The effects of contemporary treatment of DCIS on the risk of developing an ipsilateral invasive Breast cancer (iIBC) in the Dutch population.

PURPOSE: To assess the effects of contemporary treatment of ductal carcinoma in situ (DCIS) on the risk of developing an ipsilateral invasive breast cancer (iIBC) in the Dutch female population. METHODS: Clinical data was obtained from the Netherlands Cancer Registry (NCR), a nationwide registry of all primary malignancies in the Netherlands integrated with the data from PALGA, the Dutch nationwide network and registry of histo- and cytopathology in the Netherlands, on all women in the Netherlands treated for primary DCIS from 2005 to 2015, resulting in a population-based cohort of 14.419 women. Cumulative iIBC incidence was assessed and associations of DCIS treatment type with subsequent iIBC risk were evaluated by multivariable Cox regression analyses. RESULTS: Ten years after DCIS diagnosis, the cumulative incidence of iIBC was 3.1% (95% CI: 2.6-3.5%) in patients treated by breast conserving surgery (BCS) plus radiotherapy (RT), 7.1% (95% CI: 5.5-9.1) in patients treated by BCS alone, and 1.6% (95% CI: 1.3-2.1) in patients treated by mastectomy. BCS was associated with a significantly higher risk for iIBC compared to BCS + RT during the first 5 years after treatment (HR 2.80, 95% CI: 1.91-4.10%). After 5 years of follow-up, the iIBC risk declined in the BCS alone group but remained higher than the iIBC risk in the BCS + RT group (HR 1.73, 95% CI: 1.15-2.61). CONCLUSIONS: Although absolute risks of iIBC were low in patients treated for DCIS with either BCS or BCS + RT, risks remained higher in the BCS alone group compared to patients treated with BCS + RT for at least 10 years after DCIS diagnosis.

Active surveillance versus treatment in low-risk DCIS: Women's preferences in the LORD-trial.

BACKGROUND: Ductal carcinoma in situ (DCIS) can progress to invasive breast cancer (IBC), but most DCIS lesions remain indolent. However, guidelines recommend surgery, often supplemented by radiotherapy. This implies overtreatment of indolent DCIS. The non-randomised patient preference LORD-trial tests whether active surveillance (AS) for low-risk DCIS is safe, by giving women with low-risk DCIS a choice between AS and conventional treatment (CT). Here, we aim to describe how participants are distributed among both trial arms, identify their motives for their preference, and assess factors associated with their choice. METHODS: Data were extracted from baseline questionnaires. Descriptive statistics were used to assess the distribution and characteristics of participants; thematic analyses to extract self-reported reasons for the choice of trial arm, and multivariable logistic regression analyses to investigate associations between patient characteristics and chosen trial arm. RESULTS: Of 377 women included, 76% chose AS and 24% CT. Most frequently cited reasons for AS were "treatment is not (yet) necessary" (59%) and trust in the AS-plan (39%). Reasons for CT were cancer worry (51%) and perceived certainty (29%). Women opting for AS more often had lower educational levels (OR 0.45; 95% confidence interval [CI], 0.22-0.93) and more often reported experiencing shared decision making (OR 2.71; 95% CI, 1.37-5.37) than women choosing CT. CONCLUSION: The LORD-trial is the first to offer women with low-risk DCIS a choice between CT and AS. Most women opted for AS and reported high levels of trust in the safety of AS. Their preferences highlight the necessity to establish the safety of AS for low-risk DCIS.

Association of DCIS size and margin status with risk of developing breast cancer post-treatment: multinational, pooled cohort study.

OBJECTIVE: To examine the association between size and margin status of ductal carcinoma in situ (DCIS) and risk of developing ipsilateral invasive breast cancer and ipsilateral DCIS after treatment, and stage and subtype of ipsilateral invasive breast cancer. DESIGN: Multinational, pooled cohort study. SETTING: Four large international cohorts. PARTICIPANTS: Patient level data on 47 695 women with a diagnosis of pure, primary DCIS between 1999 and 2017 in the Netherlands, UK, and US who underwent surgery, either breast conserving or mastectomy, often followed by radiotherapy or endocrine treatment, or both. MAIN OUTCOME MEASURES: The main outcomes were 10 year cumulative incidence of ipsilateral invasive breast cancer and ipsilateral DCIS estimated in relation to DCIS size and margin status, and adjusted hazard ratios and 95% confidence intervals, estimated using multivariable Cox proportional hazards analyses with multiple imputed data RESULTS: The 10 year cumulative incidence of ipsilateral invasive breast cancer was 3.2%. In women who underwent breast conserving surgery with or without radiotherapy, only adjusted risks for ipsilateral DCIS were significantly increased for larger DCIS (20-49 mm) compared with DCIS <20 mm (hazard ratio 1.38, 95% confidence interval 1.11 to 1.72). Risks for both ipsilateral invasive breast cancer and ipsilateral DCIS were significantly higher with involved compared with clear margins (invasive breast cancer 1.40, 1.07 to 1.83; DCIS 1.39, 1.04 to 1.87). Use of adjuvant endocrine treatment was not significantly associated with a lower risk of ipsilateral invasive breast cancer compared to treatment with breast conserving surgery only (0.86, 0.62 to 1.21). In women who received breast conserving treatment with or without radiotherapy, higher DCIS grade was not significantly associated with ipsilateral invasive breast cancer, only with a higher risk of ipsilateral DCIS (grade 1: 1.42, 1.08 to 1.87; grade 3: 2.17, 1.66 to 2.83). Higher age at diagnosis was associated with lower risk (per year) of ipsilateral DCIS (0.98, 0.97 to 0.99) but not ipsilateral invasive breast cancer (1.00, 0.99 to 1.00). Women with large DCIS (≥50 mm) more often developed stage III and IV ipsilateral invasive breast cancer compared to women with DCIS <20 mm. No such association was found between involved margins and higher stage of ipsilateral invasive breast cancer. Associations between larger DCIS and hormone receptor negative and human epidermal growth factor receptor 2 positive ipsilateral invasive breast cancer and involved margins and hormone receptor negative ipsilateral invasive breast cancer were found. CONCLUSIONS: The association of DCIS size and margin status with ipsilateral invasive breast cancer and ipsilateral DCIS was small. When these two factors were added to other known risk factors in multivariable models, clinicopathological risk factors alone were found to be limited in discriminating between low and high risk DCIS.

