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Current literature suggests that emergency contraception, defined as a therapy aimed at preventing an unwanted pregnancy after unprotected or insufficiently protected intercourse, is used more by cancer survivors than by the general population. This may be related to reduced use of contraception in women after cancer diagnosis and, when it is used, to a choice of less effective methods, even in the absence of contraindications to hormonal options. The purpose of this review is to analyze the use of contraception in these patients, its predictors and the preferred methods, as well as to try to define timing and characteristics of an effective contraception counseling. Factors identified as predictors of contraception usage were younger age, having a partner and better sexual function, having children, past use and having received contraception counseling by a gynecologist, especially in the previous year. Contraception counseling should start before oncological therapies, together with information regarding fertility and sexual health, preferably by the gynecologist of the oncofertility unit, with a specific expertise in dealing with cancer patients. Increased awareness of oncologists and family medicine doctors is fundamental to optimize contraception use and compliance with the prescribed method. Major guidelines regarding oncological care in women of fertile age already recommend contraception counseling, but optimal timing and mode of the consultation(s) options should be further researched, to be better detailed in all relevant documents., Competing Interests: Matteo Lambertini reports advisory role for Roche, Lilly, Novartis, AstraZeneca, Pfizer, Seagen, Gilead, MSD, Exact Sciences, Pierre Fabre, Menarini; speaker honoraria from Roche, Lilly, Novartis, Pfizer, Sandoz, Libbs, Daiichi Sankyo, Takeda, Menarini, Ipsen, Knight, Gilead, AstraZeneca; travel Grants from Gilead, Daiichi Sankyo, Roche; research funding (to the Institution) from Gilead all outside the submitted work. The other authors report no conflicts of interest related to this work., (© 2024 Asinaro et al.)

Background: Optimal therapy following breast-conserving surgery in older adults with low-risk, early-stage breast cancer remains uncertain. The EUROPA trial aims to compare the effects of radiotherapy and endocrine therapy as single-modality treatments on health-related quality of life (HRQOL) and ipsilateral breast tumour recurrence (IBTR) outcomes in this population., Methods: This non-inferiority, phase 3, randomised study was conducted at 18 academic hospitals across Italy (17 centres) and Slovenia (one centre). Eligible patients were women aged 70 years or older with histologically confirmed, stage I, luminal A-like breast cancer, who had undergone breast-conserving surgery and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1) to receive single-modality endocrine therapy or radiotherapy. Endocrine therapy consisted of daily oral aromatase inhibitors or tamoxifen, for a total planned duration of 5-10 years as per clinical discretion, while radiotherapy was administered as either whole breast or partial breast irradiation, delivered in 5-15 fractions. Randomisation was stratified by health status according to the Geriatric 8 (G8) screening tool and by age, with allocation concealed and no blinding. The co-primary endpoints were the change in HRQOL, assessed by the global health status (GHS) scale of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 30-item core module at 24 months, and 5-year IBTR rates (not reported here). This preplanned interim analysis was performed once at least 152 patients completed the 24-month GHS HRQOL assessment. The safety population comprised patients who received the study intervention at least once after randomisation. The study is registered with ClinicalTrials.gov, NCT04134598, and is ongoing and actively recruiting., Findings: Between March 4, 2021, and June 14, 2024, 731 women were randomly assigned to receive radiotherapy (n=365) or endocrine therapy (n=366). This analysis included 104 patients in the radiotherapy group and 103 in the endocrine therapy group, with a median follow-up of 23·9 months (IQR 22·9-24·2). Patients were predominantly White (204 [99%] of 207) and the median age was 75·0 years (IQR 73·0-80·0) in the radiotherapy group and 74·0 years (72·0-80·0) in the endocrine therapy group. 86 patients in the radiotherapy group and 75 in the endocrine therapy group completed the 24-month HRQOL assessment. The mean baseline GHS score was 71·9 (SD 19·1) in the radiotherapy group and 75·5 (19·3) in the endocrine therapy group. At 24 months, the age-adjusted, G8 score-adjusted mean change from baseline in GHS was -3·40 (95% CI -7·82 to 1·03; p=0·13) in the radiotherapy group and -9·79 (-14·45 to -5·13; p<0·0001) in the endocrine therapy group, with an adjusted mean difference of 6·39 (0·14 to 12·65; p=0·045) favouring radiotherapy. Treatment-related adverse events were less frequent in the radiotherapy group (65 [67%] of 97 patients) compared with the endocrine therapy group (76 [85%] of 89). The most common grade 3-4 adverse events were arthralgia (six [7%] of 89 in the endocrine therapy group vs 0 of 97 in the radiotherapy group), pelvic organ prolapse (three [3%] vs 0), fatigue, hot flashes, myalgia, bone pain, and fractures (two [2%] vs 0 for each). Serious adverse events were reported in 15 (15%) patients in the radiotherapy group and 13 (15%) in the endocrine therapy group. There were no treatment-related deaths in either group., Interpretation: Endocrine therapy was associated with a greater reduction in HRQOL, as measured by GHS, compared with radiotherapy at 24 months. While these interim results suggest radiotherapy might better preserve HRQOL in older women with low-risk early breast cancer, further data on disease control outcomes and final patient accrual are needed to draw definitive conclusions., Funding: Fondazione Radioterapia Oncologica., Competing Interests: Declaration of interests IM has received occasional fees for advisory board participation supported by Eli Lilly, Novartis, Pfizer, AstraZeneca, Daiichi Sankyo, Gilead, and Menarini StemLine, outside the submitted work. ML has reported advisory roles supported by Roche, Eli Lilly, Novartis, AstraZeneca, Pfizer, Seagen, Gilead, MSD, Exact Sciences, Pierre Fabre, and Menarini StemLine; speaker honoraria from Roche, Eli Lilly, Novartis, Pfizer, AstraZeneca, Takeda, Ipsen, Sandoz, Libbs, Knight, Daiichi Sankyo, Gilead, and Menarini StemLine; and travel grants from Gilead, Daiichi Sankyo, and Roche. VS has reported honoraria from Nucletron and Elekta. TS discloses unrestricted grants for programmes of Europa Donna Slovenia, as well as speaker honoraria from Pfizer, MSD, Roche, and AstraZeneca. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

The clinical management of triple-negative breast cancer has been very difficult for a long time, being classical chemotherapy the only possible therapeutic approach given the absence of specific targets. However, the therapeutic armamentarium has recently been expanded thanks to the introduction of new molecules, in particular immunotherapy and antibody-drug conjugates (ADCs), which have made it possible to significantly improve the prognosis of this patient population both in the early and advanced settings. Since 2022, the ADC sacituzumab govitecan has been approved by the Italian Medicines Agency (Aifa) for the treatment of advanced/metastatic triple-negative breast cancer pretreated with at least two lines of systemic therapy, of which at least one for metastatic disease. In the collection of case reports, we delved into the available data on the efficacy profile and impact on quality of life of sacituzumab govitecan in several special populations of patients with triple-negative metastatic breast cancer.

