Inducing or Preventing Subsequent Malignancies for Breast Cancer Survivors? Double-edged Sword of Estrogen Receptor and Progesterone Receptor.

INTRODUCTION: Hormone receptor and human epidermal growth factor receptor 2 (HER2) status is important for breast cancer (BC) treatment. Previous studies have shown that the long-term treatment outcomes of BC are significantly impaired by the development of subsequent malignancies. Therefore, in the present study, we evaluated the effect of hormone receptor/HER2 status on subsequent malignancies in breast cancer survivors. METHODS AND MATERIALS: The Surveillance, Epidemiology, and End Results*Stat database (8.3.4) was used as the data source. We identified 535,941 female survivors with first primary BC through the database from 1973 to 2013. Of these patients, 23,964 had developed subsequent contralateral BC, 8398 had developed subsequent uterine or ovarian cancer, and 7435 patients had developed subsequent colorectal cancer. RESULTS: Estrogen receptor (ER) positivity and progesterone receptor (PR) positivity were significant protective factors against subsequent BC and ovarian cancer. However, ER+ BC and PR+ BC were significant risk factors for subsequent colorectal cancer. In addition, HER2+ status demonstrated a marginally significant risk effect for subsequent thyroid cancer. Triple-negative (ER-/PR-/HER2-) status showed elevated risk of subsequent breast, ovarian, and uterine cancer. CONCLUSION: ER+/PR+ patients were less likely develop secondary breast and ovarian malignancies, possibly owing to advancements in anti-ER/PR treatment. However, ER+/PR+ patients were more likely to develop colorectal cancer, suggesting a potential screening necessity for these patients.

Survival outcomes of patients with lobular carcinoma in situ who underwent bilateral mastectomy or partial mastectomy.

AIM: To compare the survival outcomes between patients treated with bilateral mastectomy and partial mastectomy alone as the initial surgical management for primary lobular carcinoma in situ (LCIS). PATIENTS AND METHODS: Patients with histologically confirmed LCIS underwent partial mastectomy alone or bilateral mastectomy were identified by the SEER*Stat database (version 8.3.2) released in 2016. The primary outcome measure was all-cause mortality and the secondary outcome measure was breast cancer-specific mortality. RESULTS: Of the 5964 cases included in the analysis, 208 cases underwent bilateral mastectomy and 5756 cases underwent partial mastectomy alone. The 1-, 5- and 10-year estimated overall survival rates were 99.7%, 96.7% and 91.7%, respectively. Univariate and multivariate proportional hazards regression (Cox) analyses showed no significant difference between the risk of all-cause mortality in the bilateral mastectomy group compared with the partial mastectomy group (HR = 1.106, 95% confidence interval [CI] 0.350-3.500, P = 0.86). In propensity score-matched model, bilateral mastectomy still did not show benefit to overall mortality (HR = 2.248, 95% CI 0.451-11.200). Patients older than 60 years of age showed a higher risk of all-cause mortality (HR = 7.593, 95% CI 5.357-10.764, P < 0.0001). No risk factors, including surgery type, were identified for breast cancer-specific survival. CONCLUSIONS: Survival outcomes of patients with LCIS who underwent partial mastectomy without radiotherapy were not inferior to patients who underwent bilateral prophylactic mastectomy. Breast cancer-specific mortality in patients with LCIS was extremely low; aggressive prophylactic surgery like bilateral prophylactic mastectomy should not be advocated for most patients with LCIS.

Signet-ring cell carcinoma of the breast: a case report.

Signet-ring cell carcinoma (SRCC) can arise from virtually all organs. However, primary SRCC of the breast is very rare. Until 2003, SRCC was placed under 'mucin-producing carcinomas' and separated from other carcinomas by the World Health Organization (WHO). To date, only a few cases have been reported. A case of a 46-year-old woman with primary SRCC of the breast is presented in this report. The patient underwent a right modified radical mastectomy with axillary lymph node dissection. Characteristic features and differential diagnosis of this tumor are discussed in the light of pertinent literature.

A case report of primary small cell carcinoma of the breast and review of the literature.

