Impact of neoadjuvant chemotherapy on the safety and long-term outcomes of patients undergoing immediate breast reconstruction after mastectomy.

BACKGROUND: In breast cancer patients receiving neoadjuvant chemotherapy (NAC), immediate breast reconstruction (IBR) as a breast cancer treatment option remains controversial. We assessed the impact of NAC on surgical and oncological outcomes of patients undergoing IBR. METHODS: This was a retrospective multicenter study of 4726 breast cancer cases undergoing IBR. The rate of postoperative complications and survival data were compared between IBR patients who received NAC and those who did not receive NAC. Propensity score matching analysis was performed to mitigate selection bias for survival. RESULTS: Of the total 4726 cases, 473 (10.0%) received NAC. Out of the cases with NAC, 96 (20.3%) experienced postoperative complications, while 744 cases (17.5%) without NAC had postoperative complications. NAC did not significant increase the risk of complications after IBR (Odds ratio, 0.96; 95%CI 0.74-1.25). At the median follow-up time of 76.5 months, 36 patients in the NAC group and 147 patients in the control group developed local recurrences. The 5-year local recurrence-free survival rate was 93.1% in the NAC group and 97.1% in the control group. (P < 0.001). After matching, there was no significant difference between the two groups. CONCLUSION: IBR after NAC is a safe procedure with an acceptable postoperative complication profile.

Impact of radiation therapy for breast cancer with involved surgical margin after immediate breast reconstruction: A multi-institutional observational study.

INTRODUCTION: Involved surgical margins are risk factors for local recurrence and re-excision is often difficult, particularly in patients with breast cancer undergoing immediate breast reconstruction (IBR). However, the magnitude of the effect of radiation therapy on preventing local recurrence for breast cancers with involved margins has not been sufficiently assessed. MATERIALS AND METHODS: We retrospectively assessed sites of involved surgical margins and local recurrence after mastectomy with IBR in patients with early breast cancer between 2008 and 2016. The effect of postoperative radiation therapy was evaluated in patients with involved margins, adjusted for nuclear grade, lymphatic invasion, surgical procedures, and primary systemic therapy. RESULTS: A total of 274 (5.8 %) out of 4726 patients who underwent mastectomy with IBR had involved surgical margins: 133, 68, 88, and 26 had involvement of the skin, deep margin, lateral margins, and nipple, respectively (including duplicates). Radiation therapy was administered to 54 patients with involved margins. In patients with involved margins, 7-year cumulative incidences of local recurrence were 1.9 % and 12.6 % with and without radiation therapy, respectively (adjusted hazard ratio, 0.17; 95 % CI, 0.04-0.80). Local recurrence occurred in 28 patients, and the sites were skin, subcutaneous tissue, muscle, and nipple-areola complex in 7, 17, 1, and 3 patients, respectively. Among them, 23 (82.1 %) were associated with involved margin sites. CONCLUSIONS: Radiation therapy meaningfully reduced the incidence of local recurrence in patients with breast cancer with margin involvement after mastectomy with IBR. Most local recurrences occurred at involved margin-related sites.

Long-Term Outcomes of Breast Cancer Patients with Local Recurrence After Mastectomy Undergoing Immediate Breast Reconstruction: A Retrospective Multi-institutional Study of 4153 Cases.

BACKGROUND: The number of breast cancer patients in Japan undergoing immediate breast reconstruction (IBR) has increased and the postoperative follow-up period has been extended. This study was conducted to clarify the clinical aspects of, and factors associated with, local recurrence (LR) after IBR. METHODS: This was a multicenter study which included 4153 early breast cancer patients who underwent IBR. Clinicopathological characteristics were examined and factors potentially contributing to LR were analyzed. Risk factors for LR were examined separately for non-invasive and invasive breast cancers. RESULTS: The median follow-up period was 75 months. The 7-year LR rates were 2.1% and 4.3% for non-invasive and invasive cancers, respectively (p < 0.001). The proportions of LR detected by palpation, subjective symptoms, and ultrasonography were 40.0%, 27.3%, and 25.9%, respectively. Overall, 75.7% of LR were solitary, and 92.7% of these cases had no further recurrences during the observational period. Multivariate analysis of LR for invasive cancer showed that skin-sparing mastectomy (SSM) or nipple-sparing mastectomy (NSM), the presence of lymphovascular invasion, cancer at the surgical margin, and not receiving radiation therapy were factors related to LR. The 7-year overall survival rates of the patients with LR and non-LR of invasive cancers were 92.5% and 97.3%, respectively, (p = 0.002). CONCLUSIONS: The rate of LR after IBR was acceptably low and IBR can thus be performed safely for early breast cancer patients. Invasive cancer, SSM/NSM, lymphovascular invasion, and/or cancer at the surgical margin should prompt awareness of the possibility of LR.

