Dig Dis Sci (2015) 60:2541–2543 DOI 10.1007/s10620-015-3741-6
CORRESPONDENCE
Acute Liver Failure Caused by Metastatic Breast Cancer: Can We Expect Some Results from Chemotherapy? Jacopo Giuliani1 • Andrea Bonetti1
Received: 10 May 2015 / Accepted: 1 June 2015 / Published online: 19 June 2015 Ó Springer Science+Business Media New York 2015
Dear Editor, Acute liver failure (ALF) is an uncommon disorder that leads to jaundice, coagulopathy, and multisystem organ failure [1]. Malignancy is an uncommon cause of ALF, and diffuse parenchymal metastases are a pattern that is capable of causing liver failure. Hematological malignancies are recognized to be the most common cause of diffuse parenchymal metastases, but this metastatic pattern has also been identified in many primary neoplasms, such as breast cancer [1]. The prognosis is very poor [1–3]. Recently, in a literature review performed by Mogrovejo et al. [2], 32 cases were characterized (only 25 % were diagnosed premortem, but with a statistically significant trend of increasing premortem diagnosis since 2000: p = 0.001); common signs included jaundice, hepatomegaly, shifting dullness, and bilateral leg edema; mean serum level of AST was 296.4 ± 204.0 U/l, ALT was 183.2 ± 198.9 U/l, and total bilirubin was 8.6 ± 8.3 mg/ dl. Authors reported also a new case of ALF from breast cancer (mixed ductal and lobular carcinoma) with hepatic metastases (demonstrated by liver biopsy) that occurred 21 years after original breast primary. We report too the case of a 35-year-old women, without any pathological history. Four years ago, she underwent demolitive surgery for invasive mixed ductal and lobular left breast cancer, G3, ER = 90 %, PgR = 0 %, MIB-1 = 20–30 %, HER2/NEU = 3?, pT1bpN0M0. She was treated with adjuvant chemotherapy with docetaxel (75 mg/m2), & Jacopo Giuliani [email protected] 1
Department of Oncology, Mater Salutis Hospital, ASL 21 della Regione Veneto, Via Gianella, 37045 Legnago, VR, Italy
carboplatin (AUC 6), and trastuzumab (8 mg pro kg for the first dose and 6 mg pro kg for subsequent doses) (TCH) each 21 days for six cycles, followed by the administration of three weekly trastuzumab (6 mg pro kg) for 1 year; she also started hormone therapy with tamoxifen at the dose of 20 mg/daily following chemotherapy (for 5 years total treatment provided) and enantone 3.75 mg/month. After 3 years, she presented with asthenia and right upper quadrant pain. At physical examination, jaundice and hepatomegaly were found; Eastern Cooperative Oncology Group (ECOG) performance status (PS) was 3. Abdominal ultrasonography revealed the presence of bone and liver metastases (several hypoechoic lesions in right and left hepatic lobe), ranging from 10 to 15 mm in maximum diameter as confirmed by the subsequent CT scan. Liver function test showed increased total and direct bilirubin of 5.0 and 2.5 mg/dl, respectively, AST (388 U/l), ALT (236 U/l), and cGT (449 U/l) serum levels (Table 1). Considering the young age and the bio-pathological features of the disease, we decided to start chemotherapy with weekly carboplatin (AUC 2), vinorelbine, and trastuzumab (2 mg pro kg). We have seen a progressive improvement in both the general condition of the patient (ECOG PS = 1) and the values of liver function. In particular, after 1 month of chemotherapy, values of liver function were nearly normalized: total bilirubin = 0.4 mg/dl, AST = 48 U/l, ALT = 60 U/l, and cGT = 88 U/l serum levels (Table 1). The CT scan revealed a partial remission (PR) of liver metastases. After 6 months of the onset, the patient was treated with nab-paclitaxel (80 mg/m2, for hypersensitivity reaction to the second administration of weekly paclitaxel) and trastuzumab (2 mg pro kg) for liver progression of the disease (PD). We have seen a progressive deterioration of the general condition of the patient; the patient died about 9 months after the onset of the disease for PD.
