Treatment Of Early-stage Breast Cancer Research Articles

Ability of observer and self-report measures to capture shared decision-making in clinical practice in the UK: a mixed-methods study

ObjectivesTo examine how observer and self-report measures of shared decision-making (SDM) evaluate the decision-making activities that patients and clinicians undertake in routine consultations.DesignMulti-method study using observational and self-reported measures of...

Radiation treatment in early stage triple‐negative breast cancer in New Zealand: A national database study

We aimed to investigate the impact of radiation treatment in early-stage triple negative breast cancer (TNBC). Patients with early stage (T1-3, N0-2, M0) TNBC were identified using the New Zealand breast cancer register. The outcomes of local recurrence (LRFR), local recurrence free survival (LRFS), loco-regional recurrence free rate (LRRFR), loco-regional recurrence free survival (LRRFS), breast cancer specific survival (BCSS), metastasis free (MFS) and overall survival (OS) were determined. Predefined univariate and multivariate cox regression analyses were used to explore associations between known prognostic and treatment factors. 1209 patients were identified with a median follow-up of 3.88years. The majority were post- menopausal. The mean tumour size was 26mm, the majority had grade III disease and a third were node positive. 625 patients had mastectomy and 584 had breast conservation surgery (BCS). 92% of BCS and 38% of mastectomy patients received radiation. 67% received adjuvant chemotherapy. The 5year OS was 77.6% (95% CI 74.6-80.2), 5year BSS was 82.1% (95%CI 79.1-84.7), 5year LRRFS was 73.9% (95% CI 73.87-73.93), 5year LRFS was 75.4 (75.37-75.43) and the 5year LRFR was 92.4% (95% CI 90.6-94.2). The significant prognostic/predictive factors for OS were adjuvant radiation treatment, chemotherapy, T stage, lymph node involvement and lympho-vascular space invasion. Results were similar for BSS, DMFS, LRFS and LRRFS except that LVSI was not significantly associated with BCSS, LRFS or LRRFS. When analysed by surgical type, in the WLE group, radiation was found to be significantly associated with improvement in all outcomes. In mastectomy group, radiation was not found to be significant for BCSS, LRFS, LRRFS or OS. Radiation treatment is significantly associated with improved outcomes in early stage TNBC. This argues against the hypothesis that TNBC has inherent radiation resistance.

Postmortem evidence of neuroinflammation in bipolar disorder: a systematic review

Permanent breast seed implant (PBSI) is a developing brachytherapy technique for the treatment of early-stage breast cancer. In current practice, PBSI uses manual planning strategies to generate clinical treatment plans. In this work, a simulated annealing-based algorithm is developed to demonstrate the first application of inverse optimization for PBSI.Target, skin, and chest wall muscle contours, exported from a treatment planning system in digital imaging and communications in medicine format, are used as inputs. To optimize, the user defines the dose–volume histogram objectives for the target and specifies a relative weighting for target and skin constraints. A 10-patient cohort of previously treated patients was planned by using the inverse optimization algorithm. Plan quality was compared to the clinically treated manually generated plans using the V90%, V100%, V150%, and V200% for the planning target volume (PTV), V90% and D0.2 cc for skin dose, and PTV conformity indices.For each of the 10 patients, patient-wise paired differences between inverse and manual plans were analyzed and presented in box plots. Comparing inverse and manual planning techniques, a statistical difference was not observed (p > 0.05) in PTV coverage criteria (V90%, V100%) and dose to skin2mm. A statistical difference was observed in the inverse plans as a reduction of the V150% (mean of 6.2%) and increase in conformity index of the 20%, 50%, 90%, and 100% isodose lines.This work presents the first application of inverse optimization used to generate PBSI treatment plans. A 10-patient cohort previously treated with PBSI was retrospectively planned for comparison with the clinically treated manually generated plans.

De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017.

De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017.

De-escalating adjuvant trastuzumab in human epidermal growth factor receptor 2 (HER2)-positive early-stage breast cancer: A systemic review and meta-analysis.

