Rethinking surgical revisions: impact of the MonarchE trial on axillary dissection in hormone-positive HER2-negative early breast cancer patients potentially eligible for abemaciclib.

INTRODUCTION: The MonarchE trial explored the use of abemaciclib, a CDK4/6 inhibitor, as an adjuvant treatment in high-risk early-stage luminal-like breast cancer. The study's inclusion criteria, especially the N2 status, may require revisiting surgical interventions, including invasive axillary lymph node dissection (ALND)-a procedure that current guidelines generally do not recommend. METHODS: We conducted a single-centre, retrospective, observational cohort study on non-metastatic breast cancer patients managed from 2002 to 2011, at the Institut Curie. Data collection involved clinical and histological characteristics plus treatment follow-up. RESULTS: Out of 8715 treated patients, 721 met the inclusion criteria. Overall, 12% (87) were classified as N2 ( ≥ 4 positive lymph nodes), thus eligible for abemaciclib per "node criterion." Tumour size, positive sentinel lymph nodes, and lobular histology showed a significant correlation with N2 status. Approximately 1000 ALNDs would be required to identify 120 N2 cases and prevent four recurrences. CONCLUSION: The MonarchE trial may significantly affect surgical practices due to the need for invasive procedures to identify high-risk patients for adjuvant abemaciclib treatment. The prospect of unnecessary morbidity demands less invasive N2 status determination methods. Surgical decisions must consider patient health and potential treatment benefits.

Preoperative brachytherapy of early-stage cervical cancer: A multicenter study by the SFRO brachytherapy group.

OBJECTIVE: To report the results of a multicenter cohort of preoperative brachytherapy (PBT) for treatment of early-stage cervical cancer (ESCC). METHODS: A retrospective analysis was conducted among five French comprehensive cancer centers on behalf of the SFRO Brachytherapy Group to examine the outcome of patients with ESCC who received PBT between 2001 and 2019 because of adverse prognostic factors (tumor size >2 cm, presence of lymphovascular invasion, adenocarcinoma).Brachytherapy was followed 4-8 weeks later by surgery. Local relapse free, distant metastasis-free survival, disease-free, and overall survival and adverse effects were examined. Uni- and multivariate analyses were conducted looking for oncological prognostic factors. RESULTS: A total of 451 patients were identified, with a mean tumor size of 24.7 mm. Adenocarcinoma accounted for 43.5% of cases, and lympho-vascular space invasion (LVSI) was present in 15.7%. A complete histological response was observed in 69.6%. With a mean follow-up of 75.4 months, DFS, LRFS, and OS rates at five years were 88% [95% CI (84-91), 98% [95% CI (96-99), and 92% [95% CI (87-95)], respectively. At the last follow-up, 8.2% of patients had died, including 31 (6.8%) from cervical cancer. Severe side effects range from 1.1% to 2%. At multivariate analysis, adenocarcinoma histological type, tumor size ≥2 cm, and the presence of residual tumors were prognosticators for DFS and DMFS. CONCLUSION: PBT shows excellent oncological outcomes in this cohort of patients with adverse histoprognostic factors. Favorable survival rates and low complications rates were observed, supporting this strategy in the management of ESCC.

Percutaneous Uterine Needle Biopsy with Microscopic and Array-CGH Analyses for Preoperative Sarcoma Diagnosis in Patients with Suspicious Myometrial Tumors on MRI: A Prospective Pilot Study (SARCGYN).

BACKGROUND: Unlike for soft tissue sarcomas, percutaneous biopsy is not validated for uterine myometrial tumors, leading to leiomyosarcoma inadvertent morcellation and overtreatment in childbearing patients. This study aimed to evaluate preoperative percutaneous uterine needle biopsy (PUB) with microscopic examination (M-PUB) and array-comparative genomic hybridization (MCGH-PUB). METHODS: This was a prospective single-center cohort study including all consecutive patients who were candidates for hysterectomy because of suspected uterine leiomyosarcoma on magnetic resonance imaging (MRI) who received PUB. Microscopic and array-CGH analyses with genomic index (GI) counts were performed to guide the therapeutic strategy. Smooth-muscle tumors with suspect features with a GI above 15 were deemed malignant, as were tumors without microscopic malignant features with a complex genomic profile (GI above 30 or malignant profile). Preoperative diagnoses based on M-PUB and MCGH-PUB were compared with the postsurgical pathological specimen or follow-up. RESULTS: From November 2016 to February 2022, 34 patients were included. Based on the surgical specimen (N = 23) or follow-up (N = 11), final diagnoses were 11 sarcomas and 23 non-sarcomas. The median follow-up was 12 months (IQR 6-37). The diagnostic accuracies of M-PUB and MCGH-PUB were 94% and 100%, respectively. The sensitivity, specificity, and negative predictive value of MCGH-PUB were 100%, 100%, and 100%, respectively. A high GI was significantly associated with malignancy (P < 0.001). Genomic analyses allowed malignancy upgrades for four tumors. There were no complications and no dissemination along the biopsy track. CONCLUSION: MCGH-PUB is safe and accurate for preoperatively diagnosing uterine sarcomas and should be used routinely after suspicious MRI to tailor surgery.

