National Breast Cancer Registry Research Articles

General Population Mortality Adjustment in Survival Extrapolation of Cancer Trials: Exploring Plausibility and Implications for Cost-Effectiveness Analyses in HER2-Positive Breast Cancer in Sweden.

In economic evaluations of novel therapies, assessing lifetime effects based on trial data often necessitates survival extrapolation, with the choice of model affecting outcomes. The aim of this study was to assess accuracy and variability between alternative approaches to survival extrapolation. Data on HER2-positive breast cancer patients from the Swedish National Breast Cancer Register were used to fit standard parametric distribution (SPD) models and excess hazard (EH) models adjusting the survival projections based on general population mortality (GPM). Models were fitted using 6-y data for stage I and II, 4-y data for stage III, and 2-y data for stage IV cancer reflecting an early data cutoff while maintaining sufficient events for comparison of model estimates with actual long-term outcomes. We compared model projections of 15-y survival and restricted mean survival time (RMST) to 15-y registry data and explored the variability between models in extrapolations of long-term survival. Among 11,224 patients compared with the observed registry 15-y RMST estimates across the disease stages, EH cure models provided the most accurate estimates in patients with stage I to III cancer, whereas EH models without cure most closely matched survival in patients with stage IV cancer, in which cure assumption was less plausible. The Akaike information criterion-averaged model projections varied as follows: -8.2% to +5.3% for SPD models, -4.9% to +5.2% for the EH model without a cure assumption, and -19.3% to -0.2% for the EH model with a cure assumption. EH models significantly reduced between-model variance in the predicted RMSTs over a 50-y time horizon compared with SPD models. EH models may be considered as alternatives to SPD models to produce more accurate and plausible survival extrapolation that accounts for general population mortality. Excess hazard (EH) methods have been suggested as an approach to incorporate background mortality rates in economic evaluation using survival extrapolation.We highlight that EH models with or without a cure assumption can produce more accurate survival projections and significantly reduce between-model variability in comparison with standard parametric distribution models across cancer stages.EH models may be a preferred modeling method to reduce model uncertainty in health economic modeling since models that would otherwise have produced implausible extrapolations are constrained by the EH framework.Reduced uncertainty in economic evaluations will enhance the application of evidence-based health care decision making.

Timing and type of breast reconstruction in SweBRO 3: long-term outcomes.

Breast reconstruction after mastectomy helps women with breast cancer feel better about their bodies and lives. There is debate about the best time and type of reconstruction (immediate versus delayed, and using own tissue versus implants). Long-term studies are rare. This study looked at long-term results of different breast reconstruction methods and timings in Swedish women who had mastectomies in 2000, 2005 or 2010. It focused on how satisfied the women were with their surgeries and their quality of life. The study included 5853 women from the Swedish National Breast Cancer Registry who had mastectomies in 2000, 2005 or 2010. Of these, 2904 women answered the survey, and 895 had breast reconstruction. Satisfaction and quality of life were measured using two surveys: EORTC QLQ-BRECON23 and BREAST-Q. Of the women who answered the survey, 895 (31%) had breast reconstruction. Of these, 176 (20%) had immediate reconstruction, and 719 (80%) had delayed reconstruction; 58% had implant-based reconstructions, 31% had reconstructions using their own tissue, 2% had both types and 9% did not report the type of reconstruction. There were no major differences in satisfaction between immediate and delayed reconstruction. Women who used their own tissue were more satisfied with their results and breast appearance than those with implants. Autologous reconstruction leads to better satisfaction and outcomes than implants. The timing of reconstruction (immediate versus delayed) was less of an influence on quality of life.

A population-based study on trajectories of HER2 status during neoadjuvant chemotherapy for early breast cancer and metastatic progression

BackgroundThis study aimed to investigate the distribution and changes of HER2 status in untreated tumours, in residual disease and in metastasis, and their long-term prognostic implications.MethodsThis is a population-based cohort study of patients treated with neoadjuvant chemotherapy for breast cancer during 2007–2020 in the Stockholm–Gotland region which comprises 25% of the entire Swedish population. Information was extracted from the National Breast Cancer Registry and electronic patient charts to minimize data missingness and misclassification.ResultsIn total, 2494 patients received neoadjuvant chemotherapy, of which 2309 had available pretreatment HER2 status. Discordance rates were 29.9% between primary and residual disease (kappa = 0.534), 31.2% between primary tumour and metastasis (kappa = 0.512) and 33.3% between residual disease to metastasis (kappa = 0.483). Adjusted survival curves differed between primary HER2 0 and HER2-low disease (p < 0.001), with the former exhibiting an early peak in risk for death which eventually declined below the risk of HER2-low. Across all disease settings, increasing the number of biopsies increased the likelihood of detecting HER2-low status.ConclusionHER2 status changes during neoadjuvant chemotherapy and metastatic progression, and the long-term behaviours of HER2 0 and HER2-low disease differ, underscoring the need for obtaining tissue biopsies and for extended follow-up in breast cancer studies.

