Adjuvant Chemotherapy In Women Research Articles

Effects of heavy-load strength training during (neo-)adjuvant chemotherapy on muscle strength, muscle fiber size, myonuclei, and satellite cells in women with breast cancer.

To investigate the effects of heavy-load strength training during (neo-)adjuvant chemotherapy in women with breast cancer on muscle strength, body composition, muscle fiber size, satellite cells, and myonuclei. Women with stage I-III breast cancer were randomly assigned to a strength training group (ST, n = 23) performing supervised heavy-load strength training twice a week during chemotherapy, or a usual care control group (CON, n = 17). Muscle strength and body composition were measured and biopsies from m. vastus lateralis collected before the first cycle of chemotherapy (T0) and after chemotherapy and training (T1). Muscle strength increased significantly more in ST than in CON in chest-press (ST: +10 ± 8%, p < .001, CON: -3 ± 5%, p = .023) and leg-press (ST: +11 ± 8%, p < .001, CON: +3 ± 6%, p = .137). Both groups reduced fat-free mass (ST: -4.9 ± 4.0%, p < .001, CON: -5.2 ± 4.9%, p = .004), and increased fat mass (ST: +15.3 ± 16.5%, p < .001, CON: +16.3 ± 19.8%, p = .015) with no significant differences between groups. No significant changes from T0 to T1 and no significant differences between groups were observed in muscle fiber size. For myonuclei per fiber a non-statistically significant increase in CON and a non-statistically significant decrease in ST in type I fibers tended (p = .053) to be different between groups. Satellite cells tended to decrease in ST (type I: -14 ± 36%, p = .097, type II: -9 ± 55%, p = .084), with no changes in CON and no differences between groups. Strength training during chemotherapy improved muscle strength but did not significantly affect body composition, muscle fiber size, numbers of satellite cells, and myonuclei compared to usual care.

Longitudinal trajectories of a claims-based frailty measure during adjuvant chemotherapy in women with stage I-III breast cancer.

Frailty is a dynamic syndrome characterized by reduced physiological reserve to maintain homeostasis. Prospective studies have reported frailty worsening in women with breast cancer during chemotherapy, with improvements following treatment. We evaluated whether the Faurot frailty index, a validated claims-based frailty measure, could identify changes in frailty during chemotherapy treatment and identified predictors of trajectory patterns. We included women (65+ years) with stage I-III breast cancer undergoing adjuvant chemotherapy in the SEER-Medicare database (2003-2019). We estimated the Faurot frailty index (range: 0-1; higher scores indicate greater frailty) at chemotherapy initiation, 4 months postinitiation, and 10 months postinitiation. Changes in frailty were compared to a matched noncancer comparator cohort. We identified patterns of frailty trajectories during the year following chemotherapy initiation using K-means clustering. Twenty-one thousand five hundred and ninety-nine women initiated adjuvant chemotherapy. Mean claims-based frailty increased from 0.037 at initiation to 0.055 4 months postchemotherapy initiation and fell to 0.049 10 months postinitiation. Noncancer comparators experienced a small increase in claims-based frailty over time (0.055-0.062). We identified 6 trajectory patterns: a robust group (78%), 2 resilient groups (16%), and 3 nonresilient groups (6%). Black women and women with claims for home hospital beds, wheelchairs, and Parkinson's disease were more likely to experience nonresilient trajectories. We observed changes in a claims-based frailty index during chemotherapy that are consistent with prior studies using clinical measures of frailty and identified predictors of nonresilient frailty trajectories. Our study demonstrates the feasibility of using claims-based frailty indices to assess changes in frailty during cancer treatment.

Trends in Systemic Inflammatory Reaction (SIR) during Paclitaxel and Carboplatin Chemotherapy in Women Suffering from Epithelial Ovarian Cancer.

