Survival Advantage of Lymphadenectomy in Patients with Ovarian Cancer.

We investigated the survival effect of lymphadenectomy in ovarian cancer. The five-year progression-free and overall survival in early-stage ovarian cancer were not affected. Preliminary, unadjusted analysis in advanced ovarian cancer suggested an improvement in survival. However, after adjusting for other factors, e.g. ECOG performance status and patients' age, this survival advantage vanished. Our analysis suggests that systemic pelvic and para-aortic lymphadenectomy was not associated with an improvement of the progression-free and overall survival of patients with optimally debulked ovarian cancer.

Protective effect of pre-operative conization in patients undergoing surgical treatment for early-stage cervical cancer.

OBJECTIVE: The aim of this study was to investigate the impact of pre-operative conization on disease-free survival (DFS) in early-stage cervical cancer. METHODS: In this population-based cohort study we analysed from clinical cancer registries to determine DFS of women with International Federation of Gynecology and Obstetrics (FIGO) stage IA1-IB1 cervical cancer with respect to conization preceding radical hysterectomy performed between January 2010 and December 2015. RESULTS: Out of 993 datasets available for the analysis, 235 patients met the inclusion criteria of the current study. The median follow-up was 5.4 years. During the study period, 28 (11.9%) recurrences were observed. All of these occurred in patients with FIGO stage IB1. For further evaluation, patients with FIGO IB1 tumors <2 cm were further analysed and divided into two groups, based on pre-operative conization. Pre-operative conization was associated with a reduced rate of recurrence (p = 0.007), with only three (5.2%) recurrences in this group (CO) compared to 25 recurrences (21.0%) in the group without conization (NCO) preceding radical hysterectomy. DFS was estimated at 79.0% and 94.8% in NCO and CO, respectively (p = 0.008). After adjustment for other prognostic covariates, conization remained a favourable prognostic factor for DFS (HR 0.27; 95% CI 0.08-0.93, p = 0.037). Lymph node involvement was the only unfavourable factor (HR 4.38; 95% CI 1.36-14.14, p = 0.014) in the multivariable analysis. CONCLUSIONS: Pre-operative conization is associated with improved DFS in early-stage cervical cancer independently of the surgical approach.

Adjuvant chemotherapy for breast cancer patients with axillary lymph node micrometastases.

BACKGROUND: The axillary lymph node status is one of the most important prognostic factors in patients with early breast cancer. However, the impact of axillary lymph node micrometastases on survival remains unclear. There are no consistent recommendations for adjuvant chemotherapy (CHT). In this context, we aimed to investigate the impact of micrometastases on the clinical outcome of breast cancer patients according to the adjuvant CHT performed. PATIENTS AND METHODS: We conducted a retrospective population-based registry study of 26,465 patients aged between 24 and 97 years with primary breast cancer diagnosed between 2003 and 2017. Of these patients, 8856 with early breast cancer were eligible for analysis: 8316 (93.9%) were node negative and 540 (6.1%) had lymph node micrometastases. RESULTS: The median follow-up was 7.2 years, with a confidence interval (CI) of 7.1-7.3 years. Patients with lymph node micrometastases (pN1mi) without adjuvant CHT have reduced 10-year overall survival (OS) and recurrence-free survival (RFS) compared to patients who had axillary lymph node micrometastases and received an adjuvant CHT. However, this effect disappeared after adjustment for age, tumor size and tumor grading. Furthermore, in the group of patients with lymph node micrometastases, the administration of adjuvant CHT did not improve OS or RFS, compared to patients with lymph node micrometastases without adjuvant CHT: hazard ratio for treated patients was 1.51 (95% CI 0.80-2.85, p = 0.208) for OS and 1.12 (95% CI 0.63-1.97, p = 0.705) for RFS. CONCLUSION: Patients with axillary lymph node micrometastases showed a comparable outcome to node negative patients and their outcome was not significantly improved with CHT. Thus, axillary lymph node micrometastases should not be considered in the treatment decision.

