Impact of the line of treatment on progression-free survival in patients treated with T-DM1 for metastatic breast cancer.

BACKGROUND: Trastuzumab emtansine (T-DM1) is indicated as second-line treatment for human epidermal growth factor receptor 2 (HER2)-positive metastatic or unresectable locally advanced breast cancer, after progression on trastuzumab and a taxane-based chemotherapy. We wished to determine if the line of treatment in which T-DM1 is administered has an impact on progression-free survival (PFS) and in particular, if prior treatment with capecitabine/lapatinib or pertuzumab modifies PFS of further treatment with T-DM1. PATIENTS AND METHODS: We performed a multicenter retrospective study in 3 Belgian institutions. We evaluated PFS with T-DM1 in patients treated for HER2 positive metastatic or locally advanced unresectable breast cancer between January 1, 2009 and December 31, 2016. RESULTS: We included 51 patients. The median PFS was 9.01 months. The line of treatment in which T-DM1 (1st line, 2nd line, 3rd line or 4+ lines) was administered had no influence on PFS (hazard ratio 0.979, CI95: 0.835-1.143). There was no significant difference in PFS whether or not patients had received prior treatment with capecitabine/lapatinib (9.17 vs 5.56 months, p-value 0.875). But, patients who received pertuzumab before T-DM1 tended to exhibit a shorter PFS (3.55 months for T-DM1 after pertuzumab vs 9.50 months for T-DM1 without pretreatment with pertuzumab), even if this difference was not statistically significant (p-value 0.144). CONCLUSION: Unlike with conventional chemotherapy, the line of treatment in which T-DM1 is administered does not influence PFS in our cohort of patients with advanced HER2-positive breast cancer.

The advantages of hypnosis intervention on breast cancer surgery and adjuvant therapy.

BACKGROUND: In oncology, hypnosis has been used for pain relief in metastatic patients but rarely for induction of anesthesia. MATERIAL AND METHOD: Between January 2010 and October 2015, 300 patients from our Breast Clinic (Cliniques universitaires Saint-Luc, Université catholique de Louvain) were included in an observational, non-randomized study approved by our local ethics committee (ClinicalTrials.gov - NCT03003611). The hypothesis of our study was that hypnosis intervention could decrease side effects of breast surgery. 150 consecutive patients underwent breast surgery while on general anesthesia (group I), and 150 consecutive patients underwent the same surgical procedures while on hypnosis sedation (group II). After surgery, in each group, 32 patients received chemotherapy, radiotherapy was administered to 123 patients, and 115 patients received endocrine therapy. RESULTS: Duration of hospitalization was statistically significantly reduced in group II versus group I: 3 versus 4.1 days (p = 0.0000057) for all surgical procedures. The number of post-mastectomy lymph punctures was reduced in group II (1-3, median value n = 1.5) versus group I (2-5, median value n = 3.1) (p = 0.01), as was the quantity of lymph removed (103 ml versus 462.7 ml) (p = 0.0297) in the group of mastectomies. Anxiety scale was also statistically reduced in the postoperative period among the group of patients undergoing surgery while on hypnosis sedation (p = 0.0000000000000002). The incidence of asthenia during chemotherapy was statistically decreased (p = 0.01) in group II. In this group, there was a statistically non-significant trend towards a decrease in the incidence of nausea/vomiting (p = 0.1), and the frequency of radiodermitis (p = 0.002) and post-radiotherapy asthenia (p = 0.000000881) was also reduced. Finally, the incidence of hot flashes (p = 0.0000000000021), joint and muscle pain (p = 0.0000000000021) and asthenia while on endocrine therapy (p = 0.000000022) were statistically significantly decreased in group II. DISCUSSION: Hypnosis sedation exerts beneficial effects on nearly all modalities of breast cancer treatment. CONCLUSION: Benefits of hypnosis sedation on breast cancer treatment are very encouraging and further promote the concept of integrative oncology.

Breast prosthesis infection and pets: A case report and review of the literature.

INTRODUCTION: Pets are not always the human's best friends, particularly in the presence of comorbidities such as wounds. The following case report describes a Pasteurella multocida infection of a reconstructive breast implant due to a close contact between a cat and its owner. PRESENTATION OF CASE: A 33-year-old woman developed a breast implant infection 13 days after an immediate breast reconstruction following a mastectomy for a multifocal ductal carcinoma. The wound was explored surgically and the implant removed. Culture extracted from fluid around the prosthesis evidenced the presence of P. multocida, a Gram-negative coccobacillus which is present in the oral commensal flora of cats and dogs. CONCLUSION: In the case of breast infection, surgical revision - with or without removal of the implant - is required in order to carry out a meticulous intraoperative cleaning. Antibiotherapy is always necessary in such cases. Particularly when patients presenting comorbidities are concerned, the focus must be put on avoiding close contact of the wound with pets.

