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Background: Male breast cancer (MBC) is a rare disease, and the potential influence of low expression of human epidermal growth factor receptor 2 (HER2 low) remains unexplored., Methods: In this prospective cohort study, we evaluated 870 patients treated for MBC between May 2009 and June 2023 to assess HER2 low status and its prognostic implications., Results: With a median follow-up of 43 months (range 1-175 months), 659 eligible patients were categorized into three groups based on HER2 status: 501 (76%) HER2 low, 81 (12.3%) HER2 zero, and 77 (11.7%) HER2 positive. HER2 positivity correlated with younger age, higher proliferation index, non-specific type histology, lymphovascular invasion (LVSI), and low differentiation grade. Notably, all these parameters were equally distributed between the HER2 zero and HER2 low groups. Additionally, HER2 positivity was significantly associated with increased occurrences of regional and distant lymph nodes and pulmonary metastases. However, no statistically significant difference was observed between HER2 zero and HER2 low. Disease-free and overall survival showed no significant disparities between the groups., Conclusions: Our findings suggest that HER2 low status is frequently detected in MBC. Despite this, HER2 low did not correlate with clinical and pathological parameters, nor did it impact patients' survival.

Purposes: Young breast cancer patients aged 35 years and younger are a small group of women who tend to present at high-risk form of the disease. More analysis of the data on tumor characteristics, treatment, and survival is necessary to help improving treatment and outcome., Methods: In this retrospective study, we compared the clinical and tumor characteristics, the treatments, and the survival of 257 women aged ≤ 35 years, with 6566 women aged 50-69 years. We used a registry-based data of patients with invasive, non-metastatic breast cancer diagnosed between 2000 and 2015., Results: Young women showed lower rate of hormone receptor (HR) positivity. Their tumors were more often HER2-positive, which showed lower rate of differentiation and higher rate of Ki-67 expression compared to their older counterparts. Women aged 35 years and younger were more likely to undergo neoadjuvant therapy and mastectomy. Endocrine therapy was underrepresented in young patients. 5-Year disease-free survival (DFS) was significantly lower in the younger patient group (81.7% vs. 91.3%, p < 0.001), while 5-year overall survival (OS) was not impaired (91.4% vs. 91.1%, p = 0.847)., Conclusion: The unfavorable disease-free survival in the group of younger patients might be explained by their unfavorable tumor characteristics. The surgical treatment appears to be more aggressive in young breast cancer patients and is more frequently combined with chemotherapy and immunotherapy, either in a neoadjuvant or in an adjuvant setting., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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.

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., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

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., (© 2021 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

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.

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., (Copyright © 2021 Termedia.)

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.

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.

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.

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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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.

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.

Purpose: To evaluate the pattern of endometrial cancer recurrence according to its biological subtype in a large cohort of patients., Patients and Methods: Patients were stage eligible if they had a description of registry risk of recurrence status and were not primary metastatic. Data were prospectively collected. The primary endpoints were the subtype-dependent pattern and time of recurrence., Results: The median follow-up time was 84 months. The highest 10-year recurrence-free and overall survival were seen in the group of patients at low risk of recurrence, 83.1 and 94.1%, respectively. The 10-year recurrence-free survival for intermediate and high risk group was 65.7 and 56.2%, respectively, whereas the estimated 10-year overall survival for both groups was 84.5 and 79.3%, respectively. Patients at high risk demonstrated the highest levels of disease recurrence in the first 3-4 years after diagnosis and the most common site of metastasis was the lung. In contrast, the rate of recurrence for patients at intermediate and low risk of recurrence in the first 5 years was relatively low but remained continuous up to 10 years of follow-up. Overall, the most common site of relapse was local recurrence., Conclusion: Endometrial cancer subtypes are associated with different times and patterns of recurrence and this should be considered when determining the treatment strategy.

Background: There is limited information about survival effect of vaginal brachytherapy (VBT) and its comparison to external beam pelvic radiotherapy (EBRT) and no radiotherapy (no-RT) of endometrial cancer patients., Patients and Methods: We performed a multicenter retrospective registry study of 1550 patients with endometrial cancer treated by no-RT (n = 702), VBT (n = 430) and EBRT ± VBT (n = 418). The outcome measure was overall survival., Results: RT did not improve the overall survival of patients with a low risk of recurrence. In univariate analysis, the survival effect of VBT was significant in patients with intermediate and high risk of recurrence (HR 0.42, CI 0.29-0.60, p < 0.0001). EBRT ± VBT demonstrated no survival effect in these groups. Multivariate analysis showed that VBT (HR 0.50, CI 0.36-0.71) significantly reduced the mortality risk in patients with an intermediate and high risk compared with no-RT after adjustment for age, tumor grading, tumor stage, lymphadenectomy, adjuvant therapy and comorbidities. Matching for age, histological type, tumor stage, tumor grade, and performance status between patients treated with no-RT and VBT was performed. The matching analysis again demonstrated the favorable survival effect of VBT compared to no-RT on overall survival with an absolute risk reduction of 17.7%. Notably, in a further 106 matched pairs, EBRT ± VBT did not demonstrate any survival effect over VBT among patients at intermediate and high risk of recurrence., Conclusions: VBT should be performed in patients at intermediate and high risk of recurrence of endometrial cancer, after operative determination of lymph node status.