Impact of surgery and chemotherapy in ovarian sex cord-stromal tumors from the multicentric Salomé study including 469 patients. A TMRG and GINECO group study.

OBJECTIVE: Identifying prognostic factors and evaluating the impact of adjuvant chemotherapy in patients with sex cord stromal tumors (SCST) is crucial. In this study, we aimed to address these challenges. METHODS: We conducted a retrospective analysis of data from 13 centers of the French Rare malignant gynecological tumors (TMRG) network. We enrolled 469 adult patients with malignant SCST who received upfront surgery since 2011 to July 2015. RESULTS: 75% were diagnosed with adult Granulosa cell tumors, and 23% had another subtype. With a median follow-up of 6.4 years, 154 patients (33%) developed a first recurrence, 82 (17%) two recurrences, and 49 (10%) three recurrences. Adjuvant chemotherapy was administered in 14.7% of patients at initial diagnosis. In relapse, perioperative chemotherapy was administered in 58.5%, 28.2%, and 23.8% of patients, respectively, in the first, second, and third relapse. In the first-line therapy, age under 70 years, FIGO stage, and complete surgery were associated with longer progression-free survival (PFS). Chemotherapy had no impact on PFS in early-stage disease (FIGO I-II). The PFS was similar using BEP or other chemotherapy regimens (HR 0.88 [0.43; 1.81]) in the first-line therapy. In case of recurrence, PFS was statistically prolonged by complete surgery, but perioperative chemotherapy use did not impact PFS. CONCLUSION: Chemotherapy use did not impact survival in the first-line or relapse setting in SCST. Only surgery and its quality demonstrated benefit for PFS in ovarian SCST in any lines of treatment.

Exploring the added value of pretherapeutic MR descriptors in predicting breast cancer pathologic complete response to neoadjuvant chemotherapy.

OBJECTIVES: To evaluate the association between pretreatment MRI descriptors and breast cancer (BC) pathological complete response (pCR) to neoadjuvant chemotherapy (NAC). MATERIALS AND METHODS: Patients with BC treated by NAC with a breast MRI between 2016 and 2020 were included in this retrospective observational single-center study. MR studies were described using the standardized BI-RADS and breast edema score on T2-weighted MRI. Univariable and multivariable logistic regression analyses were performed to assess variables association with pCR according to residual cancer burden. Random forest classifiers were trained to predict pCR on a random split including 70% of the database and were validated on the remaining cases. RESULTS: Among 129 BC, 59 (46%) achieved pCR after NAC (luminal (n = 7/37, 19%), triple negative (n = 30/55, 55%), HER2 + (n = 22/37, 59%)). Clinical and biological items associated with pCR were BC subtype (p < 0.001), T stage 0/I/II (p = 0.008), higher Ki67 (p = 0.005), and higher tumor-infiltrating lymphocytes levels (p = 0.016). Univariate analysis showed that the following MRI features, oval or round shape (p = 0.047), unifocality (p = 0.026), non-spiculated margins (p = 0.018), no associated non-mass enhancement (p = 0.024), and a lower MRI size (p = 0.031), were significantly associated with pCR. Unifocality and non-spiculated margins remained independently associated with pCR at multivariable analysis. Adding significant MRI features to clinicobiological variables in random forest classifiers significantly increased sensitivity (0.67 versus 0.62), specificity (0.69 versus 0.67), and precision (0.71 versus 0.67) for pCR prediction. CONCLUSION: Non-spiculated margins and unifocality are independently associated with pCR and can increase models performance to predict BC response to NAC. CLINICAL RELEVANCE STATEMENT: A multimodal approach integrating pretreatment MRI features with clinicobiological predictors, including tumor-infiltrating lymphocytes, could be employed to develop machine learning models for identifying patients at risk of non-response. This may enable consideration of alternative therapeutic strategies to optimize treatment outcomes. KEY POINTS: • Unifocality and non-spiculated margins are independently associated with pCR at multivariable logistic regression analysis. • Breast edema score is associated with MR tumor size and TIL expression, not only in TN BC as previously reported, but also in luminal BC. • Adding significant MRI features to clinicobiological variables in machine learning classifiers significantly increased sensitivity, specificity, and precision for pCR prediction.