Primary small cell carcinoma (SCC) of the breast, an exceedingly rare and aggressive tumor, is often characterized by rapid progression and poor prognosis. We report a case of primary SCC of the breast that was diagnosed through pathologic and immunohistochemical examinations. Computed tomography (CT) scans failed to reveal a non-mammary primary site. Due to the scant number of relevant case summaries, this type of tumor is proved to be a diagnostic and therapeutic challenge. Therefore, we also reviewed relevant literature to share expertise in diagnosis, clinicopathologic characteristics, treatment, and prognosis of this type of tumor. Future studies with more cases are required to define more appropriate treatment indications for this disease.

Germline mutations of the E-cadherin gene in families with inherited invasive lobular breast carcinoma but no diffuse gastric cancer.

BACKGROUND: Present data are highly suggestive but do not unequivocally prove the cosegregation of germ-line CDH1 mutations with inherited invasive lobular breast cancer (ILBC). METHODS: Two Caucasian families with 6 pathologically confirmed ILBC cases but no diffuse gastric cancer (DGC) were identified in our oncogenetics consultations. Screening for mutations of CDH1, BRCA1, and BRCA2 genes was performed on blood samples. When available, loss of heterozygosity (LOH) and immunohistochemistry (IHC) analyses were performed on tumor samples. RESULTS: No BRCA1 or BRCA2 mutation was found. Deleterious CDH1 germ-line mutations c.283C>T and c.1582del were found in all the 4 living women with ILBC in family 1 and family 2, respectively. The mutation c.283C>T was also present in a healthy 71-year-old male and 2 obligate carriers in family 1. No DGC was observed in the 2 families. Loss of the wild-type CDH1 allele in 1 of the breast tumors was confirmed by LOH and IHC studies, in accordance with the "2-hit" model of tumor suppressor genes. CONCLUSIONS: Germline CDH1 mutation can be cosegregated with ILBC in the absence of DGC. Present data do not support recommendation of prophylactic gastrectomy in CDH1 germline mutation carriers with ILBC. Cancer 2011. © 2011 American Cancer Society.

Comparison of Clinical Features and Treatment Outcome of Breast Cancers in Young and Elderly Chinese Patients.

BACKGROUND: This study aimed to investigate the clinicopathological features and prognosis of operable breast cancers in young and elderly Chinese women. PATIENTS AND METHODS: This study included 209 patients aged ≤35 years and 213 patients aged ≥60 but <70 years, who received treatment between January 2000 and December 2004. The clinicopathological features, molecular subtypes, therapeutic strategies, and prognosis were evaluated. RESULTS: Tumor size was of significant difference between the 2 groups (p = 0.018), with more T2 and T3 tumors in the young group and more lymph node involvement in young patients with stage T1 tumors (p = 0.033). There were more triple-negative and less luminal A tumors in the young group (p = 0.018). 47.1% of tumors were not detected by mammography in the young group as compared to 5.5% in the elderly group (p < 0.001). More patients received chemotherapy in the young group (p < 0.001) and preferred breast-conserving surgery (p = 0.031). The 6-year disease-free survival (DFS) was 80 and 66% in the elderly and the young group, respectively (p = 0.001), but no difference was seen in overall survival. CONCLUSIONS: Compared with elderly women, young breast cancer patients have different clinicopathological features and molecular subtypes, and poorer DFS. Furthermore, the insidious onset of breast cancer in young women suggests that clinicians should pay more attention to young women with breast abnormalities.

Radiocolloid in combination with methylene dye localization, rather than wire localization, is a preferred procedure for excisional biopsy of nonpalpable breast lesions.

BACKGROUND: Wire localization (WL) is traditionally performed before excisional biopsy for patients with nonpalpable breast lesions, but it has several disadvantages. Our current study examines whether the method of radiocolloid combined with methylene dye localization (RCML) has an advantage over WL. MATERIALS AND METHODS: From August 2006 to May 2009, 157 patients with nonpalpable breast lesions classified as BI-RADS category 5 were enrolled in our study. Of the 157 patients, 78 were assigned to WL and 79 to RCML. The status of surgical margins, weight of specimens, length of incisions, and duration of operation were compared between these two groups. RESULTS: All patients were diagnosed after first excisional biopsy. The patients with malignancy accounted for 55.1% in WL group, and 53.2% in RCML group. For malignant lesions, fewer patients undergoing RCML had close or involved surgical margins than did those who had WL (19.0% vs. 39.5%, P = .038). The mean weight of specimen was 45.2 g in WL group and 39.0 g in RCML group (P < .001). The mean length of incision was 44.8 mm in WL group and 36.3 mm in RCML group (P < .001). The mean time of operation was 16.3 min for WL and 14.7 min for RCML (P = .001). CONCLUSIONS: RCML provides precise identification of the site of the nonpalpable lesion and a visible marker to the lesion for surgeons and allows rapid, easy, and accurate excision of nonpalpable breast lesions. Therefore, RCML is a promising alternative to WL.

