Survival analysis of breast cancer patients after diagnosis of second primary malignancies, focusing on the second primary hematologic malignancy

Purpose@#Although the overall survival (OS) of breast cancer patients is increasing with improved detection and therapies, so is the risk of breast cancer patients developing subsequent malignancies. We investigated the OS of breast cancer survivors according to sites of second primary malignancies (SPM). The OS of the second primary hematologic malignancy (SPHM) was then compared with that of metastatic breast cancer (MBC). @*Methods@#We retrospectively analyzed patients diagnosed with primary breast cancer between 1998 and 2019. Only those with SPM were eligible for analysis. First, the OS of patients with SPM diagnosed as the first event after the diagnosis of breast cancer was analyzed. Next, the OS of patients with SPHM, with or without breast cancer relapse, was compared with that of patients with MBC, matched using the propensity score. @*Results@#Patients diagnosed with SPM without breast cancer relapse as the first event had a significantly better OS than did patients with MBC, but the OS of those with SPHM as the first event did not differ significantly from that of patients with MBC (hazard ratio [HR], 1.558; 95% confidence interval [CI], 0.856–2.839; P = 0.147). The OS of patients with SPHM with or without breast cancer relapse was worse than that of the MBC group after propensity score matching (HR, 1.954; 95% CI, 1.045–3.654; P = 0.036). @*Conclusion@#Prognosis of SPM diagnosed as the first event was statistically better than that of MBC, except in case of SPHM. Patients with SPHM, with or without MBC, showed poor OS before and after propensity score matching.

Can chemotherapy be omitted for patients with N0 or N1 endocrine-sensitive breast cancer treated with gonadotropin-releasing hormone agonist and tamoxifen?

Purpose@#Whether administering chemotherapy followed by tamoxifen plus a gonadotropin-releasing hormone (GnRH) agonist to treat patients with lower-risk hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer provides a greater benefit than administering tamoxifen plus GnRH agonist alone remains unclear. This study aimed to compare the outcomes of propensity score-matched (PSM) patients who underwent these 2 types of treatment plans. @*Methods@#This retrospective study included patients treated at our institution between 2009 and 2019. Eligible patients had HR-positive, HER2-negative, invasive breast cancer who had undergone surgery. There were 579 patients with HR-positive, HER2-negative breast cancer who were treated with a GnRH agonist and tamoxifen; patients with pathologic N2 and those who received neoadjuvant chemotherapy were excluded. After 1:1 PSM of patients who underwent GnRH agonist treatment and tamoxifen with versus without chemotherapy, 122 patients from these 2 groups were analyzed. Survival rates were calculated using the Kaplan-Meier method and compared via the log-rank test. @*Results@#After PSM, there were no significant differences in several baseline characteristics between the 2 groups. After a median follow-up of 62.8 months, the patients in both groups demonstrated similar outcomes with no significant difference in disease-free survival (P = 0.596). @*Conclusion@#Patients derived no significant survival benefit from undergoing a chemotherapy regimen before receiving tamoxifen and GnRH agonist therapy compared to forgoing such chemotherapy.

The Prediction of HER2-Targeted Treatment Response Using 64CuTetra- Azacyclododecanetetra-Acetic Acid (DOTA)-Trastuzumab PET/CT in Metastatic Breast Cancer: A Case Report / 한국유방암학회지

A 45-year-old woman diagnosed with breast cancer reported disease progression in the form of metastatic lung and recurrent breast lesions following chemotherapy and human epidermal growth factor receptor 2 (HER2)-targeted therapy. The patient underwent 64 Cu-tetra-azacyclododecanetetra-acetic acid (DOTA)-trastuzumab positron emission tomography/computed tomography (PET/CT) to evaluate the HER2 expression status.64 Cu-DOTA-trastuzumab accumulated in the left breast and lymph nodes but not in the lung lesions. Following trastuzumab emtansine treatment, there was a significant improvement in the lesions with 64 Cu-DOTA-trastuzumab accumulation. However, the lesions that did not accumulate 64 Cu-DOTA-trastuzumab aggravated. Therefore, it was concluded that 64 CuDOTA-trastuzumab PET/CT can be used to predict the outcome of HER2-targeted treatment by evaluating HER2 expression in breast cancer patients.

