Oncologic Outcome of Robotic-Assisted and Laparoscopic Sentinel Node Biopsy in Endometrial Cancer.

BACKGROUND: Recently, sentinel lymph node biopsy (SLNB) has been introduced in the surgical staging of endometrial cancer as an alternative to systematic lymph node dissection (LND). However, the survival impact of SLNB is not yet well characterised. METHODS: We performed a retrospective study of 419 patients with endometrial cancer treated with SLNB alone or with pelvic and para-aortic LND. For SLNB mapping, indocyanine green was used. RESULTS: Median follow-up was 66 months. After exclusions, 337 patients were eligible for analysis. Of them, 150 underwent SLNB and 187 LND. During the follow-up time, 27 (24.7%) of the 150 who underwent SLNB and 54 (28.9%) of the 187 who underwent LND were diagnosed with recurrent disease (p = 0.459). The estimated 5-year disease-free survival (DFS) rate was 76.7% and 72.2% for patients in the SLNB and LND group, respectively (p = 0.419). The 5-year overall survival (OS) rates were 80.7% and 77.0% in the SLNB and LND group, respectively (p = 0.895). Survival rates were similar in both groups independent of lymph node status. Multivariable analysis confirmed that the staging approach was not associated with oncological outcome. For patients without lymph node metastases, patient outcome was worsened by advanced tumour stage and non-endometrioid tumour histology. In the group of patients with confirmed lymph node metastases, advanced tumour stage and inadequate adjuvant treatment significantly reduced DFS and OS. CONCLUSION: Our data suggested that SLNB did not compromise the oncological outcome of patients with endometrial cancer compared to LND.

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.

G protein-coupled estrogen receptor 1 (GPER-1) and agonist G-1 inhibit growth of ovarian cancer cells by activation of anti-tumoral transcriptome responses: impact of GPER-1 mRNA on survival.

PURPOSE: The present study intended to further elucidate the role of G protein-coupled estrogen receptor 1 (GPER-1) in ovarian cancer by comparing the effects of a GPER-1 knockdown and treatment with its agonist G-1 on cell growth, apoptosis, and the transcriptome of two ovarian cancer cell lines. Furthermore, the role of GPER-1 in ovarian cancer survival was examined. METHODS: GPER-1 expression in OVCAR-3 and OAW-42 ovarian cancer cells was knocked down by RNAi. The effects on cell growth were measured by means of the fluorimetric cell titer blue assay and on the transcriptome by Affymetrix GeneChip analysis. The effect of GPER-1 on patient's survival was examined using open source mRNA and clinical data of 1657 ovarian cancer patients. RESULTS: GPER-1 knockdown resulted in a significant growth stimulation of both cell lines, whereas treatment with agonist G-1 decreased growth of both cell lines in a dose-dependent manner. Transcriptome analyses revealed a set of 18 genes being conversely regulated after GPER-1 knockdown and G-1 treatment. Generally, treatment with G-1 led to a transcriptome response associated with growth inhibition. In contrast, knockdown of GPER-1 exerted opposite effects, stimulating pathways activating mitosis, but inhibiting pathways associated with apoptosis or interferon signaling. Further analyses using open-access mRNA and clinical data by bioinformatical online tools revealed a longer OS (HR = 0.86, p = 0.057) and PFS (HR = 0.81, p = 0.0035) of ovarian cancer patients with high GPER-1 mRNA expression. CONCLUSIONS: The results of this study clearly support the hypothesis that GPER-1 acts as a tumor suppressor in ovarian cancer.

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.

GPER-1 expression is associated with a decreased response rate to primary tamoxifen therapy of breast cancer patients.

