Chemotherapy For Early-stage Breast Cancer Research Articles

Neoadjuvant Immune Checkpoint Inhibitors Plus Chemotherapy in Early Breast Cancer

Recent studies have investigated the combination of immune checkpoint inhibitors (ICIs) with (neo)adjuvant chemotherapy in early-stage breast cancer. However, there is an ongoing debate about the optimal approach for integrating this strategy. To evaluate the association of neoadjuvant ICIs with pathologic complete response (pCR) across molecular phenotypes, to quantify the survival benefits of ICIs beyond pCR status, and to estimate the incidence of specific adverse events. The PubMed database was searched on December 10, 2023, to identify all potential eligible studies. Randomized clinical trials (RCTs) that assessed (neo)adjuvant ICI plus chemotherapy in early breast cancer. Data from the eligible RCTs were extracted by 2 reviewers. An extracted individual patient data meta-analysis and a trial-level random-effect meta-analysis were performed. Outcomes were pCR, event-free survival (EFS) in patients with and without pCR, and adverse events. Hazard ratios were estimated using stratified Cox proportional hazards regression models. Nine RCTs involving 5114 patients met the inclusion criteria (2097 triple-negative breast cancer [TNBC], 1924 hormone receptor-positive [HR+]/ERBB2-negative [ERBB2-], and 1115 ERBB2+ tumors). In TNBC, the addition of ICIs was associated with an improved pCR rate regardless of programmed cell death ligand 1 (PD-L1) status (absolute improvement, >10%). In HR+/ ERBB2- tumors, the administration of ICIs was associated with improved pCR only in the PD-L1-positive (PD-L1+) population (absolute improvement, +12.2%), whereas no benefit was observed in ERBB2+ tumors. In patients with TNBC achieving a pCR, the addition of ICIs was associated with improved EFS (hazard ratio, 0.65; 95% CI, 0.42-1.00), resulting in a 5-year EFS of 92.0% with ICIs compared with 88.0% without them. In patients with residual disease, ICIs also showed better EFS (hazard ratio, 0.77; 95% CI, 0.61-0.98), resulting in a 5-year EFS of 63.3% with ICIs and 56.1% without them. Adjuvant ICI did not show numerical improvement in patients with either pCR or residual disease (all hazard ratios >1). During the neoadjuvant treatment, the incidence of grade 3 or greater immune-related adverse events with ICI was 10.3%. These findings suggest that neoadjuvant ICI therapy improves efficacy outcomes in early-stage TNBC and PD-L1+ HR+/ERBB2- tumors with an acceptable safety profile; however, no benefit was observed with adjuvant ICI. Given the financial and toxicity costs associated with ICIs, future research should prioritize identifying patients most likely to benefit from the addition of ICIs to neoadjuvant chemotherapy.

Pilot evaluation of portable scalp cooling for chemotherapy-associated alopecia in early-stage breast cancer.

12141 Background: Chemotherapy-induced alopecia significantly impacts quality of life (QOL). First-generation scalp cooling systems PAXMAN and Dignicap, while effective in reducing alopecia, are not universally adopted due to their lack of portability. Amma is a second-generation, portable and battery-powered scalp cooling system that offers the opportunity for widespread clinical usage by allowing self-administration and mobility. Here, we report first-in-human outcomes of Amma in a preliminary cohort receiving curative-intent taxane-based chemotherapy for early-stage breast cancer. Methods: We conducted a pilot clinical trial (NCT05508984) of the Amma system at Providence Cancer Institute in Oregon. Key inclusion criteria included: no baseline alopecia [Dean’s scale 0], intent to receive 4-6 cycles of taxane-based, anthracycline-sparing therapy, willingness to participate in quality-of-life questionnaires, and serial scalp photography. The primary outcome was the feasibility of Amma devices for adoption within the clinic ascertained by patient reported outcomes (PRO) and provider feedback. The secondary outcome was efficacy defined as the proportion of subjects achieving < 50% hair loss [Dean’s scale 0-2] at 30 days post-treatment, and tolerability assessed by common terminology criteria for adverse events (CTCAE). Results: 14 participants were enrolled and evaluable from 9/2022-1/2024. Participants received docetaxel/cyclophosphamide (TC x 4, n=10) or weekly paclitaxel/trastuzumab+/- pertuzumab (TH(P), n=4). 93% of participants (n=13/14) successfully completed treatment. One participant discontinued scalp cooling prematurely. Primary efficacy endpoint of <50% hair loss was achieved in 64% participants (n=9/14, [95% CI: 0.39, 0.89]) (TC: n=5/10; TH(P): n=4/4). On the validated “Was it Worth It?” questionnaire, 92% reported the treatment “worthwhile”, 85% would repeat participation, and 100% would recommend it to others. After treatment, 93% reported a similar or increased QOL with participation and 71% deemed the experience “better than expected”, paralleling PRO outcomes from previously published trials using first-generation cooling devices. Provider feedback was favorable regarding feasibility of treatment. Conclusions: Scalp cooling with the portable Amma system was both feasible and effective in this pilot study. Point estimates of efficacy were like those reported for PAXMAN (Dean’s 0-2: 50%) and DigniCap (66%). A follow-up clinical trial is planned with a primary outcome of efficacy in patients receiving taxane-based chemotherapy (NCT06215469, PI: Rugo). Clinical trial information: NCT05508984 .

