Endocrine therapy in advanced high-grade ovarian cancer: real-life data from a multicenter study and a review of the literature.

BACKGROUND: In women, ovarian cancer is the eighth most frequent cancer in incidence and mortality. It is often diagnosed at advanced stages; relapses are frequent, with a poor prognosis. When platinum resistant, subsequent lines of chemotherapy are of limited effect and often poorly tolerated, leading to quality of life deterioration. Various studies suggest a hormonal role in ovarian carcinogenesis, with a rationale for endocrine therapy in these cancers. PATIENTS AND METHODS: This multicenter, retrospective study assessed the use of endocrine treatment for high-grade ovarian epithelial carcinomas treated between 2010 and 2020. RESULTS: Eighty-one patients with ovarian cancers were included. The median duration of platinum sensitivity was 29 months. We observed a 35% disease control rate with endocrine therapy, and 10% reported symptom improvement. For 19 patients (23.5%), the disease was stabilized for more than 6 months. Median overall survival from diagnosis was 62.6 months. Regarding endocrine therapy predictive factors of response, in a multivariate analysis, 3 factors were statistically significant in favoring progression-free survival: platinum sensitivity (P = .021), an R0 surgical resection (P = .020), and the indication for hormone therapy being maintenance therapy (P = .002). CONCLUSION: This study shows real-life data on endocrine therapy in ovarian cancer. As it is a low-cost treatment with many advantages such as its oral administration and its safety, it may be an option to consider. A perspective lies in the search for cofactors to aim as future therapeutic targets to improve the effectiveness of hormone treatment by means of combination therapy.

Endogenous ether lipids differentially promote tumor aggressiveness by regulating the SK3 channel.

SK3 channels are potassium channels found to promote tumor aggressiveness. We have previously demonstrated that SK3 is regulated by synthetic ether lipids, but the role of endogenous ether lipids is unknown. Here, we have studied the role of endogenous alkyl- and alkenyl-ether lipids on SK3 channels and on the biology of cancer cells. Experiments revealed that the suppression of alkylglycerone phosphate synthase or plasmanylethanolamine desaturase 1, which are key enzymes for alkyl- and alkenyl-ether-lipid synthesis, respectively, decreased SK3 expression by increasing micro RNA (miR)-499 and miR-208 expression, leading to a decrease in SK3-dependent calcium entry, cell migration, and matrix metalloproteinase 9-dependent cell adhesion and invasion. We identified several ether lipids that promoted SK3 expression and found a differential role of alkyl- and alkenyl-ether lipids on SK3 activity. The expressions of alkylglycerone phosphate synthase, SK3, and miR were associated in clinical samples emphasizing the clinical consistency of our observations. To our knowledge, this is the first report showing that ether lipids differentially control tumor aggressiveness by regulating an ion channel. This insight provides new possibilities for therapeutic interventions, offering clinicians an opportunity to manipulate ion channel dysfunction by adjusting the composition of ether lipids.

Plasma membrane SK2 channel activity regulates migration and chemosensitivity of high-grade serous ovarian cancer cells.

No data are currently available on the functional role of small conductance Ca2+ -activated K+ channels (SKCa) in ovarian cancer. Here, we characterized the role of SK2 (KCa2.2) in ovarian cancer cell migration and chemosensitivity. Using the selective non-cell-permeant SK2 inhibitor Lei-Dab7, we identified functional SK2 channels at the plasma membrane, regulating store-operated Ca2+ entry (SOCE) in both cell lines tested (COV504 and OVCAR3). Silencing KCNN2 with short interfering RNA (siRNA), or blocking SK2 activity with Lei-Dab7, decreased cell migration. The more robust effect of KCNN2 knockdown compared to Lei-Dab7 treatment suggested the involvement of functional intracellular SK2 channels in both cell lines. In cells treated with lysophosphatidic acid (LPA), an ovarian cancer biomarker of progression, SK2 channels are a key player of LPA pro-migratory activity but their role in SOCE is abolished. Concerning chemotherapy, SK2 inhibition increased chemoresistance to Taxol® and low KCNN2 mRNA expression was associated with the worst prognosis for progression-free survival in patients with serous ovarian cancer. The dual roles of SK2 mean that SK2 activators could be used as an adjuvant chemotherapy to potentiate treatment efficacy and SK2 inhibitors could be administrated as monotherapy to limit cancer cell dissemination.

