Ozden Altundag

A Turkish Gynecologic Oncology Group study of fertility-sparing treatment for early-stage endometrial cancer.

To analyze the results of fertility‐sparing treatment of early‐stage endometrial cancer (EC) in patients treated at Turkish gynecologic oncology centers, and to present a review of the literature.

Good Outcomes of Patients with Stage IB Endometrial Cancer with Surgery Alone

BACKGROUND Most patients with endometrial cancer have stage I disease. Adjuvant therapy in stage IB (formerly IC) endometrial cancer is controversial, treatment options including observation or brachytherapy/ radiotherapy in grade 1-3 patients with or without chemotherapy. The purpose of this study was to assess the outcomes of our patients with stage IB endometrioid endometrial cancer. MATERIALS AND METHODS Sixty two patients with stage IB endometrial cancer and endometrioid histology were retrospectively evaluated. All patients were initially treated surgically by the same surgeon with comprehensive staging, i.e. total abdominal hysterectomy, bilateral salphingooopherectomy, bilateral pelvic and paraaortic lymph node dissection and omentectomy. Adjuvant radiotherapy was discussed with patients and utilized by those who accepted. Adjuvant chemotherapy was not given to any of the patients. RESULTS Median age was 62 (range, 42-95). Ninety percent of the patients had grade 1-2 disease. Thirteen patients (21%) received intra vaginal brachytherapy (IVBT) and one received whole pelvic radiotherapy (WPRT). Median follow-up time was 46 months (range, 9-77 months). Three patients experienced recurrence (4.8%), two of them died on follow-up and one was still alive at last visit. Two patients with recurrence had FIGO grade 2 tumors and one had a grade 3 tumor. Two patients (3.2%) died without evidence of recurrent disease. Relapse free survival at 5 years was 94.4% and overall survival was 93.1%. CONCLUSIONS Patients with stage IB disease in our study demonstrated relatively low recurrence rates although the majority of them received no adjuvant treatment. Surgery alone may be sufficient for most patients with this stage of endometrial cancer.

Emerging drugs in endometrial cancers.

Importance of the field: Endometrial cancer remains the most common gynecologic malignancy. The treatment of endometrial cancer is rapidly evolving. Areas covered in this review: In this article, we aim to review current and future treatment options in the medical treatment of endometrial cancers. What the reader will gain: The cornerstone of curative therapy for patients with endometrial cancer is surgical treatment. Cytotoxic chemotherapy is the mainstay of therapy for metastatic and advanced endometrial cancer. The most active chemotherapy agents are anthracyclines, platinum compounds and taxanes. Combination chemotherapy has produced higher response rates than single agent therapy. Cisplatin and doxorubicin combination chemotherapy has served as the control arm in many trials. Three-drug combination regimen has shown the highest response rate but with increased toxicity. Despite the lack of published data supporting the superiority of the paclitaxel plus carboplatin combination over doxorubicin and cisplatin, many centers prefer this regimen as a standard of care. Hormonal therapy should be considered in patients with low grade tumors and in those with a poor performance status. Recent advances in the understanding of the molecular biology of endometrial cancer have led to development of targeted therapies. Among these the more promising ones are mTOR inhibitors and antiangiogenic agents. Take home message: Clinical trials are planned to further explore how to best incorporate novel agents into the current treatment algorithm with the aim to improve outcome for women with endometrial adenocarcinomas.

Impact of Treatment Strategies on Local Control and Survival in Uterine Carcinosarcomas in Turkey

BACKGROUND The purpose of this study was to determine the clinical characteristics, patterns of recurrence and survival outcomes in patients with uterine carcinosarcomas treated in our institution. MATERIALS AND METHODS Records of 26 patients diagnosed between 2007 and 2011 with uterine carcinosarcoma were retrospectively evaluated for demographic features, tumor characteristics, treatment regimens and patient outcomes in terms of DFS and OS RESULTS: Median age was 61 (range 43-78). 10 patients (38%) had stage I disease at diagnosis, 3 (12%) had stage II, 4 (15%) had stage III and 9 (35%) had stage IV. Sixteen patients (62%) received chemotherapy with paclitaxel and carboplatin for 6 cycles. One patient underwent radiotherapy. Median follow up was 17 months. Sixteen patients relapsed and 13 died during follow up. Considering recurrence, 5 out of 16 patients had lung metastases, one had brain metastases and 9 had only intraabdominal recurrence. The 3 year DFS was 37% and the 3 year OS was 30%. CONCLUSIONS Our data show that uterine carcinosarcomas tend to be at advanced stage at diagnosis and despite the use of chemotherapy, overall prognosis is poor. Surgery remains the mainstay of treatment. More effective adjuvant strategies are needed to reduce relapse and death rates.