Contralateral lymph node metastases in patients with vulvar cancer and unilateral sentinel lymph node metastases.

INTRODUCTION: The risk of contralateral lymph node metastases following unilateral sentinel lymph node (SLN) metastases in patients with vulvar cancer(s) remains to be systematically assessed. MATERIAL AND METHODS: We performed a multicenter, retrospective registry-based study of 476 patients with vulvar cancer. The primary outcome measure was the rate of contralateral non-SLN metastases in the case of positive unilateral SLN. RESULTS: Out of 476 patients with primary vulvar cancer, 202 received SLN biopsy: 58 unilateral and 144 bilateral. Out of 66 patients with unilateral metastatic SLN, 62 (93.9%) received contralateral lymphadenectomy-18 after unilateral and 44 after bilateral SLN biopsy. In the study group, 132 SLN were assessed with a median number of 2 (range 1-4) per patient and 76 of these were positive. Lymph node-positivity was associated with advanced tumor stage, as well as lymph and vascular space invasion. In the group of patients with bilateral inguino-femoral lymphadenectomy, 1004 lymph nodes were resected with a median number of 15 (range 10-29) per patient. After full dissection of the inguino-femoral lymph nodes, no contralateral non-SLN metastases were found. CONCLUSIONS: The risk of contralateral non-SLN metastases in patients with unilateral SLN metastases was low. Therefore, the impact of contralateral lymphadenectomy on patient survival should be investigated in further studies.

Minimal-invasive or open approach for surgery of early cervical cancer: the treatment center matters.

PURPOSE: The aim of the study was to compare recurrence-free survival (RFS) and overall survival (OS) of patients with early stage cervical cancer in dependence of surgical approach and treatment center. PATIENTS AND METHODS: A population-based cohort study including women with early stage IA1-IIB2 cervical cancer treated by radical hysterectomy between January 2010 and December 2015 was performed. RESULTS: The median follow-up time was 5.6 years. After exclusions, 413 patients were eligible for analysis: 111 (26.9%) underwent minimal-invasive surgery (MIS) and 302 (73.1%) open surgery. Both treatment groups were well balanced regarding the clinical and pathological characteristics. The mean age of the patients was 51.0 years. MIS was associated with improved RFS and OS compared with the open surgery. The 5-year RFS rates were 89.2% in the MIS group and 73.4% in the open surgery group (p = 0.004). The 5-year OS rates were 93.7% in the MIS group and 81.8% in the open surgery group (p = 0.016). After adjustment for other prognostic covariates, the MIS was further associated with improved RFS (HR = 0.45, 95% CI 0.24-0.86; p = 0.015) but not with OS. Nevertheless, after adjustment for treatment center, the surgical approach was not associated with significant difference in RFS (HR = 0.61, 95% CI 0.31-1.19; p = 0.143). Overall survival of patients treated in university cancer centers was significantly increased compared to patients treated in non-university cancer centers. The treatment center remains a strong prognostic factor regarding RFS (HR = 0.49, 95% CI 0.28-0.83; p = 0.009) and OS (HR = 0.50, 95% CI 0.26-0.94; p = 0.031). CONCLUSIONS: The treatment center but not the surgical approach was associated with the survival of patients treated with radical hysterectomy for early stage cervical cancer.

The impact of G protein-coupled oestrogen receptor 1 on male breast cancer: a retrospective analysis.

