Clinical guidelines for managing menopausal symptoms in women with (a history of) breast cancer.

Background: One in eight women will be diagnosed with breast cancer. At the time of diagnosis, 75% of patients are postmenopausal. Many will receive anti-hormone therapy, which often induces menopausal symptoms. Premenopausal breast cancer patients frequently become postmenopausal as a result of the treatment and often experience menopausal symptoms. The increased incidence of breast cancer, combined with longer survival, has led to an increase in the number of women experiencing menopausal symptoms. Therefore, the management of menopausal symptoms in women with a history or current breast cancer is a relevant and common clinical problem. Objectives: To provide a clinically useful overview of the steps in the management of menopausal symptoms in women with (a history of) breast cancer. Materials and Methods: A comprehensive literature review was conducted by authors JS and WT using the PubMed and Medline databases. Abstracts were critically appraised and, where appropriate, the full text was analysed. Main Outcome Measures: Not applicable. Results: Depending on the condition, either meta-analyses, randomised controlled trials or retrospective cohorts were identified. No evidence was found for some proposed treatments. Conclusions: Menopausal symptoms in women with (a history of) breast cancer require a patient-tailored approach. Shared decision making is paramount and adequate up-to-date knowledge can help the breast cancer specialist to advise and guide patients accordingly. What is new?: A comprehensive, clinically-based overview of evidence-based treatment options for menopausal symptoms in women with (a history of) breast cancer.

Survey: acceptability of opportunistic bilateral salpingectomy in Flanders.

Background: The VVOG (Flemish Society of Obstetrics and Gynaecology) published a consensus statement promoting opportunistic bilateral salpingectomy (OBS). Objectives: The aim of the study was to obtain insight into the current opinion and general practice of Flemish gynaecologists to counsel and perform OBS. Materials and Methods: A questionnaire was distributed to Flemish gynaecologists three months following publication. Main outcome measures: The drawbacks and incentives to counsel and perform OBS were questioned. Results: Complete response rate was obtained from 99 gynaecologists (17%) and 37 trainees (19%). The majority of respondents (77%) always counselled for OBS in patients scheduled for hysterectomy without oophorectomy. Eighteen per cent counselled only above a certain age cut off and/or if patient was already menopausal. The most important incentive to counsel in cases of hysterectomy by the abdominal approach and vaginal hysterectomy (VH) was the opportunity to prevent ovarian cancer. The yet-undetermined risk of premature ovarian failure was mentioned as the most important barrier in counselling women for OBS in those undergoing hysterectomy by the abdominal approach. For VH, the respondents saw the risk of complications and increased surgical time as the most important barriers. Sixty-one percent of gynaecologists preferred to perform bilateral salpingectomy as sterilisation method. Conclusions: Our study suggests that the concept of OBS is already well known in Flanders. There is a positive attitude towards the routine implementation of OBS, although some barriers and doubts about an age cut-off still exist in practice.

European consensus statement on essential colposcopy.

This European consensus statement on essential colposcopy provides standards for the general colposcopist seeing women referred for colposcopy with an abnormal cervical screening test (including cytology and HPV tests) or with a clinically suspicious cervix. The article gives guidance regarding the aims and conduct of colposcopy. Recommendations are provided on colposcopy technique, the management of common colposcopy issues, treatment and follow-up of after treatment of CIN or early stage cervical. Colposcopists should make an informed decision on the management of each individual that is referred and organize appropriate follow-up. Cervical cancer is still a major health issue and the quality of care can only improve if there is a structured guidance for women with an abnormal smear or suspicious cervix.

A high neutrophil-lymphocyte ratio and platelet-lymphocyte ratio are associated with a worse outcome in inflammatory breast cancer.