Comparison of the Efficacy between First-Line Treatment Regimens for Patients with Hormone Receptor-Positive and HER2-Negative Metastatic Breast Cancer

Purpose@#Endocrine therapy is the first-line treatment recommended for patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer without visceral crisis. However, this recommendation has not been followed clinically because of efficacy issues. In this study, the survival of patients with HR-positive/HER2-negative metastatic breast cancer was evaluated based on the following first-line treatment regimens: the combination of palbociclib plus letrozole, conventional endocrine therapy, or chemotherapy. @*Methods@#Medical records were reviewed for this retrospective analysis. Patients with HR-positive/HER2-negative metastatic breast cancer were included. Progression-free survival (PFS) and overall survival (OS) were compared based on first-line treatment regimens. @*Results@#A total of 184 patients were included in the analysis. The first-line treatments were palbociclib plus letrozole in 46 patients (25.0%), endocrine therapy in 40 patients (21.7%), and chemotherapy in 98 patients (53.3%). The PFS of the palbociclib plus letrozole group was significantly longer than that of the endocrine therapy (hazard ratio=3.43, p<0.001) and chemotherapy (hazard ratio=2.88, p=0.001) groups. No significant difference was observed between the endocrine therapy and chemotherapy groups (p=0.430). The OS of the palbociclib plus letrozole group was significantly longer than that of the endocrine therapy (hazard ratio=5.34, p=0.009) and chemotherapy (hazard ratio 4.23, p=0.043) groups. No significant difference was observed between the endocrine therapy and chemotherapy groups (p=0.451). @*Conclusion@#The combination regimen of palbociclib and letrozole could be recommended as the first-line treatment of choice in patients with HR-positive/HER2-negative metastatic breast cancer.

Predicting the Benefit of Adjuvant Aromatase Inhibitor Therapy in Postmenopausal Breast Cancer Patients with Phosphorylated S6K1 Expression Status / 한국유방암학회지

PURPOSE: Phosphorylated ribosomal S6 kinase 1 (pS6K1) is a major downstream regulator of the mammalian target of rapamycin (mTOR) pathway. Recent studies have addressed the role of S6K1 in adipogenesis. pS6K1 may affect the outcome of estrogen depletion therapy in patients with hormone-sensitive breast cancer due to its association with adipogenesis and increased local estrogen levels. This study aimed to investigate the potential of pS6K1 as a predictive marker of adjuvant aromatase inhibitor (AI) therapy outcome in postmenopausal or ovarian function-suppressed patients with hormone-sensitive breast cancer.METHODS: Medical records were retrospectively reviewed in postmenopausal or ovarian function-suppressed patients with estrogen receptor-positive and node-positive primary breast cancer. pS6K1 expression status was scored on a scale from 0 (negative) to 3+ (positive) based on immunohistochemical analysis.RESULTS: A total of 428 patients were eligible. The median follow-up duration was 44 months (range, 1–90). In patients with positive pS6K1 expression, AIs significantly improved disease-free survival (DFS) compared to selective estrogen receptor modulators (SERMs) (5 year-DFS: 83.5% vs. 50.7%, p = 0.016). However, there was no benefit of AIs on DFS in the pS6K1 negative group (5 year-DFS 87.6% vs. 91.4%, p = 0.630). On multivariate analysis, AI therapy remained a significant predictor for DFS in the pS6K1 positive group (hazard ratio, 0.39; 95% confidence interval, 0.16–0.96; p = 0.041). pS6K1 was more effective in predicting the benefit of AI therapy in patients with ages < 50 (p = 0.021) compared to those with ages ≥ 50 (p = 0.188).CONCLUSION: pS6K1 expression may predict AI therapy outcomes and serve as a potential predictive marker for adjuvant endocrine therapy in postmenopausal and ovarian function-suppressed patients with hormone-sensitive breast cancer. AIs may be more effective in patients with pS6K1 positive tumors, while SERM could be considered an alternative option for patients with pS6K1 negative tumors.