Preventing chemotherapy-induced peripheral neuropathy with acupuncture, a multinational parallel randomized controlled trials project (PACT).

TPS12156 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a significant challenge for patients (pts) with breast cancer treated with taxanes and platinum compounds. CIPN severely affects quality of life, leading to paresthesia and pain, and often results in dose modifications and discontinuation of treatment. Although preliminary trials suggest the effectiveness of acupuncture in managing existing symptoms of CIPN, the use of acupuncture to prevent CIPN is not well studied. Prior studies provide inconclusive results, underscoring the need for more rigorous investigation. We designed an international study, PACT, to evaluate the impact of acupuncture on the prevention of CIPN in breast cancer pts who undergo adjuvant or neoadjuvant taxane-based chemotherapy. Methods: PACT is a coordinated multi-national study consisting of three parallel randomized trials in USA, China, and South Korea, using the same inclusion/exclusion criteria, randomization, interventions, and validated measures. PACT is designed to evaluate the effectiveness of acupuncture in preventing CIPN in pts undergoing taxane-based chemotherapy for early-stage breast cancer. Participants include pts with newly diagnosed stage I-III breast cancer without preexisting neuropathy, scheduled for adjuvant or neoadjuvant taxane-based chemotherapy. Target enrollment is 140 pts from three sites: Dana-Farber Cancer Institute (USA) (n=100), Jiangsu Province Hospital of Chinese Medicine (China) (n = 20) and the Daegu Catholic University Medical Center (South Korea) (n=20), randomized (1:1) to the acupuncture arm or a control. The acupuncture arm receives a standardized protocol of 1-2 sessions per week for 12 weeks (total of 14 sessions). The control arm receives relaxation exercises with nature scenery videos for 14 sessions. The follow-up period for both arms is 12 weeks. Main measures include The European Organisation for Research and Treatment of Cancer (EORTC) QLQ-CIPN20, QLQ-30 and Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) CIPN items. The primary outcome measure is the change in CIPN severity, assessed using the EORTC QLQ-CIPN20 sensory subscale, between baseline and week 12, with secondary outcomes including occurrence of CIPN and maximum CIPN scores, pain, sleep quality, and overall quality of life. A planned pooled analysis of individual patient data will be performed. The ethics review committee of each site has approved the study. Today, 89 (64%) of the planned 140 participants have been enrolled. Clinical trial information: NCT05528263 , ChiCTR2200066714, KCT0008470.

Continuous glucose monitoring and rates of hyperglycemia during chemotherapy for early-stage breast cancer.

e24134 Background: Diabetes (DM) and hyperglycemia (HG) during chemotherapy increase the risk of treatment-related toxicities. The prevalence of HG and daily patterns of HG over the course of chemotherapy in patients with early-stage breast cancer (ESBC) are currently unknown. Methods: We conducted a prospective single-arm pilot study of continuous glucose monitoring in patients with ESBC receiving chemotherapy from 12/2020 – 2/2022. Eligibility criteria included: diagnosis of Stage I-III BC, age ≥18, and planned chemotherapy with concurrent corticosteroid supportive care use. Patients were excluded if they were receiving other systemic corticosteroids or insulin. Patients wore FreeStyle Libre Pro continuous glucose monitoring sensors from the time of chemotherapy initiation (± 7 days) through completion. The sensors detected interstitial glucose levels every 15 minutes and were reapplied by the study team every 2-3 weeks. Primary endpoints were: (1) prevalence of HG, defined as number of patients with ≥1 glucose reading ≥140 mg/dL and (2) among those who developed HG, the proportion of time spent hyperglycemic, defined as number of readings ≥140 mg/dL divided by total number of readings. Key secondary endpoints included prevalence of prediabetes (pre-DM) and diabetes (DM) at baseline and changes in A1c from baseline to weeks 12 and 24. The analysis was stratified by baseline A1c (euglycemia [A1c < 5.7%], pre-DM [A1c 5.7%-6.4%], or DM [A1c ≥6.5% and clinical diagnosis of DM prior to study enrollment]). Results: Among 20 evaluable patients, the median age at baseline was 59 (range 34-78) and median body mass index (BMI) was 29.5 kg/m2 (range 19.5-41.6). The most common chemotherapy regimens included docetaxel/cyclophosphamide (25%), weekly paclitaxel ± trastuzumab (20%), paclitaxel followed by doxorubicin/cyclophosphamide (15%), docetaxel/carboplatin/trastuzumab/pertuzumab (15%), and cyclophosphamide/methotrexate/fluorouracil (15%). All 20 patients developed HG. Of 124,165 total readings, 17% were ≥140 mg/dL and mean glucose was 112.7 mg/dL. At baseline, n = 10 were euglycemic, n = 7 had pre-DM, and n = 3 had DM. By cohort, the proportion of time spent hyperglycemic was 3.9% (euglycemia group), 10% (pre-DM group), and 73.3% (DM group) (p < .0001). Mean glucose values were 95.5 mg/dL (euglycemia group), 104.5 mg/dL (pre-DM group), and 183.0 mg/dL (DM group) (p < .0001). Change in mean A1c from baseline to weeks 12 and 24 varied significantly across groups. Conclusions: Among patients receiving chemotherapy for ESBC, we found evidence of HG in all patients, and the proportion of time spent hyperglycemic during chemotherapy varied significantly by baseline A1c. Further interventions should evaluate the benefits of improved glucose control among patients with baseline A1c > 5.7%. Clinical trial information: NCT04473378 .

