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Background Prospective data on the risk of recurrence among women with hormone receptor-positive early breast cancer who temporarily discontinue endocrine therapy to attempt pregnancy are lacking. Methods We conducted a single-group trial in which we evaluated the temporary interruption of adjuvant endocrine therapy to attempt pregnancy in young women with previous breast cancer. Eligible women were 42 years of age or younger; had had stage I, II, or III disease; had received adjuvant endocrine therapy for 18 to 30 months; and desired pregnancy. The primary end point was the number of breast cancer events (defined as local, regional, or distant recurrence of invasive breast cancer or new contralateral invasive breast cancer) during follow-up. The primary analysis was planned to be performed after 1600 patient-years of follow-up. The prespecified safety threshold was the occurrence of 46 breast cancer events during this period. Breast cancer outcomes in this treatment-interruption group were compared with those in an external control cohort consisting of women who would have met the entry criteria for the current trial. Results Among 516 women, the median age was 37 years, the median time from breast cancer diagnosis to enrollment was 29 months, and 93.4% had stage I or II disease. Among 497 women who were followed for pregnancy status, 368 (74.0%) had at least one pregnancy and 317 (63.8%) had at least one live birth. In total, 365 babies were born. At 1638 patient-years of follow-up (median follow-up, 41 months), 44 patients had a breast cancer event, a result that did not exceed the safety threshold. The 3-year incidence of breast cancer events was 8.9% (95% confidence interval [CI], 6.3 to 11.6) in the treatment-interruption group and 9.2% (95% CI, 7.6 to 10.8) in the control cohort. Conclusions Among select women with previous hormone receptor-positive early breast cancer, temporary interruption of endocrine therapy to attempt pregnancy did not confer a greater short-term risk of breast cancer events, including distant recurrence, than that in the external control cohort. Further follow-up is critical to inform longer-term safety. (Funded by ETOP IBCSG Partners Foundation and others; POSITIVE ClinicalTrials.gov number, NCT02308085.).

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.

Although cancer treatment during single pregnancy has been standardized, how to manage cancer diagnosed during a multiple gestation is still unclear. Chemotherapy during pregnancy has shown to be safe, however, there are reports of increased risks of fetal complications such as intrauterine growth restriction and preterm birth. Also, how to best adjust this to the pharmacokinetic characteristics of a twin gestation has yet to be fully investigated. We report the case of an IVF twin pregnancy with a diagnosis of breast cancer recurrence shortly after conception, and how the pregnancy was managed to obtain optimal obstetric, maternal/oncological, and fetal outcomes.

Background: Breast cancer is the most common malignancy occurring during gestation and should be managed with the same protocols as for young non-pregnant women. In early-stage breast cancer during pregnancy (PrBC), breast-conserving surgery (BCS) with delayed radiation therapy (RT) is a reasonable alternative to radical mastectomy. Regrettably, no specific and widely adopted guidelines on the surgical management of these patients are available. In this study, we investigated the feasibility and safety of BCS during the first trimester of pregnancy in women with early-stage PrBC. Method: The first trimester was defined as 12 weeks and 6 days after the first day of the last menstruation. As for internal protocols, the surgical strategy for PrBC followed the same conservative-oriented schemes applied for nonpregnant patients. Only women with early-stage PrBC treated with BCS during pregnancy followed by planned RT to the whole breast after delivery were included. Exclusion criteria were i) clinical diagnosis or suspicion of inflammatory breast cancer; ii) multicentric disease; iii) diffuse malignant microcalcifications on mammography; iv) previous; v) connective tissue disease, and vi) syndromic breast cancers. All cases underwent central pathological review at the Pathology Department of the European Institute of Oncology. The primary outcome was the isolated local recurrence (ILR). Results: Among 168 PrBC patients, 67 (39.9%) were diagnosed during the first trimester of gestation. Of these, 30 patients (age range, 23-43 years; median=36 years; gestational age, 2-12 weeks; median=7 weeks; median follow-up time=6.5 years) met the inclusion criteria. None of the patients included in this study experienced perioperative surgical complications. No ILR was observed within three months (n=30), 1 year (n=27), and 5 years (n=18) after surgery. The 5-year overall survival rate for all patients was 97% (n=29/30). Four patients experienced ILR or new carcinomas after 6-13 years. These patients are still alive and disease-free after 14-17 years of follow-up. Discussion: In our study, both adjuvant endocrine therapy and anti-HER2 treatment were postponed after delivery. Local recurrences/second primary tumors were observed in 4 out of 30 patients treated with BCS. Given that patient #4 did not receive postoperative RT, but an after-delivery mastectomy for preoperative diagnostic underestimation during pregnancy, this case does not represent a post-BCS recurrence. On the other hand, cases #1-3 could be considered real relapses. Two of these tumors occurred in patients that underwent CT during pregnancy, in which the interval between the end of systemic therapies and the onset of RT was not influenced by the pregnancy. In a single patient (not eligible for systemic treatment in pregnancy), the RT was performed with a longer interval than the usual one of the non-pregnant patients. Survival was not affected by local relapse, underlining the efficacy of salvage treatment.Conclusion: The findings of this study suggest that BCS in the first trimester of pregnancy can be considered reasonably safe for both mother and the child. Mammography should be mandatory in all patients for whom conservative surgery is recommended. Given that the availability of data concerning PrBC and its treatment is scarce and heterogeneous, multicentric studies are warranted. Citation Format: Nicola Fusco, Concetta Blundo, Massimo Giroda, Elham Sajjadi, Konstantinos Venetis, M. Cristina Leonardi, Elisa Vicini, Luca Despini, Claudia F. Rossi, Letterio Runza, Eugenia Di Loreto, Giovanna Scarfone, Elena Guerini-Rocco, Giuseppe Viale, Paolo Veronesi, Barbara Buonomo, Fedro A. Peccatori, Viviana E. Galimberti. Feasibility and safety of breast-conserving surgery in early-stage breast cancers during the first trimester of pregnancy [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-18-08.

