Search

Background: Breast cancer (BC) in women aged ≤40 years carrying germline pathogenetic variants (PVs) in BRCA1/2 genes is infrequent but often associated with aggressive features. Human epidermal growth factor receptor 2 (HER2)‐low‐expressing BC has recently emerged as a novel therapeutic target but has not been characterized in this rare patient subset. Methods: Women aged ≤40 years with newly diagnosed early‐stage HER2‐negative BC (HER2‐0 and HER2‐low) and germline BRCA1/2 PVs from 78 health care centers worldwide were retrospectively included. Chi‐square test and Student t‐test were used to describe variable distribution between HER2‐0 and HER2‐low. Associations with HER2‐low status were assessed with logistic regression. Kaplan–Meier method and Cox regression analysis were used to assess disease‐free survival (DFS) and overall survival. Statistical significance was considered for p ≤.05. Results: Of 3547 included patients, 32.3% had HER2‐low BC, representing 46.3% of hormone receptor–positive and 21.3% of triple‐negative (TN) tumors. HER2‐low vs. HER2‐0 BC were more often of grade 1/2 (p <.001), hormone receptor–positive (p <.001), and node‐positive (p =.003). BRCA2 PVs were more often associated with HER2‐low than BRCA1 PVs (p <.001). HER2‐low versus HER2‐0 showed better DFS (hazard ratio [HR], 0.86; 95% CI, 0.76–0.97) in the overall population and more favorable DFS (HR, 0.78; 95% CI, 0.64–0.95) and overall survival (HR, 0.65; 95% CI, 0.46–0.93) in the TN subgroup. Luminal A–like tumors in HER2‐low (p =.014) and TN and luminal A‐like in HER2‐0 (p =.019) showed the worst DFS. Conclusions: In young patients with HER2‐negative BC and germline BRCA1/2 PVs, HER2‐low disease was less frequent than expected and more frequently linked to BRCA2 PVs and associated with luminal‐like disease. HER2‐low status was associated with a modestly improved prognosis. Approximately 32% of human epidermal growth factor receptor 2 (HER2)‐negative breast cancer in an international multicenter cohort of 3547 women ≤40 years old with germline BRCA1/2 pathogenic variants was HER2‐low, and more frequently associated with hormone receptor–positive disease and BRCA2 variants than triple‐negative and BRCA1. HER2‐low status was associated with slightly better outcomes than HER2‐0, especially in triple‐negative tumors, without prognostic differences according to BRCA1 vs. BRCA2 variants, though within HER2‐low disease, luminal A–like tumors displayed worse disease‐free survival than luminal B–like and triple negative tumors. [ABSTRACT FROM AUTHOR]

isomiRs, the sequence‐variants of microRNA, are known to be tissue and cell type specific but their physiological role is largely unknown. In our study, we explored for the first time the expression of isomiRs across different Stage I epithelial ovarian cancer (EOC) histological subtypes, in order to shed new light on their biological role in tumor growth and progression. In a multicentric retrospective cohort of tumor biopsies (n = 215) we sequenced small RNAs finding 971 expressed miRNAs, 64% of which are isomiRs. Among them, 42 isomiRs showed a clear histotype specific pattern, confirming our previously identified miRNA markers (miR192/194 and miR30a‐3p/5p for mucinous and clear cell subtypes, respectively) and uncovering new biomarkers for all the five subtypes. Using integrative models, we found that the 38% of these miRNA expression alterations is the result of copy number variations while the 17% of differential transcriptional activities. Our work represents the first attempt to characterize isomiRs expression in Stage I EOC within and across subtypes and to contextualize their alterations in the framework of the large genomic heterogeneity of this tumor. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to estimate the cumulative risks of all cancers in women from 50 to 75 years of age with a BRCA1 or BRCA2 pathogenic variant. Methods: Participants were women with BRCA1 or BRCA2 pathogenic variants from 85 centers in 16 countries. Women were eligible if they had no cancer before the age of 50 years. Participants completed a baseline questionnaire and follow‐up questionnaires every 2 years. Women were followed from age 50 until a diagnosis of cancer, death, age 75, or last follow‐up. The risk of all cancers combined from age 50 to 75 was estimated using the Kaplan–Meier method. Results: There were 2211 women included (1470 BRCA1 and 742 BRCA2). There were 379 cancers diagnosed in the cohort between 50 and 75 years. The actuarial risk of any cancer from age 50 to 75 was 49% for BRCA1 and 43% for BRCA2. Breast (n = 186) and ovarian (n = 45) were the most frequent cancers observed. For women who had both risk‐reducing mastectomy and bilateral salpingo‐oophorectomy before age 50, the risk of developing any cancer between age 50 and 75 was 9%. Conclusion: Women with a BRCA1 or BRCA2 pathogenic variant have a high risk of cancer between the ages of 50 and 75 years and should be counselled appropriately. Women with a BRCA1 or BRCA2 pathogenic variant have a high risk of cancer after age 50 and should be counseled appropriately. [ABSTRACT FROM AUTHOR]

