BRAF Mutation is associated with early stage disease and improved outcome in patients with low‐grade serous ovarian cancer

BACKGROUND:

Low‐grade serous (LGS) ovarian cancer is a chemoresistant disease that accounts for 10% of serous ovarian cancers. Prior studies have reported that 28% to 35% of serous borderline (SB)/LGS ovarian tumors harbor a BRAF mutation, suggesting that BRAF inhibitors may be a rational therapeutic approach for this disease. In the current study, the authors sought to determine whether BRAF or KRAS mutation status was associated with disease stage and/or histology in patients with SB and LGS ovarian cancer.

METHODS:

Genetic profiles were constructed for 75 SB and LGS ovarian tumors to determine BRAF and KRAS mutation status. The incidence and identity of BRAF and KRAS mutations were defined, and the results were correlated with disease stage, response to treatment, and overall survival.

RESULTS:

Of 75 samples examined, 56 tumors (75%) had SB histology, and 19 tumors (25%) had LGS histology. Fifty‐seven percent of tumors harbored either a KRAS mutation (n = 17) or a BRAF mutation (a valine‐to‐glutamate substitution at residue 600 [V600E]; n = 26). The BRAF V600E mutation was associated significantly with early disease stage (stage I/II; P < .001) and SB histology (P = .002). KRAS mutations were not associated significantly with disease stage or histology. Of the 22 patients (29%) who required chemotherapy, 20 had tumors with wild‐type KRAS/BRAF, 2 had KRAS mutant tumors, and none had tumors that harbored a BRAF mutation. All patients with BRAF tumors remained alive at a median follow‐up of 3.6 years (range, 1.9–129.3 months).

CONCLUSIONS:

V600E BRAF mutations were present in 35% of patients who had SB/LGS ovarian cancers. The presence of the BRAF V600E mutation in SB/LGS ovarian cancer was associated with early stage disease and improved prognosis. The authors concluded that patients with SB/LGS ovarian cancer who require systemic therapy are unlikely to have BRAF mutant tumors. Cancer 2013. © 2012 American Cancer Society.     

Fertility preservation in young women with epithelial ovarian cancer

BACKGROUND:

Surgical management of ovarian cancer consists of hysterectomy with bilateral oophorectomy. In young women, this results in the loss of reproductive function and estrogen deprivation. In the current study, the authors examined the safety of fertility‐conserving surgery in premenopausal women with epithelial ovarian cancers.

METHODS:

Women aged ≤50 years with stage IA or IC epithelial ovarian cancer who were registered in the Surveillance, Epidemiology, and End Results database were examined. Patients who underwent bilateral oophorectomy were compared with those who underwent ovarian conservation. A second analysis examined uterine conservation versus hysterectomy. Multivariate Poisson regression models were developed to describe predictors of fertility preservation. Survival was examined using Cox proportional hazards models and the Kaplan‐Meier method.

RESULTS:

In total, 1186 women, including 754 women (64%) who underwent bilateral oophorectomy and 432 women (36%) who underwent ovarian preservation, were identified. Younger age, later year of diagnosis, and residence in the eastern or western United States were associated with ovarian preservation (P < .05 for all). Women with endometrioid and clear cell histologies and stage IC disease were less likely to have ovarian conservation (P < .05). In a Cox model, ovarian preservation had no effect on survival (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.39‐1.20). Young age, later year of diagnosis, residence in the eastern or western United States, single women, mucinous tumors, and patients with stage IA disease were more likely to have uterine preservation (P < .05 for all). In a multivariate model, uterine preservation had no effect on survival (HR, 0.87; 95% CI, 0.62‐1.22).

CONCLUSIONS:

Ovarian and uterine‐conserving surgery were safe in young women who had stage IA and IC epithelial ovarian cancer. Cancer 2009. © 2009 American Cancer Society.     

Early stage (IA-IB) primary carcinoma of the fallopian tube: case-control comparison to adenocarcinoma of the ovary

Objective

Early stage primary carcinoma of the fallopian tube (PCFT) is an uncommon condition when strict criteria are applied. The aim of this study was to compare the outcome stage IA-IB PCFT to a matched group of ovarian cancer (OC).