INTRODUCTION: Inflammatory breast cancer (IBC) is an uncommon, but aggressive form of breast cancer that accounts for a disproportionally high fraction of breast cancer related mortality. The aim of this study was to explore the peripheral immune response and the prognostic value of blood-based biomarkers, such as the neutrophil-to-lymphocyte ratio (NLR), in a large IBC cohort. PATIENTS & METHODS: We retrospectively identified 127 IBC patients and collected lab results from in-hospital medical records. The differential count of leukocytes was determined at the moment of diagnosis, before any therapeutic intervention. A cohort of early stage (n = 108), locally advanced (n = 74) and metastatic breast cancer patients (n = 41) served as a control population. RESULTS: The NLR was significantly higher in IBC compared to an early stage breast cancer cohort, but no difference between IBC patients and locally advanced breast cancer patients was noted. In the metastatic setting, there was also no significant difference between IBC and nIBC. However, a high NLR (>4.0) remained a significant predictor of worse outcome in IBC patients (HR: 0.49; 95% CI: 0.24-1.00; P = .05) and a lower platelet-lymphocyte ratio (PLR) (≤210) correlated with a better disease-free survival (DFS) (HR: 0.51; 95% CI: 0.28-0.93; P = .03). CONCLUSION: Patients with a high NLR (>4.0) have a worse overall prognosis in IBC, while the PLR correlated with relapse free survival (RFS). Since NLR and PLR were not specifically associated with IBC disease, they can be seen as markers of more extensive disease.

The multidisciplinary approach to ovarian tumours in children and adolescents.

Ovarian tumours in children and adolescents are rare diseases. Although the majority of tumours are benign, the diagnosis and management present various challenges that require a wide range of expertise. The multidisciplinary team ensures not only accurate diagnosis and correct and minimally invasive management, but also minimal psychological impact and the preservation of fertility. This article outlines the multidisciplinary team approach to ovarian masses in children and adolescents. The team includes paediatric oncologists, gynaecological surgeons, pathologists, radiologists, fertility experts, geneticists and psycho-social services.

Infiltrating stromal immune cells in inflammatory breast cancer are associated with an improved outcome and increased PD-L1 expression.

BACKGROUND: Inflammatory breast cancer (IBC) is a rare and rapidly progressive form of invasive breast cancer. The aim of this study was to explore the clinical evolution, stromal tumour-infiltrating lymphocytes (sTIL) infiltration and programmed death-ligand 1 (PD-L1) expression in a large IBC cohort. PATIENTS AND METHODS: Data were collected prospectively from patients with IBC as part of an international collaborative effort since 1996. In total, 143 patients with IBC starting treatment between June 1996 and December 2016 were included. Clinicopathological variables were collected, and sTIL were scored by two pathologists on standard H&E stained sections. PD-L1 expression was assessed using a validated PD-L1 (SP142) assay. A validation cohort of 64 patients with IBC was used to test our findings. RESULTS: Survival outcomes of IBC remained poor with a 5-year overall survival (OS) of 45.6%. OS was significantly better in patients with primary non-metastatic disease who received taxane-containing (neo)adjuvant therapy (P = 0.01), had a hormone receptor-positive tumour (P = 0.001) and had lower cN stage at diagnosis (P = 0.001). PD-L1 positivity on immune cells (42.9%) was higher in IBC than in non-IBC in both our patient samples and the validation cohort. Furthermore, PD-L1 expression predicted pCR (P = 0.002) and correlated with sTIL infiltration (P < 0.001). sTIL infiltration of more than 10% of the stroma was a significant predictor of improved OS (HR 0.47, 95% CI 0.27-0.81, P = 0.006) in a multivariate model. CONCLUSIONS: IBC is characterised by poor survival and high PD-L1 immunoreactivity on sTIL. This suggests a role for PD1/PD-L1 inhibitors in the treatment of IBC. Furthermore, we showed that PD-L1 expression predicts response to neo-adjuvant therapy and that sTIL have prognostic significance in IBC.

VALHUDES: A protocol for validation of human papillomavirus assays and collection devices for HPV testing on self-samples and urine samples.

BACK GROUND: Systematic reviews have concluded that hrHPV DNA testing using target-amplification tests is as accurate on vaginal self-samples as on clinician-taken specimens for the detection of cervical precancer. However, insufficient evidence is available for specific HPV assay/self-sample device combinations. OBJECTIVES: The VALHUDES protocol is designed as a diagnostic test accuracy study that aims to compare the clinical sensitivity and specificity of particular hrHPV assay(s) on vaginal self-samples and first-void-urine, collected in agreement with standardized protocols, with hrHPV testing on matched clinician-taken samples. STUDY DESIGN: Five hundred enrolled women referred to a colposcopy clinic are invited to collect a first-void urine sample and one or more vaginal self-samples with particular devices before collection of a cervical sample by a clinician. Sample sets are subsequently analysed in a laboratory accredited for HPV testing. Disease verification for all enrolled patients is provided by colposcopy combined with histological assessment of biopsies. RESULTS: A first VALHUDES study has started in Belgium in December 2017 with enrolment from four colposcopy centres. The following assays are foreseen to be evaluated: RealTime High Risk HPV assay (Abbott), cobas-4800 and -6800 (Roche), Onclarity (BD), Xpert HPV (Cepheid) and Anyplex II HPV HR (Seegene). CONCLUSION: Given empirical evidence that the relative accuracy of HPV-testing on self- vs clinician-samples is robust across clinical settings, the VALHUDES protocol offers a framework for validation of HPV assay/self-sample device combinations that can be translated to a primary screening setting.

