[Can we avoid axillary lymph node dissection in patients with node positive invasive breast carcinoma?] / Peut-on surseoir au curage axillaire en cas de carcinome mammaire invasif avec envahissement ganglionnaire ?

OBJECTIVES: The indications and modalities of breast and axillary surgery are undergoing profound change, with the aim of personalizing surgical management while avoiding over-treatment. To update best practices for axillary surgery, four questions were selected by the Senology Commission of the Collège National des Gynécologues et Obstétriciens Français (CNGOF), focusing on, firstly, the definition and evaluation of targeted axillary dissection (TAD) techniques; secondly, the possibility of surgical de-escalation in case of initial lymph node involvement while performing initial surgery; thirdly, in case of surgery following neo-adjuvant systemic therapy (NAST), and fourthly, contra-indications to de-escalation of axillary surgery to allow access to particular adjuvant systemic therapies. METHODS: The Senology Commission based its responses primarily on an analysis of the international literature, clinical practice recommendations and national and international guidelines. RESULTS: Firstly, TAD is a technique that combines excision of clipped metastatic axillary node(s) and the axillary sentinel lymph nodes (ASLNs). The detection rate and sensitivity are increased but it still needs to be standardized and practices better evaluated. Secondly, TAD represents an alternative to axillary clearance in cases of metastatic involvement of a single node that can be resected. Thirdly, neither TAD nor ASLN alone is recommended in France after NAST outside of clinical trials, although it is used in several countries in cases of complete pathological response in the lymph nodes, and when at least three lymph nodes have been removed. Fourthly, as some adjuvant targeted therapies are indicated in cases of lymph node invasion of more than three lymph nodes, the place of TAD in this context remains to be defined. CONCLUSION: Axillary surgical de-escalation can limit the morbidity of axillary clearance. Having proved that TAD does not reduce patient survival, it will most probably replace axillary clearance in well-defined indications. This will require prior standardization of the method and its indications and contra-indications, particularly to enable the use of new targeted therapies.

[How could physical activity decrease the risk of breast cancer development and recurrence?] / Comment l'activité physique pourrait-elle réduire le risque de survenue et de récidive des cancers du sein ?

OBJECTIVES: Breast cancer is the most frequent and deadly cancer among women. In France, 50% of adults are currently overweight, mostly as a result of a sedentary lifestyle. Numerous studies have highlighted overweight, obesity and lack of physical activity as risk factors for the occurrence and prognosis of cancers, particularly breast cancer. The aim of this study was to understand the extent to which physical activity can improve this prognosis, and what the pathophysiology is. METHODS: The Senology Commission of the Collège national des gynécologues et obstétriciens français (CNGOF) based its responses on an analysis of the international literature using a Preferred Reporting Items for Systematic review and Meta-Analyses (PRISMA) methodology conducted on the PubMed database between 1994 and 2023. RESULTS: A total of 70 articles were selected, demonstrating the role of regular physical activity in reducing the risk of breast cancer occurrence and recurrence. This role in controlling carcinogenesis is mediated by metabolic factors such as leptin, adiponectin and insulin, sex hormones and inflammation. The signaling pathways deregulated by these molecules are known carcinogenic pathways which could be used as therapeutic targets adapted to this population, without replacing the essential hygienic-dietary recommendations. CONCLUSION: Physical activity has a protective effect on breast cancer risk and prognosis. We must therefore continue to raise awareness in the general population and promote physical activity as a means of primary, secondary, and tertiary prevention.

[Updated surgical indications and quality and safety indicators in the management of infiltrative breast carcinoma]. / Actualisation des indications chirurgicales et des indicateurs de qualité et sécurité des soins dans la prise en charge des carcinomes mammaires invasifs.