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2542 Table 1 Serum levels of liver function test before and after first-line chemotherapy
Dig Dis Sci (2015) 60:2541–2543
Serum levels before chemotherapy Total bilirubin
5.0 mg/dl
0.4 mg/dl
Direct bilirubin
2.5 mg/dl
0.2 mg/dl
AST
388 U/l
48 U/l
ALT
236 U/l
60 U/l
cGT
449 U/l
88 U/l
The general features of the reported case are similar to those reported in literature, and we agree with the author’s conclusion to promote liver biopsy for premortem diagnosis and appropriate therapy [2]. In fact, the peculiarity of the reported case was related to the quick response to chemotherapy and the prolonged survival in this particular condition, associated with an improvement in quality of life. According to another review by Allison et al. [3] concerning 21 reported cases of acute liver failure due to metastatic breast carcinoma, 18 cases died within 3 days to 2 months. In our experience, probably an attempt with chemotherapy should be considered, especially in young patients. In fact, it may have both a clinical benefit and an increase in survival, especially in potentially chemotherapy-sensitive tumors. Finally, we concluded that ALF caused by malignancy is an uncommon disorder and diffuse parenchymal metastases from breast cancer are a pattern that is capable of causing liver failure. The prognosis is very poor. However, an attempt with chemotherapy should be considered, especially in young patients, because it may have both a clinical benefit and an increase in survival. Other experiences are needed to corroborate our findings.
Reply Consideration of Chemotherapy for Acute Liver Failure from Breast Cancer Metastatic to the Liver To the Editor, Data concerning chemotherapy for patients presenting with acute liver failure (ALF) from breast cancer metastatic to the liver are extremely limited. In 2014, we reviewed all 32 reported cases of ALF from hepatic metastases from breast cancer, identified by computerized literature search of articles published since 1950 [2], and found that only one of these patients received chemotherapy after the diagnosis [4]. The other 31 patients were not offered chemotherapy; 24 patients had breast cancer metastatic to the liver only diagnosed by postmortem examination, and the seven other patients were too sick to undergo chemotherapy premortem because of the ALF itself or associated complications, such
123
Serum levels after chemotherapy
as esophageal variceal bleeding. These 31 patients had a fulminant clinical course and poor prognosis because of their massive, hepatic metastases: 26 patients (84 %) died within days to several weeks after presentation, 4 (13 %) died 1 month after presentation, and 1 (3 %) died 2 months after presentation. Nazario et al. [5], likewise, noted that chemotherapy for such patients was usually limited as an option by the ALF, concomitant infections, and multi-organ failure. Contrariwise, the thirty-second patient, who received chemotherapy, had an improved outcome; the liver function tests initially normalized, serum cancer markers, such as carcinoembryonic antigen, decreased toward normal, and the patient did relatively well clinically for 6 months, until rapidly succumbing to diffuse metastatic disease [4]. We thank Giuliani and Bonetti for their interesting letter. They report a second case of short-term reversal of ALF from breast cancer metastatic to the liver after administering chemotherapy. The patient did relatively well for 6 months before succumbing from metastases 3 months later. This second report of improvement after chemotherapy is refreshing for clinicians hoping for improved therapies and better prognosis for these unfortunate patients. Yet, this report should be interpreted cautiously. First, they report only one case that supplements one similar prior case. Confirmative data are required. Second, their patient had favorable prognostic features: presentation at a relatively young age of 34 years; no comorbidities; presentation with relatively mild ALF; presentation without complications of ALF or portal hypertension such as hepatorenal syndrome or variceal bleeding; and the absence of other reported complications, such as sepsis. Third, the liver function transiently improved, but the patient died 9 months after receiving chemotherapy. Our 32 reviewed cases spanned from 1950 to 2014 [2]. Chemotherapy has come a long way since 1950, and the dismal prognosis of this syndrome could be changing because of earlier diagnosis of metastases, improved ALF management, and advances in chemotherapy. We reported a statistically significant trend of increasing premortem diagnosis of this syndrome since 2000 (0 % diagnosed premortem before 2000 versus 50 % after 2000, p = 0.001, 95 % odds ratio confidence interval: [2.86, Fisher’s exact test) [2].
