Treatment Of Primary Breast Cancer Research Articles

CN25 Self-management interventions can promote health-related quality of life after primary treatment for early-stage breast cancer, but to what extent? A critical synthesis of evidence

CN25 Self-management interventions can promote health-related quality of life after primary treatment for early-stage breast cancer, but to what extent? A critical synthesis of evidence

Applying Risk-Based Follow-Up Strategies on the Dutch Breast Cancer Population: Consequences for Care and Costs.

An important aim of follow-up after primary breast cancer treatment is early detection of locoregional recurrences (LRR). This study compares 2 personalized follow-up scheme simulations based on LRR risk predictions provided by a time-dependent prognostic model for breast cancer LRR and quantifies their possible follow-up efficiency. Surgically treated early patients with breast cancer between 2003 and 2008 were selected from the Netherlands Cancer Registry. The INFLUENCE nomogram was used to estimate the 5-year annual LRR. Applying 2 thresholds, they were defined according to Youden's J-statistic and a predefined follow-up sensitivity of 95%, respectively. These patient's risk estimations served as the basis for scheduling follow-up visits; 2 personalized follow-up schemes were simulated. The number of potentially saved follow-up visits and corresponding cost savings for each follow-up scheme were compared with the current Dutch breast cancer guideline recommendation and the observed utilization of follow-up on a training and testing cohort. Using LRR risk-predictions for 30 379 Dutch patients with breast cancer from 2003 to 2006 (training cohort), 2 thresholds were calculated. The threshold according to Youden's approach yielded a follow-up sensitivity of 62.5% and a potential saving of 62.1% of follow-up visits and €24.8 million in 5 years. When the threshold corresponding to 95% follow-up sensitivity was used, 17% of follow-up visits and €7 million were saved compared with the guidelines. Similar results were obtained by applying these thresholds to the testing cohort of 11 462 patients from 2007 to 2008. Compared with the observed utilization of follow-up, the potential cost-savings decline moderately. Personalized follow-up schemes based on the INFLUENCE nomogram's individual risk estimations for breast cancer LRR could decrease the number of follow-up visits if one accepts a limited risk of delayed LRR detection.

Abstract LB-022: Real-time intraoperative tumor imaging in a breast cancer PDX model

Abstract Breast cancer is one of the most common types of cancer diagnosis in women of all ages. The primary treatment of breast cancer is surgical excision of the tumor with the margin of normal breast tissue surrounding the tumor. However, current clinical goals include complete resection of the tumor at the initial surgery, there is often a need for further surgery and removal of more tissue due to the difficulties inherent in getting negative margins. Therefore, there is a clinical need to optimize the excision by precisely identifying tumor margins significantly benefitting patients with breast cancer. Image-guided surgery with fluorescent agents provides surgeons numerous advantages such as real-time detection with a high-resolution image and relatively flexible instrument. We have developed a unique tumor-targeting fluorescence imaging agent. We identified a cell-penetrating peptide (CPP) p28, a fragment of azurin isolated from opportunistic pathogen Pseudomonas pathogen. p28 was chemically conjugated with Indocyanine green (ICG), a near-infrared red (NIR) fluorescent agent. ICG has been approved by the FDA for clinical applications with an excellent safety record. When p28 was conjugated to ICG, there was no significant alternation of fluorescence quantum yield (ΦF) of ICG-p28 compared to ICG alone. Triple-negative (ER, PR, HER2) human breast cancer PDX mouse model in NSG mice was used to evaluate the image-guided surgical procedure with ICG-p28. After 24h of ICG-p28 injection i.v. opportunistic 0.5 mg/kg b.w., NIR-fluorescence positive mammary tumors with a 2-mm safe margin were resected under real-time guidance of the PDE imaging unit (Mitaka USA, Hamamatsu Photonics). NIR-fluorescence negative surrounding tissues of at least two different sites (superior and inferior) were also collected separately. To validate the accuracy of tumor margin identification by the image guidance, Alu-based real-time PCR analysis was used for the quantitative detection of human cancer cells. Five ng of genomic DNA obtained from tumors and surrounding tissues were subjected to RT-PCR. Ct values were normalized by the housekeeping gene, mouse GAPDH. Our results showed that preclinical intraoperative imaging with our imaging agent, ICG-p28 at 0.5 mg/kg, significantly reduced positive margin as compared to control groups (e.g. ICG alone, p<0.01). In conclusion, nontoxic p28 is a potentially ideal CPP that can serve as a tumor-targeting carrier for an intraoperative imaging agent. Results suggest that our imaging approach will potentially provide a significant impact on resection procedure benefitting patients with breast cancer. Citation Format: Masahide Goto, Ingeun Ryoo, Samer Naffouje, Konstantin Christov, Jing Wang, Albert Green, Anne Shilkaitis, Tapas K. Das Gupta, Tohru Yamada. Real-time intraoperative tumor imaging in a breast cancer PDX model [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-022.

Loco-regional therapy for isolated locoregional lymph node recurrence of breast cancer: focusing on surgical treatment with combined therapy

Advances have been made in systemic as well as locoregional treatment of primary breast cancer. Evidence, based established therapeutic strategies, for isolated locoregional lymph node recurrence is not yet sufficient. In this series, we focused especially on isolated axillary lymph node recurrence (AR) and supraclavicular lymph node recurrence (SR) in patients receiving systemic and/or radiation therapy combined with surgery. Disease free survival (DFS) in patients with AR ranged from 20 to 36 months. From 69% to 77% of all patients underwent surgical excision. The 5-year overall survival (OS) ranged from 39% to 46%. Positive lymph node metastases of primary cancer, size of the primary tumor, and R0 resection were associated with good outcomes. Longer DFS is associated with good outcomes. Limited SR data showed DFS to range from 25–27%. Median progression free survival (PFS) was 18 months, 5-year OS rates were 24–42%, and 5-year OS were 29–34 months. Combination therapy was an independent factor associated with better PFS as compared to local therapy only. Salvage treatment and grade of the primary tumor significantly were associated with OS on multivariate analysis. Available data, retrospective and not randomized, showed therapy combining systemic treatments and/or radiotherapy with surgery might contribute to good local control, better PFS, and longer OS.