A cavernous hemangioma located in the axillary area: Challenges in preoperative diagnosis and operation

Cavernous hemangiomas are benign neoplasms of endothelial cells. Although this neoplasm has the potential to develop in all parts of the body, it rarely develops in the axilla; in fact, there are only two case reports of axillary cavernous hemangiomas in the literature. Here, we describe a third case, which occurred in a 30-year-old Korean woman. The patient presented with a palpable mass in the left axilla that was initially thought to be either a phyllodes tumor or a lymphoma based on imaging studies. However, the results of an excisional biopsy led to a diagnosis of cavernous hemangioma. Although uncommon, a cavernous hemangioma can be encountered unexpectedly, presenting as a mass in axilla. Although usually curative, surgery may be challenging not only because of the rarity of the condition, but also because of inconsistent preoperative findings and the involvement of large vessels.

Predictive Value of the Standardized Uptake Value of 18F-fluorodeoxyglucose Positron Emission Tomography-Computed Tomography in Assessing Axillary Lymph Node Metastasis in Different Subtypes of Breast Cancer

PURPOSE@#This study aimed to examine the association between the maximum standardized uptake value (SUVmax) of different molecular subtypes of primary breast cancer with axillary lymph node (ALN) metastasis.@*METHODS@#The medical records of 633 patients, who underwent 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET/CT) for preoperative staging, were retrospectively reviewed. The cohort was stratified by the following molecular subtypes with immunohistochemical examination: luminal A, luminal B, human epidermal growth factor receptor 2 positive (HER2+), and triple negative. We evaluated the optimal cutoff SUVmax to predict ALN metastasis in each subtype using the receiver operating characteristic (ROC) analysis. Moreover, the risk factors for ALN metastasis were evaluated.@*RESULTS@#Overall, the SUVmax was positively correlated with the number of metastatic ALN (p=0.001). The mean SUVmax was higher in aggressive subtypes (4.5±0.2, 6.1±0.4, 6.5±0.5, and 7.5±0.5 in luminal A, luminal B, HER2+, and triple negative, respectively, p<0.001). Upon ROC analysis, the SUVmax of the HER2+ subtype predicted ALN metastasis most accurately, with a cutoff value of 5.5, area under the curve (AUC) of 0.708, sensitivity of 74.2%, and specificity of 64.6% (p=0.002). The triple negative subtype did not show a significant difference in SUVmax between patients with and without metastasis (p=0.13). Subtype-adjusted SUVmax, HER2 positivity, lymphovascular invasion, and T stage were significant predictors for ALN metastasis.@*CONCLUSION@#The SUVmax of primary breast cancer may be an independent predictor of ALN metastasis, being the most accurate in the HER2+ subtype. As PET/CT could facilitate tailored axillary management, this approach could be considered for the initial staging and treatment planning in patients with breast cancer.

Efficacy of Combined Aromatase Inhibitor and Luteinizing Hormone-Releasing Hormone Agonist in Premenopausal Metastatic Breast Cancer

PURPOSE: Endocrine therapy is the preferred treatment for hormone receptor (HR)-positive metastatic breast cancer (MBC). We investigated the efficacy of combined aromatase inhibitor (AI) and luteinizing hormone-releasing hormone (LHRH) agonist in premenopausal patients with HR-positive MBC. METHODS: We retrospectively analyzed the medical records of 21 HR-positive premenopausal MBC patients treated with combined AI and LHRH agonist therapy. RESULTS: The median follow-up period was 32.9 months. The overall response rate was 47.6%, with three complete responses (14.3%) and seven partial responses (33.3%). Nine patients (42.9%) achieved stable disease lasting more than 6 months; thus, the clinical benefit rate was 90.4%. The median time to progression was 45.4 months. No patients experienced grade 3 or 4 toxicity. CONCLUSION: Combined AI and LHRH agonist treatment safely and effectively induced remission or prolonged disease stabilization, suggesting that this could be a promising treatment option for HR-positive premenopausal patients with MBC.