Epithelial ovarian cancer (EOC) is the most fatal gynaecological malignancy treated with cytoreductive surgery followed by adjuvant taxane-platinum-based chemotherapy. It has been shown that the pretreatment systemic inflammatory reaction (SIR) in women with OC can be evaluated using the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR) and systemic inflammatory index (SII), depending on the stage of disease, and has prognostic value for overall survival. The aim of this study was to evaluate the changes in NLR, LMR, PLR and SII during chemotherapy. A total of 107 women with EOC (23 with type I and 84 with type II tumours) were included in a retrospective single-centre analysis. The Kologomorov-Smirnoff, Kruskal-Wallis or Friedman analysis of variance tests were used for data analysis, and a p value of 0.05 was considered statistically significant. A significant decrease in NLR, PLR and SII but not LMR was observed during adjuvant treatment. Pretreatment NLR, PLR and SII were dependent on disease stage and tumour grade; however, this association was lost during therapy. Additionally, strong and positive mutual correlations between NLR, LMR, PLR and SII were sustained during the whole course of chemotherapy. During first-line adjuvant chemotherapy in women with EOC, a decrease in SIR is confirmed.

Timing of postmastectomy radiotherapy following adjuvant chemotherapy for high-risk breast cancer: A post hoc analysis of a randomised controlled clinical trial

PurposeTo investigate the appropriate timing of radiotherapy (RT) after mastectomy and adjuvant chemotherapy for women with high-risk breast cancer. Patients and methodsPost hoc analyses of 584 patients with stage II and III breast cancer from a randomised controlled clinical trial were performed. All patients underwent mastectomy followed by sequential chemotherapy and RT. The optimal cut-off values for the surgery-RT interval (SRI) and the chemotherapy-RT interval (CRI) for overall survival (OS) were determined using the hazard ratio for continuous predictors. The locoregional recurrence (LRR), distant metastasis (DM), disease-free survival (DFS), and OS rates were estimated using the Kaplan–Meier method. Multivariate analyses were performed using Cox proportional hazards regression. ResultsMedian follow-up time was 83.5 months. Median SRI and CRI were 168 and 27 days, respectively. An SRI of >210 days was independently associated with higher DM (HR 2.65, 95% CI: 1.49–4.71; HR 2.78, 95% CI 1.51–5.26), lower OS (HR 2.44, 95% CI: 1.28–4.54; HR 2.50, 95% CI: 1.41–4.35), and lower DFS (HR 2.57, 95% CI: 1.45–4.57; HR 2.70, 95% CI: 1.45–5.00) than SRI of <180 or 180–210 days. Furthermore, a CRI of more than 42 days was independently associated with higher DM (HR 1.89, 95% CI: 1.17–3.06; HR 1.96, 95% CI: 1.19–3.22), lower OS (HR 2.44, 95% CI: 1.41–4.35; HR 1.92, 95% CI: 1.10–3.33), and lower DFS (HR 1.84, 95% CI: 1.14–2.96; HR 1.82, 95% CI: 1.12–2.94) than a CRI of <28 or 28–42 days. However, SRI and CRI had no significant effect on LRR. ConclusionsBased on the present findings, the timing of the initiation of RT both after mastectomy and after the completion of adjuvant chemotherapy is crucial for patients with high-risk breast cancer.

Efficacy of Sequential Capecitabine on Adjuvant Chemotherapy of Triple-Negative Breast Cancer

This paper aims to evaluate the efficacy of capecitabine as extended adjuvant treatment after anthracycline and paclitaxel combined adjuvant chemotherapy for women with early triple-negative breast cancer (TNBC). The patients with early TNBC were randomly assigned to capecitabine sequential treatment for 4 cycles and without any sequential treatment in the control group after anthracycline and paclitaxel combined adjuvant chemotherapy. The primary end point was disease-free survival (DFS). The secondary end point was overall survival (OS). One hundred patients were enrolled in this study between June 2013 and February 2015. Median age was 49 years ranging from 25 to 66 years and treatment was well tolerance. The median follow-up time after random allocation was 58 months (range: 11–62 months). There was no significant difference in DFS and OS between the two groups (hazard ratio (HR) of DFS was 0.50; 95% CI, 0.24–1.05; P=0.066). Our study shows that although the addition of four cycles capecitabine after anthracycline and paclitaxel combining adjuvant chemotherapy does not improve DFS and OS, but the trend of DFS is improved. The possible reason is that the four-cycle treatment of capecitabine is not enough, and another possible reason is that the number of cases is not enough.

