Chemotherapy For Early Breast Cancer Research Articles

Use of a high-sensitivity anti-Mullerian hormone (AMH) assay to determine ovarian function after chemotherapy for early breast cancer.

552 Background: It is now well established that AMH can indicate the extent of chemotherapy-induced damage on the ovarian reserve. Very low AMH levels in women after chemotherapy for early breast cancer (eBC) may indicate treatment-induced premature ovarian failure (POI), but the evidence to implement its routine clinical use remains limited. Methods: AMH was measured (Roche cobas autoanalyser) in 197 women aged 40-45 years at diagnosis treated with anthracycline/cyclophosphamide/taxane based chemotherapy for eBC, with no previous endocrine therapy and no subsequent aromatase inhibitor exposure or ovarian suppression. 76% were ER positive and received tamoxifen. The primary objective was to assess the relationships between AMH levels at 6 months after chemotherapy (AMH6) with subsequent ovarian function at 30 months. This included accuracy of prediction of loss of ovarian function at 30 months (E30) after chemotherapy by AMH levels at 6 months (AMH6) and the value of other endocrine/clinical factors pretreatment and at 6 months. Multivariate analysis was performed with data were split into 70% training and 30% testing sets with results reported for model performance on the test set. Results: AMH fell from a median of 0.62 (IQR 0.21-1.31) ng/ml pretreatment to become undetectable ( < 0.01ng/ml) in 137 (70%) of women at 6 months. AMH showed very little recovery, being undetectable in 115 women at 18 months and 119 at 30 months. In those with detectable AMH at 30 months, it remained very low, median 0.07ng/ml, max 0.82ng/ml but nevertheless it reflected ovarian function. Thus median estradiol at 30 months (E30) was 50 pmol/l (IQR 34-68) in women with undetectable AMH at that time, vs 313 pmol/l (IQR 102-1052) in the 80 women with detectable AMH. AMH at 6 months was predictive of ovarian function at 30 months, as E30 was 56 pmol/l (IQR 40-104) in women with undetectable AMH6 vs 258pmol/l (IQR 69-780; p < 0.0001) in women with detectable AMH6, and the positive predictive value (PPV) of AMH being undetectable at 6 months and remaining so at 30 months was 77%. Random forest analysis identified BMI as a non-endocrine predictive factor of E30. Using a stringent cutoff of ≤50pmol/l (13.6 pg/ml) and adding 1:9 weighting to improve PPV gave a test validated PPV of 79.0% while maintaining AUC at 83.7% for prediction of E30. Other classifiers performed less well than random forests. Conclusions: Measurement of AMH at 6 months after chemotherapy has predictive value for later ovarian function, and combining this with other endocrine and baseline data improves discriminative ability. This approach indicates the potential role of multivariate analysis based on AMH measured shortly after chemotherapy to helping optimise subsequent endocrine therapy.

Impact of timing of adjuvant chemotherapy for early breast cancer: the Royal Marsden Hospital experience

The optimal time to deliver adjuvant chemotherapy has not been defined. A retrospective study of consecutive patients receiving adjuvant anthracycline and/or taxane 1993-2010. Primary endpoint included 5-year disease-free survival (DFS) in patients commencing chemotherapy <31 versus ≥31 days after surgery. Secondary endpoints included 5-year overall survival (OS) and sub-group analysis by receptor status. We identified 2003 eligible patients: 1102 commenced chemotherapy <31 days and 901 ≥31 days after surgery. After a median follow-up of 115 months, there was no difference in 5-year DFS rate with chemotherapy <31 compared to ≥31 days after surgery in the overall population (81 versus 82% hazard ratio (HR) 1.15, 95% confidence interval (95% CI) 0.92-1.43, p = 0.230). The 5-year OS rate was similar in patients who received chemotherapy <31 or ≥31 days after surgery (90 versus 91%, (HR 1.21, 95% CI 0.89-1.64, p = 0.228). For 250 patients with triple-negative breast cancer OS was significantly worse in patients who received chemotherapy ≥31 versus <31 days (HR = 2.18, 95% CI 1.11-4.30, p = 0.02). Although adjuvant chemotherapy ≥31 days after surgery did not affect DFS or OS in the whole study population, in TN patients, chemotherapy ≥31 days after surgery significantly reduced 5-year OS; therefore, delays beyond 30 days in this sub-group should be avoided.

61P Estimating the cost of adjuvant chemotherapy in ER+/HER2- early breast cancer and distant recurrence of breast cancer in the UK

Multigene assays (MGAs) can reduce over and under-treatment with adjuvant chemotherapy in oestrogen receptor positive (ER+), human epidermal growth factor 2 negative (HER2-) early breast cancer. The cost of treatment of early breast cancer and distant recurrence of breast cancer are important parameters in the economic evaluation of MGAs. The recent approval of new treatments in the UK, such as CDK4/6 inhibitors, is likely to increase the cost of management of breast cancer. This study aimed to estimate the cost of adjuvant chemotherapy in early breast cancer and the cost of treating distant recurrence in the UK using expert opinion and published sources.