Purpose: The aim of this study was to evaluate the effectiveness of CDK 4/6 inhibitors (CDK 4-6i) according to HER2 status (low/zero), and endocrine resistance/sensitivity, as well as the efficacy of second-line treatments, in a large real-world cohort., Methods: The GIM14/BIOMETA study (NCT02284581) is a retrospective/prospective study of the Gruppo Italiano Mammella evaluating treatment patterns and survival outcomes in patients with metastatic breast cancer (MBC). We retrieved data on patients with hormone receptor-positive/HER2-negative MBC receiving first-line CDK 4/6i., Results: Among 3832 patients enrolled in the GIM14-BIOMETA study, 701 were eligible. At a median follow-up of 24.80 months, no significant differences were found between HER2-zero and HER2-low subgroups in terms of first-line time to treatment discontinuation (TTD) (26.16 months [IQR 12.84-NR] vs. 27.60 months [IQR 12.12-64.44], p = 0.972) or overall survival (OS) (mOS>60 months for both groups, p = 0.398). Median TTD was 33.24 months (IQR 16.32-NR) for the endocrine sensitive subgroup, 19.92 months (IQR 8.88-51.24) for the secondary endocrine resistant subgroup and 17.40 months (IQR 7.44-24.72) for the primary endocrine resistant subset, respectively (p < 0.001). Among 239 patients receiving second-line treatment, no significant difference (p = 0.188) was found in terms of second-line TTD between those treated with capecitabine (6.11 months, IQR 2.96-11.47), taxane-based chemotherapy (5.06 months, IQR 2.99-9.99), everolimus plus exemestane (5.39 months, IQR 2.53-9.03) or fulvestrant (6.44 months, IQR 3.38-NR)., Conclusions: Endocrine therapy plus CDK 4/6i represents an effective treatment, regardless of HER2 status (low/zero). Second-line agents did not differ significantly in terms of TTD. Endocrine resistant cancers exhibit poor response to CDK 4/6i., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Chiara Molinelli reports honoraria for consultancy and consulting fees from Daiichi Sankyo, travel support to attend conferences from Gilead, Menarini and fees for medical writing from Lilly and Seagen. Eva Blondeaux reports honoraria from Eli Lilly and research funding (to institution) from Gilead. Michelino De Laurentiis reports honoraria or consultation fees for speaker, consultancy or advisory roles from Eli Lilly, Seagen, Therapeutics, GSK, Roche, Novartis, Genetic, Pfizer, Pierre Fabre, MSD, Menarini Stemline, Sophos Biotech, Max Farma, Celltrion Healthcare, Gilead, Daiichi Sankyo; institutional financial interests, financial support for clinical trials or contracted research, from: Novartis, Pierre Fabre, Pfizer, Roche, Stemline Therapeutics. Alessandra Fabi reports consulting fees and honoraria from Roche, Novartis, Lilly, Pfizer, MSD, Gilead, Seagen, Astra Zeneca, Daiichi Sankyo. Support for attending meetings and/or travel from Novartis, Lilly, Pfizer, MSD. Grazia Arpino reports research and medical writing from AstraZeneca; advisory boards, travel grants, activities as a speaker, consultancy from AstraZeneca, Daiichi Sankyo, Eisai, Eli Lilly, Gilead, Exact Science, Novartis, Roche, Seagen, Viatris. Andrea Fontana reports advisory boards from Roche, Novartis, Eli Lilly, Pfizer, MSD, Pierre Fabre, Eisai, Gilead, Seagen, Astra Zeneca, Exact Sciences; consulting fees from Dompé Farmaceutici S.p.A. D.G. Research funding from Menarini, Seagen, Novartis, AstraZeneca; advisory boards, activities as a speaker, consultancy from Seagen, Novartis, Eli Lilly, Roche, Gilead, Pfizer, Eisai, Exact Sciences. Fabio Puglisi reports advisory role for and receiving speaker honoraria from Amgen, AstraZeneca, Daichii Sankyo, Celgene, Eisai, Eli Lilly, Exact Sciences, Gilead, Ipsen, Menarini, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Seagen, Takeda, and Viatris. Travel grants from AstraZeneca, Daichii Sankyo, Novartis, Roche. Research grants (to his institution) from Astrazeneca, Eisai, Roche. Claudia Bighin reports personal fees from Roche, Novartis, Lilly, Gilead, and Daiichi. Matteo Lambertini reports advisory role for Roche, Lilly, Novartis, Astrazeneca, Pfizer, Seagen, Gilead, MSD, Exact Sciences, Pierre Fabre, Menarini; speaker honoraria from Roche, Lilly, Novartis, Pfizer, Sandoz, Libbs, Daiichi Sankyo, Takeda, Menarini, AstraZeneca; travel Grants from Gilead, Daiichi Sankyo, Roche; research funding (to the Institution) from Gilead all outside the submitted work. Lucia Del Mastro reports grants from Eli Lilly, Novartis, Roche, Daiichi Sankyo, Seagen, AstraZeneca, Gilead, and Pierre Fabre; receiving consulting fees from Eli Lilly, Gilead, and Daiichi Sankyo; receiving speaker honoraria from Roche, Novartis, Pfizer, Eli Lilly, AstraZeneca, MSD, Seagen, Gilead, Pierre Fabre, Eisai, Exact Sciences, Ipsen, GSK, and Agendia-Stemline; receiving travel grants from Roche, Pfizer, Eisai, Daiichi Sankyo, and AstraZeneca; and having an advisory role for Novartis, Roche, Eli Lilly, Pfizer, Daiichi Sakyo, Exact Sciences, Gilead, Pierre Fabre, Eisai, AstraZeneca, Agendia, GSK, and Seagen. All the other authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The incidence of early-onset cancers in adolescents and young adults (AYA) has been increasing worldwide since the 1990s. In Italy, a significant increased rate of 1.6 % per year has been reported for early-onset cancers among females between 2008 and 2016. This is mainly attributable to melanoma, thyroid, breast and endometrial cancer. The aim of our work was to describe temporal trends of the main established lifestyle risk factors (tobacco use, alcohol consumption, obesity, physical inactivity, dietary westernization and reproductive factors) over the last 20 years in the Italian AYA population. Available data on behavioural risk factors, individual and household daily life have been obtained and elaborated from PASSI, ISTAT and Eurostat reports. Lowering age of smoking initiation, an increase in alcohol drinkers among young females, and an obesity and overweight epidemic, particularly among children and adolescents as a result of physical inactivity and dietary habits, may be contributing factors behind this cancer epidemic, especially among females. In-depth investigations are needed to understand the exact role of each contributing factor, the effects of exposure to nicotine-containing products and environmental factors such as endocrine disruptors that could play a role in this phenomenon., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare that are relevant to the content of this manuscript., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose of Review: Use of adjuvant chemotherapy significantly reduces the risk of recurrence and improves overall survival (OS) in patients with early-stage breast cancer. However, few data are available on the efficacy of different adjuvant chemotherapy regimens and schedules in patients with hormone receptor positive/HER2-negative (HR+/HER2-) breast cancer. We aim to summarize the available evidence on the efficacy of adjuvant anthracycline-based chemotherapy and of the dose-dense schedule in this specific patient population. Moreover, current controversies in the management of patients with early-stage HR+/HER2- breast cancer are discussed., Recent Findings: Patient-level meta-analysis evaluating the role of the addition of an anthracycline to taxane-based chemotherapy showed that recurrence rate was lower among patients receiving anthracycline-based treatment.Patient-level meta-analysis evaluating the role of different schedules of chemotherapy administration showed that the use of adjuvant dose-dense chemotherapy is associated with significant reduction in breast cancer recurrences and breast cancer mortality. Less evidence is available in the neoadjuvant setting., Summary: For patients with high-risk HR+/HER2- breast cancer, (neo) adjuvant anthracycline and taxane-based chemotherapy, and a dose-dense regimen should still be considered the standard of care. However, in patients with intermediate risk breast cancer candidates to chemotherapy, anthracycline-free regimens could be considered the preferred treatment option., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The ubiquitous presence of plastics represents a global threat for all ecosystems and human health. In this study, we evaluated, in vitro and in vivo, the genotoxic potential of different concentrations of polystyrene microplastics (PS-MPs) and their possible synergistic interactions with bisphenol-A (BPA). For the in vitro and the in vivo assays, we used human lymphocytes and hemocytes from Lymnaea stagnalis , respectively. The genomic damage was evaluated by the micronucleus assay, and differences in eggs laid and growth of L. stagnalis were also evaluated. In human lymphocytes, PS-MPs alone at the concentration of 200 μg/mL and in association with BPA 0.100 µg/mL significantly increased the frequencies of micronuclei and nuclear buds, indicating a possible in vitro genotoxic additive action of these two compounds. Vice versa, PS-MPs did not result in genotoxicity in hemocytes. Our results indicated that PS-MPs have genotoxic properties only in vitro and at a concentration of 200 µg/mL; moreover, this compound could intensify the genomic damage when tested with BPA, indicating possible cumulative effects. Finally, PS significantly reduced the growth and the number of laid eggs in L. stagnalis.