OBJECTIVES: Breast surgery is the cornerstone of breast cancer treatment. Its indications and procedures are constantly evolving. To update best practices, four questions were submitted to the Senology Commission (SC) of the Collège national des gynécologues et obstétriciens français (CNGOF), covering the indications and modalities of tumor surgery: (1) initially, (2) following neoadjuvant systemic treatment, (3) in case of local recurrence, and (4) the quality and safety of care indicators applicable to this surgery. METHODS: The CNGOF SC essentially based its responses on the clinical practice recommendations and guidelines of the French Cancer Institute concerning invasive carcinomas of the breast. Exclusion criteria were carcinoma in situ, sarcoma and axillary surgery. RESULTS: To define the type of breast surgery, knowledge of four parameters is essential: the patient's level of risk, the presence of metastases, the size of the breast tumor and its focality (assessed by the clinical/mammography/ultrasound tripod). (1) In the case of initial management, the 6 indications for mastectomy are patient choice (particularly in case of high risk), contraindication to radiotherapy, inflammatory cancer (T4d), surgery with positive margins (after several surgical intervention), surgery that cannot be performed as a monobloc in the case of tumors with multiple foci, and poor expected aesthetic results. All other situations should be treated conservatively. (2) The same criteria apply after neoadjuvant systemic treatment, with conservative treatment still possible whatever the size (excluding carcinomatous mastitis) and focality of the initial tumor. (3) In case of local recurrence, total mastectomy is the reference treatment, with a second conservative treatment reserved for patients with no risk factors for a second recurrence, and no poor prognostic factors, after validation in a multidisciplinary meeting. (4) Four quality and safety indicators apply to breast surgery: it must be performed after obtaining a histological diagnosis, within less than 6 weeks of mammography, in a single surgery in over 80% of cases, and followed by local radiotherapy in the case of conservative treatment. CONCLUSION: The indications and modalities of breast surgery are evolving rapidly. To improve aesthetic results, oncoplastic techniques, immediate breast reconstruction, and preservation of the skin or nipple-areolar complex need to be further developed and evaluated in the long-term. These developments must necessarily be accompanied in France by a training policy for breast surgeons.

French college of gynecologists and obstetricians (CNGOF) recommendations for clinical practice: Place of breast self-examination in screening strategies.

Breast cancer is the most common female cancer in the world. Numerous studies have shown that the risk of metastatic disease increases with tumor volume. In this context, it is useful to assess whether the regular practice of formal breast self-examination (BSE) as opposed to breast awareness has an impact on the number of cancers diagnosed, their stage, the treatments used and mortality. DESIGN: The Commission of Senology (CS) of the Collège National de Gynécologie et Obstétrique Français (CNGOF) respected and followed the Grading of Recommendations Assessment, Development and Evaluation method to assess the quality of the evidence on which the recommendations were based. METHODS: The CS studied 16 questions individualizing four groups of women (general population, women aged over 75, high-risk women, and women previously treated for breast cancer). For each situation, it was determined whether the practice of BSE versus abstention from this examination led to detection of more breast cancers and/or recurrences and/or reduced treatment and/or increased survival. RESULTS: BSE should not be recommended for women in the general population, who otherwise benefit from clinical breast examination by practitioners from the age of 25, and from organized screening from 50 to 74 (strong recommendation). In the absence of data on the benefits of BSE in patients aged over 75, for those at high risk and those previously treated for breast cancer, the CS was unable to issue recommendations. Thus, if women in these categories wish to undergo BSE, information on the benefits and risks observed in the general population must be given, notably that BSE is associated with a higher number of referrals, biopsies, and a reduced quality of life.

A chyle leak following a tumorectomy and an axillary sentinel lymph node dissection: Case report.

A chyle leak following a tumorectomy is a rare complication of surgery for breast cancer. We report a case of chylous leakage after axillary sentinel lymph node dissection. A 78-year-old woman with a left breast invasive ductal carcinoma underwent a breast-conserving surgery and had two sentinel lymph nodes removed. Ten days after surgery she came back with a swelling the left breast and the axilla, the drainage fluid was "milky". She underwent a second surgery for positive margins, during which time we did a mass ligature in the axilla and placed a drain that was remove when it wasn't productive anymore.