P038 - Scenarios of cost-savings associated with Oncotype DX® test-guided decisions for adjuvant chemotherapy in early breast cancer in Germany

P038 - Scenarios of cost-savings associated with Oncotype DX® test-guided decisions for adjuvant chemotherapy in early breast cancer in Germany

Prognostic role of serum thymidine kinase 1 kinetics during neoadjuvant chemotherapy for early breast cancer

BackgroundEmerging data support the use of thymidine kinase 1 (TK1) activity as a prognostic marker and for monitoring of response in breast cancer (BC). The long-term prognostic value of TK1 kinetics during neoadjuvant chemotherapy is unclear, which this study aimed to elucidate.MethodsMaterial from patients enrolled to the single-arm prospective PROMIX trial of neoadjuvant epirubicin, docetaxel and bevacizumab for early BC was used. Ki67 in baseline biopsies was assessed both centrally and by automated digital imaging analysis. TK1 activity was measured from blood samples obtained at baseline and following two cycles of chemotherapy. The associations of TK1 and its kinetics as well as Ki67 with event-free survival and overall survival (OS) were evaluated using multivariable Cox regression models.ResultsCentral Ki67 counting had excellent correlation with the results of digital image analysis (r = 0.814), but not with the diagnostic samples (r = 0.234), while it was independently prognostic for worse OS [adjusted hazard ratio (HRadj) = 2.72, 95% confidence interval (CI) 1.19-6.21, P = 0.02]. Greater increase in TK1 activity after two cycles of chemotherapy resulted in improved event-free survival (HRadj = 0.50, 95% CI 0.26-0.97, P = 0.04) and OS (HRadj = 0.46, 95% CI 0.95, P = 0.04). There was significant interaction between the prognostic value of TK1 kinetics and Ki67 (pinteraction 0.04).ConclusionSerial measurement of serum TK1 activity during neoadjuvant chemotherapy provides long-term prognostic information in BC patients. The ease of obtaining serial samples for TK1 assessment motivates further evaluation in larger studies.

Long-term patient reported outcomes and hematologic toxicity among patients who received Granulocyte-Colony Stimulating Factors during chemotherapy for early breast cancer

We assessed long-term associations of Granulocyte-Colony Stimulating Factors (G-CSF) use with patient-reported outcomes (PROs) and hematologic toxicity among chemotherapy-treated, early-stage breast cancer patients in CANTO (NCT01993498).Among 2920 patients longitudinally followed-up until year-4 after diagnosis, 49% used G-CSF. In multivariable-adjusted mixed-models, EORTC QLQ-C30 pain and summary score were not substantially different between groups (overall adjusted mean difference, use vs no-use [95%CI]: +1.27 [-0.33 to +2.87] and −1.01 [-1.98 to −0.04], respectively). PROs were slightly worse at year-4 among patients receiving G-CSF, although differences were of trivial clinical significance. No major differences were observed in leukocyte or platelet count over time.

Performance of functionality measures and phase angle in women exposed to chemotherapy for early breast cancer.

The study aimed to analyze the influence of chemotherapy on nutritional status and the phase angle (PhA) as nutritional indicator for breast cancer women undergoing chemotherapy. A prospective study was performed. Women who were starting chemotherapy with no previous chemotherapy treatment were recruited. Quality of life (QoL) was collected using the EORTC QLQ-BR23 questionnaire. Bioelectrical impedance analysis, performance tests, and blood sample to albumin analyzes were collected at 2-time points: diagnosis (T0) and after 1 month of completion of therapy (T1). Mean, standard deviation, linear regression, and ANOVA in R were used to explore the results. 61 women were included. We did not find any changes in body composition. However, PhA, nutritional risk index (NRI), gait speed (GS), and handgrip strength (HGS) had expressive changes (p<0.001). 75.4% of women had PhA values below the cut-off point of 5.6°, and the group that had a lower average of PhA also expressed low NRI. PhA was a nutritional status marker and its values were influenced by changes in NRI (p<0.05). We have found supporting evidence for chemotherapy treatment resulting in worsening of prognostic factors such as PhA, and yet PhA was related to no nutritional risk. Besides a higher prevalence of obesity, 80% of the sample showed some nutritional risk level, implying the possibility of a sub-notification candidate who might benefit, for instance, from nutritional intervention in obesity groups. Further investigation about this theme may improve health measures for the prevention and screening of disease among breast cancer.