[Risk factor analysis of mediastinal lymph node metastasis in non-small cell lung cancer patients and the strategy of mediastinoscopy prior to surgery].

OBJECTIVE: To discuss the strategy of mediastinoscopy for the evaluation of mediastinal lymph node status (metastasis or not) of non-small cell lung cancer (NSCLC) prior to surgery. METHODS: From October 2000 to June 2007, 152 consecutive NSCLC cases pathologically proven and clinically staged I-III were enrolled in the study. Of the 152 cases, there were 118 males and 34 females. Age ranged 24-79 years old and the median age was 58. All cases underwent CT and mediastinoscopy for the evaluation of mediastinal lymph node status prior to surgery. Compared with the results of final pathology, the positive rate of mediastinoscopy and the prevalence of mediastinal lymph node metastasis were calculated in the NSCLC patients with negative mediastinal or hilar lymph nodes on CT scan (the shortest axis of mediastinal or hilar lymph nodes <1 cm). Clinical characteristics used as predictive factor including sex, age, cancer location, type of pathology, T status, cancer type (central or peripheral), size of mediastinal lymph nodes (the shortest axis <1 cm or >1 cm) on CT scan and serum CEA level were analyzed by univariate and multivariate analysis with Binary logistic regression model to identify risk factors of mediastinal metastasis. RESULTS: The positive rate of mediastinoscopy was 11.6% (8/69) and the prevalence of mediastinal metastasis was 20.1% (14/69) in NSCLC with negative mediastinal or hilar lymph nodes on CT scan respectively. In clinical stage I (cT1-2N0M0) NSCLC the positive rate of mediastinoscopy was 11.3% (7/62), N2 accounting for 6.5% (4/62) and N3 4.8% (3/62), respectively; and the prevalence of mediastinal lymph node metastasis was 19.4% (12/62), N2 ccounting for 14.6% (9/62) and N3 4.8% (3/62), respectively. In the whole group both univariate and multivariate analysis showed that adenocarcinoma or mediastinal lymph nodes > or =1 cm in the shortest axis on CT scan was an independent risk factor to predict mediastinal lymph node metastasis. In NSCLC with negative mediastinal or hilar lymph nodes on CT scan both univariate and multivariate analysis showed that adenocarcinoma was a predictor of mediastinal lymph node metastasis. Conclusion We recommend the policy of routine mediastinoscopy in NSCLC prior to surgery if the mediastinal staging was only based on CT scan. Mediastinal lymph nodes > or =1 cm in the shortest axis on CT scan mandates preoperative mediastinoscopy. Adenocarcinoma also indicates mandatory mediastinoscopy even with negative mediastinal or hilar lymph nodes on CT scan.

[Evaluation of scalene lymph node or contralateral mediastinum biopsy during mediastinoscopy for non-small cell lung cancer].

OBJECTIVE: To explore the clinical indication of N3 lymph node biopsy during mediastinoscopy for non-small cell lung cancer (NSCLC). METHODS: Cervical mediastinoscopy was performed in 89 patients with clinical stage I-IIIA non-small cell lung cancer prior to thoracotomy. Of those, 12 underwent cervical medistinoscopy combined with right scalene lymph node biopsy and 10 with anterior mediastinotomy. RESULTS: Nine patients were found to have lymph node metastasis (N3 disease) during mediastinosopy. Of those, 6 had contralateral mediastinal lymph node metastasis and 3 cases with right scalene lymph node metastasis. The incidence of N3 disease in the patients with adenocarcinoma, serum CEA > 5 ng/ml and multi-station mediastinal lymph node metastasis was significantly higher than that in those with non-adenocarcinoma, CEA < 5 ng/ml and ipsilateral uni-station mediastinal lymph nodes metastasis (P < 0.05). CONCLUSION: Biopsy of scalene lymph node or contralateral mediastinal lymph node should be performed during mediastinoscopy in order to exclude N3 disease for potentially operable NSCLC patients with adenocarcinoma, serum CEA >5 ng/ml and ipsilateral multi-station mediastinal lymph nodes metastasis.