Abstract PO3-01-14: Impact of detection mode, tumor characteristics and additional treatment on adherence to adjuvant endocrine therapy after breast cancer in Sweden

Abstract Background: Adjuvant endocrine therapy (AET) reduces recurrence and mortality in women with estrogen receptor (ER) positive early breast cancer (EBC). Adherence to AET has been shown to be lower than expected with risk of worse longtime prognosis. In a nationwide study in Sweden women with breast cancer diagnosis 2008-2010 adherence to AET at 5-year follow-up was estimated at 82,5% which is considered good related to recent published studies (manuscript is under review). Differences between regions and age-groups were shown. Present study investigates the impact on adherence of detection mode, tumor characteristics and additional treatment. Methods: Through the Swedish Cancer Registry (SCR) women with a first primary EBC diagnosed 2008-2010 were identified. From the Swedish National Breast Cancer Registry (NKBC) individual tumor and treatment data were collected. Included in the study was patients with ER positive tumors &amp;gt; 10 mm without distant metastasis at diagnosis. Through the Swedish Prescription Registry dispensed treatment from pharmacies was extracted and medication possession rate (MPR) was calculated as number of dispensed doses divided by treatment duration in days. Good adherence to treatment in a patient was set at MPR ≥80%. Adherence at 3- and 5-year follow-up by detection mode, tumor characteristics and additional treatment was estimated. Results: Out of 21 016 women with a first primary BC 2008-2010 registered in the NKBC 10 176 met the inclusion criteria for the study. Among screen-detected tumors the 3- and 5-year adherence were 90,2 respectively 85,1% and 85,4 respectively 78,4% in the non-screen-detected group. In the screen-detected group the tumors were smaller and more often node negative. There was a significantly increased 5-year adherence in patients with stage III disease compared to those with stage I disease (84,1 vs 81,3 %) but not significant at 3-year (89,2 vs 87,3). Adjuvant chemotherapy significantly increased 3- (91.0% vs 85.8%) and 5-year (85.7% vs 79.3%) adherence among screen-detected and non-screen-detected respectively. Conclusions: Adherence to AET in Sweden was good, although there were differences depending on detection mode, tumor stage and additional adjuvant treatment. Stage and additional medical adjuvant treatment depend on each other and should not be seen as independent factors for adherence for AET. Citation Format: Anne Andersson, Anna Von Wachenfeldt, Lennarth Nyström, Frida Isaksson, Pihla Ruohonen. Impact of detection mode, tumor characteristics and additional treatment on adherence to adjuvant endocrine therapy after breast cancer in Sweden [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-01-14.

Organizational Breast Cancer Data Mart: A Solution for Assessing Outcomes of Imaging and Treatment.

In the United States, a comprehensive national breast cancer registry (CR) does not exist. Thus, care and coverage decisions are based on data from population subsets, other countries, or models. We report a prototype real-world research data mart to assess mortality, morbidity, and costs for breast cancer diagnosis and treatment. With institutional review board approval and Health Insurance Portability and Accountability Act (HIPPA) compliance, a multidisciplinary clinical and research data warehouse (RDW) expert group curated demographic, risk, imaging, pathology, treatment, and outcome data from the electronic health records (EHR), radiology (RIS), and CR for patients having breast imaging and/or a diagnosis of breast cancer in our institution from January 1, 2004, to December 31, 2020. Domains were defined by prebuilt views to extract data denormalized according to requirements from the existing RDW using an export, transform, load pattern. Data dictionaries were included. Structured query language was used for data cleaning. Five-hundred eighty-nine elements (EHR 311, RIS 211, and CR 67) were mapped to 27 domains; all, except one containing CR elements, had cancer and noncancer cohort views, resulting in a total of 53 views (average 12 elements/view; range, 4-67). EHR and RIS queries returned 497,218 patients with 2,967,364 imaging examinations and associated visit details. Cancer biology, treatment, and outcome details for 15,619 breast cancer cases were imported from the CR of our primary breast care facility for this prototype mart. Institutional real-world data marts enable comprehensive understanding of care outcomes within an organization. As clinical data sources become increasingly structured, such marts may be an important source for future interinstitution analysis and potentially an opportunity to create robust real-world results that could be used to support evidence-based national policy and care decisions for breast cancer.

National long-term patient-reported outcomes following mastectomy with or without breast reconstruction: The Swedish Breast Reconstruction Outcome Study Part 2 (SweBRO 2).

The Swedish Breast Reconstruction Outcome Study (SweBRO) initiative is a nationwide study with the primary aim of assessing long-term outcomes after mastectomy with and without breast reconstruction (BR). The current part (SweBRO 2) is designed to evaluate health-related quality of life (HRQoL), with the hypothesis that BR has a positive impact on patient-reported HRQoL in the long-term. Women who underwent mastectomy in Sweden in 2000, 2005, or 2010 and were alive at the time of the survey were identified through the National Breast Cancer Registry. Eligible participants received formal invitation letters to take part in a survey evaluating their HRQoL at 5 , 10, or 15 years post-mastectomy. The EORTC QLQ-C30, EORTC QLQ-BR23, and EQ-5D-3L questionnaires were employed. Of 2904 respondents (50% of 5853 invited), 895 (31%) had received BR. Among them, 516 (58%) were reconstructed with implants and 281 (31%) with autologous tissue. Women with BR scored significantly better in the EORCT QLQ-C30 physical functioning domain (mean 90 versus 81 points), fatigue (mean 21 versus 25), and dyspnoea (mean 16 versus 22) compared to non-reconstructed women. The EORTC QLQ-BR23 revealed that women with BR experienced favourable sexual functioning compared with non-reconstructed women (mean 26 versus 14). The EQ-5D-3L visual analogue scale score was similar between groups. The current study underscores the benefits of BR for long-term well-being, for example, in terms of physical and sexual functioning. These underline the importance of informing women undergoing mastectomy about BR alternatives and its potential benefits in enhancing long-term well-being.

