Adjuvant capecitabine in triple negative breast cancer patients with residual disease after neoadjuvant treatment: real-world evidence from CaRe, a multicentric, observational study.

Background: In triple negative breast cancer patients treated with neoadjuvant chemotherapy, residual disease at surgery is the most relevant unfavorable prognostic factor. Current guidelines consider the use of adjuvant capecitabine, based on the results of the randomized CREATE-X study, carried out in Asian patients and including a small subset of triple negative tumors. Thus far, evidence on Caucasian patients is limited, and no real-world data are available. Methods: We carried out a multicenter, observational study, involving 44 oncologic centres. Triple negative breast cancer patients with residual disease, treated with adjuvant capecitabine from January 2017 through June 2021, were recruited. We primarily focused on treatment tolerability, with toxicity being reported as potential cause of treatment discontinuation. Secondarily, we assessed effectiveness in the overall study population and in a subset having a minimum follow-up of 2 years. Results: Overall, 270 patients were retrospectively identified. The 50.4% of the patients had residual node positive disease, 7.8% and 81.9% had large or G3 residual tumor, respectively, and 80.4% a Ki-67 >20%. Toxicity-related treatment discontinuation was observed only in 10.4% of the patients. In the whole population, at a median follow-up of 15 months, 2-year disease-free survival was 62%, 2 and 3-year overall survival 84.0% and 76.2%, respectively. In 129 patients with a median follow-up of 25 months, 2-year disease-free survival was 43.4%, 2 and 3-year overall survival 78.0% and 70.8%, respectively. Six or more cycles of capecitabine were associated with more favourable outcomes compared with less than six cycles. Conclusion: The CaRe study shows an unexpectedly good tolerance of adjuvant capecitabine in a real-world setting, although effectiveness appears to be lower than that observed in the CREATE-X study. Methodological differences between the two studies impose significant limits to comparability concerning effectiveness, and strongly invite further research.

Lymph node dissection in uterine leiomyosarcomas: A matched-pair study.

OBJECTIVE: To assess the impact of the lymph node dissection (LND) in the disease-free (DFS) and overall survival (OS) of the women treated surgically of uterine leiomyosarcoma (ULMS). MATERIAL AND METHODS: A multicentric retrospective study was conducted among European countries collecting patients diagnosed of uterine sarcoma (SARcoma of the UTerus - SARCUT study). A total of 390 ULMS were selected for the present study to compare patients who underwent LND and those who did not. A further matched-pair subanalysis identified 116 women, 58 pairs (58 with LND and 58 without it) comparable in age, tumor size, surgical procedures, extrauterine disease and adjuvant treatment. Demographic data, pathology results and follow-up were abstracted from medical records and analyzed. Disease-free (DFS) and overall survival (OS) were studied using Kaplan-Meier curves and Cox regression analysis. RESULTS: Among the 390 patients, the 5-year DFS was significantly higher in no-LDN group comparing to the LDN group (57.7% vs. 33.0%; HR 1.75, 95% CI 1.19-2.56; p = 0.007), but not the 5-year OS (64.6% vs. 64.3%; HR 1,10 95% CI 0,77-1,79; p = 0.704). In the matched-pair subanalysis, there were no statistical differences between the study groups. The 5- year DFS was 50.5% in the no-LND and 33.0% in the LND group (HR 1.38; 95% CI 0,83-2.31; p = 0,218) and the 5-year OS was 59.7% and 64.3% respectively (HR 0.81; 95% CI 0,45-1,49; p = 0,509). CONCLUSIONS: LND performed in women diagnosed of ULMS have no impact neither in the disease-free nor in the overall survival compared to patients without LDN in a complete homogeneous group.

Update on Prognostic and Predictive Markers in Mucinous Ovarian Cancer.

