Screening of Breast Cancer from Sweat Samples Analyzed by 2-Dimensional Gas Chromatography-Mass Spectrometry: A Preliminary Study.

Breast cancer (BC) remains one of the most commonly diagnosed malignancies in women. There is increasing interest in the development of non-invasive screening methods. Volatile organic compounds (VOCs) emitted through the metabolism of cancer cells are possible novel cancer biomarkers. This study aims to identify the existence of BC-specific VOCs in the sweat of BC patients. Sweat samples from the breast and hand area were collected from 21 BC participants before and after breast tumor ablation. Thermal desorption coupled with two-dimensional gas chromatography and mass spectrometry was used to analyze VOCs. A total of 761 volatiles from a homemade human odor library were screened on each chromatogram. From those 761 VOCs, a minimum of 77 VOCs were detected within the BC samples. Principal component analysis showed that VOCs differ between the pre- and post-surgery status of the BC patients. The Tree-based Pipeline Optimization Tool identified logistic regression as the best-performing machine learning model. Logistic regression modeling identified VOCs that distinguish the pre-and post-surgery state in BC patients on both the breast and hand area with sensitivities close to 1. Further, Shapley additive explanations and the probe variable method identified the most important and pertinent VOCs distinguishing pre- and post-operative status which are mostly of distinct origin for the hand and breast region. Results suggest the possibility to identify endogenous metabolites linked to BC, hence proposing this innovative pipeline as a stepstone to discovering potential BC biomarkers. Large-scale studies in a multi-centered VOC analysis setting must be carried out to validate obtained findings.

European Society of Gynaecological Oncology Guidelines for the Management of Patients with Vulvar Cancer - Update 2023.

BACKGROUND: As part of its mission to improve the quality of care for women with gynecological cancers across Europe, the European Society of Gynaecological Oncology (ESGO) first published in 2017 evidence-based guidelines for the management of patients with vulvar cancer. OBJECTIVE: To update the ESGO guidelines based on the new evidence addressing the management of vulvar cancer and to cover new topics in order to provide comprehensive guidelines on all relevant issues of diagnosis and treatment of vulvar cancer. METHODS: The ESGO Council nominated an international development group comprised of practicing clinicians who provide care to vulvar cancer patients and have demonstrated leadership through their expertize in clinical care and research, national and international engagement and profile as well as dedication to the topics addressed to serve on the expert panel (18 experts across Europe). To ensure that the statements were evidence-based, new data identified from a systematic search were reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the international development group. Prior to publication, the guidelines were reviewed by 206 international practitioners in cancer care delivery and patient representatives. RESULTS: The updated guidelines cover comprehensively diagnosis and referral, staging, pathology, pre-operative investigations, surgical management (local treatment, groin treatment, sentinel lymph node procedure, reconstructive surgery), (chemo)radiotherapy, systemic treatment, treatment of recurrent disease (vulvar, inguinal, pelvic, and distant recurrences), and follow-up. Management algorithms are also defined.

Prevalent versus incident breast cancers: benefits of clinical and radiological monitoring in women with pathogenic BRCA1/2 variants.

Women with pathogenic germline BRCA1 or BRCA2 variants have a higher risk of breast cancer than in the general population. International guidelines recommend specific clinical and radiological breast follow-up. This specific breast screening program has already been shown to be of clinical benefit, but no information is available concerning the use of prognostic factors or specific survival to guide follow-up decisions. We evaluated "high-risk" screening in a retrospective single-center study of 520 women carrying pathogenic germline variants of the BRCA1 or BRCA2 gene treated for breast cancer between January 2000 and December 2016. We compared two groups of women: the incidental breast cancer group (IBCG) were followed before breast cancer diagnosis (N = 103), whereas the prevalent breast cancer group (PBCG) (N = 417) had no specific follow-up for high risk before breast cancer diagnosis. Breast cancers were diagnosed at an earlier stage in the IBCG than in the PBCG: T0 in 64% versus 19% of tumors, (p < 0.00001), and N0 in 90% vs. 75% (p < 0.00001), respectively. Treatment differed significantly between the 2 groups: less neoadjuvant chemotherapy (7.1% vs. 28.5%, p < 0.00001), adjuvant chemotherapy (47.7% vs. 61.9%, p = 0.004) and more mastectomies (60% vs. 42% p < 0.0001) in the IBCG vs PBCG groups respectively. Overall and breast cancer-specific mortality were similar between the two groups. However, the patients in the IBCG had a significantly longer metastasis-free survival than those in the PBCG, at three years (96.9% [95% CI 93.5-100] vs. 92.30% [95% CI 89.8-94.9]; p = 0.02), suggesting a possible long-term survival advantage.