Digital phenotyping in young breast cancer patients treated with neoadjuvant chemotherapy (the NeoFit Trial): protocol for a national, multicenter single-arm trial.

BACKGROUND: Breast cancer (BC) has particular characteristics in young women, with diagnosis at more advanced stages, a poorer prognosis and highly aggressive tumors. In NeoFit, we will use an activity tracker to identify and describe various digital profiles (heart rate, physical activity, and sleep patterns) in women below the age of 45 years on neoadjuvant chemotherapy for BC. METHODS: NeoFit is a prospective, national, multicenter, single-arm open-label study. It will include 300 women below the age of 45 years treated with neoadjuvant chemotherapy for BC. Participants will be asked to wear a Withing Steel HR activity tracker round the clock for 12 months. The principal assessments will be performed at baseline, at the end of neoadjuvant chemotherapy and at 12 months. We will evaluate clinical parameters, such as toxicity and the efficacy of chemotherapy, together with quality of life, fatigue, and parameters relating to lifestyle and physical activity. The women will complete REDCap form questionnaires via a secure internet link. DISCUSSION: In this study, the use of an activity tracker will enable us to visualize changes in the lifestyle of young women on neoadjuvant chemotherapy for BC, over the course of a one-year period. This exploratory study will provide crucial insight into the digital phenotypes of young BC patients on neoadjuvant chemotherapy and the relationship between these phenotypes and the toxicity and efficacy of treatment. This trial will pave the way for interventional studies involving sleep and physical activity interventions. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT05011721 . Registration date: 18/08/2021.

Pregnancy, fertility concerns and fertility preservation procedures in a national study of French breast cancer survivors.

RESEARCH QUESTION: What are the real-life oncofertility practices in young women diagnosed with breast cancer? DESIGN: The FEERIC (FErtility, prEgnancy, contRaceptIon after breast Cancer in France) study is a web-based cohort study launched with the French collaborative research platform Seintinelles. The current work is based on the enrolment self-administered questionnaire of 517 patients with prior breast cancer diagnosis, free from relapse and aged 18 to 43 years at inclusion (from 12 March 2018 to 27 June 2019). RESULTS: Median age at breast cancer diagnosis was 33.6 years and 424 patients (82.0%) received chemotherapy. Overall, 236 (45.6%) patients were offered specialized oncofertility counselling, 181 patients underwent at least one fertility preservation procedure (FPP); 125 (24.2%) underwent one or more FPP with material preservation (oocytes n = 108, 20.9%; embryos n = 31, 6.0%; ovarian cryopreservation n = 6, 1.2%) and 78 patients received gonadotrophin-releasing hormone agonists (15.1%). With a median follow-up of 26.9 months after the end of treatments, 133 pregnancies had occurred in 85 patients (16.4%), including 20 unplanned pregnancies (15.0%). Most of the pregnancies were natural conceptions (n = 113, 87.6%), while 16 (12.4%) required medical interventions. For the planned pregnancies, median time to the occurrence of an ongoing pregnancy was 3 months. Patients who had an unplanned pregnancy reported lower rates of information on the consequences of the treatments on fertility (P = 0.036) at diagnosis. CONCLUSIONS: Most of the patients were not offered proper specialized oncofertility counselling at the time of breast cancer diagnosis. Naturally conceived pregnancies after breast cancer were much more frequent than pregnancies resulting from the use of cryopreserved gametes. Adequate contraceptive counselling seems as important as information about fertility and might prevent unplanned pregnancies.

Uptake of Recommendations for Posttreatment Cancer-Related Fatigue Among Breast Cancer Survivors.

