Publications by authors named "Carole Mathelin"

60 Publications

[The HRT follow-up consultation. What to do in case of breast pain. CNGOF and GEMVi clinical practice guidelines].

Authors:
Carole Mathelin

Gynecol Obstet Fertil Senol 2021 Mar 20. Epub 2021 Mar 20.

Service de chirurgie, Institut de cancérologie Strasbourg Europe (ICANS), 17 rue Albert Calmette, 67200 Strasbourg, France; IGBMC, Institut de génétique et de biologie moléculaire et cellulaire, biologie du cancer, CNRS UMR 7104, INSERM U964, Université de Strasbourg, Illkirch, France.

Breast pain is a concern in perimenopausal and postmenopausal women, quantifiable using validated tools, and may pre-exist or appear after initiation of a HRT.

Objectives: A review of the literature was conducted to evaluate the frequency of breast pain, its evolution with age, its changes under HRT, its link with a possible risk of subsequent breast cancer, and the diagnostic (breast imaging) or therapeutic management modalities (pharmacological or other) in women taking HRT.

Method: A review of the literature was carried out by consulting Medline, Cochrane Library data and international recommendations in French and English up to the end of 2019.

Results: Published data confirm the importance of breast pain in relation to breast cancer risk. Women with breast pain prior to or related to the use of HRT have a significantly increased risk of breast cancer compared to women without breast pain. The risk is increased in cases of moderate to severe breast pain. In the presence of diffuse breast pain without abnormalities on clinical examination, it is not recommended to change the usual indications for screening, whether organized or individual. For focal breast pain, breast imaging (mammography and possibly ultrasound) is recommended. In the absence of abnormalities on breast imaging, a reassuring dialogue has to take place. With regard to HRT, doses of estrogens should be reduced until the breast pain decreases, or even stop the HRT if this symptom persists despite the use of low doses. Wearing a bra brassiere-type can also reduce breast pain.
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http://dx.doi.org/10.1016/j.gofs.2021.03.027DOI Listing
March 2021

[The HRT follow-up consultation. What to do in case of breast tumour (clinical or radiological) and microcalcifications. Postmenopausal women management - CNGOF and GEMVi clinical practice guidelines].

Gynecol Obstet Fertil Senol 2021 Mar 20. Epub 2021 Mar 20.

CHRU, Hôpitaux universitaires de Strasbourg, 1, place de l'hôpital, 67091 Strasbourg, France; Unité d'imagerie mammaire, Institut de cancérologie Strasbourg Europe (ICANS), 17, rue Albert-Calmette. 67033 Strasbourg cedex, France.

Objective: The objective was to evaluate the diagnostic value of clinical examination and complementary imaging in the exploration of a breast lump or microcalcifications occurring in a postmenopausal woman taking hormonal replacement therapy (HRT), based on a systematic review of the literature in order to make recommendations for HRT management.

Methods: A literature review was conducted using Medline, Cochrane Library data and international recommendations in French and English until 2020.

Results: In the presence of a clinical breast mass in postmenopausal women, there is no clinical evidence to rule out cancer. A double evaluation by mammography and ultrasound is recommended and allows the imaging to be classified into 5 BI-RADS categories. The diagnostic management of masses classified BI-RADS 4 and 5 should be based on percutaneous sampling, with microbiopsy being the first step. A total of four situations may arise: 1. Clinical examination has detected a breast mass, but there is no imaging abnormality. In this case, the imaging NPV is high (>96%). If the clinical lesion increases in size, a tissue biopsy should be performed, while continued routine breast screening is recommended if the lesion remains stable and HRT can be continued. 2. Clinical examination, mammography, and ultrasound are in favour of a cyst. Simple cysts can be punctured if painful. There is no contraindication to continuing HRT in the case of simple cysts. Management options for complicated and complex cysts are no different from those offered to women without HRT. Continuation of HRT must consider their histological nature. 3. Clinical examination, mammography, and ultrasonography suggest a benign solid tumour. The management of these benign breast lesions (fibroadenoma…) is not different in women taking an HRT and there is no contraindication to continue the HRT. 4: Clinical examination, imaging and microbiopsy diagnose a malignant tumour. It is imperative that the HRT be stopped, whatever the hormonal dependence of the tumour and whether it is invasive or in situ. The management of the cancerous tumour must consider the updated breast cancer treatment guidelines. In the presence of microcalcifications, the course of action to be taken depends on the BI-RADS classification, established according to the morphology and arrangement of the calcifications. In case of suspicious microcalcifications (BI-RADS 4 or 5), a guided macrobiopsy should be performed. Diagnostic and therapeutic management in these patients is no different from that offered to women without HRT. Discontinuation of HRT is necessary in cases of malignancy (in situ or invasive cancer).

Conclusion: A rigorous multidisciplinary approach is necessary for the exploration of a breast mass or microcalcifications in a postmenopausal woman.
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http://dx.doi.org/10.1016/j.gofs.2021.03.026DOI Listing
March 2021

Coffee consumption and breast cancer risk: a narrative review in the general population and in different subtypes of breast cancer.

Eur J Nutr 2021 Apr 13;60(3):1197-1235. Epub 2021 Jan 13.

Surgery Unit, Institute of Cancerology Strasbourg Europe (ICANS), Strasbourg, France.