Introduction: Breast cancer during pregnancy (PrBC) accounts for ~4% of breast cancer cases in young women and its intrinsic biology is still largely undetermined. Tumor microenvironment (TME) of PrBC has been recently characterized with low levels of stromal tumor-infiltrating lymphocytes (TILs) and high relative expression of programmed death-ligand 1 (PD-L1), suggesting an increased immune evasion. The underlying immune landscape, however, has not been unveiled. Given the significant alterations of the immune system during gestation, we hypothesized that the TME of PrBC might have distinct biological traits. Here, we sought to evaluate the outcome of PrBC according to the TME characteristics and to assess whether pathogenic mechanisms of immune evasion are involved. Methods: Representative formalin-fixed paraffin-embedded tissue blocks of 83 consecutive PrBC and 89 age-matched early-onset pregnancy-unrelated breast cancers (controls) were subjected to immunohistochemistry (IHC) using antibodies against CD4, CD8, forkhead box P3 (FOXP3), and PD-L1 (clone 22C3) on a Dako Omnis platform. For all cases, TILs were evaluated according to the International TILs Working Group recommendations. Next-generation sequencing gene expression of 395 genes involved in tumor-immune interactions (Oncomine™ Immune Response Research Assay) was performed on RNA extracted from PrBC (n=20) and controls (n=16). Samples with mapped reads >1,000,000 and valid reads >800,000 were considered adequate. Fisher’s and Chi-squared tests, multinomial logistic regression models, ROC curve, and survival analyses were performed. Results: The fraction of tumors with CD8+TILs was significantly higher in PrBC than in the controls (n=71(85.0%) vs. n=61(68.5%); p=0.02), being mirrored by less cases with CD4+TILs (n=27 (32.5%) vs. n=43 (48.3%); p=0.03). Even higher differences were observed in hormone receptor (HR)+/HER2-negative tumors (CD8: n=39 (88.6%) vs. n=39 (66.1%); p=0.01). After a median follow-up of 78 (range, 1-247), 66/83 women (79.5%) with PrBC were alive and 53/83 (63.8%) relapse-free. Overall, PrBC with CD8+TILs had a better outcome compared to CD8-negative PrBC (OS 81 vs 69 months p=0.05) and CD8 expression was associated with better outcomes in HR+/HER2-negative tumors (OS p=0.02; DFS p=0.04). The overall comparison of immune-related genes in the 34 cases (PrBC, n=18; controls, n=16) that reached the quality parameters revealed significant differences in the expression of 63 immune-related genes. Of these, 4 genes (IFNA17, IFNB1, FUT4, and PECAM1) were upregulated, while 59 genes were downregulated in PrBC compared to the controls. Interestingly, IFNA17, IFNB1, and FUT4 remained upregulated in HR+ PrBC, where a slightly reduced number of differentially expressed genes was observed (n=60). In HR-/HER2- PrBC, only 25 genes were differentially expressed, of which 9, including IFNA17 and PECAM1, were significantly upregulated. Discussion: These data have the potential of improving our knowledge of the immunobiology that characterizes PrBC, suggesting that in these tumors the higher frequency of CD8+TILs might be related to an enhanced anti-tumor immune response, as CD8 expression was associated with better outcomes in PrBC. On the other hand, given that interferons (IFNs) may also trigger immune suppressive mechanisms in cancer cells, the activation of type I IFNs encoded by IFNA17 and IFNB1 seen in our RNA-seq analysis, combined with the lower frequency of CD4+TILs observed, suggest CD4+ cell suppression as a possible mechanism of immune evasion. Conclusion: PrBC TME is characterized by specific patterns of TILs subpopulations due to the possible activation of type I IFNs and its assessment might help in identifying women at high risk of death and recurrence. Citation Format: Nicola Fusco, Elham Sajjadi, Konstantinos Venetis, Barbara Buonomo, Concetta Blundo, Massimo Giroda, Eugenia Di Loreto, Giovanna Scarfone, Stefano Ferrero, Paolo Veronesi, Viviana E. Galimberti, Massimo Barberis, Giuseppe Viale, Elena Guerini-Rocco, Fedro A. Peccatori. Tumor microenvironment characteristics and prognosis in breast cancer during pregnancy: The role of differentially expressed immune-related genes [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-07-02.