Delays to Adjuvant Breast Cancer Radiotherapy Resulting from Oncotype Dx Testing in Patients with Low/Intermediate Recurrence Risk Scores

Purpose: Oncotype Dx is a 21 gene recurrence score assay that risk stratifies patients who have completed primary surgical treatment for breast cancer to low or intermediate (adjuvant chemotherapy not routinely recommended) versus high risk of recurrence (adjuvant chemotherapy recommended). 73% of patients tested are stratified to the low/intermediate risk of recurrence group [1]. However, a proportion of these patients may have delays to commencing adjuvant radiotherapy. The current median time to adjuvant radiotherapy following surgery is recorded as 60 days [2].

How effective are self-management interventions in promoting health-related quality of life in people after primary treatment for breast cancer? A critical evidence synthesis.

Self-management interventions (SMIs) are designed to empower people living beyond breast cancer and help them adjust to a new normal. This structured review aimed to critically appraise and synthesise up-to-date evidence on the effectiveness of SMIs to promote health-related quality of life (HRQoL) in people with breast cancer in the post-treatment period. According to PRISMA statement guidelines, MEDLINE, EMBASE and CINAHL were searched for peer-reviewed publications of randomised controlled trials of SMIs. Pre-specified selection criteria were applied to all retrieved records. Methodological quality and risk of bias were evaluated by using the Caldwell framework and Cochrane Collaboration Risk of Bias tool, respectively. Findings were integrated into a narrative critical evidence synthesis. Nine eligible trials were identified that tested nine SMIs. Five SMIs were based on cognitive behaviour therapy (CBT). Eight SMIs targeted recipients' decision-making and taking-action skills. Across trials, gains in one to four domains of HRQoL were reported. SMIs predominantly promoted recipients' physical and functional well-being, regardless of methodological quality or self-management skills applied, but effect sizes were consistently small. SMIs were mainly prescribed for 12 weeks, but optimal dosage cannot be confirmed currently. SMIs informed by CBT and/or offered through recipient education were marginally more effective. Evidence derived from moderate-to-good quality trials. SMIs are potentially effective after primary treatment for breast cancer, although effect sizes are small and inconsistent across HRQoL domains. More rigorous development and testing is required, while co-production from the early development stages or at the refinement phase is recommended.

Systematic screening as a tool for individualized rehabilitation following primary breast cancer treatment: study protocol for the ReScreen randomized controlled trial

BackgroundIt is well known that women suffer from negative consequences following breast cancer (BC) treatment and that their largely varying needs for rehabilitation are often unmet. Up to 43% of these women are at risk of developing chronic distress requiring complex interventions; however, how to early identify and meet these women’s needs is unknown, leaving them with suboptimal chances of rehabilitation. The aim of the ReScreen study is to develop a model for and evaluate the effect of screening-based, individualized rehabilitation following primary BC treatment.MethodsThe ReScreen study is designed as a complex intervention. Women with newly diagnosed BC are consecutively included in a three-armed randomized controlled trial. At inclusion, patients score their distress level on the Distress Thermometer (scale of 0–10) aiming to identify patients with extended rehabilitation needs. Patients scoring ≥5 are randomized to the intervention or control group while patients scoring ≤4 are followed longitudinally as an observational group. Patients in the intervention group, in conjunction with a dedicated research nurse, create an individualized rehabilitation plan based on an evidence-based decision support tool that was developed to create a solid base for the intervention. The research nurse will act as a continuous health care contact and be responsible for proactively and systematically evaluating patients’ needs to ensure that potential new problems or changed rehabilitation needs are identified throughout the 1-year follow-up period. The intervention will be evaluated through self-reported data focusing on physical and psychological outcomes as well as evaluation of satisfaction with care at baseline, 2 weeks and 3, 6, 9 and 12 months. Evaluation will also include health economic aspects based on register data and patients’ and relatives’ experiences of the rehabilitation process. In addition, optimal cut-off levels for distress as an indicator for extended rehabilitation needs will be investigated.DiscussionThis study will provide important knowledge related to effectiveness of screening-based identification of rehabilitation needs and standardized evidence-based, individualized rehabilitation after primary BC treatment. With a complex intervention design, this study has the potential to form a comprehensive knowledge base which includes tools and guidelines for implementation into clinical practice.Trial registrationClinicalTrials.gov NCT03434717. Registered February 15, 2018.

Improving the delivery of team-based survivorship care after primary breast cancer treatment through a multi-level intervention.