Oncofertility-related psycho-educational therapy for young adult patients with breast cancer and their partners: Randomized controlled trial.

BACKGROUND: A couples' psycho-educational program called Oncofertility! Psycho-Education and Couple Enrichment (O!PEACE) therapy was created and its effect when provided before cancer treatment was examined. METHODS: This multicenter randomized controlled trial with nonmasking, parallel two-group comparison enrolled women aged 20 to 39 years with early-stage breast cancer and their partners. They were randomly assigned to receive O!PEACE (37 couples) or usual care (37 couples). Primary end points were cancer-related posttraumatic stress symptoms, symptoms of depression, and anxiety. Secondary end points were stress-coping strategies, resilience, and marital relationship. RESULTS: Women receiving psycho-educational therapy had significantly reduced Impact of Event Scale-revised version for Japanese scores (p = .011, ηp 2  =  = .089). For patients with Impact of Event Scale-revised version for Japanese scores at baseline ≥18.27, O!PEACE therapy improved these scores when compared with usual care (U = 172.80, p = .027, r = 0.258). A >5-point reduction was present in 59.3% and 30% of women in the O!PEACE therapy and usual-care groups, respectively. For partners, O!PEACE therapy significantly improved stress-coping strategies (95% CI, -0.60 to -0.05; p = .018, ηp 2  =  = .074) and escape-avoidance marital communication (95% CI, -0.33 to -0.08; p = .001, ηp 2  = .136). O!PEACE therapy significantly improved the partners' support (95% CI, 0.10-0.50; p = .001, ηp 2  = .127), the rate of receiving fertility preservation consultations, and knowledge levels. CONCLUSIONS: O!PEACE therapy before cancer treatment can improve posttraumatic stress symptoms, stress-coping behavior, and marital relationships. Larger sample sizes and longer term follow-up are required. PLAIN LANGUAGE SUMMARY: A psycho-educational program, the Oncofertility! Psycho-Education and Couple Enrichment (O!PEACE) therapy program was developed and evaluated for women diagnosed with breast cancer and their partners. A multicenter randomized controlled trial showed that the O!PEACE psycho-educational therapy, with only two precancer treatment sessions, can reduce cancer-related posttraumatic stress symptoms and improve oncofertility knowledge and marital relationships in young adult patients with breast cancer. The therapy could also improve stress-coping strategies in marital communications with their partners. Couples may use O!PEACE psycho-educational therapy to consider fertility preservation and improve their psychosocial aspects.

Physicians' perception about the impact of breast reconstruction on patient prognosis: a survey in Japan.

BACKGROUND: One barrier to the widespread use of breast reconstruction (BR) is physicians' perception that BR adversely affects breast cancer prognosis. However, there is limited information regarding physicians' understanding of the impact of BR on patient prognosis and which physicians have misunderstandings about BR. METHODS: We conducted an e-mail survey regarding the impact of BR on the prognosis of patients with breast cancer among members of the Japanese Breast Cancer Society. RESULTS: Of 369 respondents, 99 (27%) said that they believe BR affects patient prognosis. Female respondents and those who treat fewer new breast cancer patients per year were more likely to state that they believe BR affects patient prognosis (P = 0.006 and 0.007). Respondents who believed that BR affects patient prognosis underestimated 5-year overall survival rates in patients who receive BR and subsequently have local or regional recurrence in different sites. CONCLUSION: Our survey demonstrated that a quarter of respondents believe that BR affects patient prognosis and underestimate survival rates in patients who receive BR and have subsequent local or regional recurrence. Because of the lack of evidence regarding the impact of BR on patient prognosis, educating physicians by providing accurate knowledge regarding BR and patient prognosis is highly recommended.