The Certificate of Competence and Advanced Studies Program is an academically recognized postgraduate program that is organized by the European School of Oncology in collaboration with the University of Ulm and the University of Zurich. It is a part-time educational activity that aims to provide physicians and scientists with advanced knowledge in the management of patients with breast cancer, lymphoma, and lung cancer. The program encloses three attendance seminars and four to five e-learning modules that extend over 12 to 14 months. To be certified, participants have to pass an online test after each module followed by a final certification exam at the end of the program. This article reports on the 8-year experience of the 166 graduated fellows who have attended the program. Supplementary Information The online version contains supplementary material available at 10.1007/s13187-021-02105-z.

BRCA1 or two mutation carriers have an increased risk of developing breast and ovarian cancer. Moreover, they may also have reduced oocyte reserve, occult primary ovarian insufficiency, decreased fertility, poorer response to ovarian stimulation and earlier age at menopause. Even if these associations are still controversial, carriers should be properly informed in order to program motherhood and fertility preservation when appropriate. Women with Lynch syndrome (LS) have an increased risk of developing endometrial cancer at an early age and a slightly increased risk of ovarian cancer. Thus, the promotion of early parity with subsequent hormonal contraception or prophylactic hysterectomy after completing childbearing should be discussed during counseling.

This is the first case report of a patient with ALK-rearranged metastatic lung adenocarcinoma who became pregnant during treatment with alectinib. A multidisciplinary team of gynecologists, neonatologists, oncologists, psychologists, and pharmacologists was set up to handle the case. According to patient's preference, the study drug was continued throughout pregnancy and the woman delivered a healthy baby girl at 35 weeks and 5 days of gestation. Fetal parameters remained normal during pregnancy. At birth, alectinib levels were 14 times higher in maternal plasma than in the fetus (259 versus 18 ng/mL). The average concentration of alectinib in the placenta was 562 ng/g. The baby was followed during her first 20 months, and no developmental anomalies were observed. After 32 months from diagnosis, the mother is well and in partial remission.

Aims: This study aimed to assess the participants' evaluation of the European School of Oncology–European Society for Medical Oncology virtual masterclasses in clinical oncology (MCOs) organized during the pandemic in 2021. Materials & methods: The participants answered an online evaluation questionnaire at the end of each MCO to evaluate the content and organization of the MCO. Results: The clinical session and case presentation scores ranged between 4.6 and 4.8 over 5. The participants strongly agreed that the MCOs offered updates to improve their knowledge and practice in 68–83% and 52–76%, respectively; 74–90% of the participants considered the quality of the meetings to be excellent. Conclusion: The participants were satisfied with the virtual MCOs during the COVID-19 pandemic. Virtual MCO may be an acceptable alternative educational modality in specific circumstances.