Perspective: Towards Personalised Metabolic Coaching in Cancer.

Although cancer survivorship has improved over the last decades, numbers of cancer incidence and prevalence are rising. Evidence is growing that lifestyle factors, such as physical activity, a healthy weight management and -diet, play an important role in first- and second line preventive strategies. When implementing a healthy lifestyle, the maintenance of the energy balance should be taken into account. The energy equilibrium is achieved when the energy intake (Ei) for one day is equal to the total daily energy expenditure (TEE). The latter is, among others, made up of the resting energy expenditure, its largest contributor (60-80% of TEE), and can be assessed by indirect calorimetry (i.e. the gold standard). The resting energy expenditure reflects the individual's minimal caloric need in 24h to support basal functions. In cancer patients, energy imbalances, expressed as a positive (Ei > TEE) or negative (Ei & TEE) energy balance, may occur and are characterised by weight gain or -loss respectively. As a corollary, shifts in fatmass and fatfree mass are reported. Adequate nutritional follow-up is necessary in order to meet the energy needs, since both positive and negative energy balances are known to have deteriorating effects on cancer prognosis and mortality. In the clinical setting, predictive formulas (e.g. Harris-Benedict equation) are often used to estimate the caloric need. However, both under- and overfeeding are reported when using equations. Therefore, we advise to use indirect calorimetry in the standard assessment of a patient's energy need in order to provide adequate metabolic coaching and -follow up.

Breast cancer and fat grafting: efficacy, safety and complications-a systematic review.

Autologous fat grafting (AFG) or lipofilling is nowadays a popular technique for breast reconstruction after breast cancer surgery. There is debate regarding the oncological safety and risks of this procedure in breast cancer patients. A systematic review of the literature published between January first 1995 and October first 2016 was conducted regarding the efficacy, safety and complications of this technique in breast cancer patients after their cancer treatment. The databases PubMed, Science Direct and Thomson Reuters Web of Science were used to search for qualified articles. Inclusion criteria were women with a personal history of breast cancer and at least one lipofilling procedure. Only studies containing a minimum of 20 patients were included in this systematic review. The search yielded a total of 23 suitable articles: 18 case series, 4 retrospective cohort studies and one prospective cohort study. The systematic review encompassed a total of 2419 patients. Medical imaging was used in the majority of the studies to assess the follow-up. Mammography was the most popular technique (65.2%), followed by ultrasound (47.8%) and MRI (30.4%). The prevalence of complications was the following: fat necrosis in 5.31%, benign lesions, like cysts or calcifications in 8.78%, infections in 0.96% and local cancer recurrence in 1.69%. AFG or lipofilling appears to be an oncological safe technique with a low morbidity in women with a history of breast cancer. In order to have a better understanding and evidence of the oncological safety a randomised controlled trial is urgently needed. We further recommend that all AFG be registered in the cancer register.

Current and future role of circulating tumor cells in patients with epithelial ovarian cancer.