7056 Background: The delivery of team-based survivorship care after primary cancer treatment remains challenging, in part due to a lack of effective interventions. We developed a multi-level intervention for breast cancer patients and their primary care and medical oncology providers to improve the delivery of team-based survivorship care called ConnectedCancerCare (CCC). CCC includes a patient-facing, personalized mobile website, and tailored feedback letters to providers. Methods: We conducted a pilot randomized controlled trial in a breast oncology clinic to establish the feasibility and acceptability of CCC. Women within one year of completing primary treatment for stages 0-II breast cancer were randomized to CCC (intervention) or a static online survivorship care plan (control). Participants completed online surveys at baseline and 3 months, ascertaining their knowledge about PCP roles in their survivorship care, their communication with their PCP about team-based care, and whether they scheduled a follow-up visit with their PCP. Multiple measures of acceptability were collected among women in the intervention arm (n = 28). Qualitative interviews were conducted at the completion of the study with 5 PCPs, 6 oncology providers, and 10 intervention patients to identify barriers and facilitators to implementing CCC. Results: Among 160 eligible women invited to participate, 66 women completed the baseline survey and were randomized (41% participation rate), and 54 completed the 3-month follow-up survey (83% response rate). Women in the intervention arm found the content of the CCC website to be highly acceptable, with 82% reporting it was easy to use, and 86% reporting they would recommend it to other patients. A greater proportion of women randomized to CCC (vs. control) reported scheduling a PCP follow-up visit (64% vs. 42%) and communicating with their PCP about provider roles (67% vs. 18%). Women in the CCC arm also reported higher mean knowledge scores regarding team-based cancer care (3.7 vs. 3.4). Providers noted challenges to implementing CCC, including integration into electronic medical records, and supporting sustained engagement with CCC over time. Conclusions: Our findings suggest deploying CCC in medical oncology practices is feasible, and the intervention content is acceptable among breast cancer patients. CCC shows promise for improving understanding and communication about provider roles in survivorship care, and facilitating patients to follow up with their PCP early in the survivorship period. Clinical trial information: NCT03618017 .

A controlled pilot trial of a nurse-led intervention (Mini-AFTERc) to manage fear of cancer recurrence in patients affected by breast cancer

BackgroundFear of cancer recurrence (FCR) is common in people affected by breast cancer. FCR is associated with increased health service and medication use, anxiety, depression and reduced quality of life. Existing interventions for FCR are time and resource intensive, making implementation in a National Health Service (NHS) setting challenging. To effectively manage FCR in current clinical practice, less intensive FCR interventions are required. Mini-AFTERc is a structured 30-min counselling intervention delivered over the telephone and is designed to normalise moderate FCR levels by targeting unhelpful behaviours and misconceptions about cancer recurrence.This multi-centre non-randomised controlled pilot trial will investigate the feasibility of delivering the Mini-AFTERc intervention, its acceptability and usefulness, in relation to specialist breast cancer nurses (SBCNs) and patients. This protocol describes the rationale, methods and analysis plan for this pilot trial of the Mini-AFTERc intervention in everyday practice.MethodsThis study will run in four breast cancer centres in NHS Scotland, two intervention and two control centres. SBCNs at intervention centres will be trained to deliver the Mini-AFTERc intervention. Female patients who have completed primary breast cancer treatment in the previous 6 months will be screened for moderate FCR (FCR4 score: 10‑14). Participants at intervention centres will receive the Mini-AFTERc intervention within 2 weeks of recruitment. SBCNs will audio record the intervention telephone discussions with participants. Fidelity of intervention implementation will be assessed from audio recordings. All participants will complete three separate follow-up questionnaires assessing changes in FCR, anxiety, depression and quality of life over 3 months. Normalisation process theory (NPT) will form the framework for semi-structured interviews with 20% of patients and all SBCNs. Interviews will explore participants’ experience of the study, acceptability and usefulness of the intervention and factors influencing implementation within clinical practice. The ADePT process will be adopted to systematically problem solve and refine the trial design.DiscussionFindings will provide evidence for the potential effectiveness, fidelity, acceptability and practicality of the Mini-AFTERc intervention, and will inform the design and development of a large randomised controlled trial (RCT).Trial registrationClinicalTrials.gov: NCT0376382. Registered 4th December 2018, https://clinicaltrials.gov/ct2/show/NCT03763825

Design of a randomized controlled trial of a partnership-based, needs-tailored self-management support intervention for post-treatment breast cancer survivors

BackgroundSelf-management is becoming essential for breast cancer survivors, but evidence about the effectiveness of self-management support (SMS) intervention is lacking. To address this issue, we developed a theory-based SMS intervention, the ‘EMPOWER’, aimed at empowering breast cancer survivors. Here we describe the rationale of the intervention and its development.MethodsThe conceptual framework of this study is the Chronic Care Model, which posits that SMS can influence patient-provider relationships and ultimately improve health outcomes. We will conduct a multi-center, 2-armed randomized controlled trial to assess the effectiveness of EMPOWER among post-treatment breast cancer survivors in South Korea. The trial will include 94 women who completed primary breast cancer treatment within the last 6 months. Participants will be randomly assigned to the intervention group or the wait-list control group (1:1). The intervention group will receive a 7-week partnership-based and needs-tailored SMS intervention via telephone counseling. The primary outcome is empowerment. The secondary outcomes include self-efficacy for post-treatment self-management behaviors, mental adjustment, psychological distress, and health-related quality of life (HRQOL). Data will be collected by self-reported questionnaire at baseline, post-intervention, and 3-month follow-up.DiscussionWe believe that the EMPOWER intervention could improve HRQOL of post-treatment breast cancer survivors by enhancing their empowerment. If found successful, it could aid clinicians engaged in the long-term care of breast cancer survivors.Trial registrationClinical Research Information Service, KCT0004794. Registered 5 March 2020.

Precision Medicine and the Role of Biomarkers of Radiotherapy Response in Breast Cancer.