Adolescent and young adult cancer survivors may experience various forms of social difficulties years or even decades after completing their cancer treatments. This article will hopefully help the Italian national project dedicated to adolescents and young adults with cancer promoting political and legal solutions to stop discrimination and supporting the right to be forgotten.

Background: Young breast cancer patients (pts) carrying a germline BRCA mutation (mBRCA) have similar outcomes as non-carriers. However, there is currently lack of evidence regarding the impact of mBRCA type and hormone receptor status on clinical behavior and outcomes of mBRCA breast cancer. We aim to address these questions in the largest dataset to date of young mBRCA breast cancer pts. Methods: This was an international, multicenter, hospital-based, retrospective cohort study. Women harboring deleterious germline mBRCA1 or mBRCA2 that received a diagnosis of stage I-III invasive early breast cancer at age ≤40 years between January 2000 and December 2012 were included. Baseline pts, tumor, and treatment characteristics, pattern and risk over time of disease-free survival (DFS) events, and survival outcomes (DFS, distant recurrence-free interval [DRFI] and overall survival [OS]) were compared between mBRCA1 and mBRCA2 pts overall and by hormone receptor status. Multivariate Cox proportional hazard models were used to compare hazard rates (HRs). Results: 1,236 young mBRCA breast cancer pts were included. Among 808 and 428 pts with mBRCA1 or mBRCA2, respectively, 191 (23.6%) and 356 (83.2%) had hormone receptor-positive tumors while 617 (76.4%) and 72 (16.8%) hormone receptor-negative disease (p Conclusions: In this large unique dataset, young mBRCA1 breast cancer pts had worse DFS than those with mBRCA2 mostly due to higher rates of second primary malignancies. Hormone receptor positivity had no positive prognostic value in young mBRCA breast cancer pts with a trend towards worse DRFI in those with hormone receptor-negative disease. These results provide important information for counseling young mBRCA breast cancer pts regarding treatment, prevention and follow-up care strategies. Citation Format: Matteo Lambertini, Marcello Ceppi, Anne-Sophie Hamy, Olivier Caron, Philip D. Poorvu, Estela Carrasco, Albert Grinshpun, Kevin Punie, Christine Rousset-Jablonski, Alberta Ferrari, Shani Paluch-Shimon, Angela Toss, Claire Senechal, Fabio Puglisi, Katarzyna Pogoda, Jose Alejandro Pérez-Fidalgo, Laura De Marchis, Riccardo Ponzone, Luca Livraghi, Maria Del Pilar Estevez-Diz, Cynthia Villarreal-Garza, Maria Vittoria Dieci, Florian Clatot, Francois P. Duhoux, Rossella Graffeo, Luis Teixeira, Octavi Córdoba, Amir Sonnenblick, Arlindo R. Ferreira, Ann H. Partridge, Antonio Di Meglio, Claire Saule, Fedro A. Peccatori, Marco Bruzzone, Lucia Del Mastro, Lieveke Ameye, Judith Balmaña, Hatem A. Azim, Jr. Clinical behavior and outcomes of BRCA-mutated breast cancer in young patients according to type of BRCA mutation and hormone receptor status: Results from an international cohort study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD10-06.