Purpose: Most of the existing literature reports no association or a slight negative association between coffee consumption and the risk of developing breast cancer. However, the level of risk differs when considering various subgroups, such as menopausal status, hormonal status of the tumor or genetic mutations. The present review based on a literature search sets the point on the potential influence of a common daily drink, coffee, on the risk of developing breast cancer in the general population, in different subgroups of women and the consequences of drinking coffee after breast cancer has been diagnosed and treated.

Results: This review confirms that in the general population, there is no association between coffee intake and breast cancer risk or a slight protective effect, even at high dosages. Coffee is inversely associated with breast cancer risk in postmenopausal women and in women carrying a BRCA1 mutation. Possible risk differences exist between slow and fast caffeine metabolizers and with weight. Coffee consumption after breast cancer diagnosis and surgery, associated with tamoxifen and/or radiotherapy, reduced the occurrence of early events. The effects of coffee intake are less clear in other subgroups, mainly premenopausal women, women carrying a BRCA2 mutation and tumors with variable hormonal status (positive or negative for ER/PR) and would need additional studies.
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http://dx.doi.org/10.1007/s00394-020-02465-0DOI Listing
April 2021

Narrative review of sentinel lymph node biopsy in breast cancer: a technique in constant evolution with still numerous unresolved questions.

Chin Clin Oncol 2020 12 18. Epub 2020 Dec 18.

Service de chirurgie, Institut de cancérologie Strasbourg Europe (ICANS), Strasbourg Cedex, France; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), UMR 7104 CNRS, U596 INSERM, ULP. BP 10142, Illkirch Cedex, France.

The aim of this narrative review was to provide an update on the use of sentinel lymph node biopsy (SLNB) for breast carcinoma (BC). Relevant studies published between 01/01/1994 and 15/08/2020 assessing the accuracy and the usefulness of SLNB were reviewed. SLNB was first used in 1977 for penile cancers. However, it took 17 years to enter in clinical practice for BC. The first procedures were based on two methods of non-specific marking of LN vmacrophages using a radioisotope (99mTc) and a blue dye (BD, Isosulfan, Patent or Methylene). To overcome side effects of radioisotopes (radiation exposure) and BD (allergic reactions), innovative tracers such as indocyanine green (ICG), superparamagnetic iron oxide (SPIO), and microbubbles have been explored. The SLN intraoperative examination is no longer performed, due to its low impact on the rate of reoperation and high time and cost of surgery. Likewise, immunohistochemistry, which can lead to an unnecessary ALND in some cases of occult metastases, is no more recommended. Except cases with metastasized LN, all contraindications aim to avoid situations where the risk of false negative would be too high (notably T3-T4 or multicentric tumors). The current indications for invasive BC are T0-T1-T2 N0 or N1 (after an accurate LN evaluation with ultrasound and/or cytology or core biopsy) and for DCIS treated by mastectomy or presenting as a palpable mass. After SLNB, axillary recurrence rates are generally below 2% after a follow up of 8–10 years, comparable to those observed after ALN. Likewise, when the SLN contains less than 2 metastases, axillary recurrence rates remain low even when ALN is omitted. In case of more than 2 metastatic SLN or capsular effraction, ALND is still indicated. For most teams, SLNB can be performed in clinically node-negative patients receiving neoadjuvant systemic therapy. The results of the literature consistently show that SLNB is extremely reliable in selected BC, as long as it is performed with a rigorous technique by teams having undergone multidisciplinary training and having gained the necessary experience.
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http://dx.doi.org/10.21037/cco-20-207DOI Listing
December 2020

Prospective Multicenter Study Validate a Prediction Model for Surgery Uptake Among Women with Atypical Breast Lesions.

Ann Surg Oncol 2021 Apr 12;28(4):2138-2145. Epub 2020 Sep 12.

Gustave Roussy, Villejuif, France.

Background: Diagnosis of atypical breast lesions (ABLs) leads to unnecessary surgery in 75-90% of women. We have previously developed a model including age, complete radiological target excision after biopsy, and focus size that predicts the probability of cancer at surgery. The present study aimed to validate this model in a prospective multicenter setting.

- Methods: Women with a recently diagnosed ABL on image-guided biopsy were recruited in 18 centers, before wire-guided localized excisional lumpectomy. Primary outcome was the negative predictive value (NPV) of the model.

Results: The NOMAT model could be used in 287 of the 300 patients included (195 with ADH). At surgery, 12 invasive (all grade 1), and 43 in situ carcinomas were identified (all ABL: 55/287, 19%; ADH only: 49/195, 25%). The area under the receiving operating characteristics curve of the model was 0.64 (95% CI 0.58-0.69) for all ABL, and 0.63 for ADH only (95% CI 0.56-0.70). For the pre-specified threshold of 20% predicted probability of cancer, NPV was 82% (77-87%) for all ABL, and 77% (95% CI 71-83%) for patients with ADH. At a 10% threshold, NPV was 89% (84-94%) for all ABL, and 85% (95% CI 78--92%) for the ADH. At this threshold, 58% of the whole ABL population (and 54% of ADH patients) could have avoided surgery with only 2 missed invasive cancers.

Conclusion: The NOMAT model could be useful to avoid unnecessary surgery among women with ABL, including for patients with ADH.

Clinical Trial Registration: NCT02523612.
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http://dx.doi.org/10.1245/s10434-020-09107-zDOI Listing
April 2021

Breast Cancer Management during the COVID 19 Pandemic: French Guidelines.

Eur J Breast Health 2020 Jul 21;16(3):160-161. Epub 2020 Apr 21.