Dig Dis Sci (2015) 60:2541–2543
Clinicians should carefully consider chemotherapy for this syndrome. Decisions should be individualized according to ALF severity, presence of complications from ALF, comorbidities, patient age, and patient’s wishes. Decisions should involve a team, with consultation by oncologists, hepatologists, internists, and social workers. More data are essential. Mitchell S. Cappell, MD, PhD, Estela Mogrovejo, MD and Palaniappan Manickam, MD, MPH Division of Gastroenterology and Hepatology, MOB 602, Department of Medicine, William Beaumont Hospital, 3535 West Thirteen Mile Road, Royal Oak, MI 48073, USA Tel: 248-551-1227 Mitchell S. Cappell, MD, PhD Oakland University William Beaumont School of Medicine, Royal Oak, MI, USA
2543
References 1. Khashab M, Tector AJ, Kwo PY. Epidemiology of acute liver failure. Curr Gastroenterol Rep. 2007;9:66–73. 2. Mogrovejo E, Manickam P, Amin M, Cappel MS. Characterization of the syndrome of acute liver failure caused by metastases from breast carcinoma. Dig Dis Sci. 2014;59:724–726. 3. Allison KH, Fligner CL, Parks WT. Radiographically occult, diffuse intrasinusoidal hepatic metastases from primary breast carcinomas: a clinicopathologic study of 3 autopsy cases. Arch Pathol Lab Med. 2004;128:1418–1423. 4. Goswami R, Babich M, Farah KF. Occult breast malignancy masquerading as acute hepatic failure. Gastroenterol Hepatol (NY). 2011;7:62–65. 5. Nazario HE, Lepe R, Trotter JF. Metastatic breast cancer presenting as acute liver failure. Gastroenterol Hepatol (NY). 2011;7:65–66.
Conflict of interest None. In particular, Dr. Cappell as a member of the FDA Advisory Committee for GI Drugs affirms that this paper does not discuss any proprietary confidential pharmaceutical data submitted to the FDA. Dr. Cappell is a speaker for AstraZeneca. This work does not discuss any drugs manufactured or marketed by AstraZeneca.
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CORRESPONDENCE
Acute Liver Failure Caused by Metastatic Breast Cancer: Can We Expect Some Results from Chemotherapy? Jacopo Giuliani1 • Andrea Bonetti1
Received: 10 May 2015 / Accepted: 1 June 2015 / Published online: 19 June 2015 Ó Springer Science+Business Media New York 2015
Dear Editor, Acute liver failure (ALF) is an uncommon disorder that leads to jaundice, coagulopathy, and multisystem organ failure [1]. Malignancy is an uncommon cause of ALF, and diffuse parenchymal metastases are a pattern that is capable of causing liver failure. Hematological malignancies are recognized to be the most common cause of diffuse parenchymal metastases, but this metastatic pattern has also been identified in many primary neoplasms, such as breast cancer [1]. The prognosis is very poor [1–3]. Recently, in a literature review performed by Mogrovejo et al. [2], 32 cases were characterized (only 25 % were diagnosed premortem, but with a statistically significant trend of increasing premortem diagnosis since 2000: p = 0.001); common signs included jaundice, hepatomegaly, shifting dullness, and bilateral leg edema; mean serum level of AST was 296.4 ± 204.0 U/l, ALT was 183.2 ± 198.9 U/l, and total bilirubin was 8.6 ± 8.3 mg/ dl. Authors reported also a new case of ALF from breast cancer (mixed ductal and lobular carcinoma) with hepatic metastases (demonstrated by liver biopsy) that occurred 21 years after original breast primary. We report too the case of a 35-year-old women, without any pathological history. Four years ago, she underwent demolitive surgery for invasive mixed ductal and lobular left breast cancer, G3, ER = 90 %, PgR = 0 %, MIB-1 = 20–30 %, HER2/NEU = 3?, pT1bpN0M0. She was treated with adjuvant chemotherapy with docetaxel (75 mg/m2), & Jacopo Giuliani [email protected] 1
