cycles significantly associated with total number of toxicity symptoms. Two symptom clusters at T1 and three at T2 were identified, with significant correlation between symptom clusters within and between chemotherapy timeframe.

Evaluation of Conservative Breast Surgery After Neoadjuvant Chemotherapy in Early Breast Cancer

Background:  The breast cancer is a frequent type of cancers.  It is associated with high mortality related to cancer in women. The treatment options transferred from radical surgery to less invasive operations. This was attributed to surgical advance and available neoadjuvant chemotherapy.  Objective: This work aimed to evaluate the conservative breast surgery feasibility and outcome for early breast cancer received neoadjuvant chemotherapy (NACT) for downstaging.  Patients and Methods: Thirty women (30) with early breast cancer were included between November 2022 and May 2023. All women were assessed in systematic manner by history, clinical, laboratory and radiological investigations before chemotherapy, before and after surgery. A true cut biopsy was drawn to estimate the histopathological nature. All surgeries were performed one and half months after the last session of NACT. A regular postoperative follow up was carried out up to six months. Any complications were recorded. Effect of NACT on the tumor grading was the primary outcome, while cosmetic results and patient satisfaction were the secondary outcomes. Results: Complications were in the form of wound infection, seroma and hematoma in 6.7%, 13.3% and 3.3% respectively. These were mild and treated conservatively. The excellent cosmetic result was achieved for 80.0% and excellent patient satisfaction was recorded for 60.0%.  The effect of chemotherapy showed significant improvement of clinical and pathological post chemotherapy tumor size values when compared to clinical tumor size values before chemotherapy, the T1 grade (≤2cm) increased from 50% to 66.7%, while the T2 grade (&gt; 2cm &lt;5 cm) decreased from 50% to33.3%.  Conclusion: NACT was associated with excellent response regarding tumor size reduction, negativity of lymph nodes as well as pathological response of early breast cancer, before breast conservation surgery (BCS). The BCS after NACT could be considered as a safe option with acceptable aesthetic outcome.

Fatigue and quality of life during neoadjuvant chemotherapy of early breast cancer: a prospective multicenter cohort study

BackgroundFew measurements of fatigue and quality of life have been performed during neoadjuvant chemotherapy of early breast cancer. This study evaluates fatigue and quality of life experienced by early breast cancer patients during neoadjuvant chemotherapy and their association with different clinical parameters.MethodsFifty-four stage I–III patients’ responses to the Multidimensional Fatigue Inventory (MFI) and to the Functional Assessment of Cancer Therapy-Breast (FACT-B) were analyzed by a linear covariance pattern model. Chemotherapy regimen, age, baseline fatigue level, body-mass-index and cancer stage were added to the model to estimate their impact on both outcomes.ResultsAll fatigue dimensions worsened in clinically relevant levels. Physical fatigue worsened the most, mental fatigue the least. For quality of life, physical and functional well-being worsened the most. Only emotional well-being improved during chemotherapy. Physical well-being worsened more during standard than during dose-dense chemotherapy, and more during anthracycline than during taxane cycles. Age, body-mass-index and cancer stage had no impact. The higher the fatigue levels at baseline, the less they worsened during chemotherapy.ConclusionsFurther actions to reduce fatigue and improve quality of life during neoadjuvant chemotherapy of early breast cancer are needed. Focus should be laid on the physical dimension. Future research should also investigate the impact of different chemotherapy sequences and densities on fatigue and quality of life.Study registrationThe study was registered in the German Clinical Trials Register in May 2019 (DRKS00016761).

SAMHD1 expression is a surrogate marker of immune infiltration and determines prognosis after neoadjuvant chemotherapy in early breast cancer.