Delay in Initiating Postmastectomy Radiotherapy is Associated With Inferior Clinical Oncologic Outcomes for High-Risk Breast Cancer

<h3>Purpose/Objective(s)</h3> To investigate the appropriate timing of radiotherapy (RT) after mastectomy and adjuvant chemotherapy for women with high-risk breast cancer. <h3>Materials/Methods</h3> A total of 584 patients with stage II-III breast cancer were analyzed from a randomized, open-label, phase 3 trial, which evaluated the non-inferiority of hypofractionated to conventional fractionated RT after mastectomy. All patients received mastectomy followed by adjuvant chemotherapy and RT without neoadjuvant treatments. Optimal cut-off value of the interval from the date of surgery to the starting date of RT (SRI) and the interval from the date of last-dose chemotherapy to the starting date of RT (CRI) for oncologic outcomes was calculated by Maxstat. Kaplan-Meier method was used to estimate the rates of locoregional recurrence (LRR), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS), and the differences were compared with log-rank test. Cox proportional hazards regression was performed for multivariate analysis. <h3>Results</h3> Median follow-up was 83.5 months (IQR 63-109). The median SRI was 168 days (range 93-357). The median CRI was 27 days (range 5-126). Compared to an SRI ≤165 days (5.5 months), an SRI > 165 days was associated with a significantly lower DFS rate (8-year 72.3% vs. 79.0%; <b>P</b> = 0.019), a higher DM rate (8-year 26.2% vs. 20.6%; <b>P</b> = 0.031), and a non-significantly higher LRR rate (8-year 9.0% vs. 6.0%, <b>P</b> = 0.065). Patients with an SRI > 180 days had a significantly lower OS rate compared with those with an SRI ≤180 days (8-year 72.2% vs. 84.1%; <b>P</b> = 0.012). Furthermore, CRI > 40 days was related to a significant decrease in DFS rate (8-year 67.0% vs. 76.9%; <b>P</b> = 0.002) and OS rate (8-year 69.0% vs. 83.0%; <b>P</b> = 0.002); and a significant increase in DM rate (8-year 33.4% vs. 21.8%; <b>P</b> = 0.001). No significant association between CRI > 40 days and LRR was found (8-year 10.4% vs. 7.2%; <b>P</b> = 0.238). After accounting for other known prognostic variables, SRI > 165 days, T stage and N stage remained significantly associated with inferior DM and DFS, while SRI > 180 days, T stage and N stage remained significantly associated with inferior OS. Meanwhile, CRI > 40 days, T stage and N stage were independently associated with inferior DM, DFS and OS. <h3>Conclusion</h3> Delay in initiating RT in patients with high-risk breast cancer is associated with inferior oncologic outcomes. We recommend RT should start within 165 days after mastectomy, and within 40 days after chemotherapy. NCT00793962

Prosigna test in breast cancer: real-life experience.

Genomic tests can guide the decision to administer adjuvant chemotherapy in women with hormone receptor (HR)-positive, Human Epidermal growth Factor 2 (HER2)-negative breast cancer (BC) at intermediate risk of recurrence. We assessed the decision-making and economic impact of the Prosigna test in a real-life setting. Retrospective cohort study of HR + , HER2- BC patients managed from 2016 to 2020, potential candidates for adjuvant chemotherapy, at intermediate risk of recurrence, in whom a Prosigna test was performed according to contemporary guidelines. The additional cost of chemotherapy over one year in terms of direct medical and non-medical costs was estimated in this study to be €9,737 (derived from a previous study, NCT02813317). The cost of the Prosigna test, as defined by the reimbursement system, was €1,849. Among the 809 patients included in this study, 2.3 Prosigna tests had to be performed to avoid adjuvant chemotherapy for one patient. The number of tests that had to be performed to avoid chemotherapy for one patient was higher for patients with grade 3 tumors and pN1mic axillary node involvement and lower for grade 1 tumors or in the absence of axillary node involvement (pN0), but did not vary according to the 10-year overall survival gain predicted by the Predict online test. The cost saving related to withholding of adjuvant chemotherapy for one patient on the basis of the Prosigna test results was €5,485. We present one of the largest cohorts of HR + , HER2- BC patients at intermediate risk of recurrence, in whom a Prosigna test was used to guide the adjuvant therapy decision in a real-life setting, resulting in a 44% decrease in the indication for chemotherapy.

