[Practical guidelines in case of nipple discharge]. / Recommandations pratiques en cas d'écoulement mamelonnaire.

Nipple discharge is a frequent reason for women to consult their physician, led by the fear of cancer. Fortunately, almost 90 % of cases have a benign aetiology. The main challenge is to rule out any malignant pathology by collecting a detailed history and clinical exam in order to define a targeted imaging. The aim of this review is to facilitate the management of nipple discharge. The most common aetiologies of nipple discharge are described, along with a systematic clinical approach to exclude any underlying malignancy and minimize invasive examinations.

L'écoulement mamelonnaire est un motif fréquent de consultation, souvent par crainte d'un cancer. Heureusement, près de 90 % des écoulements mamelonnaires présentent une étiologie bénigne. L'enjeu principal est d'écarter toute pathologie maligne en procédant à une anamnèse et un examen cliniques détaillés afin de définir le type d'écoulement et prescrire des examens complémentaires ciblés. Cet article cherche à faciliter la prise en charge des écoulements mamelonnaires et décrit leurs étiologies les plus communes. Il propose une approche clinique systématique permettant d'exclure une cause maligne sous-jacente et de minimiser les examens invasifs.

[Mastalgia : management and state of the art]. / Mastodynies : prise en charge et connaissances actuelles.

This article tries to facilitate the management of mastalgia. During their lifetime most women will experience breast pain. Many of them will visit a physician for this purpose, often led by the fear of cancer. However, in the absence of other clinical signs such as a lump or nipple discharge, the risk of malignancy remains low. In addition to the patient's medical history and physical examination, an imaging may be necessary. The absence of clinical or radiological abnormalities suffices to reassure patients in most cases. The management of mastalgia is based mainly on diet and life-style changes, the use of a well-suited bra and topical anti-inflammatory medication. In the case of mastalgia not responding to first line treatments, the patient should be referred to a breast-care unit.

Cet article cherche à faciliter la prise en charge des mastodynies. Au cours de leur vie, la majorité des femmes présenteront des mastodynies. Nombreuses sont celles qui consulteront leur médecin à cet égard, souvent par crainte d'un cancer. Cependant, en l'absence d'autres signes cliniques comme une masse ou un écoulement mamelonnaire, le risque de malignité reste faible. Outre l'anamnèse et l'examen clinique, une imagerie peut s'avérer nécessaire. L'absence d'anomalies cliniques ou radiologiques permet de rassurer les patientes dans la majorité des cas. Le traitement reposera essentiellement sur des mesures hygiéno-diététiques, le port d'un soutien-gorge adapté et l'utilisation d'anti-inflammatoires topiques. En cas de mastodynies invalidantes et réfractaires aux anti-inflammatoires, la patiente devra être adressée pour un suivi spécialisé.

What is the diagnostic performance of 18-FDG-PET/MR compared to PET/CT for the N- and M- staging of breast cancer?

PURPOSE: To compare the diagnostic performance of 18-FDG-PET/MR and PET/CT for the N- and M- staging of breast cancer. METHODS AND MATERIALS: Two independent readers blinded to clinical/follow-up data reviewed PET/MR and PET/CT examinations performed for initial or recurrent breast cancer staging in 80 consecutive patients (mean age = 48 ± 12.9 years). The diagnostic confidence for lesions in the contralateral breast, axillary/internal mammary nodes, bones and other distant sites were recorded. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) were calculated. The standard of reference included pathology and/or follow-up > 12 months. RESULTS: Nine of 80 patients had bone metastases; 13/80 had other distant metastases, 44/80 had axillary, 9/80 had internal mammary and 3/80 had contralateral breast tumours. Inter-reader agreement for lesions was excellent (weighted kappa = 0.833 for PET/CT and 0.823 for PET/MR) with similar reader confidence for the two tests (ICC = 0.875). In the patient-per-patient analysis, sensitivity and specificity of PET/MRI and PET/CT were similar (p > 0.05). In the lesion-per-lesion analysis, the sensitivity of PET/MR and PET/CT for bone metastases, other metastases, axillary and internal mammary nodes, contralateral tumours and all lesions together was 0.924 and 0.6923 (p = 0.0034), 0.923 and 0.923 (p = 1), 0.854 and 0.812 (p = 0.157), 0.9 and 0.9 (p = 1), 1 and 0.25 (p = 0.083), and 0.89 and 0.77 (p = 0.0013) respectively. The corresponding specificity was 0.953 and 1 (p = 0.0081), 1 and 1 (p = 1), 0.893 and 0.92 (p = 0.257), 1 and 1 (p = 1), 0.987 and 0.99 (p = 1) and 0.96 and 0.98 (p = 0.0075) respectively. CONCLUSIONS: Reader confidence, inter-reader agreement and diagnostic performance per patient were similar with PET/MR and PET/CT. However, for all lesions together, PET/MR had a superior sensitivity and lower specificity in the lesion-per-lesion analysis. KEY POINTS: • N and M breast cancer staging performance of PET/MR and PET/CT is similar per patient. • In a lesion-per-lesion analysis PET/MR is more sensitive than PET/CT especially for bone metastasis. • Readers' diagnostic confidence is similar for both tests.