Abstract PS8-03: Inflammation and coagulation biomarkers associated with physical resilience in older women receiving chemotherapy for early breast cancer

Abstract Background: Physical resilience, the ability to resist decline and maintain functional status despite a stressor such as chemotherapy, is a central aspect of successful aging. Understanding clinical and biological factors associated with resilience in older women receiving chemotherapy for early breast cancer may facilitate the development of targeted interventions to maintain an individual’s robustness.Methods: Women age ≥65 (N=406) with Stage I-III breast cancer who were part of a clinical study of neo/adjuvant chemotherapy in older women were recruited from 16 sites (NCT01472094, R01AG037037). The Deficit Accumulation Index (DAI), a continuous score (0-1) calculated based on 51-items from geriatric assessment data (Cohen et al Cancer 2017), was measured before and after receipt of chemotherapy. DAI was categorized as robust (0.0&amp;lt;0.2), prefrail (0.2&amp;lt;0.35) and frail (≥0.35). Baseline blood biomarkers of inflammation (interleukin-6 [IL-6], C-reactive protein [CRP]) and coagulation (D-dimer) were measured and defined as elevated if values were ≥median values in this cohort. The population of interest was older women who were robust prior to initiation of chemotherapy. The primary outcome was resilience (Yes/No); yes, defined as retaining robustness [DAI 0.0&amp;lt;0.2] before and ≤1 month after chemotherapy. Demographic, disease, and pretreatment variables associated with resilience in univariate analysis with p&amp;lt;0.1 were further adjusted using multivariable logistic regression to examine the associations between baseline biomarkers and resilience. Results: Before starting chemotherapy, 324 of 406 (80%) older women were robust. The median age was 70 (range 65-86), 61% had stage II or III disease, 29% had HER2+ disease, 22% had TNBC, 37% received an anthracycline-based regimen, 49% had planned duration of treatment &amp;gt; 12 weeks, and 74% received primary prophylaxis with WBC growth factors. Among these 324 robust older women, 253 (78%) remained robust (resilient) at the end of chemotherapy, 63 (19%) became prefrail, and 8 (3%) became frail. In univariate analyses, patients treated with anthracycline (OR=0.63, p=0.09), planned duration of treatment &amp;gt; 12 weeks (OR=0.56, p=0.04), elevated IL-6 ≥2.7 pg/ml (OR=0.59, p=0.05), elevated CRP ≥4.3 μg/ml (OR=0.57, p=0.04), elevated D-dimer ≥0.7 μg/ml (OR=0.61, p=0.07), or at least one elevated biomarker (OR=0.18, p&amp;lt;0.001) at baseline were less likely to be resilient after systemic chemotherapy. Adjusting for anthracyclines and treatment duration, patients who had one or more elevated biomarker were still significantly less likely to be resilient (OR=0.15, 95 CI 0.04-0.49, p=0.002) compared to those with no elevated biomarkers at baseline. Conclusions: In this cohort of older women with early breast cancer who were robust prior to initiation of chemotherapy, 22% became prefrail or frail at end of treatment. Resilience to chemotherapy was related to inflammatory and coagulation biomarkers. Further research is needed to examine the mechanism underlying why some older women are resilient and retain their robustness after receiving treatment, whereas others experience decline, and further explore the role of inflammation/coagulation in this phenomenon. Table 1. Multivariable associations between baseline blood biomarkers and resilienceResilient (n=253) No. %Non-resilient (n=71) No. %Multivariable OR (95%CI)P value# of elevated biomarkers*064 (25)4 (6)1.00190 (36)29 (41)0.16 (0.05-0.55)0.004255 (22)22 (31)0.14 (0.04-0.49)0.002344 (17)16 (23)0.14 (0.04-0.51)0.003No elevated biomarker64 (25)4 (6)1.00At least one elevated189 (75)67 (94)0.15 (0.04-0.49)0.002*Biomarkers were defined as elevated using the entire cohort median value as cut off points (IL-6 ≥2.7 pg/ml, CRP ≥4.3 μg/ml, and D-dimer ≥0.7 μg/ml). Combined effects of biomarkers were examined by creating a four-level categorical combination variable: 0=all three biomarkers are &amp;lt;median; 1=one of the biomarkers ≥median; 2=two of the biomarkers ≥median; and, 3=all three biomarkers ≥median. A dichotomized variable was also created comparing none (all three biomarkers are &amp;lt;median) vs at least one biomarker elevated (≥median). Citation Format: Mina S Sedrak, Canlan Sun, Hyman Muss, Rachel A. Freedman, Allison Magnuson, Cary P. Gross, William P. Tew, Heidi D. Klepin, Tanya M. Wildes, Efrat Dotan, Tracey O'Connor, Mary Ann Fenton, Ruby Sharma, Andrew Chapman, Cynthia Owusu, Selina Chow, Heeyoung Kim, Vani Katheria, Mark LaBarge, William Dale, Saro Armenian, Susan Neuhausen, Harvey J. Cohen. Inflammation and coagulation biomarkers associated with physical resilience in older women receiving chemotherapy for early breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS8-03.

