Locoregional Recurrence and Survival Outcomes by Type of Local Therapy and Trastuzumab Use Among Women with Node-Negative,HER2-Positive Breast Cancer

Background

While human epidermal growth factor receptor 2 (HER2) overexpression is an adverse breast cancer prognostic factor, it is unclear whether there are differences in outcomes between types of local treatment in this population. This retrospective study examined locoregional recurrence and survival in women with node-negative, HER2+ breast cancer treated with breast-conserving therapy (BCT) versus mastectomy.

Methods

Subjects were 748 patients with pT1–2, N0, M0 HER2+ breast cancer, treated with BCT (n = 422) or mastectomy (n = 326). Trastuzumab was used in 54 % of subjects. The 5-year Kaplan–Meier locoregional recurrence free survival (LRRFS), breast cancer specific survival (BCSS), and overall survival (OS) were compared between cohorts treated with BCT versus mastectomy. Subgroup analyses of LRR and survival were performed separately among patients treated with BCT or mastectomy to examine the effect of trastuzumab on outcomes in each group.

Results

Median follow-up was 4.4 years. Patients treated with mastectomy had higher proportions of grade 3 histology (69 vs 60 %, p = 0.004) and lower rates of hormone therapy (51 vs 64 %, p < 0.001) and trastuzumab therapy (50 vs 57 %, p = 0.04). The 5-year outcomes in women treated with BCT compared with mastectomy were: LRRFS 98.0 versus 98.3 % (p = 0.88), BCSS 97.2 versus 96.1 % (p = 0.70), and OS 95.5 versus 93.4 % (p = 0.19). Trastuzumab was associated with similar LRRFS and improved OS in both local treatment groups.

Conclusions

BCT is safe in the population of women with pT1–2, N0, HER2+ breast cancer, providing high rates of locoregional control and survival equivalent to mastectomy. Trastuzumab was associated with improved survival in both groups.     

Rate of Contralateral Prophylactic Mastectomy is Influenced by Preoperative MRI Recommendations

Background

Women with breast cancer increasingly undergo contralateral prophylactic mastectomy (CPM). We evaluated the relationship between preoperative magnetic resonance imaging (MRI) findings and CPM. Other clinicopathologic variables associated with CPM choice and the pathology found in the contralateral breast are also reported.

Methods

Newly diagnosed breast cancer patients were prospectively enrolled in the University of Iowa Breast Molecular Epidemiology Resource. Patients with stages 0–III breast cancer who underwent mastectomy for the index cancer were eligible for this analysis. Univariate logistic regression and a multivariate model were used to identify factors predictive of CPM.

Results

Among 134 patients (mean age 54.9 years), 53 (39.6 %) chose CPM. On univariate analysis, patients undergoing CPM were more likely to have a preoperative breast MRI (64.2 vs. 39.5 %, p = 0.006) and to have follow-up testing recommended for the contralateral breast (28.3 vs. 4.9 %, p = 0.001). Univariate analysis also associated CPM with younger age (p < 0.0001), BRCA testing (p < 0.0001), BRCA mutation (p = 0.034) and reconstruction performed (p = 0.001). Median age of youngest child at diagnosis varied significantly between the CPM (15.9 years) and non-CPM (24.3 years) groups (p = 0.0018). On multivariate analysis, MRI follow-up recommendation, young age, reconstruction and human epidermal growth factor receptor 2 (HER2) positivity of the index cancer were significantly associated with CPM. Of the CPM specimens, one (1.8 %) had ductal carcinoma-in situ, which had not been identified on MRI.

Conclusions

Abnormal findings in the contralateral breast on preoperative MRI, as well as young age, reconstruction and HER2-positive status correlated with CPM choice in this cohort. Occult malignancy was rare.     

Triple-Negative Breast Cancer is Not Associated with Increased Likelihood of Nodal Metastases

Background

Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer. The purpose of this study was to determine if patients with TNBC have a higher risk of lymph node (LN) metastases.