BACKGROUND: Physical activity (PA) and psychosocial interventions are recommended management strategies for cancer-related fatigue (CRF). Randomized trials support the use of mind-body techniques, whereas no data show benefit for homeopathy or naturopathy. METHODS: We used data from CANTO (ClinicalTrials.gov identifier: NCT01993498), a multicenter, prospective study of stage I-III breast cancer (BC). CRF, evaluated after primary treatment completion using the EORTC QLQ-C30 (global CRF) and QLQ-FA12 (physical, emotional, and cognitive dimensions), served as the independent variable (severe [score of ≥40/100] vs nonsevere). Outcomes of interest were adherence to PA recommendations (≥10 metabolic equivalent of task [MET] h/week [GPAQ-16]) and participation in consultations with a psychologist, psychiatrist, acupuncturist, or other complementary and alternative medicine (CAM) practitioner (homeopath and/or naturopath) after CRF assessment. Multivariable logistic regression examined associations between CRF and outcomes, adjusting for sociodemographic, psychologic, tumor, and treatment characteristics. RESULTS: Among 7,902 women diagnosed from 2012 through 2017, 36.4% reported severe global CRF, and 35.8%, 22.6%, and 14.1% reported severe physical, emotional, and cognitive CRF, respectively. Patients reporting severe global CRF were less likely to adhere to PA recommendations (60.4% vs 66.7%; adjusted odds ratio [aOR], 0.82; 95% CI, 0.71-0.94; P=.004), and slightly more likely to see a psychologist (13.8% vs 7.5%; aOR, 1.29; 95% CI, 1.05-1.58; P=.014), psychiatrist (10.4% vs 5.0%; aOR, 1.39; 95% CI, 1.10-1.76; P=.0064), acupuncturist (9.8% vs 6.5%; aOR, 1.46; 95% CI, 1.17-1.82; P=.0008), or CAM practitioner (12.5% vs 8.2%; aOR, 1.49; 95% CI, 1.23-1.82; P<.0001). There were differences in recommendation uptake by CRF dimension, including that severe physical CRF was associated with lower adherence to PA (aOR, 0.74; 95% CI, 0.63-0.86; P=.0001) and severe emotional CRF was associated with higher likelihood of psychologic consultations (aOR, 1.37; 95% CI, 1.06-1.79; P=.017). CONCLUSIONS: Uptake of recommendations to improve CRF, including adequate PA and use of psychosocial services, seemed suboptimal among patients with early-stage BC, whereas there was a nonnegligible interest in homeopathy and naturopathy. Findings of this large study indicate the need to implement recommendations for managing CRF in clinical practice.

Variation over time of the factors influencing return to work and work capacities after a diagnosis of breast cancer: a study on the behalf of the Seintinelles research network.

PURPOSE: To evaluate the dynamics of the determinants of returning to work (RTW) in a population of patients treated for breast cancer (BC) in a real-world setting. METHOD: We conducted a retrospective study including 1278 BC patients working or looking for work at the time of diagnosis. We performed a focused principal component analysis to highlight the dimensions of a persistent decline in work capacity. Logistic regression analyses were performed to identify correlates of non-RTW 1 and 2 years after treatment. RESULTS: One-third (31%, n = 389) of patients continued working during treatment. At study inclusion, 1100 patients had returned to work (89%). Three-quarters (n = 508, 75%) of the women reported a decline in work capacity 1 year after RTW and 22% (n = 148) presented a persistent decline in work capacity 2 years after the diagnosis. The odds ratio for non-RTW at 1 year was significantly higher for patients treated with a combination of chemotherapy and trastuzumab (OR = 1.72, 95% CI [1.07-2.76]), manual workers (OR = 3.99, 95% CI [1.54-10.81]), patients with lower incomes (OR = 2.33, 95% CI [1.29-4.19]), and patients experiencing fatigue (OR = 1.81, 95% CI [1.34-2.48]). The odds ratio for non-RTW at 2 years was higher for various occupational categories (OR = 3.49, 95% CI [1.89-6.74] for clerks, OR = 4.58, 95% CI [1.48-12.82] for self-employed workers, OR = 8.98, 95% CI [2.69-27.89] for manual workers), patients with comorbidities (OR = 2.80, 95% CI [1.61-4.93]), and patients experiencing anxiety symptoms (OR = 2.54, 95% CI [1.18-5.76]), while the impact of the type of treatment was no longer significantly associated with RTW. CONCLUSION: The determinants of RTW change over time. Patients should be offered supportive interventions tailored to risk factors and time from diagnosis.