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.

Association of Axillary Dissection With Systemic Therapy in Patients With Clinically Node-Positive Breast Cancer.

Importance: The role of axillary lymph node dissection (ALND) to determine nodal burden to inform systemic therapy recommendations in patients with clinically node (cN)-positive breast cancer (BC) is currently unknown. Objective: To address the association of ALND with systemic therapy in cN-positive BC in the upfront surgery setting and after neoadjuvant chemotherapy (NACT). Design, Setting, and Participants: This was a prospective, observational, cohort study conducted from August 2018 to June 2022. This was a preplanned study within the phase 3 randomized clinical OPBC-03/TAXIS trial. Included were patients with confirmed cN-positive BC from 44 private, public, and academic breast centers in 6 European countries. After NACT, residual nodal disease was mandatory, and a minimum follow-up of 2 months was required. Exposures: All patients underwent tailored axillary surgery (TAS) followed by ALND or axillary radiotherapy (ART) according to TAXIS randomization. TAS removed suspicious palpable and sentinel nodes, whereas imaging-guidance was optional. Systemic therapy recommendations were at the discretion of the local investigators. Results: A total of 500 patients (median [IQR] age, 57 [48-69] years; 487 female [97.4%]) were included in the study. In the upfront surgery setting, 296 of 335 patients (88.4%) had hormone receptor (HR)-positive and Erb-B2 receptor tyrosine kinase 2 (ERBB2; formerly HER2 or HER2/neu)-negative disease: 145 (49.0%) underwent ART, and 151 (51.0%) underwent ALND. The median (IQR) number of removed positive lymph nodes without ALND was 3 (1-4) nodes compared with 4 (2-9) nodes with ALND. There was no association of ALND with the proportion of patients undergoing adjuvant chemotherapy (81 of 145 [55.9%] vs 91 of 151 [60.3%]; adjusted odds ratio [aOR], 0.72; 95% CI, 0.19-2.67) and type of systemic therapy. Of 151 patients with NACT, 74 (51.0%) underwent ART, and 77 (49.0%) underwent ALND. The ratio of removed to positive nodes was a median (IQR) of 4 (3-7) nodes to 2 (1-3) nodes and 15 (12-19) nodes to 2 (1-5) nodes in the ART and ALND groups, respectively. There was no observed association of ALND with the proportion of patients undergoing postneoadjuvant systemic therapy (57 of 74 [77.0%] vs 55 of 77 [71.4%]; aOR, 0.86; 95% CI, 0.43-1.70), type of postneoadjuvant chemotherapy (eg, capecitabine: 10 of 74 [13.5%] vs 10 of 77 [13.0%]; trastuzumab emtansine-DM1: 9 of 74 [12.2%] vs 11 of 77 [14.3%]), or endocrine therapy (eg, aromatase inhibitors: 41 of 74 [55.4%] vs 36 of 77 [46.8%]; tamoxifen: 8 of 74 [10.8%] vs 6 of 77 [7.8%]). Conclusion: Results of this cohort study suggest that patients without ALND were significantly understaged. However, ALND did not inform systemic therapy recommendations.

Blood-Based Multi-Cancer Detection Using a Novel Variant Calling Assay (DEEPGENTM): Early Clinical Results.