Purpose: To evaluate the pattern of recurrence of breast cancer according to its biological subtype in a large cohort of patients treated with therapy representative of current practice., Patients and Methods: Patients treated between 2000 and 2016 with known biological subtype were eligible. Data were prospectively collected. Primary endpoint was the subtype-dependent pattern and time of recurrence. Loco-regional and distant site and time of recurrence were assessed., Results: Median follow-up time was 80.8 months. For 12,053 (82.5%) of 14,595 patients with primary non-metastatic invasive breast cancer a subtype classification was possible. The luminal A subtype had the highest 10-year survival followed by luminal B and luminal/HER2. The worst survival demonstrated HER2 enriched and TNBC. HER2 and TNBC had the highest rate of recurrence in the first 5 years, whereas the rate of recurrence for luminal A and luminal B tumors was initially low, but remained continuously even after 10 years of follow-up. Luminal A tumors demonstrated the lowest rate of distant metastases predominantly in bone. So did luminal B tumors. HER2 enriched subtype was characterized with increased rate of loco-regional recurrence and distant metastases in bone, liver and brain. Luminal/HER2 had pattern of relapse similar to HER2 enriched tumors, with exception of loco-regional relapse and brain metastases. TNBC had higher rate of lung, bone and brain metastases as well as loco-regional relapse., Conclusion: Breast cancer subtypes are associated with different time and pattern of recurrence and it should be considered during treatment decision.

Background: Oophorectomy is generally performed in patients with endometrial cancer despite the rate of ovarian metastasis being relatively low., Patients and Methods: A multicenter retrospective registry-based study was performed in 2329 patients with endometrial cancer. The outcome measures were the incidence of ovarian metastasis and the impact on overall survival., Results: Median follow-up was performed at 84 months. A total of 2158 women were eligible for analysis, of which 131 (6.1%) had ovarian metastasis. Women with ovarian metastasis were more likely to have > 50% myometrial invasion, undifferentiated nonendometrioid tumors, and lymph and vascular space invasion. The presence of < 50% myometrial invasion, endometrioid histology, well-differentiated cancer, and negative lymph and vascular space invasion were associated with a very low rate (0.5%) of ovarian metastasis. Notably, after matching for tumor histology and grade, myometrial invasion, and lymph and vascular space invasion, ovarian metastasis was not associated with a reduced median overall survival., Conclusions: Ovarian preservation should be offered to premenopausal women with endometrial cancer in whom myometrial invasion is less than 50%, the histological type is endometrioid and well-differentiated, and lymph and vascular space invasion is not involved.

Background: Elderly women with cervical 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 1559 patients with cervical cancer. The primary outcome was the reason for not performing the indicated treatment., Results: Median follow-up was 67.8 months. A total of 956 women were eligible for analysis: 693 (64.2%) were younger than 60 years and 387 (35.8%) were aged 61 years old and older. Elderly women were more likely to have undifferentiated cervical cancer at an advanced stage. For early stage (stage IA1-IIA), tumors patients 61 years old and older were less likely to receive surgery [odds ratio (OR) 0.39; 95% CI 0.20-0.77] and radiochemotherapy (OR 0.37; 95% CI 0.21-0.66) compared with the group of patients aged < 60 years. The rate of lymphadenectomy was similar in both age groups. Patients 61 years old and older with advanced stage (IIB-IV) cervical cancer were also less likely to receive surgery [odds ratio (OR) 0.42; 95% CI 0.27-0.66], lymphadenectomy (OR 0.30; 95% CI 0.12-0.51) and radiochemotherapy (OR 0.31; 95% CI 0.20-0.48) compared with patients aged < 60 years. Notably, the rate of indicated but not performed therapies proportionally increased with an increase in patient age and the most important reason for this phenomenon was the failing of recommendation., Conclusions: Elderly women with cervical cancer are undertreated and this is more likely because the therapy was not recommended.