Background: BRCA1 and BRCA2 gene mutations are responsible for 5% of breast cancer (BC) and 10–15% of ovarian cancer (EOC). The presence of a germline mutation and therefore the identification of subjects at high risk of developing cancer should ideally precede the onset of the disease, so that appropriate surveillance and risk‐reducing treatments can be proposed. In this study, we revisited the family history (FH) of women who tested positive for BRCA mutations after being diagnosed with BC or EOC. Methods: The National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines®), and the Italian Association of Medical Oncology (AIOM) guidelines were applied to the FH of 157 women who were referred to San Gerardo Hospital for genetic counseling. Results: Almost 85% of women had an FH of BRCA‐related cancer. 63.7% and 52.2% of women could have undergone genetic testing according to NCCN and AIOM testing criteria (p <.05) before tumor diagnosis. An FH of EOC was the most frequent NCCN criterion, followed by BC diagnosed <45 years old. Sixty‐five percent of deceased women could have undergone genetic testing before developing cancer. Conclusions: FH is a powerful tool to identify high‐risk individuals eligible for genetic counseling and testing. Testing of healthy individuals should be considered when an appropriately affected family member is unavailable for testing. [ABSTRACT FROM AUTHOR]

High‐grade serous ovarian cancer (HGS‐EOCs) is generally sensitive to front‐line platinum (Pt)‐based chemotherapy although most patients at an advanced stage relapse with progressive resistant disease. Clinical or molecular data to identify primary resistant cases at diagnosis are not yet available. HGS‐EOC biopsies from 105 Pt‐sensitive (Pt‐s) and 89 Pt‐resistant (Pt‐r) patients were retrospectively selected from two independent tumor tissue collections. Pathway analysis was done integrating miRNA and mRNA expression profiles. Signatures were further validated in silico on a cohort of 838 HGS‐EOC cases from a published dataset. In all, 131 mRNAs and 5 miRNAs belonging to different functionally related molecular pathways distinguish Pt‐s from Pt‐r cases. Then, 17 out of 23 selected elements were validated by orthogonal approaches (SI signature). As resistance to Pt is associated with a short progression‐free survival (PFS) and overall survival (OS), the prognostic role of the SI signature was assessed, and 14 genes associated with PFS and OS, in multivariate analyses (SII signature). The prognostic value of the SII signature was validated in a third extensive cohort. The expression profiles of SDF2L1, PPP1R12A and PRKG1 genes (SIII signature) served as independent prognostic biomarkers of Pt‐response and survival. The study identified a prognostic molecular signature based on the combined expression profile of three genes which had never been associated with the clinical outcome of HGS‐EOC. This may lead to early identification, at the time of diagnosis, of patients who would not greatly benefit from standard chemotherapy and are thus eligible for novel investigational approaches. What's new? About 20% of women with high‐grade serous epithelial ovarian carcinoma do not respond to platinum‐based chemotherapy but molecular parameters are lacking to predict if a tumor is responsive or not. The authors compared transcriptomic data of more than a thousand tumor biopsies and show that differences in the expression profile of five functionally related pathways distinguish the biology of platinum‐sensitive from resistant cases. Three genes in these networks, SDF2L1, PPP1R12A and PRKG1, were independently associated with survival, and may thus provide a molecular signature for patients' stratification at diagnosis. [ABSTRACT FROM AUTHOR]

Introduction: Gastric cancer during pregnancy is extremely rare and data on optimal treatment and possible chemotherapeutic regimens are scarce. The aim of this study is to describe the obstetric and maternal outcome of women with gastric cancer during pregnancy and review the literature on antenatal chemotherapy for gastric cancer.Material and Methods: Treatment and outcome of patients registered in the International Network on Cancer, Infertility and Pregnancy database with gastric cancer diagnosed during pregnancy were analyzed.Results: In total, 13 women with gastric cancer during pregnancy were registered between 2002 and 2018. Median gestational age at diagnosis was 22 weeks (range 6-30 weeks). Twelve women were diagnosed with advanced disease and died within 2 years after pregnancy, most within 6 months. In total, eight out of 10 live births ended in a preterm delivery because of preeclampsia, maternal deterioration, or therapy planning. Two out of six women who initiated chemotherapy during pregnancy delivered at term. Two neonates prenatally exposed to chemotherapy were growth restricted and one of them developed a systemic infection with brain abscess after preterm delivery for preeclampsia 2 weeks after chemotherapy. No malformations were reported.Conclusions: The prognosis of gastric cancer during pregnancy is poor, mainly due to advanced disease at diagnosis, emphasizing the need for early diagnosis. Antenatal chemotherapy can be considered to reach fetal maturity, taking possible complications such as growth restriction, preterm delivery, and hematopoietic suppression at birth into account. [ABSTRACT FROM AUTHOR]