Association of clinicopathologic variables and patient preference with the choice of surgical treatment for early-stage breast cancer: A registry-based study

IntroductionObservational studies suggest that breast conserving surgery (BCS) and radiotherapy (RT) offers superior survival compared to mastectomy. The aim was to compare patient and tumour characteristics in women with invasive breast cancer ≤30 mm treated with either BCS or mastectomy, and to explore the underlying reason for choosing mastectomy. MethodsWomen registered with breast cancer ≤30 mm and ≤4 positive axillary lymph nodes in the Swedish National Breast Cancer Register 2013–2016 were included. Logistic regression analyses were performed to assess the association of tumour and patient characteristics with receiving a mastectomy vs. BCS. ResultsOf 1860 breast cancers in 1825 women, 1346 were treated by BCS and 514 by mastectomy. Adjuvant RT was given to 1309 women (97.1 %) after BCS and 146 (27.6 %) after mastectomy. Variables associated with receiving a mastectomy vs. BCS included clinical detection (Odds Ratio (OR) 4.15 (95 % Confidence Interval (CI) 3.35–5.14)) and clinical stage (T2 vs. T1 (OR 3.68 (95 % CI 2.90–4.68)), N1 vs. N0 (OR 2.02 (95 % CI 1.38–2.96)). Women receiving mastectomy more often had oestrogen receptor negative, HER2 positive tumours of higher histological grade. The most common reported reason for mastectomy was large or multifocal tumours (53.5 %), followed by patient preference (34.5 %). ConclusionChoice of surgery is strongly associated with key prognostic factors among women undergoing BCS with RT compared to mastectomy. Failure to control for all relevant confounders may bias results in outcome studies in favour of BCS.

Estimating the Product Lifecycle Value of Trastuzumab Based on Registry Data in Sweden.

Trastuzumab was introduced in Sweden in 2000 for treatment of HER2-positive metastatic breast cancer (MBC) and later expanded to early breast cancer (EBC). The potential value of this innovative therapy was explored in economic evaluations; however, the extent to which these benefits were realised remains unknown. This study aims to estimate the lifecycle value of trastuzumab by combining randomised trial data with Swedish routine-care data. Trastuzumab impact on costs and health outcomes was estimated with Markov models for MBC and EBC. Model inputs included progression/recurrence and breast cancer-related mortality data from international randomised clinical trials, and Sweden-specific non-breast cancer-related mortality, numbers treated, and costs and utilities based on data from National Registries and literature. Model predictions were validated by observed survival rates from the National Breast Cancer Registry. From 2000 to 2021, 3936 and 11,134 patients with HER2-positive MBC and EBC, respectively, were treated with trastuzumab, resulting in 25,844 life years and 13,436per quality-adjusted life years (QALY) gained. Cost per QALY gained was lower in EBC (Swedish krona [SEK]285,000/QALY) than MBC (SEK554,000/QALY). The net-monetary value delivered (excluding drug costs) was SEK 13.714 billion, and society retained 62% of this. The modelled survival in trastuzumab-treated patients with EBC matched closely with actually observed survival in registry data. Trastuzumab provided substantial population-level health benefits for patients and society, with favourable cost effectiveness in MBC and EBC. There is some uncertainty around the magnitude of these benefits, mainly due to missing data on health outcomes and number of treated patients with MBC.

Abstract P5-01-08: Steps toward noninvasive lymph node staging (NILS) in clinically node negative patients: Artificial neural network model to preoperatively predict lymphovascular invasion