Factors associated with declining adjuvant chemotherapy in women with advanced ovarian cancer who accepted initial intervention: A National Cancer Database (NCDB) study

Objective: The aim of this study was to identify factors predicting chemotherapy nonacceptance in women with advanced ovarian cancer who accepted primary surgery. A prior National Cancer Data Base (NCDB) analysis identified factors associated with chemotherapy refusal across all ovarian cancer cases, but the population who accept initial surgery and then decline recommended chemotherapy is not well studied.

Abstract ES2-2: Evolving opportunities to personalize radiation decisions - Guiding decisions to omit radiation after breast conserving surgery for invasive breast cancer

Abstract Much as the development of molecularly based signatures (OncotypeDx®, MammaPrint®, ProSigna™, etc.) has revolutionized the decision-making process surrounding the need for adjuvant chemotherapy in women with early stage breast cancer, the development of prognostic and predictive signatures to determine the need and efficacy of radiation for women with breast cancer holds similar promise. While preliminary efforts to develop these signatures has been encouraging, much work remains in order to successfully translate these signatures into the clinic. In this educational session, we will review the current status of genomic-based signatures for radiation decision making. We will also review the barriers to clinical adoption and the molecularly stratified trials testing these signatures for treatment omission. Ultimately, for any of these tests to be translated into the clinic it will require demonstration of their accuracy and reproducibility as a test and perhaps more importantly, demonstration of clinical utility and an ability to improve outcomes for women with breast cancer. While not yet realized, the ongoing development of these signatures holds much promise as the field seeks to finally realize “personalized medicine” as it relates to radiation treatment for women with breast cancer. Citation Format: C Speers. Evolving opportunities to personalize radiation decisions - Guiding decisions to omit radiation after breast conserving surgery for invasive breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr ES2-2.

Changes in lipid profiles during and after (neo)adjuvant chemotherapy in women with early-stage breast cancer: A retrospective study.

Many different treatments may affect the serum lipid profiles of breast cancer patients. This study analyzed serum lipid levels at different periods during treatment to observe the changes in lipid profiles during and after chemotherapy and to compare the different effects of different chemotherapy regimens on serum lipid profiles. A total of 805 patients were included in this study. We measured the lipid profiles of patients who received surgery without chemotherapy prior to the operation and at 3, 6 and 12 months after operation. In addition, in patients who underwent chemotherapy, the lipid profiles were measured prior to chemotherapy, prior to the last cycle of chemotherapy and 6 months after chemotherapy. Lipid profile measurements included total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), homocysteine (HCY), and uric acid (UA). (Neo)Adjuvant chemotherapy exerted an adverse temporary effect on lipid levels (manifested as increased TG and LDL-C levels, and decreased HDL-C levels, particularly in the adjuvant chemotherapy group) during the chemotherapy periods. However, this influence was not sustained, as the lipid profiles levels were generally restored to baseline levels 6 months after chemotherapy completion. Different age groups showed different changes in lipid levels that were influenced by chemotherapy. The younger group (20–40 years old) showed a greater increase in TC and LDL-C levels during chemotherapy than the 41-65-year-old group. Chemotherapy exerts an adverse temporary effect, and the effects of different regimens on lipid levels are similar. Furthermore, lipid profiles in younger women may be more sensitive to chemotherapy.