Executive Director of Institut Universitaire de Cancérologie AP-HP, Sorbonne Université, Paris, France.

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http://dx.doi.org/10.5152/ejbh.2020.200420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337915PMC
July 2020

[Breast cancer management during the COVID 19 pandemic: the CNGOF takes action].

Gynecol Obstet Fertil Senol 2020 Apr 18. Epub 2020 Apr 18.

Pôle de Gynécologie-Obstétrique-Sénologie. CHRU. Hôpitaux Universitaires de Strasbourg, 1 place de l'Hôpital, 67091, Strasbourg Cedex, France; Président du CNGOF, 91 Boulevard de Sébastopol, 75002, Paris, France.

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http://dx.doi.org/10.1016/j.gofs.2020.04.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7166009PMC
April 2020

The Cowden Syndrome.

N Engl J Med 2020 Apr;382(15):e29

Hôpital de Hautepierre, Strasbourg, France

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http://dx.doi.org/10.1056/NEJMicm1910478DOI Listing
April 2020

Quantitative background parenchymal enhancement to predict recurrence after neoadjuvant chemotherapy for breast cancer.

Sci Rep 2019 12 16;9(1):19185. Epub 2019 Dec 16.

Department of Gynecology and Obstetrics, Strasbourg University Hospital, Strasbourg, France.

Breast background parenchymal enhancement (BPE) is an increasingly studied MRI parameter that reflects the microvasculature of normal breast tissue, which has been shown to change during neoadjuvant chemotherapy (NAC) for breast cancer. We aimed at evaluating the BPE in patients undergoing NAC and its prognostic value to predict recurrence. MRI BPE was visually and quantitatively evaluated before and after NAC in a retrospective cohort of 102 women with unilateral biopsy-proven invasive breast cancer. Pre-therapeutic BPE was not predictive of pathological response or recurrence. Quantitative post-therapeutic BPE was significantly decreased compared to pre-therapeutic value. Post-therapeutic quantitative BPE significantly predicted recurrence (HR = 6.38 (0.71, 12.06), p < 0.05).
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http://dx.doi.org/10.1038/s41598-019-55820-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6914793PMC
December 2019

Tenascin-C increases lung metastasis by impacting blood vessel invasions.

Matrix Biol 2019 10 6;83:26-47. Epub 2019 Jul 6.

INSERM U1109 - MN3T, The Microenvironmental Niche in Tumorigenesis and Targeted Therapy and, the Tumor Microenvironment group, France; Université de Strasbourg, Strasbourg, France; LabEx Medalis, Université de Strasbourg, France; Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France. Electronic address:

Metastasis is a major cause of death in cancer patients. The extracellular matrix molecule tenascin-C is a known promoter of metastasis, however the underlying mechanisms are not well understood. To further analyze the impact of tenascin-C on cancer progression we generated MMTV-NeuNT mice that develop spontaneous mammary tumors, on a tenascin-C knockout background. We also developed a syngeneic orthotopic model in which tumor cells derived from a MMTV-NeuNT tumor. Tumor cells were transfected with control shRNA or with shRNA to knockdown tenascin-C expression and, were grafted into the mammary gland of immune competent, wildtype or tenascin-C knockout mice. We show that stromal-derived tenascin-C increases metastasis by reducing apoptosis and inducing the cellular plasticity of cancer cells located in pulmonary blood vessels invasions (BVI), before extravasation. We characterized BVI as organized structures of tightly packed aggregates of proliferating tumor cells with epithelial characteristics, surrounded by Fsp1+ cells, internally located platelets and, a luminal monolayer of endothelial cells. We found extracellular matrix, in particular, tenascin-C, between the stromal cells and the tumor cell cluster. In mice lacking stromal-derived tenascin-C, the organization of pulmonary BVI was significantly affected, revealing novel functions of host-derived tenascin-C in supporting the integrity of the endothelial cell coat, increasing platelet abundance, tumor cell survival, epithelial plasticity, thereby promoting overall lung metastasis. Many effects of tenascin-C observed in BVI including enhancement of cellular plasticity, survival and migration, could be explained by activation of TGF-β signaling. Finally, in several human cancers, we also observed BVI to be surrounded by an endothelial monolayer and to express tenascin-C. Expression of tenascin-C is specific to BVI and is not observed in lymphatic vascular invasions frequent in breast cancer, which lack an endothelial lining. Given that BVI have prognostic significance for many tumor types, such as shorter cancer patient survival, increased metastasis, vessel occlusion, and organ failure, our data revealing a novel mechanism by which stromal tenascin-C promotes metastasis in human cancer, may have potential for diagnosis and therapy.
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http://dx.doi.org/10.1016/j.matbio.2019.07.001DOI Listing
October 2019

A novel machine learning-derived decision tree including uPA/PAI-1 for breast cancer care.

Clin Chem Lab Med 2019 05;57(6):901-910

Unité de Sénologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.