Determination of breast cancer prognosis after neoadjuvant chemotherapy: comparison of Residual Cancer Burden (RCB) and Neo-Bioscore.

BACKGROUND: To compare RCB (Residual Cancer Burden) and Neo-Bioscore in terms of prognostic performance and see if adding pathological variables improve these scores. METHODS: We analysed 750 female patients with invasive breast cancer (BC) treated with neoadjuvant chemotherapy (NAC) at Institut Curie between 2002 and 2012. Scores were compared in global population and by BC subtype using Akaike information criterion (AIC), C-Index (concordance index), calibration curves and after adding lymphovascular invasion (LVI) and pre-/post-NAC TILs levels. RESULTS: RCB and Neo-Bioscore were significantly associated to disease-free and overall survival in global population and for triple-negative BC. RCB had the lowest AICs in every BC subtype, corresponding to a better prognostic performance. In global population, C-Index values were poor for RCB (0.66; CI [0.61-0.71]) and fair for Neo-Bioscore (0.70; CI [0.65-0.75]). Scores were well calibrated in global population, but RCB yielded better prognostic performances in each BC subtype. Concordance between the two scores was poor. Adding LVI and TILs improved the performance of both scores. CONCLUSIONS: Although RCB and Neo-Bioscore had similar prognostic performances, RCB showed better performance in BC subtypes, especially in luminal and TNBC. By generating fewer prognostic categories, RCB enables an easier use in everyday clinical practice.

Oncologic outcomes of endometrial cancer in patients with low-volume metastasis in the sentinel lymph nodes: An international multi-institutional study.

OBJECTIVE: To assess oncologic outcomes in endometrial cancer patients with low-volume metastasis (LVM) in the sentinel lymph nodes (SLNs). METHODS: Patients with endometrial cancer and SLN-LVM (≤2 mm) from December 3, 2009, to December 31, 2018, were retrospectively identified from 22 centers worldwide. Patients with International Federation of Gynecology and Obstetrics (FIGO) stage IV, adnexal involvement, or unknown adjuvant therapy (ATx) were excluded. RESULTS: Of 247 patients included, 132 had isolated tumor cell (ITC) and 115 had micrometastasis (MM). Overall 4-year recurrence-free survival (RFS) was 77.6% (95% CI, 70.2%-85.9%); median follow-up for patients without recurrence was 29.6 (interquartile range, 19.2-41.5) months. At multivariate analysis, Non-endometrioid (NE) (HR, 5.00; 95% CI, 2.50-9.99; P < .001), lymphovascular space invasion (LVSI) (HR, 3.26; 95% CI, 1.45-7.31; P = .004), and uterine serosal invasion (USI) (HR, 3.70; 95% CI, 1.44-9.54; P = .007) were independent predictors of recurrence. Among 47 endometrioid ITC patients without ATx, 4-year RFS was 82.6% (95% CI, 70.1%-97.2). Considering 18 ITC patients with endometrioid grade 1 disease, without LVSI, USI, or ATx, only 1 had recurrence (median follow-up, 24.8 months). CONCLUSIONS: In patients with SLN-LVM, NE, LVSI, and USI were independent risk factors for recurrence. Patients with any risk factor had poor prognosis, even when receiving ATx. Patients with ITC and grade 1 endometrioid disease (no LVSI/USI) had favorable prognosis, even without ATx. Further analysis (with more patients and longer follow-up) is needed to assess whether ATx can be withheld in this low-risk subgroup.

COVID-19 in breast cancer patients: a cohort at the Institut Curie hospitals in the Paris area.