Methods

Between 1990 and 2008, 32 patients with stage IA-IB of PCFT were recorded in the database of three French Institutions. A control group of patients with OC was constituted.

Results

Eleven eligible PCFT cases and 29 OC controls fulfilled the stringent inclusion criteria. Median follow-up was 70.2 months. Five-year overall survival was 83.3% (95% confidence interval [CI], 27.3 to 97.5) for PCFT and 88.0% (95% CI, 66.9 to 96.0) for OC (p=0.93). In the subgroup of patients with grade 2-3, the outcome was similar in PCFT compared to OC patients (p=0.75). Five-year relapse-free survival was respectively 62.5% (95% CI, 22.9 to 86.1) and 85.0% (95% CI, 64.6 to 94.2) in the PCFT and OC groups (p=0.07). In the subgroup of patients (grade 2-3), there was no difference between PCFT and OC (p=0.65).

Conclusion

The findings did not reveal any difference in prognosis between early stage of PCFT and OC when grade is taken into account. Management of PCFT should mirror that of ovarian carcinoma.     

Effects of individual-level socioeconomic factors on racial disparities in cancer treatment and survival: findings from the National Longitudinal Mortality Study, 1979-2003

BACKGROUND:

This is the first study to use the linked National Longitudinal Mortality Study and Surveillance, Epidemiology, and End Results (SEER) data to determine the effects of individual‐level socioeconomic factors (health insurance, education, income, and poverty status) on racial disparities in receiving treatment and in survival.

METHODS:

This study included 13,234 cases diagnosed with the 8 most common types of cancer (female breast, colorectal, prostate, lung and bronchus, uterine cervix, ovarian, melanoma, and urinary bladder) at age ≥25 years, identified from the National Longitudinal Mortality Study‐SEER data during 1973 to 2003. Kaplan‐Meier methods and Cox regression models were used for survival analysis.

RESULTS:

Three‐year all‐cause observed survival for cases diagnosed with local‐stage cancers of the 8 leading tumors combined was ≥82% regardless of race/ethnicity. More favorable survival was associated with higher socioeconomic status. Compared with whites, blacks were less likely to receive first‐course cancer‐directed surgery, perhaps reflecting a less favorable stage distribution at diagnosis. Hazard ratio (HR) for cancer‐specific mortality was significantly higher among blacks compared with whites (HR, 1.2; 95% confidence interval [CI], 1.1‐1.3) after adjusting for age, sex, and tumor stage, but not after further controlling for socioeconomic factors and treatment (HR, 1.0; 95% CI, 0.9‐1.1). HRs for all‐cause mortality among patients with breast cancer and for cancer‐specific mortality in patients with prostate cancer were significantly higher for blacks compared with whites after adjusting for socioeconomic factors, treatment, and patient and tumor characteristics.

CONCLUSIONS:

Favorable survival was associated with higher socioeconomic status. Racial disparities in survival persisted after adjusting for individual‐level socioeconomic factors and treatment for patients with breast and prostate cancer. Cancer 2011. © 2011 American Cancer Society.     

Survival outcome of women with synchronous cancers of endometrium and ovary: a 10 year retrospective cohort study

Objective

Synchronous occurrence of endometrial and ovarian tumors is uncommon, and they affect less than 10% of women with endometrial or ovarian cancers. The aim of this study is to describe the epidemiological and clinical factors; and survival outcomes of women with these cancers.

Methods

This is a retrospective cohort study in a large tertiary institution in Singapore. The sample consists of women with endometrial and epithelial ovarian cancers followed up over a period of 10 years from 2000 to 2009. The epidemiological and clinical factors include age at diagnosis, histology types, grade and stage of disease.

Results

A total of 75 patients with synchronous ovarian and endometrial cancers were identified. However, only 46 patients met the inclusion criteria. The median follow-up was 74 months. The incidence rate for synchronous cancer is 8.7% of all epithelial ovarian cancers and 4.9% of all endometrial cancers diagnosed over this time frame. Mean age at diagnosis was 47.3 years old. The most common presenting symptom was abnormal uterine bleeding (36.9%) and 73.9% had endometrioid histology for both endometrial and ovarian cancers. The majority of the women (78%) presented were at early stages of 1 and 2. There were 6 (13.6%) cases of recurrence and the 5 year cumulative survival rate was at 84%.