Factors Associated With the Discussion of Fertility Preservation in a Cohort of 1,357 Young Breast Cancer Patients Receiving Chemotherapy.

PURPOSE: Female breast cancer (BC) patients exposed to gonadotoxic chemotherapy are at risk of future infertility. There is evidence of disparities in the discussion of fertility preservation for these patients. The aim of the study was to identify factors influencing the discussion of fertility preservation (FP). MATERIAL AND METHODS: We analyzed consecutive BC patients treated by chemotherapy at Institut Curie from 2011-2017 and aged 18-43 years at BC diagnosis. The discussion of FP was classified in a binary manner (discussion/no discussion), based on mentions present in the patient's electronic health record (EHR) before the initiation of chemotherapy. The associations between FP discussion and the characteristics of patients/tumors and healthcare practitioners were investigated by logistic regression analysis. RESULTS: The median age of the 1357 patients included in the cohort was 38.7 years, and median tumor size was 30.3 mm. The distribution of BC subtypes was as follows: 702 luminal BCs (58%), 241 triple-negative breast cancers (TNBCs) (20%), 193 HER2+/HR+ (16%) and 81 HER2+/HR- (6%). All patients received chemotherapy in a neoadjuvant (n=611, 45%) or adjuvant (n= 744, 55%) setting. A discussion of FP was mentioned for 447 patients (33%). Earlier age at diagnosis (discussion: 34.4 years versus no discussion: 40.5 years), nulliparity (discussion: 62% versus no discussion: 38%), and year of BC diagnosis were the patient characteristics significantly associated with the mention of FP discussion. Surgeons and female physicians were the most likely to mention FP during the consultation before the initiation of chemotherapy (discussion: 22% and 21%, respectively). The likelihood of FP discussion increased significantly over time, from 15% in 2011 to 45% in 2017. After multivariate analysis, FP discussion was significantly associated with younger age, number of children before BC diagnosis, physicians' gender and physicians' specialty. CONCLUSION: FP discussion rates are low and are influenced by patient and physician characteristics. There is therefore room for improvement in the promotion and systematization of FP discussion.

A New Transcutaneous Method for Breast Cancer Detection with Dogs.

We developed a new transcutaneous method for breast cancer detection with dogs: 2 dogs were trained to sniff skin secretion samples on compresses that had been worn overnight by women on their breast, and to recognize a breast cancer sample among 4 samples. During the test, the dogs recognized 90.3% of skin secretion breast cancer samples. This proof-of-concept study opens new avenues for the development of a reliable cancer diagnostic tool integrating olfactory abilities of dogs.

[Sentinel lymph node biopsy and neoadjuvant treatment in breast cancer]. / Ganglion sentinelle et chimiothérapie néoadjuvante dans le cancer du sein.

Sentinel lymph node biopsy has replaced axillary lymph node dissection in those patients with clinically node-negative axilla without compromising their oncologic outcomes. Indication of neoadjuvant chemotherapy has been extended to patients to evaluate the pathologic response and to offer more conservative breast surgery. Sentinel lymph node dissection after neoadjuvant chemotherapy is feasible and accurate in patients with clinically node-negative patients. The timing of the sentinel lymph node biopsy, before or after medical treatment has been studied with benefits for each procedure. Sentinel lymph node dissection has been explored in different randomized prospective studies in clinically positive axilla with the aim of reduce axillary lymph node dissection. However, several studies are necessary to more accurately identify residual axillary disease and the sentinel lymph node after neoadjuvant chemotherapy, to adjust the adjuvant radiotherapy protocols and to evaluate the impact on oncologic outcomes.

Multicenter prospective evaluation of the reliability of the combined use of two models to predict non-sentinel lymph node status in breast cancer patients with metastatic sentinel lymph nodes: the MSKCC nomogram and the Tenon score. Results of the NOTEGS study.

BACKGROUND: The purpose of this study was to prospectively evaluate the combined use of The Memorial Sloan Kettering Cancer Center nomogram and Tenon score to select, in patients with metastatic sentinel lymph node (SN), those at low risk of metastatic non-SN for whom additional axillary lymph node dissection (ALND) could be avoided. METHODS: From January 2011 to July 2012, a prospective non-interventional nationwide study was conducted (NCT01509963). We sought to identify the false reassurance rate (FRR, a negative test result is false) in patients with both a ⩽10% probability of metastatic non-SN with the MSKCC nomogram and a Tenon score ⩽3.5 (low risk): the proportion of patients with metastatic non-SN at additional ALND. Our hypothesis was that these patients would have a FRR⩽5%. RESULTS: Data on 2822 patients with breast cancer from 53 institutions were prospectively recorded. At least one SN was metastatic (isolated tumour cells, micro- or macrometastases) in 696 patients (24.7%). Among patients with ALND and complete data to calculate combined risk (n=504), 67 and 437 patients had low and high combined risk, respectively. Patients at low risk had less ALND (47%) compared to patients at high risk (P<0.001). This study did not meet its primary objective because the FRR in patients with low risk was 16.4% (11 out of 67) (95% confidence interval (CI): 9.7-23.1%). In the high-risk group, 33.9% (148 out of 437) (95% CI: 29.6-38.4%) had non-SN metastases (P=0.004). CONCLUSIONS: In this controlled prospective study, metastatic SN patients with both a ⩽10% probability of metastatic non-SN with the MSKCC nomogram and a Tenon score ⩽3.5 failed to identify patients at low risk of metastatic non-SN when completion ALND was not systematic.