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

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

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.

Abstract 2135: Racial disparities in symptom burden among women receiving early stage breast cancer chemotherapy

Abstract Purpose: The purpose of this study was to compare prevalent symptoms (pain, fatigue, and physical function) and changes over time between Black and White women undergoing chemotherapy for early-stage breast cancer (ESBC) employing a longitudinal, repeated measures design over the course of ESBC. Methods: Data collected as per protocol of 1R01MD012245, comparing racial differences in chemotherapy tolerance and dose modifications during chemotherapy treatment at baseline, midpoint, and endpoint, tailored to each patient's individual chemotherapy schedule. Race was collected by patient self-report and chart review. Symptom burden (fatigue, pain, and physical functioning) was measured by the PROMIS-29 Profile v 2.0). Area deprivation was measured using the Area Deprivation Index (ADI). Linear mixed models were used to assess racial differences in symptom burden across timepoints, and changes in symptom burden over time, adjusting for ADI. Results: A total of 147 patients participated in this study (36% Black and 64% white). Pain: Black patients reported significantly higher pain scores than White patients at pretherapy (MD=3.7, p=.034), midpoint (MD=5.8, p: 0.002), and endpoint (MD=7.8, p<.001). Even after adjusting for area deprivation, this disparity persisted (F(1, 390)=29.43, p<.001), with Black patients having higher pain scores at midpoint (MD=4.7, p: 0.02) and endpoint (MD=7.8, p<.001). Pain scores worsened over time for Black patients, increasing significantly by the end of chemotherapy (MDT1-T3 =6.2, p=.010; MDT2-T3=5.8, p=.024). No significant changes in pain scores were observed over time among White patients. Fatigue: After adjusting for area deprivation, fatigue significantly increased at the endpoint (MDT1-T3=8.9, p<.001) for Black patients. Among White patients, fatigue increased at midpoint (MDT1-T2=5.7) and continued to worsen at the endpoint (MDT1-T3=10.1, p<.001; MDT2-T3=4.3, p=.017). Physical Function: Black patients had significantly lower physical function than White patients at the midpoint (MD=4.0, p=.027). By the end of chemotherapy, physical function deteriorated significantly for Black patients (MDT1-T3=7.8, p<.001), and White patients (MDT1-T3=7.7, p<.001; MDT2-T3=4.8, p=.002). Correlations between the ADI and symptom severity and physical function revealed that living in more deprived areas was associated with greater pain severity (r=-.227, p=.002, 56.3 vs. 50.1) and worse physical function (r=-.190, p=-.035, 40.6 vs. 42.4) at the completion of chemotherapy. Conclusions: The findings indicate that race and area deprivation are associated with symptom trajectories over the course of ESBC chemotherapy. Further research is warranted on how to best assess and relieve symptom burden among Black ESBC patients so that existing disparities in treatment and treatment outcomes are not perpetuated. Citation Format: Elham Nasrollahi, Hiba Abujaradeh, Susan Mazanec, Julia O'Brien, Isabelle M. Schlemmer, Margaret Rosenzweig. Racial disparities in symptom burden among women receiving early stage breast cancer chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2135.

Perspectives of patients undergoing neoadjuvant chemotherapy for breast cancer during the COVID-19 pandemic.