Conclusion

In our cohort, we found that majority of women afflicted with synchronous cancer of the endometrium and ovary were younger at age of diagnosis, had early stage of cancer and good survival.     

Improved survival for BRCA2-associated serous ovarian cancer compared with both BRCA-negative and BRCA1-associated serous ovarian cancer

BACKGROUND:

Multiple observational studies have suggested that breast cancer gene (BRCA)‐associated ovarian cancers have improved survival compared with BRCA‐negative ovarian cancers. However, most of those studies combined BRCA1 and BRCA2 patients or evaluated only BRCA1 patients. The objective of the current study was to examine whether BRCA1‐associated and BRCA2‐associated ovarian cancers were associated with different outcomes.

METHODS:

This was a single‐institution, retrospective analysis of patients who had a new diagnosis of histologically confirmed stage III or IV serous ovarian, fallopian tube, or primary peritoneal cancer between January 1, 1996 and February 1, 2011 and who underwent BRCA mutation testing on 1 of 2 institutional review board‐approved follow‐up studies. Patients who had been tested for BRCA mutations beyond 24 months of diagnosis were excluded from analysis to minimize selection bias from including patients who were referred for genetic testing because of long survival.

RESULTS:

Data from 190 patients (143 BRCA‐negative patients, 30 BRCA1‐positive patients, and 17 BRCA2‐positive patients) were analyzed. During the study period, 73 deaths were observed (60 BRCA‐negative patients, 10 BRCA1‐positive patients, 3 BRCA2‐positive patients). The median follow‐up for the remaining 117 survivors was 2.5 years. At 3 years, 69.4%, 90.7%, and 100% of BRCA‐negative patients, BRCA1‐positive patients, and BRCA2‐positive patients were alive, respectively. On univariate analysis, age, BRCA2 mutations, debulking status, and type of first‐line therapy (intravenous or intraperitoneal) were significant predictors of overall survival. On multivariate analysis, BRCA2 mutations (hazard ratio, 0.20; 95% confidence interval, 0.06‐0.65; P = .007), but not BRCA1 mutations (hazard ratio, 0.70; 95% confidence interval, 0.36‐1.38; P = .31), predicted for improved overall survival compared with BRCA‐negative patients. When carriers of BRCA2 mutations were directly compared with carriers of BRCA1 mutations, BRCA2 mutations appeared to confer improved overall survival (hazard ratio, 0.29; 95% confidence interval, 0.08‐1.05; P = .060), although this finding did not reach significance.

CONCLUSIONS:

The current data suggests that BRCA2 mutations confer an overall survival advantage compared with either being BRCA‐negative or having a BRCA1 mutation in high‐grade serous ovarian cancer. This finding may have important implications for clinical trial design. Cancer 2012. © 2011 American Cancer Society.     

MEKK3 expression correlates with nuclear factor κ B activity and with expression of antiapoptotic genes in serous ovarian carcinoma

BACKGROUND:

Constitutively activated nuclear factor κ B (NFκB) contributes to the development of cancer by regulating the expression of genes involved in cell survival, metastasis, and angiogenesis. The authors have demonstrated that MEKK3 plays a critical role in cytokine‐mediated NFκB activation, and that stable expression of MEKK3 in cultured cells leads to increased NFκB activity.

METHODS:

MEKK3 expression in ovarian cancer cells or tumors was assessed by Western blotting and real‐time polymerase chain reaction. NFκB activities were analyzed by electrophoretic mobility shift assay and luciferase reporter assays. Western blot analysis for the survival factors were also performed and correlated with MEKK3 and NFκB activities. Cell survival assays were used to determine the sensitivity of ovarian cancer cells to various chemotherapeutic agents.

