Uterine Serous Cancer Research Articles

Afatinib, an irreversible ErbB family blocker, demonstrates remarkable activity against HER2 amplified uterine serous endometrial cancer in vitro and in vivo

Afatinib, an irreversible ErbB family blocker, demonstrates remarkable activity against HER2 amplified uterine serous endometrial cancer in vitro and in vivo

Trends in treatment of uterine serous cancer in the medicare population

Objectives: Only a small number of cases of uterine serous carcinoma (USC) have been reported in randomized control trials. The objective of this investigation is to evaluate the rates of chemotherapy and radiotherapy in the primary treatment of USC in the US Medicare population and its effect on survival.

Uterin Papiller Seröz Kanserde Prognostik Faktörler: Ankara Onkoloji Hastanesi Deneyimi

Amaç: Bu çalışmanın amacı, cerrahi olarak evrelendirilmiş uterin papiller seröz kanserli (UPSK) hastalarda toplam sağkalıma etki eden faktörlerin araştırılmasıdır. Gereç ve Yöntemler: 1996-2008 yılları arasında Ankara Onkoloji Eğitim ve Araştırma Hastanesi Jinekoloji Kliniğinde endometriyum kanseri tanısı almış ve primer cerrahi olarak tedavi edilmiş olan 282 hasta değerlendirilerek, bu hastalardan UPSK olan 11'i çalışmaya alındı. Hastalar 2009 FIGO evreleme sistemine göre yeniden evrelendirildi. Ameliyat öncesi radyoterapi veya kemoterapi uygulanan hastalar çalışmaya dâhil edilmedi. Olgular sağkalım üzerinde etkili olması muhtemel yaş, tümör çapı, miyometriyal invazyon durumu, peritoneal sitolojide malignite varlığı, servikal tutulum ve lenf nodu metastazı açısından araştırıldı. Sağkalım analizi için Kaplan-Meier yöntemi kullanıldı. Değerlendirilen her bir parametrenin tek değişkenli analizde anlamlı olup olmadığı log rank testi ile çalışıldı. Anlamlı bulunan parametreler çok değişkenli Cox regresyon ile değerlendirildi. Bulgular: Endometriyum kanseri olan 282 hastadan 11 (%3,9) UPSK'li hasta değerlendirildi. Bu 11 hastada toplam sağkalım %63,6 olarak izlendi. Tam cerrahi evreleme yapılan olgularda toplam sağkalım %85,7 iken, bu oran tam evrelenmemiş olgularda %25 olarak bulundu. Tümör çapı 2 cm'nin altında ve üstünde olan olgularda toplam sağkalım sırasıyla %100 ve %33,3 olarak bulundu. Malign peritoneal sitoloji negatif ve pozitif olan olgularda toplam sağkalım sırasıyla %100 ve %20 olarak bulundu. Sonuç: Tümör boyutu, malign peritoneal sitoloji ve cerrahi evreleme, UPSK'li hastalarda toplam sağkalım açısından istatistiksel olarak anlamlı belirleyiciler olarak bulundu. Objective: The aim of this study was to investigate the factors affecting overall survival in surgically staged uterine papillary serous carcinoma (UPSC) patients. Material and Methods: 282 patients with endometrial cancer were treated between 1996 and 2008, among them 11 patients were diagnosed as UPSC. Patients were restaged according to 2009 FIGO staging system. Preoperative radiotherapy or chemotherapy applied patients were not included into the study. Age, tumor size, myometrial invasion, presence of malignant peritoneal cytology, cervical involvement and lymph node metastasis were investigated in terms of whether to have an effect on survival. Kaplan-Meier method was used for survival analysis. Univariate analysis was used to evaluate the each parameter and log rank test was used for significance. The significant parameters were analyzed by multivariate Cox regression. Results: 11 (3.9%) UPSC's patients were evaluated among 282 endometrial cancer patients. In these 11 patients overall survival was observed as 63.6%. Overall survival was 85.7% in complete surgical staged patients, but 25% in suboptimal staged patients. In patients with tumor diameter less than 2 cm and ≥2 cm overall survival rates were 100% and 33.3%, respectively. In patients with malignant peritoneal cytology was negative and positive, overall survival rates were, 100% and 20%, respectively. Conclusion: Tumor size, malignant peritoneal cytology and surgical staging, were found to be statistically significant predictors for overall survival in UPSC patients.