Background uPA and PAI-1 are breast cancer biomarkers that evaluate the benefit of chemotherapy (CT) for HER2-negative, estrogen receptor-positive, low or intermediate grade patients. Our objectives were to observe clinical routine use of uPA/PAI-1 and to build a new therapeutic decision tree integrating uPA/PAI-1. Methods We observed the concordance between CT indications proposed by a canonical decision tree representative of French practices (not including uPA/PAI-1) and actual CT prescriptions decided by a medical board which included uPA/PAI-1. We used a method of machine learning for the analysis of concordant and non-concordant CT prescriptions to generate a novel scheme for CT indications. Results We observed a concordance rate of 71% between indications proposed by the canonical decision tree and actual prescriptions. Discrepancies were due to CT contraindications, high tumor grade and uPA/PAI-1 level. Altogether, uPA/PAI-1 were a decisive factor for the final decision in 17% of cases by avoiding CT prescription in two-thirds of cases and inducing CT in other cases. Remarkably, we noted that in routine practice, elevated uPA/PAI-1 levels seem not to be considered as a sufficient indication for CT for N≤3, Ki 67≤30% tumors, but are considered in association with at least one additional marker such as Ki 67>14%, vascular invasion and ER-H score <150. Conclusions This study highlights that in the routine clinical practice uPA/PAI-1 are never used as the sole indication for CT. Combined with other routinely used biomarkers, uPA/PAI-1 present an added value to orientate the therapeutic choice.
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http://dx.doi.org/10.1515/cclm-2018-1065DOI Listing
May 2019

Why and How Should We Improve Breast Cancer Management in Elderly Women?

Eur J Breast Health 2018 Jul 1;14(3):132-133. Epub 2018 Jul 1.

Unit of Breast, Strasbourg University Hospital, Strasbourg, France.

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http://dx.doi.org/10.5152/ejbh.2018.02070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092155PMC
July 2018

Invasive ductal carcinoma limited to the nipple.

Breast J 2018 11 3;24(6):1083. Epub 2018 Aug 3.

Department of Gynecology and Obstetrics, Strasbourg University Hospital, Strasbourg, France.

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http://dx.doi.org/10.1111/tbj.13090DOI Listing
November 2018

Identification of MOSPD2, a novel scaffold for endoplasmic reticulum membrane contact sites.

EMBO Rep 2018 07 1;19(7). Epub 2018 Jun 1.

Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, France

Membrane contact sites are cellular structures that mediate interorganelle exchange and communication. The two major tether proteins of the endoplasmic reticulum (ER), VAP-A and VAP-B, interact with proteins from other organelles that possess a small VAP-interacting motif, named FFAT [two phenylalanines (FF) in an acidic track (AT)]. In this study, using an unbiased proteomic approach, we identify a novel ER tether named motile sperm domain-containing protein 2 (MOSPD2). We show that MOSPD2 possesses a Major Sperm Protein (MSP) domain which binds FFAT motifs and consequently allows membrane tethering MOSPD2 is an ER-anchored protein, and it interacts with several FFAT-containing tether proteins from endosomes, mitochondria, or Golgi. Consequently, MOSPD2 and these organelle-bound proteins mediate the formation of contact sites between the ER and endosomes, mitochondria, or Golgi. Thus, we characterized here MOSPD2, a novel tethering component related to VAP proteins, bridging the ER with a variety of distinct organelles.
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http://dx.doi.org/10.15252/embr.201745453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6030701PMC
July 2018

Breast cancer and ovarian tissue cryopreservation: Review of the literature.

J Gynecol Obstet Hum Reprod 2018 Oct 21;47(8):351-357. Epub 2018 May 21.

Unité de Sénologie, CHRU, Hôpitaux Universitaires de Strasbourg, Hôpital Hautepierre, 1 avenue Molière, 67200 Strasbourg, France.

Introduction: Ovarian tissue cryopreservation is a modern technique of fertility preservation, useful before using ovariotoxic therapies in the treatment of breast cancer. The aim of our literature review was to study ovarian cryopreservation experiences for women with breast cancer, to identify guidelines, constraints and results in the oncological and obstetrical fields.

Methods: We searched articles through the PubMed/Medline database, including all French and English references from January 2000 to October 2017. The combination of key words "breast cancer" and "ovarian tissue cryopreservation" allowed us to select 50 articles. We kept 18 publications which matched our subject.

Results: Sixteen cases of ovarian transplants among patients treated for breast cancer were published with 14 pregnancies, 11 births and 3 failures. Two cases of breast recurrences were published after ovarian grafting. However, the hindsight in this technique is limited, with a first transplant published in 2004 and only a low number of cases.

Perspectives: A national census and comprehensive gathering of data among the patients treated for breast cancer using ovarian tissue cryopreservation would make it possible to better evaluate the occurrence of pregnancies and the carcinological risk of this technique.
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http://dx.doi.org/10.1016/j.jogoh.2018.05.008DOI Listing
October 2018

The Big Data Revolution for Breast Cancer Patients.

Eur J Breast Health 2018 Apr 1;14(2):61-62. Epub 2018 Apr 1.

Unité de sénologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.

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http://dx.doi.org/10.5152/ejbh.2018.0101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5939978PMC
April 2018

[Breast calciphylaxis: An uncommon and difficult pathology].

Presse Med 2018 Mar 9;47(3):288-291. Epub 2018 Mar 9.

CHRU, hôpital de Hautepierre, pôle de gynécologie et obstétrique, unité de sénologie, avenue Molière, 67200 Strasbourg, France; Université de Strasbourg, IGBMC, institut de génétique et biologie moléculaire et cellulaire, CNRS UMR 7104, Inserm U964, 1, rue Laurent-Fries, 67400 Illkirch-Graffenstaden, France; Centre hospitalier de Sarrebourg, rue des Roses, 57400 Sarrebourg, France.