Clinical Implications According to Diagnostic Methods of Human Epidermal Growth Factor Receptor 2 Positivity in Breast Cancer: A Retrospective Study

PURPOSE: According to American Society of Clinical Oncology/College of American Pathologists guidelines, breast cancer is human epidermal growth factor receptor 2 (HER2) positive if there is HER2 protein overexpression at a 3+ level on immunohistochemistry (IHC 3+) or gene amplification (more than six copies per nucleus) on fluorescence in situ hybridization (FISH+). However, there have been few reports on whether outcomes differ based on diagnosis by these two techniques. In this study, we compared outcomes based on the two methods in patients with HER2-positive breast cancer. METHODS: This study was a retrospective analysis of HER2-positive breast cancer in 18,304 patients, including 14,652 IHC 3+ patients and 3,652 FISH+ patients from the Korean Breast Cancer Society Registry. We compared breast cancer-specific survival and overall survival based on IHC 3+ and FISH+ status with or without trastuzumab. RESULTS: Breast cancer-specific survival was significantly different between the IHC 3+ and FISH+ groups, with 5-year cumulative survival rates of 95.0% for IHC 3+ and 98.5% for FISH+ patients who did not receive trastuzumab (p=0.001) in Kaplan-Meier methods. However, there were no significant differences in breast cancer-specific survival and overall survival between IHC 3+ and FISH+ groups regardless of trastuzumab treatment in Cox proportional hazards models. CONCLUSION: The survival outcomes were not affected by the different two diagnostic methods of HER2-positive breast cancer. Further research to evaluate differences in prognosis and other characteristics according to the diagnostic methods of HER2 positivity is needed in the future.

Comparative Study between Sentinel Lymph Node Biopsy and Axillary Dissection in Patients with One or Two Lymph Node Metastases / 한국유방암학회지

PURPOSE: Sentinel lymph node biopsy (SLNB) is a standard axillary surgery in early breast cancer. If the SLNB result is positive, subsequent axillary lymph node dissection (ALND) is a routine procedure. In 2011, the American College of Surgeons Oncology Group Z0011 trial revealed that ALND may not be necessary in early breast cancer with one or two positive sentinel lymph nodes. The purpose of this study was to compare outcomes among Korean patients with one or two positive axillary lymph nodes in the final pathology who did and did not undergo ALND. METHODS: A total of 131,717 patients from the Korea Breast Cancer Society registry database received breast cancer surgery from January 1995 to December 2014. Inclusion criteria were T stage 1 or 2, one or two positive lymph nodes, and having received breast-conserving surgery (BCS), whole breast radiation therapy, and no neoadjuvant therapy. We analyzed the differences in disease-specific survival (DSS) and overall survival (OS) between patients who received SLNB only and those who underwent SLNB+ALND. RESULTS: A total 4,442 patients met the inclusion criteria, with 1,268 (28.6%) in the SLNB group and 3,174 (71.4%) in the SLNB+ALND group. There were no differences in DSS and OS between the two groups (p=0.378 and p=0.925, respectively). The number of patients who underwent SLNB alone for one or two positive lymph nodes increased continuously from 2004 to 2014. CONCLUSION: Korean patients with early breast cancer and 1 or 2 positive axillary lymph nodes who received BCS plus SLNB showed no significant difference in DSS and OS regardless of whether they received ALND. The findings of this retrospective study demonstrate that omitting ALND can be considered when treating selected patients with early breast cancer who have one or two positive lymph nodes.

Factors Associated with Metastatic Breast Cancer in Patients Who Show Long-Term Stable Disease Status

PURPOSE: This study aimed to analyze the basic clinical characteristics and survival of patients with breast cancer whose disease had been stably maintained for more than 24 months after systemic therapy. METHODS: We retrospectively reviewed the medical records of patients with primary breast cancer who underwent surgery. Among these patients, patients with stage IV disease at diagnosis or those who developed distant metastasis during the follow-up period after surgery were included in this analysis. Patients whose disease remained stable for more than 24 months were classified as the long-term stable disease group. The remaining patients were classified as the control group. RESULTS: A total of 245 patients were eligible for this analysis. Patients in the long-term stable disease group showed a lower rate of histologic type III, a higher rate of hormone receptor positivity, and received less adjuvant chemotherapy. In the long-term stable disease group, the most frequent site of metastasis was the lungs, whereas in the control group, it was the bones. Overall survival was significantly better in the long-term stable disease group than in the control group (p<0.001). In univariate analysis, factors affecting the overall survival rate were the duration from diagnosis to metastasis, the absence of lymphatic infiltration, and the presence of hormone receptors. In multivariate analysis, the duration from diagnosis to metastasis and the absence of lymphatic infiltration were significant factors affecting the overall survival rate. CONCLUSION: Disease progression was observed in many patients even after the disease had been stable for more than 24 months after systemic therapy. Although these patients had better outcomes compared with the others, continuous observation and possible additional treatment might be helpful for some patients.