[FRANCOGYN group: A brief history]. / Le groupe FRANCOGYN : bilan et avenir.

OBJECTIVES: Describing the constitution of the FRANCOGYN group (a national French research group in Oncological and Gynecological Surgery) and present its current and future development. METHODS: Literature review using PUBMed database with the keyword "FRANCOGYN". OBJECTIVES: Describing the constitution of the FRANCOGYN group (a national French research group in Oncological and Gynecological Surgery) and present its current and future development. RESULTS: The FRANCOGYN group was formed in December 2015, bringing together over the years more than 17 gynecological and oncological surgical department in France. The group carries out clinical research on gynecological pelvic cancers by constituting retrospective cohorts. Its legitimacy allows it to lead or co-lead the drafting of recommendations for clinical practice in the field of gynecological cancers. It now offers prospective randomized research funded by national grants. CONCLUSION: The FRANCOGYN network allows us to propose a national reflection on the surgical management of pelvic cancers in women, resulting in numerous international reference publications.

Brachytherapy and surgery versus surgery alone for IB2 (FIGO 2018) cervical cancers: A FRANCOGYN study.

OBJECTIVE: Evaluation of the management by first brachytherapy followed by radical hysterectomy (Wertheim type) compared to radical hysterectomy alone (Wertheim type) for the treatment of IB2 cervical cancer. METHODS: Data from women with histologically proven FIGO stage IB2 cervical cancer treated between April 1996 and December 2016 were retrospectively abstracted from twelve French institutions with prospectively maintained databases. RESULTS: Of the 211 patients with FIGO stage IB2 cervical cancer without lymph node involvement included, 136 had surgical treatment only and 75 had pelvic lymph node staging and brachytherapy followed by surgery. The surgery-only group had significantly more adjuvant treatment (29 vs. 3; p = 0.0002). A complete response was identified in 61 patients (81%) in the brachytherapy group. Postoperative complications were comparable (63,2% vs. 72%, p = 0,19) and consisted mainly of urinary (36vs. 27) and digestive (31 vs 22) complications and lymphoceles (4 vs. 1). Brachytherapy had no benefit in terms of progression-free survival (p = 0.14) or overall survival (p = 0.59). However, for tumors of between 20 and 30 mm, preoperative brachytherapy improved recurrence-free survival (p = 0.0095) but not overall survival (p = 0.41). This difference was not observed for larger tumors in terms of either recurrence-free survival (p = 0.55) or overall survival (p = 0.95). CONCLUSION: Our study found that preoperative brachytherapy had no benefit for stage IB2 cervical cancers in terms of recurrence-free survival or overall survival. For tumor sizes between 2 and 3 cm, brachytherapy improves progression-free survival mainly by reducing pelvic recurrences without improving overall survival.

Adherence to ESGO guidelines and impact on survival in obese patients with endometrial cancer: a multicentric retrospective study.

OBJECTIVES: Obesity is known to be both a major risk factor for endometrial cancer and associated with surgical complexity. Therefore, the management of patients with obesity is a challenge for surgeons and oncologists. The aim of this study is to assess the adherence to European Society of Gynaecological Oncology (ESGO) guidelines in morbidly obese patients (body mass index (BMI) >40 kg/m2). The secondary objectives were the impact on overall survival and recurrence-free survival. METHODS: All the patients who were treated for an endometrial cancer in the 11 cancer institutes of the FRANCOGYN group were included and classified into three weight groups: morbid (BMI >40 kg/m2), obese (BMI 30-40), and normal or overweight (BMI <30). Adherence to guidelines was evaluated for surgical management, lymph node staging, and adjuvant therapies. RESULTS: In total, 2375 patients were included: 1330 in the normal or overweight group, 763 in the obese group, and 282 in the morbid group. The surgical management of the morbid group was in accordance with the guidelines in only 30% of cases, compared with 44% for the obese group and 48% for the normal or overweight group (p<0.001); this was largely because of a lack of lymph node staging. Morbid group patients were more likely to receive the recommended adjuvant therapy (61%) than the obese group (52%) or the normal or overweight group (46%) (p<0.001). Weight had no impact on overall survival (p=0.6) and morbid group patients had better recurrence-free survival (p=0.04). CONCLUSION: Adherence to international guidelines for surgical management is significantly lower in morbid group patients, especially for lymph node staging. However, morbidly obese patients had more often the adequate adjuvant therapies. Morbid group patients had a better recurrence-free survival likely because of better prognosis tumors.