[Prospective comparison of CT versus mediastinoscopy in preoperative evaluation of mediastinal lymph node status in patients with non-small cell lung cancer].

OBJECTIVE: To compare the value of CT and mediastinoscopy in assessment of mediastinal lymph node status in potentially operable non-small cell lung cancer (NSCLC). METHODS: From Oct. 2000 to Jun. 2007, 152 consecutive patients with pathologically proven and stage I to approximately III NSCLC were enrolled into the study. Of the 152 cases, there were 118 males and 34 females, with a median age of 58 years (range, 24 to approximately 79 years). Compared with the final pathology, the sensitivity, specificity, positive and negative predictive values and accuracy of CT and mediastinoscopy for preoperative evaluation of mediastinal lymph node status were calculated, respectively. The accuracy and diagnostic efficacy of CT and mediastinoscopy was compared by Pearson chi(2) test and ROC curve, respectively. RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of detection of mediastinal metastasis was 73.8%, 70.1%, 64.9%, 78.2% and 71.7% by CT, respectively, versus 83.1%, 100.0%, 100.0%, 88.8% and 92.8% by mediastinoscopy, respectively. Both the accuracy and diagnostic efficacy of mediastinoscopy were superior to CT (Pearson chi(2) test, P < 0.001; Z test of the areas under the ROC curve, P < 0.001). The complication rate of mediastinoscopy was 4.6%, and the false negative rate was 7.2%. CONCLUSION: Mediastinoscopy is safe and effective in preoperative assessment of mediastinal lymph node status in potentially operable NSCLC, while CT alone is inadequate.

Three immunomarker support vector machines-based prognostic classifiers for stage IB non-small-cell lung cancer.

PURPOSE: Approximately 30% of patients with stage IB non-small-cell lung cancer (NSCLC) die within 5 years after surgery. Current staging methods are inadequate for predicting the prognosis of this particular subgroup. This study identifies prognostic markers for NSCLC. PATIENTS AND METHODS: We used computer-generated random numbers to study 148 paraffin-embedded specimens for immunohistochemical analysis. We studied gene expression in paraffin-embedded specimens of lung cancer tissue from 73 randomly selected patients with stage IB NSCLC who had undergone radical surgical resection and evaluated the association between the level of expression and survival. We used support vector machines (SVM)-based methods to develop three immunomarker-SVM-based prognostic classifiers for stage IB NSCLC. For validation, we used randomly assigned specimens from 75 other patients. RESULTS: We devised three immunomarker-SVM-based prognostic classifiers, including SVM1, SVM2, and SVM3, to refine prognosis of stage IB NSCLC successfully. The SVM1 model integrates age, cancer cell type, and five markers, including CD34MVD, EMA, p21ras, p21WAF1, and tissue inhibitors of metalloproteinases (TIMP) -2. The SVM2 model integrates age, cancer cell type, and 19 markers, including BCL2, caspase-9, CD34MVD, low-molecular-weight cytokeratin, high-molecular-weight cytokeratin, cyclo-oxygenase-2, EMA, HER2, matrix metalloproteinases (MMP) -2, MMP-9, p16, p21ras, p21WAF1, p27kip1, p53, TIMP-1, TIMP-2, vascular endothelial growth factor (VEGF), and beta-catenin. The SVM3 model consists of SVM1 and SVM2. The three models were independent predictors of overall survival. We validated the classifiers with data from an independent cohort of 75 patients with stage IB NSCLC. CONCLUSION: The three immunomarker-SVM-based prognostic characteristics are closely associated with overall survival among patients with stage IB NSCLC.

[Evaluation of lymph node metastasis in the contralateral mediastinum or scalene through mediastinoscopy and para-mediastinal small incision in potentially operable non-small cell lung cancer].