Abstract Background: Lymphovascular invasion (LVI) is one of the most important predictors for nodal status in breast cancer patients [1]. Multiple models have been published for prediction of preoperatively disease-free axillary using i.a. LVI [1-2]. However, LVI detection in preoperative core needle biopsy has been reported with a failure rate of 30% [3] and the analysis is not routinely performed in Sweden. Thus, a preoperative model of LVI status would be useful in prediction models for noninvasive lymph node staging (NILS). The purpose of this study was to develop an artificial neural network (ANN) model for LVI prediction using only clinicopathological variables that are routinely available in the preoperative setting. Methods: Data gathered prospectively during 2009-2012 in Lund, Sweden from 761 clinically node negative breast cancer patients were retrospectively extracted. Inclusion criteria were female sex, primary breast cancer and that each patient was scheduled for primary surgery. Patients with metastatic disease, bilateral cancer, tumor size greater than 50 mm, previous ipsilateral breast or axillary surgery, patients omitted of standard axillary staging procedure by SLNB or ALND, and those who had neoadjuvant treatment were excluded. LVI was assessed on surgical breast specimens and was defined as the presence of tumor cells within endothelium-lined vascular channels. Out of the 761 patients in the cohort, 613 patients were documented with LVI status. The LVI full case dataset was split 80/20 for training and validation. The remaining 148 patients were set aside for model testing. Since the test dataset did not contain information on LVI status, it was used to compare the predicted fraction of LVI positive patients to that of the development dataset. Only variables possible to obtain in the preoperative setting were included in the prediction models, comprising age, menopausal status, mode of detection (mammography screening or symptomatic representation), tumor size, multifocality (yes/no), histopathological type, histological grade, ki-67 percentage, estrogen receptor status, progesterone receptor status, and human epidermal growth factor receptor 2 status. An ensemble approach was used, where each ensemble constituted 30 ANNs that were trained and validated using 5-fold cross validation. For every ensemble model, different model parameters, such as L2-regularization and the number of hidden nodes, were tested. Model selection was based on validation AUC. Results: The study cohort included female clinically node negative breast cancer patients scheduled for primary surgery. Data from 613 patients (lymph node stages N0: 67.4%, N1: 26.9%, N2+: 5.7%) were used to develop the model, and 148 patients (N0: 56.8%, N1: 35.8%, N2+: 7.4%) constituted the internal test cohort. Fifteen percentage of the patients in the development dataset were LVI positive. The selected ensemble model achieved a validation AUC of 0.80 (CI 0.75-0.85). This model predicted an LVI positive rate of 16.2% in the test dataset. Conclusion: LVI was predicted with high accuracy using an ANN model based on routine preoperative clinicopathological variables. The result of validation AUC 0.80 (CI 0.75-0.85) indicates a potential for preoperative prediction of LVI, and the model can putatively be useful when applying preoperative nodal prediction models in patients without known LVI status. To confirm these results, verification in an external dataset is needed. Validation of the LVI-model in an independent dataset from the National Breast Cancer Registry will be performed, as well as an evaluation of the usefulness of the LVI-model as an imputation in a nodal prediction model. [1] Dihge, L. et al. BMC Cancer (2019). PMID: 31226956 [2] Bevilacqua, J. L. et al. J Clin Oncol. (2007). PMID: 17664461 [3] Harris, G. C. et al. Am J Surg Pathol. (2003). PMID: 12502923 Citation Format: Malin Hjärtström, Looket Dihge, Pär-Ola Bendahl, Mattias Ohlsson, Lisa Rydén. Steps toward noninvasive lymph node staging (NILS) in clinically node negative patients: Artificial neural network model to preoperatively predict lymphovascular invasion [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-01-08.

Association of diabetes and breast cancer characteristics at diagnosis.

This study aims to examine the association of diabetes and breast cancer characteristics at diagnosis in Aotearoa/New Zealand. Patients diagnosed with invasive breast cancer between 2005 and 2020 were identified from the National Breast Cancer Register. Logistic regression modeling was used to estimate the adjusted odds ratio (OR) of having stage III-IV cancer and the OR of having stage IV cancer for women with diabetes compared to those without diabetes. The adjusted OR of having screen-detected breast cancers for patients aged 45-69years with diabetes compared to patients without diabetes was estimated. 26,968 women were diagnosed with breast cancer, with 3,137 (11.6%) patients having diabetes at the time of cancer diagnosis. The probability of co-occurrence of diabetes and breast cancer increased with time. Māori, Pacific and Asian women were more likely to have diabetes than European/Others. The probability of having diabetes also increased with age. For patients with diabetes, the probability of being diagnosed with stage III-IV cancer and stage IV cancer was higher than for patients without diabetes (OR 1.14, 95% CI 1.03-1.27; and 1.17, 95% CI 1.00-1.38). Women aged 45-69years with diabetes were more likely to have screen-detected cancer than those without diabetes (OR 1.13, 95% CI 1.02-1.26). The co-occurrence of diabetes and breast cancer is becoming more common. Overall there is a small but significant adverse impact of having advanced disease for women with diabetes that is found at the time of breast cancer diagnosis, and this may contribute to other inequities that occur in the treatment pathway that may impact on patient outcomes.

What affects the public healthcare costs of breast cancer in New Zealand?

The pressure to the healthcare system for providing ongoing monitoring and treatment for breast cancer survivors is increasing. This study aims to identify the factors that affect the public healthcare costs of stage I-III breast cancer and stage IV cancer in New Zealand. We identified women diagnosed with invasive breast cancer between July 1, 2010 and June 30, 2018 and who received services in a public hospital. Patients were identified from the National Breast Cancer Register and/or New Zealand Cancer Registry and were linked to the national administrative datasets. A two-part model was used to identify the factors that affect the public healthcare costs of stage I-III breast cancer and stage IV cancer. We identified 16,977 stage I-III and 1,093 stage IV breast cancer patients eligible for this study. The costs of stage I-III cancer in the second to fifth year post diagnosis decreased over time, and the costs of stage IV cancer in the first year post diagnosis increased over time. After adjustment for other factors, the costs of stage I-IV cancer decreased with age but increased with cancer stage. HER2+ cancers had the highest costs, followed by triple negative cancers. After adjustment for other factors, Pacific and Asian women had lower costs, and Māori had similar costs compared to others. For stage I-III cancers, women living in nonmajor urban areas had a higher chance of incurring costs in follow-up years, and screen detected patients and patients having any services in a private hospital had a decreased probability of receiving any public healthcare services. Pacific women had higher costs than others, but after adjustment for cancer stage, subtype, and other factors, they had lower costs than others. The early detection and better management of stage I-III breast cancer can lead to better outcome and lower costs in follow-up years.