RESULTS:

The authors found that 63% of the ovarian cancers had higher MEKK3 expression than the normal ovarian epithelial cells. Ovarian cancers with high MEKK3 showed correspondingly high IκB kinase and NFκB activity. Moreover, MEKK3 coimmunoprecipitated with Akt and cooperated with Akt to synergistically activate NFκB. Consistent with increased MEKK3 and NFκB activity in ovarian cancers, Bcl‐2, Bcl‐xL, survivin, and X‐linked inhibitor of apoptosis levels were increased, which correlated with increased resistance to chemotherapeutic agents. Knockdown of MEKK3 with small interfering RNA significantly increased cancer cell sensitivity to paclitaxel.

CONCLUSIONS:

MEKK3 may be aberrantly expressed in ovarian cancers and plays an important role in tumors with constitutively activated NFκB. Cancer 2009; 115:3897–3908. © 2009 American Cancer Society.     

Improvements to the FIGO staging for ovarian cancer: reconsideration of lymphatic spread and intraoperative tumor rupture

Objective

To evaluate the improvement in prognosis prediction with reassignment of International Federation of Gynecology and Obstetrics (FIGO) stages for ovarian carcinoma.

Methods

This was a retrospective study of patients with epithelial ovarian, fallopian tube, and primary peritoneal cancers. Sub-staging criteria used in stage reassignment were defined as follows: surgical spillage (IC1), capsule rupture before surgery or tumor on the surface (IC2), and positive cytology results (IC3); microscopic (IIB1) and macroscopic (IIB2) pelvic spread; microscopic extrapelvic spread (IIIA1) and retroperitoneal lymph node (LN) metastasis without extrapelvic spread (IIIA2); and supraclavicular LN metastasis (IVA) and other distant metastasis (IVB). Survival outcomes associated with the current and reassigned stages were compared.

Results

Overall, 870 patients were eligible for analysis. The median follow-up period was 45 months (range, 0 to 263 months). The 5-year overall survival rates (5YSRs) according to the current staging were 93.5% (IA), 82.5% (IC), 75.0% (IIB), 74.5% (IIC), 57.5% (IIIA), 54.0% (IIIB), 38.5% (IIIC), and 33.0% (IV). The 5YSRs of patients with IC1, IC2, and IC3 after sub-staging were 92.0%, 85.0%, and 71.0%, respectively (p=0.004). Patients who were reassigned to stage IIIA2 had a better 5YSR than those with extrapelvic tumors >2 cm (66.3% vs. 35.8%; p=0.005). Additionally, patients with newly assigned stage IVA disease had a significantly better 5YSR than those with stage IVB disease (52.0% vs. 28.0%; p=0.015).

Conclusion

The modified FIGO staging for ovarian carcinoma appears superior to the current staging for discriminating survival outcomes of patients with surgical spillage, retroperitoneal LN metastasis without extrapelvic peritoneal involvement, or distant metastasis to supraclavicular LNs.     

Effect of comorbidity and body mass index on the survival of African‐American and Caucasian patients with colon cancer

BACKGROUND:

There is a survival disparity between African Americans and Caucasians who have colon cancer. The objectives of the current study were to quantify the impact of comorbidity and body mass index (BMI) on survival and to assess whether these 2 variables account for the decreased survival among African Americans.

METHODS:

Data from patients (n = 496) who underwent surgery for a first primary colon cancer at the University of Alabama at Birmingham Hospital from 1981 to 2002 were analyzed. Hazard ratios (HRs) with 95% confidence intervals (CI) were obtained using Cox proportional hazards models for the association of race, comorbidity, BMI, and covariates with all‐cause mortality. The confounding influence of comorbidity and BMI for the increased risk of death associated with African‐American race was evaluated, and effect modification by disease stage for the association of comorbidity and BMI with mortality also was assessed.

RESULTS:

African Americans experienced an increased risk of death compared with Caucasians (HR, 1.34; 95% CI, 1.06‐1.68). The highest comorbidity burden was associated with an increased risk of all‐cause mortality (HR, 1.63; 95% CI, 1.24‐2.15). For BMI, being underweight increased the risk of death (HR, 1.54; 95% CI, 0.96‐2.45); however, being overweight/obese was protective (HR, 0.77; 95% CI, 0.61‐0.97). The effect of comorbidity was observed among those with early stage tumors, whereas the effect of BMI was confined to patients who had advanced tumors.