Classification of Local Recurrence After Nipple-Sparing Mastectomy Based on Location: The Features of Nipple-Areolar Recurrence Differ from Those of Other Local Recurrences.

BACKGROUND: Little information is available about the clinical and pathologic characteristics of local recurrence (LR) after nipple-sparing mastectomy according to the locations of LR. METHODS: This study classified 99 patients into the following two groups according to the location of LR after nipple-sparing mastectomy: nipple-areolar recurrence (NAR) group and other locations of LR (oLR) group. The study evaluated whether the location of LR was associated with disease-free survival (DFS) after LR resection. RESULTS: For about half of the patients (44.4 %) with NAR, the primary cancer was estrogen receptor (ER)-negative and human epidermal growth factor receptor 2 (HER2)-positive. Conversely, in most of the patients with oLR (79.2 %), the primary cancer was ER-positive and HER2-negative. Among the LR tumors, the frequency of noninvasive carcinoma in the NAR tumors was significantly higher than in the oLR tumors (51.9 % vs 4.2 %, respectively). During a median follow-up period of 46 months, the location of LR was not associated with DFS after LR. In the NAR group, the presence or absence of LR tumor invasiveness was the only factor associated with DFS. In the oLR group, age at primary surgery was the only factor associated with DFS. CONCLUSION: This multi-institutional retrospective study demonstrated that the features of NAR, such as the characteristics of the primary and recurrent tumors and the prognostic factors after LR resection, were quite different from those of oLR.

Strong impact of pathological node-negative on long-term overall survival of patients with triple-negative breast cancer receiving neoadjuvant chemotherapy.

Triple-negative breast cancer (TNBC) has a high pathological complete response (pCR) rate; however patients without a high pCR are reported to have a poor prognosis. The current study investigated the long-term overall survival of patients with TNBC who received neoadjuvant chemotherapy (NAC) and analyzed various prognostic factors including basal marker and claudin expressions. Between November 2005 and March 2012, the current study retrospectively reviewed the records of 323 patients with breast cancer who received anthracycline followed by taxane as NAC at the Jikei University Hospital Basal marker and claudin expression was determined via immunohistochemistry. The median age of the patients was 53.0 years. Of the 323 patients, 26 (8%) achieved a pCR, including 13 patients (19.7%) with TNBC and 13 (5.1%) with non-TNBC (P<0.001). Of the 66 patients with TNBC, 13 (19.7%) demonstrated recurrence and 8 (12.1%) died after a median follow-up time of 111.5 months [10-year disease-free survival (DFS), 80.3%; 95% confidence interval (CI), 0.68-0.88; 10-year overall survival (OS), 84.8%; 95% CI, 0.72-0.92]. Of the 257 patients with non-TNBC, 45 (17.5%) patients demonstrated recurrence and 26 (10.1%) died (10-year DFS, 82.1%; 95% CI, 0.76-0.87; 10-year OS, 88.6%; 95% CI, 0.83-0.92). There was no statistical difference between the patients with and without TNBC. In the TNBC group, patients with pathological node-negative status survived without distant recurrence. Additionally, negative lymphovascular infiltration was another favorable prognostic factor. Patients with TNBC who received NAC demonstrated comparably high prognoses to non-TNBC patients. Overall, pathological node status after NAC had a strong impact on the prognosis of patients with TNBC.

Long-term outcomes of oligometastatic breast cancer patients treated with curative intent: an updated report.