Circulating tumor cells (CTCs) are viable tumor cells that are released into the circulatory system. CTCs have shown a prognostic value in numerous solid tumors. CTC research in epithelial ovarian carcinoma (EOC) has attracted only little attention. Since the primary route of metastasis in EOC is considered to be direct peritoneal spread in the abdominal cavity and distant metastases only occur in one third of the patients, it was thought that there is not enough shedding of tumor cells in the circulation. Nevertheless recent studies revealed an important role of hematogenous spread in EOC and showed that CTC status is associated with advanced tumor stage, CA-125 levels and residual disease after surgery. Furthermore the presence of CTCs correlates with shorter overall and disease free survival. However this prognostic value of CTCs in EOC seems to depend on the used isolation and detection methods. In EOC function- or density based enrichment methods seem to offer more promising results then epithelial cell adhesion molecule (EpCAM)-based approaches. This can be explained by a low number of EpCAM positive CTCs in EOC and the downregulation of EpCAM during epithelial-to-mesenchymal transition (EMT). The presence of CTCs might also have predictive value as CTC status was associated with treatment response in two studies and CTCs showed to be a better monitoring tool then CA-125 in a small population. The (genotypic) characterization of CTCs might become even more important in the future paving the way for CTCs to a true predictive "liquid tumor biopsy".

Cross-cultural Psychometric Evaluation of the Dutch McGill-QoL Questionnaire for Breast Cancer Patients.

AIM OF THE STUDY: Assessing the cross-cultural psychometric properties of the Dutch-MQoL for breast cancer patients. METHODS: 26 patients were recruited at the Antwerp University Hospital. Eligible patients filled in the MQoL on different moments in time in order to evaluate clinimetric properties. To determine the validity; MQoL was correlated to the EORTC QLQ-C30. Internal consistency was analysed using Cronbach's and test-retest reliability was determined by ICC. For statistical responsiveness, S.E.M and MDC were calculated. RESULTS: A strong correlation was found between the 'QoL score' of the MQoL and the domain 'existential well- being' of the EORTC QLQ-C30 (r = 0.72). An excellent test-retest reliability (ICC (1,1)) was demonstrated with intraclass coefficients ranging from 0.82 to 0.92. A MDC in total score of only 1.22 (12%) was seen, needed to detect a factual change within a patients' QoL. Psychometric properties of the Dutch MQoL were found comparable to the properties of the original questionnaire. CONCLUSION: The Dutch version of the MQoL is a valid and reliable questionnaire for breast cancer patients and shows statistical responsiveness. Due to the strong to excellent reliability, this version of the MQoL is useful in clinical as well as scientific setting.

The impact of conisation on pregnancy outcome.

AIM: The objective of present study was to investigate whether conisation is associated with adverse pregnancy outcomes in Flanders, Belgium. Therefore a retrospective cohort study was conducted at the Antwerp University Hospital. MATERIALS AND METHODS: The study was approved by the Ethical Committee and based on a questionnaire as well as on medical records. Confounders, like smoking, alcohol use, drug use, chronic illness, and gynaecological disorders during pregnancy were all taken into account. A multiple logistic regression was performed for an association between adverse pregnancy outcomes and confounders. RESULTS: The study showed that there was association between conisation, low birth weight, and caesarean section. After conisation there was a significantly higher risk of 3.275 on a low birth weight. The risk of a caesarean section after conisation was tripled. A gynaecological disorder during the pregnancy had a significantly higher risk of delivering a child with a low birth weight and a higher risk of a caesarean section. Smoking and a chronic illness gave a significant higher risk of caesarean section. DISCUSSION: Conisation is easy to perform and highly effective in the prevention of cervical cancer. Conisation has a high morbidity, as it is associated with severe adverse pregnancy outcome. A conisation should therefore only be performed on a true indication; otherwise it will be the victim of its own success.

Guide wire surgery in breast cancer and why to avoid scissors.

CASE: A 58-year old woman presented with microcalcifications in her left breast. A biopsy showed a low-grade ductal carcinoma in situ. A tumorectomy was performed using a harpoon-shaped guide wire to remove the entire lesion. No additional therapy was given. Six months later during follow-up the mammography revealed that the distal end of the guide wire was still present in the left breast. CONCLUSION: When performing a tumorectomy using a guide wire, the completeness of the wire should be checked during surgery. Additionally cutting of the wire can be prevented by using a scalpel instead of scissors during surgery.

A cross-sectional, multicentre, epidemiological study on human papillomavirus (HPV) type distribution in adult women diagnosed with invasive cervical cancer in Belgium.