Radiotherapy remains an important treatment modality in nearly two thirds of all cancers, including the primary curative or palliative treatment of breast cancer. Unfortunately, largely due to tumor heterogeneity, tumor radiotherapy response rates can vary significantly, even between patients diagnosed with the same tumor type. Although in recent years significant technological advances have been made in the way radiation can be precisely delivered to tumors, it is proving more difficult to personalize radiotherapy regimens based on cancer biology. Biomarkers that provide prognostic or predictive information regarding a tumor's intrinsic radiosensitivity or its response to treatment could prove valuable in helping to personalize radiation dosing, enabling clinicians to make decisions between different treatment options whilst avoiding radiation-induced toxicity in patients unlikely to gain therapeutic benefit. Studies have investigated numerous ways in which both patient and tumor radiosensitivities can be assessed. Tumor molecular profiling has been used to develop radiosensitivity gene signatures, while the assessment of specific intracellular or secreted proteins, including circulating tumor cells, exosomes and DNA, has been performed to identify prognostic or predictive biomarkers of radiation response. Finally, the investigation of biomarkers related to radiation-induced toxicity could provide another means by which radiotherapy could become personalized. In this review, we discuss studies that have used these methods to identify or develop prognostic/predictive signatures of radiosensitivity, and how such assays could be used in the future as a means of providing personalized radiotherapy.

P7 Are women commencing Neoadjuvant Chemotherapy (NAC) for Primary Breast Cancer (PBC) more likely to experience distress compared to women undergoing surgical intervention or Adjuvant Chemotherapy (AC)?

Background and purpose In the wake of the burgeoning use of NAC as a first-line treatment for PBC, it is imperative for the multidisciplinary team to assess the manifestations of distress among this group of women to enable initiation of timely supports aimed at easing the burden of distress (Lo-Fo-Wong et al. 2016). This study aimed to compare the prevalence and aetiological contributors of distress experienced by women across three treatment modality groups. Methods This cross-sectional pilot study involved retrospective review of data extracted from validated Distress Screening Tools (DSTs) completed by 58 women upon commencement of either NAC, undergoing surgery or AC for PBC. The prevalence of distress according the distress thermometer and aetiological contributors of distress as per the 34-point problem checklist incorporating practical, family, emotional, spiritual/religious and physical problems experienced by women commencing NAC were compared to women undergoing surgical intervention or commencing AC. Results Elevated distress was experienced by 80% (n=8) of women upon receipt of NAC, compared to 67% (n=18) of women in the surgical group and 71% (n=15) of women commencing AC. Moreover, despite baring the youngest mean age of the three modality groups, yet to endure surgical recovery or potential adversities associated with chemotherapy treatment, women who underwent NAC also identified a greater number of aetiological contributors of distress. Women commencing NAC were more likely to identify emotions such as fear, nervousness and sadness, possibly generated from uneasiness associated with the back-to-front treatment regimen, questioning treatment efficacy, and being of younger age with associated additional demands imparted by family and lifestyle commitments (Beaver et al. 2016). Conclusion These results suggest the need for timely distress screening among this cohort, alerting the potential for referrals for supportive care aimed at optimising emotional well-being and easing the burden of distress. Beaver, K., Williamson, S. and Briggs, J. 2016. Exploring patient experiences of neoadjuvant chemotherapy for breast cancer. European Journal of Oncology Nursing. 20:77-86. doi:10.1016.j.ejon.2015.06.001Lo-Fo-Wong, D.N.N., de Haes, H.C.J.M., Aaronson, N.K., van Abbema, D.L., den Boer, M.D., van Hezewijk, M., Immink, M., Kaptein, A., Menke-Pluijmers, M.B.E., Reyners, A.K.L., Russell N.S., Schreik, M., Sijtsema, S., van Tienhoven G and Sprangers, M.A.G. 2016. Predictors of enduring clinical distress in women with breast cancer. Breast Cancer Research and Treatment. 158(3):563-572. https://doi.org/10.1007/s10549-016- 3896-7

Abstract GS1-09: Addition of S-1 to endocrine therapy in the post-operative adjuvant treatment of hormone receptor-positive and human epidermal growth factor receptor 2-negative primary breast cancer: A multicenter, open-label, phase 3 randomized trial (POTENT trial)

