Surgical Implications of Advanced Low-Grade Serous Ovarian Cancer: Analysis of the Database of the Tumeurs Malignes Rares Gynécologiques Network.

The surgical specificities of advanced low-grade serous ovarian carcinoma (LGSOC) have been little investigated. Our objective was to describe surgical procedures/complications in primary (PDS) compared to interval debulking surgery (neoadjuvant chemotherapy and interval debulking surgery, NACT-IDS) and to assess the survival (progression-free (PFS) and overall survival (OS)) in patients with advanced LGSOC. We retrospectively analyzed advanced LGSOC from a nationwide registry (January 2000 to July 2017). A total of 127 patients were included (48% PDS and 35% NACT-IDS). Peritoneal carcinomatosis was more severe (p = 0.01 to 0.0001, according to sites), surgery more complex (p = 0.03) and late postoperative morbidity more frequent (p = 0.03) and more severe in the NACT-IDS group. PFS and OS were similar in patients with CC0 and CC1 residual disease after PDS or IDS. Prognosis was poorest for NACT-IDS patients with CC2/CC3 resection (PFS: HR = 2.31, IC95% (1.3-4.58); p = 0.005; OS: HR = 4.98, IC95% (1.59-15.61); p = 0.006). NACT has no benefit in terms of surgical outputs in patients with advanced LGSOC. Patients with complete resection or minimal residual disease (CC0 and CC1) have similar prognoses. On the other hand, patients with CC2 and more residual disease have similar survival rates compared to nonoperated patients. Primary cytoreduction with complete or with minimal residuals should be preferred when feasible.

Can Conization Specimens Predict Sentinel Lymph Node Status in Early-Stage Cervical Cancer? A SENTICOL Group Study.

BACKGROUND: The prognosis of patients with cervical cancer is significantly worsened in case of lymph node involvement. The goal of this study was to determine whether pathologic features in conization specimens can predict the sentinel lymph node (SLN) status in early-stage cervical cancer. METHODS: An ancillary analysis of two prospective multicentric database on SLN biopsy for cervical cancer (SENTICOL I and II) was carried out. Patients with IA to IB2 2018 FIGO stage, who underwent preoperative conization before SLN biopsy were included. RESULTS: Between January 2005 and July 2012, 161 patients from 25 French centers fulfilled the inclusion criteria. Macrometastases, micrometastases and Isolated tumor cells (ITCs) were found in 4 (2.5%), 6 (3.7%) and 5 (3.1%) patients respectively. Compared to negative SLN patients, patients with micrometastatic and macrometastatic SLN were more likely to have lymphovascular space invasion (LVSI) (60% vs. 29.5%, p = 0.04) and deep stromal invasion (DSI) ≥ 10 mm (50% vs. 17.8%, p = 0.04). Among the 93 patients with DSI < 10 mm and absence of LVSI on conization specimens, three patients (3.2%) had ITCs and only one (1.1%) had micrometastases. CONCLUSIONS: Patients with DSI < 10 mm and no LVSI in conization specimens had lower risk of micro- and macrometastatic SLN. In this subpopulation, full node dissection may be questionable in case of SLN unilateral detection.

Metastasis-suppressor NME1 controls the invasive switch of breast cancer by regulating MT1-MMP surface clearance.

Membrane Type 1 Matrix Metalloprotease (MT1-MMP) contributes to the invasive progression of breast cancers by degrading extracellular matrix tissues. Nucleoside diphosphate kinase, NME1/NM23-H1, has been identified as a metastasis suppressor; however, its contribution to local invasion in breast cancer is not known. Here, we report that NME1 is up-regulated in ductal carcinoma in situ (DCIS) as compared to normal breast epithelial tissues. NME1 levels drop in microinvasive and invasive components of breast tumor cells relative to synchronous DCIS foci. We find a strong anti-correlation between NME1 and plasma membrane MT1-MMP levels in the invasive components of breast tumors, particularly in aggressive histological grade III and triple-negative breast cancers. Knockout of NME1 accelerates the invasive transition of breast tumors in the intraductal xenograft model. At the mechanistic level, we find that MT1-MMP, NME1 and dynamin-2, a GTPase known to require GTP production by NME1 for its membrane fission activity in the endocytic pathway, interact in clathrin-coated vesicles at the plasma membrane. Loss of NME1 function increases MT1-MMP surface levels by inhibiting endocytic clearance. As a consequence, the ECM degradation and invasive potentials of breast cancer cells are enhanced. This study identifies the down-modulation of NME1 as a potent driver of the in situ-to invasive transition during breast cancer progression.

