Predictive factors for response to neoadjuvant chemotherapy: inflammatory and immune markers in triple-negative breast cancer.

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) predict response to neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC) patients. However, the TIL level can be determined at a few facilities. By contrast, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are easily and objectively determined from the results of full blood counts. We conducted a retrospective study to investigate whether TILs, NLR, and PLR predict NAC efficacy and whether NLR and PLR could be surrogate markers for TILs in TNBC. METHODS: Of the 266 patients diagnosed with TNBC between 2013 and 2019, 66 who underwent radical surgery after sequential administration of anthracycline and taxane as NAC were included in the study. TILs, NLR, and PLR were evaluated as predictors of pathologic complete response (pCR) using cutoff values determined from receiver operating characteristic curves. RESULTS: The cutoff values of TILs, NLR, and PLR were 20%, 2.6, and 180, respectively. High TIL level was associated with low NLR (P = 0.01) and low PLR (P = 0.01). High TIL level (odds ratio [OR] 4.28 [95% CI 1.40-13.1]; P = 0.01), low NLR (OR 5.51 [95% CI 1.60-18.9]; P = 0.01), and low PLR (OR 3.29 [95% CI 1.13-9.57]; P = 0.03) were associated with pCR. Low NLR predicted pCR independently (OR 6.59 [95% CI 1.45-30.0]; P = 0.01). CONCLUSIONS: TILs, NLR, and PLR predicted NAC efficacy against TNBC. TIL level was associated with NLR and PLR. NLR was an independent predictive factor and may be a useful surrogate marker for TILs when predicting pCR.

Fifteen-year survival and conditional survival of women with breast cancer in Osaka, Japan: A population-based study.

BACKGROUND: In recent years, the survival of patients with breast cancer has improved. However, few published studies have a longer than 10-year follow-up. Conditional relative survival (CRS), which is relative survival (RS) of patients who have survived beyond a certain period after diagnosis, is useful for assessing excess mortality among long-term survivors compared with the general population. METHODS: This was a retrospective observational cohort study. Population-based cancer registry data in Osaka, Japan were used to determine 15-year RS and 5-year CRS of women with breast cancer diagnosed between 2001 and 2002 and followed up for at least 15 years. Fifteen-year RS and age-standardized RS (ASR) were calculated by Ederer II and cohort methods. Five-year CRS according to age group and extent of disease (localized, regional, and distant) was estimated for every year from diagnosis to 10 years. RESULTS: In the cohort of 4006 patients, the ASR declined progressively, the 5-year ASR being 85.8%, 10-year ASR 77.3%, and 15-year ASR 71.6%. The overall 5-year CRS exceeded 90% at 5 years after diagnosis, reflecting a small excess mortality compared with the general population. The 5-year CRS of patients with regional and distant disease did not reach 90% within 10 years of follow-up (89.4% for regional and 72.9% for distant disease 10 years after diagnosis), indicating that these patients had substantial excess mortality. CONCLUSION: Long-term survival data can help cancer survivors plan their lives and receive better medical care and support.

[A Case of Chronic Expanding Hematoma of the Lower Abdomen after Reconstruction of Deep Inferior Epigastric Perforator Flap for Breast Cancer].

A 49-year-old woman who had surgery for left breast cancer and subsequently underwent a two-stage deep inferior epigastric perforator(DIEP)flap reconstruction. One month postoperatively, she became aware of abdominal distention and visited a local hospital. CT scan revealed subcutaneous fluid accumulation with capsular formation in the lower abdomen. Imaging findings and physical examination showed no abdominal wall scar hernia. After multiple puncture aspirations, fluid accumulation was observed again, and the possibility of a chronic expanding hematoma was considered. Later, hematoma removal, including the capsules, was performed; pathological findings showed no evidence of malignancy. No fluid retention was observed postoperatively. In cases where imaging evaluation reveals hematoma formation with capsules, hematoma removal, including the capsules, should be performed to avert the possibility of a chronic expanding hematoma.

Risk of Abemaciclib-induced Liver Injury in Hormone Receptor-positive, HER2-negative Metastatic Breast Cancer: A Retrospective Analysis.