Treatment of Lymph Node-Negative, Early-Stage HER2-Positive Breast Cancer

TO THE EDITOR: O’Sullivan et al report a meta-analysis of five randomized trastuzumab trials with 4,221 patients who had early-stage breast cancers that were human epidermal growth factor receptor 2 (HER2) positive and 2 cm or smaller. The efficacy end points were disease-free and overall survivals. They concluded that patients with HER2positive, 2-cm or smaller tumors derive significant disease-free and overall survival benefits from the addition of trastuzumab to the treatment regimen. Although we appreciate this meta-analysis, several points warrant discussion. The prognosis of patients with T1a and T1b tumors that are node negative is uncertain even in cases of HER2 overexpression. Many studies have reported that HER2 overexpression is an independent factor of poor prognosis in patients with pT1abN0 breast tumors. The authors mentioned that the number of such occurrences had been too small to make a decision about efficacy end points and that almost all of the occurrences were obtained from the HERA trial, which used trastuzumab sequentially. In the whole study population, as in the T1a and T1b tumor groups, almost 50% of occurrences came from the HERA trial. Thus, the faith of this population may be declared, because this metaanalysis consisted of randomized trials. The same disputation is valid for the lymph node–negative group. The authors evaluated the clinical outcomes of the group of patients with one or fewer lymph nodes, including those in an N0 group. They stated that the reasons were that few events had occurred in this patient group and that greater than 90% of occurrences were from the HERA trial. We think that, because there were approximately 1,000 cases in this group, mostly from the largest prospectively designed adjuvant trastuzumab trial on which the backbone of the adjuvant treatment of HER2-positive breast cancer has been patterned, the results of this group also may be worth declaring for clinical practice. There are some conflicting data in the literature reported, not from randomized trials but instead from retrospective series. Fehrenbacher et al retrospectively investigated 234 patients with breast cancer that was HER2 positive, lymph node negative, and T1a or T1b; distant invasive recurrence was a primary end point, and locoregional recurrence was a secondary end point. They stated that the 5-year distant relapse–free interval was 98.2% for patients with T1a tumors, whereas it was 89.4% and 84.5% for those with T1b and 1-cm tumors, respectively. Of those patients, 174 (74%) did not receive any adjuvant treatment. This result raises the question of whether the use of adjuvant chemotherapy and trastuzumab is necessary in the T1a group of patients. However in the study by Rodriguez et al, 276 patients with node-negative and T1abHER2-positive breast cancer were evaluated retrospectively. A total of 47% of all patients were given adjuvant chemotherapy and trastuzumab. Of adjuvant chemotherapy protocols, 42.6% were antracycline and taxane based; 28.7% were antracycline based, and 27.9% were taxane-only based. The 40month disease-free survival was 93% for patients who had not received chemotherapy, whereas it was 99% for those who had received adjuvant therapy. In the multivariate analysis, tumor size was not associated with clinical outcomes, and the authors stated that adjuvant treatment should be discussed with all patients who have pT1ab node-negative HER2-positive breast cancer. Another important question is what type of chemotherapy is reasonable for this group of patients. The optimal regimen in patients in a T1abN0 HER2-positive group is still not precise. As was discussed in the meta-analysis, APT is a single-arm prospective study for the efficacy of adjuvant paclitaxel and trastuzumab in patients with HER2-positive, node-negative breast cancer of 3 cm or smaller. Because most of the patients in this meta-analysis received an anthracycline and taxane combination, it may be valuable, in our opinion, to compare these two patient groups (ie, those who receive paclitaxel and trastuzumab versus those who receive an anthracycline and a taxane) to decide whether it is necessary to add an anthracycline or whether it is reasonable to continue with just a taxane and trastuzumab, which could have a lower probability of adverse effects. It was stated that the number of patients who had T1abN0 tumors in the meta-analysis was low; however, the group of patients with 1to 2-cm tumors is a larger patient group, and it is also important to evaluate the chemotherapy regimens in this group. Finally, we agree that the results of APT trial do not apply to patients who have 2to 3-cmHER2-positive node-negative tumors, because the number of patients in this group is quite low. It may be possible to evaluate this subgroup from these adjuvant trials to decide upon a treatment suggestion for this subgroup. Still, the guidelines include both a regimen of anthracycline and taxane combinations with trastuzumab and a regimen of only a taxane with trastuzumab.

