ESMO Expert Consensus Statements on the management of breast cancer during pregnancy (PrBC).

The management of breast cancer during pregnancy (PrBC) is a relatively rare indication and an area where no or little evidence is available since randomized controlled trials cannot be conducted. In general, advances related to breast cancer (BC) treatment outside pregnancy cannot always be translated to PrBC, because both the interests of the mother and of the unborn should be considered. Evidence remains limited and/or conflicting in some specific areas where the optimal approach remains controversial. In 2022, the European Society for Medical Oncology (ESMO) held a virtual consensus-building process on this topic to gain insights from a multidisciplinary group of experts and develop statements on controversial topics that cannot be adequately addressed in the current evidence-based ESMO Clinical Practice Guideline. The aim of this consensus-building process was to discuss controversial issues relating to the management of patients with PrBC. The virtual meeting included a multidisciplinary panel of 24 leading experts from 13 countries and was chaired by S. Loibl and F. Amant. All experts were allocated to one of four different working groups. Each working group covered a specific subject area with two chairs appointed: Planning, preparation and execution of the consensus process was conducted according to the ESMO standard operating procedures.

ESO-ESMO fifth international consensus guidelines for breast cancer in young women (BCY5).

We dedicate this manuscript in memory of a dear friend and colleague Bella Kaufman. The fifth International Consensus Symposium for Breast Cancer in Young Women (BCY5) took place virtually in October 2020, organized by the European School of Oncology (ESO) and the European Society of Medical Oncology (ESMO). Consensus recommendations for the management of breast cancer in young women were updated from BCY4 with incorporation of new evidence to inform the guidelines. Areas of research priorities as well as specificities in different geographic and minority populations were identified. This manuscript summarizes the ESO-ESMO international consensus recommendations, which are also endorsed by the European Society of Breast Specialists (EUSOMA).

ESO-ESMO 4th International Consensus Guidelines for Breast Cancer in Young Women (BCY4).

The 4th International Consensus Conference for Breast Cancer in Young Women (BCY4) took place in October 2018, in Lugano, Switzerland, organized by the European School of Oncology (ESO) and the European Society of Medical Oncology (ESMO). Consensus recommendations for the management of breast cancer in young women were updated from BCY3 with incorporation of new evidence to inform the guidelines. Areas of research priorities were also identified. This article summarizes the ESO-ESMO international consensus recommendations, which are also endorsed by the European Society of Breast Specialists (EUSOMA).

Dealing with death in cancer care: should the oncologist be an amicus mortis?

The way death is (not) dealt with is one of the main determinants of the current crisis of cancer care. The tendency to avoid discussions about terminal prognoses and to create unrealistic expectations of fighting death is seriously harming patients, families and healthcare professionals, and the delivery of high-quality and equitable care. Drawing on different literature sources, we explore key dimensions of the taboo of death: medical, policy, cultural. We suggest that the oncologist, from a certain moment, could take on the role of amicus mortis, a classical figure in the past times, and thus accompanying patients towards the end of their life through palliation and linking them to psychosocial and ethical/existential resources. This presupposes the implementation of Supportive Care in Cancer and the ethical idea of relational autonomy based on understanding patients' needs considering their sociocultural contexts. It is also key to encourage public conversations beyond the area of medicine to re-integrate death into life.

Gynecologic cancers in pregnancy: guidelines based on a third international consensus meeting.