BACKGROUND/AIM: The efficacy of endocrine therapy combined with abemaciclib for hormone receptor-positive, HER2-negative metastatic breast cancer has been established through pivotal clinical trials. However, abemaciclib-induced liver injury (AILI) can be a cause for dose reduction or discontinuation. Therefore, it is critical to understand the risk factors for AILI. PATIENTS AND METHODS: This retrospective study analyzed data from patients who had received abemaciclib combined with endocrine therapy for metastatic breast cancer as first- or second-line therapy at our hospital between December 2018 and October 2021. Relevant data were extracted from their medical records. Logistic regression analysis was performed to identify characteristics associated with AILI. RESULTS: Of the 52 eligible patients, 12 (23%) received an aromatase inhibitor (AI), and 40 (77%) received fulvestrant, concomitantly with abemaciclib. Fifteen (29%) of the patients developed liver injury after starting abemaciclib. Univariate analysis revealed the following risk factors for AILI: age ≥65 years (p=0.047), fatty liver disease (p=0.047), and concomitant use of an AI (p=0.002). Concomitant use of an AI was identified by multivariate analysis as an independent risk factor for AILI [odds ratio (OR)=10.23, 95% confidence interval (CI)=2.02-51.91, p=0.005]. CONCLUSION: Concomitant use of an AI could be the most significant factor associated with increased risk of AILI. Future research on the mechanism by which the use of an AI plus abemaciclib can cause liver injury, and prospective studies to validate our findings regarding AILI risk factors, are warranted.

Pegfilgrastim-induced vasculitis of the subclavian and basilar artery complicated by subarachnoid hemorrhage in a breast cancer patient: a case report and review of the literature.

BACKGROUND: Pegfilgrastim (PEG) is a sustained-duration pegylated form of filgrastim, a granulocyte-colony stimulating factor agent that is widely used as prophylaxis against febrile neutropenia during chemotherapy. We report the case of a breast cancer patient who developed PEG-induced vasculitis complicated by subarachnoid hemorrhage (SAH) and review the relevant literature. CASE PRESENTATION: A 48-year-old woman had undergone surgery for breast cancer and was receiving docetaxel and cyclophosphamide as adjuvant chemotherapy (docetaxel 75 mg/m2, cyclophosphamide 600 mg/m2); on day 4 of treatment, PEG had been administered. On day 14, she was admitted to hospital with fever, general malaise, and neck pain, and her C-reactive protein level was found to be high (12.65 mg/dL). Although infection was initially suspected, antimicrobial treatment was ineffective and other laboratory test results were negative for this. Contrast-enhanced computed tomography on day 22 showed thickened vessel walls in the left subclavian artery, the origin of the common carotid artery, and the thoracoabdominal aorta. On day 26, magnetic resonance imaging of the head to investigate possible causes of headache showed signs consistent with SAH, and magnetic resonance angiography images showed irregularity in the basilar artery wall; the findings of both studies were considered to be due to PEG-induced vasculitis. Once treatment with prednisolone 40 mg/day had started, the wall thickening and irregularity improved. CONCLUSION: Although an uncommon adverse effect, vasculitis affecting vessels of various sizes may be caused by PEG. To the best of our knowledge, this report is the first to describe a case of G-CSF-induced vasculitis complicated by SAH. In cases of persistent high fever and elevated inflammatory response after PEG administration and in the absence of infection, clinicians should consider the possibility of drug-induced vasculitis.

A Comparison of the Oncological Outcomes After Breast-Conserving Surgery With or Without Latissimus Dorsi Myocutaneous Flap Reconstruction for Breast Cancer.