Prediction Models and Decision Aids for Women with Ductal Carcinoma In Situ: A Systematic Literature Review.

Even though Ductal Carcinoma in Situ (DCIS) can potentially be an invasive breast cancer (IBC) precursor, most DCIS lesions never will progress to IBC if left untreated. Because we cannot predict yet which DCIS lesions will and which will not progress, almost all women with DCIS are treated by breast-conserving surgery +/- radiotherapy, or even mastectomy. As a consequence, many women with non-progressive DCIS carry the burden of intensive treatment without any benefit. Multiple decision support tools have been developed to optimize DCIS management, aiming to find the balance between over- and undertreatment. In this systematic review, we evaluated the quality and added value of such tools. A systematic literature search was performed in Medline(ovid), Embase(ovid), Scopus and TRIP. Following the PRISMA guidelines, publications were selected. The CHARMS (prediction models) or IPDAS (decision aids) checklist were used to evaluate the tools' methodological quality. Thirty-three publications describing four decision aids and six prediction models were included. The decision aids met at least 50% of the IPDAS criteria. However, most lacked tools to facilitate discussion of the information with healthcare providers. Five prediction models quantify the risk of an ipsilateral breast event after a primary DCIS, one estimates the risk of contralateral breast cancer, and none included active surveillance. Good quality and external validations were lacking for all prediction models. There remains an unmet clinical need for well-validated, good-quality DCIS risk prediction models and decision aids in which active surveillance is included as a management option for low-risk DCIS.

Healthcare Use during the Last Six Months of Life in Patients with Advanced Breast Cancer.

New treatment options in cancer have resulted in increased use of health care resources near the end of life. We assessed health care use near the end of life of patients with advanced breast cancer (ABC). From the Southeast Netherlands Breast cancer (SONABRE) registry, we selected all deceased patients diagnosed with ABC in Maastricht University Medical Center between January 2007 and October 2017. Frequency of health care use in the last six months of life was described and predictors for health care use were assessed. Of 203 patients, 76% were admitted during the last six months, 6% to the intensive care unit (ICU) and 2% underwent cardiopulmonary resuscitation (CPR). Death in hospital occurred in 25%. Nine percent of patients received a new line of chemotherapy ≤30 days before death, which was associated with age <65 years and <1 year survival since diagnosis of metastases. In these patients, the hospital admission rate was 95%, of which 79% died in the hospital, mostly due to progressive disease (80%). In conclusion, the frequency of ICU-admission, CPR or a new line of chemotherapy ≤30 days before death was low. Most patients receiving a new line of chemotherapy ≤30 days before death, died in the hospital.

Preferences of Treatment Strategies among Women with Low-Risk DCIS and Oncologists.

As ongoing trials study the safety of an active surveillance strategy for low-risk ductal carcinoma in situ (DCIS), there is a need to explain why particular choices regarding treatment strategies are made by eligible women as well as their oncologists, what factors enter the decision process, and how much each factor affects their choice. To measure preferences for treatment and surveillance strategies, women with newly-diagnosed, primary low-risk DCIS enrolled in the Dutch CONTROL DCIS Registration and LORD trial, and oncologists participating in the Dutch Health Professionals Study were invited to complete a discrete choice experiment (DCE). The relative importance of treatment strategy-related attributes (locoregional intervention, 10-year risk of ipsilateral invasive breast cancer (iIBC), and follow-up interval) were discerned using conditional logit models. A total of n = 172 patients and n = 30 oncologists completed the DCE. Patient respondents had very strong preferences for an active surveillance strategy with no surgery, irrespective of the 10-year risk of iIBC. Extensiveness of the locoregional treatment was consistently shown to be an important factor for patients and oncologists in deciding upon treatment strategies. Risk of iIBC was least important to patients and most important to oncologists. There was a stronger inclination toward a twice-yearly follow-up for both groups compared to annual follow-up.