High‐grade serous epithelial ovarian cancer (HGS‐EOC) is a systemic disease, with marked intra and interpatient tumor heterogeneity. The issue of spatial and temporal heterogeneity has long been overlooked, hampering the possibility to identify those genomic alterations that persist, before and after therapy, in the genome of all tumor cells across the different anatomical districts. This knowledge is the first step to clarify those molecular determinants that characterize the tumor biology of HGS‐EOC and their route toward malignancy. In our study, ‐omics data were generated from 79 snap frozen matched tumor biopsies, withdrawn before and after chemotherapy from 24 HGS‐EOC patients, gathered together from independent cohorts. The landscape of somatic copy number alterations depicts a more homogenous and stable genomic portrait than the single nucleotide variant profile. Genomic identification of significant targets in cancer analysis identified two focal and minimal common regions (FMCRs) of amplification in the cytoband 3q26.2 (region α, 193 kb long) and 8q24.3 (region β, 495 kb long). Analysis in two external databases confirmed regions α and β are features of HGS‐EOC. The MECOM gene is located in region α, and 15 genes are in region β. No functional data are yet available for the genes in the β region. In conclusion, we have identified for the first time two FMCRs of amplification in HGS‐EOC, opening up a potential biological role in its etiopathogenesis. What's new? Genomic analysis of high‐grade serous epithelial ovarian cancer (HGS‐EOC) is currently based on primary tumor testing at the time of diagnosis but tumors often relapse, and metastasis within the abdominal cavity form almost instantaneously. Here the authors analyzed spatial and temporal molecular heterogeneity in HGS‐EOC by examining not only the primary tumor but also synchronous and matched relapse lesions. Despite tumor heterogeneity, two recurrent regions of focal amplification (3q26.2 and 8q24.3) were identified. Defining the functional role of the 16 genes that map to these two genomic regions will bring new insight into the pathogenesis of HGS‐EOC and possibly define new therapeutic targets for this deadly disease. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: Thyroid cancer, with 6% to 10% of cancer diagnoses, is one of the most common malignancies during pregnancy. Its treatment poses a risk for the pregnancy, as the thyroid gland plays a crucial role in the evolution of pregnancy. The aim of this study is to evaluate treatment of primary well-differentiated thyroid carcinoma during pregnancy and fetal and maternal outcomes.Study Design: This is an international cohort study.Methods: Primary thyroid cancer patients were identified from the database of the International Network on Cancer, Infertility, and Pregnancy registration study. Data on histopathological characteristics, diagnostic and therapeutic interventions, outcome (obstetrical, neonatal, and maternal) and maternal follow-up were analyzed.Results: Thirty-five patients with well-differentiated thyroid carcinoma were eligible. All 35 patients underwent surgery, 29 (83%) of which during pregnancy. Procedures during pregnancy were mainly total thyroidectomies (n = 24). The median number of days between diagnosis and surgical treatment was different between the groups with surgery during and after pregnancy (27 vs. 139 days, P < .001). Both maternal and neonatal outcomes were uncomplicated, regardless of gestational age during surgery.Conclusions: Well-differentiated thyroid carcinoma diagnosed during pregnancy has a favorable outcome for both mother and child. Surgical management during pregnancy has no negative impact on the pregnancy regardless of the trimester at the time of surgery. However, the potential negative effects of thyroid surgery early in pregnancy demand management of these patients in an experienced multidisciplinary team to provide the best possible care for these patients and their unborn babies.Level Of Evidence: 4. Laryngoscope, 128:1493-1500, 2018. [ABSTRACT FROM AUTHOR]

Objective: To compare differences in blood loss, operative time, and intra- and postoperative complications with the harmonic scalpel or conventional electrosurgery in the treatment of vulvar cancer.Methods: Consecutive patients who underwent radical vulvectomy with inguinal lymphadenectomy using the harmonic scalpel (HS) or conventional electrosurgery (CE) were compared.Results: A total of 42 patients were included, 22 in the HS group and 20 in the CE group. Mean blood loss was significantly less in the HS group compared with the CE group (127 mL vs 210 mL; P<0.05) and mean operative time was significantly shorter with the HS compared with CE (117 minutes vs 142 minutes; P<0.05). There were no significant differences between the 2 groups in postoperative complications.Conclusion: Use of the harmonic scalpel for surgical treatment of vulvar cancer is safe and has several advantages, including decreased operative time and blood loss, improved visibility in the operative field, and good postoperative outcome. [ABSTRACT FROM AUTHOR]