[Review of national and international guidelines for sentinel lymph node biopsy and complementary axillary dissection in breast cancer]. / Synthèse des recommandations nationales et internationales concernant les indications de la technique du ganglion sentinelle et du curage axillaire complémentaire après ganglion sentinelle positif dans la prise en charge des cancers du sein.

Management of breast cancer is based on national and international guidelines. These are defined on evidence-based medicine. The main purpose of this review is to compare the different guidelines for sentinel lymph node biopsy and completion axillary dissection after positive sentinel lymph node biopsy. This review of breast cancer guidelines led to identify consensus, but in some specific situations, they differ. The guidelines cannot be applied to all clinical cases, mandatoring multidisciplinary meetings are essential.

Medico-economic impact of MSKCC non-sentinel node prediction nomogram for ER-positive HER2-negative breast cancers.

BACKGROUND: Avoiding axillary lymph node dissection (ALND) for invasive breast cancers with isolated tumor cells or micrometastatic sentinel node biopsy (SNB) could decrease morbidity with minimal clinical significance. PURPOSE: The aim of this study is to simulate the medico-economic impact of the routine use of the MSKCC non-sentinel node (NSN) prediction nomogram for ER+ HER2- breast cancer patients. METHODS: We studied 1036 ER+ HER2- breast cancer patients with a metastatic SNB. All had a complementary ALND. For each patient, we calculated the probability of the NSN positivity using the MSKCC nomogram. After validation of this nomogram in the population, we described how the patients' characteristics spread as the threshold value changed. Then, we performed an economic simulation study to estimate the total cost of caring for patients treated according to the MSKCC predictive nomogram results. RESULTS: A 0.3 threshold discriminate the type of sentinel node (SN) metastases: 98.8% of patients with pN0(i+) and 91.6% of patients with pN1(mic) had a MSKCC score under 0.3 (false negative rate = 6.4%). If we use the 0.3 threshold for economic simulation, 43% of ALND could be avoided, reducing the costs of caring by 1 051 980 EUROS among the 1036 patients. CONCLUSION: We demonstrated the cost-effectiveness of using the MSKCC NSN prediction nomogram by avoiding ALND for the pN0(i+) or pN1(mic) ER+ HER2- breast cancer patients with a MSKCC score of less than or equal to 0.3.

Colpoplasty by laparoscopic modified Davydov's procedure.

OBJECTIVE: To show laparoscopic surgery to treat vaginal shortening, with functional sequelae (sexual disorders), after radiotherapy and brachytherapy for vaginal carcinoma. METHODS: Davydov's procedure was initially described to treat vaginal aplasia (Davydov & Zhvitiashvili, 1974). This surgery was then improved for the upper part of the vagina, performed by laparoscopy (Leblanc, 2010; Adamyan, 1995) [2-3]. We used surgical technique, based on Davydov's procedure, by laparoscopy, to cover the upper neovagina, with two large peritoneal flaps, one anterior with the pre-vesical peritoneum and a second one posterior with the peritoneum of Douglas pouch. This surgery can be performed with no use of intestinal gesture, skin grafting, flap or any foreign material. Leblanc et al. (2016) [4] reported promising results about eight patients with this technique. RESULTS: A 36-years old patient had been treated by chemotherapy, radiotherapy and brachytherapy for a vagina cancer with a para-rectal extension. After four years of remission, she was worried about an important vaginal atrophy related to a significant vaginal shortening (about 5cm), causing major dyspareunia. This situation had caused sexual disorders with a real impact on the quality of life. All non-invasive techniques (dilatators, lubricants…) had led to failures. A colpoplasty by laparoscopic modified Davydov's procedure was performed. The post-operative follow-up was simple without complication. The vaginal mandrel was removed after 12days. The clinical examination after 4months demonstrates that size and elasticity of the neovaginal cavity was rewarding. CONCLUSION: This surgical technique requires training and experienced team, but seems to be promising way to restore a normal vaginal length.