The Importance of Surgical Staging in Women With Uterine Serous Carcinoma: Experience in a Single Institution Reveals a Survival Benefit

ObjectiveTo assess the appropriate extent of surgical staging in women with clinically early stage uterine serous carcinoma (USC). MethodsWe conducted a single-institution retrospective cohort study of all women with USC between 2007 and 2012. Treatment practices, outcomes, and factors affecting survival were analyzed using univariate and multivariate analysis. ResultsEighty-four patients were identified, 76 of whom were included in the analysis. Preoperative pathology correctly identified USC in 73.3% of cases. Surgical stage distribution was 44.7% stage I, 7.9% stage II, 31.6% stage III, and 15.8% stage IV. Women thought to have early stage disease preoperatively encompassed 84.2% (64) of the cohort. Fifty-two (81.3%) of these women with clinically early stage disease had complete surgical staging. Thirty-four (53.1%) were determined to have surgical stage I, and the remaining 30 (46.9%) had occult advanced stage disease. Median follow-up was 43.2 months. Univariate analysis found a significant increase in progression-free survival and overall survival for women with clinically early stage disease with positive lymphovascular space invasion (P < 0.001 and P = 0.002, respectively), positive peritoneal cytology (P = 0.022 and P = 0.04, respectively), early stage (P < 0.001 and P = 0.004, respectively), and elevated serum CA125 at diagnosis (P = 0.003 and P = 0.001, respectively). On multivariate analysis, early stage (hazard ratio [HR] 9.87; 95% CI 2.79 to 34.92, P < 0.001) and complete surgical staging (HR 2.96; 95% CI 1.05 to 8.37, P = 0.040) were associated with prolonged progression-free survival, while overall survival was not affected by complete surgical staging (HR 1.92; 95% CI 0.64 to 5.76, P = 0.79). ConclusionComplete surgical staging prolongs the progression-free survival of women with clinical early-stage uterine serous cancer. Although this does not extend to overall survival, this enables patients to have an improved quality of life with a longer interval without the burden of disease.

Afatinib demonstrates remarkable activity against HER2-amplified uterine serous endometrial cancer in vitro and in vivo.

Background:Uterine serous carcinomas (USCs) are an aggressive form of uterine cancer that may rely on HER2/neu amplification as a driver of proliferation. The objective of this paper is to assess the sensitivity of USC cell lines with and without HER2/neu gene amplification to afatinib, an irreversible ErbB tyrosine kinase inhibitor, and to test the efficacy of afatinib in the treatment of HER2-amplified USC xenografts.Methods:Eight of fifteen primary USC cell lines (four with HER2 amplification and four without) demonstrating similar in vitro growth rates were treated with scalar concentrations of afatinib. Effects on cell growth, signalling and cell cycle distribution were determined by flow cytometry assays. Mice harbouring xenografts of HER2/neu-amplified USC were treated with afatinib by gavage to determine the effect on tumour growth and overall survival.Results:Primary chemotherapy-resistant USC cell lines harbouring HER2/neu gene amplification were exquisitely sensitive to afatinib exposure (mean±s.e.m. IC50=0.0056±0.0006 μM) and significantly more sensitive than HER2/neu-non-amplified USC cell lines (mean±s.e.m. IC50=0.563±0.092 μM, P<0.0001). Afatinib exposure resulted in abrogation of cell survival, inhibition of HER2/neu autophosphorylation and S6 transcription factor phosphorylation in HER2/neu overexpressing USC and inhibited the growth of HER2-amplified tumour xenografts improving overall survival (P=0.0017).Conclusions:Afatinib may be highly effective against HER2/neu-amplified chemotherapy-resistant USC. The investigation of afatinib in patients harbouring HER2/neu-amplified USC is warranted.