This review includes state-of-the-art prognostic and predictive factors of mucinous ovarian cancer (MOC), a rare tumor. Clinical, pathological, and molecular features and treatment options according to prognosis are comprehensively discussed. Different clinical implications of MOC are described according to the The International Federation of Gynecology and Obstetrics (FIGO) stage: early MOC (stage I-II) and advanced MOC (stage III-IV). Early MOC is characterized by a good prognosis. Surgery is the mainstay of treatment. Fertility-sparing surgery could be performed in patients who wish to become pregnant and that present low recurrence risk of disease. Adjuvant chemotherapy is not recommended, except in patients with high-risk clinical and pathological features. Regarding the histological features, an infiltrative growth pattern is the major prognostic factor of MOC. Furthermore, novel molecular biomarkers are emerging for tailored management of early-stage MOC. In contrast, advanced MOC is characterized by poor survival. Radical surgery is the cornerstone of treatment and adjuvant chemotherapy is recommended, although the efficacy is limited by the intrinsic chemoresistance of these tumors. Several molecular hallmarks of advanced MOC have been described in recent years (e.g., HER2 amplification, distinct methylation profiles, peculiar immunological microenvironment), but target therapy for these rare tumors is not available yet.

"Intestinal-Type" Vulvar Adenocarcinoma: A Review of the MITO Rare Tumors Group.

Intestinal-type adenocarcinoma (VAIt) represents a sporadic variant of vulvar carcinoma. It appears frequently localized to epithelial glands in the vulvar region, and it probably derives from cloacal remnants persisting in the adult. We performed a systematic review of the limited cases reported in the literature, with the intent to assess the specific peculiarities of this rare neoplasia and to state consistent management recommendations. The principal histological VAIt characteristic is that it resembles mucinous colonic carcinomas. Therefore, immunohistochemical workup, with different tumor markers including CK20, CDX2, and CK7 staining, is needed. To confirm vulvar origin, a thorough diagnostic, and radiological examination is required to rule out other primary malignancies. The gold standard of treatment for VAIt is surgery, with local excision with tumor-free margins. Lymph node staging is an option advised if the tumor size is >2 cm or if lymph node metastases are suspected on imaging. On the other hand, the role of neoadjuvant therapy is still in doubt, but a good response to adjuvant chemotherapy treatments has been described in both advanced and recurrent diseases. Sometimes, VAIt behavior can be unpredictable, with relapses even after many years, so more experiences and longer follow-up periods are needed to elucidate the best therapeutic management and its long-term prognosis.

Risk of unexpected uterine leiomyosarcoma during laparoscopic procedures: Experience from a single tertiary institute in Italy.

OBJECTIVE: To evaluate the incidence of occult uterine sarcomas and investigate whether an accurate and well-established preoperative assessment for uterine fibroids could help identify uterine sarcomas more effectively. METHODS: A retrospective analysis of patients who underwent gynecological laparoscopic surgery for presumed uterine fibroids at Sant'Anna Hospital, a single tertiary institute in Turin, Italy, between January 2003 and December 2019. RESULTS: Over the 17-year period, 5826 laparoscopic surgical procedures (myomectomies or subtotal/total hysterectomies) were performed for presumed uterine fibroids. A total of 48 patients with a final diagnosis of uterine sarcoma were identified, the majority of which (n = 39; 81.3%) were recognized as suspicious uterine sarcomas during the preoperative assessment, and morcellement was avoided. The occurrence of unexpected uterine sarcomas was 0.1% (6/5826). Morcellation was conducted in one patient with uterine sarcoma. CONCLUSION: Analysis of our data showed that unexpected uterine sarcomas are uncommon. Accurate preoperative evaluation can help avoid, but does not exclude, the possibility of morcellation of unknown uterine sarcomas.

Oncophone20 study: Patients' perception of telemedicine in the COVID-19 pandemic during follow-up visits for gynecological and breast cancers.