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http://dx.doi.org/10.1016/j.lpm.2018.01.004DOI Listing
March 2018

Antitumor Effects of Lidocaine on Human Breast Cancer Cells: An and Experimental Trial.

Anticancer Res 2018 01;38(1):95-105

Faculty of Medicine, University of Strasbourg, Strasbourg, France.

Aim: Retrospective studies have suggested a protective effect of regional anesthesia against recurrence after cancer surgery. But confirmation of the in vivo antitumor effects is lacking. We examined the in vitro antitumor effects of lidocaine on various breast cancer cell lines and then assessed these properties in vivo at clinically relevant concentrations.

Materials And Methods: In vitro experiments: normal breast epithelial cells (NBEC) MCF-10A and three tumor breast epithelial cells (TBEC) lines (MCF-7 luminal A, MDA-MB-231 triple-negative and SKBr3 HER2 positive) were exposed to increasing concentrations of lidocaine. Cell viability, migration and anchorage-independent growth were assessed by MTT, wound healing, and soft-agar growth assays. In vivo experiments: 6-week-old severe combined immunodeficient mice were injected intraperitoneally with MDA-MB-231 cells and were treated with intraperitoneal lidocaine or phosphate-buffered saline. The mice were euthanized when they reached experimental endpoints or sacrificed to determine peritoneal carcinomatosis index and global tumor volumes.

Results: Lidocaine reduced the viability of all the cell lines, inhibited migration of TBEC compared to the NBEC, and compromised the anchorage-independent growth of the triple-negative cells. Intraperitoneal lidocaine improved survival of mice with MDA-MB-231 peritoneal carcinomatosis using doses that are consistent with the current clinical settings for analgesia.

Conclusion: In agreement with the notion that local anesthesia may be beneficial for cancer therapy, lidocaine has a protective effect against breast cancer cells in experimental studies. However, the beneficial impact of local anesthetics on breast cancer needs to be strengthened by additional preclinical and clinical trials.
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http://dx.doi.org/10.21873/anticanres.12196DOI Listing
January 2018

Relevance of breast MRI in determining the size and focality of invasive breast cancer treated by mastectomy: a prospective study.

World J Surg Oncol 2017 Jul 14;15(1):128. Epub 2017 Jul 14.

MATHELIN Carole MD PhD Unité de sénologie CHRU Hôpitaux universitaires de Strasbourg, Avenue Molière, 67200, Strasbourg, France.

Background: The aim of this study was the evaluation of breast MRI in determining the size and focality of invasive non-metastatic breast cancers.

Methods: The prospective, single-centre study conducted in 2015 compared preoperative MRI with histological analysis of mastectomy.

Results: One hundred one mastectomies from 98 patients were extensively analysed. The rates of false-positive and false-negative MRI were 2 and 4% respectively. The sensitivity of breast MRI was 84.7% for the detection of all invasive foci, 69% for single foci and 65.7% for multiple foci. In the evaluation of tumour size, the Spearman rank correlation coefficient r between the sizes obtained by MRI and histology was 0.62. The MRI-based prediction of a complete response to neoadjuvant chemotherapy was 75%.

Discussion: MRI exhibits high sensitivity in the detection of invasive breast cancers. False positives were linked to the inflammatory nature of the tumour bed. False negatives were associated with small or low-grade tumours and their retro-areolar location. The size of T1 tumours was overestimated by an average of 7%, but MRI was the most efficient procedure. The sensitivity of MRI for the diagnosis of unifocal tumours was higher than that for multifocal sites. Our study confirmed the positive contribution of preoperative MRI for invasive lobular carcinomas and complete response predictions after neoadjuvant chemotherapy.
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http://dx.doi.org/10.1186/s12957-017-1197-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5513043PMC
July 2017

Medical treatment of mammary desmoid-type fibromatosis: which benefit?

World J Surg Oncol 2017 Apr 18;15(1):86. Epub 2017 Apr 18.

Unité de Sénologie, Hôpital Hautepierre, Hôpitaux Universitaires de Strasbourg, CHRU, 1 Avenue Molière, 67200, Strasbourg, France.

Background: Breast fibromatosis is a rare disease characterized by monoclonal fibroblast proliferation. It has no ability to metastasize but has a high local recurrence rate and often infiltrates surrounding tissues. Surgical treatment is the reference, but recently, new targeted therapies have emerged. We report an original case of a patient with breast fibromatosis who received exclusive medical treatment. Our aim was to analyze these treatments based on the clinical and radiological outcome, iatrogenic effects, and pharmacological action.

Case Presentation: We report the case of a 19-year-old woman who developed a desmoid-type fibromatosis of the lower inner quadrant of the right breast, measuring 50 × 25 mm (i.e., a volume of 27.4 cm). Initial surgery was not possible because of potential esthetic and functional prejudice. Thus, she had an exclusive medical treatment including several lines: NSAIDs with tamoxifen and triptorelin, followed by sorafenib, then interferon α2b, and finally sunitinib. With tyrosine-kinase inhibitors (TKIs) (sunitinib), a significant partial response was observed (57% reduction of the maximal tumoral volume). For each treatment, we provided the clinical and radiological outcome in association with known pharmacological action.

