Review Article a Multidisciplinary Evaluation for Advanced Supportive Care of Breast Cancer Patients.

Background: Cancer cases diagnosed each year are increasing, mainly because the population is ageing and, in part, due to early detection. This implies that there are more and more persons that receive medical anticancer therapies and that are interested in maintaining their quality of life. Many oncological treatments, including chemotherapy, immunotherapy, surgery, and radiotherapy, and combined therapy are associated with cutaneous toxicity and long-term side effects to different tissues and organs. This is particularly relevant when new therapies are used since these may cause new and unexpected side effects that may be short-lived but, in some cases, may become chronic or permanent. Patients often seek advice with their oncologists on what can be done and what cannot be done. Notably, many of the cutaneous side effects can be prevented or reduced by adequate interventions. Summary: The aim of this review is to highlight how oncological patients may benefit from a closer collaboration between specialists in different branches. We will focus on women with breast cancer since we think that they may derive a special benefit from this collaboration, but we will analyse other cancers in future papers. Key Messages: The working group was created to help the medical doctor in the prevention and management of all the adverse effects of the oncological treatments, supporting patients in this phase of their life, including nutritional assessment and dietary support.

Treatment of brain metastases in ALK-positive non-small cell lung cancer.

Brain metastases are quite frequent in patients with ALK-translocated non-small cell lung cancer (NSCLC): they are often not amenable to surgical resection and are generally treated with radiotherapy (RT). This however causes severe late toxic side effects that may become invalidating considering the relatively long survival provided by recent medical treatment with target therapies. Several clinical trials have demonstrated that ALK-inhibitors (crizotinib, alectinib, brigatinib) show excellent activity also against brain metastases. It is therefore reasonable, in asymptomatic patients, to start treatment with specific inhibitors: RT will be used at the time of tumor progression or when symptoms appear. This sequence provides the best quality of life for patients.

Bringing Onco-Innovation to Europe's Healthcare Systems: The Potential of Biomarker Testing, Real World Evidence, Tumour Agnostic Therapies to Empower Personalised Medicine.

Rapid and continuing advances in biomarker testing are not being matched by uptake in health systems, and this is hampering both patient care and innovation. It also risks costing health systems the opportunity to make their services more efficient and, over time, more economical. The potential that genomics has brought to biomarker testing in diagnosis, prediction and research is being realised, pre-eminently in many cancers, but also in an ever-wider range of conditions-notably BRCA1/2 testing in ovarian, breast, pancreatic and prostate cancers. Nevertheless, the implementation of genetic testing in clinical routine setting is still challenging. Development is impeded by country-related heterogeneity, data deficiencies, and lack of policy alignment on standards, approval-and the role of real-world evidence in the process-and reimbursement. The acute nature of the problem is compellingly illustrated by the particular challenges facing the development and use of tumour agnostic therapies, where the gaps in preparedness for taking advantage of this innovative approach to cancer therapy are sharply exposed. Europe should already have in place a guarantee of universal access to a minimum suite of biomarker tests and should be planning for an optimum testing scenario with a wider range of biomarker tests integrated into a more sophisticated health system articulated around personalised medicine. Improving healthcare and winning advantages for Europe's industrial competitiveness and innovation require an appropriate policy framework-starting with an update to outdated recommendations. We show herein the main issues and proposals that emerged during the previous advisory boards organised by the European Alliance for Personalized Medicine which mainly focus on possible scenarios of harmonisation of both oncogenetic testing and management of cancer patients.

First-in-human pharmacokinetics of tamoxifen and its metabolites in the milk of a lactating mother: a case study.