BACKGROUND: There is little information on the oncological outcomes of breast-conserving surgery (BCS) with immediate reconstruction using a latissimus dorsi myocutaneous flap (LDMF) for breast cancer compared with BCS alone. PATIENTS AND METHODS: We conducted a retrospective cohort study from a single institution comparing the margin positivity rates after initial surgery, re-excision rates, and local recurrence (LR) between BCS with immediate LDMF reconstruction (n = 145) and BCS alone (n = 1040) performed from 2012 to 2017 for newly diagnosed stage 0-3 breast cancer. RESULTS: The positive rates of surgical margin after initial surgery were significantly lower in the BCS with LDMF group than in the BCS alone group (4.1 vs. 10.8%; P = .006). There were no marked differences in the re-excision rates between the BCS with LDMF and BCS alone groups (P = .1). At a median follow-up of 61 months, the surgical method (BCS with LD vs. BCS alone) was not associated with the LR-free survival after adjusting for various clinicopathologic factors (P = .8). CONCLUSION: Our findings suggest that BCS with immediate LDMF reconstruction is oncologically safe for breast cancer compared with BCS alone. However, further studies are needed.

Axillary management based on American college of surgeons oncology group Z0011 criteria makes it possible to omit intraoperative diagnosis of sentinel lymph nodes in early breast cancer patients.

The ACOSOG Z0011 trial has resulted in the omission of axillary lymph node dissection (ALND) in early breast cancer patients with one or two metastatic sentinel lymph nodes (SLNs). There has been increasing interest in the necessity of intraoperative assessment of SLNs in patients treated based on the Z0011 criteria. We evaluated the utility of intraoperative assessment in these eligible patients. A total of 1396 patients were treated following the Z0011 criteria from April 2012 to December 2019. We examined the proportion and clinicopathological features of patients who underwent ALND due to three or more metastatic SLNs and the sensitivity of intraoperative assessment. Only 16 (1.1%) patients had three or more metastatic SLNs diagnosed by intraoperative assessment, and they immediately underwent ALND. Of the clinicopathological factors, high clinical tumor stage (p = 0.002) and high Ki-67 labeling index value (p = 0.056) were more likely to be associated with the presence of three or more metastatic SLNs. The major independent risk factor for three or more metastatic SLNs was high clinical tumor stage (OR 3.94 [95% CI 1.42-11.0]; p = 0.009). Intraoperative assessment had low sensitivity (70.5%) and a high false-negative rate (29.5%) in detecting SLN metastases. The main finding of our study was the small proportion of patients who required ALND due to three or more metastatic SLNs according to the Z0011 criteria. The Z0011 strategy enables intraoperative assessment of SLNs to be omitted in early breast cancer patients.

Real-world effectiveness of post-trastuzumab emtansine treatment in patients with HER2-positive, unresectable and/or metastatic breast cancer: a retrospective observational study (KBCSG-TR 1917).

BACKGROUND: Trastuzumab emtansine (T-DM1) is a second-line standard therapy for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. Evidence regarding post-T-DM1 treatments is currently lacking. We evaluated the effectiveness of post-T-DM1 drug therapy in patients with HER2-positive, unresectable and/or metastatic breast cancer. METHODS: In this multicenter, retrospective, observational study, real-world clinical data of female patients with HER2-positive breast cancer who had a history of T-DM1 treatment were consecutively collected from five sites in Japan. We investigated the effectiveness of post-T-DM1 therapy by evaluating the real-world progression-free survival (rwPFS), time to treatment failure (TTF), overall survival (OS), objective response rate (ORR), and clinical benefit rate (CBR). Tumor response was assessed by investigators according to Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) guidelines. Subgroup and exploratory analyses according to background factors were also undertaken. RESULTS: Of the 205 patients who received T-DM1 treatment between 1 January 2014 and 31 December 2018, 128 were included in this study. Among the 128 patients analyzed, 105 (82%) patients received anti-HER2 therapy and 23 (18%) patients received regimens without anti-HER2 therapy. Median (95% confidence interval [CI]) rwPFS, TTF, and OS were 5.7 (4.8-6.9) months, 5.6 (4.6-6.4) months, and 22.8 (18.2-32.4) months, respectively. CBR and ORR (95% CI) were 48% (38.8-56.7) and 23% (15.1-31.4), respectively. Cox-regression analysis showed that an ECOG PS score of 0, a HER2 immunohistochemistry score of 3+, recurrent type, ≥12 month duration of T-DM1 therapy, and anti-HER2 therapy were independent variables for rwPFS. An exploratory subgroup analysis of regimens after T-DM1 showed that those with anti-HER2 therapy had a median rwPFS of 6.3 and those without anti-HER2 therapy had a median rwPFS of 4.8 months. CONCLUSIONS: In the real-world setting in Japan, several post-T-DM1 regimens for patients with unresectable and/or metastatic HER2-positive breast cancer, including continuation of anti-HER2 therapy, showed some effectiveness; however, this effectiveness was insufficient. Novel therapeutic options are still needed for further improvement of PFS and OS in later treatment settings. TRIAL REGISTRATION: UMIN000038296 ; registered on 15 October 2019.

