Omitting re-excision for focally positive margins after breast-conserving surgery does not impair disease-free and overall survival

Purpose: In contrast to other countries, the Dutch breast cancer guideline does not recommend re-excision for focally positive margins after breast-conserving surgery (BCS) in invasive tumor and does recommend whole-breast irradiation including boost. We investigated whether omitting re-excision as compared to performing re-excision affects prognosis with a retrospective population-based cohort study. Methods: The total cohort included 32,119 women with primary BCS for T1–T3 breast cancer diagnosed between 2003 and 2008 from the nationwide Netherlands cancer registry. The subcohort included 10,433 patients in whom the resection margins were registered. Outcome measures were 5-year ipsilateral breast tumor recurrence (IBTR) rate, 5-year disease-free survival (DFS) rate, and 10-year overall survival (OS) rate. Results: In the total cohort, 25,878 (80.6%) did not have re-excision, 2368 (7.4%) had re-excision by BCS, and 3873 (12.1%) had re-excision by mastectomy. Five-year IBTR rates were 2.1, 2.8, and 2.9%, respectively (p = 0.001). In the subcohort, 7820 (75.0%) had negative margins without re-excision, 492 (4.7%) had focally positive margins without re-excision, 586 (5.6%) had focally positive margins and underwent re-excision, and 1535 (14.7%) had extensively positive margins and underwent re-excision. Five-year IBTR rate was 2.3, 2.9, 1.1, and 2.9%, respectively (p = 0.099). Compared to omitting re-excision, performing re-excision for focally positive margins was associated with lower risk of IBTR (adjusted HR 0.30, 95% CI 0.11–0.82), but not with DFS (adjusted HR 0.83 95% CI 0.59–1.17) nor with OS (adjusted HR 1.17 95% CI 0.87–1.59). Conclusion: Omitting re-excision in breast cancer patients for focally positive margins after BCS does not impair DFS and OS, provided that whole-breast irradiation including boost is given

5-year adherence to adjuvant endocrine treatment in Dutch women with early stage breast cancer:a population-based database study (2006-2016)

BACKGROUND: Hormonal receptor (HR) positive breast tumors are common. Adjuvant hormonal therapy (AHT) with tamoxifen or Aromatase Inhibitors (AIs) is beneficial depending on the stage of the tumor. Despite the fact that AHT has been shown to improve survival and recurrence, Dutch adherence rates, which were mostly dependent on Tamoxifen prescriptions until 2006, plummeted from 80% after one year to 50% after five years. Nonadherence with AHT reduces its effectiveness. This research presents more recent adherence statistics (from 2006 to 2016), on a larger sample (7,996 vs 1,451), as well as factors that influence AHT adherence. In addition to tamoxifen data, AIs are now included. OBJECTIVE: As low use of adjuvant endocrine therapy is a potentially important and modifiable risk factor for poor outcome, it is important to monitor the rate as an indicator of women's burden of disease and the direction of adherence trends. METHODS: The Netherlands Cancer Registry (NCR) was used to find women with early-stage breast cancer who started AHT within a year of surgery and were linked to the PHARMO Database Network (n = 8,679). The Kaplan-Meier approach was used to measure AHT adherence five years after treatment was started, with a 60-day gap between refills as our primary outcome. Furthermore, the Medication Possession Rate (MPR) was determined using a cutoff of =80%. Analysis was performed on influential factors of adherence. RESULTS: The proportion of persistent women declined over time to reach 46.6% at the end of the fifth year and 53.3% of the women had a MPR =80% during the fifth year. Older and being diagnosed in 2006-2010 were associated with AHT adherence. CONCLUSION: Dutch 5-year AHT adherence appears to remain poor. Improving AHT adherence in HR+ breast cancer survivors is a critical medical need

Clinical management of women with metastatic breast cancer: a descriptive study according to age group