CONCLUSIONS:

Although comorbidity and BMI had an impact on the survival of patients with colon cancer after surgery, these variables were not contributing factors to the decreased survival observed among African Americans. Cancer 2009. © 2009 American Cancer Society.     

Insurance status and survival disparities among nonelderly rectal cancer patients in the National Cancer Data Base

BACKGROUND:

Among patients with colorectal cancer, insurance status is associated with disparities in survival as well as differences in stage and treatment. The role of stage and treatment differences in these survival disparities is not clear because insurance status is also strongly correlated with race/ethnicity, socioeconomic status, and other factors.

METHODS:

The authors used data from the National Cancer Data Base, a national hospital‐based cancer registry, to examine insurance status and other factors related to survival among 19,154 rectal cancer patients aged 18 to 64 years. The authors examined the impact of 10 factors on 5‐year survival: age, sex, race/ethnicity, histologic grade, histologic subtype, neighborhood education and income levels, facility type, stage, and treatment.

RESULTS:

Adjusted only for age, the hazard ratio (HR) for death at 5 years was 1.00 (referent) among privately insured patients, 2.05 (95% confidence interval [CI], 1.89‐2.23) among Medicaid‐insured patients, and 2.01 (95% CI, 1.84‐2.19) among uninsured patients. After adjustment for all factors other than stage and treatment, the HRs were 1.88 (95% CI, 1.722.04) for Medicaid‐insured patients and 1.84 (95% CI, 1.69‐2.01) for uninsured patients. After further adjustment for stage and treatment, the HRs were 1.34 (95% CI, 1.22‐1.46) for Medicaid‐insured patients and 1.29 (95% CI, 1.18‐1.42) for uninsured patients.

CONCLUSIONS:

After adjustment for age, further adjustment for 9 other factors reduced the excess mortality among rectal cancer patients without private insurance by approximately 70%. Disparities in stage and treatment accounted for approximately 53% of the excess mortality, whereas factors other than stage and treatment accounted for approximately 17%. Cancer 2010. © 2010 American Cancer Society.     

Body mass index and risk of ovarian cancer

BACKGROUND:

Convincing epidemiologic evidence links excess body mass to increased risks of endometrial and postmenopausal breast cancers, but the relation between body mass index (BMI) and ovarian cancer risk remains inconclusive. Potential similarities regarding a hormonal mechanism in the etiology of female cancers highlight the importance of investigating associations according to menopausal hormone therapy (MHT) use. However, to the authors' knowledge, data addressing whether the relation between BMI and ovarian cancer differs by MHT use are very sparse.

METHODS:

The authors prospectively investigated the association between BMI and ovarian cancer among 94,525 US women who were followed between 1996 through 1997 to December 31, 2003. During 7 years of follow‐up, 303 epithelial ovarian cancer cases were documented.

RESULTS:

Compared with normal weight women (BMI of 18.5‐24.9 kg/m²), the multivariate relative risk (MVRR) of ovarian cancer for obese women (BMI of ≥30 kg/m²) in the cohort as a whole was 1.26 (95% confidence interval [95% CI], 0.94‐1.68). Among women who never used MHT, the MVRR for obese versus normal weight women was 1.83 (95% CI, 1.18‐2.84). In contrast, no relation between BMI and ovarian cancer was apparent among women who ever used MHT (MVRR = 0.96; 95% CI, 0.65‐1.43; P interaction = 0.02). Exploratory analyses also suggested a positive association between BMI and ovarian cancer among women without a family history of ovarian cancer (MVRR comparing obese vs normal weight women = 1.36; 95% CI, 1.00‐1.86), but no relation with BMI was apparent among women with a positive family history of ovarian cancer (MVRR = 0.74; 95% CI, 0.34‐1.62 [P interaction = .02]).

CONCLUSIONS:

Based on the results of the current study, the authors suspect that obesity is associated with enhanced ovarian cancer risk through a hormonal mechanism. Cancer 2009. Published 2009 by the American Cancer Society.     

Therapeutic role of lymphadenectomy for cervical cancer

BACKGROUND.

Despite the diagnostic value of lymphadenectomy for early‐stage cervical cancer, its therapeutic role is unknown. We examined the therapeutic potential of extensive lymphadenectomy in women with early‐stage cervical cancer.