Purpose The GeparQuinto phase III trial demonstrated a lower pathologic complete response (pCR; pT0 ypN0) rate when lapatinib was added to standard anthracycline-taxane chemotherapy compared with trastuzumab in patients with human epidermal growth factor receptor 2 (HER2) -positive breast cancer. Here, we report the long-term outcomes. Methods Patients with HER2-positive tumors (n = 615) received neoadjuvant treatment with epirubicin (E) plus cyclophosphamide (C), followed by docetaxel (T) in combination with either lapatinib (L) or trastuzumab (H; ECH-TH arm: n = 307; ECL-TL arm: n = 308). All patients received adjuvant trastuzumab for a total of 12 months and 18 months in the ECH-TH and ECL-TL arms, respectively. Median follow-up was 55 months. Results Three-year disease-free survival (DFS), distant DFS (DDFS), and overall survival (OS) were not significantly different between the two treatment arms. Long-term outcomes correlated with pCR (DFS: hazard ratio [HR], 0.63; P = .042; DDFS: HR, 0.55; P = .021; and OS: HR, 0.31; P = .004). A benefit only for OS was observed in patients who were treated with trastuzumab and achieved pCR versus no pCR (HR, 0.15; P = .010), whereas no difference was found in patients with pCR versus without pCR in the lapatinib arm. DFS and DDFS remained unchanged in both treatment arms according to hormone receptor status, whereas OS was significantly better in hormone receptor-positive patients who were treated with neoadjuvant lapatinib (HR, 0.32; P = .019), followed by adjuvant trastuzumab. No difference was observed in hormone receptor-negative patients; however, the small number of events limits this interpretation. Within the hormone receptor-negative cohort, pCR was significantly associated with DFS, DDFS, and OS ( P = .002, .005, and .002, respectively). Conclusion pCR correlated with long-term outcome. In patients with hormone receptor-positive tumors, prolonged anti-HER2 treatment-neoadjuvant lapatinib for 6 months, followed by adjuvant trastuzumab for 12 months-significantly improved survival compared with anti-HER2 treatment with trastuzumab alone.

Background: Our goal was to compare the survival advantage of tamoxifen (TAM) and aromatase inhibitor (AI) in female (FBC) and male breast cancer (MBC)., Patients and Methods: We performed a retrospective study of 2785 FBC and 257 MBC patients treated with hormonal therapy., Results: The median follow-up was 106 months (range 3-151 months) and 42 months (range 2-115 months) for FBC and MBC, respectively. The patients were divided into two groups according to the hormonal therapy used: TAM-treated and AI-treated. MBC was characterized by older age, advanced tumor stage, and higher rate of lymph node metastases, in comparison with FBC. Matching analysis was performed using six prognostic criteria: patient age, tumor stage, tumor grade, lymph node status, human epidermal growth factor receptor (HER2) status, and administration of chemotherapy. The female and male patients were matched 2:1. In this analysis, 316 women and 158 men treated with TAM, and 60 women and 30 men treated with AI, were included. The overall survival (OS) was estimated by the Kaplan-Meier method and was compared between FBC and MBC. TAM-treated FBC and MBC patients had similar 5-year OS, 85.1 and 89.2%, respectively (p = 0.972). Notably, FBC patients treated with AI had significantly greater 5-year OS (85.0%) in comparison with AI-treated MBC patients (5-year OS of 73.3%; p = 0.028)., Conclusions: The OS of TAM-treated patients with MBC was similar to the OS of TAM-treated FBC patients, whereas AI treatment is associated with poorer survival of MBC patients.

Purpose: Precise presurgical diagnosis of tumour size is essential for adequate treatment of male breast cancer (MBC). This study is aimed to compare the accuracy of clinical measurement (CE), ultrasound (US) and mammography (MG) for preoperative estimation of tumour size., Methods: This study was conducted as a prospective, multicentre register study. One hundred and twenty-nine male patients with invasive breast cancer were included. CE, US and MG were performed in 107, 110 and 75 patients, respectively, and the estimated tumour size was compared with the histopathological (HP) tumour size., Results: All methods tended to underestimate the HP tumour size. None of the methods were significantly more accurate than the others in determining the maximal tumour diameter. The sensitivity within 5 mm tolerance for US was 65.5%, which was better than for MG (61.3%) and CE (56.6%). In the group of patients with pT2 tumours, MG showed significantly better accuracy than US. The measurements obtained with each method were significantly correlated with the HP measurements. The highest correlation coefficient was observed for MG (0.788), followed by US (0.741) and CE (0.671)., Conclusions: Our data demonstrate that MG and US have similar accuracy with regard to tumour size estimation. US assessment showed the highest sensitivity in determining tumour size, followed by MG and CE. However, MG demonstrated a significant advantage for estimating the real tumour size for pT2 tumours compared to US or CE.

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.

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., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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.

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.

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.

Overexpression of human epidermal growth factor receptor 2 (HER2) predicts response to anti-HER2 therapy in breast cancer. We investigated whether hormone receptor (HR) status influences the treatment benefit of trastuzumab in patients with breast cancer. Data from 8338 patients with primary nonmetastatic breast cancer from the cancer registry of Saxony-Anhalt Germany were analyzed. A total of 5554 patients were eligible for analysis. The median follow-up of the study was 6 years. Of the 5554 patients investigated, 1128 (20.3%) showed HER2 overexpression and 656 (58.2%) of them received adjuvant trastuzumab. The 10-year overall survival (OS) in the study cohort according to HR, HER2 status, and trastuzumab treatment was as follows: 78.4% for HR-/HER2-, 85.0% for HR+/HER2-, 70.4% HR-/HER2+/TRA-, 71.4% for HR+/HER2+/TRA-, 80.9% for HR-/HER2+/TRA+, and 89.2% for HR+/HER2+/TRA+. Trastuzumab treatment improved OS in the HR- patients only in the first 3 years, whereas in the HR+ group the effect of trastuzumab was still apparent 5 years after diagnosis. Notably, the relative improvement in a patient outcome was higher for HR+ patients. Nevertheless, matching for age, histological type, tumor stage, tumor grade, and performance status between patients with HR- and HR+ tumors demonstrated that the survival effect of trastuzumab was not affected by HR status; P=0.890. Trastuzumab treatment improves patients' survival regardless of HR status and should be offered to all HER2+ patients., (© 2016 Society for Endocrinology.)