A Value of Information Analysis of Research on the 21-Gene Assay for Breast Cancer Management

ObjectivesThe 21-gene assay Oncotype DX (21-GA) shows promise as a guide in deciding when to initiate adjuvant chemotherapy in women with hormone receptor–positive early-stage breast cancer. Nevertheless, its routine use remains controversial, owing to insufficient evidence of its clinical utility and cost-effectiveness. Accordingly, we aim to quantify the value of conducting further research to reduce decision uncertainty in the use of the 21-GA. MethodsUsing value of information methods, we first generated probability distributions of survival and costs for decision making with and without the 21-GA alongside traditional risk prediction. These served as the input to a comparison of 3 alternative study designs: a retrospective observational study to update risk classification from the 21-GA, a prospective observational study to estimate prevalence of chemotherapy use, and a randomized controlled trial (RCT) of the 21-GA predictive value. ResultsWe found that current evidence strongly supports the use of the 21-GA in intermediate- and high-risk women. Further research should focus on low-risk women, among whom the cost-effectiveness findings remained equivocal. For this population, we identified a high value of reducing uncertainty in the 21-GA use for all proposed research studies. The RCT had the greatest potential to efficiently reduce the likelihood of choosing a suboptimal strategy, providing a value between $162 million and $1.1 billion at willingness-to-pay thresholds of $150 000 to $200 000/quality-adjusted life years. ConclusionFuture research to inform 21-GA decision making is of high value. The RCT of the 21-GA predictive value has the greatest potential to efficiently reduce decision uncertainty around 21-GA use in women with low-risk early-stage breast cancer.

Benefits of introduction of Oncotype DX® testing.

Decisions regarding adjuvant chemotherapy in women with oestrogen receptor positive, human epidermal growth factor receptor2 negative, node negative, early invasive breast cancer are unclear. The Recurrence Score® (RS) from Oncotype DX® (ODX) testing guides decisions based on individual cancer genomics. The aim of this study was to evaluate the impact of introducing ODX results on adjuvant treatment decisions and its potential economic benefits. Patients offered the test were identified from the ODX requesting system. Information on reasons behind chemotherapy treatment decisions were collected from clinical letters and the pathology system. The Nottingham prognostic index (NPI) scores were calculated for each individual patient. A total of 101 patients were identified as having undergone ODX testing over 21 months. The median age was 57 years (range: 41-72 years), the median NPI was 3.70 (range: 3.40-5.26) and the median RS was 17 (range: 0-59). NPI did not predict the risk category. All of the patients in the high risk group, 35.1% in the intermediate risk group and 5.4% in the low risk group received chemotherapy. The majority of low risk patients who received chemotherapy made a decision prior to the ODX result. In our unit, RS aided our decision making regarding adjuvant chemotherapy. Patients with a higher RS were more likely to receive chemotherapy. If NPI had been used alone, more women would have been offered chemotherapy. Good communication with patients prior to testing is important to ensure it is cost effective.

Changes in the microbiome induced by adjuvant chemotherapy for breast and gynecological cancer and their association with weight gain.

e22113 Background: Adjuvant chemotherapy for breast cancer is associated with weight gain and glucose intolerance. Obesity increases the risk of cardiovascular morbidity and might increase the risk of disease recurrence. In recent years the role of the intestinal microbiome in human physiology is being uncovered. The microbiome has been shown to influence metabolism and weight gain. We aimed to identify changes in the intestinal microbiome following adjuvant chemotherapy in women and to test their association with weight gain. Methods: Women treated with adjuvant chemotherapy for breast and gynecological malignancies were recruited. Fecal samplesweretaken prior to treatment, after 3-4 cycles and after treatment. Weight was measured atthese time points. Information regarding use of antibiotics and nutritional changes was systematically collected. Gut microbiota was analyzed using 16S rRNA gene sequencing. Results: Fifteen patients were recruited (13 breast cancer, 2 ovarian cancer). 5 gained 1 kg or more during treatment. Antibiotic use was not associated with weight gain. Beta diversity based on uniFrac analysis significantly changed between pre, during and post treatment samples (p = 0.002). Significant increase in the relative abundance of bacterial species from the orders Lactobacillae, Clostridiales, Pasteurellaies and Turicibacterales was seen in samples taken during chemotherapy relative to pre treatment samples. When comparing patients that did and did not gain weight we observed that Ruminococcus bromii was more abundant in pre treatment samples of patients that did not gain weight while other species from the order Clostridiales were more abundant in pre treatment samples of women that did. Alpha diversity decreased during treatment only in patients that gained weight and this difference was of borderline significance (p = 0.07). Conclusions: The composition of the microbiome changed in women during adjuvant chemotherapy for breast and ovarian cancer. We found differences in microbiome content and diversity between patients that gained weight and those that did not. Analyses with a larger sample size are needed to confirm these observations.