The COVID-19 pandemic resulted in a lapse in routine health care and cancer screenings for many individuals. This study sought to improve our understanding of the impact of the COVID-19 pandemic on women being treated for breast cancer, both in general, and specifically related to their diagnosis. Semi-structured interviews were conducted between August 2021 and February 2022 with women who were receiving neoadjuvant chemotherapy for early-stage breast cancer at the Stefanie Spielman Comprehensive Breast Center in Columbus, Ohio. Interviews were recorded and transcribed verbatim. Transcripts were coded using deductive dominant thematic analysis and inductive coding that allowed for categorization of data as well as identification of emergent themes. Data collected from our 19 interviews revealed that the COVID-19 pandemic posed important challenges for breast cancer patients including fear of COVID-19 infection and feelings of isolation. Most interviewees noted they had been vaccinated against COVID-19 because of a desire to protect themselves and others from getting sick. Some women also expressed concerns about having delayed their screening mammograms due to the pandemic. Several patients described unexpected positive aspects of the pandemic such as being able to spend more time with family and having the ability to continue working because of the option to work from home during their cancer treatment. Our findings provide important insight about the impact of COVID-19 on breast cancer patients. We highlight the positives that have been reported because of the pandemic, as well as the need to address delayed breast cancer screening.

The evolving landscape of chemotherapy for the treatment of early-stage breast cancer from 2006-2019: Results of a retrospective cohort study.

6600 Background: Chemotherapy has been a part of the evolving landscape of treatment for women with early-stage breast cancer (EBC). Over the last 20 years, standard treatment has included over 20 different drug combinations recommended by the National Comprehensive Cancer Network (NCCN), with nearly 45 variations on dosing and schedule across drug combinations. Little is known about the real-world landscape of chemotherapy used in EBC and how treatment patterns have changed with the advent of new standards of care. We evaluated chemotherapy patterns for women with EBC in the Optimal Breast Cancer Dosing (OBCD) Study, which uses electronic health record (EHR) data from KPNC (Kaiser Permanente Northern California) and Kaiser Permanente Washington (KPWA). Methods: In a cohort of 34,322 women diagnosed and treated for primary stage I-IIIA breast cancer aged 18+ at KPNC and KPWA, we explored patterns of chemotherapy use over time, from 2006 to 2019. We conducted stratified analyses based on receipt of pertuzumab and/or trastuzumab, due to their longer treatment duration. Results: Overall, 13,383 (39.0%) women received intravenous chemotherapy, with a decline observed in receipt of chemotherapy over time (40.5% in 2006 vs 35.9% in 2019) (p-trend<0.001). Of the women who received chemotherapy, 8.5% received neoadjuvant treatment, increasing from 4.1% in 2006 to 14.5% in 2019 (p-trend<0.0001). The average duration of chemotherapy was 5.4 months in 2006, increasing to 6.3 months in 2019 (p-trend<0.0001), and the number of chemotherapy infusion visits increased from an average of 10.7 visits in 2006 to an average of 12.5 in 2019 (p-trend<0.0001). Of those who received chemotherapy, 26.8% received trastuzumab or pertuzumab, with receipt of trastuzumab/pertuzumab increasing over time (p-trend<0.0001). For those receiving trastuzumab/pertuzumab, there was a decrease in treatment duration and average number of chemotherapy administration visits (p-trend<0.0001 for both). Conversely, for those not receiving trastuzumab/pertuzumab, there was an increase in the treatment duration and average number of visits (p-trend<0.0001 for both). Conclusions: While the prevalence of women receiving chemotherapy in our cohort has decreased since 2006, there has been a marked increase in neoadjuvant chemotherapy among those women receiving chemotherapy, as well as an increase in both the duration of chemotherapy treatment and number of associated chemotherapy administration visits, a pattern specifically observed in non-trastuzumab/pertuzumab containing regimens.The change in average duration and number of visits represents a shift in treatment patterns for patients and providers. Understanding trends in breast cancer chemotherapy is useful to inform clinical care and administrative planning for sites delivering chemotherapy for early-stage breast cancer.

Abstract 919: Benefit of chemotherapy in early-stage breast cancer with variant histology