Background: Young women with breast cancer (BC) have an increased chance of carrying germline BRCA pathogenic variants (PVs). Limited data exist on the prognostic impact of tumor histology (i.e. ductal versus lobular) in hereditary breast cancer., Methods: This multicenter retrospective cohort study included women aged ≤40 years with early-stage breast cancer diagnosed between January 2000 and December 2020 and known to carry germline PVs in BRCA1/2. Histology was locally assessed in each center. The Kaplan-Meier method and Cox regression analysis were used to assess disease-free survival and overall survival., Results: Of 4628 patients included from 78 centers worldwide, 3969 (86%) had pure ductal, 135 (3%) pure lobular, and 524 (11%) other histologies. Compared with ductal tumors, lobular tumors were more often grade 1/2 (57.7% versus 22.1%), stage III (29.6% versus 18.5%), and luminal A-like (42.2% versus 12.2%). Lobular tumors were more often associated with BRCA2 PVs (71.1% BRCA2), while ductal tumors were more often associated with BRCA1 PVs (65.7% BRCA1). Patients with lobular tumors more often had mastectomy (68.9% versus 58.3%), and less often received chemotherapy (83.7% versus 92.9%). With a median follow-up of 7.8 years, no significant differences were observed in disease-free survival (adjusted hazard ratio 1.01, 95% confidence interval 0.74-1.37) or overall survival (hazard ratio 0.96, 95% confidence interval 0.62-1.50) between patients with ductal versus lobular tumors. No significant survival differences were observed according to specific BRCA gene, breast cancer subtype, or body mass index., Conclusions: In this large global cohort of young BRCA carriers with breast cancer, the incidence of pure lobular histology was low and associated with higher disease stage at diagnosis, luminal-like disease and BRCA2 PVs. Histology did not appear to impact prognosis., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Most premenopausal patients with early breast cancer (eBC) are diagnosed with hormone receptor-positive disease and therefore candidate for adjuvant endocrine therapy (ET)., Patients and Methods: The Gruppo Italiano Mammella (GIM) 23-POSTER (GIM23) is a multicenter, prospective, observational study conducted in 26 Italian institutions, aiming to evaluate ET choices for premenopausal patients affected by hormone receptor-positive eBC in a real-world setting. Here we report also the results in terms of type of ET prescribed according to the definition of high-risk patients by monarchE and NATALEE trials., Results: Between October 2019 and June 2022, 600 premenopausal patients were included, with a median age of 46 years. Almost half (271, 45.2 %) of the patients had stage I disease, while 254 (42.3 %) and 60 (10.0 %) patients had stage II and III, respectively. Overall, 149 (25.1 %) patients received tamoxifen alone, 83 (14.0 %) tamoxifen with ovarian function suppression (OFS), while 361 (60.9 %) received aromatase inhibitor (AI) with OFS. Patients treated with AI and OFS had higher number of metastatic axillary nodes, higher grade and more often received chemotherapy (all p < 0.001). According to the inclusion criteria of the monarchE and NATALEE trials, 81 patients (15.6 %) were considered high-risk for the monarchE and received AI with OFS in 88.9 % of the cases, while 231 patients (44.4 %) were considered high-risk for the NATALEE trial and received AI with OFS in 74.5 % of cases., Conclusions: AI with OFS is the most prescribed adjuvant ET among premenopausal patients, especially in the presence of high-risk features., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Eva Blondeaux: speaker fee from Eli Lilly and research support from Gilead Science (to the institution). Valentina Guarneri: personal fees from EliLilly, Exact Sciences, Novartis, Pfizer, Gilead, MSD, Amgen, Sanofi, Merck Serono, and Eisai outside the submitted work. Eleonora Mioranza: personal fee from Novartis e Lilly. Fabio Puglisi: advisory role for and receiving speaker honoraria from Amgen, AstraZeneca, Daichii Sankyo, Celgene, Eisai, Eli Lilly, Exact Sciences, Gilead, Ipsen, Menarini, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Seagen, Takeda, and Viatris. Travel grants from AstraZeneca, Daichii Sankyo, Novartis, Roche. Research grants (to his institution) from Astrazeneca, Eisai, Roche. Antonella Ferro: support for attending meeting from Gilead, MSD and Pfizer; honoraria from Pfizer, Novartis, Daiichi Sankyo, Ely Lilly, Seagen, Gilead, Astra Zeneca, MSD. Vincenzo Adamo: consultancy/advisory role/speaker bureau from Amgen, Astra Zeneca, BMS, Gilead, Lilly, MSD, Novartis, Pfizer, Roche, Sandoz, Sanofi, Sevier, Takeda. Laura Biganzoli: Personal financial interests (Honoraria, consultancy or advisory role): Amgen, AstraZeneca, Boehringer-Ingelheim, Daiichi-Sankyo, Eisai, Exact Sciences, Gilead, Lilly, Menarini, Novartis, Pfizer, Pierre Fabre, Roche, Sanofi, SeaGen. Institutional financial interests: Celgene, Genomic Health, Novartis. Travel grant: AstraZeneca, Daiichi-Sankyo. Evandro de Azambuja: honoraria from or participation in advisory boards for Roche, Genentech, Novartis, SeaGen, Zodiac, Libbs, Pierre Fabre, Eli Lilly, and AstraZeneca. Francesca Poggio: fees and other support from AstraZeneca and personal fees from Eli Lilly, Novartis, Daichii Sankyo, and Gilead outside the submitted work. Matteo Lambertini: advisory role for Roche, Lilly, Novartis, AstraZeneca, Pfizer, Seagen, Gilead, MSD, and Exact Sciences; receiving speaker honoraria from Roche, Lilly, Novartis, Pfizer, Sandoz, Libbs, Daiichi Sankyo, Takeda, Knight, Ipsen, and AstraZeneca; receiving travel grants from Gilead and Daiichi Sankyo; receiving research funding (to his institution) from Gilead. Lucia Del Mastro: grants from Eli Lilly, Novartis, Roche, Daiichi Sankyo, Seagen, AstraZeneca, Gilead, and Pierre Fabre; receiving consulting fees from Eli Lilly, Gilead, and Daiichi Sankyo; receiving speaker honoraria from Roche, Novartis, Pfizer, Eli Lilly, AstraZeneca, MSD, Seagen, Gilead, Pierre Fabre, Eisai, Exact Sciences, Ipsen, GSK, and Agendia-Stemline; receiving travel grants from Roche, Pfizer, Eisai, Daiichi Sankyo, and AstraZeneca; and having an advisory role for Novartis, Roche, Eli Lilly, Pfizer, Daiichi Sakyo, Exact Sciences, Gilead, Pierre Fabre, Eisai, AstraZeneca, Agendia, GSK, and Seagen. All the other authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To compare menopausal symptoms of breast cancer survivors on adjuvant endocrine therapy with those of menopausal women., Study Design: In a retrospective nested case-control study menopausal symptoms were compared of breast cancer survivors in pre-, peri- or post-menopause at the time of diagnosis, on tamoxifen or an aromatase inhibitor, plus a gonadotrophin-releasing hormone analogue, if pre- or peri-menopausal, and age-matched control women either in the late peri-menopause, or in surgical or in physiological post-menopause on no hormone replacement therapy. Differences between women on tamoxifen and those on aromatase inhibitors were also evaluated. Weighted and non-weighted t-tests, chi-square tests, and linear or logistic regressions were applied as appropriate., Main Outcome Measures: Score on the Greene's Climacteric Scale and so of its subscales evaluating vasomotor, anxiety, depression, somatisation and sexuality symptoms., Results: A total of 99 breast cancer survivors (45 on tamoxifen, 54 on aromatase inhibitors) and 554 controls (173 in late perimenopause, 353 in natural and 28 in surgical menopause) were enrolled. The score on the Greene's Climacteric Scale was similar in cases and controls (means ± standard deviation) (21.3 ± 10.4 vs. 22.8 ± 11.5, p = 0.199), as were the subscale scores for vasomotor symptoms, anxiety, and somatisation. The depression score was lower (4.63 ± 3.3 vs. 5.98 ± 3.8; p = 0.001) in breast cancer survivors on adjuvant endocrine therapy, mainly due to a lower score of -2.132 (95 % confidence interval - 3.858/-0.407; p = 0.016) for users of aromatase inhibitors. The sexuality score was higher (1.76 ± 1.1 vs. 1.50 ± 1.1, p = 0.011) than in controls. Differences remained significant when corrected for age, menarche, body mass index, menopausal status (peri- or post-), type of menopause (natural, surgical), use of gonadotrophin-releasing hormone analogues, years of amenorrhea, smoking, alcohol use, and for breast radiotherapy, chemotherapy, tamoxifen or aromatase inhibitors. Among breast cancer survivors, women on aromatase inhibitors had lower scores for anxiety (5.75 ± 2.5vs.5.75 ± 2.5; p = 0.045) and depression (3.89 ± 2.5 vs. 5.13 ± 3.6; p = 0.046) than women on tamoxifen., Conclusions: In breast cancer survivors, adjuvant therapy induces symptoms similar in type and intensity to those of symptomatic menopausal women. Compared with menopausal women, breast cancer survivors, particularly those on aromatase inhibitors, appear to experience less severe depressive symptoms., Competing Interests: Declaration of competing interest M. Lambertini reports advisory role for Roche, Lilly, Novartis, Astrazeneca, Pfizer, Seagen, Gilead, MSD, Exact Sciences; speaker honoraria from Roche, Lilly, Novartis, Pfizer, Sandoz, Libbs, Daiichi Sankyo, Takeda, Gilead; travel Grants from Gilead, Daiichi Sankyo, Roche; research funding (to the Institution) from Gilead all outside the submitted work. Prof. Lucia L. Del Mastro reports advisory role and/or speaker honoraria for Roche, Eli Lilly, Novartis, Pfizer, Pierre Fabre, Eisai, Gilead, Astrazeneca, Daiichi Sankyio, Gilead, Exact sciences, Agendia, Menarini Stemline, Olema, Ipsen, MSD; travel grants from Gilead, daiichi Sankyo, Astrazeneca, Roche; research funding (to the institution) from Pfizer, all outside the submitted work. The other authors declare no conflict of interest with the content of the present article., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Breast cancer is the most common malignancy in women of reproductive age and chemotherapy protocols impair fertility, frequently necessitating fertility preservation (FP) referral. Embryo, oocyte, or ovarian tissue cryopreservation are established FP modalities in women with breast cancer but there are few data on their uptake over time. In this study our aim was to determine the regional time trends and utility differences for fertility preservation methods of reproductive tissue cryopreservation., Methods: This multicenter study included 1623 women diagnosed with breast cancer from 7 tertiary centers in 6 countries (Brazil, Italy, Scotland, South Korea, Turkey, USA). Participant centers provided the details of FP cryopreservation approaches broken down annually from 2012 to 2021. Women with newly diagnosed breast cancer, aged 18-45 years who were referred for FP at participating centers and had normal ovarian function at the time were included., Results: We found a mean increase of 7% per year (P = .002, adjusting for centers) in the number of women referred for FP. Of those who were referred (n = 1623), a mean 38.7% underwent FP (n = 629), with a range of 12% in South Korea) to 95% in Brazil. The number of women undergoing ovarian stimulation for FP continually increased until 2021, with oocyte cryopreservation being the most common procedure throughout the study period (P = .014 for time trend). The proportion of random start ovarian stimulation cycles increased each year from 58.3% in 2012 to 86.8% in 2021, (P = .005 for time trend, and P = .04 for 2012 vs. 2021)., Conclusions: The utility of FP has steadily increased for young women with breast cancer over the last decade, although regional differences significantly influence FP practices. The findings of our study could have value for policy making in FP care for young women with breast cancer at the local, regional, or global level., Competing Interests: Disclosure Dr. Lambertini reports advisory role for Roche, Lilly, Novartis, Astrazeneca, Pfizer, Seagen, Gilead, MSD, and Exact Sciences; speaker honoraria from Roche, Lilly, Novartis, Pfizer, Sandoz, Libbs, Daiichi Sankyo, Takeda, Knight, Ipsen, and AstraZeneca; travel Grants from Gilead, Daiichi Sankyo, Roche and a research grant (to his Institution) from Gilead, all outside the submitted work. All other authors state that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Cryopreservation of human spermatozoa is a widely used technique in the assisted reproduction technology laboratory for the storage of gametes for later use, for the fertility preservation and for sperm donation programs. Cryopreservation can cause damage to membrane, cytoskeletal, acrosome and increased oxidative stress, sperm DNA damage and transcriptome changes. To assess the impact of storage time on the transcriptome of frozen human spermatozoa, semen samples were collected from 24 normospermic donors of whom 13 had cryostored semen for a short-time (1 week) and 11 had cryostored semen for a long-time (median 9 years)., Results: RNA was extracted from each frozen-thawed sperm sample, randomized in pools, and analyzed by microarrays. Five transcripts were in higher abundance in the long-time respect to the short-time storage group. Functional annotation enrichment disclosed that that the length of cryostorage has no effect on critical pathways involved in sperm physiology and function., Conclusions: The storage time of cryopreserved human spermatozoa does not affect pathways involved in fertility., (© 2024. The Author(s).)