Methods

A prospective database review identified 3,289 patients treated with a mastectomy or with breast-conserving surgery between January 2000 and May 2012. The final analysis included those patients who underwent sentinel node biopsy (SNB) and/or axillary lymph node dissection (ALND), and the following information: age at diagnosis, tumor size, grade, stage, histologic subtype, presence of lymphovascular invasion (LVI), and the status of estrogen, progesterone, and human epidermal growth factor receptor 2 (HER2).

Results

A total of 2,967 patients met the inclusion criteria. SNB was performed in 1,094 patients, ALND in 756, and both SNB and ALND in 1,117 patients. LN metastases were detected in 1,050 (35 %) patients. On univariate analysis, the LN positivity varied across subtypes with 33 % in luminal A, 42 % in luminal B, 39 % in TNBC, and 45 % in HER-2 (p = 0.0007). However, on multivariable analysis, there was no difference in LN positivity among subtypes. Age <50, grade 2 or 3 tumors, size ≥2 cm, and presence of LVI were significant predictors of LN positivity. Four or more involved nodes were observed most commonly in the HER2 (19.4 %) and luminal B (13.7 %) subtypes, but only 9.4 % in TNBC (p < 0.0001).

Conclusions

Predictors of LN metastases include younger age, higher grade, larger tumor size, and presence of LVI. Patients with TNBC are not more likely to have involved nodes than those with non-TNBC.     

Estrogen Receptor,Progesterone Receptor,and HER2 Status Predict Lymphovascular Invasion and Lymph Node Involvement

Background

The ACOSOG Z0011 trial demonstrated that axillary dissection (ALND) is not necessary for local control or survival in women with T1/2cN0 cancer undergoing breast-conserving therapy. There is concern about applying these results to triple-negative (TN) cancers secondary to their high local-recurrence (LR) rate. We examined the frequency of lymphovascular invasion (LVI) and nodal metastases in TN cancers to determine whether ALND can be safely avoided in this subtype.

Methods

Data were obtained from a database of patients with invasive breast cancer treated at Memorial Sloan Kettering Cancer Center from January 1998 to December 2010. A total of 11,596 tumors were classifiable into clinical surrogates for molecular subtype by immunohistochemical analysis: hormone receptor (HR)+/HER2+, HR+/HER2?, HR?/HER2+, and TN (HR?/HER2?). Multivariable logistic regression analysis (MVA) was used to determine associations between clinicopathologic variables and subtype.

Results

There were differences in age, tumor size, LVI, grade, and nodal involvement among groups. On MVA controlling for size, grade, and age, ER, PR, and HER2 status were significantly associated with LVI (p < 0.0001). Relative to TN tumors, HR+/HER2?, HR+/HER2+, and HR?/HER2+ tumors had higher odds of demonstrating LVI of 1.8 (odds ratio 1.8; 95 % confidence interval 1.6–2.1), 2.5 (2.5; 2.0–3.0), and 1.7 (1.7; 1.4–2.1), respectively. On MVA adjusting for size, grade, LVI, and age, TN tumors had the lowest odds of having any or high-volume nodal involvement (≥4 nodes, p < 0.0001).

Conclusions

LVI and nodal metastases were least frequent in TN cancers compared with other subtypes, despite the uniformly worse prognosis and increased LR rate in TN tumors. This suggests TN cancers spread via lymphatics less frequently than other subtypes and ALND may be avoided in TN patients meeting Z0011 eligibility criteria.     

Chemosensitivity Predicted by BluePrint 80-Gene Functional Subtype and MammaPrint in the Prospective Neoadjuvant Breast Registry Symphony Trial (NBRST)

Purpose

The purpose of the NBRST study is to compare a multigene classifier to conventional immunohistochemistry (IHC)/fluorescence in situ hybridization (FISH) subtyping to predict chemosensitivity as defined by pathological complete response (pCR) or endocrine sensitivity as defined by partial response.

Methods

The study includes women with histologically proven breast cancer, who will receive neoadjuvant chemotherapy (NCT) or neoadjuvant endocrine therapy. BluePrint in combination with MammaPrint classifies patients into four molecular subgroups: Luminal A, Luminal B, HER2, and Basal.