Background: Pregnancy is a major concern for young breast cancer (BC) survivors. Conception after BC in women with hormone receptor positive (HR+) disease is affected by the standard 5-10 years of adjuvant endocrine therapy (ET) during which pregnancy is contraindicated and fertility may be waning. The POSITIVE Trial (IBCSG 48-14/BIG 8-13/Alliance A221405/NCT02308085) investigates the impact of temporary ET interruption to allow pregnancy. Methods: POSITIVE enrolled premenopausal women with stage I-III HR+ early BC, ≤42 years of age, who had received adjuvant ET (SERM alone, ovarian function suppression (OFS) plus SERM or AI) for 18 to 30 months, and wished to interrupt ET to attempt pregnancy. An interruption of ET for up to 2 years was foreseen to allow pregnancy (after a 3-month ET washout period), delivery, and breastfeeding if desired/feasible. Resumption of ET to complete 5-10 years of treatment was planned as soon as pregnancy/breastfeeding was completed or after it was ensured conception was not possible. We report baseline characteristics of participants enrolled in POSITIVE by region of enrollment. Results: From 12/2014 to 12/2019, 518 participants were enrolled at 116 centers in 20 countries across 4 continents. The table shows the baseline characteristics of the enrolled women. Several differences were seen across regions: A higher proportion of participants Conclusion: Regional variation of baseline characteristics of women enrolled in the POSITIVE trial may provide important insights into different medical and sociocultural attributes and attitudes of the study participants and investigators from those regions. Affiliation: POSITIVE Investigators, International Breast Cancer Study Group, Alliance for Clinical Trials in Oncology, Breast International Group, North American Breast Cancer Group CharacteristicRegion: Europe / North America / Asia-Pacific61% / 23% / 16%Median age at enrollment, yrs (IQR)37 (33-39)Caucasian race77%No children prior to enrollment74%Prior fertility preservation measures taken51%Stage I / II46% / 45%0 / 1 positive nodes65% / 21%Grade 2 / 348% / 33%HER2-negative74%Mastectomy46%Chemotherapy61%ET: SERM alone / SERM+OFS / AI+OFS41% / 35% / 16%Median duration of prior ET, mos (IQR)23 (20-27) Citation Format: Ann H Partridge, Samuel M Niman, Monica Ruggeri, Fedro A Peccatori, Hatem A Azim, Jr, Marco Colleoni, Cristina Saura, Chikako Shimizu, Anna Barbro Sætersdal, Judith Kroep, Ellen Warner, Virginia F Borges, Andrea Gombos, Akemi Kataoka, Christine Rousset-Jablonski, Simona Borstnar, Hideko Yamauchi, Jeong Eon Lee, Janice M Walshe, Manuel Ruíz Borrego, Halle CF Moore, Christobel Saunders, Fatima Cardoso, Snezana Susnjar, Vesna Bjelic-Radisic, Karen L Smith, Martine Piccart, Larissa A Korde, Aron Goldhirsch, Richard D Gelber, Olivia Pagani. Baseline characteristics of women enrolled in the POSITIVE trial (pregnancy outcome and safety of interrupting therapy for women with endocrine responsIVE breast cancer) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS12-17.

Background: Pregnancy-related issues are a priority for young breast cancer (BC) patients. Increasing evidence has shown that pregnancy after prior BC diagnosis is feasible. Nevertheless, few BC survivors conceive following anticancer treatment completion and many physicians remain concerned about the potentially detrimental effects of pregnancy after BC in terms of fetal/obstetrical outcomes and maternal prognosis. This systematic review and meta-analysis aims at providing updated and solid evidence on these important issues. Methods: A systematic literature review up to January 31, 2020 with no language restriction was conducted to identify studies including patients with a pregnancy after prior BC diagnosis. Chances of pregnancy after BC, fetal and obstetrical outcomes, disease-free survival (DFS) and overall survival (OS) were assessed. Pooled relative risks (RRs), hazard ratios (HRs) or odds ratio (ORs) with 95% confidence intervals (CI) were calculated using the random effects models. The study is registered with the PROSPERO registration number CRD42020158324. Results: Overall, 39 studies were included. Out of the 8,265,713 young women included in these studies, 8,093,401 were from the general population, 57,739 had cancers other than BC, 114,573 had BC. Among the 114,573 BC patients, 7,505 had a pregnancy after BC diagnosis and 107,068 did not. Compared to women from the general population, BC patients had 60% reduced chances of having a pregnancy following anticancer treatment completion (RR 0.40, 95% CI 0.32-0.49). Among other cancer patients, only women with prior cervical cancer had lower pregnancy rates (RR 0.33, 95% CI 0.31-0.35) than BC patients. Compared to the general population, BC survivors had significantly increased risks of low birth weight (OR 1.50, 95% CI 1.31-1.73), small for gestational age (OR 1.16, 95% CI 1.01-1.33), preterm delivery (OR 1.45, 95% CI 1.11-1.88) and caesarean section (OR 1.14, 95% CI 1.04-1.25). No significant increased risk of congenital abnormalities (OR 1.63, 95% CI 0.89-2.98) or other pregnancy or delivery complications (spontaneous or induced abortion, gestosis, antepartum or postpartum hemorrhage) was observed. Prior chemotherapy exposure or short pregnancy interval (defined as Pregnancy after BC was not associated with a negative impact on patients’ outcomes. Compared to BC patients without subsequent pregnancy, those with pregnancy after BC had better OS (HR 0.56, 95% CI 0.46-0.67) and DFS (HR 0.73, 95% CI 0.56-0.94). Similar results were observed in the studies correcting for the potential “healthy mother effect” (OS: HR 0.52, 95% CI 0.42-0.65; DFS: HR 0.74, 95% CI 0.58-0.96). No detrimental prognostic effect of pregnancy after BC was observed in patients with hormone-receptor positive disease (DFS: HR 1.10, 95% CI 0.73-1.66), while better outcomes were observed for those with hormone-receptor negative disease (DFS: HR 0.72, 95% CI 0.55-0.95). The safety of pregnancy after BC was observed irrespective of BRCA status, nodal status, previous chemotherapy exposure, pregnancy interval and pregnancy outcomes. Conclusions: This large meta-analysis provides solid evidence on the safety of pregnancy after prior BC diagnosis. The increased risk of fetal and obstetrical complications (but not of congenital abnormalities) calls for ensuring a closer monitoring of these pregnancies. The significantly reduced chances of conceiving as compared to the general population and other cancer patients should raise further awareness on the need to improve the oncofertility counseling of young BC patients wishing to complete their family planning following anticancer treatment completion. Citation Format: Eva Blondeaux, Marta Perachino, Marco Bruzzone, Richard A. Anderson, Evandro De Azambuja, Philip D. Poorvu, Hee Jeong Kim, Cynthia Villarreal-Garza, Barbara Pistilli, Ines Vaz-Luis, Cristina Saura, Kathryn J. Ruddy, Maria Alice Franzoi, Chiara Sertoli, Marcello Ceppi, Hatem A. Azim, Jr., Frederic Amant, Isabelle Demeestere, Lucia Del Mastro, Ann H. Partridge, Olivia Pagani, Fedro A. Peccatori, Matteo Lambertini. Chances of pregnancy after breast cancer, reproductive and disease outcomes: A systematic review and meta-analysis [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr GS3-09.