524 Background: One year of adjuvant trastuzumab in combination with chemotherapy is the standard of care in early-stage HER2 positive breast cancer. Existing data on shortening trastuzumab treatment show conflicting results. Methods: A search of PubMed and conferences identified randomized trials that compared abbreviated trastuzumab therapy to one year of treatment in early-stage HER2 positive breast cancer. Hazard ratios (HRs) and 95% confidence intervals (CI) were extracted for disease free survival (DFS) and overall survival (OS). Data on the number of DFS and distant relapse events were also collected as were the number of patients at risk in each group. Subgroup analyses evaluated the effect of nodal involvement, estrogen receptor (ER) expression and the duration of abbreviated trastuzumab (9-12 weeks versus 6 months). Odds ratios (ORs) and 95% CI were computed for pre-specified cardiotoxicity events including cardiac dysfunction and congestive heart failure (CHF). Results: Analysis included 6 trials comprising 11603 patients. In most studies adjuvant chemotherapy included anthracyclines and taxanes. Shorter trastuzumab treatment was associated with worse DFS (HR = 1.14, 95% CI 1.05-1.25, p = 0.002) and OS (HR = 1.15, 95% CI 1.02-1.29. p = 0.02). The effect on DFS was not influenced by ER status (p for the subgroup difference = 0.23), nodal involvement (p = 0.44) or the different duration of trastuzumab in the experimental arm (p = 0.08). In absolute terms, after an estimated median follow-up of 71 months, shorter treatment with trastuzumab was associated with an absolute increase in DFS events of 2.3%. Shorter trastuzumab treatment was associated with lower odds of cardiac dysfunction (OR = 0.67, 95% CI 0.55-0.81, p < 0.001) and CHF (OR = 0.66, 95% CI 0.50-0.86, p = 0.003). Conclusions: Compared to one year, shorter duration of adjuvant trastuzumab is associated with significantly worse DFS and OS, despite favorable cardiotoxicity profile. One year of trastuzumab should remain the standard adjuvant treatment in early-stage HER2 positive breast cancer with appropriate cardiac monitoring.

Endocrine therapy discontinuation rates in older women with early stage breast cancer who are candidates for omission of radiation.

e23018 Background: As the treatment for early-stage breast cancer continually evolves, there has been a pragmatic shift with regard to standard treatment placing a high-value on multidisciplinary management. Recent studies have shown that sentinel lymph node biopsy (SLNB) and adjuvant radiation (RT) can be omitted in a subset of older women with early-stage hormone receptor positive breast cancer who plan to take adjuvant endocrine therapy (ET). Prior analyses estimate a wide range of discontinuation rates, with studies citing 31-73%. The primary aim of this analysis is to estimate the discontinuation rate of endocrine therapy in women ages 70 and older with early stage breast cancer who omit radiation therapy at our institution. Methods: We performed a retrospective review of institutional cancer registry and EMR data to identify all women with breast cancer, ages 70 or older, AJCC 7 stage I or II, hormone receptor positive, HER2 negative, who underwent lumpectomy at the University of Michigan inclusive of years 2014 through 2017. Multiple variables of interest were collected and analyzed. Results: 174 women met initial inclusion criteria for ER/PR positive, HER2 negative, Stage I/II disease, who underwent lumpectomy. Of these, N = 10 pursued adjuvant radiation therapy with omission of ET, and N = 19 declined both ET and RT upfront. The remaining 145 women chose to pursue ET alone (N = 78) or ET+RT (N = 67). 30/145 (21%) discontinued endocrine therapy, 22% (N = 15) in the ET+RT, 19% (N = 15) in the ET alone groups. There was no statistically significant difference between groups with regard to the discontinuation of ET upon comparison, log-rank p-value 0.4. The primary reason for ET discontinuation, N = 27 (90%) was secondary to side effects. Conclusions: This review demonstrated that a significant number (54%) of older women opt to omit radiation in favor of ET alone after multidisciplinary discussion, in accordance with NCCN guidelines. Endocrine therapy discontinuation rates among older women at our institution were comparable to rates in the literature for women of all ages, and the reason for discontinuation was attributed to side effects. The pivotal clinical trials (PRIME II and CALGB 9343) exploring ET alone versus ET+RT did not report on ET discontinuation rates. In our analysis, almost 20% of women receiving ET alone discontinued ET therapy, calling into question a missed radiation treatment opportunity in a curative setting.