Background: The lymphadenectomy in the treatment of endometrial cancer is a topic of ongoing debate. The direct comparison between no lymphadenectomy, pelvic lymphadenectomy, and pelvic/para-aortic lymphadenectomy regarding overall survival of patients with endometrial cancer is missing., Methods: We performed a multicenter, retrospective, registry-based study of 1502 patients with endometrial cancer treated with no lymphadenectomy (n = 697), systemic pelvic lymphadenectomy (n = 543) and systemic pelvic/para-aortic lymphadenectomy (n = 262). The patients were divided into three groups of recurrence risk: low, intermediate, and high. The outcome measure was overall survival., Results: Median follow-up was 78 months. Lymphadenectomy did not improve overall survival of patients with low risk of recurrence. The survival effect of systemic lymphadenectomy was significant in patients with intermediate and high risk of recurrence. Multivariate analysis showed that both pelvic (HR 0.63, CI 0.38-0.82, p = 0.001) and combination of pelvic/para-aortic lymphadenectomy (HR 0.50, CI 0.43-0.81, p < 0.0001) significantly reduced the mortality risk in patients with intermediate risk compared to the patients who underwent no lymphadenectomy. In patients with high risk, only combined pelvic/para-aortic lymphadenectomy (HR 0.62, CI 0.48-0.82, p = 0.005) was associated with decreased mortality rate compared with no lymphadenectomy. Among patients with intermediate and high risk of recurrence who did not receive any adjuvant therapy, pelvic/para-aortic lymphadenectomy significantly reduced the mortality risk (HR 0.52, CI 0.37-0.73, p < 0.0001) in comparison with no lymphadenectomy. This management was superior to pelvic lymphadenectomy alone. In patients with low risk of recurrence, lymphadenectomy had no effect on overall survival., Conclusions: Pelvic/para-aortic lymphadenectomy should be performed in all patients with endometrial cancer at intermediate and high risk of recurrence.

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.

Purpose: To determine the efficacy of ultrasound (US)-guided excision of nonpalpable breast cancer and compare it to standard wire-guided breast-conserving surgery (BCS)., Methods: One hundred fifty-eight women with nonpalpable breast cancer who underwent BCS were retrospectively studied. Positive surgical margins and reexcision rates were investigated., Results: Of the total cohort, 68 patients were treated with wire-guided and 90 with US-guided tumor excision. The tumor and patient characteristics were similar in the 2 groups; 13.2% and 12.2% of patients in the wire-guided and US-guided groups, respectively, had positive margins. Patient age, menopausal status, tumor size, histologic type, and histologic grade were associated with increased risk of positive margins. The shave margins were reexcised at the time of original operation more often by wire-guided localization (26.5%) than in the US-guided group (10.0%) (P = .010). The surgeon was able to identify correctly the problematic margin in 100% via intraoperative US and in only 27.8% when the wire-guided surgery was used (P < .001). The reexcision rate by a second operation was similar in 2 groups (P = .798). Eight (11.8%) of 68 patients in the wire-guided group and 9 (10.0%) of 90 patients in the US-guided underwent a second operation., Conclusion: US-guided BCS is as effective and safe as standard wire-guided excision of nonpalpable breast tumors., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The survival effect of adjuvant radiotherapy (RT) for vulvar cancer has been poorly investigated., Patients and Methods: We performed a multicentre retrospective register study of 257 patients with primary squamous vulvar cancer. The survival effect of adjuvant RT was investigated in two groups of patients, dependent on surgical margins. The outcome measure was overall survival. All statistical tests were two-sided., Results: Of the 257 patients investigated, 192 had negative resection margins, while positive and/or close surgical margins were observed in 65 cases. Margin status was associated with unfavourable overall survival. The five-year overall survival was 66.1 and 49.2% in patients with negative and positive/close resection margins, respectively. Adjuvant RT directed to the vulva was associated with improved survival in patients with positive/close resection margins but not in patients with negative surgical margins. The 5-year overall survival of patients with positive/close surgical margins without RT was 29%, whereas with RT it increased to 67.6%. Notably, patients with positive/close surgical margins who received RT of the vulva had a 5-year survival rate similar to the patients with negative margins (67.6%). Multivariate analysis adjusted for age, stage of disease, tumour grade and lymph node metastases showed that adjuvant RT significantly reduced the mortality risk in patients with positive/close resection margins (HR 0.36, CI 0.14–0.94, p = 0.038). In the group of patients with negative resection margins, the involvement of lymph nodes was the strongest unfavourable prognostic factor., Conclusions: Adjuvant RT should be used for patients with positive/close surgical margins to improve their outcome.