PURPOSE Young women with germline BRCA mutations have unique reproductive challenges. Pregnancy after breast cancer does not increase the risk of recurrence; however, very limited data are available in patients with BRCA mutations. This study investigated the impact of pregnancy on breast cancer outcomes in patients with germline BRCA mutations. PATIENTS AND METHODS This is an international, multicenter, hospital-based, retrospective cohort study. Eligible patients were diagnosed between January 2000 and December 2012 with invasive early breast cancer at age ≤ 40 years and harbored deleterious germline BRCA mutations. Primary end points were pregnancy rate, and disease-free survival (DFS) between patients with and without a pregnancy after breast cancer. Pregnancy outcomes and overall survival (OS) were secondary end points. Survival analyses were adjusted for guarantee-time bias controlling for known prognostic factors. RESULTS Of 1,252 patients with germline BRCA mutations ( BRCA1, 811 patients; BRCA2, 430 patients; BRCA1/2, 11 patients) included, 195 had at least 1 pregnancy after breast cancer (pregnancy rate at 10 years, 19%; 95% CI, 17% to 22%). Induced abortions and miscarriages occurred in 16 (8.2%) and 20 (10.3%) patients, respectively. Among the 150 patients who gave birth (76.9%; 170 babies), pregnancy complications and congenital anomalies occurred in 13 (11.6%) and 2 (1.8%) cases, respectively. Median follow-up from breast cancer diagnosis was 8.3 years. No differences in DFS (adjusted hazard ratio [HR], 0.87; 95% CI, 0.61 to 1.23; P = .41) or OS (adjusted HR, 0.88; 95% CI, 0.50 to 1.56; P = .66) were observed between the pregnancy and nonpregnancy cohorts. CONCLUSION Pregnancy after breast cancer in patients with germline BRCA mutations is safe without apparent worsening of maternal prognosis and is associated with favorable fetal outcomes. These results provide reassurance to patients with BRCA-mutated breast cancer interested in future fertility.

Aim: This article refers to the European School of Oncology Clinical Training Centers (CTCs) program, which is a granted Fellowships program dedicated to young oncologists in training. Materials & methods: A total of 74 fellowships were offered by several CTCs during the last 7 years. Candidates were enrolled for 3–6 months of training rotations as fellows or observers in more than 30 training programs in well known Cancer Centers around Europe. Fellowships were covering medical, surgical, radiation and pediatric oncology specialties, laboratory diagnostic training and experimental, translational and clinical research. Fellows originated from Europe, Latin America and Mediterranean Africa. Results: Analysis of the questionnaire assessment showed that 95.5% of the fellows evaluated CTC programs with an ‘excellent’ or ‘very good’ score, while 100% declare that they had reached their objectives. Conclusion: The European School of Oncology CTC program designed for an additional practical education abroad meets the needs of young oncologists.