BACKGROUND: The primary aim of treatment of a patient who has developed metastatic disease is palliation. The objectives of the current study are to describe and quantify the clinical management of women with metastatic breast cancer from the diagnosis of metastatic disease until death and to analyze differences between age groups. METHODS: Data were collected from the medical files of all patients (n = 116) who had died after December 31, 1999, after a diagnosis of metastatic breast cancer in two teaching hospitals in the south of the Netherlands. RESULTS: Of the 116 patients included in our study, 10 (9%) already had metastatic disease at diagnosis and 106 developed distant disease after the diagnosis of localized breast cancer. Before they died, 70% of the 116 patients developed metastases in one or more bones, 50% in the lung and/or pleura, 50% in the abdominal viscera, 23% in the central nervous system, and 19% in the skin. Patients younger than 50 years were much more likely to develop metastases in the central nervous system than patients 50 years and older. Seventy-seven (66%) of the 116 patients with metastatic breast cancer received chemotherapy. This proportion decreased with age (p = 0.005), as did the number of schemes per patient. Together, they received 132 chemotherapy schemes, of which 35 (27%) resulted in partial remission or stabilization of the disease process. Ninety-eight patients (84%) received hormonal treatment. This proportion did not differ between the three age groups. Together, they received 216 hormonal treatments, 38 (16%) of which resulted in partial remission or stabilization of the disease process. Seventy-nine patients (68%) received palliative radiotherapy. This proportion decreased with age (p = 0.03). Together, they underwent 216 courses, 176 (77%) of which resulted in relief of the complaints. CONCLUSION: Patients aged 70 years and older are less likely to receive chemotherapy or radiotherapy. Part of this difference could be explained by their shorter survival time after the diagnosis of metastatic disease and their lower risk of developing brain and bone metastases. However, more research is needed to understand the age-related differences in the treatment of metastatic breast cancer, and especially how comorbidity and frailty limit therapeutic choices

External validation and clinical utility assessment of PREDICT breast cancer prognostic model in young, systemic treatment-naïve women with node-negative breast cancer

Background: The validity of the PREDICT breast cancer prognostic model is unclear for young patients without adjuvant systemic treatment. This study aimed to validate PREDICT and assess its clinical utility in young women with node-negative breast cancer who did not receive systemic treatment. Methods: We selected all women from the Netherlands Cancer Registry who were diagnosed with node-negative breast cancer under age 40 between 1989 and 2000, a period when adjuvant systemic treatment was not standard practice for women with node-negative disease. We evaluated the calibration and discrimination of PREDICT using the observed/expected (O/E) mortality ratio, and the area under the receiver operating characteristic curve (AUC), respectively. Additionally, we compared the potential clinical utility of PREDICT for selectively administering chemotherapy to the chemotherapy-to-all strategy using decision curve analysis at predefined thresholds. Results: A total of 2264 women with a median age at diagnosis of 36 years were included. Of them, 71.2% had estrogen receptor (ER)-positive tumors and 44.0% had grade 3 tumors. Median tumor size was 16 mm. PREDICT v2.2 underestimated 10-year all-cause mortality by 33% in all women (O/E ratio:1.33, 95%CI:1.22–1.43). Model discrimination was moderate overall (AUC10-year:0.65, 95%CI:0.62–0.68), and poor for women with ER-negative tumors (AUC10-year:0.56, 95%CI:0.51–0.62). Compared to the chemotherapy-to-all strategy, PREDICT only showed a slightly higher net benefit in women with ER-positive tumors, but not in women with ER-negative tumors. Conclusions: PREDICT yields unreliable predictions for young women with node-negative breast cancer. Further model updates are needed before PREDICT can be routinely used in this patient subset.</p

SUBMIT: Systemic therapy with or without up front surgery of the primary tumor in breast cancer patients with distant metastases at initial presentation

<p>Abstract</p> <p>Background</p> <p>Five percent of all patients with breast cancer have distant metastatic disease at initial presentation. Because metastatic breast cancer is considered to be an incurable disease, it is generally treated with a palliative intent. Recent non-randomized studies have demonstrated that (complete) resection of the primary tumor is associated with a significant improvement of the survival of patients with primary metastatic breast cancer. However, other studies have suggested that the claimed survival benefit by surgery may be caused by selection bias. Therefore, a randomized controlled trial will be performed to assess whether breast surgery in patients with primary distant metastatic breast cancer will improve the prognosis.</p> <p>Design</p> <p>Randomization will take place after the diagnosis of primary distant metastatic breast cancer. Patients will either be randomized to up front surgery of the breast tumor followed by systemic therapy or to systemic therapy, followed by delayed local treatment of the breast tumor if clinically indicated.</p> <p>Patients with primary distant metastatic breast cancer, with no prior treatment of the breast cancer, who are 18 years or older and fit enough to undergo surgery and systemic therapy are eligible. Important exclusion criteria are: prior invasive breast cancer, surgical treatment or radiotherapy of this breast tumor before randomization, irresectable T4 tumor and synchronous bilateral breast cancer. The primary endpoint is 2-year survival. Quality of life and local tumor control are among the secondary endpoints.</p> <p>Based on the results of prior research it was calculated that 258 patients are needed in each treatment arm, assuming a power of 80%. Total accrual time is expected to take 60 months. An interim analysis will be performed to assess any clinically significant safety concerns and to determine whether there is evidence that up front surgery is clinically or statistically inferior to systemic therapy with respect to the primary endpoint.</p> <p>Discussion</p> <p>The SUBMIT study is a randomized controlled trial that will provide evidence on whether or not surgery of the primary tumor in breast cancer patients with metastatic disease at initial presentation results in an improved survival.</p> <p>Trial registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT01392586">NCT01392586</a>.</p