[Place of breast self-examination in screening strategies. French College of Gynecologists and Obstetricians (CNGOF) recommendations for clinical practice]. / Recommandations pour la pratique clinique du CNGOF. Place de l'auto-examen des seins dans les stratégies de dépistage.

OBJECTIVES: Breast cancer is the most common female cancer in the world. In France, over 60,000 new cases are currently diagnosed, and 12,000 deaths are attributed to it annually. Numerous studies have shown that the risk of metastatic disease increases with tumor volume. In this context, it is useful to assess whether the regular practice of breast self-examination (BSE) has an impact on the number of cancers diagnosed, their stage, the treatments used and mortality. DESIGN: the CNGOF's Commission de Sénologie (CS), composed by 17 experts and 3 invited members, drew up these recommendations. No funding was provided for the development of these recommendations. The CS respected and followed the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method to assess the quality of the evidence on which the recommendations were based. METHODS: The CS studied 16 questions concerning BSE, individualizing four groups of women (general population, women aged over 75, high-risk women, and women previously treated for breast cancer). For each situation, it was determined whether the practice of BSE compared with abstention from this examination led to the detection of more breast cancers and/or recurrences and/or reduced treatment and/or increased survival. RESULTS: BSE should not be recommended for women in the general population, who otherwise benefit from a clinical breast examination (by the attending physician or gynecologist) from the age of 25, and from organized screening from 50 to 74 (strong recommendation). However, in the absence of data on the role of BSE in patients aged over 75, those at high risk of breast cancer and those previously treated for breast cancer, the CS was unable to issue recommendations. Thus, if women in these latter categories wish to undergo BSE, they must be given rigorous training in the technique, and information on the benefits and risks observed in the general population. Finally, the CS invites all women who detect a change or abnormality in their breasts to consult a healthcare professional without delay. CONCLUSION: BSE is not recommended for women in the general population. No recommendation can be established for women aged over 75, those at high risk of breast cancer and those previously treated for breast cancer.

Technical notes surgical treatment of a ruptured interstitial pregnancy.

Non-tubal ectopic pregnancies represent fewer than 10% of all ectopic pregnancies. However, they are associated with a high rate of mortality due to late diagnosis and uterine horn rupture which requires radical emergency surgical management. Cornuectomy via laparoscopy is a treatment of choice. We provide here a simple description of laparoscopic cornuectomy using an Endo GIA stapling system: the Endo GIA® automatic forceps. It has the advantage of removing the mass, suturing, and achieving satisfactory haemostasis in a single step.

[Non-genetic indications for risk reducing mastectomies: Guidelines of the National College of French Gynecologists and Obstetricians (CNGOF)]. / Indications des mastectomies de réduction de risque en dehors du risque avéré de prédisposition héréditaire : recommandations du Collège national des gynécologues et obstétriciens français (CNGOF).

OBJECTIVE: To determine the value of performing a risk-reducting mastectomy (RRM) in the absence of a deleterious variant of a breast cancer susceptibility gene, in 4 clinical situations at risk of breast cancer. DESIGN: The CNGOF Commission of Senology, composed of 26 experts, developed these recommendations. A policy of declaration and monitoring of links of interest was applied throughout the process of making the recommendations. Similarly, the development of these recommendations did not benefit from any funding from a company marketing a health product. The Commission of Senology adhered to the AGREE II (Advancing guideline development, reporting and evaluation in healthcare) criteria and followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) method to assess the quality of the evidence on which the recommendations were based. The potential drawbacks of making recommendations in the presence of poor quality or insufficient evidence were highlighted. METHODS: The Commission of Senology considered 8 questions on 4 topics, focusing on histological, familial (no identified genetic abnormality), radiological (of unrecognized cancer), and radiation (history of Hodgkin's disease) risk. For each situation, it was determined whether performing RRM compared with surveillance would decrease the risk of developing breast cancer and/or increase survival. RESULTS: The Commission of Senology synthesis and application of the GRADE method resulted in 11 recommendations, 6 with a high level of evidence (GRADE 1±) and 5 with a low level of evidence (GRADE 2±). CONCLUSION: There was significant agreement among the Commission of Senology members on recommendations to improve practice for performing or not performing RRM in the clinical setting.

