HOX transcription factors play an important role in determining body patterning and cell fate during embryogenesis. Accumulating evidence has shown that these genes act as positive and/or negative modulators in many types of cancer, including breast cancer, in a tissue-specific manner. We have previously reported that HOXB5 is aberrantly overexpressed in breast cancer tissues and cell lines. Here, we investigated the biological roles and clinical relevance of HOXB5 in breast cancer. Immunohistochemical analysis of HOXB5 on tissue microarray (TMA) including 34 normal and 67 breast cancer specimens revealed that HOXB5 was highly expressed in cancer tissues, particularly from estrogen receptor (ER)-positive breast cancer patients. An online survival analysis confirmed the correlation between HOXB5 expression and poor distant metastasis-free survival in ER-positive, but not in ER-negative, breast cancer. In vitro studies indicated that HOXB5 silencing in ER-positive cells significantly decreased cell proliferation and anchorage-independent cell growth. In contrast, overexpression of HOXB5 displayed EMT characteristics with a greater invasive ability, higher cell proliferation and colony formation in soft agar. HOXB5 knockdown or overexpression led to changes in the expression levels of RET, ERBB2, and EGFR, but not of ESR1. In conclusion, we suggest that HOXB5 acts as a positive modulator most likely by promoting cell proliferative response and invasiveness in ER-positive breast cancer. These results would help predict prognosis of breast cancer and identify a new valuable therapeutic target.

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BackgroundThe National Health Insurance Service (NHIS) established a healthcare claim database for all Korean citizens. This study aimed to analyze the NHIS data and investigate the patterns of breast cancer treatments.MethodsWe constructed a retrospective female breast cancer cohort by analyzing annual incident cases. The annual number of newly diagnosed female breast cancer was compared between the NHIS data and Korea National Cancer Incidence Database (KNCIDB). The annual treatment patterns including surgery, chemotherapy, radiation therapy, endocrine therapy and targeted therapy were analyzed.ResultsA total of 148,322 women with newly diagnosed invasive breast cancer during 2006–2014 was identified. The numbers of newly diagnosed invasive breast cancer cases were similar between the NHIS data and KNCIDB, which demonstrated a strong correlation (r = 0.995; P < 0.001). The age distribution of the breast cancer cases in the NHIS data and KNCIDB also showed a strong correlation (r = 1.000; P < 0.001). About 85% of newly diagnosed breast cancer patients underwent operations. Although the proportions of chemotherapy use have not changed during 2006–2014, the total number of chemotherapy prescriptions sharply increased during this period. The proportions of radiotherapy and anti-hormonal therapy increased. Among the anti-hormonal agents, tamoxifen was the most frequently prescribed medication, and letrozole was the most preferred endocrine treatment in patients aged ≥ 50 years.ConclusionAlong with the increased breast cancer incidence in Korea, the frequencies of breast cancer treatments have increased. The NHIS data can be a feasible data source for future research.

Background There is a controversy about late‐onset congestive heart failure (CHF) among breast cancer survivors. This study investigated the incidence rate and risk factors of late‐onset CHF more than 2 years after the breast cancer diagnosis. Methods A nationwide, retrospective study was conducted with the National Health Information Database. With 1:3 age‐ and sex‐matched noncancer controls, Cox proportional hazard regression models were used to analyze the incidence and risk factors of late CHF. The cumulative incidence rate of late CHF was evaluated with a Kaplan‐Meier analysis and a log‐rank test. Results A total of 91,227 cases (286,480 person‐years) and 273,681 controls (884,349 person‐years) were evaluated between January 2007 and December 2013. The risks of late CHF were higher in cases than controls (hazard ratio [HR], 1.396; 95% confidence interval [CI], 1.268‐1.538). Younger survivors (age ≤ 50 years) showed a higher risk of late CHF than their younger counterparts (HR, 2.903; 95% CI, 2.425‐3.474). Although older age was a risk factor for late CHF, older survivors (age ≥ 66 years) showed no difference in the risk of late CHF in comparison with their counterparts (HR, 0.906; 95% CI, 0.757‐1.084). Anthracyclines and taxanes were risk factors for late CHF, although trastuzumab, radiation, and endocrine therapy were not. Conclusions Young breast cancer survivors have a greater risk of late CHF than the young population without cancer. More attention should be paid to young breast cancer survivors who receive taxane‐ or anthracycline‐based regimens over the long term.