The variability of aggressiveness of grade 1 breast cancer.

BACKGROUND: Grade 1 breast cancer represents the lowest grade of invasive breast cancer and is associated with a low risk of recurrence and distant metastasis. However, when grade 1 breast cancer is associated with lymph node involvement, the prognosis may be worse than that of grade 1 breast cancer without lymph node involvement. METHOD: The study population included all patients who were managed in our institution between January 1, 2007 and December 31, 2013 for grade 1 breast cancer . We compared patients who had lymph node involvement to those who had no lymph node involvement. RESULTS: During the study period 291 grade 1 carcinomas were included of which 23% had associated positive lymph node involvement. Overall survival did not differ significantly between patients without lymph node involvement and those with lymph node involvement, nor was there a significant difference in the risk of local recurrence free survival. However, a significant difference was found in survival without distant metastasis with a significant level of a p at 0.029. CONCLUSION: Our findings confirm that tumor size and LVSI are strong predictors of axillary lymph node involvement, which is a key determinant of distant metastasis-free survival.

Prognostic impact of cytoreductive surgery conducted with primary intent, versus cytoreductive surgery after neoadjuvant chemotherapy, in the management of patients with advanced epithelial ovarian cancers: a multicentre, propensity score-matched study from the FRANCOGYN group.

OBJECTIVE: To compare survival and morbidity rates between primary cytoreductive surgery (pCRS) and interval cytoreductive surgery (iCRS) for epithelial ovarian cancer (EOC), using a propensity score. DESIGN: We conducted a propensity score-matched cohort study, using data from the FRANCOGYN cohort. SETTING: Retrospective, multicentre study of data from patients followed in 15 French department specialized in the treatment of ovarian cancer. SAMPLE: Patients included were those with International Federation of Gynaecology and Obstetrics (FIGO) stage III or IV EOC, with peritoneal carcinomatosis, having undergone CRS. METHODS: The propensity score was designed using pre-therapeutic variables associated with both treatment allocation and overall survival (OS). MAIN OUTCOME MEASURES: The primary outcome was OS. Secondary outcomes included recurrence-free survival (RFS), quality of CRS and other variables related to surgical morbidity. RESULTS: A total of 513 patients were included. Among these, 334 could be matched, forming 167 pairs. No difference in OS was found (hazard ratio, HR = 0.8, p = 0.32). There was also no difference in RFS (median = 26 months in both groups) nor in the rate of CRS leaving no macroscopic residual disease (pCRS 85%, iCRS 81.4%, p = 0.76). The rates of gastrointestinal tract resections, stoma, postoperative complications and hospital stay were significantly higher in the pCRS group. CONCLUSIONS: Analysis of groups of patients made comparable by propensity score matching showed no difference in survival, but lower postoperative morbidity in patients treated with iCRS.

A Suggested Modification to FIGO Stage IV Epithelial Ovarian Cancer.