OBJECTIVE: The purpose of this study was to investigate the clinical characteristics of lymph node metastasis in the contralateral mediastinum and scalene in patients with potentially operable nonsmall cell lung cancer (NSCLC). METHODS: Cervical mediastinoscopy was performed for 89 patients with clinical stage I-III A non-small cell lung cancer prior to thoracotomy. Of these, 12 underwent cervical medistinoscopy combined with right scalene lymph node biopsy and 10 with anterior para-mediastinal small incision. RESULTS: A total of 9 patients were found have N3 disease on mediastinosopy, with cancer-cell-positive lymph nodes in the contralateral mediastinum in 6 and 3 in the right scalene. Statistical analysis revealed that the incidence of N3 disease in adenocarcinoma group was higher than that in patients with nonadenocarcinoma (P < 0.05), which was also higher in the patients with serum CEA >5 ng/ml than that in the patients with CEA <5 ng/ml (P < 0.05), and it was higher in the patients with ipsilateral mediastinal multi-station lymph node metastasis than that in the patients with uni-station lymph node metastasis (P < 0.05). CONCLUSION: Biopsy of contralateral mediastinal lymph nodes or scalene lymph node should be performed in order to exclude N3 disease for potentially operable NSCLC patients with adenocarcinoma, serum CEA >5 ng/ml or ipsilateral multi-station mediastinal lymph node metastasis.

[Detection of sentinel lymph node in patients with early stage breast cancer].

BACKGROUND & OBJECTIVE: Axillary lymph node dissection (ALND) is routinely performed during surgery for breast cancer, but whether ALND could increase survival rate of early stage breast cancer patients remains controversial. Recently, replacing ALND with sentinel lymph node (SLN) biopsy has became a hotspot in breast cancer research. This study aimed to evaluate the reliability and accuracy of SLN biopsy for early stage breast cancer, and to discover the significance of multiple step section level cytokeratin immunohistochemistry in identifying micrometastatic disease. METHODS: SLN biopsy was performed on 121 patients with T1 or T2 breast cancer: methylene blue-labeling was used in 38 patients (methylene blue group), double-labeling of (99m)Tc sulfur colloid and methylene blue was used in 83 patients (combination group). Lymphoscintigraphy and hand-hold gamma detector were used to localize SLNs before operation. All SLNs and ALND lymph nodes were pathologically examined. The tumor-negative SLNs were cut at three levels, and detected by immunohistochemistry. RESULTS: Success rates were 81.6% in methylene blue group, and 95.2% in combination group; accurate detection rates of axillary lymph nodes were 93.5% in methylene blue group, and 97.5% in combination group. SLNs were found in 19 patients (23%) by lymphoscintigraphy, and 76 patients (92%) by hand-hold gamma detector, respectively (P=0.04). A total of 194 negative SLNs, detected by routine pathologic examination, were re-examined by multiple step section level cytokeratin immunohistochemistry; micrometastatic diseases were identified in 21 SLNs of 13 patients. The accuracy rate of combined examinations was 98.7%, and the false-negative rate was 3.2%. CONCLUSIONS: The axillary node status can be predicted by SLN biopsy; double-staining is better than methylene blue-labeling. The role of lymphoscintigraphy in SLN biopsy needs further explore. Multiple step section level cytokeratin immunohistochemistry can improve detection rate of micrometastatic diseases.

[Clinical value of cervical mediastinoscopy in non-small cell lung cancer of stage I].

BACKGROUND & OBJECTIVE: Whether to apply routine mediastinoscopy to non-small cell lung cancer (NSCLC) of stage I remains controversial. This study was to evaluate application of cervical mediastinoscopy in detecting mediastinal lymph nodes status of NSCLC of stage I. METHODS: The cervical mediastinoscopy was performed in 31 patients with NSCLC of stage I prior to thoracotomy from Oct. 2000 to Feb. 2004. Mediastinoscopy-positive (stage N2) patients received neoadjuvant chemotherapy. RESULTS: Of the 31 patients, 2 had disease of stage N2, and 1 had disease of stage N3 (right scalenus lymph node metastasis); positive rate of mediastinosopy was 10% (3/31), sensitivity, specificity, and accuracy of mediastinoscopy were 75%, 100%, and 97%, respectively. CONCLUSION: Mediastinoscopy might be a routine examination for patients with NSCLC of stage I.