Abstract BACKGROUND: Although long-term prognostic outcomes of primary breast cancer (PBC) patients have been improved remarkably in recent years, the disease recurrence remains a serious problem. We have previously investigated a role for oral fluoropyrimidines in postoperative adjuvant treatments.In this study, we aimed to verify the usefulness of S-1 in combination with adjuvant endocrine therapy for PBC patients having luminal disease. PATIENTS AND METHODS: This open-label, randomized, phase 3 trial was carried out in 139 centers in Japan. StageI-IIIPBC patients, who had hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negativestatus and intermediate or higher risk of recurrence were randomly assigned (1:1) to receive standard endocrine therapy alone (control arm) or endocrine therapy plus S-1 (S-1 arm). Recurrence risk assessment was performed using anatomical stage, pathological findings such as histologic grade, and centrally confirmed proliferative marker status. S-1 was administered postoperatively in combination with standard endocrine therapy. For patients who underwent multi-drug postoperative adjuvant or preoperative neoadjuvant chemotherapy, S-1 was administered following the multi-drug chemotherapy. Cases having no residual cancer in the breast and axillary node after the preoperative chemotherapy were excluded from this study. The S-1 dosage was chosen among 80 mg/day, 100 mg/day, and 120 mg/day according to the body surface area of each patient, and S-1 was administered for one year with a 2 weeks on/1 week off administration schedule. The primary endpoint was invasive disease-free survival (iDFS), defined as time from randomization to invasive disease recurrence, occurrence of second invasive cancer event, or death, and was analyzed on an intent-to-treat basis. Secondary endpoints included DFS, distant DFS, overall survival, and safety profile. RESULTS: From Feb 2012 to Feb 2016, 1959 patients were enrolled and 1932 patients were included in the full analysis set (control arm, 973; S-1 arm, 959). The results of the prespecified interim analysis met the primary end point, and this trial was terminated early. Median follow-up was 51.4 months. S-1 significantly reduced invasive events; 153 iDFS events were reported in the control arm and 99 iDFS events were reported in the S-1 arm [hazard ratio, 0.63 (95%CI, 0.49-0.81); p-value, 0.0003]. The 5-year iDFS estimate was 81.5% in the control arm and 86.9% in the S-1 arm. Distant recurrence as the first disease event was observed in 6.8% of patients in the S-1 arm and in 9.5% of those in the control arm. The safety data in patients treated with S-1 was consistent with the known profile of S-1. The S-1 treatment was well tolerated and manageable. CONCLUSIONS: It was concluded that the postoperative adjuvant use of an oralfluoropyrimidine S-1 significantly reduced iDFS events and improved 5-year iDFS estimate in PBC patients having HR-positive and HER2-negative disease, in the combination with standard endocrine therapy, with a feasible safety profile. Funding: This study was funded by the Comprehensive Support Project (CSP) of the Public Health Research Foundation. The research fund was provided to CSP by Taiho Pharmaceutical Co., Ltd. This trial was conducted as a study of ‘Advanced Medical Care,’ the Ministry of Health, Labour and Welfare, Japan. JRCT ID: jRCTs051180057, UMIN000003969 Citation Format: Masakazu Toi, Shigeru Imoto, Takanori Ishida, Yoshinori Ito, Hiroji Iwata, Norikazu Masuda, Hirofumi Mukai, Shigehira Saji, Akira Shimizu, Takafumi Ikeda, Hironori Haga, Toshiaki Saeki, Kenjiro Aogi, Tomoharu Sugie, Takayuki Ueno, Takayuki Kinoshita, Yuichiro Kai, Masahiro Kitada, Yasuyuki Sato, Kenjiro Jimbo, Nobuaki Sato, Hiroshi Ishiguro, Masahiro Takada, Yasuo Ohashi, Shinji Ohno. Addition of S-1 to endocrine therapy in the post-operative adjuvant treatment of hormone receptor-positive and human epidermal growth factor receptor 2-negative primary breast cancer: A multicenter, open-label, phase 3 randomized trial (POTENT trial) [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 GS1-09.

Abstract P3-08-72: Poor prognosis in elderly patients with breast cancer resulted from under-treatment in patients with triple negative breast cancer and mortality from other than breast cancer

Abstract Background: Breast cancer is the leading cause of malignant disease in Korean women nest to thyroid cancer. Age is one of the significant risk factor and Korean population is aging rapidly, almost 1.5 times older than a half century ago, from 52.4 years in 1960 to 78.5years at 2005. While it is uncertain the proportional incidence is also increasing, absolute number of elderly patients is increasing and unmet clinical needs and unanswered questions are remained in the clinical practice for elderly patients. The aim of this study is to outline breast cancer in elderly patients and examine survivals by clinicopathologic factors such as age, stage and disease subtype. Material and Methods: Patients who were diagnosed and completed their primary treatment for breast cancer from 2000 to 2013 were included. Clinicopathologic data was collected with retrospective data review and survival data and risk factors, if the survival was statistically significant, were obtained. Results: 1103 patients with invasive breast cancer were included. Mean age was 52.71±11.478(22-89). Subjects were divided into three group, <40 (n=147, 35.9±3.704), 40-60 (n=680,49±5.131), >60(n=276,68.6±5.62). Patients over 60 had statistically worse overall survival(p=0.011) and distant disease free survival(p=0.012) with Kaplan-Meier method with log rank test and hazard ratio(HR) of elderly was 2.206 with 1.046-4.658 96% Confidence Interval(CI). For the worse prognosis of elderly, triple negative breast cancer who got less than standard systemic treatment (HR=4.836, 95% CI, 1.514-15.452) and mortality from other than breast(HR=2.395, 95% CI,1.106-5.188) cancer were significantly correlated with higher mortality in elderly patients. Conclusion: Elderly patients with breast cancer experience significant worse survival when they got less than standard systemic treatment or second primary disease other than breast cancer in their follow up period. Citation Format: Gilseong Moon, Ji wool Ko, Hany Noh, In-Jeong Cho, Jong-in Lee, Airi Han. Poor prognosis in elderly patients with breast cancer resulted from under-treatment in patients with triple negative breast cancer and mortality from other than 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 P3-08-72.

Abstract P3-11-22: Efficacy of two kinds of granulocyte colony-stimulating factors to support neoadjuvant dose-dense chemotherapy in primary breast cancer

