Mortality Rates Among Early-Stage Hormone Receptor-Positive Breast Cancer Patients: A Population-Based Cohort Study in Denmark

Christiansen, Peer; Bjerre, Karsten; Ejlertsen, Bent; Jensen, Maj Britt; Rasmussen, Birgitte Buur; Laenkholm, Anne Vibeke; Kroman, Niels; Ewertz, M.; Offersen, Birgitte Vrou; Toftdahl, Dorte B.; Møller, Susanne; Mouridsen, Henning T.

doi:10.1093/jnci/djr299

Cited by 56 publications

(38 citation statements)

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“…Women with early breast cancer are increasingly being exposed to adjuvant systemic therapies, which can safely be omitted in only a small subgroup of node negative patients aged 60 or older with estrogen receptor (ER) positive, HER2 negative, grade I tumors of 10 mm or less [11]. Endocrine treatment is the key component of the adjuvant therapy in patients with ER positive tumors and its duration has gradually been extended [12][13][14].…”

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confidence: 99%

Improvements in breast cancer survival between 1995 and 2012 in Denmark: The importance of earlier diagnosis and adjuvant treatment

et al. 2016

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Background Breast cancer mortality has declined from 1995 through 2012 which may be attributed to earlier diagnosis, changes in lifestyle risk factors, and improved treatments. To a large extent the relative contribution of these modalities are unknown. Mammography screening was introduced late in Denmark; in 1995 around 20% of the Danish female population aged 50-69 was covered by population-based screening, and this was in 2008 extended to the entire population. Breast conserving surgery gradually replaced mastectomy, and sentinel node biopsy was introduced. In the same period adjuvant treatment was extended considerable. Methods A population-based study of 68 842 breast cancer patients registered in the clinical database of the Danish Breast Cancer Cooperative Group in 1995-2012. Comprehensive data on prognostic factors, comorbidity and treatment together with complete follow-up for survival were used to evaluate improvements in mortality and standardized mortality rate in successive time periods. Results The results from this study demonstrated a significant improvement in prognosis in successive time periods covering 1995-2012. Apart from patients with a high Charlson Comorbidity Index (CCI) improvements were seen in all subgroups of patients. Prognostic factors were more favorable in the latest time period accordingly to the introduction of nationwide screening. In the study period adjuvant treatment was extended considerable. Conclusion The impact of screening was by nature of limited magnitude. The modified treatment strategies implemented by the use of nationwide guidelines seemed to have a major impact on the substantial survival improvements.

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confidence: 99%

Improvements in breast cancer survival between 1995 and 2012 in Denmark: The importance of earlier diagnosis and adjuvant treatment

et al. 2016

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“…These results also indicated that ∼60% of patients may be overexposed to hormonal therapy toxicity and incur costs to the health care system with little or no clinical benefit under the traditional clinical‐pathological decision‐making approach. Another study showed that adjuvant hormonal therapy can be omitted for a small group of early stage of ER+ patients . Identifying these low risk patients is of clinical importance to spare patients from overtreatment and reduce the burden on the health care system.…”

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confidence: 99%

A 16 Yin Yang gene expression ratio signature for ER+/node− breast cancer

Jia

Cai

et al. 2017

Int. J. Cancer

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Breast cancer is one of the leading causes of cancer death in women. It is a complex and heterogeneous disease with different clinical outcomes. Stratifying patients into subgroups with different outcomes could help guide clinical decision making. In this study, we used two opposing groups of genes, Yin and Yang, to develop a prognostic expression ratio signature. Using the METABRIC cohort we identified a16-gene signature capable of stratifying breast cancer patients into four risk levels with intention that low-risk patients would not undergo adjuvant systemic therapy, intermediate-low-risk patients will be treated with hormonal therapy only, and intermediate-high- and high-risk groups will be treated by chemotherapy in addition to the hormonal therapy. The 16-gene signature for four risk level stratifications of breast cancer patients has been validated using 14 independent datasets. Notably, the low-risk group (n = 51) of 205 estrogen receptor-positive and node negative (ER+/node-) patients from three different datasets who had not had any systemic adjuvant therapy had 100% 15-year disease-specific survival rate. The Concordance Index of YMR for ER+/node negative patients is close to the commercially available signatures. However, YMR showed more significance (HR = 3.7, p = 8.7e-12) in stratifying ER+/node- subgroup than OncotypeDx (HR = 2.7, p = 1.3e-7), MammaPrint (HR = 2.5, p = 5.8e-7), rorS (HR = 2.4, p = 1.4e-6), and NPI (HR = 2.6, p = 1.2e-6). YMR signature may be developed as a clinical tool to select a subgroup of low-risk ER+/node- patients who do not require any adjuvant hormonal therapy (AHT).

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“…And more recently, by combining a number of factors, data from large cohorts of patients entering different DBCG programs have been utilized to better identify patients eligible for systemic therapy 14,15…”

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confidence: 99%

Danish Breast Cancer Cooperative Group

Christiansen¹,

Ejlertsen²,

Jensen³

et al. 2016

CLEP

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Aim of databaseDanish Breast Cancer Cooperative Group (DBCG), with an associated database, was introduced as a nationwide multidisciplinary group in 1977 with the ultimate aim to improve the prognosis in breast cancer. Since then, the database has registered women diagnosed with primary invasive nonmetastatic breast cancer. The data reported from the departments to the database included details of the characteristics of the primary tumor, of surgery, radiotherapy, and systemic therapies, and of follow-up reported on specific forms from the departments in question.Descriptive dataFrom 1977 through 2014, ~110,000 patients are registered in the nationwide, clinical database. The completeness has gradually improved to more than 95%. DBCG has continuously prepared evidence-based guidelines on diagnosis and treatment of breast cancer and conducted quality control studies to ascertain the degree of adherence to the guidelines in the different departments.ConclusionUtilizing data from the DBCG database, a long array of high-quality DBCG studies of various designs and scope, nationwide or in international collaboration, have contributed to the current updating of the guidelines, and have been an instrumental resource in the improvement of management and prognosis of breast cancer in Denmark. Thus, since the establishment of DBCG, the prognosis in breast cancer has continuously improved with a decrease in 5-year mortality from ~37% to 15%.

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Mortality Rates Among Early-Stage Hormone Receptor-Positive Breast Cancer Patients: A Population-Based Cohort Study in Denmark

Abstract: A small subgroup of breast cancer patients who were 60 years or older and had hormone-responsive early-stage tumors up to 10 mm, and received no systemic adjuvant therapy, were not at increased risk of mortality compared with women in this age-group in the general population.

Cited by 56 publications

References 31 publications

Improvements in breast cancer survival between 1995 and 2012 in Denmark: The importance of earlier diagnosis and adjuvant treatment

Improvements in breast cancer survival between 1995 and 2012 in Denmark: The importance of earlier diagnosis and adjuvant treatment

A 16 Yin Yang gene expression ratio signature for ER+/node− breast cancer

Danish Breast Cancer Cooperative Group

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