Several myths and misconceptions exist about hormones in women with familial predisposition to cancer, and there are few real-life data on their prescription and uptake. To better understand how they are prescribed and accepted in healthy carriers of a BRCA1/2 pathogenetic variant, an online survey was uploaded on Google Forms and shared through social media closed groups of patients’ associations, aBRCAcadabra and ACTO Campania. A total of 241 questionnaires were collected. Sexual quality of life was considered of the utmost importance by most of the respondents (mean score of 7 ± 2.8/10), but they felt the counseling they received by healthcare professionals on the topic was insufficient (4.9 ± 3.2/10). Only 57 women out of 233 (24.5%) had used hormonal contraception after being diagnosed as carriers of a BRCA pathogenetic variant, and 42 out of 148 (28.4%) underwent menopause hormonal therapy. The majority of women (53.6% for contraception and 61.5% for menopause) reported being dissatisfied with the counseling received, and 58.2% were not aware of the protective effect of hormonal contraception on the risk of ovarian cancer. An educational effort is desirable to guarantee healthy BRCA carriers reliable contraception and evidence-based menopause counseling.

‘Oncohumanities’ is a new field of oncology and humanities which integrates a rich gamut of humanity disciplines and oncological expertise to tackle patients’ real needs and priorities. To promote knowledge and awareness on this topic, we propose a training programme that will blend conceptual knowledge underpinning oncology practice with and person-centred care based on the humanisations of care, on empowerment of patients, and on respect for their diversities. Oncohumanities differs from most existing medical humanities training as it is integrated and engaged with oncology (rather than an add-on). This means that its agenda is driven by the real needs and priorities arising out of daily oncological practice. It is our hope that this new Oncohumanities programme and approach will contribute to guiding future efforts to foster a strong integrated partnership between humanities and oncology.

Adolescents and young adults with cancer have substantially different clinical and psychological needs compared to those of pediatric patients and of older adult patients. We describe the development of an Italian national project dedicated to adolescents and young adults with cancer.

Background: The potential gonadotoxicity of anti-HER2 agents remains largely unknown, and limited, conflicting evidence exists for taxanes. Antimüllerian hormone (AMH) is an established biomarker of ovarian reserve that may aid in quantifying anticancer treatment–induced gonadotoxicity. Patients and Methods: The present biomarker analysis of the randomized phase III neoadjuvant NeoALTTO trial included premenopausal women aged ≤45 years at diagnosis of HER2-positive early breast cancer with available frozen serum samples at baseline (ie, before anticancer treatments), at week 2 (ie, the “biological window” of anti-HER2 therapy alone), and/or at the time of surgery (ie, after completing paclitaxel + anti-HER2 therapy, before starting adjuvant chemotherapy). Results: The present analysis included 130 patients with a median age of 38 years (interquartile ratio [IQR], age 33–42 years). AMH values at the 3 time points differed significantly (PPPConclusions: This NeoALTTO biomarker analysis showed that anti-HER2 therapies alone had limited gonadotoxicity but that the addition of weekly paclitaxel resulted in marked AMH decline with possible negative implications for subsequent ovarian function and fertility.

Simple Summary Genetic predisposition to a disease obliges women to face the fear of transmitting cancer to their offspring. This might affect their willingness to seek pregnancy and adhere to fertility preservation programs. This often-neglected issue should be discussed during fertility counseling, and patients should be offered options to overcome the problem (i.e., PGT-M, egg donation and adoption). This opinion paper arose from the authors’ multiple discussions and meetings on this subject. Abstract Genetic predisposition could have an important role in the pathogenesis of cancers in children and adolescents. A recent study by our group showed that, among female survivors of cancers in childhood and adolescence, the proportion of cases involving a possible genetic predisposition was sizable (at least one in five). Our sample is too small to be representative of the general population, but it gave us an opportunity to reappraise this issue. Women with a genetic predisposition can transmit the risk of cancer to their offspring, and their awareness of this may influence their reproductive and fertility preservation choices. In our experience, a predisposition to cancer receives little attention in the fertility counseling and decision-making process unless a patient already has a definitive molecular diagnosis of a hereditary cancer syndrome. We feel it is essential to empower women on this issue, particularly as there are ways to overcome the problem, including preimplantation genetic testing (PGT-M) in definitively diagnosed cases, egg donation and adoption. In the context of fertility counseling for survivors of cancer in childhood and adolescence who have reached adulthood, the risk of transmitting a predisposition to cancer should be discussed with patients, if relevant and desired.