Comparative efficacy of neoadjuvant to adjuvant chemotherapy for the treatment of early-stage HER2 negative breast cancer: A population-based analysis.

e12100 Background: The use of neoadjuvant treatment has increased over the past decade due to its ability to assess tumour sensitivity to systemic treatment in vivo, and to downstage women for increased breast conserving surgery. Recent studies have stratified patients with residual disease to receive additional treatment, which has resulted in meaningful improvements in survival. However, meta-analysis data suggest similar long-term outcomes for patients treated with neoadjuvant chemotherapy (NACT) compared to adjuvant chemotherapy (ACT) in historical randomized trials. The comparative efficacy in a real-world setting utilizing modern chemotherapy regimens is unknown. Methods: A retrospective review of the BC Cancer Breast Cancer Outcomes Unit (BCOU) was performed to identify patients with stage I-III HER-2 negative breast cancer treated with chemotherapy at the BC Cancer Agency from 2005-2010. Patients were then divided into 2 groups: those who received neoadjuvant chemotherapy (NACT) and those who received adjuvant chemotherapy (ACT). A matched analysis (age, stage, subtype) for patients treated with NACT vs ACT (matched 1:3) was then performed using a propensity scoring method to compare distant disease-free survival (DDFS), breast cancer specific survival (BCSS) and overall survival (OS). No patients received adjuvant chemotherapy for residual disease after NACT. Results: A total of 656 patients met the inclusion criteria, consisting of 164 NACT and 492 ACT cases. Median age was 49 years (37-68) in the NACT group vs 49 (37-65) in the ACT group (p = 0.71). The majority had stage 3 disease, 64% in both groups (p = 1.0). Most were hormone receptor positive (HR+), 67.1% vs 70.7% in the NACT vs ACT groups, respectively (p = 0.41). 5-year DDFS was 75% with NACT (95%CI 67, 82) and 77% with ACT (95%CI 72, 81), p = 0.87. 5-year OS for patients treated with NACT was 77% (95%CI 71, 84) and 80% (95%CI 75, 85) for patients treated with ACT, p = 0.33. 5-year BCSS was 80% with NACT (95% CI 70, 86) and 82% (95%CI 77, 86) with ACT, p = 0.75. Multivariate analysis for tumour size, nodal involvement and subtype are ongoing. Conclusions: The use of NACT compared to ACT in a population-based setting did not result in significant differences in DDFS, OS or BCSS. Acknowledging the comparative efficacy of these approaches will be informative to determine if the addition of subsequent adjuvant treatment for patients with residual disease after NACT will lead to differential benefits in a population-based setting.

Deescalating Adjuvant Trastuzumab in HER2-Positive Early-Stage Breast Cancer: A Systemic Review and Meta-Analysis.

BackgroundOne year of adjuvant trastuzumab in combination with chemotherapy is the standard of care in early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Existing data on shortening trastuzumab treatment show conflicting results.MethodsA search of PubMed and abstracts from key conferences identified randomized trials that compared abbreviated trastuzumab therapy to 1 year of treatment in early-stage HER2-positive breast cancer. Hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted for disease-free survival (DFS) and overall survival (OS). Subgroup analyses evaluated the effect of nodal involvement, estrogen receptor expression, and the duration of abbreviated trastuzumab (9–12 weeks vs 6 months). Odds ratios (ORs) and 95% confidence intervals were computed for prespecified cardiotoxicity events including cardiac dysfunction and congestive heart failure. P values were two-sided.ResultsAnalysis included six trials comprising 11 603 patients. Shorter trastuzumab treatment was associated with worse DFS (HR = 1.14, 95% CI = 1.05 to 1.25, P = .002) and OS (HR = 1.15, 95% CI = 1.02 to 1.29. P = .02). The effect on DFS was not influenced by estrogen receptor status (P for the subgroup difference = .23), nodal involvement (P = .44), or the different duration of trastuzumab in the experimental arm (P = .09). Shorter trastuzumab treatment was associated with lower odds of cardiac dysfunction (OR = 0.67, 95% CI = 0.55 to 0.81, P < .001) and congestive heart failure (OR = 0.66, 95% CI = 0.50 to 0.86, P = .003).ConclusionsCompared with 1 year, shorter duration of adjuvant trastuzumab is associated with statistically significantly worse DFS and OS despite favorable cardiotoxicity profile. One year of targeted HER2 treatment should remain the standard adjuvant treatment in early-stage HER2-positive disease with appropriate cardiac monitoring.