Personalized treatment of women with early breast cancer: a risk-group specific cost-effectiveness analysis of adjuvant chemotherapy accounting for companion prognostic tests OncotypeDX and Adjuvant!Online

BackgroundDue to high survival rates and the relatively small benefit of adjuvant therapy, the application of personalized medicine (PM) through risk stratification is particularly beneficial in early breast cancer (BC) to avoid unnecessary harms from treatment. The new 21-gene assay (OncotypeDX, ODX) is a promising prognostic score for risk stratification that can be applied in conjunction with Adjuvant!Online (AO) to guide personalized chemotherapy decisions for early BC patients. Our goal was to evaluate risk-group specific cost effectiveness of adjuvant chemotherapy for women with early stage BC in Austria based on AO and ODX risk stratification.MethodsA previously validated discrete event simulation model was applied to a hypothetical cohort of 50-year-old women over a lifetime horizon. We simulated twelve risk groups derived from the joint application of ODX and AO and included respective additional costs. The primary outcomes of interest were life-years gained, quality-adjusted life-years (QALYs), costs and incremental cost-effectiveness (ICER). The robustness of results and decisions derived were tested in sensitivity analyses. A cross-country comparison of results was performed.ResultsChemotherapy is dominated (i.e., less effective and more costly) for patients with 1) low ODX risk independent of AO classification; and 2) low AO risk and intermediate ODX risk. For patients with an intermediate or high AO risk and an intermediate or high ODX risk, the ICER is below 15,000 EUR/QALY (potentially cost effective depending on the willingness-to-pay). Applying the AO risk classification alone would miss risk groups where chemotherapy is dominated and thus should not be considered. These results are sensitive to changes in the probabilities of distant recurrence but not to changes in the costs of chemotherapy or the ODX test.ConclusionsBased on our modeling study, chemotherapy is effective and cost effective for Austrian patients with an intermediate or high AO risk and an intermediate or high ODX risk. In other words, low ODX risk suggests chemotherapy should not be considered but low AO risk may benefit from chemotherapy if ODX risk is high. Our analysis suggests that risk-group specific cost-effectiveness analysis, which includes companion prognostic tests are essential in PM.

206P - Incidence of permanent alopecia following adjuvant chemotherapy in women with early stage breast cancer

206P - Incidence of permanent alopecia following adjuvant chemotherapy in women with early stage breast cancer

Incidence of permanent alopecia following adjuvant chemotherapy in women with early stage breast cancer.

e21576 Background: Alopecia is one of the most distressing toxicities of adjuvant chemotherapy for patients with breast cancer. Historically, oncologists have reassured patients (pts) that chemotherapy-induced alopecia is temporary, and followed by full hair recovery. More recently there have been troubling reports of permanent alopecia following adjuvant taxanes (Tax). We studied the incidence of long-term hair loss in patients treated on adjuvant trials in our institution. Patients who were enrolled on clinical trials involving Tax (D-Docetaxel, P-Paclitaxel) and/or Anthracyclines (A) were included. Methods: We conducted a telephone interview survey of pts who had completed adjuvant or neo adjuvant A and/or T chemotherapy on clinical trials more than one year before. Ongoing alopecia was graded as 0 (full hair recovery), 1 (mild hair loss) or 2(severe/total). The study was approved by the hospital audit committee. Results: We studied 295 pts who has been treated on 12 studies. Drug exposure: D-260 pts (D nonA-185, D+A-75); A-nonTax-12 pts ; A+P 23 pts. The overall incidence of alopecia was 15% (11% grade 1 and 4% grade 2). For all D the incidence was 15% (12% Grade 1 and 3% Grade 2). For D+A-24% (19% Grade 1 and 5% Grade 2). For D non A the incidence was 13% ( 8% grade 1 and 5% grade 2). For A non T 8% (Grade 2-8%). For PA-13% ( 4% grade 1 and 9% grade 2). For patients receiving D non-A regimens, there were two levels of D exposure, 300mg/m2 (90 pts) or 450 mg/m 2 (95 pts). The incidence of alopecia was significantly D dose dependent: D300- 7% (all grade 1) and D 450-19% (14% grade 1, 5% grade 2) (p = .02 chi2 ). Among the higher dose D group, the companion drug choices carboplatin for HER2 positive, (55 pts) or cyclophosphamide (40 pts) were associated with similar incidences of permanent alopecia (22% v 16%). Conclusions: Permanent alopecia is a common complication of adjuvant chemotherapy. The risk appears to be highest in regimens which contain A and Tax, but it is also seen in AP and in A non-Tax. For patients receiving D non A, the risk is dose-dependent. Our data set contains few P pts, and does not contain any pts undergoing low dose weekly P. Oncologists should warn all patients undergoing adjuvant therapy of the risk of permanent alopecia.