Abstract PS13-04: Impact of delayed initiation of adjuvant chemotherapy in early breast cancer: Analysis from Taiwan National breast cancer registry database

Abstract Background:In 2017, there are more than 14,000 cases of newly diagnosed breast cancer in Taiwan. With the popularity of early screening policy and social-awareness, the proportion of early breast cancer has increased significantly in the last decades. For the high risk group with early breast cancer, adjuvant systemic chemotherapy could provide lower breast cancer recurrence rate and better overall survival rate. In Taiwan, every citizen must join the National Health Insurance (NIH), and the NIH would cover the whole expanse of adjuvant chemotherapy. Theoretically, all breast cancer patients could receive their condign chemotherapy regardless of their social economic status. The optimal initiation timing of adjuvant chemotherapy is undiscovered, and the effect of delay initiation is still under contestation. In this study, we try to identify the relationship between initiation time of chemotherapy and survival outcome, and different breast cancer subtypes would be analyzed separately. We also evaluate many associated factors that may delay chemotherapy initiation or survival status.Material and Methods:In this observational, populational-based study using Taiwan national breast cancer registry database, we studied 110,784 patients diagnosed with Stage I~III breast cancer between January 1, 2006 and Deccember 31, 2016. Time to chemotherapy(TCC) was defined as the days between surgery and the initial dose of adjuvant chemotherapy. We categorized patients into initiate chemotherapy within 30 days, 31~60 days, 61~90 days, and more than 91 days. The patient demography, tumor biology, lymph node status, type of breast surgery, receiving reconstructive surgery or not, radiation therapy, immunohistochemistry data (estrogen receptor, progesterone receptor, and human epidermal growth factor 2[HER2]), and we categorized patients according to different breast cancer subtypes. Univariate analysis with Kaplan-Meier method is used to evaluate TTC influence, and log-rank test is used to compare differences between groups. Multivariate logistic regression model is used to identify important factors associated with delayed chemotherapy initiation and survival.Preliminary Results:Totally 72840 patients were enrolled in this study, and the median age at initial diagnosis was 52.4 years old. Delayed wound healing and breast reconstruction are the main factors associated with delated TTC. Comparing with TTC&amp;lt;30 days group, TTC of 31~60 days group showed no difference in disease-free survival and overall survival, while TTC of 61~91 days group had a trend of lower disease-free survival (p=0.12). TTC more than 91 days had worse disease-free survival (HR=1.16, 95%CI=1.03~1.38) and overall survival (HR=1.23, 95%CI=1.08~1.52). We assumed initiate first chemotherapy more than 90 days as delated TTC as generally accepted in previous publications. In subgroup analysis, delayed TTC caused worse disease-free survival especially in triple negative group (HR=1.42, 95%CI=1.21~1.68) and HER2 group (HR=1.38, 95%CI=1.22~1.55).Conclusion:For breast cancer patients who assumed to receive adjuvant systemic chemotherapy, delayed in initiation of chemotherapy (more than 90 days) may result in worse outcome, especially in triple negative breast cancer and HER2 group. Besides the above preliminary result, other multivariate analysis and intergroup comparison are still ongoing. More information will reveal in SABCS 2020. Citation Format: Junping Shiau, Fang-Ming Chen, Ming-Feng Hou. Impact of delayed initiation of adjuvant chemotherapy in early breast cancer: Analysis from Taiwan National breast cancer registry database [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-04.

Abstract PS6-54: Prognostic significance of residual micrometastatic axillary involvement with complete pathologic breast response after neoadjuvant chemotherapy for early breast cancer