Abstract Introduction: Breast cancer (BC) is a heterogenous disease with multiple histological variants (HV) differing in their aggressiveness, survival, and response to treatments. Given the rarity of the HVs, very little is known about their treatment and chemosensitivity. The benefit of chemotherapy (CT) is unclear in hormone receptor-positive HER2 negative (HR+) subtype in the mucinous, medullary, cribriform, and papillary HVs in the NCCN guidelines. We aim to study the benefit of CT in these BC histologies. Method: We queried the SEER database from 2010-2018 for stage I, II, and III HR+ BC patients (pts) with mucinous, medullary, cribriform, and papillary histologies and examined their overall survival (OS) and disease-specific survival (DSS). Pts with metastatic disease and carcinoma in situ were excluded. The population was divided into two cohorts based on the receipt of adjuvant CT (CT positive (CT+) and CT negative (CT-) groups (gps)). Mann Whitney U and Fisher’s Exact test were used to compare continuous and categorical variables, respectively. Multivariate cox regression models were used for studying the association of CT with OS and DSS, controlling for confounding variables such as surgery, radiation, stage, grade, race, age, sex, and lymph node status. All analyses were conducted in RStudio v4.0.2 at a significance level of 0.05. Results: In the mucinous histology, out of a total of 11,745 pts, 94% (n= 6,788) were HR+. Among them, 8.5% (n= 580) were CT+ and 91.5% (n= 6208) were CT-. The 5-year (yr) OS was higher for CT+ compared to CT- among all stages (Stage I: 99% vs 92%, HR= 0.12; II: 96% vs 84%, HR= 0.22; III: 94% vs 40%, HR= 0.08, all p<0.001). The benefit of CT in 5-yr DSS was observed only in stage III (96% vs 73%, HR= 0.2, both p<0.001). In the medullary histology, out of a total of 1,787 pts, 34% (n= 265) were HR+. Among these HR+ BC, all stage III pts received CT and their 5-yr OS was 94%. In stages I and II, CT+ had better 5-yr OS compared to CT- gp, (stage I: 99% vs 90%, p= 0.03, HR= 0.12, p= 0.07; II: 96% vs 91%, p= 0.03, HR= 0.23, p= 0.05). No 5-yr DSS benefit with CT was observed in any stage. Out of the total 1,110 BC pts with cribriform histology, 93% (n= 617) were HR+. Among them, 13.2% (n= 82) were CT+. The 5-yr OS was higher in CT+ compared to CT- in stage II (98% vs 82%, p=0.02, HR= 0.2, p= 0.036), but not in stage I or III. 5-yr DSS was not significantly better with CT in any stage. In the papillary histology, out of the total 1,698 pts, 83% (n= 889) were HR+. Among them, CT+ had better 5-yr OS compared to CT- only in stage II (86% vs 78%, p= 0.04, HR= 0.46, p= 0.047). There was no statistically significant DSS benefit with CT at any stage. Conclusion: In this large retrospective study, we observed that in mucinous and medullary histologies, adjuvant CT has OS benefit in HR+ BC subtype. In HR+ papillary and cribriform histologies, CT can be considered in higher stages. Multicenter clinical trials would be beneficial to assess the impact of CT in HVs and to formulate guidelines. Citation Format: Arya Mariam Roy, Syed Maaz Abdullah, Kayla Catalfamo, Kristopher Attwood, Shipra Gandhi. Benefit of chemotherapy in early-stage breast cancer with variant histology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 919.

Anthracycline-containing and taxane-containing chemotherapy for early-stage operable breast cancer: a patient-level meta-analysis of 100 000 women from 86 randomised trials

Anthracycline-taxane chemotherapy for early-stage breast cancer substantially improves survival compared with no chemotherapy. However, concerns about short-term and long-term side-effects of anthracyclines have led to increased use of taxane chemotherapy without anthracycline, which could compromise efficacy. We aimed to better characterise the benefits and risks of including anthracycline, and the comparative benefits of different anthracycline-taxane regimens. We did an individual patient-level meta-analysis of randomised trials comparing taxane regimens with versus without anthracycline, and updated our previous meta-analysis of anthracycline regimens with versus without taxane, as well as analysing 44 trials in six related comparisons. We searched databases, including MEDLINE, Embase, the Cochrane Library, and meeting abstracts to identify trials assessing anthracycline and taxane chemotherapy. Adjuvant or neoadjuvant trials were eligible if they began before Jan 1, 2012. Primary outcomes were breast cancer recurrence and cause-specific mortality. Log-rank analyses yielded first-event rate ratios (RRs) and CIs. 28 trials of taxane regimens with or without anthracycline were identified, of which 23 were deemed eligible, and 15 provided data on 18 103 women. Across all 15 trials that provided individual data, recurrence rates were 14% lower on average (RR 0·86, 95% CI 0·79-0·93; p=0·0004) with taxane regimens including anthracycline than those without. Non-breast cancer deaths were not increased but there was one additional acute myeloid leukaemia case per 700 women treated. The clearest reductions in recurrence were found when anthracycline was added concurrently to docetaxel plus cyclophosphamide versus the same dose of docetaxel plus cyclophosphamide (10-year recurrence risk 12·3% vs 21·0%; risk difference 8·7%, 95% CI 4·5-12·9; RR 0·58, 0·47-0·73; p<0·0001). 10-year breast cancer mortality in this group was reduced by 4·2% (0·4-8·1; p=0·0034). No significant reduction in recurrence risk was found for sequential schedules of taxane plus anthracycline when compared with docetaxel plus cyclophosphamide (RR 0·94, 0·83-1·06; p=0·30). For the analysis of anthracycline regimens with versus without taxane, 35 trials (n=52 976) provided individual patient data. Larger recurrence reductions were seen from adding taxane to anthracycline regimens when the cumulative dose of anthracycline was the same in each group (RR 0·87, 0·82-0·93; p<0·0001; n=11 167) than in trials with two-fold higher cumulative doses of non-taxane (mostly anthracycline) in the control group than in the taxane group (RR 0·96, 0·90-1·03; p=0·27; n=14 620). Direct comparisons between anthracycline and taxane regimens showed that a higher cumulative dose and more dose-intense schedules were more efficacious. The proportional reductions in recurrence for taxane plus anthracycline were similar in oestrogen receptor-positive and oestrogen receptor-negative disease, and did not differ by age, nodal status, or tumour size or grade. Anthracycline plus taxane regimens are most efficacious at reducing breast cancer recurrence and death. Regimens with higher cumulative doses of anthracycline plus taxane provide the greatest benefits, challenging the current trend in clinical practice and guidelines towards non-anthracycline chemotherapy, particularly shorter regimens, such as four cycles of docetaxel-cyclophosphamide. By bringing together data from almost all relevant trials, this meta-analysis provides a reliable evidence base to inform individual treatment decisions, clinical guidelines, and the design of future clinical trials. Cancer Research UK, UK Medical Research Council.