Results

A total of 426 patients had definitive surgery. Thirty-seven of 211 (18 %) IHC/FISH hormone receptor (HR)+/HER2? patients were reclassified by Blueprint as Basal (n = 35) or HER2 (n = 2). Fifty-three of 123 (43 %) IHC/FISH HER2+ patients were reclassified as Luminal (n = 36) or Basal (n = 17). Four of 92 (4 %) IHC/FISH triple-negative (TN) patients were reclassified as Luminal (n = 2) or HER2 (n = 2). NCT pCR rates were 2 % in Luminal A and 7 % Luminal B patients versus 10 % pCR in IHC/FISH HR+/HER2? patients. The NCT pCR rate was 53 % in BluePrint HER2 patients. This is significantly superior (p = 0.047) to the pCR rate in IHC/FISH HER2+ patients (38 %). The pCR rate of 36 of 75 IHC/FISH HER2+/HR+ patients reclassified as BPLuminal is 3 %. NCT pCR for BluePrint Basal patients was 49 of 140 (35 %), comparable to the 34 of 92 pCR rate (37 %) in IHC/FISH TN patients.

Conclusions

BluePrint molecular subtyping reclassifies 22 % (94/426) of tumors, reassigning more responsive patients to the HER2 and Basal categories while reassigning less responsive patients to the Luminal category. These findings suggest that compared with IHC/FISH, BluePrint more accurately identifies patients likely to respond (or not respond) to NCT.     

Prediction of Lymph Node Involvement in Patients with Breast Tumors Measuring 3–5 cm in a Middle-Income Setting: the Role of CancerMath

Background

In settings with limited resources, sentinel lymph node biopsy (SNB) is only offered to breast cancer patients with small tumors and a low a priori risk of axillary metastases.

Objective

We investigated whether CancerMath, a free online prediction tool for axillary lymph node involvement, is able to identify women at low risk of axillary lymph node metastases in Malaysian women with 3–5 cm tumors, with the aim to offer SNB in a targeted, cost-effective way.

Methods

Women with non-metastatic breast cancers, measuring 3–5 cm were identified within the University Malaya Medical Centre (UMMC) breast cancer registry. We compared CancerMath-predicted probabilities of lymph node involvement between women with versus without lymph node metastases. The discriminative performance of CancerMath was tested using receiver operating characteristic (ROC) analysis.

Results

Out of 1,017 patients, 520 (51 %) had axillary involvement. Tumors of women with axillary involvement were more often estrogen-receptor positive, progesterone-receptor positive, and human epidermal growth factor receptor (HER)-2 positive. The mean CancerMath score was higher in women with axillary involvement than in those without (53.5 vs. 51.3, p = 0.001). In terms of discrimination, CancerMath performed poorly, with an area under the ROC curve of 0.553 (95 % confidence interval CI 0.518–0.588). Attempts to optimize the CancerMath model by adding ethnicity and HER2 to the model did not improve discriminatory performance.

Conclusion

For Malaysian women with tumors measuring 3–5 cm, CancerMath is unable to accurately predict lymph node involvement and is therefore not helpful in the identification of women at low risk of node-positive disease who could benefit from SNB.     

Is Axillary Lymph Node Dissection Necessary After Sentinel Lymph Node Biopsy in Patients with Mastectomy and Pathological N1 Breast Cancer?

Background

The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial reported that axillary lymph node dissection (ALND) did not change the recurrence and overall survival (OS) rates in patients with lumpectomy and one to two positive nodes detected by sentinel lymph node biopsy (SLNB). The aim of this study was to determine whether patients with mastectomy and pathological N1 disease found by SLNB could forego ALND.