We aimed to provide comprehensive protocols and promote effective management of pregnant women with gynecological cancers. New insights and more experience have been gained since the previous guidelines were published in 2014. Members of the International Network on Cancer, Infertility and Pregnancy (INCIP), in collaboration with other international experts, reviewed existing literature on their respective areas of expertise. Summaries were subsequently merged into a manuscript that served as a basis for discussion during the consensus meeting. Treatment of gynecological cancers during pregnancy is attainable if management is achieved by collaboration of a multidisciplinary team of health care providers. This allows further optimization of maternal treatment, while considering fetal development and providing psychological support and long-term follow-up of the infants. Nonionizing imaging procedures are preferred diagnostic procedures, but limited ionizing imaging methods can be allowed if indispensable for treatment plans. In contrast to other cancers, standard surgery for gynecological cancers often needs to be adapted according to cancer type and gestational age. Most standard regimens of chemotherapy can be administered after 14 weeks gestational age but are not recommended beyond 35 weeks. C-section is recommended for most cervical and vulvar cancers, whereas vaginal delivery is allowed in most ovarian cancers. Breast-feeding should be avoided with ongoing chemotherapeutic, endocrine or targeted treatment. More studies that focus on the long-term toxic effects of gynecologic cancer treatments are needed to provide a full understanding of their fetal impact. In particular, data on targeted therapies that are becoming standard of care in certain gynecological malignancies is still limited. Furthermore, more studies aimed at the definition of the exact prognosis of patients after antenatal cancer treatment are warranted. Participation in existing registries (www.cancerinpregnancy.org) and the creation of national tumor boards with multidisciplinary teams of care providers (supplementary Box S1, available at Annals of Oncology online) is encouraged.

Axillary staging for breast cancer during pregnancy: feasibility and safety of sentinel lymph node biopsy.

BACKGROUND: Safety of sentinel lymph node (SLN) biopsy for breast cancer during pregnancy is insufficiently explored. We investigated efficacy and local recurrence rate in a large series of pregnant patients. PATIENTS AND METHODS: Women diagnosed with breast cancer who underwent SLN biopsy during pregnancy were identified from the International Network on Cancer, Infertility and Pregnancy, the German Breast Group, and the Cancer and Pregnancy Registry. Chart review was performed to record technique and outcome of SLN biopsy, locoregional and distant recurrence, and survival. RESULTS: We identified 145 women with clinically N0 disease who underwent SLN during pregnancy. The SLN detection techniques were as follows: 99mTc-labeled albumin nanocolloid only (n = 96; 66.2%), blue dye only (n = 14; 9.7%), combined technique (n = 15; 10.3%), or unknown (n = 20; 13.8%). Mapping was unsuccessful in one patient (0.7%) and she underwent an axillary lymph node dissection (ALND). Mean number of SLNs was 3.2 (interquartile range 1-3; missing n = 15). Positive SLNs were found in 43 (29.7%) patients and 34 subsequently underwent ALND. After a median follow-up of 48 months (range 1-177), 123 (84.8%) patients were alive and free of disease. Eleven patients experienced a locoregional relapse, including 1 isolated ipsilateral axillary recurrence (0.7%). Eleven (7.6%) patients developed distant metastases, of whom 9 (6.2%) died of breast cancer. No neonatal adverse events related to SLN procedure during pregnancy were reported. CONCLUSIONS: SLN biopsy during pregnancy has a comparably low axillary recurrence rate as in nonpregnant women. Therefore, this method can be considered during pregnancy instead of standard ALND for early-stage, clinically node-negative breast cancer.

Ovarian suppression using luteinizing hormone-releasing hormone agonists during chemotherapy to preserve ovarian function and fertility of breast cancer patients: a meta-analysis of randomized studies.