Conclusions: TKI had been an interesting alternative option to initial surgery, providing at least a partial response and potentially allowing less mutilating surgery. However, no pharmacological mechanism can unequivocally explain TKI efficacy. In general, breast fibromatosis should be treated along with oncologist and interventional radiologists in a trans-disciplinary modality, thus offering an adapted treatment for this particular desmoid-type fibromatosis localization.
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http://dx.doi.org/10.1186/s12957-017-1148-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5395853PMC
April 2017

Does the Number of Neoadjuvant Chemotherapy Cycles before Interval Debulking Surgery Influence Survival in Advanced Ovarian Cancer?

Oncology 2016 27;91(6):331-340. Epub 2016 Oct 27.

Département de Gynécologie Obstétrique, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.

Objective: To evaluate the overall survival (OS) of patients with initially inoperable advanced ovarian cancer, tubal carcinoma, or primary peritoneal carcinoma of stages III or IV undergoing neoadjuvant chemotherapy (NAC) followed by cytoreductive surgery, according to the number of cycles performed.

Methods: This retrospective study was conducted in three main oncology centres in the east of France, reviewing the charts of all patients who underwent NAC between January 1, 1998 and October 31, 2012. We performed an OS analysis using multivariate Cox regression models adjusted for potential confounders. We also analysed progression-free survival (PFS) as well as chemotherapy- and surgery-related morbidity.

Results: Of the 204 patients included, 75 (36.8%) underwent ≤4 NAC cycles and 129 (63.2%) ≥5 NAC cycles. Characteristic data were similar in the two groups. Five-year OS was 35.0 and 25.8%, respectively. This difference was non-significant [HR = 1.06 (0.70-1.59), p = 0.79]. We also found no differences in PFS or morbidity between the two groups.

Conclusions: The number of NAC cycles does not seem to play a role in the OS of patients with advanced ovarian cancer. Further evidence and prospective data are needed to assess the value of a high/low number of NAC cycles among these patients.
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http://dx.doi.org/10.1159/000449203DOI Listing
January 2017

A prospective study to assess the clinical utility of serum HER2 extracellular domain in breast cancer with HER2 overexpression.

Breast Cancer Res Treat 2016 11 5;160(2):249-259. Epub 2016 Oct 5.

Unité de Sénologie, Hôpitaux Universitaires de Strasbourg, 1 avenue Molière, 67098, Strasbourg, France.

Purpose: We explored the clinical utility of human epidermal growth factor receptor-2 extracellular domain (HER2/ECD) in patients treated for an invasive breast cancer with HER2 overexpression.

Methods: We prospectively studied HER2/ECD levels in the sera of 334 women included between 2007 and 2014, all treated with trastuzumab. HER2/ECD levels were measured at diagnosis, during treatments, and along the follow-up. We investigated the relationship of HER2/ECD with other clinicopathological parameters at diagnosis, its prognosis value, and its utility during the monitoring of a neoadjuvant treatment and the follow-up.

Results: Elevated HER2/ECD at diagnosis correlated positively with parameters associated with tumor aggressiveness. Disease-free survival of non-metastatic patients was significantly shorter in patients with high HER2/ECD at diagnosis (HR = 13.6, 95 % CI 1.6-113.6, P < 0.0001). Progression-free survival of metastatic patients was better for patients with low HER2/ECD (HR = 2.6, 95 % CI 1.2-5.3, P = 0.033). A multivariate analysis revealed that HER2/ECD level at diagnosis was an independent prognosis factor. During neoadjuvant therapy, a significant decrease in HER2/ECD was reported only for the complete histological response group (P = 0.031). During the follow-up, HER2/ECD helped predict relapse, disease progression, and metastases before imaging in 18.6 % cases of the studied cohort.

Conclusions: HER2/ECD is a prognosis factor that is valuable in evaluating the neoadjuvant treatment efficiency. HER2/ECD also appears to be a helpful surveillance biomarker for the early diagnosis of relapses and to predict the fate of metastases. This study brings evidences to support the use of HER2/ECD in the management of HER2-positive breast cancer.
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http://dx.doi.org/10.1007/s10549-016-4000-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5065601PMC
November 2016

[Multidisciplinary team meetings settings on the management of women at high risk of inherited breast cancer. A French study].

Bull Cancer 2016 Jun 11;103(6):571-83. Epub 2016 May 11.

CHRU de Strasbourg, hôpitaux universitaires de Strasbourg, UF6948 oncogénétique : évaluation familiale et suivi, pôle d'hématologie et oncologie, 1, place de l'Hôpital, BP 426, 67091 Strasbourg cedex, France.

Introduction: In France, 126 centers for cancer genetics coordinate genetic testing and high-risk cancer surveillance for individuals and their families with hereditary cancer syndromes. Since 2012, the French National Cancer Institute (INCa) supports 17 projects to promote and manage the monitoring of individuals genetically predisposed to cancer. They were assigned 4 missions by INCa including expertise for difficult cases.

Methods: We initiated a national survey to assess how the oncogenetic clinics responded to the 4th mission for women at high risk of developing breast cancers. We sent the survey to all the French oncogeneticists. We aimed at evaluating the modalities and the extent of implementation of the Multidisciplinary team (MDT) meetings regarding the management of women who have genetically higher risks to develop breast cancer.

Results: Fourteen people from 12 administrative regions, who represent 10 of the 17 projects, answered the form. Eleven participants reported the submission of medical cases in Oncogenetics MDT meetings (79 %), 5 in senology MDT meetings (36 %), 5 in MDT meetings dedicated to patients at high risk for breast cancer (36 %) and 2 in network meetings (14 %). Some structures discuss medical cases through different MDT meetings.