Sentinel lymph node in cervical cancer: time to move forward.

In early-stage cervical cancer, lymph node status is of paramount importance to determine the best therapeutic strategy and is one of the most important prognostic factors of survival. According to main international guidelines, pelvic full lymphadenectomy is recommended for lymph node staging. Sentinel lymph node (SLN) biopsy is an accurate method for the assessment of lymph nodal involvement and has been suggested instead of systematic pelvic lymph node dissection (PLND). The SLN technique requires a learning-curve to be well performed. Combined detection with technetium-99 and blue dye has been widely used but the recent introduction of indocyanine green (ICG) is of growing interest since it could improve SLN detection. SLN biopsy offers a more accurate anatomical staging by finding potential metastatic nodes outside of usual lymphadenectomy areas. SLN biopsy improves the diagnostic value of lymph node staging with ultrastaging and detection of low-volume nodal metastases [isolated tumor cells (ITCs) and micrometastases]. Appropriate selection of patient and minimal training combined with some simple rules may guarantee a low false negative rate. Several studies have shown that SLN mapping in these patients is feasible, with excellent detection rates and sensitivity. Less-radical lymph node dissection decreases the associated morbidity of PLND, especially the risk of lower-limb lymphoedema, which severely affects patient quality of life. Some points are still subject to debate such as the low accuracy of intraoperative SLN status assessment by frozen section and the impact of micrometastasis on prognosis. Although international guidelines consider SLN biopsy as an alternative to PLND, SLN biopsy alone is not the gold-standard yet due to lack of prospective evidence on long-term oncological safety. The 3 ongoing prospective trials SENTIX, PHENIX and SENTICOL III will most probably give an answer to these issues.

Impact of obesity on surgical and oncologic outcomes in patients with endometrial cancer treated with a robotic approach.

AIM: The surgical treatment of endometrial cancer (EC) can be more complicated in obese patients. Robotic surgery could simplify the surgical approach in these patients. The aim of our study was to compare the outcomes of robotic surgery in obese (body mass index ≥30 kg/m2 ) and nonobese patients. METHODS: We performed a retrospective study on patients with EC benefitting from a robotic approach in our institution. The primary outcome was the 5-year overall survival (OS). We also assessed the 5-year recurrence-free survival (RFS), type of surgery, laparotomy conversion rate, adjuvant treatment and postoperative morbidity. RESULTS: We analyzed 175 consecutive patients with EC who underwent robotic surgery, 42 patients with obesity and 133 patients without. The median follow-up length was 37 months [1-120]. The OS rate was 97% in the whole population and the RFS was 74%. Obesity did not impact prognosis. Laparotomy conversion rate was low in both groups (5% in patients with obesity vs 3%, P = 0.619). There were no significant differences in terms of postoperative complications (5 vs 9%, P = 0.738). There were significantly less pelvic lymphadenectomies in patients with obesity (5 vs 12%, P = 0.005). In the subgroup of patients with high-risk EC, rate of lymphadenectomy and of adjuvant treatments did not differ between patients with or without obesity. CONCLUSION: Obese patients with EC can be safely treated with a robotic approach, with a low complication rate and similar oncological outcomes compared to nonobese patients.

Use of fluorescence to guide surgical resection in vulvo-vaginal neoplasia: Two case reports.

We report hereby two cases of fluorescence-guided surgical resection with Indocyanine green in vulvo-vaginal neoplasia. The first case was a 86-year old patient who had a high-grade squamous intraepithelial lesion of the left small lip and on the vulvar fork. After a first incomplete surgery, a second fluorescence-guided vulvectomy was performed with ICG injected intravenously to determine intraoperatively surgical margins. At final pathologic examination, surgical margins were free of disease and postoperative course was uneventful. The second case was a 44-year old patient who had a clear cell carcinoma of the upper vagina. She underwent a fluorescence-guided colpo-hysterectomy with pelvic lymphadenectomy. ICG was injected one centimeter around the tumor and highlighted intraoperatively the limits of the vaginal resection. On the specimens, surgical margins were also negative. Peritumoral or intravenous injection of ICG are promising techniques for the intraoperative identification of surgical margins in gynecologic malignancies.

Validation of the 2018 FIGO Classification for Cervical Cancer: Lymphovascular Space Invasion Should Be Considered in IB1 Stage.