Materials and Methods

This is a retrospective study of 214 patients diagnosed with primary invasive breast cancer who were treated by mastectomy and lymph node staging surgery (SLNB or ALND) at the Revlon/UCLA Breast Center between January 2002 and December 2010. Patients with pathological N1 disease were separated by their first nodal surgery into SLNB (subgroups: observation, radiation, and additional ALND with or without radiation) and ALND groups (subgroups: ALND with or without radiation).

Results

After a median follow-up of 43.6 months, the OS and systemic relapse-free survival (RFS) rate of the radiation group and additional ALND group were significantly better than the observation group (p = 0.031 and 0.046, respectively). Human epidermal growth factor receptor 2 (HER2) expression was found to predict OS and patients’ age, histological grade and HER2 expression predicted systemic recurrence. Compared with the SLNB group, pain (p = 0.021) and lymphedema (p = 0.043) occurred more frequently in the ALND group.

Conclusion

Radiation was as effective as ALND in patients with mastectomy and N1 disease for OS and RFS rates, yet radiation after SLNB had fewer side effects than ALND. SLNB followed by radiation could replace ALND in patients with mastectomy and pathological N1 breast cancer identified by SLNB.     

An Investigation into the Serum Thioredoxin,Superoxide Dismutase,Malondialdehyde, and Advanced Oxidation Protein Products in Patients with Breast Cancer

Background

Reactive oxygen species (free radicals) play an important role in carcinogenesis. Extensive antioxidant defense mechanisms counteract free radicals in mammalian cells. Oxidative stress is a disturbance in the balance between the production of free radicals and antioxidant defenses. There is direct evidence that oxidative stress and lipid peroxidation (LPO) are linked to the etiology of breast cancer. The increasing global incidence of breast cancer emphasizes the need to understand the various mechanisms involved in breast tumorigenesis. The present study was undertaken to investigate the oxidative stress and antioxidant status in the blood samples of patients with breast cancer.

Methods

The present study was based on 23 women who were surgically treated at Gazi University, Faculty of Medicine, Department of General Surgery. The malondialdehyde (MDA) levels as an index of LPO along with the examination of superoxide dismutase (SOD) activities and advanced oxidation protein product (AOPP) and thioredoxin (Trx) levels were determined in the blood samples of 23 patients with breast cancer and 13 healthy controls.

Results

MDA, AOPP, and Trx levels and SOD activities were significantly higher in patients with breast cancer than the controls.

Conclusions

The results showed that oxidative stress may be related to breast cancer and especially some molecules, such as Trx and AOPP, may be useful biomarkers in breast cancer diagnosis and treatment. More detailed knowledge related to the pathophysiology of these molecules could provide valuable information on the origin and development of malignant tumors, such as breast cancer.     

Comparison of Nodal Metastasis Between BRCA Mutation Carriers and Non-BRCA Mutation Carriers with Breast Cancer

Objective

This study evaluates whether nodal status differs between breast cancer patients with BRCA mutations and those confirmed not to harbor mutations.

Methods

A prospective database identified patients with breast cancer who underwent genetic testing and axillary staging. Comparative variables included age, as well as tumor characteristics such as size, grade, lymphovascular invasion (LVI), estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (HER2-neu), and nodal status.

Results

Overall, 235 patients with breast cancer underwent genetic testing for BRCA mutations from June 2000 to May 2012. Of these patients, 74 (31.4 %) were found to express BRCA 1 and/or 2 mutations, and 161 (68.5 %) patients were verified to have no detectable BRCA mutation. Among the entire 235 patients tested, 92 (39.1 %) were found to have nodal disease. In univariable analysis, only LVI and tumor size correlated with presence of nodal metastasis. Of the 74 BRCA mutation carriers, 34 (45.9 %) had nodal metastasis compared with 58 of the 161 (36 %; p = 0.15) patients without a BRCA mutation. BRCA mutation carriers with nodal disease were more likely to have poorly differentiated tumors than those without mutations who had nodal disease (24/33 [72.7 %] vs. 27/57 [47.4 %]; p = 0.027).

Conclusion

BRCA mutations are not themselves predictive of nodal metastasis. Patients with BRCA mutations did not have a statistically significant higher prevalence of nodal metastasis than those without mutations.     