Patient-reported health problems and healthcare use after treatment for early-stage breast cancer

BackgroundA clear picture of treatment-related health problems following breast cancer treatment is useful in anticipating the informational and other needs of patients during follow-up. This study aimed to identify treatment-related health problems in breast cancer patients up to five years after diagnosis. Secondly, the use of care associated with these health problems was identified. Methods876 surgically-treated female patients diagnosed between 2012 and 2016 with early-stage breast cancer were asked to complete an online survey about their current health problems and use of care. Multivariate logistic regression analyses were applied to determine the effect of patient and treatment characteristics on health problems. Results404 patients responded (46%). The median age was 62.0 years (SD:10.9). Apart from breast surgery, patients had been treated with radiotherapy (72%), chemotherapy (49%), anti-hormonal therapy (57%), and axillary dissection (21%). Ninety-three percent experienced one or more health problems. Over 50% of respondents experienced fatigue, psychological problems, and health problems regarding the breast, and/or musculoskeletal, central nervous, and reproductive system. Treatment with chemotherapy was significantly associated (p < 0.05) with an increased risk of health problems, respectively fatigue (OR:2.00), respiratory (OR:1.81), gastrointestinal (OR:1.87), central nervous (OR:3.40), and skin problems (OR:2.62). Use of healthcare for one or more health problems was reported by 64% of respondents. DiscussionAlmost all patients experienced health problems up to five years after breast cancer diagnosis, with a range of complaints that were consistently present over time. Factors associated with the development of health problems are useful for better informing patients beforehand and targeting follow-up care.

Would Plastic Surgeons Choose Breast Conservation Therapy?

Breast conservation therapy is defined as partial mastectomy with subsequent radiation therapy and is the treatment for early-stage breast cancer. However, the unwanted risks of radiation must be considered as well as the impact on future breast reconstruction options. The purpose of this study was to assess the preference of plastic surgeons when given the hypothetical diagnosis of breast cancer. A survey assessing treatment preference of 3 hypothetical breast cancer diagnosis scenarios was designed and distributed by American Society of Plastic Surgeons via e-mail invite to its members. The risk of cancer recurrence was the most common reason for treatment preferences of all three choices. However, for ductal carcinoma in situ, unilateral mastectomy with implant-based reconstruction is the preferred option with the second most influential reason of avoiding the risks of radiation therapy. For invasive ductal carcinoma node negative, unilateral mastectomy with implant-based reconstruction was the preferred option also due to risks of radiation therapy and anxiety of future surveillance. For invasive ductal carcinoma node positive, bilateral mastectomy with implant-based reconstruction was the preferred choice because of anxiety of future surveillance and also risks of radiation therapy. In general, plastic surgeons did not prefer breast conservation therapy for in situ and early-stage breast cancer. Although the most common rationale for total mastectomy was risk of cancer recurrence for all disease severity, risks of radiation therapy are real and play an integral role in the decision-making process. In understanding our own biases, we can help better empathize with patients in consultation for breast reconstruction.

QIM19-139: Reflex Testing of Oncotype DX Recurrence Score: A Single Institution Review of a Quality Improvement Protocol

Background: Implementation of genomic assays has led to treatment of early-stage breast cancers with high risk of recurrence with adjuvant systemic chemotherapy while sparing those with a low risk of recurrence from systemic therapy with minimal benefit. Genomic assays are becoming a more widely used tool, evident by the eighth edition of the American Joint Committee on Cancer (AJCC) Breast Cancer Staging System, which includes recurrence score as part of the treatment algorithm in certain subgroups of tumors. Our institution identified the time to assay result as a quality improvement opportunity. We instituted a protocol to have a reflex testing of Oncotype DX based on certain criteria to decrease time to assay results and ultimately time to treatment. Methods: Our Multidisciplinary Breast Leadership Committee instituted a policy for reflex Oncotype DX testing on patients under the age of 70 with estrogen receptor positive, HER2-neu protein–negative, and node-negative invasive breast cancers measuring between 0.5 cm to 5 cm in January 2018. We compared our data available from pre- and postimplementation using the single factor analysis of variance (ANOVA) as well as an independent t-test and a post-hoc Tukey-Kramer test. Results: We have observed 45 cases that met the criteria for reflex Oncotype Dx testing since the initiation of this quality improvement protocol. The recurrence scores ranged from 0 to 55. There was a statistically significant difference in the number of days from operation to result day from 2016 to 2018 (55 days vs 18 days; P&lt;.001). The number of days from the test order date to result date also saw a significant improvement from 2016 to 2018 (12 vs 9 days; P&lt;.05). Conclusions: Breast cancer treatment options continue to evolve, particularly with the use of genomic assays. Our single institution review confirms the utility of our reflex Oncotype DX protocol with a decreased time to result with reflex testing of patients in the appropriate clinical setting. Further development of similar pathways may be necessary to streamline our patients’ care in the treatment of breast cancer.