BackgroundBreast cancer represents the most frequent neoplasm diagnosed in women of childbearing age. When the tumour is oestrogen receptor-positive, tamoxifen is among the recommended endocrine treatments. Lactating women are advised not to breastfeed while receiving tamoxifen. However, information about tamoxifen transfer into breast milk is lacking.MethodsWe measured the concentration of tamoxifen and its metabolites by liquid chromatography-tandem mass spectrometry in the milk of a nursing mother that was treated for pregnancy-associated breast cancer diagnosed a few months after delivery. She was advised not to breastfeed her child and she collected milk samples for 23 days while the baby was fed with formula.ResultsTamoxifen concentrations in milk increased reaching a maximum of 214 nM. The two active metabolitesZ-4-hydroxy-tamoxifen and Z-endoxifen, could not be quantified in milk the first days after tamoxifen intake, but increased over time and reached clinically significant levels after day 18.ConclusionThis study demonstrates for the first time in human that tamoxifen and its metabolites transfer into milk. Since tamoxifen has a complete oral bioavailability, a long half-life (>7 days) and may interfere with the normal development of the infant, mothers should not breastfeed during tamoxifen treatment.

Lactation during and after Breast Cancer.

Breastfeeding is an important aspect of mother-newborn relationship and is of great benefit for the baby. Unfortunately, many drugs taken by the mother may pass into her milk and exert an effect on the newborn. Very limited data is available and a cautionary approach is warranted especially when the woman receives anticancer treatment including chemotherapy , hormonal treatment and the recently introduced target agents as well as monoclonal antibodies. In all these conditions breastfeeding should be put on hold.More and more often physicians are faced with women that are pregnant years after the diagnosis of cancer: this has long been considered dangerous for the mother, but data show that prognosis is definitely not worse. If the woman is no longer being actively treated, breastfeeding is advisable every time it is possible, even if patients that received breast radiation may be unable to produce a sufficient amount of milk on that side.

Pregnancy and Lactation: Risk or Protective Factors for Breast Cancer?

Pregnancy and lactation represent the most effective protective elements against breast cancer; counter-intuitively breast cancer incidence shows a small but noticeable increase up to 5 years after delivery. The cumulative effect is however favourable and women show a reduction in breast cancer risk which is proportional to the total duration of lactation and to the number of full-term pregnancies.

Propelling Healthcare with Advanced Therapy Medicinal Products: A Policy Discussion.

Recent advances in biomedicine are opening the door to new approaches, and treatment and prevention are being transformed by novel medicines based on genetic engineering, innovative cell-based therapies and tissue-engineered products, and combinations of a medical device with embedded cell or tissue components. These advanced therapy medicinal products (ATMPs) hold one of the keys to making a reality of genuinely personalised medicine. There are an estimated 450 companies across the globe working on the development of gene therapies and more than 1,000 clinical trials underway worldwide, and some 20-30 new ATMPs filings are expected in Europe annually over the next 5 years. But challenges confront the sector, complicating the translation from research into patient access. Scientific, clinical development and regulatory issues are compounded by limited experience with clinical and commercial use, limited manufacturing know-how, high costs, and difficulties in accessing development funding and investment. Pricing and reimbursement and market access issues are an additional challenge, particularly in Europe, where unfamiliarity with the technology and uncertainty over the use of real-world evidence induce caution among clinicians, health technology assessment bodies and payers. There is a need for a review of the suitability of the regulatory and market access framework for these products, focused development of data, public/private partnerships, and fuller collaboration governments, doctors, insurers, patients, and pharmaceutical companies. This paper makes specific recommendations for all stakeholders, ranging from early dialogue on potential products, linking of clinical data and patient registries or standardisation of control frameworks, to a comprehensive approach to evidence generation, assessment, pricing, and payment for ATMPs.

Bringing Greater Accuracy to Europe's Healthcare Systems: The Unexploited Potential of Biomarker Testing in Oncology.