Impact of management on the prognosis of pure uterine papillary serous cancer — A Taiwanese Gynecologic Oncology Group (TGOG) study

ObjectiveTo investigate the clinical and pathological characteristics and the management of uterine papillary serous carcinoma (UPSC) in relation to patients' outcomes. MethodsClinicopathological data and the management of patients treated between 1991 and 2010 at 11 member hospitals of the Taiwanese Gynecologic Oncology Group (TGOG) were retrospectively reviewed. The Kaplan–Meier method was used to generate survival curves, and factors predictive of outcome were compared using the log-rank test and Cox regression analysis. ResultsA total of 119 pure UPSC patients were recruited. Stages I, II, III, and IV were identified in 34.5%, 2.5%, 36.1%, and 26.9% of the patients, respectively. The recurrence rate was 20.5% in FIGO stage I/II disease and 55.2% in FIGO stage III/IV disease. The 5-year overall survival rates for the patients with stage I, II, III, and IV disease were 92.0%, 66.7%, 34.2%, and 17.3%, respectively. Multivariate analysis showed that tumor stage (stage III/IV hazard ratio [HR] 8.65, 95% confidence interval [CI] 3.00–24.9) and optimal cytoreduction (HR 0.40, 95% CI 0.22–0.73) independently influenced the overall survival rate of UPSC patients. In addition, optimal cytoreduction (HR 0.36, 95% CI 0.17–0.78) and the combination of chemotherapy and radiation (HR 0.11, 95% CI 0.04–0.37) improved the overall survival of the advanced stage (FIGO stage III/IV) UPSC patients. ConclusionsUPSC represents an aggressive subtype of endometrial cancer commonly accompanied by extra-uterine disease. Comprehensive surgical staging with cytoreductive surgery is mandatory and beneficial for UPSC patients. Systemic chemotherapy combined with radiation should be considered as an adjuvant therapy for advanced stage UPSC patients.

Serous endometrial intraepithelial carcinoma: a case series and literature review

BackgroundMinimal uterine serous cancer (MUSC) or serous endometrial intraepithelial carcinoma (EIC) has been described by many different names since 1998. There have been very few cases reported in literature since EIC/MUSC was recognized as a separate entity. The World health Organization (WHO) Classification favors the term serous EIC. Although serous EIC is confined to the uterine endometrium at initial histology diagnosis, a significant number of patients could have distal metastasis at diagnosis, without symptoms. Serous EIC is considered as being the precursor of uterine serous cancer (USC), but pure serous EIC also has an aggressive behavior similar to USC. It is therefore prudent to have an accurate diagnosis and appropriate surgical staging. There are very few published articles in literature that discuss the pure form of serous EIC. The aim of this series is to share our experience and review evidence for optimum management of serous EIC.Patients and methodsWe report a series of five women treated in our institute in the last 3 years. We reviewed the relevant literature on serous EIC and various management strategies, to recommend best clinical practice.ConclusionPure serous EIC is a difficult histopathological diagnosis, which requires ancillary immunohistochemical staining. It can have an aggressive clinical behavior with early recurrence and poor survival. Optimum surgical staging, with appropriate adjuvant treatment, should be discussed when treating these patients.

Recurrence rates in patients with uterine papillary serous cancer with and without breast cancer.