The lack of validated surrogate biomarkers is still an unmet clinical need in the management of early breast cancer cases that do not achieve complete pathological response after neoadjuvant chemotherapy (NACT). Here, we describe and validate the use of SAMHD1 expression as a prognostic biomarker in residual disease in vivo and in vitro. SAMHD1 expression was evaluated in a clinical cohort of early breast cancer patients with stage II-III treated with NACT. Heterotypic 3D cultures including tumor and immune cells were used to investigate the molecular mechanisms responsible of SAMHD1 depletion through whole transcriptomic profiling, immune infiltration capacity and subsequent delineation of dysregulated immune signaling pathways. SAMHD1 expression was associated to increased risk of recurrence and higher Ki67 levels in post-NACT tumor biopsies of breast cancer patients with residual disease. Survival analysis showed that SAMHD1-expressing tumors presented shorter time-to-progression and overall survival than SAMHD1 negative cases, suggesting that SAMHD1 expression is a relevant prognostic factor in breast cancer. Whole-transcriptomic profiling of SAMHD1-depleted tumors identified downregulation of IL-12 signaling pathway as the molecular mechanism determining breast cancer prognosis. The reduced interleukin signaling upon SAMHD1 depletion induced changes in immune cell infiltration capacity in 3D heterotypic in vitro culture models, confirming the role of the SAMHD1 as a regulator of breast cancer prognosis through the induction of changes in immune response and tumor microenvironment. SAMHD1 expression is a novel prognostic biomarker in early breast cancer that impacts immune-mediated signaling and differentially regulates inflammatory intra-tumoral response.

EFFICACY AND SAFETY OF A DEXAMETHASONE-BASED MOUTHWASH TO PREVENT CHEMOTHERAPY-INDUCED STOMATITIS IN WOMEN WITH BREAST CANCER: A MULTICENTRE, OPEN-LABEL, RANDOMISED PHASE 2 STUDY.

No standard approach other than oral care is available for preventing chemotherapy-induced stomatitis in patients with breast cancer. In this randomized, controlled phase 2 trial, we aimed to assess the efficacy and safety of a dexamethasone-based mouthwash in preventing chemotherapy-induced stomatitis in patients with early breast cancer. Patients with breast cancer scheduled for epirubicin and cyclophosphamide (EC) or docetaxel and cyclophosphamide (TC) therapy were selected and allocated in a 1:1 ratio to the intervention and control groups. The intervention group received chemotherapy, oral care, and a dexamethasone-based mouthwash, whereas the control group received chemotherapy and oral care. The primary endpoint was the incidence of stomatitis. This was a phase 2 study, and the significance level for the analysis of the primary endpoint was set a priori at 0.2. Data pertaining to 58 patients in the control group and 59 patients in the intervention group were analyzed. Stomatitis incidence was 55% and 38% in the control and intervention groups, respectively (risk ratio, 0.68; 80% confidence interval, 0.52-0.88; P = .052). Stomatitis severity was lower in the intervention group than in the control group (P = .03). The proportion of patients who adhered to the mouthwash regimen was 87% (interquartile range, 67.8%-95.3%). No severe oral infections were observed. The dexamethasone-based mouthwash safely reduced stomatitis incidence and severity in patients receiving chemotherapy for early breast cancer. Phase 3 clinical trials are warranted for validating our results.

Cost-utility analysis of genomic profiling in early breast cancer in Colombia

BackgroundIn Colombia, the best strategy to establish indication for adjuvant chemotherapy in early breast cancer (EBC) remains unknown. This study aimed to identify the cost-utility of Oncotype DX™ (ODX) or Mammaprint™ (MMP) tests to establish the necessity of adjuvant chemotherapy.MethodsThis study used an adapted decision-analytic model to compare cost and outcomes of care between ODX or MMP tests and routine care without ODX or MMP tests (adjuvant chemotherapy for all patients) over a 5-year time horizon from the perspective of the Colombian National Health System (NHS; payer). Inputs were obtained from national unit cost tariffs, published literature, and clinical trial database. The study population comprised women with hormone-receptor-positive (HR +), HER2-negative, lymph-node-negative (LN0) EBC with high-risk clinical criteria for recurrence. The outcome measures were discounted incremental cost-utility ratio (ICUR; 2021 United States dollar per quality-adjusted life-year [QALY] gained) and net monetary benefit (NMB). Probabilistic (PSA) and deterministic sensitivity analysis (DSA) were performed.ResultsODX increases QALYs by 0.05 and MMP by 0.03 with savings of $2374 and $554 compared with the standard strategy, respectively, and were cost-saving in cost-utility plane. NMB for ODX was $2203 and for MMP was $416. Both tests dominate the standard strategy. Sensitivity analysis revealed that with a threshold of 1 gross domestic product per capita, ODX will be cost-effective in 95.5% of the cases compared with 70.2% cases involving MMP.DSA showed that the variable with significant influence was the monthly cost of adjuvant chemotherapy. PSA revealed that ODX was a consistently superior strategy.ConclusionsGenomic profiling using ODX or MMP tests to define the need of adjuvant chemotherapy treatment in patients with HR + and HER2 −EBC is a cost-effective strategy that allows Colombian NHS to maintain budget.