BACKGROUND: Oligometastatic breast cancer (OMBC) is characterized by limited metastatic tumor numbers and sites. We have reported a 20-year overall survival (OS) rate and relapse-free rate (RFR) of 34.1% and 27.4%, respectively, in a retrospective analysis of OMBC patients treated with curative intent including a multidisciplinary approach. Metastatic breast cancer (MBC) is generally incurable; however, OMBC might be a potentially curable subset. The previous analysis included isolated locoregional recurrence (ILRR) cases, which differs from distant metastasis in treatment strategies. Therefore, in this study, we excluded ILRR cases and provided an update on clinical outcomes. We also performed a detailed subgroup analysis of OMBC patients by introducing new prognostic variables. METHODS: Data of 73 OMBC patients, including 10 ILRR cases, treated in our institution between 1980 and 2010 were retrospectively analyzed. OMBC was defined as the presence of metastatic lesions in 1-2 organs, < 5 lesions per metastasized organ, and lesion diameter < 5 cm. RESULTS: The median follow-up duration was 151 (range 12-350) months. Twenty-eight (44%) patients received local therapy. Excluding ILRR cases, the OS rates were 28.3% and 18.9% and RFRs were 26.7% at 20 and 25 years, respectively. In multivariate analysis, single-organ involvement and three or fewer metastatic lesions per organ were associated with a longer progression-free and relapse-free interval (RFI). CONCLUSIONS: Relapse-free interval reached a plateau after 20 years at approximately 25% probability. Patients with long-term survival without disease relapse are considered cured. Curative-intent therapy should be considered for OMBC patients, especially those with low tumor volume.

A Retrospective Analysis of Perioperative Chemotherapy and Coronavirus Disease in Patients With Breast Cancer.

BACKGROUND/AIM: Since January 2020, coronavirus disease (COVID-19) cases have been confirmed in Japan, and the number of patients with COVID-19 has been increasing. Two emergency declarations have been made previously and one is currently in effect. Based on our experience of a situation that could affect cancer treatment, this study retrospectively examined the correlation between perioperative anticancer therapy and COVID-19 incidence in patients with breast cancer. PATIENTS AND METHODS: Patients who underwent perioperative anticancer therapy for breast cancer at our hospital from February 2020 to February 2021 were included in this study. The presence or absence of COVID-19, timing of anticancer drug initiation, and clinical data were collected. RESULTS: No cases of COVID-19 were diagnosed in patients receiving perioperative anticancer therapy at our hospital. CONCLUSION: Regimen modification, active use of supportive care, and patient lifestyle were factors reducing the incidence of COVID-19.

Clinical implications of drug-screening assay for recurrent metastatic hormone receptor-positive, human epidermal receptor 2-negative breast cancer using conditionally reprogrammed cells.

Various new drugs have been developed for treating recurrent hormone receptor-positive (HR+)/human epidermal receptor 2-negative (HER2-) breast cancer. However, directly identifying effective drugs remains difficult. In this study, we elucidated the clinical relevance of cultured cells derived from patients with recurrent HR+/HER2- metastatic breast cancer. The recently established conditionally reprogrammed (CR) cell system enables us to examine heterogeneity, drug sensitivity and cell function using patient-derived tumour samples. The results of microarray analysis, DNA target sequencing and xenograft experiments indicated that the mutation status and pathological features were preserved in CR cells, whereas RNA expression was different from that in the primary tumour cells, especially with respect to cell adhesion-associated pathways. The results of drug sensitivity assays involving the use of primary breast cancer CR cells were consistent with gene expression profiling test data. We performed drug-screening assays using liver metastases, which were sensitive to 66 drugs. Importantly, the result reflected the actual clinical course of this patient. These results supported the use of CR cells obtained from the metastatic lesions of patients with HR+/HER2- breast cancer for predicting the clinical drug efficacy.

Long-Term Follow-Up of Node-Negative Breast Cancer Patients Evaluated via Sentinel Node Biopsy After Neoadjuvant Chemotherapy.