e16529 Background: Women with uterine papillary serous carcinoma (UPSC) are at increased risk for breast cancer and the converse is true. A genetic association between breast cancer and UPSC was recently described and counseling women faced with more than one cancer diagnosis can be difficult. Our objective was to evaluate recurrence rates of women with UPSC to those with UPSC and a personal history of breast cancer (UPSCBR). Methods: Data was collected for UPSCBR patients at two academic institutions between 7/1990 and 7/2012. Patient demographics, pathology, disease stage, and treatments were recorded. A UPSC literature review was performed focusing on recurrences per number of at-risk patients by stage. We used the fixed effect Mantel-Haenszel method to estimate the common pooled effect (recurrence rate) for the UPSC studies and compared these to UPSCBR patients. Results: Forty-three UPSCBR patients were identified. Median age at diagnosis was 72 (49-93). Twenty-six patients were Caucasian, 14 African-American and 3 other. Twenty-four (56%) had early stage at diagnosis (IA-IC) and 19 (44%) had late stage (III-IV). All but one underwent surgical staging/debulking; 36 (90%) were optimally debulked. Twelve (50%) early stage and 17 (89.5%) late stage patients underwent adjuvant therapy with radiation and/or chemotherapy. Nine studies were identified with available recurrence data for early stage UPSC; 8 for late stage. The recurrence rate for stage IA UPSCBR patients was 2/11 (18%) [95% CI: 2 to 52%] compared to 11% [95% CI: 9.8 to 13%] in the UPSC literature. In IB/IC UPSCBR patients we had 3/13 (23%) [95% CI: 5 to 54%] recur versus 21% [95% CI: 19 to 23%]. In later stages III/IV, 7/19 (37%) [95% CI:16 to 62%] UPSCBR patients had recurrences compared to 58% [95% CI: 56 to 60%] of UPSC patients. Conclusions: There is an association between breast cancer and UPSC with regard to incidence. We failed to find evidence of an appreciable difference in recurrence rates between our UPSCBR patients and UPSC patient groups from other reported studies. While diagnosis with two primary malignancies can be challenging for patients, this does not appear to impact their risk of recurrence.

The Clinical Relevance of Rising CA-125 Levels Within the Normal Range in Patients With Uterine Papillary Serous Cancer

The utility of cancer antigen 125 (CA-125) levels as an adjunct method of monitoring patients with uterine papillary serous carcinoma (UPSC) or endometrial serous carcinoma after surgery and adjuvant treatment has been reported. Our goal was to determine the significance of rising CA-125 levels within the normal range in these patients in the posttreatment surveillance setting. All patients with UPSC who underwent surgical staging and had preoperative CA-125 measurement from 1999 to 2008 were included in this analysis. Information was extracted from records to assess the changes in CA-125 values with clinical and/or radiographic detection of recurrence. Of the 56 evaluable patients, 23 (41%) recurred. Of the 23 patients that recurred, 11 had serial CA-125 levels measured in remission. Elevated CA-125 levels at diagnosis were significantly associated with disease recurrence and advanced stage (P = .01, P = .001, respectively). The rise in CA-125 by 10 U/mL in the normal range and ≥ 15 U/mL were associated with disease recurrence (P < .001, P < .001, respectively). In multivariate analysis, only CA-125 level ≥ 15 U/mL was significantly associated with worse progression-free survival. In this small cohort of patients with recurrent UPSC after remission, surveillance of CA-125 levels may have a role in disease surveillance and management.

Vaginal brachytherapy for early stage uterine papillary serous and clear cell endometrial cancer

ObjectiveTo report clinical outcomes following adjuvant high-dose-rate (HDR) vaginal brachytherapy (VB) for early-stage uterine papillary serous (UPSC) and clear cell (CC) endometrial cancer. MethodsA retrospective study of Stage I and II papillary serous and clear cell endometrial cancer treated with post-operative HDR VB between October 2005 and May 2012 was performed. A total of 37 patients were identified, 26 with UPSC, 9 with CC and 2 with mixed UPSC/CC. After total hysterectomy and bilateral salpingo-oophorectomy, VB was administered without external-beam radiation with a dose of 24Gy in 6 fractions prescribed to the vaginal surface. Chemotherapy was given to 30 patients (75%). ResultsThe median follow up time was 24.8months (range, 2.0 to 71.5months). Four patients relapsed, 2 with UPSC and 2 with CC. The initial site of relapse was concurrent vagina, pelvic/para-aortic nodes and abdominal wall (1), pelvic/para-aortic nodes (1) and para-aortic nodes alone (2). The 2-year vaginal-control rate was 96.8%. The pelvic-control rate including vaginal and nodal relapse was 93.5%. The 2-year disease-free and overall survival rates were 89.3% and 100%, respectively. ConclusionHDR VB as the sole adjuvant treatment modality for early-stage UPSC/CC is associated with a low rate of vaginal relapse and excellent survival outcomes. This novel low-dose regimen for VB is safe and effective.