Long-Term Risk of Heart Failure in Breast Cancer Patients After Adjuvant Chemotherapy With or Without Trastuzumab

ObjectivesThis study sought to evaluate the long-term risk of developing heart failure (HF) in patients receiving trastuzumab therapy. BackgroundTrastuzumab has improved the prognosis in patients with HER2-positive breast cancer, but it can induce left ventricular dysfunction with reduced ejection fraction or HF during treatment. The long-term risk of HF is less well described. MethodsIn a nationwide Danish retrospective cohort study, 9,901 patients scheduled for adjuvant treatment for early-stage breast cancer were identified in the Danish Breast Cancer Cooperative Group database. Of these, 8,812 patients (25% HER2-positive; 51.7 ± 8.5 years of age) received chemotherapy including anthracycline; and if they were HER2 positive, trastuzumab was added. The primary endpoint was a diagnosis of HF assessed before and after 18 months in a landmark analysis to distinguish short- and long-term risks. ResultsMedian follow-up was 5.4 years (interquartile range [IQR]: 4.1 to 6.8 years). In the trastuzumab group, 60 patients had HF by 9 years versus 51 in the group who were treated with chemotherapy alone, corresponding to incidence rates per 1,000 patient years of 5.3 (95% confidence interval [CI]: 4.1 to 6.8) versus 1.4 (95% CI: 1.1 to 1.8), respectively. The cumulative incidence of HF was higher in the trastuzumab group at both the short- and long-term (p < 0.01), yielding adjusted hazard ratios of 8.7 (95% CI: 4.6 to 16.5; p < 0.01) for early HF and 1.9 (95% CI: 1.2 to 3.3; p = 0.01) for late HF associated with trastuzumab treatment. ConclusionsTrastuzumab treatment is associated with a 2-fold increased risk of late HF compared with chemotherapy treatment alone.

Abstract P4-08-34: MammaTyper© – An in vitro quantitative local gene expression test as a predictor of OncotypeDX©- and EndoPredict©-results

Abstract Background: Risk stratification in early-stage breast cancer patients still remains a clinical challenge. It is well known that expression of ER/ PR, HER2 and Ki-67 are valuable prognostic and predictive markers. According to the commonly used St. Gallen classification (2013), breast cancer treatment decisions can be based on four different subtypes (Luminal A-like, Luminal B-like [HER2+/-], HER2 + [non-luminal] and Basal-like). Immunohistochemistry is predominantly used to determine the receptor status, although semi-quantitative analysis shows significant inter-observer variability. Several quantitative gene expression tests – such as Oncotype DX© and EndoPredict© – are available as diagnostic tools but their use is often limited due to financial considerations. MammaTyper© has been shown to be a precise and reproducible biomarker determination tool to investigate the expression of ER/ PR, HER2 and Ki-67 and may prove to be a cost efficient quantitative diagnostic tool. Methods: This study tested ESR-1, PGR, MKI67 and ERBB2 mRNA-levels by RT-qPCR in 100 FFPT-samples using MammaTyper© kit. The test identified breast cancer subgroups according to St. Gallen classification. RT-qPCR results were correlated to IHC-test results via χ2-Test and to risk groups of Oncotype DX©- (n=55) and EndoPredict©-testing (n=45). Oncotype©-Recurrence Score levels were separated into low (RS &amp;lt;18), intermediate (RS 18-30) and high risk (RS ≥ 31). EndoPredict© EPScore© and EPclin Risk Score© cut off levels defining high and low risk levels were 7.0, respectively 3.3. Linear regression model was performed investigating the prediction of EPscore© and Recurrence Score© via MammaTyper© mRNA-results. Results: IHC-testing resulted in 43 Luminal A-like samples (43%) and 57 Luminal B-like [HER2 negative] (57%) tumors. MammaTyper ©-based classification showed significant correlation to IHC-based classification (χ2=12,68; p=0,005). EndoPredict©-data showed low-risk levels in 36 patients (80%) and high-risk status in 9 cases (20%). Correlation to mRNA-based St. Gallen-subtypes approved significance (χ2=17,32, p&amp;lt;0,001). In linear regression model only MKI67-mRNA showed independent correlation to EPScore© (p&amp;lt;0,001; R2 0,290) A total of 34 patients (61,8%) showed low risk, 13 (26,3%) intermediate risk (RS 18-30) and 8 (14,5%) high-risk recurrence score levels (RS≥31) in OncotypeDX©. MammaTyper© results correlated to OncotypeDX© risk-levels (χ2=27,98; p&amp;lt;0,001). In linear regression model mRNA-levels of ESR-1, PGR and MKI67 were significant predictors of OncotypeDX© RS (p-values: p=0,003, p&amp;lt;0,001, p=0,033, R2= 0,602) Conclusion: This study shows mRNA-testing is a valid marker to identify breast cancer subtypes. Additionally, MammaTyper© results are significantly correlated to Oncotype DX©- and EndoPredict©-results, indicating it might be an efficient as well as cost effective diagnostic instrument. However a large prospective multicenter study should be performed to prove its diagnostic validity in predicting the most appropriate and effective treatment in early-stage breast cancer. Citation Format: Eckhoff K, Pokorny J, Baumann K, Perner S, Pursche T, Rody A. MammaTyper© – An in vitro quantitative local gene expression test as a predictor of OncotypeDX©- and EndoPredict©-results [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-08-34.