Differences in Breast Cancer Costs by Cancer Stage and Biomarker Subtype in New Zealand.

BackgroundBreast cancer requires the greatest expenditure among all cancer types, and the costs vary by cancer stage and biomarker status.ObjectiveThis study aimed to examine the differences in public healthcare costs of breast cancer in New Zealand by stage and subtype.MethodThis study included patients diagnosed with invasive breast cancer between 1 July 2010 and 30 June 2018 and receiving services in public hospitals. These patients were identified from the National Breast Cancer Register and/or New Zealand Cancer Registry. Linking with the Pharmaceutical Collection, National Minimum Dataset, National Non-Admitted Patient Collection, and Mortality Collection, we estimated the median public healthcare costs of breast cancer by cancer stage and biomarker subtype.ResultsWe identified 22,948 eligible patients. The median costs of breast cancer increased with stage of disease, from $NZ26,930 for stage I disease to $NZ50,388 for stage IV disease. The median costs for human epidermal growth factor receptor 2-positive (HER2+) disease were three times those for HER2-negative (HER2−) disease: $NZ106,428 for HER2+ cancers compared with$NZ28,481 for oestrogen receptor-positive (ER+)/HER2− cancers and $NZ31,722 for triple negative disease. Over 55% of the costs for HER2+ breast cancers were targeted therapy costs. For HER2− cancers, surgery incurred the biggest cost, followed by radiotherapy.ConclusionsTreating patients with early-stage breast cancer is less costly than treating those with metastatic disease. The costs vary considerably between the subtypes. Patients with HER2+ cancer incurred three times the costs of those with HER2− cancers. These results provide baseline costing data for clinicians and policy makers when considering new targeted treatments.Supplementary InformationThe online version contains supplementary material available at 10.1007/s41669-022-00327-5.

Abstract P3-20-02: The association of clinicopathological variables and patient´s preference with surgical decision-making for early breast cancer

Abstract Background: Mastectomy (Mx) and breast conserving surgery (BCS) when combined with adjuvant whole breast radiotherapy (RT) have been shown to give equivalent outcome in randomized trials . In recent years, a number of retrospective population-based studies suggest that BCS offers superior survival compared to Mx. In these studies, treatment has not been randomized, but selected based on patient and tumour characteristics or patient´s own choice. The aim of this study was to compare clinicopathological variables in women with tumours less than 30mm in size treated with either BCS or Mx, where both surgical methods would have been feasible based on postoperatively recorded tumour characteristics. Our second aim was to explore the underlying reason for choosing Mx as surgical approach. Method: The study is a population-based retrospective analysis of prospectively collected data from the Swedish National Breast Cancer Register (NBCR). The source population are women registered with primary invasive breast cancer with a tumour size up to 30 mm and no more than four positive axillary lymph nodes, treated between 2013-2016 in the northern health care region in Sweden. During this time period, the reason for selecting Mx was registered in this region with five optional alternatives: 1.Age &amp;lt; 40 years, 2.Large tumour size/extent relative breast volume, 3.Multifocality/multicentricity, 4.RT contraindicated due to comorbidity and 5.Patient´s own choice. All cases with male breast cancer and patients treated with neoadjuvant therapy were excluded.Logistic regression analyses were performed to assess the association of tumour and patient characteristics with receiving a mastectomy shown as odds ratios with 95% confidence intervals (CI). Results: A total of 1860 women met our inclusion criteria, 1346 of which had undergone BCS (mean age 63) and 514 Mx (mean age 66). For 1309 women (97.1%) in the BCS group and 146 (27.6%) in the Mx group adjuvant RT was added to the breast, chest wall and/or ipsilateral regional lymph nodes after surgery. Clinical detection, OR 3.35 (95%CI 3.32-5.14), higher T stage OR 2.66 (2.00-3.54), N stage OR 1.84 (1.46-2.32) and multifocality, OR 4.59 (3.56-5.92) were associated with a higher likelihood of receiving Mx. Women treated with Mx had more lobular tumours, OR 1.42 (1.05-1.92), higher grade, OR 2.27 (1.65-3.13), more hormone receptor negative, 1.47 (1.09-1.98) and HER2 positive tumours, OR 1.61 (1.19-2.17) compared to women treated with BCS.The most common reason for choosing Mx was large tumour size and/or multifocality (52.8%). The second most common reason was the woman´s own preference (36.6%). In 9 % of the cases RT was considered contraindicated, hence Mx was recommended by the treating surgeon or tumour board. Conclusion: Women with invasive breast cancer up to 30mm selected for treatment with Mx have less favourable prognostic characteristics than those treated with BCS. Selection bias may largely explain the survival benefits of BCS compared to Mx demonstrated in observational studies. Table 1: Distribution of factors listed as reason of mastectomy as surgical treatment. Table based on a a total of 431 mastectomy cases where reason for Mx were listed. RT = Radiotherapy No. of patients%Age &amp;lt; 40 years61.4large tumour size/extent relative breast volume13531.3Multifocality/multicentricity9321.5RT contraindicated due to comorbidity399.0Patients own choice15836.6 Citation Format: Emma Söderberg, Malin Sund, Fredrik Wärnberg, Lars Holmberg, Greger Nilsson, Hans Garmo, Carl Blomqvist, Charlotta Wadsten. The association of clinicopathological variables and patient´s preference with surgical decision-making for early breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-20-02.