Prognostic impact of lymphadenectomy in uterine serous cancer

To estimate the survival impact of lymphadenectomy in women diagnosed with uterine serous cancer. Women with a diagnosis of uterine serous cancer were identified from the Surveillance, Epidemiology and End Results Program (SEER) from 1988 to 2007. Only surgically treated women were included. The Surveillance, Epidemiology and End Results Program database provided data from 17 registries. The study population comprised 4178 women. Statistical analyses using Student's t-test, Kaplan-Meier survival methods and Cox proportional hazards regression were performed. Overall survival. Three thousand, one hundred and ninety-four (67.7%) women underwent lymphadenectomy. Older women (≥65 years) and Caucasian women (relative to Asian) were less likely to have lymphadenectomy (P < 0.001). The prevalence of nodal metastasis in women having lymphadenectomy was 32%. Of the 1997 women who had disease grossly confined to the uterus and underwent lymphadenectomy, 387 (19%) were found to have nodal metastasis. Lymphadenectomy was associated with improved survival; women who underwent lymphadenectomy were 41% (hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.54-0.64; P < 0.001) less likely to die than women who did not have the procedure. Moreover, more extensive lymphadenectomy correlated positively with survival. Compared with women with 1-10 nodes removed, those with more extensive lymphadenectomy (>10 nodes removed) were 26% (HR, 0.74; 95% CI, 0.67-0.83; P < 0.001) less likely to die. The impact of the extent of lymphadenectomy on survival was significant in both node-negative and node-positive women. Age and race influenced the prevalence of lymphadenectomy in our cohort. This study suggests that the extent of lymphadenectomy is associated with significant improvement in survival of women with uterine serous cancer.

Demographics of uterine serous cancer (USC) patients: A single institutional experience.

e15581 Background: The common uterine cancer (UC) occurs in obese, diabetic (DM), hypertensive (HTN), postmenopausal women and are estrogen dependent. Small institutional series suggest USC occurs in older, thin women and is not associated with estrogen dependency. The objective of this study is to report demographic features of USC patients (pts) in a large single-institution experience and compared them with SEER data for UC (National Cancer Institute, SEER 2004-2008, uterine cancer. http://seer.cancer.gov/statistics/ ). Methods: Institutional records were reviewed from 1987 to 2009. Pts age, menopause status, race, disease stage, histology, past medical history (PMH) and additional demographics were collected. Results: 334 USC (pts) were identified. Their average age at diagnosis was 69.1 years (range 37-92). 282 (88.1%) were Caucasian and 32 (10%) were African Americans. The FIGO stage was IA 121 (36.2%), IB 36 (10.8%), II 27 (8.1%), IIIA 39 (11.7%), IIIB 2 (0.6%), IIIC1 32 (9.6%), IIIC2 9 (2.7%), IVA 28 (8.4%) and IVB 40 (12%). PMH revealed 177 of 221 (80%) had HTN and 69 of 221 (32%) had DM. 132 of 292 (45.3%) were obese; 95 (32.5%) had BMI between 30-39,31 (10.6%) had BMI between 40-49 and 6 (2.1%) had BMI &gt;50. 89 of 315 (28.2%) smoked cigarettes, 48 of 250 (19.2%) used oral contraceptives for an average of 4 years (range 1-15) and 42/299 (14%) used HRT for an average of 4 years (range 1-20). 35 (17.3%) had a prior history of breast cancer, 5 (2.5%) colon cancer and 13 (6.4%) had other forms of cancer. Compared to published SEER data1 for all UC, more USC pts were diagnosed with advanced stage disease (II-IVB) 53% vs. 28%. USC patients were older at diagnosis (mean age of 69 vs. 61 years). Conclusions: Like UC, USC often presents in obese (45.3%), hypertensive (80%) diabetic (33%) women who have a prior history of breast cancer (17%). However, USC typically is found in older pts and at a more advanced stage.