BACKGROUND: The role of temporary ovarian suppression with luteinizing hormone-releasing hormone agonists (LHRHa) in the prevention of chemotherapy-induced premature ovarian failure (POF) is still controversial. Our meta-analysis of randomized, controlled trials (RCTs) investigates whether the use of LHRHa during chemotherapy in premenopausal breast cancer patients reduces treatment-related POF rate, increases pregnancy rate, and impacts disease-free survival (DFS). METHODS: A literature search using PubMed, Embase, and the Cochrane Library, and the proceedings of major conferences, was conducted up to 30 April 2015. Odds ratios (ORs) and 95% confidence intervals (CIs) for POF (i.e. POF by study definition, and POF defined as amenorrhea 1 year after chemotherapy completion) and for patients with pregnancy, as well hazard ratios (HRs) and 95% CI for DFS, were calculated for each trial. Pooled analysis was carried out using the fixed- and random-effects models. RESULTS: A total of 12 RCTs were eligible including 1231 breast cancer patients. The use of LHRHa was associated with a significant reduced risk of POF (OR 0.36, 95% CI 0.23-0.57; P < 0.001), yet with significant heterogeneity (I(2) = 47.1%, Pheterogeneity = 0.026). In eight studies reporting amenorrhea rates 1 year after chemotherapy completion, the addition of LHRHa reduced the risk of POF (OR 0.55, 95% CI 0.41-0.73, P < 0.001) without heterogeneity (I(2) = 0.0%, Pheterogeneity = 0.936). In five studies reporting pregnancies, more patients treated with LHRHa achieved pregnancy (33 versus 19 women; OR 1.83, 95% CI 1.02-3.28, P = 0.041; I(2) = 0.0%, Pheterogeneity = 0.629). In three studies reporting DFS, no difference was observed (HR 1.00, 95% CI 0.49-2.04, P = 0.939; I(2) = 68.0%, Pheterogeneity = 0.044). CONCLUSION: Temporary ovarian suppression with LHRHa in young breast cancer patients is associated with a reduced risk of chemotherapy-induced POF and seems to increase the pregnancy rate, without an apparent negative consequence on prognosis.

High-dose chemotherapy in relapsed or refractory Hodgkin lymphoma patients: a reappraisal of prognostic factors.

High-dose chemotherapy (HDCT) has a consolidated role in the treatment of patients with refractory or relapsed Hodgkin lymphoma (HL). We report clinical results of 97 HL patients who underwent HDCT for refractory (62 patients) or relapsed (35 patients) diseases in Istituto Europeo di Oncologia, from 1995 to 2009. Treatment included high-dose carmustine, etoposide, cytarabine and melphalan in 84 patients and high-dose idarubicin and melphalan in 13 patients with subsequent peripheral hemopoietic stem cells transplant. Outcomes were evaluated in terms of progression-free survival (PFS) and overall survival (OS). In order to identify prognostic factors for outcome, a multivariate analysis for age, sex, disease status (refractory/relapsed), disease stage, B symptoms, presence of extranodal involvement, bulky disease, elevated lactate dehydrogenase, number of previous chemotherapy lines, remission status before transplant, 18F-fluoro-deoxy-d-glucose positron emission tomography ((18) FDG-PET) status before and after transplant was done. A clinical response was achieved in 91% of patients, with complete remissions in 76/97 patients. With a median follow-up of 45 months (range 1-164 months), 5-year PFS and OS were 64% and 71%, respectively. Remission status after induction therapy, 18F-fluoro-deoxy-d-glucose positron emission tomography status before and after transplant were the most important prognostic factors for PFS and OS in univariate or multivariate analyses. HDCT is able to induce a high remission rate and a prolonged PFS in more than 50% of the patients with refractory and relapsed HL.

Cancer burden in adolescents and young adults in Europe.

BACKGROUND: Cancer epidemiology is unique in adolescents and young adults (AYAs; aged 15-39 years). The European Society for Medical Oncology/European Society for Paediatric Oncology (ESMO/SIOPE) AYA Working Group aims to describe the burden of cancers in AYAs in Europe and across European Union (EU) countries. PATIENTS AND METHODS: We used data available on the Global Cancer Observatory. We retrieved crude and age-standardised (World Standard Population) incidence and mortality rates. We reported about AYA cancer burden in Europe and between 28 EU member states. We described incidence and mortality for all cancers and for the 13 cancers most relevant to the AYA population. RESULTS: Incidence and mortality varied widely between countries with the highest mortality observed in Eastern EU countries. Cancers of the female breast, thyroid and male testis were the most common cancers across countries followed by melanoma of skin and cancers of the cervix. Variations in cancer incidence rates across different populations may reflect different distribution of risk factors, variations in the implementation or uptake of screening as well as overdiagnosis. AYA cancer mortality disparities may be due to variation in early-stage diagnoses, different public education and awareness of cancer symptoms, different degrees of access or availability of treatment. CONCLUSIONS: Our results highlight the future health care needs and requirements for AYA-specialised services to ensure a homogeneous treatment across different countries as well as the urgency for preventive initiatives that can mitigate the increasing burden.