Characterization and Treatment of Local Recurrence Following Breast Conservation for Ductal Carcinoma In Situ

Purpose

The optimal treatment strategy for ductal carcinoma in situ (DCIS) continues to evolve and should consider the consequences of initial treatment on the likelihood, type, and treatment of recurrences.

Methods

We conducted a retrospective cohort study using two data sources of patients who experienced a recurrence (DCIS or invasive cancer) following breast-conserving surgery (BCS) for index DCIS: patients with an index DCIS diagnosed from 1997 to 2008 at the academic institutions of the National Comprehensive Cancer Network (NCCN; N = 88) and patients with an index DCIS diagnosed from 1990 to 2001 at community-based integrated healthcare delivery sites of the Health Maintenance Organization Cancer Research Network (CRN) (N = 182).

Results

Just under half of local recurrences in both cohorts were invasive cancer. While 40 % of patients in both cohorts underwent mastectomy alone at recurrence, treatment of the remaining patients varied. In the earlier CRN cohort, most other patients underwent repeat BCS (39 %) with only 18 % receiving mastectomy with reconstruction, whereas only 16 % had repeat BCS and 44 % had mastectomy with reconstruction in the NCCN cohort. Compared with patients not treated with radiation, those who received radiation for index DCIS were less likely to undergo repeat BCS (NCCN: 6.6 vs. 37 %, p = 0.001; CRN: 20 vs. 48 %, p = 0.0004) and more likely to experience surgical complications after treatment of recurrence (NCCN: 15 vs. 4 %, p = 0.17; CRN: 40 vs. 25 %, p = 0.09).

Conclusion

We found that treatment of recurrences after BCS and subsequent complications may be affected by the use of radiotherapy for the index DCIS. Initial treatment of DCIS may have long-term implications that should be considered.     

Impact of Availability of Immediate Breast Reconstruction on Bilateral Mastectomy Rates for Breast Cancer across the United States: Data from the Nationwide Inpatient Sample

Background

Availability of immediate breast reconstruction (IBR) varies among institutions, yet the impact of IBR availability on the rates of bilateral mastectomy (BM) versus unilateral mastectomy (UM) for breast cancer is unknown.

Methods

From the 2002 to 2010 Nationwide Inpatient Sample, we identified women with breast cancer undergoing UM or BM with and without IBR using ICD-9 codes. Hospitals were classified as performing IBR if at least one hospitalization included both mastectomy and reconstruction and then by IBR volume. Statistical comparisons utilized Chi square tests, tests for trend, and multivariable logistic regression.

Results

We identified 130,420 women undergoing UM (76.9 %) or BM (23.1 %) for breast cancer. Of 6,579 hospitals, 3,358 (51.0 %) performed no IBRs, while in the remaining 3,221 hospitals, 1 to 638 IBRs were performed per year. Large, teaching, urban, and Northeastern hospitals were more likely to have higher IBR volumes. BM rates were significantly higher in patients treated at those hospitals with higher IBR volumes, from 33.1 % at hospitals performing ≥24 IBRs per year to 9.0 % at hospitals without IBR (p < 0.001). Upon adjusted analysis, patients who elected BM were more likely to be seen at hospitals performing ≥24 IBRs per year (odds ratio 1.69 vs. UM, p < 0.001).

Conclusions

In this analysis of national data, BM rates were higher in hospitals where IBR was available, suggesting a significant influence of institutional factors on treatment options for breast cancer patients. Efforts are needed to ensure patients have access to IBR when desired and to better understand the reasons for hospital variation in BM rates.     

Initial Experience with Genomic Profiling of Heavily Pretreated Breast Cancers

Background

Rapidly evolving advances in the understanding of theorized unique driver mutations within individual patient’s cancers, as well as dramatic reduction in the cost of genomic profiling, have stimulated major interest in the role of such testing in routine clinical practice. The aim of this study was to report our initial experience with genomic testing in heavily pretreated breast cancer patients.