BACKGROUND: The aim of this study was to assess the prognostic impact of Lymphovascular space invasion (LVSI) in IB1 stage of the revised 2018 International Federation of Gynecology and Obstetrics (FIGO) classification for cervical cancer. METHODS: A secondary analysis of two French prospective multicentric trials on Sentinel Lymph node biopsy for cervical cancer was performed. Patients with 2009 FIGO IB1 stage who underwent radical surgery between January 2005 and July 2012 from 28 French expert centers were included. The stage was modified retrospectively according to the new 2018 FIGO staging system. RESULTS: According to the 2009 FIGO classification, 246 patients had IB1 disease stage and fulfilled the inclusion criteria. The median follow-up was 48 months (4-127). Twenty patients (8.1%) experienced a recurrence, and the 5-year Disease Free Survival (DFS) was 90.0%. Compared to 2018 IB1 staged patients, new IB2 had significantly decreased 5-year DFS, 78.6% vs. 92.9%, p = 0.006 whereas IIIC patients had similar 5-year DFS (91.7%, p = 0.95). In the subgroup of patients with FIGO 2018 IB1 stage, the presence of LVSI was associated with a significant decrease in DFS (82.5% vs. 95.8%, p = 0.04). CONCLUSIONS: LVSI is associated with decreased 5-year DFS in IB1 2018 FIGO stage and LVSI status should be considered in early-stage cervical cancer for a more precise risk assessment.

Indocyanine green for sentinel lymph node detection in early breast cancer: Prospective evaluation of detection rate and toxicity-The FLUOBREAST trial.

INTRODUCTION: Detection of sentinel lymph node in early breast cancer is commonly based on the combination of patent blue dye and a radioisotope 99m Technetium. Each of these two tracers has advantages and disadvantages leading to the development of the use of indocyanine green. METHODS: We conducted a prospective clinical trial to compare the detection rate of indocyanine green with 99mTe. Each patient undergoing a sentinel lymph node biopsy for an early breast cancer received both indocyanine green and radioisotopes. The trial was registered: FLUOBREAST EudraCT N 2015-000698-11, ClinicalTrials.gov: NCT02875626. RESULTS: Among a total of 88 patients, 77 were assessable for a total of 205 nodes. Detection rates were 93% for the isotope and 96% for the indocyanine green. The combined detection rate was 99%. The overall concordance rate per patient was 91%. The median number of excised sentinel nodes was 2.3 for each tracer and 2.7 for the combined method (P = .21). All the macrometastatic nodes were detected by both indocyanine green and radioisotopes. The median time between incision of the axilla and removal of the last node was 14 minutes. There was neither allergy nor radio-sensitization linked with the use of indocyanine green. CONCLUSIONS: Indocyanine green delivers a high detection rate and sensitivity for the sentinel lymph node biopsy in early breast cancer, with short operative time and a normal number of excised sentinel lymph nodes. Allergy is extremely rare and there is no toxicity. Indocyanine green could be an alternative to radioisotopes to provide an accurate staging of the axilla. Its routine use should be approved.

Pre-operative surgical algorithm: sentinel lymph node biopsy as predictor of parametrial involvement in early-stage cervical cancer.

INTRODUCTION: Radical hysterectomy is the gold standard in the management of early-stage cervical cancer. Parametrectomy aims to remove occult disease but is associated with significant surgical morbidity. Avoiding unnecessary parametrectomy in a subset of patients at low risk of parametrial involvement may decrease the incidence of such morbidity. The purpose of this study was to identify patients at low risk of parametrial involvement in early-stage cervical cancer potentially eligible for less radical surgery based on pre-operative criteria and sentinel lymph node (SLN) status. METHODS: We performed an ancillary analysis of data from two prospective trials on sentinel node biopsy for cervical cancer (SENTICOL I and II). Patients with International Federation of Gynecology and Obstetrics (FIGO) IA-IIA cervical cancer who underwent primary radical surgery and bilateral SLN mapping were identified between 2005 and 2012 from 25 French oncologic centers. Patients who underwent pre-operative brachytherapy or did not undergo radical surgery (simple trachelectomy, simple hysterectomy, or lymph node staging only) were excluded. RESULTS: Of 174 patients who fullfiled the inclusion criteria, 9 patients (5.2%) had parametrial involvement and 24 patients (13.8%) had positive SLN. Most patients had 2018 FIGO stage IB1 disease (86.1%) and squamous cell carcinomas (68.9%). Parametrial involvement was significantly associated with tumor size ≥20 mm on pelvic magnetic resonance imaging (MRI) (adjusted odds ratio (ORa) 9.30, 95% CI 1.71 to 50.57, p=0.01) and micrometastic or macrometastatic SLN (ORa 8.98, 95% CI 1.59 to 50.84, p=0.01). Of 114 patients with tumors <20 mm on pre-operative MRI and negative SLN after ultrastaging, only one patient had parametrial involvement (0.9%). By triaging patients with both of these criteria in a two-step surgical procedure, unjustified and contra-indicated radical hysterectomy would have been avoided in 65.5% and 8.6% of cases, respectively. CONCLUSIONS: Less radical surgery may be an option for patients with bilateral negative SLN after ultrastaging and tumors <20 mm. SLN status should be integrated into the decision-making process for tailored surgery in early-stage cervical cancer.