Abstract P5-15-08: Economic Impact of MammaPrint (70-gene signature) in a clinical high risk population: A 10yr Markov model, 6,000-patient retrospective analysis of US claim data

Abstract Background: MINDACT provided evidence that MammaPrint (MP) can identify patients (pts) with early-stage breast cancer (ESBC) who can safely forego adjuvant chemotherapy (CT). As a result, 46% of clinicopathologically high-risk pts were spared from unnecessary CT toxicities. This study investigates direct and indirect costs for pts and payers during ESBC treatment regimens. The study objective was to quantify average cost of care and savings in a clinical high-risk group where the value of CT is unclear, and MP demonstrates economic and clinical impact. Methods: Risk assessment was based on 6,000 MP tests performed on BCBS members (2016-17). CT claims were retrospectively analyzed utilizing a Blue Cross Blue Shield (BCBS) member database (January-December 2016). Case data was restricted to HR+HER2- ESBC and filtered by authorization for the MP test. All CT claims were including, but not limited to standard of care (SOC) systemic drugs such as cyclophosphamide, docetaxel, paclitaxel and doxorubicin. HCPCS codes were utilized to filter member CT claims. Exclusion criteria: &amp;lt;3 SOC CT claims and previous history of BC. A hybrid decision tree-Markov model was used to estimate cost effectiveness of MP compared to modified Adjuvant Online (mAOL) from a US healthcare payer perspective over a 10yr timeframe. Overall, distant metastasis free survival, and test-utility scores were collected from MINDACT for HR+HER2- pts, and costs derived from the BCBS registry and literature (2016 US dollars). Two scenarios were modelled (1) all women classified as high-risk received CT plus endocrine therapy (ET) while low-risk pts received ET; (2) MP guided treatment was modelled based on the IMPACT study (91% MP Low Risk pts received ET and 83% MP High Risk pts received CT). Outcome measures were quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). Results: The majority, 3,540 (59.0%) pts were Low Risk or could safely forgo CT; 2,460 (41.0%) were High Risk. The primary driver for cost differences was whether all services were performed in a physician office ($4.6M) or an outpatient setting ($2M). Including provider settings (inpatient, outpatient, emergency), SOC CT regimens and related services the final average amount authorized was $39,675 per patient. In the first scenario, MP guided treatment was associated with a 0.06 QALY gain (0.05 in scenario 2) compared to mAOL. For cost savings and QALY gain MP was dominant over mAOL in both scenarios. Budget impact analysis estimated cost savings of 88.2- 96.6 million dollars based on BCBS registry data. Given the new cases of BC that are expected to be diagnosed in women in the U.S. annually, pts covered in this population by BCBS (˜30%) and MP eligible cohort (˜36K pts), projected cost savings are estimated at 529.2-644.3 million dollars per annum for the health insurer. Conclusions: CT was associated with significant annual costs from both patient and payer perspectives. As demonstrated in MINDACT, less treatment for some pts is optimal without risk to safety or survival. These findings suggest that MP is cost effective and provides substantial value by sparing pts from toxicities, both therapeutic and financial. Citation Format: Blumencranz LE, Høst-Ragab A, Retèl VP, Garlich H, Hwang C, Neijenhuis S, Habibi M, Audeh W. Economic Impact of MammaPrint (70-gene signature) in a clinical high risk population: A 10yr Markov model, 6,000-patient retrospective analysis of US claim data [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-15-08.