In this article, we report on the clinical case presentations that have been delivered during the ESO or ESO-ESMO Masterclasses in Clinical Oncology in the last 10 years. Masterclasses have been held in three different geographical continents including Europe, Middle East, and Latin America, in which participants had to submit a clinical case and present it either in front of a tumor board (multidisciplinary-like sessions) or in small groups. Clinical case presentation is a unique part of the educational program preparing young oncologists to present and discuss their own patients with distinguished experts. In each Masterclass, between 40 and 55 clinical cases-depending on the number of participants-are presented. All presentations are assessed and evaluated by faculty members as well as by the rest of the participants.

Postpartum breast cancer (PPBC) - which according to new data, can extend to 5-10 years after the birth - are estimated to represent 35-55% of all cases of breast cancer in women younger than 45 years. Increasing clinical evidence indicates that PPBC represents a high-risk form of breast cancer in young women with an approximately 2-fold increased risk for metastasis and death. Yet, the exact mechanisms that underlay this poor prognosis are incompletely understood and, hence, it is unknown why postpartum breast cancer has an enhanced risk for metastasis or how it should be effectively targeted for improved survival. This article is an accompanying resource of the original article entitled "Breast cancer diagnosed in the post-weaning period is indicative for a poor outcome" and present epidemiological data that compare standard prognostic parameters, first site of metastatic disease and survival and metastatic rates in young women with primary invasive breast cancer diagnosed within two years postpartum (PP-BC), in young women diagnosed during pregnancy (Pr-BC) and nulliparous women (NP-BC). Via an international collaboration of 13 centres participating in the International Network on Cancer, Infertility and Pregnancy (INCIP), retrospective data of 1180 patients with primary invasive breast cancer, aged 25-40 years and diagnosed between January 1995 and December 2017 were collected. In particular, tumour-, patient, and therapy-related characteristics were collected. Furthermore, patient files were reviewed thoroughly to assess, for each parity, if and for how long breastfeeding was given. For PP-BC patients, breastfeeding history was used to differentiate breast cancers identified during lactation (PP-BCDL) from those diagnosed post-weaning (PP-BCPW). Primary exposures were prior childbirth or no childbirth, time between most recent childbirth and breast cancer diagnosis, time between cessation of lactation and breast cancer diagnosis and time between breast cancer diagnosis and metastasis or death. Distribution of standard prognostic parameters and first site of distant metastasis among study groups was determined applying fisher's exact, chi-squared, One-Way ANOVA or Kruskal-Wallis tests or logistic regression models, where applicable. The risks for metastasis and death were assessed using Cox proportional hazards models. A subgroup analysis was performed in PP-BCPW patients that never lactated (PP-BCPW/NL), lactated ≤3 months (PP-BCPW/Lshort) or lactated >3 months (PP-BCPW/Llong). ispartof: DATA IN BRIEF vol:38 ispartof: location:Netherlands status: published

BACKGROUND: In young women, a breast cancer diagnosis after childbirth increases the risk for metastasis and death. Studies in rodents suggest that post-weaning mammary gland involution contributes to the poor prognosis of postpartum breast cancers. However, this association has not been investigated in humans, mainly because of missing information on the patient's lactation status at diagnosis. PATIENTS AND METHODS: Clinicopathological data of 1180 young women with primary invasive breast cancer, diagnosed within 2 years postpartum (PP-BC), during pregnancy (Pr-BC), or nulliparous (NP-BC), were collected. For PP-BC patients, breastfeeding history was retrieved to differentiate breast cancers identified during lactation (PP-BCDL) from those diagnosed post-weaning (PP-BCPW). Differences in prognostic parameters, first site of distant metastasis, and risks for metastasis and death were determined between patient groups. RESULTS: Cox proportional hazard models pointed to a twofold increased the risk of metastasis and death in PP-BCPW patients compared with PP-BCDL (hazard ratio [HR] 2.1 [PDRS = 0.021] and 2.9 [POS = 0.004]), Pr-BC (HR 2.1 [PDRS