α-Methylacyl-CoA racemase: a useful immunohistochemical marker of breast carcinoma with apocrine differentiation.

Carcinoma with apocrine differentiation is an androgen receptor (AR)-positive subset of triple-negative breast carcinomas. In addition to carcinoma with apocrine differentiation, other AR-positive triple-negative breast carcinomas occur, albeit less frequently. We found that α-methylacyl-CoA racemase (AMACR), also known as P504S, is overexpressed in carcinoma with apocrine differentiation and non-neoplastic apocrine metaplasia. We aimed to evaluate AMACR as a possible marker of carcinoma with apocrine differentiation. We immunohistochemically examined the expression of AMACR in carcinoma with apocrine differentiation and nonapocrine carcinomas and compared it with that of gross cystic disease fluid protein-15 (GCDFP-15). In total, 212 breast carcinomas were evaluated: 39 carcinomas with apocrine differentiation, 28 ductal carcinomas in situ with apocrine morphology (ADCIS), and 145 nonapocrine breast carcinomas. AMACR was expressed in 38 of 39 (97.4%) carcinomas with apocrine differentiation and in 27 of 28 (96.4%) ADCIS, consistent with the expression of GCDFP-15. However, in nonapocrine carcinomas, AMACR expression was observed in 32 of 145 (22.0%) lesions, whereas GCDFP-15 expression was observed in 91 of 145 (62.7%) lesions. For carcinoma with apocrine differentiation, AMACR was as sensitive as GCDFP-15 (both 97.1%) but more specific (77.9% versus 37.2%). In selected cases, AMACR messenger RNA (mRNA) levels were quantitatively determined relative to that of TATA-binding protein mRNA, and they comprised 5.23, 1.33, and 0.60 for carcinomas with apocrine differentiation, nonapocrine carcinomas, and normal breast tissue, respectively. CONCLUSION: Our findings demonstrate that AMACR expression may be used for differentiating carcinoma with apocrine differentiation from nonapocrine carcinomas and indicate that AMACR is a more sensitive carcinoma with apocrine differentiation marker than GCDFP-15.

Prevalence of BRCA1 and BRCA2 mutations in Japanese patients with triple-negative breast cancer: A single institute retrospective study.

Numerous databases for risk assessment of BRCA1/2 gene mutations contain insufficient data about Asians. Furthermore, few studies have reported the prevalence of germline BRCA1/2 mutations in Japanese patients, particularly those with triple-negative breast cancer (TNBC). The present study was a retrospective analysis of data from patients with TNBC who underwent BRCA1/2 mutation testing at Osaka International Cancer Institute (Osaka, Japan) between October 2014 and March 2020. A total of 65 patients with TNBC underwent a test for BRCA1/2 mutations, and 13 (20.0%) had deleterious mutations in the BRCA1 or BRCA2 genes. Furthermore, 12 out of 29 patients with a family history of breast or ovarian cancer had deleterious BRCA1/2 mutations, and only 1 of 34 without a family history had a mutation (41.4 vs. 2.9%; P=0.014). No patients aged >60 years had BRCA1/2 mutations; however, the age of diagnosis was not a significant risk factor for BRCA1/2 mutations (P=0.60). The prevalence of BRCA1/2 mutations in the present cohort of Japanese patients with TNBC was slightly higher than those reported in other larger studies from Europe and North America. Further data from large prospective studies are required to more precisely define the prevalence of BRCA1/2 mutations.