Phosphorylated S6 Kinase-1 as Predictive Marker of Lapatinib Efficacy in Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer Patients

PURPOSE: The 40S ribosomal protein S6 kinase-1 (S6K1) is a crucial downstream effector of the PI3K/AKT/mTOR pathway. S6K1 overexpression is found in 10% to 30% of breast cancers and is associated with aggressive disease and poor prognosis. Herein, we investigated the relationship between the expression of phosphorylated S6K1 (p-S6K1) and efficacy of lapatinib in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. METHODS: We retrospectively analyzed the data of 36 patients with HER2-positive metastatic breast cancer treated with lapatinib between January 2010 and September 2014. The p-S6K1 expression status of the primary tumor was assessed via immunohistochemistry using a mouse monoclonal antibody. RESULTS: Fourteen of the 36 patients (38.9%) had p-S6K1-positive tumors. The median progression-free survival (PFS) of patients with p-S6K1-positive tumors was significantly longer than that of patients with p-S6K1-negative tumors (13.4 months vs. 7.1 months, p=0.025). In multivariate analysis, p-S6K1 positivity remained an independent, favorable predictive factor for PFS (hazard ratio, 0.32; 95% confidence interval, 0.11–0.97; p=0.044). CONCLUSION: The high expression of p-S6K1 was significantly associated with prolonged PFS, suggesting that p-S6K1 can be a potential biomarker for predicting the efficacy of lapatinib in patients with HER2-positive metastatic breast cancer.

The Examination of Ovarian Reserve in Premenopausal Patients with Hormone Receptor Positive Breast Cancer / 이화의대지

The evaluation of menopausal status is an important subject in the field of treatment of hormone receptor positive breast cancer. According to the menopausal status, endocrine therapy should be categorized by individual patient. However, the gonadal injury caused by various therapeutic drugs and its recovery would confuse the interpretation of clinical and biological markers for ovarian reserve. There are some methods to examine the functional ovarian reserve indirectly. Ultrasonography for counting follicles is a relatively reliable procedure, although it is not feasible because of time-labor consumption and high cost. Biological marker from blood samples such as serum follicle stimulating hormone (FSH), serum estradiol (E2), serum inhibin, or anti-Müllerian hormone (AMH) would be a better choice. The examination of serum FSH and E2 is already recommended as biomarkers for measuring functional ovarian reserve in many guidelines. However, there are limitation of serum FSH and E2 in patients with chemotherapy-induced amenorrhea and treated by tamoxifen. AMH is promising biomarker in the field of infertility treatment even in the patients treated by chemotherapy. It might be a possible biomarker to determine the menopausal status for decision-making whether aromatase inhibitor could be applicable or not in hormone positive breast cancer patients with chemotherapy induced amenorrhea or treated by tamoxifen.

The Molecular Subtype Dependent Effect of Concurrent Radiotherapy and Systemic Therapy on Breast Cancer: Analysis of a Human In Vivo Model of Metastatic Brain Lesions

PURPOSE: The molecular subtype of breast cancer is an important predictive factor. Therefore, we investigated the effects of concurrent or serial radiotherapy and systemic therapy on metastatic brain lesions according to the molecular subtype of breast cancer. METHODS: The present retrospective study examined data from 66 patients with breast cancer and metastatic brain lesions, who were treated using radiotherapy between January 1990 and July 2014. Patients were classified into the following three subtypes based on their hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status: HR+/HER2− (luminal A, 13 patients), HR+/HER2+ (luminal B, 21 patients), HR−/HER2+ (HER2, 22 patients), or HR−/HER2− (triple negative, 10 patients). The brain lesions and their responses to treatment were evaluated using brain computed tomography or magnetic resonance imaging. Progression of brain disease was defined by a ≥20% increase in the sum of the lesion's diameters or the development of a new brain lesion. Progression-free survival was calculated from the initiation of radiotherapy to the first instance of brain disease progression or last follow-up. RESULTS: Patients in the HER2 group who had received concur-rent radiotherapy and systemic therapy (mainly HER2-targeted therapy) exhibited significantly better progression-free survival than did patients who had received radiotherapy followed by systemic therapy (p=0.037). However, concurrent radiotherapy and systemic therapy did not significantly improve progression-free survival in the luminal A (p=0.527), luminal B (p=0.462), or triple negative (p=0.558) groups. CONCLUSION: Concurrent radiotherapy and mainly HER2-targeted systemic therapy significantly prolonged progression-free survival in the HER2 group.