Rapid and continuing advances in biomarker testing are not being matched by take-up in health systems, and this is hampering both patient care and innovation. It also risks costing health systems the opportunity to make their services more efficient and, over time, more economical. This paper sets out the potential of biomarker testing, the unfolding precision and range of possible diagnosis and prediction, and the many obstacles to adoption. It offers case studies of biomarker testing in breast, ovarian, prostate, lung, thyroid and colon cancers, and derives specific lessons as to the potential and actual use of each of them. It also draws lessons about how to improve access and alignment, and to remedy the data deficiencies that impede development. And it suggests solutions to outstanding issues - notably including funding and the tangled web of obtaining reimbursement or equivalent coverage that Europe's fragmented health system implies. It urges a European evolution towards an initial minimum testing scenario, which would guarantee universal access to a suite of biomarker tests for the currently most common conditions, and, further into the future, to an optimum testing scenario in which a much wider range of biomarker tests would be introduced and become part of a more sophisticated health system articulated around personalised medicine. For exploiting genomics to the full, it argues the need for a new policy framework for Europe. Biomarker testing is not an issue that can be treated in isolation, since the purpose of testing is to improve health. Its use is therefore always closely linked to specific health challenges and needs to be viewed in the broader policy context in the EU and more widely. The paper is the result of extensive engagement with experts and decision makers to develop the framework, and consequently represents a wide consensus of views on how healthcare systems should respond from push and pull factors at local, national and cross-border and EU level. It contains strong views and clear recommendations springing from the convictions of patients, clinicians, academics, medicines authorities, HTA bodies, payers, the diagnostic, pharmaceutical and ICT industries, and national policy makers.

Breast cancer risk of hormonal contraception: Counselling considering new evidence.

The possibility that the use of hormonal contraceptives may increase the risk of breast cancer has been raised since many years. In the past this hypothesis has been dismissed on the basis that available data were generally derived from "old" studies in which relatively high hormone doses had been used. The recent publication of two studies that analysed data from women receiving low-dose hormonal contraception and showed a statistically significant increase in breast cancer contradicts this reassuring belief. The topic however is not settled, since different results were obtained in other studies and since hormonal contraception (HC) also has unquestionable positive effects such as a decrease in ovarian and in endometrial cancer. The aim of the present paper is to provide evidence that may help gynaecologists and oncologists in discussing with their patients the use of HC. Even if cancer phobia is a strong reason for not using or limiting HC, patients must be informed that notwithstanding the slightly increased breast cancer risk, the overall cancer risk may still be lower than non-users. Proper counselling may help the woman choose the most suitable contraception in the different phases of her life and on the basis of other conditions that may increase cancer risk such as overweight, smoking or family history.

Comparison of 18F FDG PET-CT AND CECT in pretreatment staging of adults with Hodgkin's lymphoma.

We compared 2-[fluorine-18] fluoro-2-deoxy-d-glucose PET-CT and contrast-enhanced computed tomography (CECT) in 62 consecutive patients with newly diagnosed Hodgkin Lymphoma (HL), aiming to provide evidences that may spare CECT from the staging procedures of HL patients. Among a total of 1448 nodal sites examined, disease involvement was detected in 232 (16%) and 280 (19.3%) nodal areas by CECT and PET-CT, respectively (P < 0.01). Sensitivity of CECT in detecting disease involvement ranged from 0% for internal mammary region (7 cases) and Waldayer's ring (1 case) to 100% for mediastinum. A total of 248 extranodal areas were examined. CECT and PET-CT identified disease involvement in 19 (7.7%) and 25 (10.1%) extranodal areas, respectively (P = n.s). Compared to PET-CT, CECT detected a lower number of cases with bone and/or bone marrow involvement (P = 0.05), whereas no differences were detected at the level of lung. By contrast, CECT identified liver lesions in four patients versus three identified by PET-CT. In comparison to CECT, PET-CT upstaged 6 patients (9.7%) and downstaged 1 patient (1.6%). We showed that PET-CT modified treatment strategy in five (8.1%) cases not only as a result of stage advancement (2 cases) but also of a different prognostic stratification in patients with localized disease (3 cases), due to the better sensitivity in detecting nodal involvement. In conclusion, our data, confirm the superiority of PET-CT in detecting disease involvement at diagnosis of HL, and further supports the possibility to replace CECT with PET-CT in the initial staging of HL.