Abstract P3-18-03: Long-term outcomes for breast conservation plus radiotherapy versus mastectomy in early breast cancer after neoadjuvant systemic therapy: Results from the Swedish national breast cancer register (NKBC)

Abstract Background: Population-based studies have consistently shown improved long-term outcomes with breast conserving surgery (BCS) plus radiotherapy (RT) vs. mastectomy in primarily operated breast cancer (BC) patients. However, the survival impact of type of local therapy following modern neoadjuvant systemic therapy (NST) is unclear. Methods: The population-based Swedish National Breast Cancer Register (NKBC), a prospectively collected population-based cohort, was used to identify female BC patients who were diagnosed from January, 2007 until December, 2017 and received NST in the Stockholm region. Patients were divided into BCS+RT and mastectomy groups, and the prognostic factors reflecting the response to NST like pathologic complete response (pCR) and Neo-bioscore calculated by pre/postoperative TNM stage, nuclear grade, and receptors status, were used for stratification. Disease-free survival (DFS), locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS) and overall survival (OS) were evaluated using inverse probability of treatment weighted (IPTW) Cox proportional hazards model, which enables covariates like age, St Gallen subtypes, cTNM and ypTNM stages to be balanced between the two groups. Results: Among 1,409 eligible women, 456 (32.4%) were treated with BCS+RT, and 953 (67.6%) with mastectomy. Overall, 87 (6.2%) local recurrences, 256 (18.2%) distant metastases, and 282 (20.0%) deaths occurred over a median follow-up of 61 months. Patients diagnosed during later years, younger patients, patients with earlier stage and higher-grade tumors were more likely to receive BCS+RT. After adjusting for age at diagnosis, Neo-bioscore, adjuvant chemotherapy and radiotherapy, significant improvements for BCS+RT compared with mastectomy were observed in DFS (weighted-multivariate hazard ratio (HR), 0.51; 95%CI, 0.28-0.93; median 5-year DFS: 79.1% vs 73.6%) and DMFS (HR, 0.44; 95%CI, 0.23-0.82; median 5-year DMFS: 83.7% vs 74.8%), but no difference was identified in LRFS (HR, 0.94; 95%CI, 0.29-3.07; median 5-year LRFS: 89.9% vs 92.0%) or OS (HR, 0.7; 95%CI, 0.34-1.45; median 5-year OS: 88.4% vs 81.2%). The DFS benefit was observed regardless of pCR status, but varied by Neo-bioscore. Patients with Neo-bioscore 4-7 treated with BCS+RT had better DFS (HR, 0.31; 95%CI, 0.12-0.81) compared with those undergoing mastectomy, whereas low-risk patients with Neo-bioscore 0-3 had similar DFS between the two groups. Both triple negative (N=252; HR for DFS, 0.26; 95%CI, 0.07-0.97) and HER2-positive (N=533; HR for DFS, 0.24, 95%CI, 0.09-0.68) BC patients benefited from BCS+RT, but not patients with luminal tumors (N=589; HR for DFS, 0.82, 95%CI, 0.31-2.18). Similarly, superior DFS with BCS+RT was also seen in patients with neoadjuvant anti-HER2 targeted therapy (N=505; HR, 0.19; 95%CI, 0.05-0.75) or neoadjuvant chemotherapy alone (N=594; HR, 0.47; 95%CI, 0.21-1.06), but not among those receiving neoadjuvant endocrine therapy (N=162; HR, 0.53; 95%CI, 0. 1-2.85). Conclusion: After adjusting for response to NST and other confounders, BCS+RT was associated with reduced risks of tumor recurrence or metastasis compared with mastectomy. This benefit was more pronounced in patients with high Neo-bioscore, indicating that Neo-bioscore rather than pCR status has the potential to tailor breast surgery after NST. Further studies with larger sample size or prospective randomized clinical trials are warranted to confirm our findings. Citation Format: Kang Wang, Aafke Duinmeijer, Alexios Matikas, Renske Altena, Hemming Johansson, Hanna Fredholm, Theodoros Foukakis. Long-term outcomes for breast conservation plus radiotherapy versus mastectomy in early breast cancer after neoadjuvant systemic therapy: Results from the Swedish national breast cancer register (NKBC) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-18-03.

Age-Dependent Heterogeneity of Lymph Node Metastases and Survival Identified by Analysis of a National Breast Cancer Registry.

