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  • There were limitations to this study Specifically although


    There were limitations to this study. Specifically, although rigorously examined for accuracy, the NCDB and SEER databases still suffer from issues with data entry and completeness of the treatment record. Of note, although the data were collected on a modern cohort of patients treated from 2010 to 2013, the NCDB noted that only 18% of HER2+ patients were treated with HER2-targeted therapy. This would be expected to be an error in recording. On the basis of a recent examination of the National Comprehensive Cancer Network Breast Cancer Outcomes Database, 83% of HER2+ women received HER2-targeted therapy with trastuzumab. Thus, it is likely that the majority of this patient population did indeed receive HER2-targeted therapy at one point in the management of their breast cancer. Another limitation may be the relatively short follow-up time for the patients included. Unfortunately, NCDB and SEER did not record the HER2 status until 2010; thus, this examination provides the longest possible follow-up for these data sets. Although longer follow-up may reveal more metastases in the ER+ subgroup, it would not likely alter the preferential T-5224 to bone for these tumors, or their better BCSS and OS. This large study shows ER+/HER2+ and ER−/HER2+ breast cancers have different metastatic patterns. ER+/HER2+ breast cancer patients can be treated with targeted agents against both ER and HER2 receptors, and thus have improved survival compared to ER−/HER2+ patients. Meanwhile, ER−/HER2+ cancer patients, with their relatively worse prognosis in comparison to ER+/HER2+ breast cancer, may require a more aggressive approach, even when presenting with oligometastatic bone metastasis.
    Acknowledgments Supported in part by the Winship Research Informatics Shared Resource of Winship Cancer Institute of Emory University and National Institutes of Health/National Cancer Institute under award P30CA138292.
    Introduction Human epidermal growth factor receptor 2 (HER2) is a receptor tyrosine kinase that activates several growth-promoting signaling pathways including phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) and extracellular signal–regulated kinase/mitogen-activated protein kinase (ERK/MAPK).HER2 gene amplification and receptor overexpression occur in 15% to 20% of breast cancer patients and are associated with worse prognosis. In addition, HER2-positive status is regarded as a predictive marker of response to anti-HER2 therapies. The administration of trastuzumab has led to significant improvement in disease-free survival (DFS) and overall survival of HER2-positive breast cancer patients when combined with standard chemotherapy in the adjuvant and metastatic settings.4, 5 Despite this achievement, primary and acquired resistance to trastuzumab represents a major obstacle in the clinical management of HER2-positive breast cancer patients. Therefore, there is an urgent need to identify factors that could influence trastuzumab response in HER2-positive breast cancer patients. There is increasing evidence that lifestyle factors including tobacco and alcohol consumption might affect survival of breast cancer patients.7, 8, 9 Notably, associations between tobacco and ethanol exposure and HER2 expression have been reported in the literature. It has been shown that 4-(methylnitrosamino)-1-3-(3-pyridyl)-1-butanon, a potent tobacco-specific carcinogen, activates the ERK/MAPK signaling pathway (a growth-promoting signaling pathway activated by HER2) in human normal mammary epithelial cells. Furthermore, a study that examined the association between tobacco consumption at time of breast cancer diagnosis and risk of recurrence in a cohort of 3340 breast cancer patients showed that recurrence risk was significantly increased in trastuzumab-naive, HER2-positive breast cancer patients (n = 177) who smoked at the time of diagnosis, suggesting that the tobacco effect might be particularly strong in this molecular subtype of breast cancer. The only study that analyzed the association between tobacco use and response to trastuzumab in a cohort of 248 metastatic trastuzumab-treated HER2-positive breast cancer patients reported that the response rate in smokers (former and active) was not statistically different from that of never smokers. Concerning alcohol consumption, a recent study performed in a cohort of 105,972 women highlighted that alcohol consumption might represent a risk factor for HER2-positive breast cancer subtype. Furthermore, it has been reported that HER2 overexpression was associated with an increased response to ethanol-stimulated cell proliferation, suggesting that HER2 overexpression may amplify ethanol-induced signaling and enhance invasion capacity of breast cancer cells promoted by alcohol. To our knowledge, no study has yet evaluated the impact of alcohol consumption on trastuzumab response in HER2-positive breast cancer patients.