Overexpression and/or amplification of human epidermal growth factor receptor 2 (HER2) is associated with poor prognosis in breast cancer and predicts response to anti-HER2 therapy in breast cancer. The prognostic relevance of moderate expression of HER2 is unclear. Data of 9872 patients with primary nonmetastatic breast cancer from the cancer registries of Magdeburg and Halle, Germany, were analyzed retrospectively. A total of 5907 patients with complete data sets including follow-up were eligible for analysis. HER2 status was determined as recommended by international guidelines. Of 5907 patients investigated, 5023 (68.4%) had HER2 0 and 1+ expression and 884 (12.0%) had HER2 (2+)/HER2- expression. Patients with hormone receptor positive (HR+) and HER2 (2+) tumors had a shorter median disease-free survival (DFS; P<0.0001) and breast cancer specific survival (BCSS; P=0.019) than HR+ patients with HER2 (0/1+) tumors. Among patients with HR- breast cancer there was no significant difference between HER2 (2+) and HER2 (0/1+) tumors. In multivariate analysis after adjustment for other prognostic factors, HER2 (2+) status remained an unfavorable prognostic factor for DFS (hazard ratio (HR)=1.217, 95% CI=1.052-1.408; P=0.008) but not for BCSS (HR=1.045, 95% CI=0.926-1.178; P=0.474). The HER2 (2+) status is an unfavorable prognostic factor for survival of patients with HR+ breast cancer. The impact of anti-HER2 therapy in this group of patients should be evaluated., (© 2015 Society for Endocrinology.)

Unlabelled: Tumor specimens from 410 patients with primary invasive breast cancer were investigated to identify the clinically relevant features of tumor-associated intraductal component (IDC) surrounding invasive breast cancer. A tumor-associated IDC associated with invasive tumor was mostly localized between the tumor and nipple. Thus, segmental resection of breast tissue is suggested., Introduction: The goal of the present study was to identify the clinically relevant features of tumor-associated intraductal component (IDC) surrounding invasive breast cancer., Patients and Methods: The tumor specimens from 410 patients with primary invasive breast cancer were investigated. The distance between the surgical margins and tumor edge (invasive and intraductal areas) was measured prospectively., Results: Of the 410 investigated patients, 395 were eligible for analysis. An IDC was observed in 241 specimens (61.0%) and was associated with a younger age at diagnosis, postmenopausal status, and positive estrogen receptor, progesterone receptor, and human epidermal growth factor 2 (HER2) expression status. Most cases with tumor-associated ductal carcinoma in situ (DCIS) were found in the upper-outer quadrants of the breasts. An extended intraductal component (EIC) tended to be present in the outer and lower quadrants of the breasts. In the study cohort of 187 patients with tumor-associated DCIS, 1496 surgical margins were investigated. IDC was associated with invasive tumor growth predominantly in the nipple direction. The nipple-associated growth of DCIS correlated with patient age > 40 years, tumor size ≤ 2 cm, poor histologic differentiation of the noninvasive and invasive components, and positive estrogen and progesterone receptor status and negative HER2 status., Conclusions: Our data provide evidence that in patients with primary breast cancer, the EIC areas will be mostly segmentally localized between the invasive tumor and the nipple. Therefore, if EIC is present or assumed, surgery should consist of segmental resection of the breast tissue, at least in patients with breast cancer who are > 40 years old, with a tumor size of < 2 cm, and with hormone receptor-positive and HER2-negative, poorly differentiated tumors., (Copyright © 2015 Elsevier Inc. All rights reserved.)

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.

Purpose: Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor, has shown increased pathological complete response rates when added to neoadjuvant chemotherapy. In various cancer types, bevacizumab treatment was accompanied by an increased risk of bleedings and other surgical complications. We assessed associated surgical complications., Methods: In the GeparQuinto trial, 1,948 patients were randomized to receive four cycles epirubicin/cyclophosphamide (EC, 90/600 mg/m(2) q3w) followed by four cycles docetaxel (D, 100 mg/m(2) q3w) each with (ECB-DB) or without (EC-D) bevacizumab (B, 15 mg/kg q3w) concurrent with chemotherapy. Surgery had to be performed not earlier than 28 days after the last bevacizumab infusion, but within days 21 and 35 after the last chemotherapy., Results: In 743 (38.1 %) patients, a surgical complication (bleedings, hematomas, necrosis, wound infections, abscess) was documented prospectively. Baseline characteristics of the patients were well balanced between both arms. The breast-conserving surgery (BCS) rate (N = 502) was 69.1 % (EC-D) and 71.9 % (ECB-DB; p = 0.464). The first surgical procedure was performed at a median of 29 (EC-D) and 34 days (ECB-DB) after last chemotherapy with or without bevacizumab infusion (p < 0.001). Surgical complications were documented in 38 (10.9 %; EC-D) and 59 (15.0 %; ECB-DB) patients (p = 0.103). Surgical complications were significantly higher after ECD-DB only in patients treated with BCS (N = 53; p = 0.029) or in those requiring repeat surgery in order achieve clear margins (N = 23; p = 0.037) compared to the EC-D group., Conclusions: Addition of bevacizumab to neoadjuvant chemotherapy might be associated with an increased risk for surgical complications in patients treated with BCS or after repeated surgeries.