Nomogram Predicting the Likelihood of Parametrial Involvement in Early-Stage Cervical Cancer: Avoiding Unjustified Radical Hysterectomies.

BACKGROUND: We aimed to establish a tool predicting parametrial involvement (PI) in patients with early-stage cervical cancer and select a sub-group of patients who would most benefit from a less radical surgery. METHODS: We retrospectively reviewed patients from two prospective multicentric databases-SENTICOL I and II-from 2005 to 2012. Patients with early-stage cervical cancer (FIGO 2018 IA with lympho-vascular involvement to IIA1), undergoing radical surgery (hysterectomy or trachelectomy) with bilateral sentinel lymph node (SLN) mapping with no metastatic node or PI on pre-operative imaging, were included. RESULTS: In total, 5.2% patients (11/211) presented a histologic PI. After univariate analysis, SLN status, lympho-vascular space invasion, deep stromal invasion and tumor size were significantly associated with PI and were included in our nomogram. Our predictive model had an AUC of 0.92 (IC95% = 0.86-0.98) and presented a good calibration. A low risk group, defined according to the optimal sensitivity and specificity, presented a predicted probability of PI of 2%. CONCLUSION: Patients could benefit from a two-step approach. Final surgery (i.e. radical surgery and/or lymphadenectomy) would depend on the SLN status and the probability PI calculated after an initial conization with bilateral SLN mapping.

Fertility and prognosis of borderline ovarian tumor after conservative management: Results of the multicentric OPTIBOT study by the GINECO & TMRG group.

OBJECTIVES: Description of fertility and prognosis of patients with borderline ovarian tumor (BOT) treated by fertility-sparing surgery through a longitudinal study from the French national cancer network. METHODS: All consecutive patients diagnosed with BOT from the French National Network dedicated to Ovarian Malignant Rare Tumors from 2010 and 2017 were selected. In 2018, an update was made by sending a questionnaire regarding recurrence and fertility to patients aged under 43 years at diagnosis and treated conservatively. We compared the characteristics of the patients with/without recurrence and with/without live birth. RESULTS: Fifty-two patients aged 18 to 42 years presented a desire of pregnancy. Thirty patients (58%) presented a FIGO IA tumor, and 20 patients were treated by bilateral cystectomies (38%). We observed at least one live birth for 33 patients (63%) and local recurrences in 20 patients (38%). Both recurrence and live birth in 17 patients (33%) were reported, with recurrence occurring before pregnancy, after a second fertility-sparing treatment, in half of the cases. No factors associated with recurrence or live birth in this study were identified. Moreover, in this population, both recurrence and live birth were independent of age, with a linear risk along time. Disease-free survival was worse for patients treated with bilateral cystectomy (n = 20, 38%), with no difference in terms of fertility. CONCLUSION: Two third of the patients experienced life birth after conservation surgery. We did not highlight an age/time from surgery for which the risk of recurrence outweighs the chance of pregnancy and to radicalize surgery. Moreover, almost a quarter of the live birth occurred after recurrence, with no more further event to date in these patients. The results encourage to consider a second fertility-sparing surgery after local borderline recurrence in the case of pregnancy desire. All these decisions must be discussed in specialized multidisciplinary boards.

[Sentinel lymph node biopsy in early-stage cervical cancer: current state of art]. / Place du ganglion sentinelle dans les cancers du col utérin débutants.