Abstract Background and objective: Adjuvant chemotherapy is a critical part of systematic treatment of primary breast cancer. Chemotherapy induced neutropenia (CIN) is a common adverse event during adjuvant chemotherapy as well as a major factor limiting the implementation of the planned schedule of chemotherapy, causing the delay and drug reduction. Recombinant human granulocyte-colony stimulating factor (rhG-CSF) effectively stimulates the proliferation of neutrophil progenitors, promotes differentiation of these cells into mature neutrophils, and promote the release of neutrophils from the marrow, thus reducing the probability of CIN and related complications. Dose-Dense (DD) chemotherapy has become a commonly recommended regimen for primary breast cancer because of improvement of disease-free survival (DFS) and Overall Survival (OS). rhG-CSF should be administered prophylactically due to the high incidence of marrow suppression during dose-dense regimen. Little high-level clinical evidence to determine a unified rhG-CSF regimen. Single injection of long-acting pegfilgrastim and continuous multiple usage of short-acting filgrastim are two major ways to support dose-dense adjuvant chemotherapy. Based on a single database, we retrospectively assessed the efficacy and safety of two different rhG-CSF in supporting the dose-dense adjuvant chemotherapy (ddEC) in primary breast cancer, aiming to test the effectiveness of two different rhG-CSF as well as comparison of the advantages and disadvantages of the two methods. Methods: Data of patients who received dose-dense neoadjuvant chemotherapy with support of rhG-CSF at Peking University Cancer Hospital Breast Cancer Prevention and Treatment Center from Jul, 2015 to Jun, 2018 were retrospectively collected. All of these patients were planned to receive four cycles of ddEC (Epirubicin 100mg/m2 and cyclophosphamide 600 mg/m2) with using one of the following rhG-CSF schedules in parallel: 1) filgrastim 200-300μg/d on day 4, 6, 8, 10; 2) pegfilgrastim 6mg on day 2. The relative dose intensity (RDI) was calculated. Results: A total of 555 patients were enrolled and 2,176 cycles were completed in this study, 254 were treated with pegfilgrastim and 301 were treated with short-term filgrastim. 536 patients (96.6%, 95%CI: 95.1%-98.1%) completed all four cycles of treatment. Chemotherapy delay occurred in 42 patients (7.6%, 95%CI: 5.4%-9.8%) for 47 cycles (2.2%, 95%CI:11.6%-2.8%). 18 patients (3.2%, 95%CI:1.7% - 4.7%) had CIN-related chemotherapy delay. 532 patients achieved RDI≥85% (99.4%, 95%CI:98.7%-100%). FN occurred in 25 patients (4.5%, 95%CI:2.8% - 6.2%). In the subgroup of using pegfilgrastim, Chemotherapy delay occurred in 10 patients (3.9%, 95%CI:1.5%-6.3%), 243 patients achieved RDI≥85% (99.4%, 95%CI: 98.7%-100%), and FN occurred in 11 patients (4.3%, 95%CI: 1.8%-6.8%). In the subgroup of using short-term filgrastim, chemotherapy delay occurred in 15 patients (5.0%, 95%CI: 2.5%-7.5%), 289 patients achieved RDI≥85% (96%, 95CI: 93.8%-98.2%), and FN occurred in 14 patients (4.7%, 95%CI: 2.3%-7.1%). FN is more likely in patients using short-term filgrastim (6.3%vs2.8%, p=0.048), causing more chemotherapy delay (10.8%vs4.1%, p=0.003). Age, tumor size, status of axillary lymph nodes, pathological type and baseline of ANC were not correlated with non-febrile neutropenia in patients using short-term filgrastim. Conclusion: Two schedules of rhG-CSF are effective and safe in supporting four cycles of neoadjuvant ddEC. The effects of these two methods were similar in the completion rate of chemotherapy(RDI≥85%) and safety(incidence of FN). Citation Format: Jingyi Zhao, Yingjian He, Zhaoqing Fan, Jinfeng Li, Xinguang Wang, Yang Yang, Xue Chen, Tao Ouyang. Efficacy of two kinds of granulocyte colony-stimulating factors to support neoadjuvant dose-dense chemotherapy in primary 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 P3-11-22.

Abstract P2-16-04: National utilisation of neoadjuvant systemic therapy and impact on surgical treatment - A prospective multi-centre cohort study