International Federation of Gynecology and Obstetrics (FIGO) staging classification for stage IV epithelial ovarian cancer (EOC) separates stages IVA (pleural effusion) and IVB (parenchymal and/or extra-abdominal lymph node metastases). We aimed to evaluate its prognostic impact and to compare survival according to the initial metastatic location. We conducted a multicenter study between 2000 and 2020, including patients with a FIGO stage IV EOC. Primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS) and recurrence rates. We included 307 patients: 98 (32%) had FIGO stage IVA and 209 (68%) had FIGO stage IVB. The median OS and PFS of stage IVA patients were significantly lower than those of stage IVB patients (31 versus 45 months (p = 0.02) and 18 versus 25 months (p = 0.01), respectively). Recurrence rate was higher in stage IVA than IVB patients (65% versus 47% (p = 0.004)). Initial pleural involvement was a poor prognostic factor with a median OS of 35 months versus 49 months for patients without initial pleural involvement (p = 0.024). Patients with FIGO stage IVA had a worse prognosis than patients with FIGO stage IVB EOC. Pleural involvement appears to be relevant for predicting survival. We suggest a modification of the current FIGO staging classification.

Endometrial cancer of the very elderly: Management and survival in the Francogyn population.

INTRODUCTION: We aimed to describe management and survival of patients with endometrial cancer (EC) ≥80 years to identify poor prognosis criteria. METHODS: We collected clinical, histologic, surgical and follow-up data for patients with EC ≥ 80 years included in a multicenter French cohort (FRANCOGYN) who underwent primary surgical treatment from 1999 to 2019. The outcomes were overall survival (OS) and disease-free survival (DFS). We performed a descriptive analysis then a survival time analysis and comparison using the Kaplan Meier method and log-rank test. RESULTS: Of the 1647 patients with EC who received treatment during the study period, 184 (11.17%) were ≥80 years. The mean age was 84 years (±3.34). Thirty-three patients (25.4%) died during the follow-up period and 26 relapsed (18.4%). Forty-nine patients were lost to follow-up (27.37%). The median follow-up time was 15.3 months (4.9-28.8). The median OS and DFS was 16.4 months (6.3-24.9) and 13.6 months (4.5-26.6), respectively. Eighty-three patients received adjuvant therapy (45.11%), out of 95 who had a formal or relative indication. Four patients received adjuvant chemotherapy (2.6%), out of 61 who had a formal or relative indication. Inappropriate or underuse of chemotherapy was significantly associated with a lower median OS of 12.6 months [3.73-24] versus 17.3 months [7.93-41.77] when performed appropriately (HR = 4.14, CI 95% [1.62-10.56]), and a lower median DFS of 10.83 months [3.73-24] versus 17.3 months [7.93-28.5] (HR = 9.04, CI 95% [2.04-40.12]). CONCLUSION: Our results suggest that very elderly patients with EC should receive adjuvant chemotherapy according to the standard care guidelines.

Total Polyunsaturated Fatty Acid Level in Abdominal Adipose Tissue as an Independent Predictor of Recurrence-Free Survival in Women with Ovarian Cancer.

Prognostic factors for epithelial ovarian cancers (EOCs) are in particular clinical factors such as pathology staging at diagnosis (FIGO stages), genetic mutation, or histological phenotypes. In the present study, FIGO stage, tumor residue after surgery, and body mass index were clinical predictors of recurrence-free survival (RFS). Nonetheless, a number of studies support a lipid metabolism disorder in ovarian cancer patients. The objective of this pilot study was to explore whether fatty acid composition of adipose reflecting the qualitative dietary intake and fatty acids metabolism may be associated with RFS. Forty-six women with EOCs and six with borderline ovarian tumors between March 2017 and January 2020 were included in this prospective study at Tours university teaching hospital (central France). The patients involved in the present study are part of the METERMUS trial (clinicaltrials.gov NCT03027479). Adipose tissue specimens from four abdominal locations (superficial and deep subcutaneous, visceral (pericolic), and omental) were collected during surgery or exploratory laparoscopy. A fatty acid profile of adipose tissue triglycerides was established by gas chromatography. Fatty acids composition was compared among the four locations using nonparametric Friedman's ANOVA test for repeated measures. Median follow-up of EOC patients was 15 months and patients' RFS was analyzed using Kaplan−Meier survival curves and log-rank test by separating patients into two groups according to median fatty acid levels. The content of long-chain saturated fatty acids (SFAs) was increased and that of long-chain polyunsaturated fatty acids (PUFAs) decreased in deep versus superficial subcutaneous adipose tissue in EOC patients. Nevertheless, the content of total SFAs was ~28%, monounsaturated fatty acids (MUFAs) ~55%, PUFAs n-6 ~11.5%, and PUFAs n-3 about 1.3%, whatever the adipose tissue. When EOC patients were separated into two groups by median fatty acid content, total PUFAs (n-6+n-3) levels, whatever the adipose tissue, were positively and independently associated with RFS. RFS was about two times longer in EOC patients with high versus low total PUFA content (median survival: 12 vs. 27 months, p = 0.01 to <0.0001 according to the tissue). Content of total PUFAs (n-6+n-3) in abdominal adipose tissue (visceral and subcutaneous) are new prognostic factors in EOC.