Background: Hormone receptor expression is a known positive prognostic and predictive factor in breast cancer; however, limited evidence exists on its prognostic impact on prognosis of young patients harboring a pathogenic variant (PV) in the BRCA1 and/or BRCA2 genes., Patients and Methods: This international, multicenter, retrospective cohort study included young patients (aged ≤40 years) diagnosed with invasive breast cancer and harboring germline PVs in BRCA genes. We investigated the impact of hormone receptor status on clinical behavior and outcomes of breast cancer. Outcomes of interest [disease-free survival (DFS), breast cancer-specific survival (BCSS), and overall survival (OS)] were first investigated according to hormone receptor expression (positive versus negative), and then according to breast cancer subtype [luminal A-like versus luminal B-like versus triple-negative versus human epidermal growth factor receptor 2 (HER2)-positive breast cancer]., Results: From 78 centers worldwide, 4709 BRCA carriers were included, of whom 2143 (45.5%) had hormone receptor-positive and 2566 (54.5%) hormone receptor-negative breast cancer. Median follow-up was 7.9 years. The rate of distant recurrences was higher in patients with hormone receptor-positive disease (13.1% versus 9.6%, P < 0.001), while the rate of second primary breast cancer was lower (9.1% versus 14.7%, P < 0.001) compared to patients with hormone receptor-negative disease. The 8-year DFS was 65.8% and 63.4% in patients with hormone receptor-positive and negative disease, respectively. The hazard ratio of hormone receptor-positive versus negative disease changed over time for DFS, BCSS, and OS (P < 0.05 for interaction of hormone receptor status and survival time). Patients with luminal A-like breast cancer had the worst long-term prognosis in terms of DFS compared to all the other subgroups (8-year DFS: 60.8% in luminal A-like versus 63.5% in triple-negative versus 65.5% in HER2-positive and 69.7% in luminal B-like subtype)., Conclusions: In young BRCA carriers, differences in recurrence pattern and second primary breast cancer among hormone receptor-positive versus negative disease warrant consideration in counseling patients on treatment, follow-up, and risk-reducing surgery., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Anticancer treatments have significantly contributed to increasing cure rates of breast cancer in the last years; however, they can also lead to short- and long-term side effects, including gonadotoxicity, and compromised fertility in young women. Oncofertility is a crucial issue for young patients who have not yet completed their family planning at the time of cancer diagnosis., Areas Covered: This review aims to cover all the latest available evidence in the field of oncofertility, including the gonadotoxicity of currently adopted anticancer therapies in the curative breast cancer setting, the available strategies for fertility preservation and the feasibility of achieving a pregnancy following anticancer treatment completion., Expert Opinion: Over the past years, a significant progress has been made in oncofertility care for young women with breast cancer. In the context of the currently available evidence, every young woman with newly diagnosed breast cancer should receive a proper and complete oncofertility counseling before starting any anticancer treatment to increase her chances of future pregnancies.