Abstract Introduction: Potential advantages of neoadjuvant systemic therapy (NST) include downstaging disease to minimise surgery, and in vivo assessment of tumour sensitivity to therapeutic drugs. Considerable variation in NST use remains, however, and it is unclear whether pathological response rates reflect those reported in trials, or whether downstaging achieved impacts on surgical decision-making. The NeST prospective multicentre study will address these questions through investigating patterns of care in the UK. Methods: Women undergoing NST as their primary breast cancer treatment (chemotherapy (CT), endocrine (ET) and targeted therapies) in UK centres between December 2017 and November 2018 were included. Anonymised data was collected at 37 participating centres, and uploaded to REDCap. Results: 1179 patients received neoadjuvant treatment during the study period. 41% had HER2+ disease, 28% TNBC and 31% ER+ HER2- disease. 48% were node positive and 52% node negative. Cited indications for neoadjuvant treatment were (more than one option applicable to each patient): Downstaging (mastectomy to breast conservation) 37% Facilitate dual antiHER2 therapy 33% Inoperable disease 19% Improved cosmesis (reduced volume of excision) 17% Facilitate BRCA testing 9% Inflammatory breast cancer 6% In patients recommended to receive NST, the MDT decision was for neoadjuvant CT in 87% of cases and neoadjuvant ET in 13%. For ER+ disease, the commonest reasons for prescribing CT were high grade disease and pre-menopausal status. The majority were treated with anthracycline-taxane combinations. 21% of TNBC patients were treated with platinum-containing regimens. In HER2+ disease, 54% were treated with dual antiHER2 therapies/chemotherapy, with 10% receiving chemotherapy/single antiHER2 agent (trastuzumab). Centres were asked to indicate primary breast surgical treatment recommended prior to/without NST. At abstract submission, this data was available for 887 patients. 31 had inoperable disease. A total of 477 were considered to require mastectomy, with disease not amenable to breast conservation surgery (BCS). A further 379 patients were considered candidates for BCS. Data on final surgical procedure was available for 765 patients. Of those patients determined suitable only for mastectomy at diagnosis, 123 underwent BCS as their primary operation - a downstaging rate of 26%. The overall mastectomy rate in this cohort was 48%, with 33% having mastectomy and 15% mastectomy with immediate reconstruction. Pathological response data was available in 672 patients, with an overall pathological complete response (pCR) rate of 29% (defined as no residual invasive or in situ disease). pCR rate according to molecular subtype was 37% for HER2+ disease, 35% for TNBC and 7% for ER+, HER2-ve disease. The pCR rate in patients downstaged from mastectomy to BCS was 27%. Conclusions: This UK national prospective study suggests that surgical downstaging remains a key indication for the use of NST. This is reflected in the fact that 26% of patients in this series were downstaged from an original surgical plan for mastectomy, with NST enabling BCS in these patients. However, based on this data it appears that surgical downstaging is no more likely in those with pCR compared to those without a pCR. Additional indications for NST are emerging, according to disease biology. There is widespread use of dual antiHER2 targeted therapies in this setting, with increasing use of platinum-containing regimens for TNBC. Neoadjuvant CT continues to be frequently used in the treatment of ER+ disease, despite known low pCR rates in this context, which are again confirmed. Low rates of neoadjuvant ET use are reported. Data collection is ongoing; updated data will be presented in December 2019. Citation Format: Stuart A McIntosh, Gareth W Irwin, Finian Bannon, Charlotte Coles, Ellen Copson, Ramsey Cutress, Rajiv Dave, Margaret Grayson, Chris Holcombe, Sheeba Irshad, Ciara O'Brien, Rachel O'Connell, Carlo Palmieri, Abeer M Shaaban, Nisha Sharma, Jagdeep Singh, Ian Whitehead, Shelley Potter. National utilisation of neoadjuvant systemic therapy and impact on surgical treatment - A prospective multi-centre cohort study [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 P2-16-04.

Abstract P5-08-11: Applying risk-based follow-up strategies on the Dutch breast cancer population: Consequences for care and costs

Abstract Purpose: An important aim of follow-up after primary breast cancer treatment is early detection of locoregional recurrences (LRR) to improve survival. This study proposes and simulates two personalized follow-up schemes based on LRR risk predictions provided by the INFLUENCE-nomogram (a time-dependent prognostic model for breast cancer-LRR) and quantifies their possible follow-up efficiency. Methods: Patients with early breast cancer who received surgery with curative intent between 2003 and 2008 were selected from the Netherlands Cancer Registry. The INFLUENCE-nomogram was used to estimate five annual LRR risks for every patient. Applying two thresholds, defined according to (a) Youden’s J-statistic, and (b) a pre-defined follow-up sensitivity of 95%, these risk estimations served as basis to decide when to schedule follow-up visits; thus, two personalized follow-up schemes were simulated. The number of potentially saved follow-up visits and corresponding cost savings for each follow-up scheme were compared to the current Dutch breast cancer guideline on a training and testing cohort. Results: Using LRR risk predictions for 30,379 Dutch breast cancer patients from 2003 to 2006 (training cohort), two thresholds were calculated. The threshold according to Youden’s approach yielded a follow-up sensitivity of 62.5% and a potential saving of 62.1% of follow-up visits and 24.8 M €. When the threshold corresponding to 95% follow-up sensitivity is used, 17.0% of follow-up visits and 7.0 M € could be saved. Similar results were obtained by applying these thresholds to the testing cohort of 11,462 patients from 2007 to 2008. Conclusion: Personalized follow-up schemes based on the INFLUENCE-nomogram’s individual risk estimations for breast cancer-LRR could decrease the number of follow-up visits if one accepts a limited risk of delayed LRR detection. Citation Format: Teresa Draeger, Vinzenz Voelkel, Catharina GM Groothuis-Oudshoorn, Miha Lavric, Jeroen Veltman, Anneriet Dassen, Lisbeth J. Boersma, Annemieke Witteveen, Gabe S. Sonke, Hendrik Koffijberg, Sabine Siesling. Applying risk-based follow-up strategies on the Dutch breast cancer population: Consequences for care and costs [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 P5-08-11.

Abstract P2-18-03: Breast cancer treatment and association with clinicopathologic features in TCGA