OBJECTIVE: To analyze oncological patients' perception of telemedicine during the COVID-19 pandemic. METHODS: A total of 345 women, of whom 267 experienced breast cancer and 78 experienced a gynecological cancer, were enrolled. Specific questionnaires about their experiences and feelings about telemedicine in the COVID-19 era were collected. RESULTS: In the breast group, "enhanced care" showed moderate positive perception (mean 4.40) among less-educated women that was slightly lower among better-educated women (mean 4.14) with a significant difference (P = 0.034). "satisfaction" had an opposite pattern: a mean of 3.99 for a lower level of education and 4.78 for a higher level of education, with a strong significant difference (P < 0.001). "privacy and discomfort" approached neutrality for less-educated women, while for higher-educated women the lower mean of 2.93 indicted a more positive perception (P = 0.007). In the pelvic group, younger women had a better perception towards telemedicine for "telemedicine as a substitution" (mean 3.68) compared to older women (mean 3.05). The privacy and discomfort subscale was in favor of better-educated women (mean 2.57) compared to less-educated women (mean 3.28; P = 0.042). CONCLUSION: Telemedicine was generally well accepted, not only among younger and higher-educated women but also by women needing intensive care, in both cancer groups.

A simplified fascial model of pelvic anatomical surgery: going beyond parametrium-centered surgical anatomy.

The classical surgical anatomy of the female pelvis is limited by its gynecological oncological focus on the parametrium and burdened by its modeling based on personal techniques of different surgeons. However, surgical treatment of pelvic diseases, spreading beyond the anatomical area of origin, requires extra-regional procedures and a thorough pelvic anatomical knowledge. This study evaluated the feasibility of a comprehensive and simplified model of pelvic retroperitoneal compartmentalization, based on anatomical rather than surgical anatomical structures. Such a model aims at providing an easier, holistic approach useful for clinical, surgical and educational purposes. Six fresh-frozen female pelves were macroscopically and systematically dissected. Three superficial structures, i.e., the obliterated umbilical artery, the ureter and the sacrouterine ligament, were identified as the landmarks of 3 deeper fascial-ligamentous structures, i.e., the umbilicovesical fascia, the urogenital-hypogastric fascia and the sacropubic ligament. The retroperitoneal areolar tissue was then gently teased away, exposing the compartments delimited by these deep fascial structures. Four compartments were identified as a result of the intrapelvic development of the umbilicovesical fascia along the obliterated umbilical artery, the urogenital-hypogastric fascia along the mesoureter and the sacropubic ligaments. The retroperitoneal compartments were named: parietal, laterally to the umbilicovesical fascia; vascular, between the two fasciae; neural, medially to the urogenital-hypogastric fascia and visceral between the sacropubic ligaments. The study provides the scientific rational for a model of pelvic retroperitoneal anatomy based on identifiable anatomical structures and suitable for surgical planning and training.

ß-thalassemia patients and gynecological approach: review and clinical experience.

Significant improvements in therapy and life expectancy of ß-thalassemia patients in last decades result in the need of commitment for gynecologists and obstetricians as the complexity of organ impairment needs a specific multidisciplinary approach. After a review of clinical manifestations of ß-thalassemia from a gynecologic point of view, we present the experience of a gynecologic center in treating ß-thalassemia patients from more than 20 years.

The heterochronic microRNA let-7 inhibits cell motility by regulating the genes in the actin cytoskeleton pathway in breast cancer.

The heterochronic gene let-7 serves as a tumor suppressor microRNA by targeting various oncogenic pathways in cancer cells. Considerable evidence indicates that reduced expression of let-7 might be associated with poor clinical outcome in patients with cancer. Here, we report that the expression levels of three let-7 family members, let-7a, let-7b, and let-7g, were significantly decreased in the patients with breast cancer with lymph node metastasis compared with those without lymph node metastasis. Enforced expression of let-7b significantly inhibits breast cancer cell motility and affects actin dynamics. Using bioinformatic and experimental approaches, four genes in the actin cytoskeleton pathway, including PAK1, DIAPH2, RDX, and ITGB8, were identified as let-7 direct targets. Blocking the expression of PAK1, DIAPH2, and RDX significantly inhibits breast cancer cell migration induced by let-7b repression. Our results indicate that reconstitution of let-7 expression in tumor cells could provide a novel therapeutic strategy for the treatment of metastatic disease.

Physical activity and breast cancer survival: an epigenetic link through reduced methylation of a tumor suppressor gene L3MBTL1.