STK11 loss drives rapid progression in a breast cancer patient resulting in pulmonary tumor thrombotic microangiopathy.

We experienced a case of breast cancer in which liver metastases spread rapidly and the patient died of pulmonary tumor thrombotic microangiopathy (PTTM). PTTM is a fatal cancer-associated respiratory complication disease. To reveal genetic alterations of the clinical course, we performed next generation sequencing of the serial specimens using the Ion AmpliSeqTM Comprehensive Cancer Panel and RNA sequencing for transcriptomic data, followed by gene set analysis. The analysis revealed an oncogenic TP53 R213* mutation in all specimens and STK11 loss in tissues sampled after disease progression. Immunohistochemistry with an anti-STK11 antibody confirmed no STK11 expression in the samples after progression. Transcriptome analysis showed a significant downregulation of proteins associated with apoptosis in the specimens with STK11 loss. STK11 loss may have triggered the rapid progression of PTTM from a comprehensive genomic analysis.

[Primary Rhabdomyosarcoma of the Breast in a 16-Year-Old Girl].

We report a case of primary breast rhabdomyosarcoma. A 16-year-old girl noticed tumor of her right breast and consulted a local clinic. From the result of core needle biopsy, breast sarcoma was suspected, so she attended our hospital. Breast ultrasonography showed a mosaic pattern tumor occupying the whole right breast. CT images revealed an axillary node metastasis and no distant organ metastasis. Immunohistochemical staining of the tumor yielded positive results for desmin, MyoD1, and myogenin. Based on reverse transcription polymerase chain reaction(RT-PCR), she was diagnosed as an alveolar rhabdomyosarcoma with PAX3-FKHR(FOXO1)fusion transcripts[t(2;13)(q35;q14)]. She underwent total mastectomy and dissection of axillary lymph nodes. After surgery, the whole-body magnetic resonance imaging(MRI) demonstrated metastases of sacrum and left foot, so she was under systemic chemotherapy.

A prospective feasibility study applying the ACOSOG Z0011 criteria to Japanese patients with early breast cancer undergoing breast-conserving surgery.

BACKGROUND: In patients undergoing breast-conserving surgery and having positive sentinel lymph nodes (SLNs), the ACOSOG Z0011 trial showed equivalent loco-regional outcomes for patients receiving SLN dissection (SLND) alone and those receiving axillary lymph node dissection (ALND). We conducted a prospective single-arm study to confirm the applicability of the Z0011 criteria to Japanese patients with breast cancer. METHODS: Patients meeting the Z0011 inclusion criteria and providing consent to receive no additional ALND were prospectively enrolled at the Osaka International Cancer Institute from April 2012 to December 2016. Cumulative incidence of loco-regional recurrence was estimated and compared to that of the Z0011 study. RESULTS: Among a total of 881 patients who underwent breast-conserving surgery, 189 fulfilling the Z0011 criteria were enrolled and eligible for the subsequent analysis. Adjuvant chemotherapy was given to 113 (59.8%) patients, adjuvant hormone therapy to 170 (89.9%), and whole breast irradiation to 183 (96.8%). The frequency of tumors with positive lymphovascular invasion (p < 0.0001) and macrometastases in SLNs (p < 0.0001) were significantly higher in our study than in the Z0011 study. At the median follow-up of 36 months (range 10-64 months), only 2 of 189 patients (1.1%) experienced loco-regional recurrence. The 5-year cumulative rate of loco-regional recurrences was 1.3% (95% CI 0-3.1%), and the 3-year distant DFS rate was 96.8% (95% CI 94.0-99.6%). CONCLUSIONS: Our prospective study showed that it is feasible to apply the Z0011 strategy to Japanese patients with clinically node-negative breast cancer undergoing breast-conserving surgery with planned whole breast irradiation.

pTis and pT1a Ipsilateral Breast Tumor Recurrence Is Associated with Good Prognosis after Salvage Surgery.