Texture analysis on MR images helps predicting non-response to NAC in breast cancer.

BACKGROUND: To assess the performance of a predictive model of non-response to neoadjuvant chemotherapy (NAC) in patients with breast cancer based on texture, kinetic, and BI-RADS parameters measured from dynamic MRI. METHODS: Sixty-nine patients with invasive ductal carcinoma of the breast who underwent pre-treatment MRI were studied. Morphological parameters and biological markers were measured. Pathological complete response was defined as the absence of invasive and in situ cancer in breast and nodes. Pathological non-responders, partial and complete responders were identified. Dynamic imaging was performed at 1.5 T with a 3D axial T1W GRE fat-suppressed sequence. Visual texture, kinetic and BI-RADS parameters were measured in each lesion. ROC analysis and leave-one-out cross-validation were used to assess the performance of individual parameters, then the performance of multi-parametric models in predicting non-response to NAC. RESULTS: A model based on four pre-NAC parameters (inverse difference moment, GLN, LRHGE, wash-in) and k-means clustering as statistical classifier identified non-responders with 84 % sensitivity. BI-RADS mass/non-mass enhancement, biological markers and histological grade did not contribute significantly to the prediction. CONCLUSION: Pre-NAC texture and kinetic parameters help predicting non-benefit to NAC. Further testing including larger groups of patients with different tumor subtypes is needed to improve the generalization properties and validate the performance of the predictive model.

The place of extensive surgery in locoregional recurrence and limited metastatic disease of breast cancer: preliminary results.

UNLABELLED: The aims of this study were first to clearly define two different entities: locoregional recurrences and limited metastatic disease and secondly to evaluate the place of extensive surgery in these two types of recurrence. MATERIAL AND METHODS: Twenty-four patients were followed from June 2004 until May 2014. All patients underwent surgery but for 1 patient this surgery was stopped because the tumour was unresectable. RESULTS: The median interval between surgery for the primary tumour and the locoregional recurrence or metastatic evolution was 129 months. Eight patients had pure nodal recurrences, 4 had nodal and muscular recurrences, 5 had muscular + skin recurrences, and 8 had metastatic evolution. Currently, all patients are still alive but 2 have liver metastases. Disease free survival was measured at 2 years and extrapolated at 5 years and was 92% at these two time points. No difference was observed for young or older women; limited metastatic evolution and locoregional recurrence exhibited the same disease free survival. CONCLUSION: Extensive surgery has a place in locoregional and limited metastatic breast cancer recurrences but this option must absolutely be integrated in the multidisciplinary strategy of therapeutic options and needs to be planned with a curative intent.

Intraoperative use of ketorolac or diclofenac is associated with improved disease-free survival and overall survival in conservative breast cancer surgery.

BACKGROUND: An association between the use of non-steroidal anti-inflammatory drugs (NSAIDs) and better outcome after mastectomy and lung surgery for cancer has been recently suggested. In a retrospective analysis, we investigated the association between intraoperative NSAIDs use in conservative breast cancer surgery and breast cancer disease-free survival (DFS). Similarly, we also evaluated the association between breast cancer DFS and preoperative neutrophil:lymphocyte ratio (NLR). METHODS: A retrospective analysis of a single-centre cohort was performed in breast cancer patients (n=720) with uni- and multivariate analyses, using a Cox regression model. RESULTS: In conservative breast cancer surgery, the intraoperative use of NSAIDs (ketorolac or diclofenac) was associated with an improved DFS {hazard ratio (HR)=0.57 [95% confidence interval (CI): 0.37-0.89], P=0.01} and an improved overall survival (OS) [HR=0.35 (95% CI: 0.17-0.70), P=0.03]. In these patients, an NLR >3.3 (identified by a receiver-operating characteristic curve) was associated with a shorter DFS [HR=1.99 (95% CI: 1.16-3.41), P=0.01] and OS [HR=2.35 (95% CI: 1.02-5.43), P=0.046]. CONCLUSIONS: Intraoperative NSAIDs and higher preoperative NLR are associated with improved outcome in conservative breast cancer surgery. Prospective, randomized trials to evaluate if these associations are causal are warranted.

Genomic grade adds prognostic value in invasive lobular carcinoma.