BACKGROUND: Cancer patients have been reported to be at higher risk of COVID-19 complications and deaths. We report the characteristics and outcome of patients diagnosed with COVID-19 during breast cancer treatment at Institut Curie hospitals (ICH, Paris area, France). METHODS: An IRB-approved prospective registry was set up at ICH on March 13, 2020, for all breast cancer patients with COVID-19 symptoms or radiologic signs. Registered data included patient history, tumor characteristics and treatments, COVID-19 symptoms, radiological features, and outcome. Data extraction was done on April 25, 2020. COVID-19 patients were defined as those with either a positive RNA test or typical, newly appeared lung CT scan abnormalities. RESULTS: Among 15,600 patients actively treated for early or metastatic breast cancer during the last 4 months at ICH, 76 patients with suspected COVID-19 infection were included in the registry and followed. Fifty-nine of these patients were diagnosed with COVID-19 based on viral RNA testing (N = 41) or typical radiologic signs: 37/59 (63%) COVID-19 patients were treated for metastatic breast cancer, and 13/59 (22%) of them were taking corticosteroids daily. Common clinical features mostly consisted of fever and/or cough, while ground-glass opacities were the most common radiologic sign at diagnosis. We found no association between prior radiation therapy fields or extent of radiation therapy sequelae and extent of COVID-19 lung lesions. Twenty-eight of these 59 patients (47%) were hospitalized, and 6 (10%) were transferred to an intensive care unit. At the time of analysis, 45/59 (76%) patients were recovering or had been cured, 10/59 (17%) were still followed, and 4/59 (7%) had died from COVID-19. All 4 patients who died had significant non-cancer comorbidities. In univariate analysis, hypertension and age (> 70) were the two factors associated with a higher risk of intensive care unit admission and/or death. CONCLUSIONS: This prospective registry analysis suggests that the COVID-19 mortality rate in breast cancer patients depends more on comorbidities than prior radiation therapy or current anti-cancer treatment. Special attention must be paid to comorbidities when estimating the risk of severe COVID-19 in breast cancer patients.

HPV DNA integration site as proof of the origin of ovarian metastasis from endocervical adenocarcinoma: three case reports.

BACKGROUND: Most endocervical adenocarcinomas are human papillomavirus (HPV)-related cancers associated with p16 immunostaining. Ovarian metastasis from cervical cancer is a rare phenomenon, the mechanism of dissemination remains unclear. The diagnosis of metastasis may be difficult to establish when the ovarian neoplasm presents features consistent with primary tumor. Immunohistochemical expression of p16 in ovarian tumors can guide the diagnosis of metastasis from HPV-related cervical cancer, but p16 positivity is nonspecific. Identical HPV genotype in the paired endocervical and ovarian tumors is a better marker for cervical origin, which may also be confirmed by identical HPV integration site. CASE PRESENTATION: Two women presented with HPV18 cervical adenocarcinoma. No signs of disease were visible on MRI after treatment. After several years of follow-up, mucinous ovarian tumors were discovered in both patients. Molecular analyses showed that the ovarian lesions were HPV18-positive; indicating a primary cervical origin. A third woman was diagnosed with grade 1 ovarian endometrioid carcinoma with no peritoneal carcinomatosis. Final histological examination and HPV genotyping revealed HPV18-related in situ endometrioid adenocarcinoma in the endocervix and HPV18-related invasive endometrioid adenocarcinoma in the endometrium and both ovaries. Additional molecular analyses performed in two patients identified the same HPV integration sites in both the ovarian and cervical tumors, confirming that the ovarian mass was a metastasis from the cervical adenocarcinoma. CONCLUSION: We report three new cases of ovarian neoplasia in which the diagnosis of metastasis from cervical cancer was supported by the same HPV genotype and the same integration site in the paired cervical and ovarian tumors. To our knowledge, this is the first report of molecular evidence of the cervical origin of an ovarian metastasis. HPV screening should be performed in ovarian tumors for all patients with history of cervical neoplasia.

Lymphovascular invasion after neoadjuvant chemotherapy is strongly associated with poor prognosis in breast carcinoma.

PURPOSE: Few studies evaluated the prognostic value of the presence of lymphovascular invasion (LVI) after neoadjuvant chemotherapy (NAC) for breast cancer (BC). METHODS: The association between LVI and survival was evaluated in a cohort of BC patients treated by NAC between 2002 and 2011. Five post-NAC prognostic scores (ypAJCC, RCB, CPS, CPS + EG and Neo-Bioscore) were evaluated and compared with or without the addition of LVI. RESULTS: Out of 1033 tumors, LVI was present on surgical specimens in 29.2% and absent in 70.8% of the cases. Post-NAC LVI was associated with impaired disease-free survival (DFS) (HR 2.54; 95% CI 1.96-3.31; P < 0.001), and the magnitude of this effect depended on BC subtype (Pinteraction = 0.003), (luminal BC: HR 1.83; P = 0.003; triple negative BC: HR 3.73; P < 0.001; HER2-positive BC: HR 6.21; P < 0.001). Post-NAC LVI was an independent predictor of local relapse, distant metastasis, and overall survival; and increased the accuracy of all five post-NAC prognostic scoring systems. CONCLUSIONS: Post-NAC LVI is a strong independent prognostic factor that: (i) should be systematically reported in pathology reports; (ii) should be used as stratification factor after NAC to propose inclusion in second-line trials or adjuvant treatment; (iii) should be included in post-NAC scoring systems.