Abstract Introduction and objectives Pathologic complete response (pCR, ypT0/Tis ypN0) after neoadjuvant chemotherapy (nCT) in early breast cancer (BC) is associated with higher survival rate. Controversy about the prognostic significance of low-volume or micrometastatic axillary residual disease (ypN1mi-RD) exists. Essentially, it is considered equivalent to high-volume nodal disease (ypN1/ypN2-RD) for the indication of lymphadenectomy after nCT. Clarifying ypN1mi-RD prognostic value would be useful for planning adjuvant therapy. Thus, our objective was to assess the prognostic significance of ypN1mi-RD in the context of primary breast tumor pCR. Material and methodsRetrospective, single-center analysis of a cohort of early BC patients treated with nCT between 2010 and 2018 who achieved breast pCR (ypT0/Tis) combined with axillary pCR (ypN0) or ypN1mi-RD or ypN1/ypN2-RD. Cases with pre-nCT sentinel lymph node biopsy were excluded. 5-year disease-free survival (DFS) and overall survival (OS) were analyzed using Cox regression models.ResultsAmong 470 early BC patients treated with nCT, 134 (28.5%) had in-breast pCR, of whom: 97 (20.6%) were ypN0; 7 (1.5%) were ypN1mic; 10 (2.1%) were ypN1 and 5 (1.1%) were ypN2. Clinicopathological characteristics of the groups are shown in the Table. Median follow-up: 33 months. Eight patients relapsed, 4 of 97 with nodal pCR and 4 of 22 with axillary residual disease: 2/7 ypN1mic; 1/10 ypN1 and 1/5 ypN2. Patients who relapsed predominantly presented pre-nCT clinical lymph node involvement, hormone receptor negativity, ki67&amp;lt;20% and absence of complete clinical response (100%). Globally, patients with axillary residual disease had lower DFS rates (95% vs. 69%, p = 0.03), with no apparent differences between ypN1-RD vs. ypN2-RD in the subgroup analysis (75% vs. 80%, respectively). ypN1mic-RD patients showed the poorest DFS (33%, p &amp;lt;0.01). In the multivariable analysis, ypN1mic-RD had worse DFS than nodal pCR (HR 13.98, 95%CI 1.95-100.24, p = 0.01), but no differences were observed between the low and high-volume residual axillary disease categories (HR 0.24, 95%CI 0.03-1.74, p = 0.16). Due to the low rate of events, no differences in terms of OS were observed (p = 0.77).Conclusion In the context of in-breast pCR after nCT for early BC, ypN1mic-RD not only presented a higher risk of relapse than nodal pCR, but also was not associated with a better prognosis than that observed for ypN1/ypN2-RD. Micrometastatic axillary residual disease behaves as an independent adverse prognostic factor, comparable to high-volume axillary residual disease, and might be considered as a factor for the indication of post-nCT adjuvant treatment. Table. Clinicopathologic characteristics of the cohort of early BC patients treated with nCT betweenypT0/TisypT0/TisypN1mic-RDypN1/N2-RDpCR(N=7)(N=15)(N=97)Age (median, range)49 (25-83)47 (40-77)47 (25-80)Menstrual statusPostmenopausal3 (42,8%)4 (26,7%)42 (43,3%)Premenopausal4 (57,1%)11 (73,3%)55 (56,7%)ECOGECOG 05 (71,4%)13 (86,7%)78 (80,4%)ECOG 12 (28,5%)2 (13,3%)19 (19,6%)Histologic subtypeInvasive ductal carcinoma7(100,0%)14 (93,3%)95 (97,9%)Other subtypes0 (0,0%)1 (6,7%)2 (2,0%)Histologic gradeGrade 10 (0,0%)0 (0,0%)1 (1,0%)Grade 23 (42,9%)5 (33,3%)17 (17,5%)Grade 34 (57,1%)8 (53,3%)67 (69,1%)Unknown0 (0,0%)2 (13,3%)0 (0,0%)cTcT11 (14,2%)4 (26,7%)8 (8,2%)cT24 (57,1%)5 (33,3%)63 (64,9%)cT32 (28,6%)6 (40,0%)24 (24,7%)cT4a-d0 (0,0%)0 (0,0%)2 (2,1%)cNcN01 (14,3%)0 (0,0%)27 (27,8%)cN13 (42,9%)5 (33,3%)34 (35,1%)cN21 (14,3%)6 (40,0%)24 (24,7%)cN32 (28,6%)4 (26,7%)11 (11,3%)Molecular subtypeHR+ HER2-1 (14,3%)8 (53,3%)11 (11,3%)HR+ HER2+3 (42,9%)1 (6,7%)30 (30,9%)HR- HER2+2 (28,6%)3 (20,0%)21 (21,6%)TNBC1 (14,3%)3 (20,0%)35 (36,1%)Breast surgeryConservative7 (100%)10 (66,7%)67 (69,1%)Mastectomy0 (0,0%)5 (33,3%)30 (30,9%)Nodal surgerySLN biopsy0 (0,0%)0 (0,0%)22 (22,7%)ALND7 (100,0%)15 (100,0%)75 (77,3%)ypTypT05 (71,4%)7 (46,7%)80 (82,5%)ypTis2 (28,6%)8 (53,3%)17 (17,5%)Relapse typeMetastatic2 (28,6%)2 (28,6%)2 (2,1%)Local/contralateral0 (0,0%)0 (0,0%)2 (2,1%)Deaths0 (0,0%)1 (6,7%)1 (1,0%)BC: breast cancer. HR: hormone receptor. nCT: neoadjuvant chemotherapy. pCR: pathologic complete response. SLN: sentinel lymph node. TN: triple negative. ypN1mic-RD: micrometastatic axillary residual disease. ypN1/N2-RD: high-volume axillary residual disease. Citation Format: Esmeralda García-Torralba, Maria Esperanza Guirao Garcia, Pilar de la Morena Barrio, Alejandra Ivars Rubio, Elena Garcia Martinez, Elisa Garcia Garre, Gema Marin Zafra, Beatriz Alvarez Abril, Esther Navarro Manzano, Francisco Ayala de la Peña. Prognostic significance of residual micrometastatic axillary involvement with complete pathologic breast response after neoadjuvant chemotherapy for early breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-54.