Department of Oncology, Mater Salutis Hospital, ASL 21 della Regione Veneto, Via Gianella, 37045 Legnago, VR, Italy
carboplatin (AUC 6), and trastuzumab (8 mg pro kg for the first dose and 6 mg pro kg for subsequent doses) (TCH) each 21 days for six cycles, followed by the administration of three weekly trastuzumab (6 mg pro kg) for 1 year; she also started hormone therapy with tamoxifen at the dose of 20 mg/daily following chemotherapy (for 5 years total treatment provided) and enantone 3.75 mg/month. After 3 years, she presented with asthenia and right upper quadrant pain. At physical examination, jaundice and hepatomegaly were found; Eastern Cooperative Oncology Group (ECOG) performance status (PS) was 3. Abdominal ultrasonography revealed the presence of bone and liver metastases (several hypoechoic lesions in right and left hepatic lobe), ranging from 10 to 15 mm in maximum diameter as confirmed by the subsequent CT scan. Liver function test showed increased total and direct bilirubin of 5.0 and 2.5 mg/dl, respectively, AST (388 U/l), ALT (236 U/l), and cGT (449 U/l) serum levels (Table 1). Considering the young age and the bio-pathological features of the disease, we decided to start chemotherapy with weekly carboplatin (AUC 2), vinorelbine, and trastuzumab (2 mg pro kg). We have seen a progressive improvement in both the general condition of the patient (ECOG PS = 1) and the values of liver function. In particular, after 1 month of chemotherapy, values of liver function were nearly normalized: total bilirubin = 0.4 mg/dl, AST = 48 U/l, ALT = 60 U/l, and cGT = 88 U/l serum levels (Table 1). The CT scan revealed a partial remission (PR) of liver metastases. After 6 months of the onset, the patient was treated with nab-paclitaxel (80 mg/m2, for hypersensitivity reaction to the second administration of weekly paclitaxel) and trastuzumab (2 mg pro kg) for liver progression of the disease (PD). We have seen a progressive deterioration of the general condition of the patient; the patient died about 9 months after the onset of the disease for PD.
123
2542 Table 1 Serum levels of liver function test before and after first-line chemotherapy
Dig Dis Sci (2015) 60:2541–2543
Serum levels before chemotherapy Total bilirubin
5.0 mg/dl
0.4 mg/dl
Direct bilirubin
2.5 mg/dl
0.2 mg/dl
AST
388 U/l
48 U/l
ALT
236 U/l
60 U/l
cGT
449 U/l
88 U/l
The general features of the reported case are similar to those reported in literature, and we agree with the author’s conclusion to promote liver biopsy for premortem diagnosis and appropriate therapy [2]. In fact, the peculiarity of the reported case was related to the quick response to chemotherapy and the prolonged survival in this particular condition, associated with an improvement in quality of life. According to another review by Allison et al. [3] concerning 21 reported cases of acute liver failure due to metastatic breast carcinoma, 18 cases died within 3 days to 2 months. In our experience, probably an attempt with chemotherapy should be considered, especially in young patients. In fact, it may have both a clinical benefit and an increase in survival, especially in potentially chemotherapy-sensitive tumors. Finally, we concluded that ALF caused by malignancy is an uncommon disorder and diffuse parenchymal metastases from breast cancer are a pattern that is capable of causing liver failure. The prognosis is very poor. However, an attempt with chemotherapy should be considered, especially in young patients, because it may have both a clinical benefit and an increase in survival. Other experiences are needed to corroborate our findings.