OBJECTIVE: Despite an advanced national cervical cancer screening and vaccination programme cervical cancer is still the third most frequent diagnosed gynaecological tumour in Belgium. The goal of this study is to present the Belgian data of a cross-sectional, multicentre, epidemiological study on human papillomavirus (HPV) type distribution in adult women diagnosed with invasive cervical cancer (ICC) conducted in 12 European countries. MATERIAL AND METHODS: Centres in four major Belgian cities (Antwerp, Brussels, Ghent and Liège) participated in this study. Tissue samples from women with ICC were collected from the period 2001 - 2008. All slides were centrally reviewed and analysed for HPV. The total enrolled cohort included 278 subjects. RESULTS: The histologically eligible cohort comprised of 255 patients (mean age 51.3 ± 15.1 years) and 237 were confirmed HPV positive (mean age 50.6 ± 14.9 years). A single HPV infection was present in 95.8%. The five most frequent HPV types were HPV 16 (68.7%), HPV18 (12.3%), HPV 31 (6.2%), HPV 33 (5.3%) and HPV 45 (1.8%). Multiple HPV types were present in 3.4%, with two HPV types in 2.5% and three HPV types in 0.8%. In the various HPV type combinations observed in multiple infected women, HPV 31 (62.5%) and HPV 33 (50.0%) were the most frequent. The ratio of adenocarcinoma (ADC) versus squamous cell carcinoma (SCC) cases in the histologically eligible cohort was 1:8. Compared to the pooled European data the Belgium HPV 16 is 1.1, HPV 33 is 1.2 and HPV 31 is 1.7 higher and the HPV 18 is 0.8 and HPV 45 is 0.34 lower. CONCLUSION: The 5 most frequent HPV types in Belgium are the same as in the rest of Europe, but the distribution is different. Cervical cancer screening should therefore be HPV type specific and HPV prophylactic vaccination should also focus on other types then HPV 16 and HPV 18. A national registry is needed in order to follow the trends of HPV types in the society and to measure the impact of prevention, for which the data presented in this study can be an important basis.

Ductal carcinoma in situ: a disease entity that merits more recognition.

Ductal carcinoma in situ (DCIS) is a non-invasive breast carcinoma that remains in the milk ducts. It is a poorly understood disease and its natural history is not well known. This is because once diagnosed, DCIS is usually treated. It is known however that ductal carcinoma is a precursor of invasive breast carcinoma, as 14-53% can become invasive over a period of 10 years, if left untreated. With increasing knowledge about the molecular biology of DCIS, more insight is given in its relation to invasive breast cancer. Diagnosis of ductal carcinoma in situ is increasing in the last few years. This is likely caused by the increased mammographic screening for breast cancer and the higher quality of mammographic images. DCIS represents about one fifth of all mammographically detected breast cancers. Risk factors for the development of ductal carcinoma in situ are: low parity, late age at first birth and menopause, and Body Mass Index. The Van Nuys Prognostic Index is a useful scoring system to grade DCIS. DCIS is graded by scoring four characteristics: patient's age, margin width, tumor size and pathological classification. It allows us to divide DCIS lesions into different groups according to risk of local recurrence: low risk, intermediate risk and high risk. Each group requires a different treatment, respectively: local excision of the tumor; local excision and radiotherapy; and mastectomy. The use of tamoxifen in the treatment of DCIS is still controversial, but research so far has encouraging results. Interesting developments have been made in the use of Her-2 pulsed dendritic cell vaccination before DCIS surgery.

The socio-economical impact of intravenous (IV) versus subcutaneous (SC) administration of trastuzumab: future prospectives.

Trastuzumab was the first targeted therapy for HER2 positive breast cancer. It has become the standard of care for HER2 positive metastatic breast cancer since 2000 and in the adjuvant setting since 2006. Adjuvant it is given for a year and in patients with metastatic disease until progression. The standard mode of administration is intravenous. Recently a subcutaneous form has become available. A phase III study showed that there is no difference between the intravenous and subcutaneous form in terms of safety and efficacy. The patient's preference however significantly favoured the subcutaneous form. It is estimated that the use of the SC form could contribute to a cost saving between 758 and 2576 euro per annual course. For Belgium alone this could mean an estimated saving of 1.4 to 4.6 million euros per year. The potential benefit of the SC administration for healthcare facilities could be further increased when applied in a LEAN working day-care chemotherapy unit. After reviewing the existing literature we suggest to further validate the potential financial impact of SC trastuzumab compared to the traditional IV form and to introduce a scientific proposal incorporating the benefits of this formulation in a LEAN working healthcare unit.