Abstract PS18-27: Integrated immuno-genomic analyses in early breast cancer: Results from the Scandinavian breast group 2004-1 (SBG-2004-1) randomized phase II trial

Abstract Background: Given the emerging role of immune-related biomarkers in breast cancer (BC), little is known about specific immune cell composition patterns and genomic alterations and how these could interact in early BC setting. The aim of this proof-of-principle study is to describe immuno-genomic correlates within the tumor microenvironment using newly developed techniques for multiplexed fluorescent immunohistochemistry (mfIHC, Mezheyeuski et al., J Pathol. 2018) and high-throughput low-input genome sequencing (CUTseq, Zhang et al., Nat Commun 2019). Methods: The randomized SBG-2004-1 phase II trial evaluated the feasibility of tailored and dose-dense epirubicin and cyclophosphamide followed by docetaxel (EC→T) as adjuvant chemotherapy for early BC, enrolling a total of 124 patients. CUTseq was applied to gDNA extracted from archival low-input formalin-fixed paraffin-embedded (FFPE) tissue as well as peripheral blood samples of BC patients. mfIHC was performed on FFPE tissue microarrays, allowing simultaneous detection of six immune markers (CD4, CD8, PD-L1, PD-1, FoxP3, CD68) and quantification in an automated and tissue-compartment manner (Vectra® Polaris™ automated quantitative pathology imaging system and inForm® software, Akoya Biosciences). Patient characteristics and 10-year follow-up data were also available. Associations of different immune cell patterns and DNA copy number alterations (CNAs) with clinicopathological parameters and survival outcomes were evaluated using standard statistical methods.Results: 69/124 (55.6%) and 82/124 (66.1%) FFPE samples were available for CNA profiling (blood gDNA for normalization, n=33) and mfIHC, respectively. MYC gene was the most commonly amplified cancer-associated gene (n=44, 63.8%), and other frequent alterations included ERBB2 (n=31, 44.9%) and PIK3CA (n=14, 20.3%) amplification as well as TP53 (n=29, 42%) and PTEN (n=16, 23.2%) deletion. CNA burden (i.e., the percentage of the genome either amplified or deleted) was significantly correlated with higher tumor grade (p=0.013) but was not prognostic for relapse-free survival. CD4+ T-cells were the most abundant immune cell subpopulation, followed by CD68+ macrophages. The immune checkpoint markers PD-L1 and PD-1 were mostly expressed in CD4+ T-cells in both tumor and stroma compartments, while stromal PD-1+CD8+ and PD-1+CD68+ cell subsets were also among the ones with the higher cell density. CD4+ T-cell density was significantly correlated with tumor size, whereas the different immune cell infiltration patterns were not found to be prognostic. Combined immuno-genomic analyses revealed that high CNA burden was inversely associated with intra-tumoral CD4+ (Spearman’s r=-0.33, p=0.01) and CD8+ infiltration (Spearman’s r=-0.37, p=0.004). Conclusions: The present study indicates the feasibility of CNA profiling by CUTseq and immuno-profiling by mfIHC in FFPE samples obtained from BC patients. Moreover, our data provide a link between genomic alterations and the immune landscape in early BC and set the basis for further application of CUTseq and mfIHC in larger patient cohorts. Citation Format: Ioannis Zerdes, Michele Simonetti, Alexios Matikas, Luuk Harbers, Ning Zhang, Dimitrios Salgkamis, Susanne Agartz, Markella Zacharouli, Pablo Moreno-Ruiz, Johan Hartman, Artur Mezheyeuski, Jonas Bergh, Nicola Crosetto, Theodoros Foukakis. Integrated immuno-genomic analyses in early breast cancer: Results from the Scandinavian breast group 2004-1 (SBG-2004-1) randomized phase II trial [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS18-27.

Statin Exposure and Risk of Heart Failure After Anthracycline- or Trastuzumab-Based Chemotherapy for Early Breast Cancer: A Propensity Score‒Matched Cohort Study.