OBJECTIVES: Patients with ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery have a poor prognosis. There is little information regarding the prognostic impact of the tumor size in patients with IBTR. METHODS: A total of 143 patients who had histologically confirmed IBTR without distant metastases and who underwent salvage surgery between 1989 and 2013 in our hospital were included. Distant disease-free survival (DDFS) was calculated according to the invasive tumor size of IBTR. The median follow-up period was 4.6 years. RESULTS: Patients with pT1b or more advanced IBTR have a high (≥20%) 5-year distant recurrence risk. There were significant differences in DDFS between patients with pTis or pT1a and those with pT1b or a more advanced stage (5-year DDFS: 94.4 vs. 70.1%, respectively, p value = 0.006). This significance remained after adjusting for other clinicopathological factors (p value = 0.04). CONCLUSION: Patients with pTis or pT1a IBTR have a good prognosis after salvage surgery for IBTR, and the omission of adjuvant chemotherapy could be considered. Further research and validation studies are needed.

Safety for Repeat Lumpectomy Without Radiotherapy for Ipsilateral Breast Tumor Recurrence.

BACKGROUND: There is little information on the local recurrence risk of patients who undergo repeat lumpectomy without radiotherapy after salvage surgery for ipsilateral breast tumor recurrence (IBTR). PATIENTS AND METHODS: Sixty-five patients who underwent repeat lumpectomy without radiotherapy after IBTR were retrospectively analyzed. The risk factors of second IBTR, including the breast cancer subtype of IBTR defined by the estrogen receptor (ER) and HER2 status, were assessed. RESULTS: The median follow-up period was 62 months. The 5-year second IBTR-free survival rate was 83%. Patients with the ER-positive/HER2-negative subtype of IBTR had a significantly better second IBTR-free survival rate than those with other subtypes of IBTR (88% vs. 75%, respectively, p=0.02). Multivariate analysis revealed that the breast cancer subtype of IBTR was a significantly independent predictive factor of second IBTR-free survival (p=0.003). A low-risk group for second IBTR, defined by the breast cancer subtype of IBTR and margin status of primary surgery, was detected (5-year second IBTR-free survival rate: 100%). CONCLUSION: Patients in the low-risk group defined by the breast cancer subtype of IBTR and margin status of primary surgery could safely undergo repeat lumpectomy without radiotherapy for IBTR.

Distant recurrence risk following early ipsilateral breast tumor recurrence.

At present, the risk factors for distant recurrence among patients with early ipsilateral breast tumor recurrence (IBTR) require further investigation. Early IBTR is defined as occurring within 3 years following the initial surgery. In the current study, 40 patients with early IBTR were examined to determine the risk factors for distant recurrence. A node-positive status at the time of primary surgery and the administration of adjuvant chemotherapy following the primary surgery were significantly correlated with poorer distant disease-free survival (P=0.001 and P=0.002, respectively). Multivariate analyses revealed that the nodal status at the time of primary surgery was an independent predictive factor for distant recurrence (P=0.050). Therefore, the results of the current study revealed that the nodal status at the time of primary surgery was an independent predictive factor for distant recurrence among patients with early IBTR.

Efficacy and safety of re-induction therapy with bevacizumab and paclitaxel for metastatic breast cancer.

BACKGROUND: In many trials (including E2100), bevacizumab (Bmab) monotherapy has been continued if toxicity of paclitaxel (PTX) becomes unacceptable during combined treatment with Bmab and PTX. When progression occurs on Bmab monotherapy, one possible option is re-induction with the combination of Bmab and PTX (rBP therapy), because PTX was previously stopped due to toxicity rather than progression. However, we have no data about rBP therapy. Therefore, we investigated the efficacy and safety of rBP therapy in this study. METHODS: We retrospectively investigated 46 patients who started Bmab and PTX between October 2011 and April 2013 at our institution. RESULTS: After induction with Bmab and PTX, 19 patients subsequently received Bmab monotherapy and 12 patients received rBP therapy. The overall response rate and clinical benefit rate of rBP therapy was 25 % (3/12) and 58 % (7/12), respectively, while the median time to failure of rBP therapy was 174 days (95 % CI 49-273). The median overall survival time of the 46 patients was 777 days (95 % CI 543-NA). Adverse events of grade 3 or worse associated with rBP therapy were neutropenia (25 %), fatigue (8 %), and gastrointestinal bleeding (8 %). CONCLUSIONS: This is the first report about rBP therapy, which was found to be both safe and effective. The OS of all 46 patients in this study (including 12 patients given rBP therapy) was better than in past reports. Selecting rBP therapy for patients with progression on Bmab monotherapy might have contributed to better overall survival, but a randomized controlled trial will be needed to confirm these findings.