PURPOSE: Endocrine therapies using tamoxifen and/or aromatase inhibitors are important therapeutic options for the targeted treatment of hormone-responsive breast cancer. In addition to nuclear estrogen receptors ERα and ß, G-protein-coupled estrogen receptor GPER-1 is a third receptor-mediating estrogen effects in breast cancer cells. The aim of this study was to examine to what extent GPER-1 expression might affect the efficacy of primary endocrine treatment of breast cancer. METHODS: GPER-1 expression was determined in tissue samples from patients with early breast cancer by means of immunohistochemistry and a GPER-1 score of ≥ 3 was considered to be positive. In a total of 165 patients, the response to a primary therapy with tamoxifen (TAM) or aromatase inhibitors (AI) was assessed by ultrasound imaging for up to 6 months. The primary endpoint of this study was the response to treatment evaluated by RECIST 1.1 criteria. RESULTS: GPER-1 expression was observed in 127 (77.0%) out of 165 cases. Based on GPER-1 expression and the type of endocrine treatment, the patients were divided into 4 groups: GPER-1 negative/TAM (12.1%), GPER-1 negative/AI (10.9%), GPER-1 positive/TAM (44.8%), and GPER-1 positive/AI (32.1%). The groups were well balanced regarding different clinical and pathological factors. After 4 and 6 months of treatment, a high level of stable disease or progressive disease was observed in the GPER-1 positive/TAM group only (p < 0.0001), whereas in the other three groups of patients, the most common objective response was classified as partial response. We observed a continuous reduction of mean tumor size in patients treated with aromatase inhibitors irrespective of the GPER-1 status and in GPER-1 negative patients treated with TAM. In contrast, in GPER-1 positive patients treated with TAM, a reduction of mean tumor size was observed only in the first 2 months after beginning of treatment. Four and six months after start of treatment, no reduction, but even a slight increase of tumor size was observed in this patients group. CONCLUSIONS: GPER-1 expression is significantly associated with a reduced effect of primary treatment with tamoxifen in breast cancer patients.

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.

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.

G-protein-coupled estrogen receptor GPER-1 expression in hormone receptor-positive breast cancer is associated with poor benefit of tamoxifen.

BACKGROUND: The role of G-protein-coupled estrogen receptor 1 (GPER-1) in the development of tamoxifen resistance in breast cancer is a highly controversial issue. The aim of this study was to determine the expression of GPER-1 in the clinical routine under conditions of endocrine treatment. PATIENTS AND METHODS: GPER-1 expression was analyzed in 442 patients with primary invasive breast cancer. GPER-1 score of > 3 was determined as positive. Expression data were correlated with clinical and pathological characteristics and patient survival. RESULTS: GPER-1 expression was observed in 352 (80.9%) cases, and positively correlated with estrogen and progesterone receptor status (p = 0.0001). GPER-1 positivity was associated with an increased grade of differentiation (p = 0.0001) and with a low level of Ki-67 expression (p = 0.0001). High GPER-1 expression was associated with a decreased level upon systemic treatment (p = 0.011). In the whole cohort, GPER-1 expression was associated with prolonged disease-free survival (DFS). DFS between tamoxifen- and aromatase inhibitor-treated GPER-1-positive patients was similar (p = 0.090). Notably, after matching the analysis for the most important prognostic factors, DFS for tamoxifen-treated GPER-1-positive patients was 69.1%, which is a percentage that is significantly lower compared to DFS for GPER-1-positive patients treated with aromatase inhibitors (92.7%) (p = 0.005). CONCLUSION: GPER-1 expression is a favorable prognostic factor in breast cancer patients. Its predictive role for poor benefit form tamoxifen treatment should be investigated in further studies.

Endometrial cancer subtypes are associated with different patterns of recurrence.

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.

Vaginal brachytherapy for endometrial cancer.

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.

Patterns of breast cancer relapse in accordance to biological subtype.

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.

Ovarian metastasis in patients with endometrial cancer: risk factors and impact on survival.

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.

Management of elderly women with cervical cancer.

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.

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.

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.

GPER Promoter Methylation Controls GPER Expression in Breast Cancer Patients.

Recently, we found that G-protein-coupled estrogen receptor (GPER) protein expression decreased during breast carcinogenesis, and that GPER promoter is methylated. Here we analyzed GPER promoter methylation in 260 primary breast cancer specimens by methylation-specific polymerized chain reaction. The results demonstrated that GPER protein down-regulation significantly correlated with GPER promoter hypermethylation (p < .001). Comparison of 108 tumors and matched normal breast tissues indicated a significant GPER down-regulation in cancer tissues correlating with GPER promoter hypermethylation (p < .001). The latter was an unfavorable factor for overall survival of patients with triple-negative breast cancer (p = .025). Thus GPER promoter hypermethylation might be used as a prognostic factor.

Hormone receptor status does not alter the effect of trastuzumab in breast cancer.

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.

Survival advantage of lymphadenectomy in endometrial cancer.

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.