Toxicity of Adjuvant Radiotherapy in Patients with Breast Cancer: A Review Study Toxicity of Breast Adjuvant Radiotherap

Conservative treatment in early-stage breast cancer is considered a standard approach. Breast preserving surgery with adjuvant radiotherapy is as effective as mastectomy in the early stages of breast cancer to control local disease and distant metastasis and maintain the overall survival rate. Minimally invasive surgery for the treatment of axillary spread and new techniques of breast preservation surgery will probably lead to a reduction in mastectomy-related complications. However, the complications of adjuvant radiotherapy remain a challenge. Cutaneous, cardiac, and pulmonary toxicity are the main complications of adjuvant breast irradiation. The multidisciplinary features (systemic treatment, endocrine therapy, and surgery), patient profile (history of underlying diseases, age, and habits), and irradiation-associated parameters are the factors affecting safe adjuvant radiotherapy. Advances in irradiation techniques and facilities related to the preservation of organs at risk (such as IGRT, tracing and tracking systems, and respiratory gating) are modern tools for reducing the risk of toxicity. Reported data from clinical trials or retrospective surveys greatly help physicians in consulting the patients on the efficacy and potential side effects of treatment and leads to the improvement of the decision making process.

Rising Rates of Contralateral Prophylactic Mastectomy as a Treatment for Early-Stage Breast Cancer.

The rate of contralateral prophylactic mastectomy (CPM) in women with unilateral mastectomy is increasing with no plateau. The aim of this study was to improve the understanding of patient- and tumor-related factors that influenced the choice of mastectomy with CPM as treatment for early-stage breast cancer at an academic medical center in New Jersey. This was a retrospective analysis of 10 years of breast cancer data including 1556 women aged 40 to 80 years treated for breast cancer at an academic medical center. Logistic regression models identified possible associations between type of surgery and various patient- and tumor-related characteristics. Women most likely to be treated with CPM were younger (P < .0001), white (P = .003), and privately insured (P < .0001). Factors that increased the odds of receiving CPM included year of surgery (odds ratio, 1.441; confidence interval, 1.328-1.564) and residing in a relatively wealthy community (odds ratio, 11.159; confidence interval, 3.467-35.917). The rate of CPM as a treatment for unilateral breast cancer continues to rise, and this treatment decision seems to be relatively independent of tumor-related factors and clinical evidence of efficacy. More research is needed to ascertain why women are choosing this surgical option. The large majority who are choosing CPM are doing so regardless of the lack of clinical efficacy, yet there are few articles in the nursing literature preparing nurses to understand and counsel these women who may be asking for advice. Nurses are well situated to provide unbiased and fact-based information to help women making potentially life-altering decisions in response to a cancer diagnosis.

Targeting neratinib-induced diarrhea with budesonide and colesevelam in a rat model.

Neratinib is an irreversible pan-ErbB tyrosine kinase inhibitor used for the extended adjuvant treatment of early-stage HER2-positive breast cancer. Its use is associated with the development of severe diarrhea in up to 40% of patients in the absence of proactive management. We previously developed a rat model of neratinib-induced diarrhea and found inflammation and anatomical disruption in the ileum and colon. Here we tested whether anti-diarrheal interventions, budesonide and colesevelam, can reduce neratinib-induced diarrhea and intestinal pathology. Rats were treated with 50mg/kg neratinib via oral gavage for 14 or 28days (total n = 64). Body weight and diarrhea severity were recorded daily. Apoptosis was measured using immunohistochemistry for caspase-3. Inflammation was measured via a multiplex cytokine/chemokine assay. ErbB levels were measured using PCR and Western Blot. Budesonide co-treatment caused rats to gain significantly less weight than neratinib alone from day 4 of treatment (P = 0.0418). Budesonide (P = 0.027) and colesevelam (P = 0.033) each reduced the amount of days with moderate diarrhea compared to neratinib alone. In the proximal colon, rats treated with neratinib had higher levels of apoptosis compared to controls (P = 0.0035). Budesonide reduced histopathological injury in the proximal (P = 0.0401) and distal colon (P = 0.027) and increased anti-inflammatory IL-4 tissue concentration (ileum; P = 0.0026, colon; P = 0.031) compared to rats treated with neratinib alone. In the distal ileum, while budesonide decreased ErbB1 mRNA expression compared to controls (P = 0.018) (PCR), an increase in total ErbB1 protein was detected (P = 0.0021) (Western Blot). Both budesonide and colesevelam show potential as effective interventions against neratinib-induced diarrhea.