Prognostic factors and treatment-related outcomes in patients with uterine serous cancer (USC).

5099 Background: USC an uncommon (10%) but aggressive form of uterine cancer, causes 50% of uterine cancer deaths. The purpose of this study is to report a large single-institution experience with USC investigating the effects of clinicopathological parameters and treatment on overall (OS) and disease-free survival (DFS). Methods: Records from our institution were reviewed from 1987-2009. All 334 USC patients (pts) identified were surgically staged. Postoperative treatments used were: (1) observation (OBS, n=33); (2) platinum-based chemotherapy (PCH, n=78); (3) whole pelvis radiation therapy (WPRT, n=16); (4) PCH and vaginal apex brachytherapy (PCHR, n=165); (5) vaginal apex brachytherapy (VAB, n=35). The cancer stages were 121 pts IA (36.2%), 36 IB (10.8%), 27 II (8.1%), 39 IIIA (11.7%), 2 IIIB (0.6%), 32 IIIC1 (9.6%), 9 IIIC2 (2.7%), 28 IVA (8.4%) and 40 IVB (12%). Results: The 5-year OS for stage IA/IB, II, IIIA/IIIB, IIIC1/IIIC2, IVA/IVB were 82%, 70%, 64%, 36%, and 9%, respectively. The 5-year DFS for stage IA/IB, II, IIIA/IIIB, IIIC1/IIIC2, IVA/IVB were 82%, 68%, 56%, 24%, 6%, respectively. Advanced stage was associated with significantly shorter OS and DFS (p &lt;0.01). The 5-year OS for stage IA/IB disease was 94% for pts who received PCHR, 90% for OBS, 75% for PCH, 65% for VAB and 0% for WPRT. The 5-year DFS for PCHR, OBS, PCH, VAB and WPRT for Stage IA/IB were 89%, 82%, 86%, 72% and 0% respectively. For stage II-IVB pts, the 5-year OS was 51% for PCHR, 0% for OBS, 23% for PCH and 20% for WPRT. The 5-year DFS for stage II-IVB with PCHR, OBS, PCH and WPRT were 42%, 0%, 17% and 13% respectively. Older age pts had worse survival, (p&lt;0.01). Race and BMI did not impact survival. Incomplete surgical debulking (p&lt;0.01), depth of myometrial invasion &gt;50% (p&lt;0.01) and lymph node metastasis (p&lt;0.01) were all associated with worse prognosis. Conclusions: PCHR overall exhibited better OS and DFS regardless of disease stage. Age, incomplete surgical debulking, depth of myometrial invasion and lymph node involvement were independent prognostic factors in USC patients in this study.

A proteomic analysis of surgical cytoreduction in patients with advanced ovarian cancer.

e15560 Background: Optimal surgical cytoreduction (&lt;1 cm residual tumor) has been shown to improve overall survival compared to suboptimal (&gt;1cm) debulking as primary treatment for advanced stage epithelial ovarian cancer (EOC). Molecular descriptions of optimally and suboptimally debulked ovarian tumors are lacking. We have performed a global, quantitative proteomic analysis of optimally and suboptimally debulked EOC tumor samples. Methods: A cohort of 16 optimally (8) and suboptimally (8) debulked patients with archival formalin-fixed, paraffin-embedded tumor specimens was identified. Homogenous tumor cell populations were collected and protein digests were prepared and analyzed by high resolution mass spectrometry for identification and quantification by spectral counting. Immunohistochemistry (IHC) was performed and slides were scored using a semi-quantitative method (H-score). Results: An average of 1,110 proteins were identified within each cohort, of which 21 possessed significant (p&lt;0.05) differential abundances. Specifically, three proteins (annexin A1, S100-A11, and synuclein-gamma, or SNCG) which have significant roles in cell migration and cancer biology were identified. Although no H-score was statistically significant, comparison of positively-staining cells for SNCG showed a trend toward increased expression in suboptimally debulked patients, p=0.08. Conclusions: Overexpression of SNCG has been shown to be predictive of worse prognosis in papillary serous uterine cancer cell lines, and increased expression of SNCG in breast cancer correlates with advanced stage and aggressiveness of disease. Our data suggest SNCG may have similar predictive value in EOC, as tumors with elevated levels of this protein may be less amenable to optimal cytoreduction.