Objective: To explore the clinicopathologic findings and oncological outcome of early-stage synchronous endometrial and ovarian malignancies.Methods: A retrospective study of 93 women with synchronous stage I ovarian and stage I-II endometrial cancer treated between December 1981 and August 2005 in the gynecologic oncology department of San Gerardo Hospital, Italy.Results: Fifty-one percent of the ovarian tumors were stage Ia and 71% of the endometrial cancers had minimal myometrial invasion. Endometrioid histology and grade 2 disease were prevalent in both sites. Hyperplasia and endometriosis coexisted in 71% and 22% of endometrial and ovarian cancers, respectively. The actuarial 5-year disease-free and overall survival rates were 83% and 96%, respectively.Conclusion: The incidence of synchronous endometrial and ovarian cancer is not negligible, especially among young women. Synchronous cancers show very favorable pathologic features and have an excellent oncologic outcome. Adjuvant therapy should be tailored according to surgical staging and histology. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To evaluate the effect of TachoSil in preventing postoperative complications after groin dissection performed for primary or recurrent gynecologic malignancy. Methods: In a case–control analysis, the incidence of postoperative complications—including lymphocyst formation, wound breakdown and/or infection, and chronic lymphedema—was examined among 8 patients who received TachoSil and 16 controls (standard technique) treated for vulvar cancer or recurrent ovarian/breast cancer at San Gerardo Hospital, Monza, Italy, from 2008 to 2011. Results: Thirty-eight inguinal dissections were performed in the 24 patients. Bilateral groin dissection was performed in 14 patients (n=4 in the study group; n=10 in the control group). Patients in the study group had a lower mean daily drainage volume than those in the control group (133mL [range, 50–356mL] vs 320mL [range, 67–472mL]; P <0.001) and a lower incidence of lymphocyst requiring drainage (25.0% vs 62.5%), cellulitis (12.0% vs 25.0%), and wound infection (0.0% vs 25.0%). Conclusion: The use of TachoSil seems to be effective in reducing the rate of postoperative complications after inguinofemoral lymphadenectomy in cases of gynecologic malignancy. [Copyright &y& Elsevier]

Malignant transformation of extragonadal endometriosis is a described. A 40-year-old multiparous woman presented with dyspareunia and dysmenorrhea. Physical examination revealed a 3 × 3.5 cm vaginal nodule. The histological examination of a bioptic sample revealed a moderately differentiated endometrioid adenocarcinoma. The patient was treated with neoadjuvant chemotherapy followed by surgery and is free from disease after 24 months. The frequency of malignant transformation of vaginal endometriosis is unknown. Obesity, hyperestrogenism, and exposure to unopposed estrogen are known risk factors, but were not present in the medical history of the present patient. In our case, preoperative chemotherapy allowed a complete resection without a vaginal demolitive surgery. This therapeutic option may be considered in order to reduce surgical resection and to preserve sexual function. However, because of the rarity of this disease, it is difficult to establish a standard treatment. [ABSTRACT FROM AUTHOR]

Objective Design Setting Population Methods Main Outcome Measures Results Conclusions To characterise pregnant women diagnosed with primary or recurrent cancer who died during pregnancy, during delivery or within 1 year postpartum.A descriptive study.The registry of the International Network on Cancer, Infertility and Pregnancy (INCIP).Women diagnosed with cancer during pregnancy between 2000 and 2022.Using the INCIP registry database, we compared the characteristics of all women with cancer who died during pregnancy, delivery or within 1 year postpartum with those of all women with cancer who survived the first year postpartum.Maternal and tumour characteristics and obstetrical and neonatal outcomes.Of the 2359 women registered in INCIP, there were 131 cases (5.6%) of maternal mortality. Lung cancer (9/14, 64.3% of all registered women with lung cancer), gastro‐oesophageal cancer (13/21, 61.9%) and acute leukaemia (17/105, 16.2%) had the highest rates of maternal mortality. Maternal mortality was associated with fewer live births compared with the control group without maternal mortality (99/131, 75.6%, vs 1952/2163, 90.0%; P < 0.001), more elective caesarean sections (64/104, 60.4%, vs 756/1836, 41.2%; P < 0.001) and a lower gestational age at (induced) delivery (34.0 vs 37.1 weeks; P < 0.001), resulting in more preterm births.Maternal mortality occurred in 5.6% of cancer‐in‐pregnancy cases and is associated with adverse perinatal outcomes. [ABSTRACT FROM AUTHOR]