Development of an e-health app to support women prescribed adjuvant endocrine therapy after treatment for breast cancer.

BackgroundAdjuvant endocrine therapy (AET) is prescribed to women for 5–10 years after treatment for estrogen receptor positive (ER+ve), early-stage breast cancer. AET has proven effectiveness in reducing the risk of recurrence of breast cancer and mortality. However, adherence is known to be suboptimal with around 20% discontinuing by 2 years and up to 50% discontinuing by 5 years. Interventions are needed to support women taking AET after breast cancer. The aim of this study was to develop and pilot test an e-health app for this population.MethodsTwo focus groups (n=15) and five interviews were conducted with women following treatment for early-stage breast cancer to assess the likely acceptability of an e-health app and to inform the content (Phase I). Following development of a prototype e-health app, a simple heuristic usability test was completed by five women in order to identify any design usability problems (Phase II). A further 18 women used the app for 1 month between July and August 2016, after which they were interviewed by telephone to collect their experiences and views of the app (Phase III).ResultsThe prototype e-health app included evidence-based information on effectiveness of AET, an electronic side-effects diary, a peer support forum, a repeat prescription reminder, suggested strategies for facilitating adherence and managing any side effects that occur, and a link to further evidence and useful organizations for further information and support. The app was received positively by women. Women found the app useful as it emphasized the importance of taking AET, helped them manage their side effects and provided details of support organizations, while offering empathy and exchange of suggestions for self-management strategies through the peer support forum.ConclusionOverall, findings suggest that this novel e-health app has potential as a feasible medium for promoting adherence to AET. Future research should evaluate the efficacy of the app in supporting women and promoting adherence.

Neratinib for the Treatment of Early-Stage HER2-Positive Breast Cancer

The treatment of breast cancer has been revolutionized by the development of HER2-targeted treatments for patients who are HER2 positive. The HER2 protein is present at high levels in about 30% of breast cancer patients. These high levels are associated with a greater chance of metastasis, relapse, and decreased survival. The current standard of care for early-stage HER2-positive patients includes treatment with 1 year of trastuzumab therapy. Although trastuzumab has improved outcomes, there is still a 20% chance for tumor recurrence and a 16% chance of death. Neratinib was developed to give patients with early-stage HER2-positive breast cancer an option to increase the disease-free survival rate. The 5-year invasive disease-free survival rate was 90.2% (95% confidence interval = 88.3-91.8) in the neratinib group and 87.7% (95% confidence interval = 85.7-89.4) in the placebo group.

From Research to Policy Implementation: Trastuzumab in Early-Stage Breast Cancer Treatment in Thailand

To evaluate the adjuvant therapy of trastuzumab cost and quality-adjusted life-years (QALYs) in lifetime horizon and describe the use of an economic evaluation in supporting policy-making decisions in the treatment of early-stage breast cancer in Thailand. A Markov model was used to evaluate the cost effectiveness of 1-year adjuvant trastuzumab for patients with early-stage breast cancer who were considered human epidermal growth factor receptor 2/neu-positive with a societal perspective and lifetime horizon. The research variables were probability of health state change, health utility, and cost of treatment. A sensitivity analysis was conducted using probabilistic methods. A budget impact analysis was also performed. The results revealed that the treatment cost and QALYs in the trastuzumab group yielded 4.59 QALYs. The incremental cost-effectiveness ratio was $3387 (THB 118 572; THB = Thai baht) per QALY. On the basis of the willingness-to-pay threshold in Thailand, a 1-year adjuvant trastuzumab treatment for breast cancer was a cost-effective therapy. A combination therapy that includes trastuzumab is a preferable choice and should be used in early-stage breast cancer treatment. The Thai government has listed trastuzumab on the National List of Essential Medicines to be used for the early stages of breast cancer since 2014.