BackgroundStatins are hypothesized to reduce the risk of cardiotoxicity associated with anthracyclines and trastuzumab. Our aim was to study the association of statin exposure with hospitalization or emergency department visits (hospital presentations) for heart failure (HF) after anthracycline‐ and/or trastuzumab‐containing chemotherapy for early breast cancer.Methods and ResultsUsing linked administrative databases, we conducted a retrospective cohort study of women aged ≥66 years without prior HF who received anthracyclines or trastuzumab for newly diagnosed early breast cancer in Ontario between 2007 to 2017. Statin‐exposed and unexposed women were matched 1:1 using propensity scores. Trastuzumab‐treated women were also matched on anthracycline exposure. We matched 666 statin‐discordant pairs of anthracycline‐treated women and 390 pairs of trastuzumab‐treated women (median age, 69 and 71 years, respectively). The 5‐year cumulative incidence of HF hospital presentations after anthracyclines was 1.2% (95% CI, 0.5%–2.6%) in statin‐exposed women and 2.9% (95% CI, 1.7%–4.6%) in unexposed women (P value, 0.01). The cause‐specific hazard ratio associated with statins in the anthracycline cohort was 0.45 (95% CI, 0.24–0.85; P value, 0.01). After trastuzumab, the 5‐year cumulative incidence of HF hospital presentations was 2.7% (95% CI, 1.2%–5.2%) in statin‐exposed women and 3.7% (95% CI, 2.0%–6.2%) in unexposed women (P value 0.09). The cause‐specific hazard ratio associated with statins in the trastuzumab cohort was 0.46 (95% CI, 0.20–1.07; P value, 0.07).ConclusionsStatin‐exposed women had a lower risk of HF hospital presentations after early breast cancer chemotherapy involving anthracyclines, with non‐significant trends towards lower risk following trastuzumab. These findings support the development of randomized controlled trials of statins for prevention of cardiotoxicity.

Patient-reported symptom severity, interference with daily activities, and adverse events in older and younger women receiving chemotherapy for early breast cancer

Patient-reported symptom severity, interference with daily activities, and adverse events in older and younger women receiving chemotherapy for early breast cancer

Societal costs of chemotherapy in the UK: an incidence-based cost-of-illness model for early breast cancer

AimTo estimate annual societal costs associated with chemotherapy for early breast cancer in the UK.DesignMixed methods: (a) an incidence-based cost-of-illness model was developed of indirect costs in patients with breast...

OP447 Feasibility And Validity Of Real-World Data As Evidence Of Effectiveness - Experience From Breast Cancer Care In Scotland

IntroductionData from randomized controlled trials (RCTs) are the primary source for health technology assessment (HTA) however these are limited by strict patient inclusion criteria, leading to concerns about whether treatment benefit estimates are accurate for all patients (generalizability). Real-World Data (RWD) have been proposed as a solution however as these are observational data there is additional potential for bias when estimating treatment effectiveness. To maximize the utility of RWD it is useful to consider the whole process of evidence generation and robustly address issues of feasibility and validity.MethodsA series of complementary studies investigated whether population-based routinely collected health data from Scotland are suitable for estimating the effectiveness of chemotherapy for early breast cancer. Firstly, a prognostic score was validated in this population. Secondly, a comparison of RWD and randomized trial effectiveness estimates was made to investigate feasibility and validity of several methods – Propensity Score Matching (PSM), Instrumental variables (IV) and Regression Discontinuity. Finally, effectiveness estimates in trial underrepresented groups were produced.ResultsPSM and IV were feasible and produced results in relatively close agreement with randomized data. Effectiveness estimates in trial underrepresented groups (women over 70 years and women with high comorbidity) were consistent with an approximate one-third reduction in the risk of death from breast cancer. This is equivalent to approximately a 3–4 percentage point difference in all cause mortality over 10 years in these groups.ConclusionsRWD are a feasible for generating estimates of effectiveness of adjuvant chemotherapy in early stage breast cancer. The process of using RWD for this purpose should include careful assessment of data quality and comparison of alternative strategies for causal identification in the context of available randomized data.

PCN98 Scenarios of Cost-Savings Associated with Oncotype DX® Test - Guided Decisions for Adjuvant Chemotherapy in EARLY Breast Cancer in Germany

PCN98 Scenarios of Cost-Savings Associated with Oncotype DX® Test - Guided Decisions for Adjuvant Chemotherapy in EARLY Breast Cancer in Germany

Patient-reported symptom severity, interference with daily activities, and adverse events in older and younger women receiving chemotherapy for early breast cancer.

To the authors' knowledge, it is unknown whether patient-reported symptom severity and symptom interference with daily activities differ between younger (aged <65 years) and older (aged ≥65 years) women receiving similar chemotherapy regimens for early breast cancer (EBC). Study participants rated 17 side effects of chemotherapy regimens currently in use in clinical practice (2014-2019). Of 284 women with EBC (stage I-III), approximately 57% were aged <65 years and 43% were aged ≥65 years. For anthracycline-based regimens, a higher percentage of younger women reported moderate, severe, or very severe (MSVS) hot flashes (49% vs 18%) (P < .001). For nonanthracycline regimens, a higher percentage of younger women reported MSVS hot flashes (38% vs 19%) (P = .009) and a lower percentage reported MSVS arthralgia (28% vs 49%) (P = .005). With regard to symptom interference with daily activities, a higher percentage of younger women being treated with anthracycline-based regimens reported MSVS hot flashes (32% vs 7%) (P = .001) and myalgia (38% vs 18%) (P = .02). For nonanthracycline chemotherapy, a higher percentage of younger women reported MSVS interference for hot flashes (26% vs 9%) (P = .006) and lower percentages reported abdominal pain (13% vs 28%) (P = .02). Overall, there were no significant differences noted among younger versus older patients with regard to hospitalizations (19% vs 12%; P = .19), dose reductions (34% vs 31%; P = .50), dose delays (22% vs 25%; P = .59), or early treatment discontinuation (16% vs 16%; P = .9546). Older and younger women with EBC who were treated with identical chemotherapy regimens generally experienced similar levels of symptom severity, symptom-related interference with daily activities, and adverse events. In this study, women receiving chemotherapy for early breast cancer rated the severity of 17 symptoms and symptom interference with their activities of daily living. Older (aged ≥65 years) and younger (aged <65 years) women who received identical chemotherapy regimens generally experienced similar levels of symptom severity, symptom-related interference with daily activities, and adverse events.