METHODS.

Women with stage IA2‐IIA cervical cancer who underwent radical hysterectomy with lymphadenectomy in the Surveillance, Epidemiology, and End Results (SEER) database were analyzed. Patients were stratified according to the number of nodes removed. The effect of the extent of lymphadenectomy on overall and cancer‐specific survival was examined using multivariable Cox proportional hazards models. Separate analyses were performed for node positive and node negative patients.

RESULTS.

Among 5522 women, 893 (16%) had <10 nodes, 2030 (37%) had 11‐20, 1487 (27%) had 21‐30 nodes, and 1112 (20%) had >30 nodes removed. Black women, those >65 years of age and those diagnosed later in the study, were less likely to have 10 or more nodes removed (P < .05 for all). Among women with positive lymph nodes, a more extensive lymphadenectomy had no effect on survival (HR = 0.75; 95% CI, 0.47‐1.22). For women with negative lymph nodes, a more extensive lymphadenectomy was associated with improved survival. Compared with node negative patients with less than 10 nodes removed, patients with 21‐30 nodes removed were 24% (HR = 0.76; 95% CI, 0.53‐1.09) less likely to die, whereas those with >30 nodes removed were 37% (HR = 0.64; 95% CI, 0.43‐0.96) less likely to die from their tumors.

CONCLUSIONS.

Node negative, early‐stage cervical cancer patients who undergo a more extensive lymphadenectomy have an improved survival. Cancer 2011. © 2010 American Cancer Society.     

Combined weekly topotecan and biweekly bevacizumab in women with platinum-resistant ovarian, peritoneal, or fallopian tube cancer: results of a phase 2 study

BACKGROUND:

A phase 2 trial was conducted to determine the toxicity and efficacy of combined weekly topotecan and biweekly bevacizumab in patients with primary or secondary platinum‐resistant ovarian, peritoneal, or fallopian tube cancer (OC).

METHODS:

Patients were treated with bevacizumab 10 mg/kg on days 1 and 15 and topotecan 4 mg/m² on days 1, 8, and 15 of a 28‐day cycle until progressive disease (PD) or excessive toxicity. The primary endpoint was progression‐free survival (PFS); secondary objectives included overall survival (OS), objective response, and toxicity.

RESULTS:

Patients (N = 40) received a median of 8 treatment cycles. Toxicity was generally mild or moderate, with neutropenia (18%), hypertension (20%), gastrointestinal toxicity (18%), pain (13%), metabolic toxicity (15%), bowel obstruction (10%), and cardiotoxicity (8%) being the most common grade 3 and 4 adverse events. No bowel perforations, febrile neutropenia, or treatment‐related deaths occurred. Median PFS and OS were 7.8 (95% confidence interval [CI], 3.0‐9.4) and 16.6 months (95% CI, 12.8‐22.9), with 22 (55%) patients progression‐free for ≥6 months. Ten (25%) patients had partial response (PR), 14 (35%) had stable disease (SD), and 16 (40%) had PD. Patients treated with 2 prior regimens received greater benefit than patients treated with 1: PR/SD, 78.9% versus 42.9% (P = .03); median PFS, 10.9 versus 2.8 months (P = .08); median OS, 22.9 versus 12.8 months (P = .02).

CONCLUSIONS:

A weekly topotecan and biweekly bevacizumab combination demonstrates acceptable toxicity and encouraging efficacy in patients with platinum‐resistant OC; further study is warranted. Cancer 2011;. © 2011 American Cancer Society.     

Incidence of cutaneous sebaceous carcinoma and risk of associated neoplasms: insight into Muir-Torre syndrome

BACKGROUND.

Sebaceous tumors of the skin occurring in association with an internal malignancy characterize Muir‐Torre syndrome (MTS), a variant of hereditary nonpolyposis colon cancer (Lynch syndrome). To the authors' knowledge, only limited information exists regarding incidence patterns of sebaceous carcinoma (SC), and no prior study has quantified risks of associated cancers.

METHODS.