This is an early clinical analysis of the DEEPGENTM platform for cancer detection. Newly diagnosed cancer patients and individuals with no known malignancy were included in a prospective open-label case-controlled study (NCT03517332). Plasma cfDNA that was extracted from peripheral blood was sequenced and data were processed using machine-learning algorithms to derive cancer prediction scores. A total of 260 cancer patients and 415 controls were included in the study. Overall, sensitivity for all cancers was 57% (95% CI: 52, 64) at 95% specificity, and 43% (95% CI: 37, 49) at 99% specificity. With 51% sensitivity and 95% specificity for all stage 1 cancers, the stage-specific sensitivities trended to improve with higher stages. Early results from this preliminary clinical, prospective evaluation of the DEEPGENTM liquid biopsy platform suggests the platform offers a clinically relevant ability to differentiate individuals with and without known cancer, even at early stages of cancer.

Tailored axillary surgery in patients with clinically node-positive breast cancer: Pre-planned feasibility substudy of TAXIS (OPBC-03, SAKK 23/16, IBCSG 57-18, ABCSG-53, GBG 101).

AIM: We developed tailored axillary surgery (TAS) to reduce the axillary tumor volume in patients with clinically node-positive breast cancer to the point where radiotherapy can control it. The aim of this study was to quantify the extent of tumor load reduction achieved by TAS. METHODS: International multicenter prospective study embedded in a randomized trial. TAS is a novel pragmatic concept for axillary surgery de-escalation that combines palpation-guided removal of suspicious nodes with the sentinel procedure and, optionally, imaging-guided localization. Pre-specified study endpoints quantified surgical extent and reduction of tumor load. RESULTS: A total of 296 patients were included at 28 sites in four European countries, 125 (42.2%) of whom underwent neoadjuvant chemotherapy (NACT) and 71 (24.0%) achieved nodal pathologic complete response. Axillary metastases were detectable only by imaging in 145 (49.0%) patients. They were palpable in 151 (51.0%) patients, of whom 63 underwent NACT and 21 had residual palpable disease after NACT. TAS removed the biopsied and clipped node in 279 (94.3%) patients. In 225 patients with nodal disease at the time of surgery, TAS removed a median of five (IQR 3-7) nodes, two (IQR 1-4) of which were positive. Of these 225 patients, 100 underwent ALND after TAS, which removed a median of 14 (IQR 10-17) additional nodes and revealed additional positive nodes in 70/100 (70%) of patients. False-negative rate of TAS in patients who underwent subsequent ALND was 2.6%. CONCLUSIONS: TAS selectively reduced the tumor load in the axilla and remained much less radical than ALND.

Prognostic value of the Residual Cancer Burden index according to breast cancer subtype: Validation on a cohort of BC patients treated by neoadjuvant chemotherapy.

INTRODUCTION: The Residual Cancer Burden (RCB) quantifies residual disease after neoadjuvant chemotherapy (NAC). Its predictive value has not been validated on large cohorts with long-term follow up. The objective of this work is to independently evaluate the prognostic value of the RCB index depending on BC subtypes (Luminal, HER2-positive and triple negative (TNBCs)). METHODS: We retrospectively evaluated the RCB index on surgical specimens from a cohort of T1-T3NxM0 BC patients treated with NAC between 2002 and 2012. We analyzed the association between RCB index and relapse-free survival (RFS), overall survival (OS) among the global population, after stratification by BC subtypes. RESULTS: 717 patients were included (luminal BC (n = 222, 31%), TNBC (n = 319, 44.5%), HER2-positive (n = 176, 24.5%)). After a median follow-up of 99.9 months, RCB index was significantly associated with RFS. The RCB-0 patients displayed similar prognosis when compared to the RCB-I group, while patients from the RCB-II and RCB-III classes were at increased risk of relapse (RCB-II versus RCB-0: HR = 3.25 CI [2.1-5.1] p<0.001; RCB-III versus RCB-0: HR = 5.6 CI [3.5-8.9] p<0.001). The prognostic impact of RCB index was significant for TNBC and HER2-positive cancers; but not for luminal cancers (Pinteraction = 0.07). The prognosis of RCB-III patients was poor (8-years RFS: 52.7%, 95% CI [44.8-62.0]) particularly in the TNBC subgroup, where the median RFS was 12.7 months. CONCLUSION: RCB index is a reliable prognostic score. RCB accurately identifies patients at a high risk of recurrence (RCB-III) with TNBC or HER2-positive BC who must be offered second-line adjuvant therapies.

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.