Severe cytopenia during adjuvant chemotherapy for early breast cancer in a patient with idiopathic CD4+ lymphocytopenia.

Idiopathic CD4+ lymphocytopenia (ICL) is a rare immunodeficiency disorder characterized by decreased CD4+ T-cell counts in the absence of human immunodeficiency virus (HIV) infection. Similar to HIV infection, ICL is commonly associated with acquired immunodeficiency syndrome-defining cancers, such as Kaposi sarcoma, non-Hodgkin lymphoma and cervical cancer; however, the presentation of breast cancer in a patient with ICL is rare. The current study presented the clinical course of a patient with early breast cancer and ICL. Following surgery, the patient underwent adjuvant chemotherapy comprising doxorubicin plus cyclophosphamide, followed by paclitaxel. The patient's immunodeficiency status required the prophylactic administration of clarithromycin, trimethoprim-sulfamethoxazole and valganciclovir. Throughout the course of chemotherapy, the patient experienced severe complications of febrile neutropenia, anemia, neutropenia and thrombocytopenia, and was eventually forced to discontinue anticancer chemotherapy, as the relative dose intensity (RDI) could not be maintained. Similar hematological complications and reduced RDI, leading to worse outcomes, are also common in patients with HIV infection receiving chemotherapy, suggesting that CD4+ T cell-deficient patients are prone to developing cytopenia during chemotherapy. The present study demonstrates the importance of further data accumulation in patients with ICL with cancer and the development of a methodology for maintaining the RDI.

Satisfaction with and perceived benefits of needs-assessment related to rehabilitation after chemotherapy among patients with breast cancer

Purpose To investigate satisfaction with and perceived benefits of a model of needs-assessment related to rehabilitation (NARR) in women with early breast cancer after (neo)adjuvant chemotherapy. Materials and methods Mixed methods were applied using survey (N = 200) along with interviews (N = 20). The survey included measurement of distress and self-assessed need of and satisfaction with the NARR. Type of experienced side/late effects were registered along with numbers of and reasons for referrals to rehabilitation. Individual semi-structured interviews were conducted. Quantitative data were analyzed using descriptive statistics, and qualitative data were analyzed with thematic analysis. Results Overall, 217 patients participated in a NARR and 200 (92%) accepted participation in the survey. Furthermore, 20/37 (54%) invited patients were interviewed. After the NARR, 39 patients (20%) were referred to rehabilitation. While satisfaction was high, findings regarding distress and need of the NARR were equivocal and indicated a need for talking about experiences throughout the cancer trajectory. Conclusions While only 20% had rehabilitation needs, satisfaction with the NARR was high and patients benefitted from being confirmed in normality of their experiences. It is recommended to address patients’ side/late effects after chemotherapy for early breast cancer to identify rehabilitation needs, reduce distress, and improve quality of life.

Toxicity and Healthcare Utilisation of Dose-dense Chemotherapy for Early Breast Cancer

Purpose: Clinical trials provide evidence that dose-dense chemotherapy (ddC) is more efficacious than standard chemotherapy schedules in the treatment of early breast cancer (EBC). The impact on toxicity and healthcare utilisation remains uncertain in real-world populations. The aim of this retrospective adjusted cohort comparison was to measure the impact following adoption of ddC.