Lymph node status is the most important prognostic factor of survival in women with early stage cervical cancer. Sentinel lymph node (SLN) biopsy is an accurate method for the assessment of lymph nodal involvement in early-stages cervical cancer and has been increasingly used instead of systematic pelvic lymph node dissection (PLND). Less-radical lymph node dissection decreases the associated morbidity of PLND, especially the risk of lower-leg lymphoedema, which affects severely patient quality of life. SLN biopsy allows nodes ultrastaging and provides supplementary histological information by increasing the detection of tumor low-volume (isolated tumors cells and micrometastases). Moreover, SLN biopsy provides accurate anatomical information on pelvic lymphatic drainage pathway by identifying nodes outside of routine lymphadenectomy areas. Selection of a population at low-risk of nodal metastasis, a minimal training, and simple rules may ensure a low false negative rate. Several studies have shown that SLN mapping in these patients is feasible, with excellent detection rates and sensitivity. Combined detection with technetium-99 and blue dye has been widely used but recently, there has been increasing interest in the use of fluorescent dies such as indocyanine green (ICG) which would improve SLN detection. Although recent international guidelines recommend performing SLN biopsy in addition to PLND, SLN biopsy alone is not the gold-standard yet due to lack of prospective evidence, especially on long-term oncological safety. Some points remain controversial such as the low accuracy of intraoperative SLN status assessment by frozen section and the impact of micrometastasis on prognostic. The prospective randomized clinical trial SENTICOL III will answer to these problematics.

Assessing reliability of intra-tumor heterogeneity estimates from single sample whole exome sequencing data.

Tumors are made of evolving and heterogeneous populations of cells which arise from successive appearance and expansion of subclonal populations, following acquisition of mutations conferring them a selective advantage. Those subclonal populations can be sensitive or resistant to different treatments, and provide information about tumor aetiology and future evolution. Hence, it is important to be able to assess the level of heterogeneity of tumors with high reliability for clinical applications. In the past few years, a large number of methods have been proposed to estimate intra-tumor heterogeneity from whole exome sequencing (WES) data, but the accuracy and robustness of these methods on real data remains elusive. Here we systematically apply and compare 6 computational methods to estimate tumor heterogeneity on 1,697 WES samples from the cancer genome atlas (TCGA) covering 3 cancer types (breast invasive carcinoma, bladder urothelial carcinoma, and head and neck squamous cell carcinoma), and two distinct input mutation sets. We observe significant differences between the estimates produced by different methods, and identify several likely confounding factors in heterogeneity assessment for the different methods. We further show that the prognostic value of tumor heterogeneity for survival prediction is limited in those datasets, and find no evidence that it improves over prognosis based on other clinical variables. In conclusion, heterogeneity inference from WES data on a single sample, and its use in cancer prognosis, should be considered with caution. Other approaches to assess intra-tumoral heterogeneity such as those based on multiple samples may be preferable for clinical applications.

Interaction between Molecular Subtypes and Stromal Immune Infiltration before and after Treatment in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy.

PURPOSE: High levels of tumor-infiltrating lymphocytes (TIL) before neoadjuvant chemotherapy (NAC) are associated with higher pathologic complete response (pCR) rates and better survival in triple-negative breast cancer (TNBC) and HER2-positive breast cancer. We investigated the value of TIL levels by evaluating lymphocyte infiltration before and after NAC. EXPERIMENTAL DESIGN: We assessed stromal TIL levels in 716 pre- and posttreatment matched paired specimens, according to the guidelines of the International TIL Working Group. RESULTS: Pre-NAC TIL levels were higher in tumors for which pCR was achieved than in cases with residual disease (33.9% vs. 20.3%, P = 0.001). This was observed in luminal tumors and TNBCs, but not in HER2-positive breast cancers (P Interaction = 0.001). The association between pre-NAC TIL levels and pCR was nonlinear in TNBCs (P = 0.005). Mean TIL levels decreased after chemotherapy completion (pre-NAC TILs: 24.1% vs. post-NAC TILs: 13.0%, P < 0.001). This decrease was strongly associated with high pCR rates, and the variation of TIL levels was strongly inversely correlated with pre-NAC TIL levels (r = -0.80, P < 0.001). Pre-NAC TILs and disease-free survival (DFS) were associated in a nonlinear manner (P < 0.001). High post-NAC TIL levels were associated with aggressive tumor characteristics and with impaired DFS in HER2-positive breast cancers (HR, 1.04; confidence interval, 1.02-1.06; P = 0.001), but not in luminal tumors or TNBCs (P Interaction = 0.04). CONCLUSIONS: The associations of pre- and post-NAC TIL levels with response to treatment and DFS differ between breast cancer subtypes. The characterization of immune subpopulations may improve our understanding of the complex interactions between pre- or post-NAC setting, breast cancer subtype, response to treatment, and prognosis.