Chemotherapy for early-stage breast cancer: the more the better?

Chemotherapy for early-stage breast cancer: the more the better?

Racial Disparities in Pathological Complete Response Among Patients Receiving Neoadjuvant Chemotherapy for Early-Stage Breast Cancer

Among patients with breast cancer, inconsistent findings have been published on racial disparities in achieving pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT). To investigate whether racial disparities exist in achieving pCR and what factors contribute to them. Within the ongoing Chicago Multiethnic Epidemiologic Breast Cancer Cohort (ChiMEC), which consists of a prospectively ascertained cohort of patients with breast cancer, 690 patients with stage I to III breast cancer receiving NACT were identified for this single-institution study at the University of Chicago Medicine. Patients diagnosed between 2002 and 2020 (median follow-up: 5.4 years) were included; next-generation sequencing data on tumor-normal tissue pairs were available from 186 ChiMEC patients, including both primary and residual tumor samples. Statistical analysis was performed from September 2021 to September 2022. Demographic, biological, and treatment factors that could contribute to disparities in achieving pCR. pCR was defined as the absence of invasive cancer in the breast and axillary nodes, irrespective of ductal carcinoma in situ. The study included 690 patients with breast cancer, with a mean (SD) age of 50.1 (12.8) years. Among the 355 White patients, 130 (36.6%) achieved pCR compared to 77 of the 269 Black patients (28.6%; P = .04). Not achieving pCR was associated with significantly worse overall survival (adjusted hazard ratio, 6.10; 95% CI, 2.80-13.32). Black patients had significantly lower odds of achieving pCR compared with White patients in the hormone receptor-negative/ERBB2+ subtype (adjusted odds ratio, 0.30; 95% CI, 0.11-0.81). Compared with White patients with ERBB2+ disease, Black patients were more likely to have MAPK pathway alterations (30.0% [6 of 20] vs 4.6% [1 of 22]; P = .04), a potential mechanism of anti-ERBB2 therapy resistance. Tumor mutational burden and somatic alterations in several genes (eg, FGF4, FGF3, CCND1, MCL1, FAT1, ERCC3, PTEN) were significantly different between the primary and residual tumors. In this cohort study of patients with breast cancer, racial disparities in response to NACT were associated with disparities in survival and varied across different breast cancer subtypes. This study highlights the potential benefits of better understanding the biology of primary and residual tumors.

Phase angle is associated with muscle health and cardiorespiratory fitness in older breast cancer survivors

Phase angle (PhA) obtained from bioelectrical impedance analysis (BIA) is an indicator of cellular integrity and relates to several chronic conditions. The purpose of this secondary analysis was to evaluate the association of PhA with health-related physical fitness, namely, cardiorespiratory fitness, skeletal muscle volume, and myosteatosis (i.e. muscle health) in older breast cancer survivors. Twenty-two women ≥60 years with a body mass index (BMI) ≥25kg/m2 and who completed chemotherapy for early-stage breast cancer were included. BIA, cardiopulmonary exercise tests and magnetic resonance imaging scans were completed before and after eight weeks of time-restricted eating. At baseline, PhA was associated with cardiorespiratory fitness (R2=0.54, p<0.01) and skeletal muscle volume (R2=0.83, p<0.01) and myosteatosis (R2=0.25, p=0.02). Results were similar at follow-up. Findings from this pilot study suggest that higher values of PhA are associated with better health-related physical fitness among older breast cancer survivors.