Trastuzumab in metastatic breast cancer after complete remission: How long is enough?

Anti-human epidermal growth factor receptor 2 (HER2) therapies added to standard chemotherapy agents have been shown to improve disease-free survival (DFS) and overall survival (OS) via either single or dual blockade in HER2-amplified metastatic breast cancer patients [1]. The approved anti-HER2-directed drugs are monoclonal antibodies as trastuzumab, pertuzumab; dual tyrosine kinase inhibitor lapatinib and an antibody–drug conjugate trastuzumab emtansine. As is customary, maintanence treatment with an anti-HER2 drug until progression of disease remains the standard after response to first-line combined treatment of chemo and anti-HER2 agent that is mostly trastuzumab. Since tumors classified as HER2 positive are a heterogenous group, the optimal duration of trastuzumab for patients achieving complete response and the predictive markers for such patients is still a matter of debate. The longest relapse-free period with trastuzumab maintenance after complete remission was reported to be almost 9 years in a 46-year-old, hormone-receptor-negative breast cancer patient with liver and bone metastases at diagnosis. The reported progression-free values are between 6 months to 9 years in the literature. Among the 7 published cases with prolonged complete remission periods, all but one had metastases in the liver and 5 of them were hormone receptor negative. Six patients were reported to be in complete remission, all but one with trastuzumab maintanence [2]. In the report by Yan et al., 2 triple-negative locally advanced breast cancer patients were found to have HER2-positive, hormone-receptor-negative metastases during the follow-up. Because of financial problems, they could not receive trastuzumab at the time of metastases and anti-HER2 agent was added to treatment approximately after 1 year. Despite multiple metastatic sites including brain, both patients continued maintenance trastuzumab treatment up to now. One is still on complete remission while on trastuzumab maintenance for 28 months, and the other patient has been reported to be doing quite well with a partial response and still being on trastuzumab maintenance for 15 months [3]. In all of these cases, cardiac toxicity was not reported to be a clinically relevant adverse event. In the phase II HERLAP study, the predictive biomarkers for long-term efficacy of anti-HER2 agents without addition of chemotherapy were evaluated [4]. Although closed early with only 19 patients being enrolled, median progression-free and overall survivals were 7.3 (1.6–38?) and 43 (14–81?) months, respectively, quite similar to that reported with combined chemotherapy and single-agent anti-HER2 therapy trials [1]. Gene expression data and protein expression analysis revealed that patients with HER2-enriched tumors and with increasing values of quantitative HER2/p95HER2 (H2T/p95HER2) protein expression ratios showed significant increases in persistence on protocol, compared to patients with luminal A & B tumors and with lower H2T/p95HER2 ratios [4]. This finding can be a clue for choosing patients that will benefit most from long-term trastuzumab maintenance after achieving complete response with first-line combined therapy. Furthermore, studies analyzing the clinical outcomes with second-line trastuzumab after progression on first-line & Arzu Oguz oguzarzu@yahoo.com

Breast Carcinoma with Choriocarcinomatous Differentiation: A Rare Case

Objectives : Breast carcinoma with choriocarcinomatous differentiation is a rare entity, generally presenting with high-grade disease and an aggressive clinical course with overall survival of less than a year Case : A 69-year-old woman with a diagnosis of pT1N0M0 invasive ductal carcinoma with choriocarcinomatous differentiation received six cycles of adjuvant chemotherapy and is still disease free on the 23rd month after diagnosis, showing a better prognosis than most other cases reported in the literature. Conclusion : The reason for the poor prognosis for this type of breast carcinoma remains unclear. Standard chemotherapeutic agents administered for breast carcinoma may be used for choriocarcinomatous differentiation.