BACKGROUND: Sentinel node biopsy (SNB) is used to accurately assess axillary lymph node status in patients with node-negative breast cancer. However, its use after neoadjuvant chemotherapy (NAC) is controversial. We retrospectively assessed the usefulness of SNB after NAC by comparing axillary recurrence rates and other parameters in patients with clinically node-negative breast cancer who underwent SNB after NAC or without NAC. PATIENTS AND METHODS: At our hospital, 1179 patients with clinically node-negative breast cancer underwent SNB from April 2007 to December 2013. The clinicopathological and survival data of patients who underwent SNB after NAC (the NAC group) and those who underwent SNB without NAC (the control group) were compared. Patients with a metastatic sentinel node underwent axillary lymph node dissection. RESULTS: The number of patients in the NAC and control groups was 183 (15.5%) and 996 (84.5%), respectively. At diagnosis, tumors were significantly larger in the NAC group (P < .0001). Sentinel nodes were identified in almost all patients in both groups (99.5% in the NAC group vs. 99.8% in the control group). They were nonmetastatic in 147 (80.8%) patients in the NAC group and 849 (85.5%) patients in the control group. At the median follow-up time of 51.1 months, 6 patients (0.6%) in the control group had axillary lymph node recurrence compared with no patients in the NAC group. CONCLUSION: SNB after NAC was as accurate as SNB without NAC in patients with clinically node-negative breast cancer. Axillary recurrence-free survival rates were excellent regardless of whether NAC was performed before SNB.

Primary ectopic breast cancer of the vulva, treated with local excision of the vulva and sentinel lymph node biopsy: a case report.

Primary breast cancer fairly infrequently occurs in ectopic breast tissue, and primary ectopic breast cancer of the vulva is particularly rare. Only 26 cases have been published in the English-language literature, and there has been no report of primary breast carcinoma of the vulva in Japan. We report a rare case of primary ectopic breast cancer of the vulva that was treated with local excision of the vulva and sentinel lymph node biopsy (SLNB). The patient was a 72-year-old woman who had noticed a right vulvar tumor 10 years earlier. The tumor was excised by the Department of Plastic Surgery of our hospital. The histology of the vulvar tumor revealed an invasive ductal carcinoma of the breast, and immunohistochemical staining of the vulvar specimen showed the tumor cells to be 100% estrogen-receptor-positive and 100% progesterone-receptor-positive. All margins of resection were positive for neoplastic involvement. An additional local excision of the vulva and right inguinal SLNB were performed in our department. The intraoperative frozen section was negative for metastasis, and lymph node dissection was not performed. The final pathology was negative for residual disease, and a partially normal ductal component was present. Adjuvant hormonal therapy with an aromatase inhibitor was indicated post-operatively. The patient was asymptomatic and free of detectable disease at a 6-month follow-up. Due to the rarity of this diagnosis, there are no established guidelines for treatment. Although cases in which SLNB was performed are rare, we consider SLNB to be an effective alternative to inguinal node dissection for ectopic primary breast cancer of the vulva.

Nonrecurrent inferior laryngeal nerves and anatomical findings during thyroid surgery: report of three cases.

A nonrecurrent inferior laryngeal nerve (NRILN) is found more frequently on the right side than on the left, and it is closely associated with an aberrant right subclavian artery. The presence of the aberrant right subclavian artery on preoperative computed tomography (CT) scan suggests NRILN; however, different types of branching locations and pathways exist. Here, we report three NRILN cases with different pathways where the vagus nerve arises more medial than usual and a review of the literature. Case 1: A 30-year-old Japanese female presented with papillary thyroid carcinoma. Preoperative CT scan revealed an aberrant right subclavian artery, and an operation was performed under suspicion of NRILN. During the operation, the vagus nerve was found to arise more medially than usual and two NRILNs originated from it at the level of the cricoid cartilage and at a more caudal position; the two NRILNs were preserved. Case 2: A 33-year-old Japanese female with a thyroid nodule of increased size underwent surgery. Preoperative CT scan revealed an aberrant right subclavian artery, which suggested NRILN. During the operation, the vagus nerve was identified to run more medially than usual and NRILN was found to originate at the level of the cricoid cartilage; NRILN was preserved. Case 3: A 78-year-old Japanese female underwent an operation with a diagnosis of papillary thyroid carcinoma. Preoperative CT scan showed an aberrant right subclavian artery. During the operation, NRILN was found to originate from the vagus nerve at the level of the lower pole of the thyroid gland, and the vagus nerve ran medial to the common carotid artery at the caudal level.

Triple-negative breast cancer exhibits a favorable response to neoadjuvant chemotherapy independent of the expression of topoisomerase IIα.