Abstract P2-20-02: Enrichment of atypical memory double negative (CD27— IgD—) tumour infiltrating B cells following neoadjuvant chemotherapy for early-stage breast cancer

Abstract Background: Humoral immune responses have previously been associated with improved outcomes, with B cell infiltrates able to independently predict pathologic complete response to neoadjuvant chemotherapy (NACT). B cells represent a diverse population of cells and the complex interplay between specific B cell subsets in the context of chemotherapy treated breast cancers remains unclear. Here, we investigate the dynamic changes in the B cell immune landscape before and after NACT treatment across different breast cancer subtypes. Methods: Treatment naïve, mid-treatment and post-NACT breast tumour tissue samples were dissociated into single cells, stained with two panels of B cell-specific antibodies recognising a total of 24 target proteins, and analysed by flow cytometry. In addition, PMBC before and after NACT were also profiled. B cell subsets were classified as either naïve (CD27—IgD+), class-switched memory (CD27+IgD—), unswitched memory (CD27+IgD+) or double negative (DN)(CD27—IgD—). DN B cells were further characterised into DN1 (CXCR5+CD21+) and DN2 (CXCR5—CD21—) subsets. In vitro co-cultures of breast cancer cell line spheroid and PBMC were carried out. Results: In both treatment naïve and chemotherapy treated samples, we observed a significant expansion in the DN B cell population within the TME compared to the periphery. DN B cells represented on average 40.96% of B cells in treatment naïve tumours vs 9.48% in PBMCs (p&amp;lt; 0.0001), and 71.80% vs 6.34% of B cells in post-NACT tumour vs PBMC samples respectively (p&amp;lt; 0.05). Interestingly, in treatment naïve PBMC and tumour tissue samples, the largest proportion of the DN subset consisted of DN1 cells, 69.35% and 64.11% respectively. In contrast, following NACT, DN2 cells constituted the majority of the DN population both within the TME (86.30%) and in the periphery (50.44%). Although the specific functions of these B cell subsets remain unclassified, deeper phenotyping suggests DN1 cells more closely resemble the phenotype of class-switched memory cells, whilst DN2 cells are thought to have antibody-secreting properties and more closely resemble the plasmablast phenotype. scRNA sequencing of B cells pre- and post NACT is currently underway. Conclusion: To our knowledge, this work is the first to identify an expanded population of DN B cells in breast tumour tissue and highlights the requirement for further investigation into these cells to decipher their role in the context of chemotherapy treatment and resistance in breast cancer. Citation Format: Esme Carpenter, Thanussuyah Alaguthurai, Farhana Hossain, Rosalind Graham, Helen Kakkassery, Sean Keane, Sheeba Irshad. Enrichment of atypical memory double negative (CD27— IgD—) tumour infiltrating B cells following neoadjuvant chemotherapy for early-stage breast cancer [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 P2-20-02.

Anthracycline- and taxane-containing chemotherapy for early-stage breast cancer

Anthracycline- and taxane-containing chemotherapy for early-stage breast cancer

Abstract B106: Racial differences in baseline financial distress, basic needs, social support, and symptom distress among women receiving early-stage breast cancer chemotherapy

Abstract Little is known about how baseline financial health for patients with breast cancer (BC) influences racial disparity in outcomes. Thus, this study sought to: 1) describe financial hardship in women prior to chemotherapy for early-stage breast cancer (baseline) and how that varies by race; 2) examine associations between baseline financial health, perceived stress, symptom distress and social support Methods: This analysis employed a descriptive correlational comparative design using data from the baseline time point of SEMOARS: The Symptom Experience, Management and Outcomes According to Race and Social Determinants of Health a multi-site, repeated measures, mixed-methods study comparing the symptom experience of Black and White women with BC. Inclusion criteria were female, Black or White race, 18 years of age or older, prescribed chemotherapy for a diagnosis of stages 1–3 BC. Measures included demographic characteristics, self-reported race, and basic needs assessment of food, housing, utilities, and health. Economic Hardship, the 17-item Psychological Sense of Economic Hardship includes 4 subscales reflecting recent economic strain. The Interpersonal Support Evaluation List (ISEL) assesses the perceived availability of social support, and the Symptom Distress Scale (SDS) evaluates the current symptom experiences of 11 symptoms. Descriptive, comparative and correlational statistics were used. Results: A total of 248 women were included in this cross-sectional analysis. Participants had a mean age of 52.99±12.31 years; were 58.9% White and 41.1% Black, 54% partnered, 57.3% employed, and 70.8% had some college education. Almost all participants (98%) had some form of insurance. Almost one fifth (18.5%) of patients reported inadequate household income to meet their basic needs and 41.5% reported somewhat or extreme difficulty in paying for their basic needs. Compared to White patients, Black patients reported significantly higher (worse) levels of economic hardship (1.17±2.95 vs. -0.70±2.36; p&amp;lt;.001) and reported inadequate income to meet basic needs (30.5% vs. 10.5%; p&amp;lt;.001), and somewhat or extreme difficulty in paying for their basic needs (50.5% vs. 27.6%; 9.5% vs. 3.9%, ps&amp;lt;.001 respectively). Economic hardship had significant weak to moderate correlations with symptom distress (r=0.389, p&amp;lt;.001) and social support subscales (r= -0.333 to -0.445, all p&amp;lt;.001), in the expected directions. Black race was associated with worse economic hardship, its subscales, and inadequate current household income (rs= -0.208 to -0.334; all ps &amp;lt;.001). Using multiple linear regression, 34% of the variance in economic hardship was explained for this cohort (F(6, 169)=19.81, p&amp;lt;0.001). Of the predictor variables, Black race was significantly associated with economic hardship (Beta= -0.239, p&amp;lt;0.001, 95% CI: -2.10 to -0.58). Discussion: Black patients begin BC chemotherapy with greater financial distress, less social support, and higher physical symptoms than White patients. This holds implications for racial differences in the ability to tolerate chemotherapy Citation Format: Margaret Q. Rosenzweig, Catherine Bender, Susan Sereika, Mary Connolly, Hiba Abujaradeh, Susan Mazanec. Racial differences in baseline financial distress, basic needs, social support, and symptom distress among women receiving early-stage breast cancer chemotherapy [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B106.