The authors calculated cutaneous SC incidence rates (IRs) and IR ratios in 9 US Surveillance, Epidemiology, and End Results program registries (1973‐2003). Indirectly standardized incidence ratios and 95% confidence intervals (95% CIs) were calculated for subsequent cancers among 2‐month survivors of SC and for subsequent SC after other primary cancers.

RESULTS.

Among 664 cases of cutaneous SC, nearly 90% were diagnosed among whites (IR, 0.11 per 100,000 person‐years), with significantly lower IR noted among blacks (IR, 0.04). Whereas eyelid SC IRs demonstrated no sex differences and stabilized in recent years, IRs of noneyelid SC predominated in men and rose steadily over time. Survivors of SC had a 43% (95% CI, 15%‐76%) increased risk of subsequent cancer, and risk of SC was elevated by 52% (95% CI, 24%‐84%) among survivors of other cancers. Whether before or after SC, the significant excesses of other primary cancers were limited to noneyelid SC. Patterns suggestive of genetic predisposition included >20‐fold risks for early‐onset (diagnosed in patients aged <50 years) SC associated with colon, pancreatic, ovarian, or uterine corpus cancers, whereas late‐onset SC (diagnosed in patients aged ≥50 years) predisposed to ureter cancer.

CONCLUSIONS.

This population‐based study of cutaneous SC revealed an association with a spectrum of early‐onset cancers consistent with MTS. Etiologic heterogeneity was suggested by differences between eyelid and noneyelid SC in incidence patterns and associated cancer risks. Cancer 2008. Published 2008 by the American Cancer Society.     

Effect of mammographic service screening on stage at presentation of breast cancers in Sweden

BACKGROUND

Previous results have shown a reduction in mortality with service screening in Sweden on the order of 40%. If the rate of tumors at a later stage were similarly reduced, this would give further support to the mortality findings.

METHODS

The rates of lymph node‐positive cancers, of tumors >2 cm in pathological size, and of tumors of TNM stage II or worse before and after the introduction of screening were compared in 13 areas in Sweden, adjusted for changes in overall incidence during the period of study and stratified by age (40–49 and 50–69 years).

RESULTS

Data were obtained on a total of 23,092 cancers and 10,177,113 person‐years of observation. In women exposed to screening in the screening epoch, there was a significant 45% reduction in tumors of size >2 cm compared with the prescreening (relative risk [RR] = 0.55, 95% confidence interval [CI]: 0.46–0.66) in the 40–49 age group, and a 33% reduction in the 50–69 group (RR = 0.67, 95% CI: 0.62–0.72). For lymph node‐positive and stage II+ disease, there were smaller but still significant reductions. No reduction in incidence in later‐stage disease was observed in the unexposed women in the screening epoch.

CONCLUSIONS

Screening has significantly and substantially reduced the rates of larger tumors and lymph node‐positive breast cancer in Sweden, and the magnitude of the reduction is consistent with the reduction in breast cancer mortality. Cancer 2007. © 2007 American Cancer Society.     

Metformin intake is associated with better survival in ovarian cancer

BACKGROUND:

The objective of this case‐control study was to identify any association of metformin intake with the survival of patients with ovarian cancer.

METHODS:

In this retrospective case‐control study, women with ovarian cancer who received metformin (cases) were compared with women with ovarian cancer who did not receive metformin (controls). A 2‐layered analysis was conducted. In preliminary analysis, all cases (the OC cohort) were compared with controls at a 1:2 ratio. Subsequently, in definitive analysis, only patients who had epithelial ovarian cancer (the EOC cohort) were compared with controls at a 1:3 ratio. In the EOC cohort, cases were matched with controls for age (±5 years), International Federation of Gynecology and Obstetrics stage, and residual disease. Prognostic variables and disease specific survival were compared using chi‐square tests, the Kaplan‐Meier (log‐rank) method, and Cox proportional hazards analysis.