The present study retrospectively analyzed the utility of topoisomerase IIα expression as a prognostic marker to predict the neoadjuvant chemotherapeutic response and survival among different breast cancer subtypes. The patients were subtyped and the expression of topoisomerase IIα was determined using immunohistochemistry. All patients (n=147) received an anthracycline-containing regimen preoperatively, and 139 (95%) patients also received docetaxel. Of the 147 patients, 25 (17%) were triple-negative and 20 (17%) were human epidermal growth factor receptor 2 (HER2)-positive. Among these subtypes, a significantly higher a rate (P<0.0001) and higher incidence of topoisomerase IIα expression (P=0.036) were observed compared with that in the hormone receptor-positive and HER2-negative breast cancer types. However, the expression of topoisomerase IIα revealed no correlation with the treatment response or survival in any of the subtypes. Therefore, these results indicated that the favorable response to anthracycline-containing chemotherapy among triple-negative and HER2-positive breast cancer was independent of the expression of topoisomerase IIα.

Optimization of Region of Interest Drawing for Quantitative Analysis: Differentiation Between Benign and Malignant Breast Lesions on Contrast-Enhanced Sonography.

OBJECTIVES: This study was performed to evaluate the diagnostic utility of quantitative analysis of benign and malignant breast lesions using contrast-enhanced sonography. METHODS: Contrast-enhanced sonography using the perflubutane-based contrast agent Sonazoid (Daiichi Sankyo, Tokyo, Japan) was performed in 94 pathologically proven palpable breast mass lesions, which could be depicted with B-mode sonography. Quantitative analyses using the time-intensity curve on contrast-enhanced sonography were performed in 5 region of interest (ROI) types (manually traced ROI and circular ROIs of 5, 10, 15, and 20 mm in diameter). The peak signal intensity, initial slope, time to peak, positive enhancement integral, and wash-out ratio were investigated in each ROI. RESULTS: There were significant differences between benign and malignant lesions in the time to peak (P < .05), initial slope (P < .001), and positive enhancement integral (P < .05) for the manual ROI. Significant differences were found between benign and malignant lesions in the time to peak (P < .05) for the 5-mm ROI; the time to peak (P < .05) and initial slope (P< .05) for the 10-mm ROI; absolute values of the peak signal intensity (P< .05), time to peak (P< .01), and initial slope (P< .005) for the 15-mm ROI; and the time to peak (P < .05) and initial slope (P < .05) for the 20-mm ROI. There were no statistically significant differences in any wash-out ratio values for the 5 ROI types. CONCLUSIONS: Kinetic analysis using contrast-enhanced sonography is useful for differentiation between benign and malignant breast lesions.

Breast cancer screening and the changing population pyramid of Japan.

BACKGROUND: Breast cancer has been the most prevalent cancer in Japan since the 1990s. The mortality from breast cancer is increasing in Japan, whereas in other industrialized countries it has been decreasing since 1990. On the other hand, Japan faces unparalleled growth in its aging population. The aim of this study was to report the mammography screening among Japanese women and the related upcoming changes in the population pyramid of Japan. DATA SOURCES AND METHODS: The reference data for our study were obtained from the Center for Cancer Control and Information Services, Japan Ministry of Internal Affairs and Communications, Ministry of Health, Labour and Welfare, the Japanese Cancer Society, and the National Institute of Population and Social Security. The survey data were obtained from breast cancer and mammography screenings in the Tokyo Prefecture in 2008. The following parameters were analyzed: annual breast cancer incidence, current screening rates, average life-span, and predicted demographic statistics. RESULTS: Our results showed that breast cancer incidence and mortality have been increasing annually in Japan. The average age of breast cancer patients increased to 58.40 years in 2010. The incidence of breast cancer in women aged 65 years and older increased from 25.3 to 32.9 % in the last 10 years and is expected to continue to increase in the future. The check-up rate was 16.0-20.0 % for women aged 65-74 years and 43.0-46.0 % for women aged 40-54 years. According to our questionnaire survey, concerns about breast cancer and mammography screening were high in the young and low in the elderly women. The Japanese population aged 65 years and older was 30,740 (24.1 %) in 2012 and is estimated to increase by 40 % over the next 20 years despite Japan's declining population size. CONCLUSION: Breast cancer incidence has increased in Japan, even among patients aged 65 years and older. Breast cancer has become increasingly prevalent in older Japanese women. As the population pyramid of Japan changes, women aged 65 years and older, who think that there is no longer need to receive mammography screening and are not educated regarding self-examinations, should be encouraged to receive regular check-ups for breast cancer.