The risk for omental metastases and the impact on overall survival in patients with uterine papillary serous and clear cell endometrial cancer

The risk for omental metastases and the impact on overall survival in patients with uterine papillary serous and clear cell endometrial cancer

Uterine Serous Carcinoma: Increased Familial Risk for Lynch-Associated Malignancies

Serous uterine cancer is not a feature of any known hereditary cancer syndrome. This study evaluated familial risk of cancers for patients with serous uterine carcinoma, focusing on Lynch syndrome malignancies. Fifty serous or mixed serous endometrial carcinoma cases were prospectively enrolled. Pedigrees were developed for 29 probands and tumors were assessed for DNA mismatch repair (MMR) abnormalities. Standardized incidence ratios for cancers in relatives were estimated. A second-stage analysis was undertaken using data from Gynecologic Oncology Group (GOG)-210. Incidence data for cancers reported in relatives of 348 patients with serous and mixed epithelial and 624 patients with endometrioid carcinoma were compared. Nineteen of 29 (65.5%) patients in the single-institution series reported a Lynch-related cancer in relatives. Endometrial and ovarian cancers were significantly overrepresented and a high number of probands (6 of 29, 20.7%) reported pancreatic cancers. None of the probands' tumors had DNA MMR abnormalities. There was no difference in endometrial or ovarian cancer incidence in relatives of serous and endometrioid cancer probands in the case-control study. Pancreatic cancers were, however, significantly more common in relatives of patients with serous cancer [OR, 2.39; 95% confidence interval (CI), 1.06-5.38]. We identified an excess of endometrial, ovarian, and pancreatic cancers in relatives of patients with serous cancer in a single-institution study. Follow-up studies suggest that only pancreatic cancers are overrepresented in relatives. DNA MMR defects in familial clustering of pancreatic and other Lynch-associated malignancies are unlikely. The excess of pancreatic cancers in relatives may reflect an as yet unidentified hereditary syndrome that includes uterine serous cancers.

Development of targeted therapy in uterine serous carcinoma, a biologically aggressive variant of endometrial cancer

Endometrial cancer (EC) is the most common female genital malignancy in the USA. Most carcinomas arising from the uterus are estrogen dependent and are associated with obesity and hypertension. They are designated type I ECs and typically, due to their early diagnosis secondary to postmenopausal bleeding, have a good prognosis. By contrast, type II ECs develop in older patients, are not hormone dependent and are responsible for most recurrences and deaths from EC. Uterine serous cancer constitutes up to 10% of all endometrial tumors, and represents the most biologically aggressive variant of type II EC. This article will describe the most salient molecular markers that have been identified in uterine serous cancer, thus far with emphasis on the use of erbB2 (HER2/neu) as the first of a series of therapeutic markers for the treatment of this highly-aggressive subset of ECs.

Evaluation of adjuvant therapy in women with uterine papillary serous cancer

BACKGROUND AND OBJECTIVEUterine papillary serous cancer (UPSC) represents only 10% of all uterine cancers and is associated with a significantly worse prognosis compared with other histological types of endometrial cancers. It closely resembles the behavior of ovarian carcinoma.DESIGN AND SETTINGRetrospective study in a referral center covering period from February 1989 to January 2009.PATIENTS AND METHODSEighteen patients who underwent definitive surgery followed by adjuvant therapy—platinum-based chemotherapy, radiotherapy, or both—were reviewed. Median age was 62 years (range, 52–76 years). All patients underwent total abdominal hysterectomy and salpingo-oophorectomy. Positive lymph nodes were found in 4 of 7 patients who underwent lymph node sampling/dissection. Seven patients had stage I/II disease, whereas 11 patients had stage III disease. Six patients received chemotherapy, 5 patients received radiation therapy, while 7 patients received both chemotherapy and radiation therapy.RESULTMedian follow-up was 27 months. The median survival and relapse-free survival were 33 and 23 months, respectively. Eight patients were alive and free of disease, of whom 5 patients were stage I/II and 4 patients were stage III. Distant metastasis was the most common site of relapse. Early stage (I/II) was associated with significant improvement in relapse-free survival (RFS) and overall survival (OS) (P=.004 and P=.05, respectively). The combined-modality treatment including chemotherapy-radiotherapy showed statistically significant improvement in RFS (P=.012), while the improvement in OS did not reach statistical significance (P=.12).CONCLUSIONThis study indicates that postoperative combined treatment with chemotherapy and radiation therapy plays a role in the management of UPSC by improving RFS. Distant metastasis remains the major site of relapse. Future studies using combined-modality therapy are needed to improve the outcome in patients with UPSC.