Breast cancer survival in the US and Europe: a CONCORD high-resolution study.

Breast cancer survival is reportedly higher in the US than in Europe. The first worldwide study (CONCORD) found wide international differences in age-standardized survival. The aim of this study is to explain these survival differences. Population-based data on stage at diagnosis, diagnostic procedures, treatment and follow-up were collected for about 20,000 women diagnosed with breast cancer aged 15-99 years during 1996-98 in 7 US states and 12 European countries. Age-standardized net survival and the excess hazard of death up to 5 years after diagnosis were estimated by jurisdiction (registry, country, European region), age and stage with flexible parametric models. Breast cancers were generally less advanced in the US than in Europe. Stage also varied less between US states than between European jurisdictions. Early, node-negative tumors were more frequent in the US (39%) than in Europe (32%), while locally advanced tumors were twice as frequent in Europe (8%), and metastatic tumors of similar frequency (5-6%). Net survival in Northern, Western and Southern Europe (81-84%) was similar to that in the US (84%), but lower in Eastern Europe (69%). For the first 3 years after diagnosis the mean excess hazard was higher in Eastern Europe than elsewhere: the difference was most marked for women aged 70-99 years, and mainly confined to women with locally advanced or metastatic tumors. Differences in breast cancer survival between Europe and the US in the late 1990s were mainly explained by lower survival in Eastern Europe, where low healthcare expenditure may have constrained the quality of treatment

Predicting the extent of nodal involvement for node positive breast cancer patients: Development and validation of a novel tool

Background: This study aimed to develop an easy to use prediction model to predict the risk of havin

Prognostic Value of Stromal Tumor-Infiltrating Lymphocytes in Young, Node-Negative, Triple-Negative Breast Cancer Patients Who Did Not Receive (neo)Adjuvant Systemic Therapy

PURPOSE: Triple-negative breast cancer (TNBC) is considered aggressive, and therefore, virtually all young patients with TNBC receive (neo)adjuvant chemotherapy. Increased stromal tumor-infiltrating lymphocytes (sTILs) have been associated with a favorable prognosis in TNBC. However, whether this association holds for patients who are node-negative (N0), young (< 40 years), and chemotherapy-naïve, and thus can be used for chemotherapy de-escalation strategies, is unknown. METHODS: We selected all patients with N0 TNBC diagnosed between 1989 and 2000 from a Dutch population-based registry. Patients were age < 40 years at diagnosis and had not received (neo)adjuvant systemic therapy, as was standard practice at the time. Formalin-fixed paraffin-embedded blocks were retrieved (PALGA: Dutch Pathology Registry), and a pathology review including sTILs was performed. Patients were categorized according to sTILs (< 30%, 30%-75%, and ≥ 75%). Multivariable Cox regression was performed for overall survival, with or without sTILs as a covariate. Cumulative incidence of distant metastasis or death was analyzed in a competing risk model, with second primary tumors as competing risk. RESULTS: sTILs were scored for 441 patients. High sTILs (≥ 75%; 21%) translated into an excellent prognosis with a 15-year cumulative incidence of a distant metastasis or death of only 2.1% (95% CI, 0 to 5.0), whereas low sTILs (< 30%; 52%) had an unfavorable prognosis with a 15-year cumulative incidence of a distant metastasis or death of 38.4% (32.1 to 44.6). In addition, every 10% increment of sTILs decreased the risk of death by 19% (adjusted hazard ratio: 0.81; 95% CI, 0.76 to 0.87), which are an independent predictor adding prognostic information to standard clinicopathologic variables (χ2 = 46.7, P < .001). CONCLUSION: Chemotherapy-naïve, young patients with N0 TNBC with high sTILs (≥ 75%) have an excellent long-term prognosis. Therefore, sTILs should be considered for prospective clinical trials investigating (neo)adjuvant chemotherapy de-escalation strategies