[Effectiveness of "threshold" in the management of ovarian cancer: A review of the literature]. / Efficacité des « seuils ¼ dans la prise en charge des cancers de l'ovaire : revue de la littérature.

OBJECTIVE: The "Institut national du cancer" has established since 2007 a minimum threshold of 20 patients per year per center to treat patients with gynecologic cancer. This review aims to assess whether the literature data validate this approach, and specifically for ovarian cancer. METHODS: A search of the MEDLINE database was conducted, to reference all relevant articles evaluating one hand the links between the survival of patients with ovarian cancer and the average volume of patients per center and by operator; and secondly the relationship between quality of oncological surgery and these volumes. RESULTS: Nineteen studies met our inclusion criteria; seventeen were retrospective and two were prospective; population samples ranged from 476 to 96,802 patients. The most important data, quantitatively and qualitatively, concern the evaluation of survival based on the average volume per center, with 8 out of 13 studies finding a statistically significant correlation between average volume per center and survival. Data on the quality of surgery are less abundant and more heterogeneous, depending on the definition of the "optimal" surgery by the authors. CONCLUSION: The establishment of threshold centers appears to be an effective way to improve survival in ovarian cancer. However, these thresholds would have to be specific to ovarian cancer and not extended to "gynecological cancers."

Outcome of oncoplastic breast-conserving surgery following bracketing wire localization for large breast cancer.

PURPOSE: The purpose of this study was to evaluate the outcome of breast conserving surgery comparing oncoplastic surgery (OS) and standard lumpectomy (SL) after preoperative bracketing wire localization of large neoplastic lesions. METHODS: We retrospectively reviewed the medical records and the mammograms of patients operated on at the Institut Curie between May 2005 and September 2011 after bracketing wire localization under mammographic and/or sonographic guidance. RESULTS: 113 patients underwent surgery for a pre-operative diagnosis of DCIS (n = 80), micro-invasive carcinoma (n = 9) or invasive carcinoma (n = 24), by OS (n = 73) or SL (n = 40). In the OS group, radiological size (52 mm vs 39 mm, p < 0.001) and resection volumes (246 cc vs 88 cc, p < 0.00001) were significantly higher than in the SL group. Rates of clear histologic margins (60 vs 62%, NS), complete excision of microcalcifications (78% vs 72%, NS) and re-intervention rate (40% vs 42%, NS) were equivalent. The rate of local recurrence at 24 months was 3% [0-7.1] in patients with conservative treatment (n = 3). With a median follow-up of 40 months, 5 local relapses (two with axillary metastatic involvement), two distant metastatic evolution, one contralateral breast cancer and one death unrelated to cancer occurred. CONCLUSION: Following bracketing wire localization, OS allowed the conserving management of significantly larger lesions with wider resection volumes, without significant increase in margin involvement or re-intervention rate, and equivalent rate of microcalcifications clearance compared to SL.

Management of phyllodes breast tumors.

Phyllodes tumors are a rare distinctive fibroepithelial tumors of the breast and their management continues to be questioned. The aim of our study was to examine the treatment and outcome of 165 patients with phyllodes tumors and to review the options for surgical management. This is a retrospective study of 165 patients who presented to the Institut Curie between January 1994 and November 2008 for benign, borderline or malignant phyllodes tumors. The median follow-up was 12.65 months [range 0-149.8]. The median age at diagnosis was 44 years [range 17-79]. One hundred and sixty patients (97%) had breast-conserving treatment, of whom 3 patients (1.8%) had oncoplastic breast surgery. Younger women had a significantly higher chance of having a benign phyllodes tumor (p = 0.0001) or a tumor of small size (p < 0.0001). Histologic examination showed 114 benign (69%), 37 borderline (22%) and 14 malignant tumors (9%). The median tumor size was 30 mm [range 5-150]. The tumor margins were considered incomplete (< 10 mm) in 46 out of 165 cases (28%) with 52% revision surgery. Only the tumor grade was a significant risk factor for incomplete tumor margins (p = 0.005). Fifteen patients developed local recurrence (10%) and two, metastases. In univariate analysis, the histologic grade (p = 0.008), and tumor size (p = 0.02) were significative risk factors for local recurrence with an accentuated risk for "borderline" tumors and tumors of large size.).Similar results were obtained using multivariate analysis (p = 0.07). The mainstay of treatment for phyllodes tumors remains excision with a safe surgical margin, taking advantage breast conserving surgery where amenable. For borderline or malignant phyllodes tumors or in cases of local tumor recurrence, mastectomy, and immediate breast reconstruction may become the preferred option. Genetic analysis will potentially supplement classical histologic examination in order to improve our management of these tumors. The role of adjuvant treatments is unproven and must be considered on a case-by-case basis.