The clinical implication of lymph nodes micrometastases and isolated tumor cells in patients with cervical cancer: A systematic review.

Lymph node macroscopic involvement in cervical cancer is a well-known prognostic factor, allows the gynecologic-oncologist to identify women at increased risk for recurrence. Since the development of sentinel node biopsy, micrometastases (MMs) and Isolated Tumor Cells (ICTs) have been increasingly identified in cervical cancer, however their prognostic value and treatment are still controversial. We reviewed the literature (MEDLINE and EMBASE database analysis) from inception up to January 2019, concerning the incidence of lymph nodes MMs and ITCs in cervical cancer, their controversial histologic and molecular biology definition, their anatomic distribution, the role of frozen section and the prognostic value and treatment options for women diagnosed with lymph nodes MMs/ITCs.

Prognostic impact of initial tumor load and intraperitoneal disease dissemination patterns in patients with advanced ovarian cancer undergoing complete cytoreductive surgery.

INTRODUCTION: Complete removal of disease is the most important prognostic factor for patients with advanced epithelial ovarian carcinoma. However, the influence of carcinomatosis distribution on prognosis is unknown and the prognostic impact of implant size according to their location is poorly studied. Our objective was to assess the impact of peritoneal carcinomatosis quantitative and qualitative localizations on progression free survival (PFS) in patients with advanced epithelial ovarian carcinoma (AEOC) after complete cytoreductive surgery. METHODS: We conducted a monocentric cohort study, retrospective from October 2001 to July 2014. Inclusion criteria were high-grade AEOC patients without residual disease (CC0) after primary debulking surgery (PDS) or after interval debulking surgery (IDS) following neoadjuvant chemotherapy (NACT). Peritoneal carcinomatosis was assessed according to qualitative criteria and quantitative criteria. RESULTS: One hundred and one patients were included. Median PFS was 21·2 months and median OS was 62·2 months. On the whole population, involvement of adipocytes-enriched areas tended to be associated with a decreased PFS and was significantly associated with a decreased OS. Any localization was associated with PFS or OS in the "IDS" subgroup. In the "PDS" subgroup, PCI score and involvement of the right mesocolic area were associated with a decreased PFS. CONCLUSION: Initial tumor load has not been found associated with PFS after complete surgery. Adipocytes-enriched areas and right mesocolic areas involvement were associated with poor prognosis in patients receiving primary debulking surgery. Larger-scale studies are needed to assess whether initial tumor load has a prognostic impact even after complete cytoreductive surgery is achieved.

Three-Dimensional Modelization of the Female Human Inferior Hypogastric Plexus: Implications for Nerve-Sparing Radical Hysterectomy.

BACKGROUND/AIMS: This study aims to describe the autonomic nervous network of the female pelvis with a 3D model and to provide a safe plane of dissection during radical hysterectomy for cervical cancer. METHODS: Pelvises of 3 human female fetuses were studied by using the computer-assisted anatomic dissection. RESULTS: The superior hypogastric plexus (SHP) was located at the level of the aortic bifurcation in front of the sacral promontory and divided inferiorly and laterally into 2 hypogastric nerves (HN). HN ran postero-medially to the ureter and in the lateral part of the uterosacral ligament until the superior angle of the inferior hypogastric plexus (IHP). IHP extended from the anterolateral face of the rectum, laterally to the cervix and attempted to the base of the bladder. Vesical efferences merged from the crossing point of the ureter and the uterine artery and ran through the posterior layer of the vesico-uterine ligament. CONCLUSIONS: The SHP could be injured during paraaortic lymphadenectomy. Following the ureter and resecting the medial fibrous part of the uterosacral ligament may spare the HN. No dissection should be performed under the crossing point of the ureter and the uterine artery.

Author Correction: New insight for pharmacogenomics studies from the transcriptional analysis of two large-scale cancer cell line panels.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Pathological complete response and prognosis after neoadjuvant chemotherapy for HER2-positive breast cancers before and after trastuzumab era: results from a real-life cohort.

This corrects the article DOI: 10.1038/bjc.2017.85.

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.