Socioeconomic Disparities in Neoadjuvant Chemotherapy for Early-Stage Breast Cancer.

Neoadjuvant chemotherapy (NCT) is often used for patients with early-stage breast cancer. Disparities in the use of NCT based on clinical, demographic, and socioeconomic factors have not been evaluated. Data from the National Cancer Database was analyzed for patients with T1-2, N0-1 breast cancer from 2006 to 2015. Univariate and multivariate analysis determined which factors predicted for the receipt of NCT. We found 159946 eligible patients. Factors associated with receipt of NCT included T2 vs. T1 disease, N1 vs. N0, and treatment at an academic facility. Race itself was not significant; however, a higher level of education amongst Black populations correlated with the receipt of NCT. Clinical factors are the greatest determinants for receipt of NCT in early-stage breast cancer. Disparities exist that cannot be explained by race alone; socioeconomic and demographic factors are important. Cancer care should be evaluated in the context of the intersectionality of these health determinants.

Rationale and design of IMPACT-women: a randomised controlled trial of the effect of time-restricted eating, healthy eating and reduced sedentary behaviour on metabolic health during chemotherapy for early-stage breast cancer.

Metabolic dysfunction and excess accumulation of adipose tissue are detrimental side effects from breast cancer treatment. Diet and physical activity are important treatments for metabolic abnormalities, yet patient compliance can be challenging during chemotherapy treatment. Time-restricted eating (TRE) is a feasible dietary pattern where eating is restricted to 8 h/d with water-only fasting for the remaining 16 h. The purpose of this study is to evaluate the effect of a multimodal intervention consisting of TRE, healthy eating, and reduced sedentary time during chemotherapy treatment for early-stage (I-III) breast cancer on accumulation of visceral fat (primary outcome), other fat deposition locations, metabolic syndrome and cardiovascular disease risk (secondary outcomes) compared with usual care. The study will be a two-site, two-arm, parallel-group superiority randomised control trial enrolling 130 women scheduled for chemotherapy for early-stage breast cancer. The intervention will be delivered by telephone, including 30-60-minute calls with a registered dietitian who will provide instructions on TRE, education and counselling on healthy eating, and goal setting for reducing sedentary time. The comparison group will receive usual cancer and supportive care including a single group-based nutrition class and healthy eating and physical activity guidelines. MRI, blood draws and assessment of blood pressure will be performed at baseline, after chemotherapy (primary end point), and 2-year follow-up. If our intervention is successful in attenuating the effect of chemotherapy on visceral fat accumulation and cardiometabolic dysfunction, it has the potential to reduce risk of cardiometabolic disease and related mortality among breast cancer survivors.

Effect of Secondary Prophylactic G-CSF on the Occurrence of Febrile Neutropenia in Breast Cancer.

Docetaxel and cyclophosphamide (TC) combination therapy is widely used as adjuvant chemotherapy for early-stage breast cancer and is associated with a high incidence of febrile neutropenia (FN). Granulocyte colony-stimulating factor (G-CSF) is recommended in the primary prevention of febrile neutropenia (FN). This study aimed to evaluate the FN-suppressing effect of G-CSF in patients with breast cancer receiving TC. We performed 272 treatment cycles after FN onset in 106 patients with breast cancer receiving TC. We retrospectively evaluated the effect of G-CSF as secondary prophylaxis. The frequency of FN was calculated based on the treatment cycles to adjust for differences in the number of cycles per case and FN occurrence. FN occurred in 58 cycles (21.3%). The incidence of FN with and without secondary prophylactic G-CSF was 10.1% and 25.9%, respectively (p=0.003). Multivariate analysis showed secondary prophylactic G-CSF administration to be an independent predictor of FN incidence [odds ratio (OR)=0.33, 95% confidence interval (CI)=0.14-0.74, p=0.007]. Secondary prophylaxis with G-CSF is recommended for patients with breast cancer undergoing TC chemotherapy to reduce the incidence of FN.