Distant Recurrence Risk after Late Ipsilateral Breast Tumor Recurrence: Results of a Retrospective, Single-Institution Study.

OBJECTIVES: There is limited information regarding risk factors for distant recurrence in patients with late ipsilateral breast tumor recurrence (IBTR). METHODS: Late IBTR was defined as IBTR occurring >5 years after the initial surgery. Seventy-eight patients with late IBTR were reviewed to examine the risk factors of distant recurrence. RESULTS: The negative estrogen receptor and positive HER2 statuses of IBTR were significantly correlated with poorer distant disease-free survival (p=0.03 and 0.02, respectively). Multivariate analyses demonstrated that the HER2 status of IBTR was an independent predictive factor of distant recurrence (p=0.04). CONCLUSIONS: The results of our retrospective, single-institution study revealed that the HER2 status of IBTR was an independent predictive factor of distant recurrence in patients with late IBTR.

Potential biological insights revealed by an integrated assessment of proteomic and transcriptomic data in human colorectal cancer.

In the post-genomic era, the main aim of cancer research is organizing the large amount of data on gene expression and protein abundance into a meaningful biological context. Performing integrated analysis of genomic and proteomic data sets is a challenging task. To comprehensively assess the correlation between mRNA and protein expression, we focused on the gene set enrichment analysis, a recently described powerful analytical method. When the differentially expressed proteins in 12 colorectal cancer tissue samples were considered a collective set, they exhibited significant concordance with primary tumor gene expression data in 180 colorectal cancer tissue samples. We found that 53 upregulated proteins were significantly enriched in genes exhibiting elevated gene expression levels (P<0.001, ES=0.53), indicating a positive correlation between the proteomic and transcriptomic data. Similarly, 44 downregulated proteins were significantly enriched in genes exhibiting elevated gene expression levels (P<0.001, ES -0.65). Moreover, we applied gene set enrichment analysis to identify functional genetic pathways in CRC. A relatively large number of upregulated proteins were related to the two principal pathways; ECM receptor interaction was related to heparan sulfate proteoglycan 2 and vitronectin, and ribosome to RPL13, RPL27A, RPL4, RPS18, and RPS29. In conclusion, the integrated understanding of both genomic and proteomic data sets can lead to a better understanding of functional inference at the physiological level and potential molecular targets in clinical settings.

Exploration of potential genomic portraits associated with intrahepatic recurrence in human hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a heterogeneous disease with recognized variability in virus infection, genetic features, and clinical outcome. To date, transcriptional profilings of HCC have been used to predict recurrence or survival/prognosis. However, there remains a challenge to identify specific genomic prints associated with HCC recurrence, which could lead to novel therapies or effective treatment. Here we examine the association between biological signals and intrahepatic recurrence using global gene expression profiles and powerful analytical methods. MATERIALS AND METHODS: Gene expression profiles were generated in 24 HCC patients with hepatitis B infections (B-type HCC) and 60 HCC patients with hepatitis C infections (C-type HCC). Gene set enrichment analysis (GSEA) was applied to the entire ranked gene lists related to early intrahepatic recurrence, based on "ideal discriminator method." RESULTS: GSEA revealed Ribosomal Proteins as a common regulatory pathway in B-type (P < .001) and C-type (P = .003) HCC recurrence. In addition, Proteasome (P < .001) and Pentose Phosphate Pathway (P = .01) were identified as specific pathways in each type of HCC recurrence, respectively. CONCLUSIONS: Understanding these biologically common and different mechanisms related to intrahepatic recurrence in B-type and C-type HCC could be useful in the development of new therapeutic strategies in our fight against HCC.