Background: Breast cancer (BC) in women aged ≤40 years carrying germline pathogenetic variants (PVs) in BRCA1/2 genes is infrequent but often associated with aggressive features. Human epidermal growth factor receptor 2 (HER2)-low-expressing BC has recently emerged as a novel therapeutic target but has not been characterized in this rare patient subset., Methods: Women aged ≤40 years with newly diagnosed early-stage HER2-negative BC (HER2-0 and HER2-low) and germline BRCA1/2 PVs from 78 health care centers worldwide were retrospectively included. Chi-square test and Student t-test were used to describe variable distribution between HER2-0 and HER2-low. Associations with HER2-low status were assessed with logistic regression. Kaplan-Meier method and Cox regression analysis were used to assess disease-free survival (DFS) and overall survival. Statistical significance was considered for p ≤ .05., Results: Of 3547 included patients, 32.3% had HER2-low BC, representing 46.3% of hormone receptor-positive and 21.3% of triple-negative (TN) tumors. HER2-low vs. HER2-0 BC were more often of grade 1/2 (p < .001), hormone receptor-positive (p < .001), and node-positive (p = .003). BRCA2 PVs were more often associated with HER2-low than BRCA1 PVs (p < .001). HER2-low versus HER2-0 showed better DFS (hazard ratio [HR], 0.86; 95% CI, 0.76-0.97) in the overall population and more favorable DFS (HR, 0.78; 95% CI, 0.64-0.95) and overall survival (HR, 0.65; 95% CI, 0.46-0.93) in the TN subgroup. Luminal A-like tumors in HER2-low (p = .014) and TN and luminal A-like in HER2-0 (p = .019) showed the worst DFS., Conclusions: In young patients with HER2-negative BC and germline BRCA1/2 PVs, HER2-low disease was less frequent than expected and more frequently linked to BRCA2 PVs and associated with luminal-like disease. HER2-low status was associated with a modestly improved prognosis., (© 2024 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Background: The phase III GIM2 trial showed improved disease-free survival (DFS) and overall survival (OS) with adjuvant dose-dense (DD) as compared with standard-interval (SI) chemotherapy in women with node-positive early-stage breast cancer (BC). This exploratory analysis aimed to investigate the benefit of different schedules according to body mass index (BMI) in this trial., Patients and Methods: This analysis explored the efficacy, in terms of DFS and OS, of different chemotherapy schedules according to BMI. Univariate and multivariable Cox proportional hazard models, adjusted for relevant prognostic factors, were used., Results: Out of 2091 patients enrolled, 1925 with known baseline BMI were randomized in the DD versus SI comparison and therefore included in this analysis: 31.6% were overweight and 19.3% obese. Overweight and obesity were significantly associated with postmenopausal status, pT >2, and pN >2 tumors. After a median follow-up of 15.0 years (interquartile range 8.4-16.3 years), multivariable Cox survival models demonstrated no association of different BMI categories on DFS [adjusted hazard ratio (adjHR) 0.96, 95% confidence interval (CI) 0.80-1.15 and adjHR 1.11, 95% CI 0.91-1.35 for overweight and obese patients, respectively, compared to patients with normal BMI] or OS (adjHR 0.90, 95% CI 0.71-1.14 and adjHR 1.18, 95% CI 0.92-1.52 for overweight and obese patients, respectively). No significant interaction was found between BMI and treatment schedule in terms of DFS (P for interaction  = 0.56) or OS (P for interaction  = 0.19). The survival benefit of DD chemotherapy was observed irrespective of different BMI categories, with a more pronounced benefit for overweight and obese patients., Conclusion: In node-positive BC patients, DD schedule should be considered the preferred schedule irrespective of BMI., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Oncofertility is an extremely significant topic that is increasingly being discussed owing to increased evidence indicating that fertility preservation does not affect the treatment outcomes of patients with cancer but significantly contributes to preserving life quality. The effect of chemotherapy can range from minimal effects to complete ovarian atrophy. Limited data are available on the effects of monoclonal antibodies and targeted therapies on the ovaries and fertility. Temporary ovarian suppression by administering a gonadotropin-releasing hormone agonist (GnRHa) during chemotherapy decreases the gonadotoxic effect of chemotherapy, thereby diminishing the chance of developing premature ovarian insufficiency (POI). At present, the concomitant administration of GnRH analogs during chemotherapy is the only accepted pharmacological method for preserving ovarian function. Notably, most randomized studies on the effectiveness of luteinizing hormone-releasing hormone agonists during chemotherapy in preventing POI have been conducted in women with breast cancer, with a considerably small number of studies on patients with hematological malignancies. Furthermore, most randomized controlled trials on breast cancer have revealed a decrease in treatment-induced POI risk, regardless of the hormone receptor status. In addition, studies on hematological malignancies have yielded negative results; nevertheless, the findings must be interpreted with caution owing to numerous limitations. Current guidelines from the American Society of Clinical Oncology and ESMO Clinical Practice Guidelines recommend sperm, oocyte, and embryo cryopreservation as a standard practice and only offering GnRHa to patients when proven fertility preservation methods are not feasible. In this manuscript, we present a comprehensive literature overview on the application of ovarian suppression with GnRHa during chemotherapy in patients with cancer by addressing preclinical and clinical data, as well as future perspectives in this field that upcoming research should focus on., Competing Interests: Ana Cvetanovic: Speaking fee and/or advisory board: Roche, MSD, Astra Zeneca, Pfizer, Novartis, Lilly (all outside of submitted work). Lazar S. Popovic: Speaking fee and/or advisory board: Roche, MSD, BMS, Astra Zeneca, Pfizer, Novartis, Gilead, Sandoz, Takeda, Astellas, Janssen, Sanofi, Abbvie, Merck, Lilly (all outside of submitted work). Gorana Matovina Brko: Speaking fee and travel support: Roche, Pfizer, Novartis, Astellas, Janssen, Sanofi, Merck (all outside of submitted work). Maja Popovic Speaking fee and travel support: Roche, BMS, Pfizer, Merck, Takeda, Astellas, Janssen (all outside of submitted work). Kevin Punie: Travel support from AstraZeneca, Pfizer, PharmaMar, and Roche (outside the submitted work). His institution received honoraria for advisory/consultancy roles for AstraZeneca, Eli Lilly, Gilead Sciences, Novartis, Pfizer, Pierre Fabre, Roche, Teva and Vifor Pharma, Speaker fees for Eli Lilly, Medscape, MSD, Mundi Pharma, Novartis, Pfizer, and Roche, and Research funding from MSD and Sanofi (all outside the submitted work). Matteo Lambertini acted as a consultant for Roche, Pfizer, Lilly, MSD, Seagen, Gilead, AstraZeneca, and Novartis, and received honoraria from Sandoz, Takeda, Ipsen, Roche, Lilly, Pfizer, and Novartis (all outside the submitted work). Marijana Milovic Kovacevic-Speaking fee and/or advisory board: Roche, MSD, Astra Zeneca, Pfizer, Novartis, and Lilly (all outside of submitted work)., (© 2024 Cvetanovic et al.)

Introduction: The CLEOPATRA trial (NCT00567190) established a dual anti-HER2 blockade in combination with docetaxel as the first-line standard of care for patients with metastatic HER2-positive breast cancer. While this treatment is overall associated with significant improvement in progression-free survival (PFS) and overall survival (OS), not all patients respond equally. We hypothesized that a radiological complete response (CR) at week 9 (i.e., first disease re-evaluation) is associated with prolonged OS and PFS compared to radiological partial response (PR) or stable disease (SD)., Methods: We performed an exploratory analysis of the CLEOPATRA study to address this question., Results: Out of 362 patients treated with docetaxel, trastuzumab, and pertuzumab eligible for our analysis, 46 (12.7%) had radiological CR at week 9, 243 (67.1%) PR, and 73 (20.2%) SD per central RECIST v1.0. Radiological CR at first tumor re-evaluation was associated with a 60% risk reduction for death compared to SD (adjusted HR = 0.40 95% confidence interval (CI) 0.23-0.70), whereas no significant impact on survival was observed for PR (adjusted HR = 0.85 95% CI 0.60-1.20). The same was observed for PFS with adjusted HR = 0.30 (95% CI 0.18-0.48) for the CR subgroup and adjusted HR = 0.81 (95% CI 0.60-1.09) for the PR subgroup. In multivariate analysis, no variables were associated with radiological CR., Conclusions: Our findings suggest that radiological CR at first disease re-evaluation is associated with more prolonged survival; this might result from stronger dependence on HER2 pathway addiction, supporting the need for further translational research., Competing Interests: Disclosure VD, MB, MC, FJ: none; EA: consultancy fee/honoraria from Eli Lilly, Sandoz, AstraZeneca. Research grant to my Institution from Gilead; Support to attend medical conferences (travel/accommodation/expenses) from Novartis, Roche, Eli Lilly, Genetic, IstitutoGentili, Daiichi Sankyo (all outside the submitted work); CM: honoraria from Novartis and Lilly; DMB: declares full-time employment from the European Society for Medical Oncology since September 1, 2023; speaker's engagement from AstraZeneca, Daiichi Sankyo; meeting/travel grant from Novartis; institutional research funding from Eli Lilly, F. Hoffmann-La Roche Ltd, Novartis; non-remunerated activity as a member of the board of directors for Associaҫão de Investigaҫão e Cuidados de Suporte em Oncologia; non-remunerated leadership role as prior Portuguese Young Oncologists; Committee Chair of Sociedade Portuguesa de Oncologia; GNM: support to attend medical conferences: Roche and Bayer (all outside the submitted work); ML: honoraria and/or advisory board from Roche, Novartis, Lilly, Pfizer, AstraZeneca, Daiichi Sankyo, Gilead, Seagen, MSD, Exact Sciences, Takeda, Ipsen, Sandoz, Libbsand Knight, a travel grant from Gilead and research support (to the Institution) from Gilead (all outside the submitted work); EdA: honoraria and/or advisory board from Roche/GNE, Novartis, Seattle Genetics, Zodiac, Libbsand Pierre Fabre. Travel grants from Roche/GNE and GSK/Novartis. Research grant to his institution from Roche/GNE, Astra-Zeneca, GSK/Novartis, and Servier(all outside the submitted work)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The therapeutic landscape for early breast cancer (eBC) has expanded by introducing novel anticancer agents into clinical practice. During their reproductive years, women with eBC should be informed of the potential risk of premature ovarian insufficiency (POI) and infertility with the proposed systemic therapy. Although the topic of female fertility is becoming increasingly relevant in patients with cancer, limited information is available on the gonadotoxicity of new agents available for eBC treatment. Analyses from clinical trials and prospective data on ovarian function biomarkers are lacking. The purpose of this systematic review is to report the available preclinical and clinical data on female fertility risk with the use of the new agents that are part of clinical practice use or under development for eBC management. This review highlights the clear need to perform additional research efforts to improve our understanding on the gonoadtoxicity of new anticancer agents., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Matteo Lambertini reports advisory roles for Roche, Lilly, Novartis, AstraZeneca, Pfizer, Seagen, Gilead, MSD, Pierre Fabre, Exact Sciences; speaker honoraria from Roche, Lilly, Novartis, Pfizer, Sandoz, Libbs, Daiichi Sankyo, Takeda, and Gilead; travel Grants from Gilead, Daiichi Sankyo, Roche; and research funding (to the Institution) from Gilead, all outside the submitted work. Andrea Botticelli has advisory and consulting roles for Roche, MSD, Novartis, Pfizer, Lilly, Amgen, BMS, Gilead, Sofos, Daichii, and AstraZeneca. Simone Scagnoli reported speaker fees from Novartis, Pfizer, Roche, Lilly, BMS, and MSD. Advisory role for AstraZeneca and Daiichi-Sankyo., (Copyright © 2024. Published by Elsevier Ltd.)