The study was conducted to determine the effect of physical activity on DNA methylation and to predict the consequence of this effect concerning gene expression and breast cancer survival. Blood samples, collected from 12 breast cancer patients who participated in a randomized clinical trial of exercise, were examined for exercise-related changes in DNA methylation using a methylation microarray. Tumor samples of 348 breast cancer patients were analyzed with qRT-PCR and qMSP to determine gene expression and methylation identified in the microarray analysis. Cox regression models were developed to predict survival outcomes in association with gene expression and methylation. After 6 months of moderate-intensity aerobic exercise, changes in DNA methylation (P < 5 × 10(-5)) in peripheral blood leukocytes were detected in 43 genes from a panel of 14 495. Based on the list, we analyzed gene expression in association with overall survival in breast tumors and found three genes whose methylation was reduced after exercise were favorably in association with overall survival, i.e., higher expression associated with better survival. Of the three genes, L3MBTL1 was a putative tumor suppressor gene with known function to repress chromatin for transcription, which is activated mainly in germline stem cells. Further analyses of tumor features among patients indicated that high expression of L3MBTL1 was associated with low grade and hormone receptor-positive tumors, as well as low risk of disease recurrence and breast cancer death. In conclusion, the study suggests that increasing physical activity after a breast cancer diagnosis may affect epigenetic regulation of tumor suppressor genes, which have favorable impacts on survival outcomes of breast cancer patients.

Telomerase expression and telomere length in breast cancer and their associations with adjuvant treatment and disease outcome.

INTRODUCTION: Telomere length plays important roles in maintaining genome stability and regulating cell replication and death. Telomerase has functions not only to extend telomere length but also to repair DNA damage. Studies have shown that telomerase may increase cancer cell resistance to DNA-damaging anticancer agents; tamoxifen may suppress telomerase expression in breast cancer cells. This study aimed to investigate the role of telomere length and telomerase activity in breast cancer prognosis. METHODS: qPCR and qRT-PCR were used to analyze telomere length and telomerase expression, respectively, in tumor samples of 348 breast cancer patients. Cox regression analysis was performed to examine telomere length and telomerase expression in association with disease-free survival and cause-specific mortality. RESULTS: Telomere length had no relation to tumor features or disease outcomes. Telomerase expression was detected in 53% of tumors. Larger tumors or aggressive disease were more likely to have telomerase expression. Among patients treated with chemotherapy, high telomerase was found to be associated with increased risk of death (hazard ratio (HR) = 3.15; 95% CI: 1.34 to 7.40) and disease recurrence (HR = 2.04; 95% CI: 0.96 to 4.30) regardless of patient age, disease stage, tumor grade, histological type or hormone receptor status. Patients treated with endocrine therapy had different results regarding telomerase: high telomerase appeared to be associated with better survival outcomes. Telomerase expression made no survival difference in patients who received both chemotherapy and endocrine therapy. CONCLUSIONS: Overall, telomerase expression was not associated with disease outcome, but this finding may be masked by adjuvant treatment. Patients with high telomerase expression responded poorly to chemotherapy in terms of disease-free and overall survival, but fared better if treated with endocrine therapy.

Posterior intravaginal slingplasty: efficacy and complications in a continuous series of 118 cases.

INTRODUCTION AND HYPOTHESIS: Posterior intravaginal slingplasty (PIVS) is a minimally invasive procedure that aims to suspend vaginal vault. Our study evaluated efficacy and complications of PIVS at long-term follow-up. METHODS: One hundred eighteen consecutive women underwent PIVS operation for Pelvic Organ Prolapse Quantification stage 3 or 4 vaginal cuff prolapse (VCP; 25 patients) or utero-vaginal prolapse (UVP; 93 patients). Apical vaginal wall at stage 0 or 1 was considered as cured. RESULTS: Follow-up mean duration was 58.6 months (range, 24-84 months). The success rate of PIVS was 96.6%. Some 8.5% mesh erosion (20% in patients with VCP and 5.4% with UVP), 2.5% vaginal-perineal fistula, and 3.4% paravaginal hematoma occurred. Neither erosion nor fistulas occurred with monofilament polypropylene mesh. CONCLUSION: PIVS seems a safe and effective procedure for VCP and UVP. Vaginal erosion was mainly observed in patients with VCP treated with multifilament polypropylene mesh.