Malignant breast myoepithelioma: A systematic review.

OBJECTIVES: We performed a systematic review in order to describe the clinical presentation, therapeutic management and outcomes of malignant myoepitelioma of the breast. SEARCH STRATEGY: A systematic search of MEDLINE and EMBASE references from January 1980 to Marsh 2020 was performed. We included articles that reported cases of malignant breast myoepithelioma. Data from eligible studies were independently extracted onto standardized forms by two reviewers. RESULTS: 31 articles including 47 cases of malignant breast myoepithelioma and 3 other unpublished cases managed in our establishment were included in this systematic review. The average age at diagnosis was 60.7 years old [range 30-81]. The average size of the tumor was 46mm [range 10 -230]. 30 patients had a partial mastectomy and 18 a total mastectomy. Only 15% of patient (7/48) had an axillary sentinel lymph node biopsy of whom one was positive. 33% of patients (16/48) had an axillary lymph node dissection which was positive for one patient. 19% (n=9) had adjuvant radiotherapy and 15% (n=7) had adjuvant chemotherapy. 33% (n=10) of patients with partial mastectomy had at least one recurrence, versus 5.5% (n=1) after a total mastectomy. The average time between the diagnosis and the first recurrence was 25.4 months [range: 1-50]. 64% (n=7) had a second partial mastectomy and only 18% (n=2) had a total mastectomy. 27% of patient had chemotherapy after their first recurrence and 27% had radiotherapy if it was not received in first line treatment. 40% (n=4/10) of patients with partial mastectomy who recurred have had at least 2 breast recurrences. 28% (n=14) of all patients had distant metastases. 20% of patients (n=10) died whose 80% (n=8) had distant metastatic disease. CONCLUSIONS: This systematic review provided a precise summary of the clinical characteristics and treatment of patients presenting with Malignant breast myoepithelioma in the past 40 years. We anticipate that these results will help inform current investigations and treatment.

Presentation and Prognosis of Primary Expansile and Infiltrative Mucinous Carcinomas of the Ovary.

Objective: The aim of the present study was to evaluate evolution and prognosis of mucinous ovarian carcinomas (mOC), with respect to the two invasive patterns: expansile and infiltrative invasion. Methods: This was a descriptive, retrospective, multicenter study conducted in 13 French centres from 1 January 2001 to 31 December 2019. All patients operated on for epithelial ovarian neoplasia of the mucinous type (infiltrative/expansile) were included, whether the surgery was performed immediately or after neoadjuvant chemotherapy. Results: A total of 94 women with mucinous carcinomas were included in the present study. Mucinous tumours were divided into 35 expansile (37%) and 59 infiltrative (63%) mOC. There was a statistically significant difference in early and late stages at initial diagnosis between expansile and infiltrative mOC. None of the expansile mOC showed metastatic lymph nodes, whereas almost a quarter of the infiltrative mOC were metastatic to the pelvic/para-aortic region. There was a clear difference in RFS, in favour of expansile mOC, with 90% survival at 5 years, compared with 60% for infiltrative mOC. Conclusions: Although infiltrative and expansile mOC belong to the same histological family, they present many distinctions in clinical presentation, histological invasion, and disease course.

Risk Factors for Recurrence of Borderline Ovarian Tumours after Conservative Surgery and Impact on Fertility: A Multicentre Study by the Francogyn Group.