INTRODUCTION: The G protein-coupled oestrogen receptor 1 (GPER-1) is a potential prognostic marker in breast cancer. However, its role in male breast cancer (MBC) is still unknown. This study evaluates the expression of GPER-1 in MBC samples and correlates these data with clinical and pathological parameters including patients' survival. MATERIAL AND METHODS: For this retrospective analysis of a prospectively maintained cohort of patients with MBC, we examined 161 specimens for GPER-1 expression using immunohistochemistry. An immunoreactive score (IRS) was calculated based on staining intensity and the percentage of positive tumour cells. Then, we correlated GPER-1 IRS with clinical and pathological parameters, and overall and relapse-free survival. RESULTS: About 40% of MBC samples were positive for GPER-1 expression (IRS ≥ 4). There was no significant correlation with clinicopathological parameters, such as hormone receptor status or grading. However, a statistical trend was observed for tumour size (≥ 2 cm, p = 0.093). Kaplan-Meier survival analysis revealed no significant correlation with relapse-free survival. However, there was a significant correlation with overall survival, but when we adjusted the log-rank p-value to compensate for the cut-off point optimization method, it rose above 0.1. Additionally, GPER-1-positive patients were older at diagnosis. When adjusted for age by multivariable Cox regression analysis, the significance of GPER-1 status for survival was further reduced. CONCLUSIONS: We found no significant prognostic value of GPER-1 in this MBC cohort as anticipated from studies on female BC. Future studies with higher sample size are needed to further verify a potential sex-specific role of GPER-1.

Survival benefit of tamoxifen in male breast cancer: prospective cohort analysis.

BACKGROUND: Due to the lack of prospective data, current treatment of male breast cancer (MBC) is based on information obtained from retrospective analysis or by extrapolation from studies on female patients. In this prospectively enrolled cohort study, we retrospectively examined the survival effect of tamoxifen in MBC patients. METHODS: In this prospectively enrolled cohort study, 448 patients with MBC were treated between May 2009 and June 2018. The primary endpoint was disease-free survival (DFS). RESULTS: Between May 2009 and June 2018, 448 men with breast cancer were identified, with a median age at diagnosis of 69 years (range 27-96 years). The median follow-up was 39 months (range 3-89 months). Most tumours were larger than 20 mm; invasive ductal carcinoma was of no special histological type and with an intermediate grade of differentiation. Almost half of the men were diagnosed with positive axillary lymph nodes (43.5%). Hormone receptor (HR) positivity was observed in 98.4% of the patients. Notably, DFS among men who did not receive tamoxifen was significantly reduced as compared with those who underwent tamoxifen therapy (P = 0.002). The recurrence rate and mortality in the group of patients without and with tamoxifen treatment were 18.2% and 11.2%, respectively. The most common localisation of metastases was the bone. After adjustment for prognostic factors, we found that tamoxifen was found to reduce the recurrence rate by 68% (hazard ratio HR = 0.32; 95% confidence interval, CI: 0.14-0.74). CONCLUSIONS: Tamoxifen treatment was associated with improved DFS for MBC patients. CLINICAL TRIAL REGISTRATION: DRKS00009536.

Comparison of survival of patients with endometrial cancer undergoing sentinel node biopsy alone or systematic lymphadenectomy.

BACKGROUND: Recently, sentinel lymph node mapping was introduced in the surgical staging of endometrial cancer as alternative to systematic lymphadenectomy. However, the survival impact of sentinel node mapping is not well characterized yet. METHODS: We performed retrospective study of 104 patients with endometrial cancer treated with sentinel lymph node alone (n = 52) or with pelvic and para-aortic lymphadenectomy (n = 52). For sentinel node mapping, indocyanine green was used. The outcome measure was disease-free survival. RESULTS: Median follow-up was 42 months. Fifty-two patients staged by sentinel lymph node mapping were matched in 1:1 ratio with 52 patients staged by lymphadenectomy using patient age, histological type, tumor stage, tumor grade and lymph and vascular space invasion as matching criteria. The median number of removed lymph node was 3 (range 1-6) and 36 (13-63) in the sentinel and lymphadenectomy group, respectively. The rate of lymph node metastases was not significantly higher in the sentinel group (19.2%) in comparison with the lymphadenectomy group (14.3%). The overall detection rate of sentinel lymph nodes was 100% with a bilateral mapping of 98.1%. Most of the 152 lymph nodes identified and removed were localized in upper paracervical pathway (n = 143, 94.1%). During the follow-up period, overall 21 (20.2%) events were observed, 8 (15.4%) in the sentinel group and 13 (25.0%) in the lymphadenectomy group. The estimated disease-free survival was 84.6% and 75.0% for patients in the sentinel and lymphadenectomy groups, respectively. The survival curves demonstrated similar disease-free survival in two groups (p = 0.774). CONCLUSION: Sentinel lymph node mapping did not compromise the outcome of patients with endometrial cancer.