Genetyka i onkologia (część 2.). Podstawy medycyny personalizowanej w leczeniu raka piersi i raka jajnika

Individualisation of medical management based on prognostic and predictive markers (personalised medicine) allows customisation of prophylaxis and optimisation of treatment by increasing its efficiency and minimisation of adverse effects. In the case of breast cancer, therapy selection is still based on histopathology and immunohistochemical assessment including analysis of estrogen receptor (ER) expression, progesterone receptor (PgR) expression and over-expression or amplification of receptor tyrosine kinase erbB-2 gene ( ERBB2 aka HER2 ). An additional role, facilitating decision on appli­cation or waiver of chemotherapy in early breast cancer, may be played by panels assessing gene expression within tDNA (tumour DNA, i.e. DNA isolated from tumour cells) and evaluation of concentration of uPA (urokinase-type plasminogen activator) and PAI-1 (plasminogen activator inhibitor type 1) in tumour cells. Growing hope surrounds the new, targeted therapies, including: inhibitors of CDK 4/6 (cyclin-dependant kinases 4 and 6), mTOR inhibitors (rapamycin’s mammalian target), inhibitors of poly(ADP-ribose)polymerase(PARP) or inhibitors of PI3K (phosphatidylinositol-4,5-bisphosphate 3-ki­nases). For ovarian cancer, treatment selection is based on assessment of the histopathologic type, malignancy degree, FIGO classification and platinum sensitivity of the tumour. However, the increasing use of PARP inhibitors and angiogenesis inhibitors is noteworthy. In the context of personalised medicine for both these cancers, an important element involves also individualisation of prophylactic and therapeutic recommendations in carriers of germline mutations associated with hereditary cancer syndromes.

Serial Assessment of Depression and Anxiety by Patients and Providers in Women Receiving Chemotherapy for Early Breast Cancer.

Depression and anxiety are common in patients with breast cancer and associated with worse quality of life and treatment outcomes. Yet, these symptoms are often underrecognized and undermanaged in oncology practice. The objective of this study was to describe depression and anxiety severity and associated patient factors during adjuvant or neoadjuvant chemotherapy in women with early breast cancer using repeated single-item reports. Depression and anxiety were measured from consecutive patients and their clinicians during chemotherapy infusion visits. Associations between psychiatric symptoms and patient characteristics were assessed using Fisher's exact tests for categorical variables and t tests for continuous variables. The joint relationship of covariates significant in unadjusted analyses was evaluated using log-binomial regression. Cohen's kappa was used to assess agreement between patient- and clinician-reported symptoms. In a sample of 256 patients, 26% reported at least moderately severe depression, and 41% reported at least moderately severe anxiety during chemotherapy, representing a near doubling in the prevalence of these symptoms compared with before chemotherapy. Patient-provider agreement was fair (depression: κ = 0.31; anxiety: κ = 0.28). More severe psychiatric symptoms were associated with being unmarried, having worse function, endorsing social activity limitations, using psychotropic medications, and having a mental health provider. In multivariable analysis, social activity limitations were associated with more severe depression (relative risk [RR], 2.17; 95% confidence interval [CI], 1.36-3.45) and anxiety (RR, 1.48; 95% CI, 1.05-2.09). Oncologists frequently underestimate patients' depression and anxiety and should consider incorporating patient-reported outcomes to enhance monitoring of mental health symptoms. In this sample of 256 patients with breast cancer, depression and anxiety, measured using single-item toxicity reports completed by patients and providers, were very common during adjuvant or neoadjuvant chemotherapy. Patient-reported depression and anxiety of at least moderate severity were associated with multiple objective indicators of psychiatric need. Unfortunately, providers underrecognized the severity of their patients' mental health symptoms. The use of patient-reported, single-item toxicity reports can be incorporated into routine oncology practice and provide clinically meaningful information regarding patients' psychological health.

21 - Updated results of the MINDACT trial: 70-gene signature to guide de-escalation of chemotherapy in early breast cancer

21 - Updated results of the MINDACT trial: 70-gene signature to guide de-escalation of chemotherapy in early breast cancer