The goal of this study was to assess the size of the ultrasound-measured margin associated with an adequate surgical margin during breast-conserving surgery (BCS). The study was designed as a prospective cohort study. Patients with primary invasive breast cancer undergoing BCS were included. The ultrasound-measured surgical margins were compared with the pathological margins. 147 patients were eligible for analysis. 21 (14.3 %) patients had close or positive resection margins and 13 (8.8 %) underwent a second operation. Small excision volume, multifocality, postmenopausal status, high grade tumor-associated intraductal component, and invasion of lymph vessels and lymph nodes were associated with increased risk of positive excision margins. In the study cohort, 882 Ultrasonography (US) margins were measured and a good correlation to the pathological margins was observed. Overestimation of the US-measured margins relative to the pathological margins was increased with younger age, premenopausal status, and intraductal component. The estimated positive and negative predictive values, sensitivity and specificity were 81.0, 96.2, 48.4, and 99.1 %, respectively. We found that a sonographically estimated margin of ≥ 4 mm was associated with an adequate pathological margin of ≥ 1 mm in 100 % of tumors that did not have a high grade intraductal component. However, this was not applicable for tumor-associated high grade intraductal component where a US margin of 14 mm was associated with clear pathological margins in 100 % of cases. Intraoperative ultrasonography is a safe and feasible method to obtain clear surgical margins by BCS.

Introduction: The aim of this study was to determine the efficacy of ultrasonography (US)-guided excision of palpable breast cancer and to compare it with the standard palpation-guided breast-conserving surgery (BCS)., Methods: For this purpose, 335 women with palpable breast cancer who underwent BCS were retrospectively studied. The positive surgical margins and re-excision rates were investigated., Results: Of the total cohort, 137 patients were treated with palpation-guided BCS and 198 underwent US-guided tumor excision. The tumor and patient characteristics were similar in both groups. Patient age, postmenopausal status, tumor size, histological grade, intraductal tumor component, lobular histology, and palpation-guided tumor excision were associated with increased risk of positive margins. The shave margins were re-excised at the time of original operation more often by palpation-guided localization (28.5%) than by the US-guided procedure (11.1%) (P < .0001). A surgeon was able to correctly identify the "problematic" margin in 81.1% of cases via intraoperative US and in only 17.9% via palpation (P < .0001). The re-excision rate during a second operation was significantly reduced by US-guided tumorectomy (P = .004). Of 198 patients in the US-guided group, 23 (11.6%) underwent a second operation, as did 33 of 137 patients in the palpation group (24.1%). The sensitivity and specificity of US-guided excisions were 52.7% and 97.5%, respectively, whereas the sensitivity and the specificity of palpation-guided tumor excisions were 15.5% and 65.9%, respectively., Conclusion: US-guided BCS is superior to palpation-guided excision in predicting the closest margins, obtaining clear surgical margins, and reducing re-operations., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the oncologic safety and cosmetic results after breast cancer surgery for central breast cancer by the B technique., Methods: Seventy women with operable breast cancer located in the central portion of the breast that had received resection surgery with the B technique were recruited. The primary outcome was the oncological safety, quantified as rate of positive resection margins and the cosmetic outcome evaluated by postsurgical self-assessment of the cosmetic outcome via questionnaire. The median follow-up period was 61.4 months (range 7.9-142.6 months)., Results: With one exception all patients had T1-2 tumors less than 5 cm in diameter. Most patients had invasive ductal breast cancers (57.1 %), followed by ductal carcinoma-in situ (27.1 %) and invasive lobular breast cancers (8.6 %). The incidence of positive resection margins was 17.1 %. No local tumor recurrence occurred during follow-up; one patient had distant metastases. In total, 80 % of the patients reported that the cosmetic results met or exceeded their expectations., Conclusions: The B technique is a safe breast conservation surgery for the excision of tumors located in the central portion of the breast and yields a high rate of satisfactory cosmetic results.

Background: The goal of this population-based study was to determine the impact of post-mastectomy radiation therapy on long-term overall survival (OS) of male patients with breast cancer., Patients and Methods: We investigated 20-year OS rates of 664 patients diagnosed with primary stage I-III breast cancer in former East Germany between 1970 and 1989. Patients had a radical mastectomy with axillary lymph node dissection without systemic adjuvant therapy., Results: Median follow-up time was 26.2 years (range 19-38 years). 52.4% of the patients had post-mastectomy radiotherapy. Radiotherapy showed different effects in each stage group after 20 years. Whereas there was an OS trend for radiotherapy to harm patients with stage I disease (hazard ratio (HR) 1.45; 95% confidence interval (CI) 0.98-2.15; p = 0.065), radiotherapy showed no benefit in patients with stage II disease (HR 0.82; 95% CI 0.62-1.1; p = 0.15). There was a significant survival benefit for patients with stage III disease receiving radiotherapy (HR 0.60; 95% CI 0.41-0.88; p = 0.008)., Conclusion: Post-mastectomy radiotherapy is associated with longer OS in male patients with stage III breast cancer. Male breast cancer patients at stages I and II do not seem to benefit from radiotherapy, but obsolete irradiation techniques might explain adverse long-term effects in earlier stages.