Systematic lymphadenectomy in early stage endometrial cancer.

BACKGROUND: The positive effect of systematic lymphadenectomy on survival of patients with endometrial cancer is a topic of ongoing debate. METHODS: We aimed to investigate whether systemic lymphadenectomy is beneficial for patients with early endometrial cancer. For this purpose, we analyzed a population-based registry with of 2392 women with endometrioid endometrial cancer, stage I and II at intermediate and high risk of recurrence. The primary outcome measure was overall survival. RESULTS: After exclusions, 868 women were eligible for analysis. Of those, 511 and 357 were categorized as intermediate (pT1A G3 and pT1B G1-2) and high risk (pT1B G3 and pT2 G1-3) early stage endometrial cancer, respectively. Lymphadenectomy was performed in 527 (60.7%) of the cases. Patients in the lymphadenectomy group were significantly younger, presented with more tumors of intermediate or undifferentiated grade and exhibited significantly lower co-morbidity rates and Eastern Cooperative of Oncology Group (ECOG) performance status. Median follow-up was 6.7 years. Recurrence-free survival was not improved by lymphadenectomy in the intermediate and high-risk group of patients. During the follow-up period, 111 (12.8%) women had disease recurrence and 302 (34.8%) died. Systematic lymphadenectomy was associated with significant improvement of overall survival in the pT1A G3 and pT1B G3 patient subgroups. Notably, adjustment for patient age and ECOG status abolished the improvement of overall survival by systematic lymphadenectomy in all groups. Thus, lymphadenectomy did not improve recurrence-free survival in the intermediate risk or the high-risk group of patients CONCLUSIONS: Systematic pelvic and para-aortic lymphadenectomy did not improve the survival of patients with early stage I and II endometrioid endometrial cancer at intermediate and high risk of recurrence.

Tamoxifen treatment for male breast cancer and risk of thromboembolism: prospective cohort analysis.

PURPOSE: Thromboembolism is a common adverse event in women treated with tamoxifen (TAM) for breast cancer. The risk in male breast cancer patients is poorly investigated. We aimed to examine the risk of thrombotic events after TAM in male breast cancer patients. PATIENTS AND METHODS: In this prospective cohort study, 448 patients treated between May 2009 and July 2017 for male breast cancer (BC) were assessed for eligibility. Patients with follow-up shorter than 6 months were excluded. The cumulative risk of thromboembolism was evaluated. RESULTS: The median follow-up was 47 months (range 6-101 months) with a median age of 69.4 years (range 27-89 years). Oestrogen receptor and progesterone receptor expression levels were observed in 98.3 and 94.9% of cases, respectively. During the follow-up period, thrombotic events were documented in 21 (11.9%) of 177 patients receiving TAM and in 1 (2.5%) of 41 patients who did not receive tamoxifen. The estimated incidence was 51.9 per 1000 person-years and 21.5 per 1000 person-years, respectively. Notably, the highest risk was identified in the first 18 months, where 81% of the observed thrombotic events occurred. Patients aged older than 71 years had a significantly increased risk of thrombotic event under TAM treatment than their younger counterparts (p = 0.033). History of thrombotic event, cardiovascular and liver disease, as well as additional adjuvant treatment were not associated with increased thrombotic risk. CONCLUSION: The risk of thrombotic event in men treated with TAM for breast cancer is markedly increased in the first 18 months of treatment, and should be considered during treatment decisions.

Loss of HER2 after HER2-targeted treatment.