Conclusion: Although MDT meetings are valuable practices to optimize treatment or management options for patients, its settings might be subject to difficulties to federate the appropriate-number of participants as well as cost-effectiveness issues. This survey thus suggests the need of a standardized process of MDT meetings while taking account specificities of oncogenetics.
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http://dx.doi.org/10.1016/j.bulcan.2016.03.006DOI Listing
June 2016

Clinical practice guidelines from the French College of Gynecologists and Obstetricians (CNGOF): benign breast tumors - short text.

Eur J Obstet Gynecol Reprod Biol 2016 May 28;200:16-23. Epub 2016 Feb 28.

Department of Gynecology, Obstetrics and Reproductive Medicine, Hôpital Tenon, AP-HP, Inserm UMRS938, 4 rue de la Chine, 75020 Paris, France.

Screening with breast ultrasound in combination with mammography is needed to investigate a clinical breast mass (Grade B), colored single-pore breast nipple discharge (Grade C), or mastitis (Grade C). The BI-RADS system is recommended for describing and classifying abnormal breast imaging findings. For a breast abscess, a percutaneous biopsy is recommended in the case of a mass or persistent symptoms (Grade C). For mastalgia, when breast imaging is normal, no MRI or breast biopsy is recommended (Grade C). Percutaneous biopsy is recommended for a BI-RADS category 4-5 mass (Grade B). For persistent erythematous nipple or atypical eczema lesions, a nipple biopsy is recommended (Grade C). For distortion and asymmetry, a vacuum core-needle biopsy is recommended due to the risk of underestimation by simple core-needle biopsy (Grade C). For BI-RADS category 4-5 microcalcifications without any ultrasound signal, a minimum 11-G vacuum core-needle biopsy is recommended (Grade B). In the absence of microcalcifications on radiography cores additional samples are recommended (Grade B). For atypical ductal hyperplasia, atypical lobular hyperplasia, lobular carcinoma in situ, flat epithelial atypia, radial scar and mucocele with atypia, surgical excision is commonly recommended (Grade C). Expectant management is feasible after multidisciplinary consensus. For these lesions, when excision margins are not clear, no new excision is recommended except for LCIS characterized as pleomorphic or with necrosis (Grade C). For grade 1 phyllodes tumor, surgical resection with clear margins is recommended. For grade 2 phyllodes tumor, 10mm margins are recommended (Grade C). For papillary breast lesions without atypia, complete disappearance of the radiological signal is recommended (Grade C). For papillary breast lesions with atypia, complete surgical excision is recommended (Grade C).
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http://dx.doi.org/10.1016/j.ejogrb.2016.02.017DOI Listing
May 2016

Oleogranulomatous Mastitis: A Topical Subject.

Plast Reconstr Surg Glob Open 2015 Oct 14;3(10):e536. Epub 2015 Oct 14.

Strasbourg University Hospital: Pole of Obstetrics and Gynecology, Hautepierre Hospital, Strasbourg, France; Department of Plastic and Reconstructive Surgery, Civil Hospital, Strasbourg, France; and Breast Diseases Center, Pole of Obstetrics and Gynecology, Hautepierre Hospital, Strasbourg, France.

Paraffin and petrolatum have been known for more than 100 years as volumizing products. Certain countries still use them despite important complications. The authors report the case of a 39-year-old patient presenting a bilateral oleogranulomatous mastitis. An injection of petrolatum had been realized 2 years ago in Chechnya for cosmetic reasons. Clinically, she presented dense, erythemic, and painful breasts. The radiological examination found diffuse oily cysts. After first abdominal expansion, a bilateral mastectomy with immediate reconstruction was performed. The authors present a literature review about the clinical and radiological data and the possible treatments, and underline the numerous risks of this procedure, which should be strictly forbidden.
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http://dx.doi.org/10.1097/GOX.0000000000000513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4634173PMC
October 2015

HER2 gene and protein expression status of breast carcinoma can be reliably tested on a single slide.

Virchows Arch 2015 Aug 19;467(2):169-75. Epub 2015 May 19.

Department of Pathology, University Hospitals of Strasbourg, 1 avenue Molière, 67098, Strasbourg, France,

Human epidermal growth factor receptor 2 (HER2) status in breast carcinomas serves as a predictor of benefit from anti-HER2 therapy. In providing clinicians with the information necessary to decide whether or not to treat with targeted therapy, it might be necessary to choose between methods assessing HER2 protein overexpression or gene amplification. A new diagnostic approach could be a combination of both tests on the same slide. If accurate and reproducible, this approach might optimize patient stratification for therapy. In this study, formalin-fixed paraffin-embedded tumor samples from 77 breast cancer patients were examined for HER2 by immunohistochemistry (IHC) and silver in situ hybridization (SISH) using HER2 IHC (clone 4B5), HER2/CEN17SISH, and combined IHC and SISH assay, called gene protein (GP). Cases were selected to ensure a sufficient number of borderline cases on the basis of IHC scores (0, 1+, 2+, 3+), obtained during diagnostic histopathological workup. The concordance between the HER2 IHC score obtained during diagnostic histopathological workup and GP was 93 %. Discordances had no influence on therapy decisions. The concordance between ISH results using dual ISH (DISH) and GP was 96 %. Of the 77 cases studied by GP, three cases with a ratio close to 2 would have been called amplified by DISH. The use of GP reduced the time for slide reading for a trained pathologist by up to 25 %, relative to sequential reading of IHC followed by SISH. For cases with an IHC score of 2+, the final result was obtained in 1 day, while the sequential technique would have required retesting by ISH on a second day. In conclusion, assessment of HER2 status by GP is an improvement for pathologists and facilitates clinical decision-making for breast cancer management.
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http://dx.doi.org/10.1007/s00428-015-1781-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4529453PMC
August 2015

Intracystic papillary carcinoma of the breast: a diagnostic challenge with major clinical impact.