149P HER2-low status and response to neoadjuvant chemotherapy in early breast cancer

149P HER2-low status and response to neoadjuvant chemotherapy in early breast cancer

Abstract P1-11-01: Trastuzumab deruxtecan vs treatment of physician’s choice in patients with HER2-low unresectable and/or metastatic breast cancer: Subgroup analyses from DESTINY-Breast04

Abstract Background: DESTINY-Breast04 demonstrated that the HER2 targeting antibody–drug conjugate trastuzumab deruxtecan (T-DXd) significantly prolonged progression-free survival (PFS) and overall survival (OS) vs treatment of physician’s choice (TPC) in patients (pts) with HER2-low (immunohistochemistry [IHC] 1+ or IHC 2+/in situ hybridization negative) metastatic breast cancer (mBC) in pts in the hormone receptor−positive (HR+) cohort and all pts (HR+ and HR-; median PFS, 9.9 vs 5.1 months [mo], hazard ratio: 0.50; median OS, 23.4 vs 16.8 mo, hazard ratio: 0.64; both P &amp;lt; 0.0001; Modi et al. N Engl J Med 2022). Objective response rate (ORR) with T-DXd was ≥50% across cohorts. These subgroup analyses examine pt history and disease characteristics that may correlate with response to therapy. Methods: N = 557 pts with centrally confirmed HER2-low mBC were randomized 2:1 to T-DXd or TPC. Randomization was stratified by HER2 status (IHC 1+ vs 2+), 1 vs 2 prior lines of chemotherapy, and HR+ (with vs without prior treatment with cyclin-dependent kinase 4/6 inhibitor [CDK4/6i]) vs HR−. With the exception of the PFS and OS analyses by prior CDK4/6i use, all other described efficacy analyses were assessed post-hoc. Results: Benefit of T-DXd vs TPC was consistent in pts with or without prior CDK4/6i use (Table 1). Pts with high disease burden (ie, ≥3 metastatic sites) also benefited from T-DXd vs TPC (Table 2). There was a small subgroup (n = 22) among all pts (HR+ [n = 18] and HR− disease [n = 4]) with rapid progression prior to enrollment (disease progression within 6 mo of concluding a prior course of chemotherapy in early breast cancer). T-DXd showed responses in 7/14 (50%) pts in this subgroup vs 0/8 with TPC; this subgroup also had prolonged median PFS with T-DXd vs TPC (Table 3). Efficacy data for HER2 IHC 1+ vs 2+ and prior chemotherapy subgroups will be presented. Median OS was not reached for many subgroups (insufficient events in each group [data not shown]); however, subgroups in general showed OS benefit consistent with the primary analysis. With T-DXd, rates of interstitial lung disease/pneumonitis were similar in pts with/without prior CDK4/6i use. Conclusions: T-DXd treatment for HER2-low mBC in the phase 3 study DESTINY-Breast04 showed consistent efficacy independent of disease burden, prior CDK4/6i treatment, or rapid progression status. ILD is an important identified risk and requires proactive monitoring and management. These data continue to support the use of T-DXd as the new standard of care across subgroups of pts with HER2-low mBC. Editorial Acknowledgment Under guidance of the authors, assistance in medical writing and editorial support was provided by Eileen McIver, PhD, and Soniya Patel, PhD, of ApotheCom, and was funded by Daiichi Sankyo. Funding This study was funded by Daiichi Sankyo and AstraZeneca. Table 1. Efficacy by Prior CDK4/6i Treatment in Pts With HER2-Low Breast Cancer, HR+ Cohort. Table 2. Efficacy by Disease Burdena in Pts With HER2-Low Breast Cancer, ITT. Table 3. Efficacy by Rapid Progressor Statusa in Pts With HER2-Low Breast Cancer, ITT. Citation Format: Nadia Harbeck, Shanu Modi, William Jacot, Toshinari Yamashita, Joo Hyuk Sohn, Maria Vidal, Junji Tsurutani, Naoto T. Ueno, Aleix Prat, Naoki Niikura, Binghe Xu, Hope Rugo, Konstantinos Papazisis, Javier Cortés, Ian Krop, Dhiraj Gambhire, Lotus Yung, Yibin Wang, Jasmeet Singh, David Cameron. Trastuzumab deruxtecan vs treatment of physician’s choice in patients with HER2-low unresectable and/or metastatic breast cancer: Subgroup analyses from DESTINY-Breast04 [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-11-01.

