Scott Howell, DO, MPH & TM, CPE from Echosens discusses Underlying nonalcoholic fatty liver disease is a significant factor for breast cancer recurrence after curative surgery.
Instract
Breast cancer is the world’s most common cancer among women and is a leading cause of death in women. Metabolic components are important risk factors for non-alcoholic fatty liver disease growth, as with breast cancer (NAFLD). We aimed to determine the prevalence of NAFLD in breast cancer patients and the influence of NAFLD on the prognosis of breast cancer in this retrospective cohort analysis.
From January 2007 to June 2017, patients with breast cancer were enrolled in the study. By calculating Hounsfield units in the liver and spleen, respectively, hepatic steatosis was assessed by non-enhanced computed tomography scan; 123 healthy controls undergoing non-enhanced computed tomography scans were also analyzed.
The prevalence of NAFLD was 15.8 percent (251/1587) in breast cancer patients, which was substantially greater than in safe controls (8.9 percent, 11/123) (P = .036). There was no substantial difference between the groups with and without NAFLD in overall survival (P = .304). In patients without NAFLD, however, recurrence-free survival was significantly higher than in those with NAFLD (P = .009). The NAFLD group reported a higher cumulative incidence of serious liver injury in breast cancer patients undergoing endocrine care than the non-NAFLD group (P < .001).
NAFLD incidence is substantially higher in breast cancer patients than in safe controls. In addition, NAFLD breast cancer patients showed a worse prognosis in terms of recurrence. Therefore in the management of breast cancer patients, diagnostic evaluation for NALFD is significant.
Analysis
Advances in imaging technologies and breast cancer care modalities have contributed to mortality decreases in breast cancer patients. Breast cancer, however, remains the most prevalent cancer and the leading cause of female mortality.[6] NAFLD is also a condition in which the incidence of breast cancer is steadily growing worldwide.[18] The prevalence of breast cancer and NAFLD are therefore likely to be closely linked, and NAFLD may be an important factor in breast cancer development or outcomes. We have observed in this large-scale, retrospective cohort study that NAFLD is very common in breast cancer patients and is associated with higher recurrence after curative surgery.
A high prevalence of NAFLD in breast cancer patients has previously been documented in some reports. However, the intensity of these results was constrained by the small number of patients involved in these studies.[12,13] In this study we examined 1587 newly diagnosed patients with breast cancer and compared the prevalence of NAFLD between these patients and safe controls during the same span. In patients with breast cancer, the prevalence of NAFLD was found to be substantially higher than in safe controls. Moreover, after PSM, this meaning was retained. The production of NAFLD, such as obesity, diabetes, and HTN, is associated with many metabolic diseases.[1] Since breast cancer is also considered to be associated with obesity and diabetes, it is possible that the prevalence of NAFLD is increased in breast cancer patients.
While the liver biopsy is the gold standard for NAFLD diagnosis, in all patients with suspected NAFLD, there are many limitations on the performance of liver biopsy, such as expense, inconvenience, sampling error, inter- and intra-observer variability, and invasiveness.[19] Several attempts have been made to evaluate hepatic steatosis through imaging studies, including sonography, CT scan, and MRI. Therefore, when the mean liver attenuation was lower than 40 HU or 10 HU lower than that of the spleen, NAFLD was diagnosed.[23,24] The main drawback of this procedure is the low precision in the diagnosis of mild hepatic steatosis,[24] so the prevalence of NAFLD in our control group (8.9 percent) was lower than the global prevalence (25.24 percent).[1] Boyce et al registered a 6.9 percent p p
As it is not only a risk factor for obesity, type 2 diabetes, dyslipidemia, metabolic syndrome, and polycystic ovary syndrome, NAFLD is associated with many other non-liver-related diseases, but also with other adverse effects, including cardiovascular disease and extra hepatic cancer.[26] Long-term outcomes have been reported to be weak in patients with NAFLD, showing lower overall survival, A bidirectional association between NAFLD and metabolic syndrome may be correlated with cancer development in NAFLD patients, although the exact mechanism of this interaction remains unclear.[5] A more recent study indicated that sonography-diagnosed NAFLD was associated with breast cancer development in women.[28] Our findings showed a significantly increased prevalence of NALFD in patients. NALFD is also known to be a risk factor for breast cancer growth and one of the most common co-morbidities in breast cancer patients.
Berrino et al stated that in breast cancer patients, metabolic syndrome is a significant prognostic factor.[29] A number of components of metabolic syndrome have been associated with recurrence of breast cancer, particularly hypertriglyceridemia and low HDL. Our research also found that NAFLD was an effective prognostic factor for breast cancer recurrence following curative surgery, even though it was not an important factor for overall survival. The close monitoring of breast cancer recurrence after surgery and the development of imaging modalities may be attributed to this discrepancy. In fact, most of the recurrent patients had undergone curative resection, and some of the patients had undergone surgery three times. Nonetheless, NAFLD patients displayed a lower overall survival tendency, without statistical significance, than non-NAFLD patients. Breast cancer patients with NAFLD can also need more careful monitoring after surgery for recurrence than those with no evidence of NAFLD.
The key treatment modality for ER-positive cancer is endocrine therapy.[14] In patients with ER-positive tumors, 5-year tamoxifen or aromatase inhibitor therapy substantially improved overall survival and reduced postoperative recurrence in patients with early breast cancer.[30] Tamoxifen, however, is associated with other side effects, including endometrial cancer, pulmonary embolism, Among these 1102 patients, during endocrine therapy, 62 patients suffered a serious liver injury. There was a greater frequency of serious liver damage in patients with NAFLD. Tamoxifen substantially increased the risk of transaminase elevation relative to other endocrine drugs in patients with NAFLD. Therefore in patients with NAFLD undergoing endocrine treatment, more attention should be paid to transaminase abnormalities, especially in the case of tamoxifen treatment. Most patients with severe liver damage, however, temporarily stopped endocrine therapy in response. Breast cancer recurred in just three of those 37 patients who stopped endocrine therapy due to severe liver injury. This result suggests that the cessation of endocrine therapy in the short term is not an effective factor for the recurrence of breast cancer.
There are multiple drawbacks to this research. A significant drawback is that this is a retrospective review, which may contribute to a lack of medical background knowledge and laboratory data. Many breast cancer patients were, however, repeatedly admitted to the hospital and their medical histories were sufficiently accurate. In order to make sure that there were no lost documents, we also performed a thorough examination of patient medical charts. Secondly, there is a risk that hepatic steatosis may have been caused by underlying liver disease. We excluded patients with underlying liver disease, especially patients with a history of alcohol abuse, using both doctors’ and nurses’ records to avoid this bias. Finally, hepatic steatosis, which could be slightly unreliable in the mild stage of steatosis, was evaluated by CT scanning. More specific evaluation methods, such as controlled attenuation parameters, MRI-estimated fat fraction of proton mass, and MR spectroscopy, should be favored in future studies.
In conclusion, in breast cancer patients, the prevalence of NAFLD is substantially higher than in safe controls. In addition, the co-existence of NALFD can be an important prognostic factor for tumor recurrence after curative surgery in breast cancer patients. While on the basis of the present findings, it is difficult to draw a definitive conclusion, interdisciplinary expertise should be considered in evaluating the presence of NAFLD in breast cancer patients. In addition, NAFLD patients had to undergo a stricter examination of recurrence and metabolic syndrome treatment. To improve the prognosis in breast cancer patients with NAFLD, more studies concerning therapeutic treatments are required.