INTRODUCTION: Borderline ovarian tumours (BOT) represent 10-20% of epithelial tumours of the ovary. Although their prognosis is excellent, the recurrence rate can be as high as 30%, and recurrence in the infiltrative form accounts for 3% to 5% of recurrences. Affecting, in one third of cases, women of childbearing age, the surgical strategy with ovarian conservation is now recommended despite a significant risk of recurrence. Few studies have focused exclusively on patients who have received ovarian conservative treatment in an attempt to identify factors predictive of recurrence and the impact on fertility. The objective of this study was to identify the risk factors for recurrence of BOT after conservative treatment and the impact on fertility. MATERIAL AND METHODS: This was a retrospective, multicentre study of women who received conservative surgery for BOT between February 1997 and September 2020. We divided the patients into two groups, the "R group" with recurrence and the "NR group" without recurrence. RESULTS: Of 175 patients included, 35 had a recurrence (R group, 20%) and 140 had no recurrence (NR group, 80%). With a mean follow-up of 30 months (IQ 8-62.5), the overall recurrence rate was 20%. Recurrence was BOT in 17.7% (31/175) and invasive in 2.3% (4/175). The mean time to recurrence was 29.5 months (IQ 16.5-52.5). Initial complete peritoneal staging (ICPS) was performed in 42.5% of patients (n = 75). In multivariate analysis, age at diagnosis, nulliparity, advanced FIGO stage, the presence of peritoneal implants, and the presence of a micropapillary component for serous tumours were factors influencing the occurrence of recurrence. The post-surgery fertility rate was 67%. CONCLUSION: This multicentre study is to date one of the largest studies analysing the risk factors for recurrence of BOT after conservative surgery. Five risk factors were found: age at diagnosis, nulliparity, advanced FIGO stage, the presence of implants, and a micropapillary component. Only 25% of the patients with recurrence underwent ICPS. These results reinforce the interest of initial peritoneal staging to avoid ignoring an advanced tumour stage.

Comparison of retroperitoneal and transperitoneal surgical routes in laparoscopic nodal staging for locally advanced cervical cancers (FIGO IB3-IVA).

BACKGROUND: This study compares morbidity and mortality associated with retroperitoneal and transperitoneal para-aortic lymphadenectomy (PAAL) for pretherapeutic nodal staging of locally advanced cervical cancers (FIGO IB3-IVA). METHODS: Pre-, per- and postoperative data of patients treated for locally advanced stage cervical cancer between 1999 and 2018 in 12 French referral centers (FRANCOGYN Study Group) were retrospectively collected. RESULTS: The study was conducted using a sample of 448 patients, of whom 223 (49,8%) underwent retroperitoneal (group 1) and 225 (50,2%) had transperitoneal PAAL (group 2). No differences were noted concerning clinical and histological characteristics between the two groups. Among these 448 patients, 23 (5,1%) had an intraoperative complication (9 (2,0%) in group 1 and 14 (3,1%) in group 2, p = 0.28) and 47 (10,5%) had a postoperative complication (22 (4,9%) in group 1 and 25 (5,6%) in group 2, p = 0.44), only one of which required revision surgery but the patient died. The length of hospital stay was significantly shorter in group 1 than in group 2 (3.97 versus 4.88 days, p < 0.001). There was no significant difference in mortality between the two groups; 34 of 223 patients in group 1 (15.3%) and 40 of 225 patients in group 2 (15.6%) died (HR = 0.968, 95% CI [0.591-1.585]). There was no significant difference in recurrence-free or overall survival between the two groups. CONCLUSION: Retroperitoneal PAAL appears as a valuable and safety surgical route for nodal staging in locally advanced cervical cancer compared with standard transperitoneal PAAL.

Trachelectomy: How is it actually done? A review from FRANCOGYN group Titre: Trachélectomie: comment faire en pratique ? Revue de la littérature par le groupe FRANCOGYN.