Impact of age on indication for chemotherapy in early breast cancer patients: results from 104 German institutions from 2008 to 2017

PurposeToday, the decision to treat patients with chemotherapy for early breast cancer (EBC) is made based on the patient’s individual risk stratification and tumor biology. In cases with chemotherapy indication, the neoadjuvant application (NACT) is the preferred option in comparison with primary surgery and adjuvant chemotherapy (ACT). Age remains a relevant factor in the decision-making process. The aim of the present study was to illustrate the impact of age on the use of systemic therapy in clinical routine.MethodsThe study separately analyzed chemotherapy use among six age cohorts of EBC patients who had been treated at 104 German breast units between January 2008 and December 2017.ResultsIn total, 124,084 patients were included, 46,279 (37.3%) of whom had received chemotherapy. For 44,765 of these cases, detailed information on treatment was available. Within this cohort, chemotherapy was administered as NACT to 14,783 patients (33.0%) and as ACT to 29,982 (67.0%) patients. Due to the higher prevalence of unfavorable tumor subtypes, younger patients had a higher rate of chemotherapy (≤ 29y: 74.2%; 30–39y: 71.3%) and a higher proportion of NACT administration ( ≤ 29y: 66.9%; 30–39y: 56.0%) in comparison with elderly patients, who had lower rates for overall chemotherapy (60–69y: 37.5%; ≥ 70y: 17.6%) and NACT (60–69y: 25.5%; ≥ 70y: 22.8%). Pathologic complete response was higher in younger than in older patients (≤ 29y: 30.4% vs. ≥ 70y: 16.7%), especially for HER2− subtypes.ConclusionThe data from the nationwide German cohort reveal relevant age-dependent discrepancies concerning the use of chemotherapy for EBC.

Neoadjuvant docetaxel and capecitabine (TX) versus docetaxel and epirubicin (TE) for locally advanced or early her2-negative breast cancer: an open-label, randomized, multi-center, phase II Trial

PurposeThe combination of taxanes and anthracyclines is still the mainstay of chemotherapy for early breast cancer. Capecitabine is an active drug with a favorable toxicity profile, showing strong anti-tumor activity against metastatic breast cancer. This trial assessed the efficacy and safety of the TX regimen (docetaxel and capecitabine) and compared it with the TE (docetaxel and epirubicin) regimen in locally advanced or high risk early HER2-negative breast cancer.Patients and methodsThis randomized clinical trial was conducted at five academic centers in China. Eligible female patients were randomly assigned (1:1) to the TX (docetaxel 75 mg/m2 d1 plus capecitabine 1000 mg/m2 twice d1–14, q3w) or TE (docetaxel 75 mg/m2 d1 plus epirubicin 75 mg/m2 d1, q3w) groups for four cycles. The primary endpoint was a pathological complete response in the breast (pCR). Secondary endpoints included pCR in the breast and axilla, invasive disease-free survival (iDFS), overall survival (OS), and safety.ResultsBetween September 1, 2012, and December 31, 2018, 113 HER2-negative patients were randomly assigned to the study groups (TX: n = 54; TE: n = 59). In the primary endpoint analysis, 14 patients in the TX group achieved a pCR, and nine patients in the TE group achieved a pCR (25.9% vs. 15.3%), with a not significant difference of 10.6% (95% CI -6.0–27.3%; P = 0.241). In a subgroup with high Ki-67 score, TX increased the pCR rate by 24.2% (95% CI 2.2–46.1%; P = 0.029). At the end of the 69-month median follow-up period, both groups had equivalent iDFS and OS rates. TX was associated with a higher incidence of hand-foot syndrome and less alopecia, with a manageable toxicity profile.ConclusionThe anthracycline-free TX regimen yielded comparable pCR and long-term survival rates to the TE regimen. Thus, this anthracycline-free regimen could be considered in selected patients.Trial RegistrationACTRN12613000206729 on 21/02/2013, retrospectively registered.

42 (PB-042) Poster - Comparison of Technetium (Tc)- and SPIO-guided Sentinel Lymph Node Biopsy (SLNB) in Patients with Neoadjuvant Chemotherapy in Early Breast Cancer – first retrospective data

Background: Super-paramagnetic iron oxide particle (SPIO)-techniques are reasonable alternatives to Technetium-(Tc)-localization of SLNB/TAD in early breast cancer with a similar detection rate but superiority in logistics. These results have to be confirmed in a neoadjuvant setting (PST).

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.