Abstract Background: For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data were analyzed and a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource was created. However, TCGA treatment data are not systematically analyzed. Here we focus on TCGA primary breast cancer (TCGA-BC) treatment data to assess their completeness, regimen patterns, and association with clinicopathologic features. Method: 814 TCGA-BC patients with treatment data diagnosed from 2001 to 2013 were selected for this study. The treatment data were prepared and classified to be adjuvant Chemotherapy (CT), adjuvant Radiation Therapy (RT), and adjuvant Hormone Therapy (HT). An in-house Clinical Breast Care Project (CBCP) treatment dataset (n=1051 from 2001 to 2017), which were relatively complete, were used as a reference for data completeness. Multinomial logistic regression was used to analyze the associations between different therapies and clinical features. Results: There is no consistent treatment data difference between TCGA-BC and CBCP. In TCGA-BC, 68.7%, 64.4%, and 64.5% of patients received CT, RT, and HT respectively, whereas in CBCP, the corresponding percentages were 59.0%, 71.2%, and 77.1%. The percentages of patients receiving combined therapies are even more comparable between the two cohorts (data not shown due to many combinations). The associations between treatment and clinicopathologic features were analyzed using multinomial logistic regressions with age, race, menopausal status, AJCC stage, and PAM50 subtype as covariates. Several of these covariates significantly associate with the use of therapies. Compared to patients with age < 50, patients with age ≥ 65 were significantly more likely to receive HT, HT+RT, or RT than CT only (OR=11.34, 9.25, 4.82; p=0.001, 0.002, and 0.024 respectively); Compared to pre-menopausal patients, post-menopausal patients were significantly more likely to receive HT+RT than CT only (OR=4.12, p=0.034); Compared to patients with early stages (I, II), patients with advanced stages (III, IV) were more likely to receive CT+HT+RT (OR=1.92, p=0.038) or CT+RT (OR=2.38, p=0.010) than CT only, and less likely to receive CT+HT (OR=0.39, p=0.033) or HT (OR=0.30, p=0.008) than CT only. PAM50 subtype also significantly associates with the use of therapies. Compared to Luminal A patients, patients with Basal subtype were significantly less likely to receive CT+HT (OR=0.14, p=1.3e-05), CT+HT+RT (OR=0.06, p=3.0e-10), HT+RT (OR=0.01, p=9.2e-06), or HT (OR=0.02, p=3.8e-07) than CT alone. Patients with HER2+ subtype showed similar patterns (note targeted therapies were classified as CT). In addition, patients with Basal subtype were significantly more likely to receive CT+RT (OR=2.47, p=0.01) than CT only. Conclusion: TCGA-BC patient treatment data are relatively as complete as our in-house CBCP patient treatment data, enabling us to perform a preliminary analysis of the former for association with clinicopathologic features of the patients. The significant associations of age, menopausal status, AJCC stage, and PAM50 subtype with treatment regimens are consistent with clinical knowledge, suggesting potential validity of TCGA BC treatment data for research use. Disclaimer: The contents of this publication are the sole responsibility of the author(s) and do not necessarily reflect the views, opinions or policies of Uniformed Services University of the Health Sciences (USUHS), The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., the Department of Defense (DoD), the Departments of the Army, Navy, or Air Force. Mention of trade names, commercial products, or organizations does not imply endorsement by the U.S. Government. Citation Format: Jianfang Liu, J. Leigh Fantacone-Campbell, Albert J. Kovatich, Brenda Deyarmin, Bradley J. Mostoller, Jeffrey A. Hooke, Hallgeir Rui, Craig D. Shriver, Hai Hu. Breast cancer treatment and association with clinicopathologic features in TCGA [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 P2-18-03.

Photodynamic Therapy in Primary Breast Cancer.

Photodynamic therapy (PDT) is a technique for producing localized necrosis with light after prior administration of a photosensitizing agent. This study investigates the nature, safety, and efficacy of PDT for image-guided treatment of primary breast cancer. We performed a phase I/IIa dose escalation study in 12 female patients with a new diagnosis of invasive ductal breast cancer and scheduled to undergo mastectomy as a first treatment. The photosensitizer verteporfin (0.4 mg/kg) was administered intravenously followed by exposure to escalating light doses (20, 30, 40, 50 J; 3 patients per dose) delivered via a laser fiber positioned interstitially under ultrasound guidance. MRI (magnetic resonance imaging) scans were performed prior to and 4 days after PDT. Histological examination of the excised tissue was performed. PDT was well tolerated, with no adverse events. PDT effects were detected by MRI in 7 patients and histology in 8 patients, increasing in extent with the delivered light dose, with good correlation between the 2 modalities. Histologically, there were distinctive features of PDT necrosis, in contrast to spontaneous necrosis. Apoptosis was detected in adjacent normal tissue. Median follow-up of 50 months revealed no adverse effects and outcomes no worse than a comparable control population. This study confirms a potential role for PDT in the management of early breast cancer.

Measurement of Pectoralis Minor Muscle Length in Women Diagnosed With Breast Cancer: Reliability, Validity, and Clinical Application.

Decreased pectoralis minor muscle length is common after primary breast cancer treatment and can result in an abnormal position of the scapula. This position can contribute to shoulder pain and pathomechanics and can lead to problems such as impingement syndrome, rotator cuff tears, and frozen shoulder. Currently, there are limited reliable methods for measuring pectoralis minor length. The objective of this study was to examine the reliability and validity of measuring pectoralis minor length in women diagnosed with breast cancer. This was a cross-sectional reliability and validity study. Bilateral pectoralis minor length (in centimeters) was assessed using a palpation meter in women (N=29) diagnosed with breast cancer by 2 licensed physical therapists who were masked to the measures. Bilateral pectoralis minor length was also measured using a motion capture system to assess validity. Intratester reliability (intraclass correlation coefficient, ICC [3,k]=0.971; 95% confidence interval [CI]=0.939-0.986; standard error of measurement [SEM]=0.16cm) and intertester reliability (ICC[3,k]=0.915; 95% CI=0.81-0.962; SEM=0.31cm) were excellent for the palpation meter on the affected side and the unaffected side (intratester reliability: ICC[3,k]=0.951; 95% CI=0.897-0.977; SEM=0.19cm; intertester reliability: ICC[3,k]=0.945; 95% CI=0.877-0.975; SEM=0.22cm). Significant correlations were found between the motion capture system and the palpation meter on the affected side (r=0.87) and the unaffected side (r=0.81). Bland-Altman plots between the palpation meter and the motion capture system demonstrated that all the measures fell within the limits of agreement. This study encountered possible errors with the accuracy of the motion capture system tracking because of the proximity of the markers and inherent volumetric restrictions. The palpation meter is a reliable, valid, easily administered, and cost-effective tool for assessing pectoralis minor length in women with breast cancer.