Cancer in pregnancy: an association to make one shiver-highlights from 'Cancer in pregnancy: 15 years after', 10-11 October 2019, Milan, Italy.

Although rare, the treatment of pregnant women with cancer remains a challenging situation that requires strict collaboration between different specialities and experts in different fields. Frequent lack of experience and knowledge about this condition could lead to late diagnosis, imprecise management, suboptimal treatment, and foetal and maternal harm. Until recently, the choice for a woman diagnosed with cancer during pregnancy was either to sacrifice the foetus by administering effective treatment to the mother or to risk potential harm to the mother by withholding chemotherapy. This conference report aims to summarise all different aspects of cancer and pregnancy discussed at this 2-day meeting. Data on the safety (for mother and child) of chemotherapy administered after the first trimester of pregnancy are accumulating together with the recommendation to bring pregnancy as close as possible to its natural duration. Several aspects such as the poor prognosis of breast cancer diagnosed in the year after delivery and the delayed growth of foetuses exposed to chemotherapy despite the quasi-normal duration of pregnancy require further investigation. In this apparently tragic situation, results are excellent and comforting data accumulate so that we can transmit an optimistic feeling to women facing cancer during pregnancy.

Biology, staging, and treatment of breast cancer during pregnancy: reassessing the evidences.

Breast cancer is one of the most frequently diagnosed malignancies during pregnancy. Here, we review the management of women with breast cancer during pregnancy (BCP), focusing on biology, diagnosis and staging, local and systemic treatments, obstetric care and long-term follow-up of children with prenatal exposure to anticancer treatments.

Whole body MRI for systemic staging of breast cancer in pregnant women.

When breast cancer is diagnosed during pregnancy, treatment should be as close; as possible to what is used in non-pregnant patients. This requires accurate local and systemic staging: ultrasound (US) is used for local staging and allows adequate evaluation of the liver and pelvis, but chest and bones cannot be explored and imaging techniques involving exposure to ionizing radiation would be needed. However, since imaging techniques involving ionizing radiation and the use of radionuclides should be limited, whole body magnetic resonance imaging (WB-MRI) without administration of contrast agent represents a very interesting alternative, but limited data is available. In this paper we describe the obstetrical and oncological outcome of 14 patients in whom breast cancer was diagnosed during the second or third trimester of pregnancy and that were staged using WB-MRI. Median age of the patient at diagnosis was 35 years (range 20-36), median gestational age at MRI was 30 weeks (range 13-32) and median age at delivery was 38 weeks (range 32-38). At birth, one new-born presented respiratory distress syndrome and one jaundice. We conclude that diffusion-weighted MRI is feasible accurate and safe for the mother and for the foetus. It may represent the staging technique of choice in pregnant women diagnosed with breast cancer after the first trimester of pregnancy.

Mechanisms of chemotherapy-induced ovarian damage in breast cancer patients.

Fertility preservation in breast cancer patients is an increasingly relevant topic. In the present paper we review available data on the mechanism of ovarian damage caused by anticancer agents currently used for the treatment of breast cancer. We also describe current methods to preserve fertility including oocytes or ovarian tissue freezing and administration of LH-RHa during chemotherapy. The aim of the paper is to provide clinical oncologists with an adequate knowledge of the subject to enable them to give a correct counselling to young women that must receive chemotherapy and want to increase their possibilities of maintaining fertility.

The Pros and Comms of Gene Sequencing.

Full-gene sequencing undoubtedly comes with its pluses and its minuses. In this article, the authors aim to weigh up the pros and cons not only from the point of view of the patient but also in view of the doctor's possible perspective. Either party may be for or against it for a variety of reasons - for example, a fear of knowing too much on the part of the patient, and concerns about possible over-treatment on the part of the healthcare professional. One thing is certain: the possibility of full-gene sequencing is here and here to stay. At the very least, doctors need to make patients aware of their options, while offering balanced advice.