Safety of pregnancy after breast cancer in young women with hormone receptor-positive disease: a systematic review and meta-analysis.

BACKGROUND: Despite increasing evidence on the safety of pregnancy after anticancer treatments in breast cancer survivors, many physicians and patients remain concerned about a potential risk of pregnancy specifically in the case of hormone receptor-positive breast cancer. MATERIALS AND METHODS: A systematic literature search of Medline, Embase and Cochrane library with no language or date restriction up to 31 March 2023 was carried out. To be included, articles had to be retrospective and prospective case-control and cohort studies as well as clinical trials comparing survival outcomes of premenopausal women with or without a pregnancy after prior diagnosis of hormone receptor-positive breast cancer. Disease-free survival (DFS) and overall survival (OS) were the outcomes of interest. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. Study protocol is registered in PROSPERO (n. CRD42023394232). RESULTS: Out of 7796 screened studies, 8 were eligible to be included in the final analysis. A total of 3805 patients with hormone receptor-positive invasive early breast cancer were included in these studies, of whom 1285 had a pregnancy after breast cancer diagnosis. Median follow-up time ranged from 3.8 to 15.8 years and was similar in the pregnancy and non-pregnancy cohorts. In three studies (n = 987 patients) reporting on DFS, no difference was observed between patients with and those without a subsequent pregnancy (HR 0.96, 95% CI 0.75-1.24, P = 0.781). In the six studies (n = 3504 patients) reporting on OS, patients with a pregnancy after breast cancer had a statistically significant better OS than those without a pregnancy (HR 0.46, 95% CI 0.27-0.77, P < 0.05). CONCLUSIONS: This systematic review and meta-analysis of retrospective cohort studies provides updated evidence that having a pregnancy in patients with prior history of hormone receptor-positive invasive early breast cancer appears safe without detrimental effect on prognosis.

Antiblastic treatment of haematological malignancies during pregnancy: a crucial decision.

Antiblastic treatment of hematological malignancies during pregnancy poses a number of issues related to the curability of the maternal disease, the need of a prompt treatment and the potential toxicity of chemotherapy for the fetus. Here we report the results of a systematic literature search about the management of the most frequent hematological malignancies that may occur during pregnancy, focusing on specific issues related to gestational age at diagnosis, fetal toxicity and efficacy on the maternal side. The standard approach in non-pregnant women is illustrated as reference.

Obstetrical, fetal and postnatal effects of gestational antiblastic chemotherapy: how to counsel cancer patients.

At least one in a thousand pregnancies is complicated by cancer and, as the maternal age at pregnancy increases, numbers are growing. If chemotherapy cannot be postponed, both doctors and patients face complex medical and ethical issues. There is a conflict between optimal maternal therapy and fetal wellbeing. Treatment during the first trimester increases the risk of congenital malformations, spontaneous abortions and fetal death. Second and third trimester exposure is less risky, but it can cause intrauterine growth retardation and low birth weight. Other effects on pregnancy after the first trimester include premature birth, stillbirth, impaired functional development, myocardial toxicity and myelosuppression. Counseling and management of these cases are difficult, because literature is mostly represented by case reports or retrospective series while randomized prospective studies or guidelines are lacking. Moreover, personal experience is often scanty due to the rarity of the condition. This article reviews the available data regarding the different aspects of systemic treatment of cancer during pregnancy to help oncologist and obstetricians in counseling their patients and treat them accordingly.

Adolescents and young adults (AYA) with cancer: a position paper from the AYA Working Group of the European Society for Medical Oncology (ESMO) and the European Society for Paediatric Oncology (SIOPE).