Vulvar and vaginal melanomas: A retrospective study spanning 19 years from a tertiary center.

INTRODUCTION: Mucosal melanomas (MM) of the female genital tract are rare a. We aimed to study the prognostic factors of vulvar and vaginal locations of MM. MATERIAL AND METHOD: A multicenter, retrospective cohort study conducted between 01/01/2000 and 01/06/2019. RESULT: Of the 33 patients included 25 (75.8 %) had vulvar (VuM) and eight (24.2 %) vaginal melanomas (VaM). VaMs were deeper: median Breslow index: 17.5mm [3.5-22] versus 4.3mm [0.35-18] (p=0.013). Average follow-up was 24.0±59.8 months. Twenty-six patients (78.8 %) experienced recurrence. Disease-free survival was 52.9 % at 1year (64.7 % for VuM and 14.3 % for VaM) and 8.4 % at 3 years (11 % for VuM and 0% for VaM) (p=0.002). Median time to the first recurrence was 9.01 months [CI95 %: 2.07-56.71]. VaM recurred earlier than VuM (3.12 months [CI95 %: 2.07-12.49] versus 17.72 [CI95 %: 3.58-56.71], p=0.011). VaM had a higher risk of recurrence (HR=5.64 [CI95 %: 2.01-15.82], p=0.001) in multivariate analysis. Overall survival was 88.5 % at 1year (100 % for VuM and 50 % for VaM), and 59.4 % at 3 years (69.3 % for VuM and 25 % for VaM). Women with VaM died earlier: median specific death occurrence of 8.76 months [CI95 %: 6.54-24.72] versus 39.61 [CI95 %: 21.89-209.21], p=0.013 (HR=5.08 [CI95 %: 1.39-18.60], p=0.014). A lesion size ≥3cm was associated with an increased risk of mortality (HR=8.45 [CI95 %: 1.60-44.52], p=0.012). In multivariate analysis, vaginal location remained an independent and predictive variable of a higher risk of specific death (HR=8.56 [CI95 %: 1.95-37.64], p=0.005). CONCLUSION: A vaginal location of MM is associated with a poorer prognosis than a vulvar location.

Early, On-Treatment Levels and Dynamic Changes of Genomic Instability in Circulating Tumor DNA Predict Response to Treatment and Outcome in Metastatic Breast Cancer Patients.

BACKGROUND: Circulating tumor DNA (ctDNA) offers high sensitivity and specificity in metastatic cancer. However, many ctDNA assays rely on specific mutations in recurrent genes or require the sequencing of tumor tissue, difficult to do in a metastatic disease. The purpose of this study was to define the predictive and prognostic values of the whole-genome sequencing (WGS) of ctDNA in metastatic breast cancer (MBC). METHODS: Plasma from 25 patients with MBC were taken at the baseline, prior to treatment (T0), one week (T1) and two weeks (T2) after treatment initiation and subjected to low-pass WGS. DNA copy number changes were used to calculate a Genomic Instability Number (GIN). A minimum predefined GIN value of 170 indicated detectable ctDNA. GIN values were correlated with the treatment response at three and six months by Response Evaluation Criteria in Solid Tumours assessed by imaging (RECIST) criteria and with overall survival (OS). RESULTS: GIN values were detectable (>170) in 64% of patients at the baseline and were significantly prognostic (41 vs. 18 months OS for nondetectable vs. detectable GIN). Detectable GIN values at T1 and T2 were significantly associated with poor OS. Declines in GIN at T1 and T2 of > 50% compared to the baseline were associated with three-month response and, in the case of T1, with OS. On the other hand, a rise in GIN at T2 was associated with a poor response at three months. CONCLUSIONS: Very early measurements using WGS of cell-free DNA (cfDNA) from the plasma of MBC patients provided a tumor biopsy-free approach to ctDNA measurement that was both predictive of the early tumor response at three months and prognostic.