Background:For several cancers, including those of the breast, young age at diagnosis is associated with an adverse prognosis. Although this effect is often attributed to heritable mutations such as BRCA1/2, the relationship between pathologic features, young age of onset, and prognosis for breast cancer remains unclear. In the present study, we highlight links between age of onset and lymph node metastasis (NM) in US women with breast cancer.Methods:Case listings from Surveillance, Epidemiology, and End Result (SEER) 18 registry data for women with breast cancer, which include information on race, were used. NM and its associated outcomes were evaluated for a subset of women with receptor subtype information and then compared against a larger, pre-subtype validation set of data from the same registry. Age of diagnosis was a 5-category variable; under 40 years, 40–49 years, 50–59 years, 60–69 years and 70+ years. Univariate and adjusted multivariate survival models were applied to both sets of data.Results:As determined with adjusted logistic regression models, women under 40 years old at diagnosis had 1.55 times the odds of NM as women 60–69 years of age. The odds of NM for (HR = hormone receptor) HR+/HER2+, HR-/HER2+, and triple-negative breast cancer subtypes were significantly lower than those for HR+/HER2-. In subtype-stratified adjusted models, age of diagnosis had a consistent trend of decreasing odds of NM by age category, most noticeable for HR+ subtypes of luminal A and B. Univariate 5-year survival by age was worst for women under 40 years, with NM attributable for 49% of the hazard of death from cancer in adjusted multivariate models.Conclusions:Lymph node metastasis is age-dependent, yet not all molecular subtypes are clearly affected by this relationship. For <40-yr-old women, NM is a major cause for shorter survival. When stratified by subtype, the strongest associations were in HR+ groups, suggesting a possible hormonal connection between young age of breast cancer onset and NM.

Trends in adjuvant therapy after breast-conserving surgery for ductal carcinoma in situ of breast: a retrospective cohort study using the National Breast Cancer Registry of Japan.

Radiotherapy (RT) and endocrine therapy (ET) are standard treatment options after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS). We investigated the national patterns of adjuvant therapy use after BCS for DCIS in Japan. We obtained relevant data of patients diagnosed with DCIS undergoing surgery and treated with BCS between 2014 and 2016 from the Japanese Breast Cancer Registry database. The relationship between the clinicopathologic, institutional, and regional factors, and adjuvant treatment was examined using multivariable analyses. We identified 9516 patients who underwent BCS for DCIS. Overall, 23% received no adjuvant treatment, 71% received RT, 32% received ET, and 26% received combination therapy. The percentages of patients who received ET and combination therapy in 2016 were significantly lower [odds ratio (OR): 0.71, 0.77, respectively] than in 2014. The proportion of RT was low among young or elderly patients (OR: 0.75, 0.44, respectively) and in non-certified facilities (OR: 0.56). The proportion of ET was high in non-certified facilities (OR: 1.58) and among patients with positive margins (OR: 1.62). Combination therapy was higher among patients with positive margins (OR: 1.53). Our study found a distinct adjuvant treatment pattern after BCS for DCIS depending on clinicopathologic factors, year, age, which indicate that physicians provide individualized treatment according to the background of the patients and the biology of DCIS. The facilities and regions remain significant factors of influencing adjuvant treatment pattern.

St Gallen 2019 guidelines understage the axilla in lobular breast cancer: a population-based study.

The St Gallen 2019 guidelines for primary therapy of early breast cancer recommend omission of completion axillary lymph node dissection (cALND), regardless of histological type, in patients with one or two sentinel lymph node (SLN) metastases. Concurrently, adjuvant chemotherapy is endorsed for luminal A-like disease with four or more axillary lymph node (ALN) metastases. The aim of this study was to estimate the proportion of patients with invasive lobular cancer (ILC) versus invasive ductal cancer of no special type (NST) with one or two SLN metastases for whom cALND would have led to a recommendation for adjuvant chemotherapy. Patients with ILC and NST who had surgery between 2014 and 2017 were identified in the National Breast Cancer Register of Sweden. After exclusion of patients with incongruent or missing data, those who fulfilled the St Gallen 2019 criteria for cALND omission were included in the population-based study cohort. Some 1886 patients in total were included in the study, 329 with ILC and 1507 with NST. Patients with ILC had a higher metastatic nodal burden and were more likely to have a luminal A-like subtype than those with NST. The prevalence of at least four ALN metastases was higher in ILC (31.0 per cent) than NST (14.9 per cent), corresponding to an adjusted odds ratio of 2.26 (95 per cent c.i. 1.59 to 3.21). Luminal A-like breast cancers with four or more ALN metastases were over-represented in ILC compared with NST, 52 of 281 (18.5 per cent) versus 43 of 1299 (3.3 per cent) (P < 0.001). Patients with ILC more often have luminal A-like breast cancer with at least four nodal metastases. Omission of cALND in patients with luminal A-like invasive lobular cancer and one or two SLN metastases warrants future attention as there is a risk of nodal understaging and undertreatment in one-fifth of patients.

Bahcesehir long-term population-based screening compared to National Breast Cancer Registry Data: effectiveness of screening in an emerging country.