BACKGROUND: The prognostic value of histologic grade (HG) in invasive lobular carcinoma (ILC) remains uncertain, and most ILC tumors are graded as HG2. Genomic grade (GG) is a 97-gene signature that improves the prognostic value of HG. This study evaluates whether GG may overcome the limitations of HG in ILC. METHODS: Gene expression data were generated from frozen tumor samples, and GG calculated according to the expression of 97 genes. The prognostic value of GG was assessed in a stratified Cox regression model for invasive disease-free survival (IDFS) and overall survival (OS). RESULTS: A total of 166 patients were classified by GG. HG classified 33 (20%) tumors as HG1, 120 (73%) as HG2 and 12 (7%) as HG3. GG classified 106 (64%) tumors as GG low (GG1), 29 (17%) as GG high (GG3) and 31 (19%) as equivocal (cases not classified as GG1 or GG3). The median follow-up time was 6.5 years. In multivariate analyses, GG was associated with IDFS [HR(GG3 vs GG1) 5.6 (2.1-15.3); P < 0.001] and OS [HR(GG3 vs GG1) 7.2, 95% CI (1.6-32.2); P = 0.01]. CONCLUSIONS: GG outperformed HG in ILC and added prognostic value to classic clinicopathologic variables, including nodal status.

Fibroadenoma: can fine needle aspiration biopsy avoid short term follow-up?

OBJECTIVE: To confirm whether fine needle aspiration biopsy (FNAB) can avoid close monitoring, a source of worry for women patients with a suspected fibroadenoma found by ultrasound, and requiring their compliance. PATIENTS AND METHODS: Over 39months, 427 nodules with a diagnosis of fibroadenoma were sampled in 372 patients using ultrasound-guided FNAB. The sonographic appearance of all the nodules suggested BI-RADS category 3 fibroadenomas. The mean size of the fibroadenomas was 9mm. The mean duration of follow-up was 29.7months. RESULTS: Seven nodules had atypical cytology: a microbiopsy and/or excision found a simple fibroadenoma (n=3), mastitis (n=1), a fibroadenoma associated with a papilloma (n=1), fibrosis (n=1) and normal tissue (n=1). Seven other nodules were resected during treatment for synchronous cancer, and were diagnosed as fibroadenomas. Two hundred and seventy-six nodules were followed-up (121 patients were lost to follow-up [n=132]) and the appearance of 263 nodules (95.29%) was stable. Seven nodules, which had increased in size, underwent another FNAB or microbiopsy or surgery. Five nodules were not found again. The borders of one nodule showed modifications. CONCLUSION: The use of fine needle aspiration biopsy, interpreted by an experienced cytologist, means that short term follow-up of fibroadenomas can be avoided.

[Breast liposarcoma]. / Breast liposarcoma.

Liposarcoma of the breast constitutes 1% of all malignant breast tumors. We report the case of a 42-year-old woman presented with a 5 cm-mass in the left breast. Mammography, ultrasonography and MRI showed a non-specific appearance and the histological evaluation was necessary for definitive diagnosis.

[Contribution of MRI for monitoring response to neoadjuvant chemotherapy in the management of breast cancer]. / Contribution of MRI for monitoring response to neoadjuvant chemotherapy in the management of breast cancer.

In the management of breast neoplasms, two breast MR examinations are performed, one before initiation of neoadjuvant chemotherapy (NAC) and one at the end. However, a third MR exam may be performed between two courses of chemotherapy in order to assess tumor response to treatment. The assessment criterion currently used is measurement of tumor diameter according to RECIST (Response Evaluation Criteria In Solid Tumors) and WHO. But according to the preliminary results of the American College of Radiology Imaging Network protocol, using measurement of tumor volume as a reference may be valuable. Larger series are therefore necessary to estimate the value of diffusion MR, spectroscopy and diffusion studies.

[Contribution of sonoelastography to the characterization of breast lesions]. / In Process Citation.

We evaluate the performances of sonoelastography in the characterization of breast nodules with histologic correlation. Elastosonography was performed immediately after mode B sonography in 59 patients (65 nodules) by two radiologists, independently. All sequences of elastosonography were recorded. An intra and inter -observers correlation was calculated. Each nodule was classified with BI-RADS lexicon and with Ueno elastography classification. The scores 1-3 were considered as benign and 4-5 as malignant. A cytologic/histologic diagnosis was available for all nodules. At histology, 16 nodules were malignant and 49 nodules were benign. The intra and inter-observer correlations of elastosonography were excellent. The sensitivity, specificity, PPV, NPV of sonoelastography were 87.5%, 98%, 93.3%, 96%, respectively comparing with 100%, 93.9%, 84%, 100% of Mode B sonography. Thus, 95% (36/38 nodules) of BI-RADS 3 nodules were reclassified score 2 or 1 with elastosonography, decreasing the rates of fine needle aspiration and short-term follow-up. Elastosonography is a simple, rapid and complementary method to mode B sonography that can improve the specificity in the characterization of breast nodules and the management of BI-RADS 3 nodules, leading to a decrease of false-positive and short term follow-up rates.