The emerging era of precision medicine is characterized by an increasing availability of targeted anticancer therapies and by the parallel development of techniques to obtain more refined molecular data, whose interpretation may not always be straightforward. Molecular tumor boards gather various professional figures, in order to leverage the analysis of molecular data and provide prognostic and predictive insights for clinicians. In addition to healthcare development, they could also become a tool to promote knowledge and research spreading. A growing body of evidence on the application of molecular tumor boards to clinical practice is forming and positive signals are emerging, although a certain degree of heterogeneity exists. This work analyzes molecular tumor boards' potential workflows, figures involved, data sources, sample matrices and eligible patients, as well as available evidence and learning examples. The emerging concept of multi-institutional, disease-specific molecular tumor boards is also considered by presenting two ongoing nationwide experiences., Competing Interests: Declaration of Competing Interest Giulia Buzzatti reports personal fees for consultancy/advisory role from Novartis, Eli Lilly and AstraZeneca. Umberto Malapelle reports personal fees for consultancy/advisory role from Boehringer Ingelheim, Roche, MSD, Amgen, ThermoFisher Scientific, Eli Lilly, Diaceutics, GlaxoSmithKline, Merck and AstraZeneca; personal fees for speakers’ bureau from Boehringer Ingelheim, AstraZeneca, Roche, MSD, Amgen, Merck, ThermoFisher Scientific, Eli Lilly, Diaceutics, GlaxoSmithKline and QIAGEN. Carmine De Angelis reports personal fees as consultant and/or speakers' bureau from Roche, Eli Lilly, GSK, Novartis, Pfizer, AstraZeneca, Gilead and Seagen; research grant to the Institution from Novartis. Maria Vittoria Dieci reports personal fees for consultancy/advisory role from Eli Lilly, Exact Sciences, Novartis, Pfizer, Seagen, Gilead, MSD, AstraZeneca, Daiichi Sankyo and Roche. Matteo Lambertini reports personal fees for advisory role from Roche, Eli Lilly, Novartis, AstraZeneca, Pfizer, Seagen, Gilead, MSD and Exact Sciences; speaker honoraria from Roche, Eli Lilly, Novartis, Pfizer, Sandoz, Libbs, Daiichi Sankyo and Takeda; travel grants from Gilead; research support (to the Institution) from Gilead. Angela Toss reports personal fees for consultancy/advisory role from Eli Lilly, Novartis, Pfizer, Seagen, Gilead, MSD, AstraZeneca and Daiichi Sankyo. Alberto Farolfi reports personal fees for consultancy/advisory role from AstraZeneca, GSK-Tesaro, Clovis and Janssen. Sandro Pignata reports speaker honoraria from AstraZeneca, Roche, PharmaMar, Tesaro, Pfizer and MSD; personal fees for consultancy/advisory role from AstraZeneca, Roche, PharmaMar, Pfizer, Tesaro and Clovis Oncology; research funding (to the Institution) from Roche, AstraZeneca, MSD and Pfizer. Michele Bartoletti reports personal fees for advisory board from GSK, MSD and EISAI; speaker fees from GSK and AstraZeneca; research grant from AstraZeneca and Roche; data monitoring committee for Novartis. Lorenzo Gerratana reports advisory/consultancy fees from AstraZeneca, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Incyte, Novartis, Pfizer, MSD, Menarini Stemline, Abbvie; research funding from Menarini Silicon Biosystems; travel expenses from Menarini Stemline. Fabio Puglisi reports speaker honoraria from Roche, MSD, AstraZeneca, Novartis, Pierre Fabre, Daiichi Sankyo, Eisai, Eli Lilly, Pfizer and Exact Sciences; consulting or advisory role for Roche, Amgen, Novartis, Pfizer, Eisai, Seagen, Pierre Fabre, AstraZeneca/Daiichi Sankyo, Viatris, Eli Lilly, Gilead Sciences and Daiichi Sankyo Europe GmbH; research funding (to the Institution) from Eisai, AstraZeneca and Roche; travel and accommodation expenses fees from Roche, Celgene, GlaxoSmithKline, Amgen, AstraZeneca, MSD, Novartis, Eli Lilly and Pfizer. All reported potential conflicts of interest are outside the submitted work. All other authors have declared no potential conflicts of interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Approximately 10% to 15% of breast cancer cases in young women are diagnosed in patients harbouring germline (g) pathogenic or likely pathogenic variants (PVs) in the BReast CAncer 1 ( BRCA1 ) or BReast CAncer 2 ( BRCA2 ) genes. Preclinical and clinical studies showed a potential negative effect of germline BRCA 1/2 (g BRCA1/2 ) PVs on ovarian reserve and reproductive potential, even before starting anticancer therapies. The aim of this article is to summarize the current literature on the fertility potential of young g BRCA1/2 PVs carriers with breast cancer and the risk of gonadotoxicity associated with anticancer treatments. Moreover, we describe the available evidence on the efficacy of fertility preservation techniques in young g BRCA1/2 PVs carriers and the safety data on having a pregnancy after breast cancer treatment., (© The Author(s) 2024.)

Lung cancer has traditionally been associated with advanced age; however, its increasing incidence among young adults raises concerning questions regarding its etiology and unique considerations for this population. In contrast to the older population, the onset of lung cancer at younger age may be attributed to a complex interplay of incompletely understood individual susceptibility and prevalent environmental risk factors beyond tobacco smoke exposure, such as radon gas and air pollution, which are widespread globally. Consequently, this leads to distinct clinical and molecular profiles, requiring a tailored approach. Furthermore, a diagnosis of cancer represents a threatening event during the prime years of a young person's life, prompting concern about career development, social aspects, fertility aspirations, and physical independence. This poses significant additional challenges for health care professionals in a field that remains underexplored. This comprehensive review recognizes lung cancer in young adults as a distinct entity, exploring its clinical and molecular characteristics, diverse predisposing factors, and priorities in terms of quality of life, with the aim of providing practical support to oncologists and enhancing our understanding of this under-researched population.

The European Society for Radiotherapy and Oncology (ESTRO) has advocated the establishment of guidelines to optimise precision radiotherapy (RT) in conjunction with contemporary therapeutics for cancer care. Quality assurance in RT (QART) plays a pivotal role in influencing treatment outcomes. Clinical trials incorporating QART protocols have demonstrated improved survival rates with minimal associated toxicity. Nonetheless, in routine clinical practice, there can be variability in the indications for RT, dosage, fractionation, and treatment planning, leading to uncertainty. In pivotal trials reporting outcomes of systemic therapy for breast cancer, there is limited information available regarding RT, and the potential interaction between modern systemic therapy and RT remains largely uncharted. This article is grounded in a consensus recommendation endorsed by ESTRO, formulated by international breast cancer experts. The consensus was reached through a modified Delphi process and was presented at an international meeting convened in Florence, Italy, in June 2023. These recommendations are regarded as both optimal and essential standards, with the latter aiming to define the minimum requirements. A template for a case report form (CRF) has been devised, which can be utilised by all clinical breast cancer trials involving RT. Optimal requirements include adherence to predefined RT planning protocols and centralised QART. Essential requirements aim to reduce variations and deviations from the guidelines in RT, even when RT is not the primary focus of the trial. These recommendations underscore the significance of implementing these practices in both clinical trials and daily clinical routines to generate high-quality data., Competing Interests: Declaration of competing interest IMe declares advisory boards supported by Eli Lilly, Novartis, Pfizer, Pierre Fabre, SeaGen, Daiichi Sankyo, Astra Zeneca. CB declares honoraria supported by declares advisory boards supported by Eli Lilly, Novartis, Pfizer, and Amgen. ML received honoraria and/or participated in advisory board from Roche, Novartis, Lilly, Pfizer, AstraZeneca, Daiichi Sankyo, Gilead, SeaGen, MSD, Exact Sciences, Takeda, Ipsen, Sandoz, Libbs & Knight, a travel grant from Gilead and research support to the Institution from Gilead. EdA disclosed honoraria and/or advisory board from Roche/GNE, Novartis, SeaGen, Zodiac, Libbs, Pierre Fabre, Lilly, AstraZeneca. JC disclosed consulting/advisor for Roche, Celgene, Cellestia, AstraZeneca, SeaGen, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Merck Sharp & Dohme, GSK, Leuko, Bioasis, Clovis Oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Gemoab, Gilead, Menarini, Zymeworks, Reveal Genomics, Expres2ion Biotechnologies. NH disclosed honoraria for lectures and/or consulting from AstraZeneca, Daiichi-Sankyo, Gilead, Lilly, MSD, Novartis, Pierre-Fabre, Pfizer, Roche, Sanofi, Sandoz, SeaGen. HSR disclosed institutional research support by Astellas Pharma Inc., AstraZeneca, Daiichi Sankyo Inc., F. Hoffmann-La Roche AG/Genentech, Inc., Gilead Sciences Inc., GlaxoSmithKline, Lilly, Merck & Co. Inc., Novartis Pharmaceuticals Corporation, OBI Pharma, Pfizer, Pionyr Immunotherapeutics, Sermonix Pharmaceuticals Inc., Taiho Oncology Inc., and Veru Inc. GC reports personal fees for consulting, advisory role and speakers’ bureau from Roche/Genentech, Novartis, Pfizer, Lilly, Foundation Medicine, Samsung and Daiichi Sankyo; honoraria from Ellipses Pharma and fees for travel and accommodations from Roche/Genentech and Pfizer. LV declares participation on advisory board from Daiichi Sankyo and Pfizer. ME declares advisory board supported by Pfizer and Novartis and lecture fees supported by AstraZeneca. GM declares consultancy honoraria from Roche, Novartis, AstraZeneca, Pfizer, Jensen, Lilly, and Sanofi. LDM declares consulting fees from Roche, Novartis, Eli Lilly, MSD, Daiichi Sankyo, SeaGen, Gilead, Eisai, Pierre Fabre, AstraZeneca, Stemline Menarini, Exact Sciences, Agendia, GSK, Pfizer. No other competing interests declared., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Glufosinate-ammonium (GLA), an organophosphate herbicide, is released at high concentrations in the environment, leading to concerns over its potential genotoxic effects. However, few articles are available in the literature reporting the possible cellular and nuclear effects of this compound. We assessed, by in vitro and in vivo micronucleus assays, the genotoxicity of GLA on cultured human lymphocytes and Lymnaea stagnalis hemocytes at six concentrations: 0.010 (the established acceptable daily intake value), 0.020, 0.050, 0.100, 0.200, and 0.500 µg/mL. In human lymphocytes, our results reveal a significant and concentration-dependent increase in micronuclei frequency at concentrations from 0.100 to 0.500 μg/mL, while in L. stagnalis hemocytes, significant differences were found at 0.200 and 0.500 μg/mL. A significant reduction in the proliferation index was observed at all tested concentrations, with the only exception of 0.010 μg/mL, indicating that the exposure to GLA could lead to increased cytotoxic effects. In L. stagnalis, a significant reduction in laid eggs and body growth was also observed at all concentrations. In conclusion, we provided evidence of the genomic and cellular damage induced by GLA on both cultured human lymphocytes and a model organism's hemocytes; in addition, we also demonstrated its effects on cell proliferation and reproductive health in L. stagnalis .