Preoperative quality of life questionnaires are an adequate tool to select women with genital prolapse for laparoscopic sacrocolpopexy.

INTRODUCTION AND HYPOTHESIS: No clear consensus exists on the selection of patients with pelvic organ prolapse (POP) for surgery. There is a need to preoperatively identify candidates who will benefit from surgery as there is no strict correlation between POP anatomical abnormalities and changes in symptoms and quality of life (QOL) after surgical treatment. Therefore, our objectives were to evaluate the changes in QOL after laparoscopic sacrocolpopexy (LSC) for POP using validated questionnaires and to assess their relevance in selecting women for surgery. METHODS: This was a prospective study of 48 women with advanced stages of POP treated by LSC from March 2005 to January 2015. We developed a recursive partitioning model from QOL PFDI-20 and PFIQ-7 questionnaire scores to determine a preoperative cut-off score for predicting improvement after surgery. The model was then validated in 84 consecutive women. RESULTS: Optimal anatomical results were obtained in 129 of the 132 women (97.7%). Both questionnaires revealed a significant improvement after LSC (p < 0.01). The probability of improvement after surgery was 0% in women with a preoperative PFIQ-7 score of <45.25, and 84% in women with a PFIQ-7 score of ≥45.25. The probability of improvement after surgery was 0% in women with a preoperative PFDI-20 score of <52.15, 88.2% in those with a PFDI-20 score of ≥ 98.45, and 42.9% in those with a PFDI-20 score between 52.15 and 98.45. In the validation set, the discriminatory accuracies of the model were 0.96 (95% CI 0.925-0.998) and 0.75 (95% CI 0.64-0.85) for the PFIQ-7 and PFDI-20 questionnaires, respectively. The performance was accurate with a significant difference between observed outcome frequencies and predicted probabilities (p = 1). CONCLUSIONS: Our results support the use QOL questionnaires to select women for LSC.

Impact of preterm birth on infant mortality for newborns with congenital heart defects: The EPICARD population-based cohort study.

BACKGROUND: Congenital heart defects (CHD) and preterm birth (PTB) are major causes of infant mortality. However, limited data exist on risk of mortality associated with PTB for newborns with CHD. Our objective was to assess impact of PTB on risk of infant mortality for newborns with CHD, while taking into account the role of associated anomalies and other potentially confounding factors. METHODS: We used data on 2172 live births from a prospective population-based cohort study of CHD (the EPICARD Study) and compared neonatal, post-neonatal and overall infant mortality for infants born at <32, 32-34 and 35-36 weeks vs. those born at term (37-41 weeks). RESULTS: Preterm newborns had a 3.8-fold higher risk of infant death (17.9%) than term newborns (4.7%), RR 3.8, 95%CI 2.7-5.2; the risk associated with PTB was more than four-fold higher for neonatal (RR 4.3, 95% CI 2.9-6.6) and three-fold higher for post-neonatal deaths (RR 3.0, 95% CI 1.7-5.2). Survival analysis showed that newborns <35 weeks had a higher risk of mortality, which decreased but persisted after exclusion of associated anomalies and adjustment for potential confounders. CONCLUSIONS: Preterm birth is associated with an approximately four-fold higher risk of infant mortality for newborns with CHD. This excess risk appears to be mostly limited to newborns <35 weeks of gestation and is disproportionately due to early deaths.

Supervised Clustering of Adipokines and Hormonal Receptors Predict Prognosis in a Population of Obese Women with Type 1 Endometrial Cancer.