[Juvenille papillomatosis]. / Papillomatose juvénile mammaire.

The authors report a patient with juvenile papillomatosis of the breast presenting with a palpable mass and illustrate the correlation between mammographic, sonographic and pathologic features.

LH-RH agonists offer very good protection against the adverse gynaecological effects induced by tamoxifen.

This study was initiated to evaluate the efficacy of luteinizing hormone-releasing hormone (LH-RH) agonists in protecting premenopausal patients against the adverse gynaecological effects induced by tamoxifen. Between January 1998 and January 2000, 85 premenopausal breast cancer patients were included in this prospective study. All were to receive LH-RH agonists and tamoxifen for a minimum of two years. All patients underwent a pretreatment gynaecological evaluation and annual follow-up. Bone density was also measured at the start of treatment and then after 2, 3 and 4 years. Pretreatment evaluation revealed 2 polyps. At one and two years of follow-up, no abnormal symptoms were noted and echographic findings were normal. At three years of follow-up, a polyp associated with adnexal masses was discovered. Histology revealed ovarian and endometrial metastases of infiltrating lobular breast carcinoma. Bone density evaluation after 2, 3 and 4 years of treatment showed no significant bone loss. LH-RH agonists offer safe protection against the gynaecological side-effects of tamoxifen in premenopausal breast cancer patients.

[Localization of non-palpable breast lesions with black carbon powder (experience of the Catholic University of Louvain)]. / Repérage au noir de carbone dans les lésions mammaires non palpables (expérience de l'UCL).

PURPOSE: The authors report their experience in presurgical localization of non palpable lesions with black carbon powder. MATERIALS AND METHODS: 153 cases of primary tumorectomies and mastectomies have been reviewed. The suspension is prepared in the hospital's pharmacy, the procedure is performed days or weeks before scheduled surgery without diffusion in the surrounding tissues. RESULTS: In 92% of cases, the carbon marker was observed less than 5 mm from the target and no significant interference with the pathologic diagnosis has been observed. CONCLUSION: Patient tolerance is good and providing close collaboration between the different members of the treating team, the authors believe that this technique may be a good alternative to wire localization.

Immunolocalisation of cytochrome P-450 3A enzymes in human breast carcinoma: relationship with tumour differentiation and steroid receptors.

Cytochrome P-450 3A enzymes belong to the most abundant subfamily of the cytochrome P-450 system. They are predominantly found in the liver where they metabolize numerous drugs and endogenous substances such as oestrogens. However, they are also expressed by normal and tumoural extrahepatic tissues. Accordingly, immunolocalization was assessed in malignant breast tumours (n=32) and normal counterparts, by using a monoclonal antibody that recognizes all human CYP3A proteins. We investigated a potential relation between expression of CYP3A protein expression, the degree of tumour differentiation assessed by the histological grade and the proliferation index assessed by Ki-67 immunostaining. Immunodetection of CYP3A was observed in 27 of the 32 tumours analyzed (84%). A focal staining was also observed in the adjacent normal breast tissue in 33% of the samples, but expression was always fainter than in tumours. A significant negative association was found between CYP3A and the proliferation index, but there was no relation with receptor status or tumour differentiation. While CYP3A protein expression can be found in normal breast tissues, these data highlight higher and more frequent CYP3A in malignant breast cells. Such expression in malignant breast cells appears inversely related to the proliferation index whereas no relation is found with tumour differentiation.

The Place of Whole-Body PET FDG for the Diagnosis of Distant Recurrence of Breast Cancer.

Purpose: To study the role of positron emission tomography 18F-fluorodeoxyglucose (PET FDG) imaging in patients with a suspicion of breast cancer recurrence.Procedures: Whole-body PET FDG was performed in 39 women. Thirty-four were included because of asymptomatic tumor marker increase. PET findings were confirmed by oriented imaging or by biopsy. Follow-up data were collected over a period of at least 12 months.Results: PET FDG depicted 37/39 sites in 31/33 patients with recurrence. PET missed one locoregional recurrence and in one patient peritoneal carcinomatosis developed 6 months after a negative PET. False positive PET FDG corresponded to lung infection, degenerative bone disease, and reconstruction artifact. The conventional imaging work-up depicted sites of recurrence in 6/33 patients.Conclusion: Whole-body PET FDG is highly sensitive for the detection of distant breast cancer recurrence. Prospective studies are mandatory to address its potential impact on patient management and survival.