Clinical relevance and low tumor-initiating properties of oligometastatic breast cancer in pulmonary metastasectomy.

Metastatic breast cancer is a systemic disease. However, certain subsets of patients, such as those with oligometastatic breast cancer (OMBC), have long-term survival prospects. Our aim was to evaluate the clinical relevance of OMBC in pulmonary metastasectomy of recurrent breast cancer. We also investigated lung metastases for the prevalence of CD44+/CD24-/low tumor cells and evaluated their prognostic significance. We reviewed data from a registry of breast cancer patients with lung metastases who underwent pulmonary metastasectomy at Jikei University Hospital. We analyzed prognostic factors for overall survival (OS) and progression-free survival (PFS) after metastasectomy and examined the prognostic difference between OMBC and non-OMBC patients. CD44+/CD24-/low tumor cells were detected by immunohistochemical analysis of lung metastases sites. Among 17 breast cancer patients with lung metastasis, 5-year OS and PFS rates were 72 and 36 %, respectively. Better OS was observed among patients with OMBC. Patients with OMBC, estrogen receptor-positive cells, and disease-free intervals of >8 years had better PFS. The presence of CD44+/CD24-/low tumor cells influenced progression after lung metastasectomy, with median PFS of only 6 months in patients with a high prevalence of cancer-initiating cells. CD44+/CD24-/low cells with cancer-initiating properties were present in only 9 % ± 3 of patients with OMBC, but were found in 73 % ± 12 of patients with non-OMBC. Pulmonary metastasectomy may be a treatment option for OMBC patients with lung metastases. Better prognosis of OMBC may be associated with low levels of cancer-initiating cells.

An Extracellular Matrix Molecule, Secreted by the Epithelial-Mesenchymal Transition is Associated With Lymph Node Metastasis of Thyroid Papillary Carcinoma.

BACKGROUND: Papillary thyroid carcinoma often has lymph node metastasis, compared with follicular thyroid carcinoma. The study showed that epithelial-mesenchymal transition occurs in carcinoma cells during the first stage of metastasis, where some extracellular matrix molecules are secreted in large quantities. Sialic acid carried by fibronectin as the antigen of the monoclonal antibody (MoAb) JT-95, was detected in 90% of papillary thyroid carcinoma cases, and in a few follicular thyroid carcinomas, in the extracellular matrix of thyroid carcinoma cells. OBJECTIVES: The current study was conducted to investigate the association between increasing the number of extracellular matrix molecules, fibronectin, and lymph node metastasis. We also co-cultured a thyroid carcinoma cell line and lymphocyte cell line, with and without MoAb JT-95, in order to investigate the mechanism of cell to cell interaction. PATIENTS AND METHODS: Immunostaining with JT-95 was performed in 45 papillary thyroid carcinoma cases, and 20 follicular type tumors, to investigate the association between the quantity of fibronectin expression and the frequency of lymph node metastasis. The thyroid carcinoma cell line (SW1736), which secreted fibronectin, and the B cell-lymphoma cell line (Daudi), which held integrin on the cell surface, were co-cultured to observe the adhesion of cells to each other. The SW1736 cell line, pretreated with JT-95, was also co-cultured with the Daudi cell line. RESULTS: There were 39 cases with lymph node metastasis in 59 malignant tumors, and 0 cases in 6 benign follicular type tumors. The staining scores by JT-95 of the 39 tumors with lymph node metastasis were 5+ in eight cases and 6+ in 31 cases. On the other hand, the scores of 20 malignant tumors without lymph node metastasis were < 4+ in all of the cases. In the co-cultured assay, numerous adhesions were observed between the SW1736 and Daudi cells. In contrast, the inhibition of adherences was observed in proportion to the concentrations of JT-95. CONCLUSIONS: Increased fibronectin expression in thyroid malignancies is correlated with lymph node metastasis.