Oncotype DX TM predicts benefit from adjuvant chemotherapy in women with early breast cancer at intermediate risk of distant recurrence

Introduction: Not all women with primary breast cancer benefit equally from adjuvant chemotherapy. Selecting who to treat from those considered at intermediate risk of recurrence is challenging. Oncotype DXTM is a clinically validated genomic assay which evaluates 21 genes to assess tumour biology. It is validated to predict individual risk of distant recurrence at 10 years and is NICE approved.

Impact of adjuvant chemotherapy on survival of women with T1N0M0, hormone receptor negative breast cancer

BackgroundThe benefit of adjuvant chemotherapy in women with T1N0M0 breast cancers is unclear. While gene expression-based prognostic assays may aid management of women with early estrogen receptor (ER) positive tumors, therapeutic decision-making in women with early stage ER negative tumors remains fraught with difficulties. We investigated the association between adjuvant chemotherapy and overall survival in women with T1N0M0, hormone receptor negative breast cancers. MethodAll newly diagnosed breast cancer patients with node-negative and hormone receptor negative tumors measuring≤2cm at the University Malaya Medical Centre (Malaysia) from 1993 to 2013 were included. Mortality of patients with and without adjuvant chemotherapy were compared and adjusted for possible confounders using propensity score. ResultsOf 6732 breast cancer patients, 341 (5.1%) had small (≤2cm), node-negative and hormone receptor negative tumors at diagnosis. Among them, only 214 (62.8%) received adjuvant chemotherapy. Five-year overall survival was 88.1% (95% confidence interval (CI): 82.0%–94.2%) for patients receiving chemotherapy and 89.6% (95% CI: 85.1%–94.1%) for patients without chemotherapy. Chemotherapy was not associated with survival following adjustment for age, ethnicity, tumor size, tumor grade, HER2 status, lympho-vascular invasion, type of surgery and radiotherapy administration. However, chemotherapy was associated with a significant survival advantage (adjusted hazard ratio: 0.35, 95%CI: 0.14–0.91) in a subgroup of women with high-grade tumors. ConclusionAdjuvant chemotherapy does not appear to be associated with a survival benefit in women with T1N0M0, hormone receptor negative breast cancer except in those with high-grade tumors.

Abstract OT3-04-03: The impact of the 21 gene recurrence score (RS) on chemotherapy prescribing in estrogen receptor (ER) positive, lymph node positive early stage breast cancer in Ireland