PURPOSE: HER2 expression has been reported to be discordant between primary tumor and metastatic tissue. PATIENTS AND METHODS: HER2 discordance and relation to HER2-targeted treatment was investigated in 227 patients with primary breast cancer. RESULTS: HER2 discordance between primary biopsy and second biopsy after neoadjuvant or adjuvant treatment was observed in 20.7%. This discordance was related only to the use of HER2-targeted treatment: 30 of 33 (90.9%) women with downgraded HER2 expression underwent a HER2-targeted therapy, whereas in the group of patients with concordant HER2 expression, only 32 of 180 (17.8%) received HER2-targeted treatment (p < 0.0001). HER2 discordance was associated with reduced disease-free survival but not overall survival. In a second cohort, including patients with HER2 overexpressing tumors, trastuzumab treatment was associated with change of HER2 expression from positive to negative in 47.3% of cases. Addition of pertuzumab increased the rate of HER2 loss up to 63.2%. Notably, the interval between last HER2-targeted treatment and the time of surgical excision of the tumor after neoadjuvant chemotherapy (NACT) or the biopsy of the metachronous metastasis was associated with a significant change in HER2 expression. The median time between NACT and the time of surgical excision was 23 days (range 5-81 days) for tumors with decreased HER2 expression and 51 days (range 10-179 days) for tumors with concordant HER2 expression. Furthermore, median time between the end of adjuvant treatment and second histology of the metachronous metastases accounted for 15 days (range 2-165 days) and 478 days (range 7-2739 days) was observed in the group of patients with decreased or unchanged HER2 expression, respectively. CONCLUSION: The interval between anti-HER2 treatment and the determination of HER2 in second histology is strongly associated with HER2 expression.

Lymph node micrometastases and outcome of endometrial cancer.

BACKGROUND: The relationship between nodal micrometastases and clinical outcome of endometrial cancer is unclear. PATIENTS AND METHODS: We performed a multicenter, retrospective registry-based study of 2392 patients with endometrial cancer with and without nodal micrometastases. The primary outcome measure was disease-free survival. RESULTS: After exclusions, the final study involved 428 patients: 302 (70.6%) with node-negative endometrial cancer, who did not receive adjuvant treatment, 95 (22.2%) with nodal micrometastases who received adjuvant treatment, and 31 (7.2%) with nodal micrometastases who did not receive adjuvant treatment. The median follow-up was 84.8 months. Without adjuvant therapy the disease-free survival in the cohort of patients with micrometastases was significantly reduced as compared with disease-free survival in the node-negative cohort (p = 0.0001). With adjuvant therapy the median disease-free survival of patients with nodal micrometastases was similar with those of node-negative patients (p = 0.648). The adjusted hazard ratio for disease events among patients with micrometastases and no adjuvant therapy, as compared with node-negative patients, was 2.23 (95% confidence interval [CI] 1.26-3.95). In the cohort with micrometastases the relative risk of events was significantly decreased by adjuvant therapy (HR 0.29, 95%CI 0.13-0.65) even after adjustment for age at diagnosis, myometrial invasion, histological grade and type, and performance status. CONCLUSIONS: Nodal micrometastases are associated with decreased disease-free survival of patients with endometrial cancer. Adjuvant therapy was associated with improved disease-free survival of patients with micrometastases.

Management of small T1a/b breast cancer by tumor subtype.

BACKGROUND: The treatment of patients with small (T1a/b) breast cancer is based on retrospective analysis. The influence of intrinsic tumor subtypes on patients' outcome and treatment decision remains unclear. PATIENTS AND METHODS: This is a prospective cohort register study including 1008 patients with small T1a/b breast cancer treated between 2003 and 2011. Tumors were grouped by biological characteristics into four different subtypes: luminal A, luminal B, human epidermal growth factor receptor 2 (HER2)-enriched, and triple-negative breast cancer (TNBC). RESULTS: The median follow-up time was 6.5 years. From 919 eligible patients, 408 (44.4%) were classified as luminal A, 246 (26.8%) as luminal B, 183 (19.9%) as HER2 enriched, and 82 (8.9%) as TNBC. A total of 305 (34.2%) patients were treated with systemic therapy. Patients receiving systemic therapy were significantly younger and had lymph node metastasis, higher tumor grade, negative HR, and positive HER2 status. Patients with luminal A tumors demonstrated the best survival rate which improved with systemic therapy. The survival rate of patients with luminal B cancer, HER2-enriched tumors, and TNBC improved by addition of systemic treatment. The effect of systemic treatment was significant in luminal B (p = 0.040) and HER2 overexpressing tumors (p = 0.016). The treatment effect of systemic therapy in HER2-enriched tumors remained significant even after adjustment of other prognostic factors (HR 0.43, CI 0.19-0.98; p = 0.047). Notably, tumor size was not associated with patients' survival and treatment decision. CONCLUSION: The treatment decision of small breast cancer should be made by biological subtype and not by tumor size or lymph node status.