Importance: Biologic features may affect pathologic complete response (pCR) and event-free survival (EFS) after neoadjuvant chemotherapy plus ERBB2/HER2 blockade in ERBB2/HER2-positive early breast cancer (EBC)., Objective: To define the quantitative association between pCR and EFS by intrinsic subtype and by other gene expression signatures in a pooled analysis of 3 phase 3 trials: CALGB 40601, NeoALTTO, and NSABP B-41., Design, Setting, and Participants: In this retrospective pooled analysis, 1289 patients with EBC received chemotherapy plus either trastuzumab, lapatinib, or the combination, with a combined median follow-up of 5.5 years. Gene expression profiling by RNA sequencing was obtained from 758 samples, and intrinsic subtypes and 618 gene expression signatures were calculated. Data analyses were performed from June 1, 2020, to January 1, 2023., Main Outcomes and Measures: The association of clinical variables and gene expression biomarkers with pCR and EFS were studied by logistic regression and Cox analyses., Results: In the pooled analysis, of 758 women, median age was 49 years, 12% were Asian, 6% Black, and 75% were White. Overall, pCR results were associated with EFS in the ERBB2-enriched (hazard ratio [HR], 0.45; 95% CI, 0.29-0.70; P < .001) and basal-like (HR, 0.19; 95% CI, 0.04-0.86; P = .03) subtypes but not in luminal A or B tumors. Dual trastuzumab plus lapatinib blockade over trastuzumab alone had a trend toward EFS benefit in the intention-to-treat population; however, in the ERBB2-enriched subtype there was a significant and independent EFS benefit of trastuzumab plus lapatinib vs trastuzumab alone (HR, 0.47; 95% CI, 0.27-0.83; P = .009). Overall, 275 of 618 gene expression signatures (44.5%) were significantly associated with pCR and 9 of 618 (1.5%) with EFS. The ERBB2/HER2 amplicon and multiple immune signatures were significantly associated with pCR. Luminal-related signatures were associated with lower pCR rates but better EFS, especially among patients with residual disease and independent of hormone receptor status. There was significant adjusted HR for pCR ranging from 0.45 to 0.81 (higher pCR) and 1.21-1.94 (lower pCR rate); significant adjusted HR for EFS ranged from 0.71 to 0.94., Conclusions and Relevance: In patients with ERBB2/HER2-positive EBC, the association between pCR and EFS differed by tumor intrinsic subtype, and the benefit of dual ERBB2/HER2 blockade was limited to ERBB2-enriched tumors. Immune-activated signatures were concordantly associated with higher pCR rates and better EFS, whereas luminal signatures were associated with lower pCR rates.

Background: Cutaneous melanoma (CM) is one of the most lethal tumors among skin cancers and its incidence is rising worldwide. Recent data support the role of microRNAs (miRNAs) in melanoma carcinogenesis and their potential use as disease biomarkers., Methods: We quantified the expression of miR-146a-5p and miR-21-5p in 170 formalin-fixed paraffin embedded (FFPE) samples of CM, namely 116 superficial spreading melanoma (SSM), 26 nodular melanoma (NM), and 28 lentigo maligna melanoma (LMM). We correlated miRNA expression with specific histopathologic features including Breslow thickness (BT), histological subtype, ulceration and regression status, and mitotic index., Results: miR-146a-5p and miR-21-5p were significantly higher in NM compared to SSM and LMM. The positive correlation between miR-146a-5p and miR-21-5p expression and BT was confirmed for both miRNAs in SSM. Considering the ulceration status, we assessed that individual miR-21-5p expression was significantly higher in ulcerated CMs. The increased combined expression of the two miRNAs was strongly associated with ulceration ( p = 0.0093) and higher mitotic rate (≥1/mm 2 ) ( p = 0.0005). We demonstrated that the combination of two-miRNA expression and prognostic features (BT and ulceration) can better differentiate cutaneous melanoma prognostic groups, considering overall survival and time-to-relapse clinical outcomes. Specifically, miRNA expression can further stratify prognostic groups among patients with BT ≥ 0.8 mm but without ulceration. Our findings provide further insights into the characterization of CM with specific prognostic features. The graphical abstract was created with BioRender.com.

Sperm cryopreservation is a procedure widely used to store gametes for later use, to preserve fertility in patients prior to gonadotoxic treatments or surgery, and for sperm donation programs. The purpose of the study was to assess the impact of cryopreservation on human sperm transcriptome. Semen samples were collected from 13 normospermic men. Each sample was divided into two aliquots. The total RNA was immediately extracted from one aliquot. The second aliquot was frozen and total RNA was extracted after a week of storage in liquid nitrogen. The RNA samples were randomized in four pools, each of six donors, and analyzed by microarrays. The paired Significance Analysis of Microarray was performed. We found 219 lower abundant transcripts and 28 higher abundant transcripts in cryopreserved sperm than fresh sperm. The gene ontology analysis disclosed that cryopreservation alters transcripts of pathways important for fertility (i.e., spermatogenesis, sperm motility, mitochondria function, fertilization, calcium homeostasis, cell differentiation, and early embryo development), although the increase of some transcripts involved in immune response can compensate for the harmful effects of freezing., Competing Interests: M.L. reports advisory role for Roche, Lilly, Novartis, Astrazeneca, Pfizer, Seagen, Gilead, MSD, and Exact Sciences and speaker honoraria from Roche, Lilly, Novartis, Pfizer, Sandoz, Libbs, Daiichi Sankyo, Knight, and Takeda, Travel Grants from Gilead and Daiichi Sankyo, and research support (to the Institution) from Gilead outside the submitted work. P.A. reports speaker honoraria from Gedeon Richter, Merck, and Organon outside the submitted work. The other authors declare no conflicts of interest.

Background: Trastuzumab deruxtecan (T-DXd) demonstrated unprecedented efficacy in patients with pretreated HER2+ metastatic breast cancer (mBC). However, few data are available about its efficacy in routine clinical practice. In this multicenter retrospective study, we examined effectiveness and safety of T-DXd in a real-world population., Methods: Clinico-pathological information about patients with HER2+ mBC who received T-DXd were collected from 12 Italian hospitals. HER2 status was determined locally. Patients who received at least one administration of T-DXd, as any therapy line for advanced disease were included in the analysis. The primary endpoint was real-word PFS (rwPFS)., Results: One hundred and forty-three patients were included. Median age was 66 (range: 37-90), and 4 men were included. Hormone receptor (HR) status was positive in 108 (75%) patients and negative in 35(25%). T-DXd was administered as first, second, third, or subsequent lines in 4 (3%), 16 (11%), 42 (29%), and 81 (57%) patients, respectively. Among 123 patients with measurable disease, the ORR was 68%, and the DCR was 93% (9 CRs, 74 PRs, and 30 SD). Nine (7%) patients had a primary resistance to T-DXd. With a median follow-up of 12 months, the median rwPFS was 16 months. RwPFS was 84%, 59%, and 39% at 6, 12, and 18 months, respectively. A favorable trend in rwPFS was reported in patients receiving T-DXd as I/II line versus further lines (17 vs. 15 months; P = .098). Any-grade toxicity was registered in 84 patients (59%). Most common adverse events (AEs) reported were nausea (33%), neutropenia (21%), and asthenia (21%). Liver toxicity and diarrhea were uncommon (5% and 1%). Severe toxicities was registered in 18% of patients, and the most frequent were neutropenia, nausea/vomiting, and ILD observed in 15, 2, and 3 patients. AEs led to dose reduction in 37 patients (26%). Dose reduction and AEs do not affect patients' response and survival outcomes., Conclusions: Efficacy and safety of T-DXd were confirmed in an unselected real-world population of HER2+ mBC. These results are consistent with the results of known findings, and no new safety concerns were reported., (© The Author(s) 2023. Published by Oxford University Press.)