Reply Consideration of Chemotherapy for Acute Liver Failure from Breast Cancer Metastatic to the Liver To the Editor, Data concerning chemotherapy for patients presenting with acute liver failure (ALF) from breast cancer metastatic to the liver are extremely limited. In 2014, we reviewed all 32 reported cases of ALF from hepatic metastases from breast cancer, identified by computerized literature search of articles published since 1950 [2], and found that only one of these patients received chemotherapy after the diagnosis [4]. The other 31 patients were not offered chemotherapy; 24 patients had breast cancer metastatic to the liver only diagnosed by postmortem examination, and the seven other patients were too sick to undergo chemotherapy premortem because of the ALF itself or associated complications, such
123
Serum levels after chemotherapy
as esophageal variceal bleeding. These 31 patients had a fulminant clinical course and poor prognosis because of their massive, hepatic metastases: 26 patients (84 %) died within days to several weeks after presentation, 4 (13 %) died 1 month after presentation, and 1 (3 %) died 2 months after presentation. Nazario et al. [5], likewise, noted that chemotherapy for such patients was usually limited as an option by the ALF, concomitant infections, and multi-organ failure. Contrariwise, the thirty-second patient, who received chemotherapy, had an improved outcome; the liver function tests initially normalized, serum cancer markers, such as carcinoembryonic antigen, decreased toward normal, and the patient did relatively well clinically for 6 months, until rapidly succumbing to diffuse metastatic disease [4]. We thank Giuliani and Bonetti for their interesting letter. They report a second case of short-term reversal of ALF from breast cancer metastatic to the liver after administering chemotherapy. The patient did relatively well for 6 months before succumbing from metastases 3 months later. This second report of improvement after chemotherapy is refreshing for clinicians hoping for improved therapies and better prognosis for these unfortunate patients. Yet, this report should be interpreted cautiously. First, they report only one case that supplements one similar prior case. Confirmative data are required. Second, their patient had favorable prognostic features: presentation at a relatively young age of 34 years; no comorbidities; presentation with relatively mild ALF; presentation without complications of ALF or portal hypertension such as hepatorenal syndrome or variceal bleeding; and the absence of other reported complications, such as sepsis. Third, the liver function transiently improved, but the patient died 9 months after receiving chemotherapy. Our 32 reviewed cases spanned from 1950 to 2014 [2]. Chemotherapy has come a long way since 1950, and the dismal prognosis of this syndrome could be changing because of earlier diagnosis of metastases, improved ALF management, and advances in chemotherapy. We reported a statistically significant trend of increasing premortem diagnosis of this syndrome since 2000 (0 % diagnosed premortem before 2000 versus 50 % after 2000, p = 0.001, 95 % odds ratio confidence interval: [2.86, Fisher’s exact test) [2].
Dig Dis Sci (2015) 60:2541–2543
Clinicians should carefully consider chemotherapy for this syndrome. Decisions should be individualized according to ALF severity, presence of complications from ALF, comorbidities, patient age, and patient’s wishes. Decisions should involve a team, with consultation by oncologists, hepatologists, internists, and social workers. More data are essential. Mitchell S. Cappell, MD, PhD, Estela Mogrovejo, MD and Palaniappan Manickam, MD, MPH Division of Gastroenterology and Hepatology, MOB 602, Department of Medicine, William Beaumont Hospital, 3535 West Thirteen Mile Road, Royal Oak, MI 48073, USA Tel: 248-551-1227 Mitchell S. Cappell, MD, PhD Oakland University William Beaumont School of Medicine, Royal Oak, MI, USA
2543
References 1. Khashab M, Tector AJ, Kwo PY. Epidemiology of acute liver failure. Curr Gastroenterol Rep. 2007;9:66–73. 2. Mogrovejo E, Manickam P, Amin M, Cappel MS. Characterization of the syndrome of acute liver failure caused by metastases from breast carcinoma. Dig Dis Sci. 2014;59:724–726. 3. Allison KH, Fligner CL, Parks WT. Radiographically occult, diffuse intrasinusoidal hepatic metastases from primary breast carcinomas: a clinicopathologic study of 3 autopsy cases. Arch Pathol Lab Med. 2004;128:1418–1423. 4. Goswami R, Babich M, Farah KF. Occult breast malignancy masquerading as acute hepatic failure. Gastroenterol Hepatol (NY). 2011;7:62–65. 5. Nazario HE, Lepe R, Trotter JF. Metastatic breast cancer presenting as acute liver failure. Gastroenterol Hepatol (NY). 2011;7:65–66.
Conflict of interest None. In particular, Dr. Cappell as a member of the FDA Advisory Committee for GI Drugs affirms that this paper does not discuss any proprietary confidential pharmaceutical data submitted to the FDA. Dr. Cappell is a speaker for AstraZeneca. This work does not discuss any drugs manufactured or marketed by AstraZeneca.
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