Adjuvant hysterectomy after radiochemotherapy for locally advanced cervical cancer.

BACKGROUND: External beam radiation therapy (EBRT) with concomitant chemotherapy (cCT) (=RCT) plus intracavitary (±interstitial) brachytherapy (iBT) is standard of care for advanced cervical cancer. The aim of this study was to evaluate morbidity and survival outcome of simple adjuvant hysterectomy (AH) after EBRT/cCT and to compare it with the standard treatment. PATIENTS AND METHODS: Patients with FIGO stage III cervical cancer were treated with EBRT/cCT and then divided in two groups: group 1 was further treated with standard intracavitary/interstitial BT, while group 2 underwent AH. RESULTS: From 881 women with cervical cancer, 248 were eligible for analysis: 161 received iBT and 87 underwent AH. The median follow-up of the study was 53 months. Clinical and pathological characteristics were well balanced in the two groups. After EBRT/cCT, complete clinical response was observed in 121 (48.8%) of 246 patients. Clinical complete response was observed in 81 (50.3%) of 161 patients in group 1. At 6 weeks after EBRT/cCT, 40 (46.0%) of 87 patients in the surgery group had pathological complete response. Intra- and postoperative complications were observed in 10 (11.5%) of 87 cases. The rates of locoregional recurrence and metastasis were similar in both groups. Progression-free (PFS) and disease-specific overall survival (DOS) for these patients were similar between the control and surgery group. Interestingly, PFS and DOS were significantly improved by AH for the patients with residual tumor. CONCLUSION: AH could improve survival in patients with residual disease after RCT and is characterized by a low complication rate.

Management of elderly women with endometrial cancer.

BACKGROUND: Elderly women with endometrial cancer receive less therapy in comparison with their younger counterparts. The exact reason(s) for this treatment strategy remains unclear. PATIENTS AND METHODS: We performed a multicenter, retrospective registry-based study of 1550 patients with endometrial cancer. The outcome measure was the reason for not performing the indicated treatment. RESULTS: Median follow-up was 76.8months. A total of 1550 women were eligible for analysis: 353 (22.7%) were younger than 60years, 521 (33.6%) 61-70years, 515 (33.2%) 71-80years, and 161 (10.4%) were aged 81years old and older. Elderly women were more likely to have non-endometrioid, undifferentiated endometrial cancer at an advanced stage. Patients younger than 60years were more likely to receive lymphadenectomy, brachytherapy, external-beam radiotherapy (EBRT) and systemic therapy compared with the group of patients aged older than 70years. We investigated the reason why elderly women were undertreated. The rate of indicated therapies that were not recommended by the physicians proportionally increased with an increase in patient age. Interestingly, the rate of contraindications because of performance status and/or medical disease also increased proportionally with increasing patient age. Notably, in the groups of patients older than 70years, patient refusal was a very uncommon reason for failure to perform the indicated therapy. CONCLUSIONS: Elderly women with EC are more likely undertreated because the therapy was not recommended by the physicians based on performance status and medical diseases rather than patient refusal.

Perinatal and maternal outcomes at term in low-risk pregnancies according to NICE criteria: comparison between a tertiary obstetrical hospital and midwife-attended units.