To determine the impact of adjuvant treatment with tamoxifen and aromatase inhibitors (AI) on the survival of men with breast cancer. We analyzed 257 male patients with hormone-receptor-positive breast cancer from numerous German population-based cancer registries treated with tamoxifen (N = 207) or aromatase inhibitors (N = 50). The median follow-up was 42.2 (range 2-115) months. Median age at diagnosis was 68 (range 36-91) years. Thirty-seven (17.9 %) patients treated with tamoxifen and 16 (32.0 %) patients treated with AI died (log rank p = 0.007). After the adjustment for the patient's age, tumor size, node status, and tumor grading, the AI treatment was linked to a 1.5-fold increase in risk of mortality compared to tamoxifen (HR 1.55; 95 % CI: 1.13-2.13; p = 0.007). The overall survival in male breast cancer was significantly better after adjuvant treatment with tamoxifen compared to an aromatase inhibitor. Tamoxifen should be considered as the treatment of choice for hormone-receptor-positive male breast cancer.

Purpose: To identify the most appropriate magnetic resonance (MR) sequence for breast biopsy with regard to lesion visibility and artifact size and to assess feasibility and safety of this approach in a clinical setting., Materials and Methods: MR-guided interventions were performed in an open 1.0-T MR imager between November 2009 and January 2011. The prospective clinical study was approved by the institutional review board. Written informed consent was obtained. Four different fast dynamic sequences (balanced steady-state free precession, T1-weighted turbo gradient-echo, T1-weighted turbo spin-echo [SE], and T2-weighted single-shot SE sequences) were evaluated for artifact size of biopsy needle and in vivo for lesion visibility. In vivo breast biopsies were performed with the freehand technique and without immobilization or a positioning device by using an interactive MR mode that allowed continuous imaging in two orthogonal planes for guidance., Results: On the basis of good lesion detection in combination with small artifact size, T1-weighted SE imaging was used for biopsy. A total of 75 biopsies were performed successfully in 69 patients (mean age, 53 years; age range, 35-78 years) (mean lesion size, 7.1 mm; range, 4-15 mm). The interactive MR platform enabled immediate localization and correction of intended needle trajectory. Average time for freehand biopsy was 12 minutes (range, 8-23 minutes). No major complications were recorded., Conclusion: MR-guided freehand biopsy of breast lesions with the near-real-time interactive MR platform in an open 1.0-T MR imager is safe and feasible in a clinical setting. The method simplifies work flow and intervention performance., (© RSNA, 2012)

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.).

Recently, we have shown that the new G-protein-coupled estrogen receptor GPR30 plays an important role in the development of tamoxifen resistance in vitro. This study was undertaken to evaluate the correlation between GPR30 and tamoxifen resistance in breast cancer patients. GPR30 protein expression was evaluated by immunohistochemical analysis in 323 patients with primary operable breast cancer. The association between GPR30 expression and tamoxifen resistance was confirmed in a second cohort of 103 patients treated only with tamoxifen. Additionally, we evaluated GPR30 expression in 33 primary tumors and in recurrent tumors from the same patients. GPR30 expression was detected in 56.7% of the breast cancer specimens investigated and it correlated with overexpression of HER-2 (P = 0.021), EGFR (P = 0.024) and lymph node status (P = 0.047). In a first cohort, survival analysis showed that GPR30 was negatively correlated with relapse-free survival (RFS) only in patients treated with tamoxifen (tamoxifen with or without chemotherapy). GPR30 expression was associated with shorter RFS (HR = 1.768; 95% CI, 1.156-2.703; P = 0.009). In a subset of patients treated only with tamoxifen, multivariate analysis revealed that GPR30 expression is an independent unfavorable factor for RFS (HR = 4.440; 95% CI, 1.408-13.997; P = 0.011). In contrast, GPR30 tended to be a favorable factor regarding RFS in patients who did not receive tamoxifen. In 33 paired biopsies obtained before and after adjuvant therapy, GPR30 expression significantly increased only under tamoxifen treatment (P = 0.001). GPR30 expression in breast cancer independently predicts a poor RFS in patients treated with tamoxifen.