RESULTS:

In a preliminary analysis of the OC cohort (72 cases and 143 controls), cases had better survival (5‐year disease‐specific survival for cases vs controls, 73% vs 44%; P = .0002). In the definitive analysis of the EOC cohort (61 cases and 178 controls), the distribution of age, disease stage, optimal cytoreduction, serous histology, and platinum chemotherapy remained similar between cases and controls (P > .05). Despite these similarities, cases had significantly better survival (5‐year disease‐specific survival for cases vs controls, 67% vs 47%; P = .007). On multivariate analysis, metformin remained an independent predictor of survival (hazard ratio, 2.2; 95% confidence interval, 1.2‐3.8; P = .007) after controlling for disease stage, grade, histology, chemotherapy, body mass index, and surgical cytoreduction.

CONCLUSIONS:

The results of this study indicated an association of metformin intake with survival in patients with ovarian cancer. The receipt of metformin was associated with better survival, and the authors concluded that metformin is worthy of clinical trials in ovarian cancer. Cancer 2013. © 2012 American Cancer Society.     

Fallopian tube cancer. The Roswell Park experience

Sixty-four patients with primary fallopian tube cancer treated at Roswell Park Memorial Institute from 1964 to 1987 underwent retrospective clinicopathologic review. In 40 patients fallopian tube cancer was the only primary, but in 24 patients primary fallopian tube cancer was part of a multifocal upper genital tract malignancy. Of the 40 patients with unifocal fallopian disease, the median survival was 28 months. Only 15% of patients were alive and disease free with follow-up ranging from 22 to 141 months (median, 90.5 months). Survival was not associated with stage of disease, tumor histology, grade, or depth of invasion in this series. Fourteen patients who received cisplatin-based chemotherapy were evaluable for response. Three patients (21%) responded; two complete and one partial. Twelve patients without clinical evidence of disease underwent second-look procedures, ten laparotomy and two laparoscopy. Four of ten second-look laparotomies were negative. Secondary debulking was done in three of four patients with gross disease, one of which had a negative third-look laparotomy. Negative laparotomy, second-look or third-look, was associated with improved survival (P = 0.016). One of the two laparoscopies was negative, but the patient recurred. In the remaining 24 patients cancer of the fallopian tube was part of a multifocal upper genital tract malignancy. In 12 patients tubal disease was invasive, and in 12, it was in situ. Separate primaries occurred in the ovaries (n = 20); uterus (n = 7); and cervix (n = 2). This represents 1.3% of ovarian malignancies treated at Roswell Park Memorial Institute during the study period. Fallopian tube cancer seems as virulent as ovarian cancer with few long-term survivors. It is frequently associated with other sites of upper genital tract malignancy. Second-look laparotomy is an important predictor of survival. Second-look laparoscopy may be useful if positive.     

Oncologic Safety of Gonadotropin-Releasing Hormone Agonist for Ovarian Function Protection During Breast Cancer Chemotherapy

Background

Receipt of a gonadotropin-releasing hormone (GnRH) agonist has been reported to protect against ovarian failure. We sought to determine the oncologic effect of a GnRH agonist with chemotherapy for breast cancer patients.

Early detection of ovarian and fallopian tube cancer by examination of cytological samples from the endometrial cavity

Background:

Accumulating evidence suggests that many ovarian high-grade serous carcinomas (HGSCs) originate in the fallopian tube. Malignant cells shed by tubal lesions can be detected by examination of cytological samples from the endometrial cavity (endometrial cytological testing). To evaluate the use of this method for detecting HGSC, we examined epithelial ovarian, fallopian tube, and primary peritoneal cancer patients.

Methods:

Endometrial cytological testing was performed for endometrial cancer screening in asymptomatic women and for pre-treatment evaluation in symptomatic suspected ovarian, tubal, and peritoneal cancer patients.

Results:

Of the 122 ovarian, tubal, and peritoneal cancer patients, malignant cells were identified in 5 patients who did not show detectable abnormalities on imaging studies. Cervicovaginal cytology was positive in only one of these five patients. Four patients were asymptomatic and one was symptomatic. Three asymptomatic patients had early-stage HGSCs, and the other asymptomatic patient had positive peritoneal cytology findings but no detectable tumour. HGSC patients were significantly more likely to have positive findings on endometrial cytology than patients with other histological types (23% vs 6%, P=0.02).

Conclusion:

Endometrial cytological testing can detect early-stage ovarian, tubal, and peritoneal HGSCs without detectable pelvic masses and may be useful for ovarian cancer screening.