We aimed to show the effects of long-term screening on clinical, pathologic, and survival outcomes in patients with screen-detected breast cancer and compare these findings with breast cancer patients registered in the National Breast Cancer Registry Data (NBCRD). Women aged 40-69 years, living in Bahcesehir county, Istanbul, Turkey, were screened every 2 years using bilateral mammography. The Bahcesehir National Breast Cancer Registry Data (BMSP) data were collected during a 10-year screening period (five rounds of screening). BMSP data were compared with the NBCRD regarding age, cancer stage, types of surgery, tumor size, lymph node status, molecular subtypes, and survival rates. During the 10-year screening period, 8758 women were screened with 22621 mammograms. Breast cancer was detected in 130 patients; 51 (39.2%) were aged 40-49 years. The comparison of breast cancer patients in the two programs revealed that BMSP patients had earlier stages, higher breast-conserving surgery rates, smaller tumor size, more frequent negative axillary nodal status, lower histologic grade, and higher ductal carcinoma in situ rates than NBCRD patients (p = 0.001, for all). These results indicate the feasibility of successful population-based screening in middle-income countries.

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

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

Gonadotrophin stimulation and risk of relapse in breast cancer.

STUDY QUESTIONIs gonadotrophin stimulation as part of IVF associated with an increased risk of relapse in breast cancer?SUMMARY ANSWERControlled ovarian stimulation (COS) in connection with IVF in women with previous breast cancer was not associated with an increased risk of breast cancer relapse.WHAT IS KNOWN ALREADYBreast cancer is the most common malignancy among women worldwide and the leading cause of cancer death among females. The use of COS with gonadotrophins with subsequent cryopreservation of oocytes or embryos in order to enhance the chances of pregnancy after cancer treatment is the current most established fertility preservation method for women with breast cancer. To date, there are only a few small retrospective hospital-based controlled studies evaluating the risk of breast cancer relapse in patients undergoing fertility preservation with or without COS, showing no evident risk of relapse in breast cancer after the use of gonadotoxic agents.STUDY DESIGN, SIZE, DURATIONThis was a retrospective, population-based cohort study comprising 5857 women with previous breast cancer of whom 337 were exposed to COS. Exposure (COS) and outcomes (relapse and death) were identified for all patients from 2005 to 2014 by assessing the National Quality Register for Assisted Reproduction, the Swedish Medical Birth Register, the National Patient Register, the Swedish Prescribed Drug Register, the Swedish Cause of Death Register, the National Breast Cancer Register and the Swedish Cancer Register. Matching according to set criteria was possible for 334 women, who constituted the control group. A total of 274 women had undergone IVF after completing breast cancer treatment and 63 women had undergone COS for fertility preservation at the time of breast cancer diagnosis.PARTICIPANTS/MATERIALS, SETTING, METHODSWomen aged 20–44 years previously diagnosed with breast cancer and exposed to COS were matched for age at breast cancer diagnosis ±5 years, tumour size and lymph node involvement with a non-exposed control group, including women with known T- and N-stages. In a subsequent analysis, the matched cohort was assessed by also including women with unknown T- and N-stages. A secondary analysis comprised the entire non-matched cohort, including all women with known T- and N-stages. Also here, a subsequent analysis included women with missing data for T- and N-stages. The risk of relapse in breast cancer was estimated as crude hazard ratios (HRs) and 95% CI using Cox proportional hazards models in the primary and secondary analyses where T- and N-stages were known: otherwise the risks of relapse were only given descriptively.MAIN RESULTS AND THE ROLE OF CHANCEIn the primary matched analysis, relapse occurred in 20 of 126 women exposed to COS (15.9%) compared with 39 of 126 (31.0%) in the control cohort (HR = 0.70; 95% CI 0.39–1.45; P = 0.22). In the subsequent analysis, also including women with unknown T- and N-stages, relapse occurred in 27 of 337 (8.0%) women having undergone COS compared with 71/334 (21.3%) among the non-exposed. In the secondary adjusted analysis, relapse occurred in 20 of 126 (15.9%) exposed women and in 918 of 3729 (24.6%) non-exposed women (HR = 0.81; 95% CI 0.49–1.33; P = 0.70). In the subsequent analysis, including unknown T- and N-stages, relapse occurred in 27 of 337 (8.0%) women in the exposed group and 1176 of 5520 (21.3%) in the non-exposed cohort.LIMITATIONS, REASONS FOR CAUTIONA substantial degree of missing data on important prognostic variables was a limitation, particularly when analysing the total cohort. Furthermore, data on confounding factors, such as BMI, were not completely covered. Another limitation was that a pre-specified variable for relapse was not in use for the majority of the National Breast Cancer Register. Furthermore, the follow-up time from available register data (2005–2014) is rather short. Finally, we cannot be sure whether the prognostic information from receptor status, showing a lower incidence in the exposed group, is representative. Information on T- and N-stages was missing in more than half of the patients.WIDER IMPLICATIONS OF THE FINDINGSIn this large, retrospective, matched cohort study, we found no increased risk of relapse in breast cancer among women who had been exposed to gonadotrophins as part of IVF. This is reassuring but might be confounded by the selection of a group of women with a more favourable prognosis than those not undergoing IVF. The present study strengthens previous findings by being large, national and register based. Its results are applicable to women undergoing fertility preservation as well as to those undergoing regular IVF treatment.STUDY FUNDING/COMPETING INTEREST(S)Supported in part by grants from the Swedish state under the agreement between the Swedish government and the county councils the ALF-agreement (ALFGBG-720291), The Assar Gabrielsson Fund (FB 15-20), The Breast Cancer Fund and the Swedish Association of Local authorities and Regions, SKR. There are no conflicts of interest to declare.TRIAL REGISTRATIONN/A