PURPOSE: The aim of this study was to evaluate the perinatal and maternal outcomes at term at a single tertiary, university hospital in women with low-risk pregnancies. PATIENTS AND METHODS: We performed a retrospective cohort study of women with low-risk pregnancies, who delivered at University Women's Hospital Magdeburg between January 2010 and December 2014. Data were compared with data published by Brocklehurst et al. 2011. RESULTS: Of the 6052 women investigated, 2014 were classified as low risk according to the NICE criteria and were eligible for analysis. In 94.8%, a spontaneous vertex birth was observed. There were only 2 (0.1%) perinatal complications and 52 (2.5%) maternal complications. Ventouse delivery, forceps delivery, and caesarean sections were performed in 2.5, 1, and 3.1% of the cases, respectively. Episiotomy was performed in 37.7% of women. The third and fourth degree perineal trauma were observed in 0.3% of births investigated. Complications during the third stage of labour and blood transfusions were observed in 0.25 and 0.2%, respectively. In comparison with the births at home, we had lower rate of fetal complications for nulliparous women, but not for multiparous women, lower rate for blood transfusions, third and fourth degree perineal trauma and forceps delivery, and higher rate of spontaneous vertex birth, epidural analgesia, and episiotomy. The rate of vacuum extractions and caesarean sections were similar between both the places of birth. CONCLUSIONS: The tertiary-level obstetric unit is safe place of birth for women with low-risk pregnancies.

Should the hyperechogenic halo around malignant breast lesions be included in the measurement of tumor size?

The estimation of tumor size is important for treatment strategies of breast cancer. The hyperechogenic zone around breast cancer is a recognized criterion for malignancy, but its impact on preoperative tumor size estimations has been poorly investigated. Data of prospectively maintained database of 513 patients with primary breast tumors were analyzed retrospectively. A total of 196 patients with complete datasets including preoperative ultrasound (US) were eligible for analysis. The median age of the patients was 58.5 years (range 33-87). With all of the 196 patients, US has been performed. In 170 of 196 (86.7 %) cases, an echogenic halo was detected. We use two ways to measure tumor size with US: without (US-0) and with (US-1) echogenic halo. Mammography (MG) was used as standard. Tumor size measured by US and MG was compared with the actual histopathological (HP) tumor size. Mean differences between the sizing obtained by US-0, US-1, and MG and the HP sizing were -6.5, -1.5, and -1.8 mm, respectively. All three methods tend to underestimate the tumor size. The US-1 measurement was the closest to the HP size in comparison to the MG and US-0 measurements and the match was higher in tumors <2 cm. The estimated Pearson correlation coefficients (r) were 0.72, 0.68, and 0.61 for US-1, US-0, and MG, respectively. Moreover, the predictive value of US-1 regarding tumor size was not influenced by histological type and grade of the tumor, receptor status, and presence of intraductal component. Estimation of tumor size by US should include the hyperechogenic zone around the tumor.

Peritoneal closure during laparoscopic supracervical hysterectomy.

OBJECTIVE: Our goal was to compare postoperative pain and analgesic requirements regarding closure and non-closure of the peritoneum in women undergoing laparoscopic supracervical hysterectomy (LSH). STUDY DESIGN: A prospective cohort study was designed to investigate the impact of peritoneal closure for LSH. Postoperative pain was measured by a visual analogue scale (VAS) and analgesic requirements were assessed. Intra- and postoperative complications and operative time were recorded. RESULTS: A total of 104 patients were enrolled. Fifty-two (50 %) women underwent a LSH with peritoneal closure and 52 (50 %) underwent LSH without closure. The baseline characteristics were well balanced between the groups except for age; women undergoing LSH without peritoneal closure were significantly younger (p < 0.008, t test). The median operative time was 53 (26-105) minutes for LSH with peritoneal closure and 44 (24-83) minutes for LSH without peritoneal closure, a median reduction of 9 minutes (p = 0.007). No differences were found in uterine weight, intra- and post-operative complications, median haemoglobin drop or time in hospital when contrasting both groups. Both groups had similar VAS-pain scores and needed similar analgesic therapies. CONCLUSIONS: The peritoneal closure at LSH provides no short-term postoperative advantages over a non-closure approach, and it prolongs the operative time and anaesthetic exposure. Our data suggest that peritoneal closure is not necessary in LSH.

Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer.

BACKGROUND: Bevacizumab, a monoclonal antibody against vascular endothelial growth factor A, has shown clinical efficacy in patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer. We evaluated the efficacy, measured according to the rate of pathological complete response (absence of invasive and intraductal disease in the breast and the axillary lymph nodes), and the safety of adding bevacizumab to neoadjuvant chemotherapy in patients with early-stage breast cancer. METHODS: We randomly assigned 1948 patients with a median tumor size of 40 mm on palpation to receive neoadjuvant epirubicin and cyclophosphamide followed by docetaxel, with or without concomitant bevacizumab. Patients with untreated HER2-negative breast cancer were eligible if they had large tumors, hormone-receptor-negative disease, or hormone-receptor-positive disease with palpable nodes or positive findings on sentinel-node biopsy, and no increased cardiovascular or bleeding risk. RESULTS: Overall, the rates of pathological complete response were 14.9% with epirubicin and cyclophosphamide followed by docetaxel and 18.4% with epirubicin and cyclophosphamide followed by docetaxel plus bevacizumab (odds ratio with addition of bevacizumab, 1.29; 95% confidence interval, 1.02 to 1.65; P=0.04); the corresponding rates of pathological complete response were 27.9% and 39.3% among 663 patients with triple-negative tumors (P=0.003) and 7.8% and 7.7% among 1262 patients with hormone-receptor-positive tumors (P=1.00). Breast-conserving surgery was possible in 66.6% of the patients in both groups. The addition of bevacizumab, as compared with neoadjuvant therapy alone, was associated with a higher incidence of grade 3 or 4 toxic effects (febrile neutropenia, mucositis, the hand-foot syndrome, infection, and hypertension) but with a similar incidence of surgical complications. CONCLUSIONS: The addition of bevacizumab to neoadjuvant chemotherapy significantly increased the rate of pathological complete response among patients with HER2-negative early-stage breast cancer. Efficacy was restricted primarily to patients with triple-negative tumors, in whom the pathological complete response is considered to be a reliable predictor of long-term outcome. (Funded by Sanofi-Aventis and Roche, Germany; ClinicalTrials.gov number, NCT00567554.).

Moderate level of HER2 expression and its prognostic significance in breast cancer with intermediate grade.

Overexpression of human epidermal growth factor receptor 2 (HER2) is an important prognostic and predictive marker of response to anti-HER2 therapy in breast cancer. Our goal was to analyze the prognostic significance of moderate expression of HER2 in breast cancer with intermediate differentiation grade. We performed a multicenter retrospective register study of 8494 patients with primary non-metastatic breast cancer admitted between 2000 and 2011 to eight Clinics in Saxony-Anhalt, federal state of Germany. Patients were divided into three groups according to their HER2 score: 4073 were classified as HER2 negative (HER2 0 and 1+), 822 HER2 moderate (HER2 2+/HER2), and 1238 HER2 positive (HER2 3+ or HER2 2+/HER2+). HER2-positive cases were excluded from analysis. Tumors with moderate HER2 (HER2 2+) expression demonstrated an aggressive behavior and worse patient survival compared with HER2 0 and 1+ status. HER2 2+ status was associated with shorter median overall survival (OS) (P < 0.0001) in breast cancer patients with an intermediate grade of differentiation. Comparing low-grade and high-grade tumors, HER2 moderate expression did not significantly influence patient survival. In multivariate analysis after adjustment for other prognostic factors HER2 2+ status remained an unfavorable prognostic factor for OS (HR 1.224, 95 % CI 1.059-1.415, P = 0.006) in breast cancer patients with an intermediate grade of differentiation. HER2 2+ status is an unfavorable prognostic factor regarding the OS of breast cancer patients with intermediate grade of differentiation and could be used to identify patients, who may benefit from adjuvant therapy.