Objective: This study was undertaken to evaluate the potential role of G-protein-coupled estrogen receptor in endometrial pathology associated with tamoxifen treatment of breast cancer patients., Study Design: We investigated whether G-protein-coupled estrogen receptor plays a role in mediating proliferating effect of tamoxifen in endometrial carcinoma cells. These results were compared with the G-protein-coupled estrogen receptor expression pattern in endometrial tissue from a cohort of 95 breast cancer patients, who received tamoxifen or another adjuvant therapy., Results: In vitro tamoxifen significantly stimulated the mitogen-activated protein kinase phosphorylation and cell proliferation of endometrial cell lines via G-protein-coupled estrogen receptor. In vivo, there was a significant correlation between G-protein-coupled estrogen receptor expression and the tamoxifen-induced endometrial pathology (P = .006). Moreover, G-protein-coupled estrogen receptor positivity was predictive of an earlier development of symptoms, such as bleeding or suspect endometrial thickness, induced by tamoxifen therapy (P = .019)., Conclusion: G-protein-coupled estrogen receptor plays an important role in tamoxifen-induced endometrial abnormalities., (Copyright © 2010. Published by Mosby, Inc.)

SUMMARY: INTRODUCTION: We aimed to take a snapshot of breast units in the European Union 9 years after the publication of the European Society of Mastology (EUSOMA) position paper. METHODS: In order to obtain information on breast units throughout the European Union, we designed a questionnaire comprising 5 questions on certification, audit frequency and number of breast units in each country. Our primary contacts were national cancer societies, breast cancer study groups, breast cancer organizations, national associations and societies of breast treatment, as well as experts in the field of breast cancer. RESULTS: Information on characteristics of the certification process and number of breast units was obtained for 9 countries of the European Union. 7 of the 9 countries (78%) have a certification process of the breast units. Certification is carried out by public authorities in 4 (57%) countries and by private companies in 3 (43%) countries. Information on frequency of auditing was reported in 4 countries and varied between annual audits (Austria, Ireland and Germany) and audits once every 3 years (United Kingdom). CONCLUSIONS: The current study suggests that the European breast unit landscape is a heterogeneous field. 9 years after the EUSOMA position paper, we do not have any standard European guidelines, neither for the development nor for the mandatory prerequisites of a breast unit. The development and operation of breast units are still country specific.

Introduction: Despite the fact that people older than 65 years of age have the highest incidence of developing breast cancer, these patients are excluded from clinical trials in most cases. Furthermore, most physicians tend towards therapy regimens without the use of dose-dense, highly active taxane-based treatments because of a lack of data regarding toxicities of these compounds in older patients., Methods: Pooled side-effect data were analyzed from four prospective, randomized clinical trials in which patients of different age groups (< 60 years, between 60 and 64 years, and > 64 years) with primary breast cancer received taxane-based chemotherapy., Results: Dose delays, dose reductions, hospitalization, and therapy discontinuation increased with age. Hematologic toxicities and some nonhematologic toxicities were generally more common in older patients. Leucopenia increased from 55.3% in patients aged < 60 years to 65.5% in patients aged > 64 years (P < 0.001), and neutropenia increased from 46.9% to 57.4% (P < 0.001). There was no difference, however, in clinically more relevant febrile neutropenia between the different age groups. Thrombopenia shows a similar age-dependent increase, whereas there is no difference between the age groups concerning anemia. Hot flushes and elevated liver enzymes decreased with increasing age., Conclusions: The present pooled analysis of a substantial cohort of older primary breast cancer patients demonstrates that taxane-containing (neo)adjuvant chemotherapy is feasible in older patients and that toxicity can be reduced by sequential therapy regimens.

Tamoxifen is increasingly used in adjuvant endocrine therapy for postsurgery breast cancer patients and in chemoprevention for high-risk patients. We present a case of bilateral ovarian cyst development with consecutive unilateral cyst torsion and elevated serum estradiol in a premenopausal patient treated with tamoxifen after breast-conserving surgery.

Background: The goal of the present study was to investigate the changes in concentration of the important lymph-angiogenesis factors vascular endothelium-derived growth factor (VEGF) and VEGF-D under adjuvant chemotherapy., Materials and Methods: The blood plasma of a total of 142 patients with breast carcinoma and with 1 to 3 affected lymph nodes was investigated, using the quantitative sandwich enzyme immunoassay technique, prior to and following chemotherapy, within the framework of a randomized phase III study: the patients received either conventional or dose-intensified chemotherapy., Results: In general, there was a significant reduction in VEGF levels after chemotherapy only in patients with large tumors (T3) (p = 0.043). There was also an almost significant reduction in patients with an overexpression of c-erbB-2 (Dako Score +3, p = 0.052). In contrast, the clearest reduction in VEGF-D occurred in patients with a positive hormone receptor status (p = 0.04) or in patients with a low expression of c-erbB-2 (Dako Score +1, p = 0.05). A significant effect of chemotherapy on VEGF-D was determined only in patients who had a baseline level that was above the normal (conventionel treatment p = 0.005; dose-intensified treatment p = 0.004)., Conclusion: Both VEGF and VEGF-D levels changed after chemotherapy, depending on the patient and tumor characteristics. With respect to changes in the plasma levels of VEGF and VEGF-D, there were no significant differences between dose-intensified and conventional chemotherapy.