Abstract BACKGROUND For Estrogen Receptor (ER) positive, early stage breast cancer, the 21 gene Recurrence Score (RS) has clinical use both as a prognostic tool and to predict chemotherapy benefit. The availability of this tool in Ireland has led to a reduction in the use of adjuvant chemotherapy for women with lymph node (LN) negative disease. However, the RS is not routinely funded for patients with LN positive (LN+) breast cancer in Ireland. In addition, there are limited international data on the use of this tool in the preoperative setting. In this prospective observational study, we are investigating whether access to the 21 gene RS leads to a reduction in the receipt of chemotherapy for patients with ER+, LN+ breast cancer, and to correlate the 21 gene RS with response to preoperative systemic therapy. TRIAL DESIGN This is a national, multi-site, prospective, observational study that will examine the impact of the 21 gene RS on chemotherapy recommendations in both the neoadjuvant and adjuvant setting. Prior to and following tumor testing with the 21 gene RS, Physicians will complete a questionnaire which details type and strength of systemic therapy recommendations. ELIGIBILITY Cohort 1 (postoperative) will include patients with ER+ tumors of any size with involvement of 1-3 lymph nodes (N1 including micrometastases). Cohort 2 (preoperative) will include patients with ER+, T2-T4 tumors with biopsy proven nodal metastases. Both cohorts will have ECOG PS 0 or 1 and be fit for consideration of chemotherapy as determined by the Investigator. SPECIFIC AIMS The primary endpoint is the percentage reduction in the number of patients for whom treating physicians recommend chemotherapy after testing with 21 gene RS. Secondary endpoints include the correlation between the 21 gene RS and residual cancer burden score, as well as pathological, clinical and radiological response rates. The economic impact of the 21 gene RS in ER+, LN+ will also be assessed. STATISTICAL METHODS The sample size is based on similar decision impact studies conducted in other countries. Physician recommendations for chemotherapy pre 21-gene RS and recommendations post 21-gene RS testing will be compared and percentage change estimated with 95% confidence intervals. For secondary endpoints, the Pearson correlation coefficient (rho) will be used to examine the strength of the correlation between the 21 gene RS category and response. A budget impact model will be used to estimate the cost reduction in adjuvant chemotherapy as a result of 21-gene RS testing. PRESENT ACCRUAL AND TARGET ACCRUAL Target accrual is 75 in each of the neoadjuvant and adjuvant cohorts to total 150 patients. Supported by Genomic Health. Citation Format: Keegan NM, Milewski M, Kelly CM, Murphy V, Chao C, Walsh J, Kennedy MJ, O'Connor M, Murphy C, O'Reilly S, Keane M, Duffy K, Hennessy B, Morris PG. The impact of the 21 gene recurrence score (RS) on chemotherapy prescribing in estrogen receptor (ER) positive, lymph node positive early stage breast cancer in Ireland [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT3-04-03.

Algorithms for prediction of the Oncotype DX recurrence score using clinicopathologic data: a review and comparison using an independent dataset.

Given the potential savings in cost and resource utilization, several algorithms have been proposed to predict Oncotype DX recurrence score (ODX RS) using commonly acquired histopathologic variables. Although it is promising, additional independent validation of these surrogate markers is needed prior to guide the patient management. In this retrospective study, we analyzed 305 patients with invasive breast cancer at our institution who had ODX RS available. We selected five equations that provide a surrogate measure of ODX as previously published by Klein et al. (Magee equations1-3), Gage et al., and Tang et al. All equations used estrogen receptor status and progesterone receptor status along with different combinations of grade, proliferation indices (Ki-67, mitotic rate), HER2 status, and tumor size. Of all surrogate scores tested, the Magee equation2 provided the highest correlation with ODX both with regard to raw score (Pearson's correlation coefficient=0.66 95% CI 0.59-0.72) and categorical correlation (Cohen's kappa=0.43, 95% CI 0.33-0.53). Although Magee equation2 provided a way to reliably identify high-risk disease by assigning 95% of the patients with high ODX RS to either the intermediate- or high-risk group, it was unable to reliably identify the potential for patients to have intermediate- or high-risk disease by ODX (66% of such patients identified). Although commonly available surrogates for ODX appear to predict high-risk ODX RS, they are unable to reliably rule out the presence of patients with intermediate-risk disease by ODX. Given the potential benefit of adjuvant chemotherapy in women with intermediate-risk disease by ODX, current surrogates are unable to safely substitute for ODX. Characterizing the true recurrence risk in patients with intermediate-risk disease by ODX is critical to the clinical adoption of current surrogate markers and is an area of ongoing clinical trials.