Anticancer Res 2014 Sep;34(9):5017-20

Breast Diseases Center, Hospital Hautepierre-University Hospital, Strasbourg, France

Background: Intracystic papillary carcinoma (IPC) is a ductal carcinoma of papillary variety that develops in a cystic space surrounded by a fibrous capsule. It is a rare clinicopathological entity, the in situ or invasive character of which is difficult to establish, particularly on biopsy. The treatment is surgical and breast conservation depends on the tumor size. Lymph node exploration is still debated. The diagnosis of IPC is a challenge for the pathologist: the negativity of the basement membrane markers and of myoepithelial cells carries a risk of over-diagnosis on biopsy that can lead to over-treatment.

Case Report: To illustrate this risk, we report the case of a breast mass of 8 cm; its biopsy evoked invasive papillary carcinoma (no hormone receptors and overexpression of Human Epidermal Receptor-2 (HER-2) and for which neoadjuvant chemotherapy associated with trastuzumab was firstly proposed.

Results: The analysis of all anatomical radio-clinical data in a multidisciplinary context, however, allowed suspecting IPC, thus leading to first-line surgery (mastectomy with negative sentinel lymph nodes). With this diagnosis being confirmed on surgical specimen, no systemic treatment was then necessary. After 48 months, the patient is in complete remission.
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September 2014

First report of trastuzumab treatment after postoperative Takotsubo cardiomyopathy.

Anticancer Res 2014 Jul;34(7):3579-82

Breast Diseases Center, Department of Obstetrics and Gynaecology, Hautepierre Hospital, CHRU, University Hospital Strasbourg, Strasbourg; France

Background: Trastuzumab is a humanized monoclonal antibody used for the treatment of HER2-positive breast cancer. Cardiotoxicity is a well-known adverse event of trastuzumab use but little has been documented regarding its use in patients with a history of cardiac disease.

Case Report: We describe a case in which trastuzumab treatment was administered to a 40-year-old female patient with early breast cancer after acute heart failure secondary to postoperative Takotsubo cardiomyopathy. After one year of follow-up with close monitoring by echocardiography, there have been no heart-related symptoms. Additional surgery was performed because of positive resection margins at first surgery, without complications, despite the risk of recurrence of Takotsubo cardiomyopathy.

Conclusion: Trastuzumab can be safely administered after acute heart failure secondary to postoperative Takotsubo cardiomyopathy.
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July 2014

[Legal value of the recomendations of good practice: example for breast cancer hormonotherapy].

Bull Cancer 2014 Mar;101(3):283-94

Université de Strasbourg, Hôpitaux universitaires de Strasbourg, Pôle de gynécologie-obstétrique, Unité de sénologie, avenue Molière, 67200 Strasbourg, France.

On April 27th 2011, the French Supreme Administrative Court (Conseil d'État) granted the Recommendations for Good Practice set out by the French National Authority for Health (Haute Autorité de santé--[HAS]) a legal status, considering that they "must be regarded as (…) decisions which may be subject to an action for annulment". The judge came to this conclusion through a quasi-syllogistic reasoning. Firstly, the French Code of Medical Ethics requires physicians to care for their patients in accordance with established scientific knowledge. Secondly, the HAS recommendations recall in particular this established scientific knowledge. Treating patients according to established scientific knowledge requires then that physicians follow the HAS recommendations. While the case at bar does not directly involve liability for medical malpractice-since the applicant only sought to have an HAS recommendation declared void-it is nonetheless necessary to examine the impact of this ruling for health professionals. Indeed, this decision raises a number of concerns for everyday medical practice. Guidelines concerning the endocrine treatment of hormonodependant breast cancers are plentiful. In January 2010, the HAS and the French National Institute for Cancer (Institut national du cancer) issued a "Guide for long-term illnesses-Breast cancer" (Guide ALD - Cancer du sein). In addition to these nation-wide guidelines, the Regional Networks for Cancer (réseaux régionaux de cancérologie) issued their own recommendations. Other guidelines are also set out in the framework of consensus conferences, such as the Nice Saint-Paul-de-Vence (France) and St. Gallen (Switzerland) conferences. In the United States, the National Comprehensive Cancer Network (NCCN) and the American Society of Clinical Oncology (ASCO), and in Europe, the European Society of Medical Oncology (ESMO) make recommendations as well. Therefore, the HAS recommendations are hardly the sole source of information for physicians and these documents sometimes contradict each other. Besides, these can quickly become obsolete, what still limits their relevance. Nevertheless, in the judge's mind, there is no place for conflicting interpretations; scientific knowledge must be consistent, homogeneous and objective. However, the reality is quite the opposite. This simplistic vision shared by judges does not seem to grasp the complexity of everyday medical practice. After a critical reading of the Conseil d'État judgment, we shall consider the potential issues and concerns raised by this ruling in medical practice using the example of hormone therapy for breast cancer patients.
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http://dx.doi.org/10.1684/bdc.2014.1906DOI Listing
March 2014