Obesity is a major risk factor for endometrial cancer (EC). Yet, its impact on prognosis is controversial. Obesity is associated with metabolic and hormonal dysregulation as well as adipokines increase. The aim of this study was to characterize the expression of biological factors related to obesity within the tumor and evaluate their impact on prognosis. One hundred and thirty-six patients, including 55 obese patients, with endometrioid type I EC operated by total hysterectomy were included in this retrospective study conducted in a Tertiary teaching hospital between 2000 and 2013. Immunohistochemistry (IHC) study was performed on type I EC tumor samples using five adipokines (SPARC, RBP4 (Retinol Binding Protein 4), adiponectin, TNF α, IL-6) and hormonal receptors (estrogen receptor and progesterone receptor). Supervised clustering of immunohistochemical markers was performed to identify clusters that could be associated with prognostic groups. The prognosis of the obese population was not different from the prognosis of the general population. Adipokine expression within tumors was not different in these two populations. In obese population, we found three clusters where co-expression was associated with a recurrence group in comparison with a non-recurrence group and four clusters where co-expression was associated with the high risk FIGO (International Federation of Gynecology and Obstetrics) stage I group in comparison of low risk FIGO stage I group. While obesity does not appear as a prognostic factor in endometrioid type I EC, the co-expression of biological factors in IHC on hysterectomy specimens allowed to distinguish two prognostic groups in obese population.

Identification of microRNA expression profile related to lymph node status in women with early-stage grade 1-2 endometrial cancer.

Conventional methods used for histologic classification and grading of endometrial cancer (EC) are not sufficient to predict lymph node metastases. microRNA signatures have recently been related to EC pathologic characteristics or prognosis. The aim of this study was to evaluate whether microRNA profiles of grade 1-2 endometrioid adenocarcinomas can be related to nodal status and used as a tool to adapt surgical staging in early-stage EC. microRNA expression was assessed in nine formalin-fixed paraffin-embedded (FFPE) EC primary tumors with positive lymph node and in 27 FFPE EC primary tumors with negative lymph node, matched for grade, stage, and lymphovascular space involvement status. A microarray analysis showed that there was more than a twofold significant difference in the expression of 12 microRNAs between the two groups. A quantitative reverse transcriptase-PCR assay was used to confirm these results: the expression levels of five microRNAs (microRNA-34c-5p, -375, -184, -34c-3p, and -34b-5p) were significantly lower in the EC primary tumor with positive lymph node compared with those with negative lymph node. A minimal P-value approach revealed that women with a microRNA-375-fold change <0.30 were more likely to have positive lymph node (n=8; 53.3%) compared with those with a microRNA-375-fold change >0.30 (n=1; 4.8%), P=0.001. Furthermore, women with a microRNA 184-fold change <0.30 were more likely to have positive lymph node (n=6; 60.0%) compared with those with a microRNA 184-fold change >0.30 (n=3; 11.5%), P=0.006. This is the first study investigating the relative expression of mature microRNA genes in early-stage grade 1-2 EC primary tumors according to the nodal status. This microRNA expression profile provides a potential basis for further study of the microRNA function in EC and could be used as a diagnostic tool for nodal status.

Single-Port Extra- and Transperitoneal Approach for Paraaortic Lymphadenectomy in Gynecologic Cancers: A Propensity-Adjusted Analysis.

BACKGROUND: Endoscopic paraaortic lymphadenectomy (PALN), an important step in the management of gynecologic cancers, is associated with low morbidity. However, some concerns exist about the completeness of PALN according to the route (transperitoneal vs. single-port extraperitoneal). METHODS: This study retrospectively reviewed the records of patients who had undergone an endoscopic PALN for a gynecologic cancer from May 2010 to August 2014 at the authors' center. The findings showed that 44 patients had a single-port extraperitoneal PALN and 56 had a transperitoneal PALN. The factors independently related to technical performances were tested with a multivariate model adjusted for a propensity score. RESULTS: A median of 16 lymph nodes were removed by the transperitoneal route and 12 by the extraperitoneal route (p = 0.04). No difference in the number of lymph nodes removed was observed after adjustment for the propensity score of patients who underwent the extraperitoneal approach (p = 0.9). The transperitoneal route was associated with more lymphocysts (20 vs. 2% for the extraperitoneal approach) (p = 0.008). The success rate for the extraperitoneal PALN was 91% (n = 40), with the three remaining patients requiring conversion to the transperitoneal route due to a peritoneal breach. CONCLUSION: This propensity-score-adjusted study supports the conclusion that the efficacy of the single-port extraperitoneal route is similar to that of the transperitoneal route for PALN.