Role of Adjuvant Chemotherapy in Patients With Early Stage Uterine Papillary Serous Cancer

Uterine papillary serous carcinoma (UPSC) is an aggressive subtype of endometrial cancer. We studied survival outcomes in patients with stages I/II UPSC. A retrospective, multi-institutional study of patients with stages I/II UPSC was conducted. Patients underwent surgical staging followed by observation, adjuvant platinum-based chemotherapy (CT), or radiation therapy (RT). Continuous variables were compared via Wilcoxon rank sum test; Fisher exact test was used for the unordered categorical variables. Kaplan-Meier curves were used to estimate survival. Thirty-nine women were diagnosed with stage I (n = 30) or II (n = 9) UPSC, with a median follow-up of 52 months. Of the 26 patients who did not receive adjuvant CT, 9 developed recurrences and 8 died of their disease. Of the 10 patients with no myometrial invasion who did not receive adjuvant CT, 3 developed recurrences and died. Of the 7 patients who underwent RT, 2 developed distant recurrences and died. Of the 13 patients who underwent CT, 1 developed vaginal recurrence. The 5-year overall (OS) and progression-free survival (PFS) rates for the adjuvant CT group were 100% and 92%, respectively, compared with 69% and 65% for those who did not receive CT (P = 0.002 OS, P = 0.002 PFS). The 5-year OS and PFS rates for RT group were both 71%. Patients with stages I/II UPSC are at significant risk for distant recurrence and poor survival. Platinum-based adjuvant CT may decrease recurrence rate and improve survival in women with early and well-staged UPSC.

The importance of chemotherapy and radiation in uterine papillary serous carcinoma

Purpose To identify prognostic and predictive factors of overall survival (OS), relapse-free survival (RFS) and toxicity for patients with uterine papillary serous carcinoma (UPSC). Materials and methods Patient, tumor, treatment and relapse characteristics of 135 women with Stages I–IVA UPSC treated between 1980 and 2006 at Dana–Farber/Brigham and Women's Cancer Center (DF/BWCC) were analyzed using Cox regression models to determine prognostic and predictive factors for OS, RFS and toxicity. Results Mean follow-up was 5.5 years (range, 0.01–25.2). Median 5-year OS was 52%, and RFS was 42% for all patients. On Cox regression analysis, increasing age, stage, and myometrial invasion were prognostic factors associated with shorter OS and RFS. A paclitaxel–platinum chemotherapy regimen was significantly associated with longer OS (hazard ratio [HR] = 0.34, 95% confidence interval [CI] 0.15–0.74, p = 0.007) and RFS (HR = 0.45, 95% CI 0.22–0.92, p = 0.03). RFS was improved for patients treated with RT (HR = 0.44, 95% CI 0.25–0.77, p = 0.004). The 5-year grade 3+ toxicity rate was 3.5% for those who received RT and was 2.9% for those who did not (p = NS). Conclusion Uterine papillary serous cancer can be an aggressive tumor type with a poor prognosis. RFS was improved by radiation and chemotherapy with few grade 3 or higher complications. Using radiation and paclitaxel–platinum chemotherapy should be attempted whenever feasible for patients with UPSC who do not have distant metastases at diagnosis.