Because of the peak incidence of cervical cancer between the ages of 35 and 44 and the increasing age of first pregnancy, the issue of fertility preservation in cases of early-stage cervical cancer in women in this reproductive age category arises. Early-stage cervical cancer patients have a good prognosis and are surgically treated in cases of mildly aggressive human papillomavirus-related histological type (squamous cell carcinoma, adenocarcinoma), FIGO stage IA to IB1 (i.e., <2 cm), with shallow stromal invasion (<10 mm) and without the presence of lymph-vascular space invasion or lymph node or regional involvement. Under these conditions, conservative treatment by trachelectomy, which has recurrence-free and overall survival rates equivalent to that of hysterectomy, may be considered. After a complete pre-therapeutic assessment, including pelvic lymphadenectomy, to eliminate all contraindications to conservative treatment, a simple or enlarged trachelectomy can be chosen. According to some authors, the route of entry (vaginal, simple or robot-assisted laparoscopy, laparotomy) has no significant effect on survival or fertility, although the literature on the subject is limited. Trachelectomy offers good results in terms of fertility, with an estimated pregnancy rate of between 23% and 55% and a live birth rate of 70%. The significant reduction of the cervix associated with the procedure increases the risk of prematurity. However, this can be prevented by the use of a permanent cerclage. Close follow-up of these patients is essential for a minimum period of 5 years in order to detect any recurrence or postoperative complications.

Impact of severe obesity in the management of patients with high-risk endometrial cancer: A FRANCOGYN study.

OBJECTIVE: To assess the surgical management and survival of severely obese patients with high-risk endometrial cancer. MATERIALS AND METHODS: Data from 269 patients with high-risk endometrial cancer who were treated between 2001 and 2018 were collected from a multicenter database (11 centers). We classified the patients according to their BMI and compared outcomes in two groups: a normal weight group of women with a BMI < 25 kg/m2, and a severe obesity group of women with a BMI ≥ 35 kg/m2. The groups were compared for epidemiologic, pathologic, management, relapse-free survival (RFS) and overall survival (OS) elements. RESULTS: Patients in the severe obesity group were younger (64 years vs. 68 years, p < 0.05) and had more comorbidities (hypertension, diabetes). They also had more locally advanced tumors and pelvic lymph node involvement (47% vs 24%, p < 0.05). The severely obese patients were less likely to undergo recommended surgical staging, with fewer lumbar aortic dissections than women of normal weight (23% vs 36%, p < 0.05) and fewer pelvic sentinel lymph node biopsies (26.5% vs 12.1%, p < 0.05). No difference in RFS or OS were observed between the two groups. CONCLUSION: Patients with severe obesity and high-risk endometrial cancer have more locally advanced tumors, and are less likely to be managed according to surgical recommendations. However, RFS and OS do not seem to be affected.

Accumulation of Arachidonic Acid, Precursor of Pro-Inflammatory Eicosanoids, in Adipose Tissue of Obese Women: Association with Breast Cancer Aggressiveness Indicators.

While obesity is linked to cancer risk, no studies have explored the consequences of body mass index (BMI) on fatty acid profiles in breast adipose tissue and on breast tumor aggressiveness indicators. Because of this, 261 breast adipose tissue samples of women with invasive breast carcinoma were analyzed. Fatty acid profile was established by gas chromatography. For normal-weight women, major changes in fatty acid profile occurs after menopause, with the enrichment of long-chain polyunsaturated fatty acids (LC-PUFAs) of both n-6 and n-3 series enrichment, but a stable LC-PUFAs n-6/n-3 ratio across age. BMI impact was analyzed by age subgroups to overcome the age effect. BMI increase is associated with LC-PUFAs n-6 accumulation, including arachidonic acid. Positive correlations between BMI and several LC-PUFAs n-6 were observed, as well as a strong imbalance in the LC-PUFAs n-6/n-3 ratio. Regarding cancer, axillary lymph nodes (p = 0.02) and inflammatory breast cancer (p = 0.08) are more frequently involved in obese women. Increased BMI induces an LC-PUFAs n-6 accumulation, including arachidonic acid, in adipose tissue. This may participate in the development of low-grade inflammation in obese women and breast tumor progression. These results suggest the value of lifestyle and LC-PUFAs n-3 potential, in the context of obesity and breast cancer secondary/tertiary prevention.