Methods

Patients with primary or recurrent breast cancer managed at any of our five hospitals and whose malignancy had failed to respond to therapy or had progressed on all recognized standard-of-care options were offered the opportunity to have their cancer undergo next-generation sequencing genomic profiling.

Results

Of a total of 101 patients, 98 (97 %) had at least one specific genomic alteration identified. A total of 465 different somatic genetic abnormalities were revealed in this group of patients. Although 52 % of patients were found to have an abnormality for which an U.S. Food and Drug Administration (FDA)-approved drug was available, 69 % of patients had an FDA-approved agent for an indication other than breast cancer. The most common genomic alterations of potential clinical consequence were PIK3 (25 %), FGFR1 (16 %), AKT (11 %), PTEN (10 %), ERBB2 (8 %), JAK2 (6 %), and RAF1 (5 %).

Conclusions

Almost all advanced breast cancers possess at least one well-characterized genomic alteration that might be actionable at the clinical level. Further, in most cases, a plausible argument can be advanced for the potential biological and clinical relevance of an FDA-approved antineoplastic agent not currently indicated in the treatment of breast cancer.     

Implementing a Screening Tool for Identifying Patients at Risk for Hereditary Breast and Ovarian Cancer: A Statewide Initiative

Background

The Georgia Breast Cancer Genomic Health Consortium is a partnership created with funding from the Centers for Disease Control and Prevention (CDC) to the Georgia Department of Public Health to reduce cancer disparities among high-risk minority women. The project addresses young women at increased risk for hereditary breast and ovarian cancer (HBOC) syndrome through outreach efforts.

Methods

The consortium provides education and collects surveillance data using the breast cancer genetics referral screening tool (B-RST) available at www.BreastCancerGeneScreen.org. The HBOC educational protocol was presented to 73 staff in 6 public health centers. Staff used the tool during the collection of medical history. Further family history assessments and testing for mutations in the BRCA1/2 genes were facilitated if appropriate.

Results

Data was collected from November 2012 through December 2013, including 2,159 screened women. The majority of patients identified as black/African American and were 18–49 years old. Also, 6.0 % (n = 130) had positive screens, and 60.9 % (n = 67) of the 110 patients who agreed to be contacted provided a detailed family history. A total of 47 patients (42.7 %) met National Comprehensive Cancer Network guidelines when family history was clarified. Fourteen (12.7 %) underwent genetic testing; 1 patient was positive for a BRCA2 mutation, and 1 patient was found to carry a variant of uncertain significance.

Conclusions

The introduction of genomics practice within public health departments has provided access to comprehensive cancer care for uninsured individuals. The successful implementation of the B-RST into public health centers demonstrates the opportunity for integration of HBOC screening into primary care practices.     

Hormone Receptor Status Does Not Affect Prognosis in Metaplastic Breast Cancer: A Population-Based Analysis with Comparison to Infiltrating Ductal and Lobular Carcinomas

Background

Metaplastic breast cancer is a rare histologic variant among breast cancers. We sought to investigate the impact of hormone receptor status in metaplastic breast cancer and compare outcomes with common histologic variants of breast cancer.

Methods

The study was performed utilizing the Surveillance, Epidemiology, and End Results database. A query was made for patients with metaplastic breast cancer from 2000 to 2010. A separate query identified all patients with infiltrating ductal (IDC) or lobular (ILC) carcinoma during the same period. Effect of hormone receptor status was evaluated using Cox regression analysis. Significance was assessed for p < 0.05.

Results

A total of 2,338 patients with metaplastic breast cancer were available for study. Most tumors were hormone receptor negative (79.0 %) and greater than or equal to grade 3 (82.9 %). For comparison, 382,667 and 44,813 patients with IDC and ILC, respectively, were obtained. Overall 5-year survival for metaplastic breast cancer was 62.2 % compared with 81.2 % for IDC (p < 0.001) and 80.2 % for ILC (p < 0.001). For metaplastic cases, no difference in 5-year survival was found between hormone-positive and hormone-negative tumors (65.7 vs. 63.5 %; p = 0.70). Multivariate analysis demonstrated metaplastic histology as an independent risk factor for cancer-related mortality both among hormone-positive (hazard ratio [HR] 2.4; 95 % confidence interval [CI] 1.8–3.0; p < 0.001) and hormone-negative (HR 1.7; 95 % CI 1.5–1.9; p < 0.001) breast cancers.