It is well recognised that adolescents and young adults (AYA) with cancer have inequitable access to oncology services that provide expert cancer care and consider their unique needs. Subsequently, survival gains in this patient population have improved only modestly compared with older adults and children with cancer. In 2015, the European Society for Medical Oncology (ESMO) and the European Society for Paediatric Oncology (SIOPE) established the joint Cancer in AYA Working Group in order to increase awareness among adult and paediatric oncology communities, enhance knowledge on specific issues in AYA and ultimately improve the standard of care for AYA with cancer across Europe. This manuscript reflects the position of this working group regarding current AYA cancer care, the challenges to be addressed and possible solutions. Key challenges include the lack of specific biological understanding of AYA cancers, the lack of access to specialised centres with age-appropriate multidisciplinary care and the lack of available clinical trials with novel therapeutics. Key recommendations include diversifying interprofessional cooperation in AYA care and specific measures to improve trial accrual, including centralising care where that is the best means to achieve trial accrual. This defines a common vision that can lead to improved outcomes for AYA with cancer in Europe.

Safety of assisted reproductive techniques in young women harboring germline pathogenic variants in BRCA1/2 with a pregnancy after prior history of breast cancer.

BACKGROUND: Knowledge is growing on the safety of assisted reproductive techniques (ART) in cancer survivors. No data exist, however, for the specific population of breast cancer patients harboring germline BRCA1/2 pathogenic variants. PATIENTS AND METHODS: This is a multicenter retrospective cohort study across 30 centers worldwide including women diagnosed at ≤40 years with stage I-III breast cancer, between January 2000 and December 2012, harboring known germline BRCA1/2 pathogenic variants. Patients included in this analysis had a post-treatment pregnancy either achieved through use of ART (ART group) or naturally (non-ART group). ART procedures included ovulation induction, ovarian stimulation for in vitro fertilization or intracytoplasmic sperm injection, and embryo transfer under hormonal replacement therapy. RESULTS: Among the 1424 patients registered in the study, 168 were eligible for inclusion in the present analysis, of whom 22 were in the ART group and 146 in the non-ART group. Survivors in the ART group conceived at an older age compared with those in the non-ART group (median age: 39.7 versus 35.4 years, respectively). Women in the ART group experienced more delivery complications compared with those in the non-ART group (22.1% versus 4.1%, respectively). No other apparent differences in obstetrical outcomes were observed between cohorts. The median follow-up from pregnancy was 3.4 years (range: 0.8-8.6 years) in the ART group and 5.0 years (range: 0.8-17.6 years) in the non-ART group. Two patients (9.1%) in the ART group experienced a disease-free survival event (specifically, a locoregional recurrence) compared with 40 patients (27.4%) in the non-ART group. In the ART group, no patients deceased compared with 10 patients (6.9%) in the non-ART group. CONCLUSION: This study provides encouraging safety data on the use of ART in breast cancer survivors harboring germline pathogenic variants in BRCA1/2, when natural conception fails or when they opt for ART in order to carry out preimplantation genetic testing.

The effect of endocrine responsiveness on high-risk breast cancer treated with dose-intensive chemotherapy: results of International Breast Cancer Study Group Trial 15-95 after prolonged follow-up.

BACKGROUND: The role of adjuvant dose-intensive chemotherapy and its efficacy according to baseline features has not yet been established. PATIENTS AND METHODS: Three hundred and forty-four patients were randomized to receive seven courses of standard-dose chemotherapy (SD-CT) or three cycles of dose-intensive epirubicin and cyclophosphamide (epirubicin 200 mg/m(2) plus cyclophosphamide 4 mg/m(2) with filgrastim and progenitor cell support). All patients were assigned tamoxifen at the completion of chemotherapy. The primary end point was disease-free survival (DFS). This paper updates the results and explores patterns of recurrence according to predicting baseline features. RESULTS: At 8.3-years median follow-up, patients assigned DI-EC had a significantly better DFS compared with those assigned SD-CT [8-year DFS percent 47% and 37%, respectively, hazard ratio (HR) 0.76; 95% confidence interval 0.58-1.00; P = 0.05]. Only patients with estrogen receptor (ER)-positive disease benefited from the DI-EC (HR 0.61; 95% confidence interval 0.39, 0.95; P = 0.03). CONCLUSIONS: After prolonged follow-up, DI-EC significantly improved DFS, but the effect was observed only in patients with ER-positive disease, leading to the hypothesis that efficacy of DI-EC may relate to its endocrine effects. Further studies designed to confirm the importance of endocrine responsiveness in patients treated with dose-intensive chemotherapy are encouraged.