The Landscape and Therapeutic Implications of Molecular Profiles in Epithelial Ovarian Cancer.

Epithelial ovarian cancer (EOC) affects 43,000 women worldwide every year and has a five-year survival rate of 30%. Mainstay treatment is extensive surgery and chemotherapy. Outcomes could be improved by molecular profiling. We conducted a review of the literature to identify relevant publications on molecular and genetic alterations in EOC. Approximately 15% of all EOCs are due to BRCA1 or BRCA2 mutations. Four histologic subtypes characterized by different mutations have been described: serous, endometrioid, mucinous, and clear-cell. Between 20-30% of high-grade serous EOCs have a BRCA mutation. Tumors with BRCA mutations are unable to repair double-strand DNA breaks, making them more sensitive to platinum-based chemotherapy and to PolyAdenosine Diphosphate-Ribose Polymerase (PARP) inhibitors. Olaparib is a PARP inhibitor with proven efficacy in BRCA-mutated ovarian cancer, but its effectiveness remains to be demonstrated in tumors with a BRCAness (breast cancer) profile (i.e., also including sporadic tumors in patients with deficient DNA repair genes). A universally accepted molecular definition of BRCAness is required to identify optimal theranostic strategies involving PARP inhibitors. Gene expression analyses have led to the identification of four subgroups of high-grade serous EOC: mesenchymal, proliferative, differentiated, and immunoreactive. These subtypes are not mutually exclusive but are correlated with prognosis. They are not yet used in routine clinical practice. A greater understanding of EOC subtypes could improve patient management.

Prognostic and predictive value of circulating tumor DNA during neoadjuvant chemotherapy for triple negative breast cancer.

Response to neoadjuvant chemotherapy (NAC) in triple negative breast cancer (TNBC) is highly prognostic and determines whether adjuvant chemotherapy is needed if residual tumor is found at surgery. To evaluate the predictive and prognostic values of circulating tumor DNA (ctDNA) in this setting, we analyzed tumor and serial bloods from 26 TNBC patients collected prior, during, and after NAC. Individual digital droplet PCR assays were developed for 121 variants (average 5/patient) identified from tumor sequencing, enabling ctDNA detection in 96% of patients at baseline. Mutant allele frequency at baseline was associated with clinical characteristics. Levels drastically fell after one cycle of NAC, especially in patients whose tumors would go on to have a pathological complete response (pCR), but then rose significantly before surgery in patients with significant residual tumor at surgery (p = 0.0001). The detection of ctDNA early during treatment and also late at the end of NAC before surgery was strongly predictive of residual tumor at surgery, but its absence was less predictive of pCR, especially when only TP53 variants are considered. ctDNA detection at the end of neoadjuvant chemotherapy indicated significantly worse relapse-free survival (HR = 0.29 (95% CI 0.08-0.98), p = 0.046), and overall survival (HR = 0.27 95% CI 0.075-0.96), p = 0.043). Hence, individualized multi-variant ctDNA testing during and after NAC prior to surgery has prognostic and predictive value in early TNBC patients.

Atypical epithelial hyperplasia of the breast: state of the art.

INTRODUCTION: Atypical epithelial hyperplasia (AEH) of the breast is considered benign histological lesions with breast cancer risk. This review focuses on clinical signification and management of AEH that remains controversial. AREAS COVERED: A review of published studies was performed using medline database. In this review, we fully describe the current evidence available. In particular, we describe 1) data from immunohistochemistry and molecular studies that suggest AEH is a precursor of breast cancer; 2) epidemiological studies demonstrate low rate of breast cancer in women with AEH; 3) surgical excision is necessary after diagnosis of AEH, such as lobular carcinoma in situ or atypical ductal hyperplasia, on core needle biopsy; 4) although current recommendations are evolving to fewer (if not no) excisions for flat epithelial with atypia and classic lobular neoplasia found on percutaneous biopsy (without radiologic indications for excision). Expert commentary: HEA management steel need prospective evidences, but recent retrospective data give some clue for less invasive management for some of HEA.