Conclusion

Metaplastic breast cancer is an aggressive histologic variant that portends a poor prognosis compared with common breast cancer subtypes. Contrary to other breast cancers, hormone receptor positivity does not improve prognosis in metaplastic breast cancer.     

Peritoneal transport rate,systemic inflammation,and residual renal function determine peritoneal protein clearance in continuous ambulatory peritoneal dialysis patients

Background

Peritoneal protein clearance (Pcl) is related to the mortality of patients on continuous ambulatory peritoneal dialysis (CAPD) as well as technique failure. In this prospective observational study, we aimed to investigate factors associated with the level of Pcl.

Methods

We prospectively enrolled 344 prevalent CAPD patients. A standard peritoneal equilibrium test was conducted for each patient. Baseline demographics, biochemistry, and Pcl were recorded.

Results

The average Pcl of the patients was 97.40 ± 54.14 mL/day. Peritoneal transport level, serum high-sensitivity C-reactive protein (hsCRP), and residual glomerular filtration rate (rGFR) were independently related to Pcl. The standard β values were 0.53, 0.17, and ?0.10, respectively. Moreover, compared with non-diabetic patients, diabetic patients had a non-significantly higher level of Pcl (104.90 ± 48.65 vs. 96.15 ± 54.97 mL/day; P = 0.06).

Conclusion

Continuous ambulatory peritoneal dialysis patients lose a high amount of protein through the peritoneum each day. The Pcl value is positively related to the level of peritoneal transport and hsCRP and negatively related to the rGFR.     

SMO Expression in Colorectal Cancer: Associations with Clinical,Pathological, and Molecular Features

Background

Smoothened, frizzled family receptor (SMO) is an important component of the hedgehog signaling pathway, which has been implicated in various human carcinomas. However, clinical, molecular, and prognostic associations of SMO expression in colorectal cancer remain unclear.

Methods

Using a database of 735 colon and rectal cancers in the Nurse’s Health Study and the Health Professionals Follow-up Study, we examined the relationship of tumor SMO expression (assessed by immunohistochemistry) to prognosis, and to clinical, pathological, and tumor molecular features, including mutations of KRAS, BRAF, and PIK3CA, microsatellite instability, CpG island methylator phenotype (CIMP), LINE-1 methylation, and expression of phosphorylated AKT and CTNNB1.

Results

SMO expression was detected in 370 tumors (50 %). In multivariate logistic regression analysis, SMO expression was independently inversely associated with phosphorylated AKT expression [odds ratio (OR) 0.48; 95 % confidence interval (CI) 0.34–0.67] and CTNNB1 nuclear localization (OR 0.48; 95 % CI 0.35–0.67). SMO expression was not significantly associated with colorectal cancer-specific or overall survival. However, in CIMP-high tumors, but not CIMP-low/0 tumors, SMO expression was significantly associated with better colorectal cancer-specific survival (log-rank P = 0.012; multivariate hazard ratio, 0.36; 95 % CI 0.13–0.95; P _interaction = 0.035, for SMO and CIMP status).

Conclusions

Our data reveal novel potential associations between the hedgehog, the WNT/CTNNB1, and the PI3K (phosphatidylinositol-4,5-bisphosphonate 3-kinase)/AKT pathways, supporting pivotal roles of SMO and hedgehog signaling in pathway networking. SMO expression in colorectal cancer may interact with tumor CIMP status to affect patient prognosis, although confirmation by future studies is needed.     

Breast Cancer Subtype and Distant Recurrence after Ipsilateral Breast Tumor Recurrence

Background

There is little information about the impact of breast cancer subtype on prognosis after ipsilateral breast tumor recurrence (IBTR).