Evaluation of the Survival Benefit of Different Chemotherapy Regimens in Patients with T1-2N0 Triple-Negative Breast Cancer / 한국유방암학회지

PURPOSE: This study aimed to evaluate the survival benefit of different adjuvant chemotherapy regimens in patients with T1-2N0 triple-negative breast cancer. METHODS: Of 67,321 patients who were registered in the Korean Breast Cancer Society nationwide database between January 1999 and December 2008, 4,033 patients with T1-2N0 triple-negative breast cancer were included. The overall survival of patients who did not receive adjuvant chemotherapy was compared with those treated with adjuvant anthracycline and cyclophosphamide (AC), 5-fluorouracil, anthracycline, and cyclophosphamide (FAC), or cyclophosphamide, methotrexate, and 5-fluorouracil (CMF). RESULTS: The median follow-up was 52.5 months. Chemotherapy was used in 87.4% of patients; it was used more commonly in patients with T2 tumors, those who were younger, had a higher histologic grade, and who showed lymphovascular invasion. The 5-year cumulative overall survival rate was 95.4%. Younger age, breast-conserving surgery, and adjuvant chemotherapy were significantly associated with improved overall survival. The 5-year cumulative overall survival rate of patients who did not receive adjuvant chemotherapy and those treated with AC, FAC, and CMF were 92.5%, 95.9%, 95.3%, and 95.9%, respectively. On multivariate analysis, the administration of any adjuvant chemotherapy regimen was significantly associated with improved overall survival (p=0.038). No significant difference in survival benefit was observed among the three different treatment groups. CONCLUSION: A standard adjuvant chemotherapy regimen with the least drug-related toxicity might be a reasonable treatment for patients with T1-2N0 triple-negative breast cancer.

Serial Serum HER2 Measurements for the Detection of Breast Cancer Recurrence in HER2-Positive Patients / 한국유방암학회지

PURPOSE: The measurement of serum human epidermal growth factor receptor 2 (HER2) extracellular domain levels is a well-established method for evaluating whether a metastatic HER2-positive breast cancer patient will respond to HER2-targeted treatment. However, little is known about the value of serum HER2 for detecting disease relapse following curative surgical treatment in breast cancer patients. The purpose of this study was to evaluate the sensitivity of serum HER2, carcinoembryonic antigen (CEA), and carcinoma antigen 15-3 (CA 15-3) for the detection of disease recurrence in postoperative breast cancer patients with a primary HER2-positive tumor. METHODS: Serial measurements were taken of serum HER2, CEA, and CA 15-3 levels in patients with primary invasive HER2-positive breast cancer who underwent curative surgical treatment between January 2008 and December 2010. Following treatment, serum HER2 levels were monitored every 6 months using a chemiluminescence immunoassay. RESULTS: Overall, 264 patients were analyzed in this retrospective study. The median follow-up period was 27.7 months, and 24 patients relapsed during follow-up. The sensitivity of serum HER2, CEA, and CA 15-3 for the detection of disease recurrence was 37.5%, 25.1%, and 12.5%, respectively. Sensitivity increased to 45.8% when all three tumor markers were combined in the analysis. In a subgroup of patients without liver disease, the sensitivity of serum HER2, CEA, and CA 15-3 was 57.1%, 21.4%, and 14.3%, respectively. Of the 264 patients in this study, 80 patients had chronic hepatitis, liver cirrhosis, or abnormal aspartate aminotransferase or alanine aminotransferase levels during the follow-up period. Following the exclusion of these patients, the sensitivity of serum HER2 for the detection of disease recurrence increased to 57.1%. CONCLUSION: Serial serum HER2 measurement may be useful for the detection of disease relapse in patients with HER2-positive breast cancer. Abnormal liver function can result in elevated serum HER2 in the absence of disease recurrence.