Methods

One hundred eighty-five patients were classified according to breast cancer subtype, as approximated by estrogen receptor, human epidermal growth factor receptor 2 (HER2), and Ki-67, of IBTR, and we evaluated whether breast cancer subtype was associated with distant recurrence after IBTR.

Results

There was a significant difference in distant disease-free survival (DDFS) after IBTR according to breast cancer subtype defined by a cutoff of the Ki-67 index of 20 % (p = 0.0074, log-rank test). The 5-year DDFS rates for patients with luminal A, luminal B, triple-negative, and HER2 types were 86.3, 57.1, 56.6, and 65.9 %, respectively. In addition, breast cancer subtype was significantly associated with distant recurrence after IBTR on adjustment for various clinicopathologic factors (p = 0.0027, Cox proportional hazards model).

Conclusions

Our study suggests that breast cancer subtype based on immunohistochemical staining predicts the outcomes of patients with IBTR. Further analyses are needed (UMIN-CTR number UMIN000008136).     

The Protective Effect of Parity in Hormone Receptor-Positive,Ki-67 Expressing Breast Cancer

Background

Epidemiologic studies showed that the experience of pregnancy is associated with a reduced risk of breast cancer. We hypothesized that parity may differentially be associated with the development of invasive breast cancer by each subtype.

Methods

We reviewed the clinical, radiological, and pathological records of women diagnosed with invasive ductal carcinoma of the breast at Samsung Medical Center between 2005 and 2009. Clinicopathologic results were assessed by χ² and Fisher’s exact tests with a Bonferroni correction for categorical variables, and by the Kruskal–Wallis test for nonparametric continuous variables. A multinomial logistic regression model was used for multivariate analysis.

Results

Among a total of 3,095 patients, 283 (9.14 %) patients were nulliparous. Older age, higher pN, and expression of HER2 were associated with parity. In the analysis between parity and molecular subtypes, parity also had a variable influence on breast cancer subtypes (p = 0.032). Intergroup analysis with multiple comparison showed that luminal B subtype was related to nulliparity compared with HER2-positive subtypes (p = 0.03).

Conclusions

The effect of parity on the development of breast cancer differed by hormone receptor and HER2 expression. It seems that parity might have a protective effect against hormone receptor-positive breast cancer, especially cancers expressing HR+ and Ki-67. Further basic research to define and understand this result is ongoing.     

Screening Mammography Following Autologous Breast Reconstruction: An Unnecessary Effort

Background

Currently, no standard guidelines exist regarding routine screening imaging in breast cancer patients following autologous reconstruction. Concern over nonpalpable chest wall recurrence has prompted many to pursue screening imaging. We analyzed the pattern of locoregional recurrence (LRR) and yield of screening imaging and exam in these patients.

Methods

We performed a retrospective chart review of all patients who had mastectomy with autologous reconstruction between 2000 and 2009. Presentation of LRR and utility of imaging and breast exam were analyzed. Screening mammography was performed at the discretion of the treating physicians.

Results

A total of 615 patients were identified and follow-up data were available for 541. Median follow-up from time of reconstruction was 7 years. Twenty-seven patients developed a LRR (5.0 %). Among patients screened with mammography (n = 397), an abnormality led to 25 biopsies in 25 patients, and 2 were malignant (8 %). Among patients receiving routine clinical exam (n = 537), an abnormality led to 77 biopsies in 66 patients, and 30 were malignant (39 %). The median time from cancer surgery to LRR was 2.6 years. LRR was detected on clinical exam in 24 of 27 patients (88.9 %). Screening mammography detected two recurrences that were palpable on follow-up exam. One patient had an incidental chest wall recurrence found on PET/CT. In summary, 26 of 27 (96.3 %) patients had a clinically detectable LRR.

Conclusions

Diligent surveillance with clinical breast exam is a reliable method of detecting LRR after autologous reconstruction, identifying 96.3 % of recurrences in our study. Our results do not support routine mammographic screening in this population.