Importance: The association of tumor-infiltrating lymphocyte (TIL) abundance in breast cancer tissue with cancer recurrence and death in patients with early-stage triple-negative breast cancer (TNBC) who are not treated with adjuvant or neoadjuvant chemotherapy is unclear., Objective: To study the association of TIL abundance in breast cancer tissue with survival among patients with early-stage TNBC who were treated with locoregional therapy but no chemotherapy., Design, Setting, and Participants: Retrospective pooled analysis of individual patient-level data from 13 participating centers in North America (Rochester, Minnesota; Vancouver, British Columbia, Canada), Europe (Paris, Lyon, and Villejuif, France; Amsterdam and Rotterdam, the Netherlands; Milan, Padova, and Genova, Italy; Gothenburg, Sweden), and Asia (Tokyo, Japan; Seoul, Korea), including 1966 participants diagnosed with TNBC between 1979 and 2017 (with follow-up until September 27, 2021) who received treatment with surgery with or without radiotherapy but no adjuvant or neoadjuvant chemotherapy., Exposure: TIL abundance in breast tissue from resected primary tumors., Main Outcomes and Measures: The primary outcome was invasive disease-free survival [iDFS]. Secondary outcomes were recurrence-free survival [RFS], survival free of distant recurrence [distant RFS, DRFS], and overall survival. Associations were assessed using a multivariable Cox model stratified by participating center., Results: This study included 1966 patients with TNBC (median age, 56 years [IQR, 39-71]; 55% had stage I TNBC). The median TIL level was 15% (IQR, 5%-40%). Four-hundred seventeen (21%) had a TIL level of 50% or more (median age, 41 years [IQR, 36-63]), and 1300 (66%) had a TIL level of less than 30% (median age, 59 years [IQR, 41-72]). Five-year DRFS for stage I TNBC was 94% (95% CI, 91%-96%) for patients with a TIL level of 50% or more, compared with 78% (95% CI, 75%-80%) for those with a TIL level of less than 30%; 5-year overall survival was 95% (95% CI, 92%-97%) for patients with a TIL level of 50% or more, compared with 82% (95% CI, 79%-84%) for those with a TIL level of less than 30%. At a median follow-up of 18 years, and after adjusting for age, tumor size, nodal status, histological grade, and receipt of radiotherapy, each 10% higher TIL increment was associated independently with improved iDFS (hazard ratio [HR], 0.92 [0.89-0.94]), RFS (HR, 0.90 [0.87-0.92]), DRFS (HR, 0.87 [0.84-0.90]), and overall survival (0.88 [0.85-0.91]) (likelihood ratio test, P < 10e-6)., Conclusions and Relevance: In patients with early-stage TNBC who did not undergo adjuvant or neoadjuvant chemotherapy, breast cancer tissue with a higher abundance of TIL levels was associated with significantly better survival. These results suggest that breast tissue TIL abundance is a prognostic factor for patients with early-stage TNBC.

Opinion Statement: Around 90% of breast tumours are diagnosed in the early stage, with approximately 70% being hormone receptor-positive. The cornerstone of adjuvant therapy for early-stage hormone receptor-positive breast cancer is endocrine therapy, tailored according to disease stage, biological characteristics of the tumour, patient's comorbidities, preferences and age. In premenopausal patients with hormone receptor-positive breast cancer, ovarian function suppression is a key component of the adjuvant endocrine treatment in combination with an aromatase inhibitor or tamoxifen. Moreover, it can be used during chemotherapy as a standard strategy for ovarian function preservation in all breast cancer subtypes. In the metastatic setting, ovarian function suppression should be used in all premenopausal patients with hormone receptor-positive breast cancer to achieve a post-menopausal status. Despite its efficacy, ovarian function suppression may lead to several side effects that can have a major negative impact on patients' quality of life if not properly managed (e.g. hot flashes, depression, cognitive impairment, osteoporosis, sexual dysfunction, weight gain). A deep knowledge of the side effects of ovarian function suppression is necessary for clinicians. A correct counselling in this regard and proactive management should be considered a fundamental part of survivorship care to improve treatment adherence and patients' quality of life., (© 2024. The Author(s).)

Background: Intermediate clinical endpoints (ICEs) are frequently used as primary endpoint in randomised trials (RCTs). We aim to assess whether changes in different ICEs can be used to predict changes in overall survival (OS) in adjuvant breast cancer trials., Methods: Individual patient level data from adjuvant phase III RCTs conducted by the Gruppo Italiano Mammella (GIM) and Mammella Intergruppo (MIG) study groups were used. ICEs were computed according to STEEP criteria. Using a two-stage meta-analytic model, we assessed the surrogacy of each ICE at both the outcome (i.e., OS and ICE are correlated irrespective of treatment) and trial (i.e., treatment effects on ICE and treatment effect on OS are correlated) levels. The following ICEs were considered as potential surrogate endpoints of OS: disease-free survival (DFS), distant disease-free survival (DDFS), distant relapse-free survival (DRFS), recurrence-free survival (RFS), recurrence-free interval (RFI), distant recurrence-free interval (DRFI), breast cancer-free interval (BCFI), and invasive breast cancer-free survival (IBCFS). The estimates of the degree of correlation were obtained by copula models and weighted linear regression. Kendall's τ and R 2  ≥ 0.70 were considered as indicators of a clinically relevant surrogacy., Findings: Among the 12,397 patients enrolled from November 1992 to July 2012 in six RCTs, median age at enrolment was 57 years (interquartile range (IQR) 49-65). After a median follow-up of 10.3 years (IQR 6.4-14.5), 2131 (17.2%) OS events were observed, with 1390 (65.2%) attributed to breast cancer. At the outcome-level, Kendall's τ ranged from 0.69 for BCFI to 0.84 for DRFS. For DFS, DDFS, DRFS, RFS, RFI, DRFI, BCFI, and IBCFS endpoints, over 95% of the 8-year OS variability was attributable to the variation of the 5-year ICE. At the trial-level, treatment effects for the different ICEs and OS were strongly correlated, with the highest correlation for RFS and DRFS and the lowest for BCFI., Interpretation: Our results provide evidence supporting the use of DFS, DDFS, DRFS, RFS, RFI, DRFI, and IBCFS as primary endpoint in breast cancer adjuvant trials., Funding: This analysis was supported by the Italian Association for Cancer Research ("Associazione Italiana per la Ricerca sul Cancro", AIRC; IG 2017/20760) and by Italian Ministry of Health-5 × 1000 funds (years 2021-2022)., Competing Interests: Eva Blondeaux reports research support (to the Institution) from Gilead outside the submitted work. Wanling Xie served as consultant to Convergent Therapeutics, Inc outside the submitted work. Carmine De Angelis reports advisory role for Roche, Lilly, Novartis, Astrazeneca, Pfizer, Seagen, Daicii-Sankyo, Gilead, and GSK and speaker honoraria from Roche, Lilly, Novartis, Pfizer, Seagen, GSK, GILEAD, and Daiichi-Sankio. Travel Grants from Gilead and research support (to the Institution) from Novartis, GILEAD, and Daiichi-Sankyo outside the submitted work. Fabio Puglisi reports honoraria for advisory boards, activities as a speaker, travel grants, research grants from Amgen–Astrazeneca–Daiichi Sankyo–Celgene–Eisai–Eli Lilly-–Exact Sciences- Gilead–Ipsen—Menarini- MSD–Novartis–Pierre Fabre–Pfizer–Roche–Seagen–Takeda—Viatris and research funding from Astrazeneca—Eisai—Roche outside the submitted work. Mauro Mansutti reports honoraria for advisory boards, activities as a speaker, travel grants: Accord Healthcare, Amgen, Astra Zeneca, Eli Lilly, Gilead, MSD, Novartis, Pfizer, Seagen outside the submitted work. Alessandra Fabi reports advisory board from Roche, Novartis, Lilly, Pfizer, MSD, Pierre Fabre, Eisai, Epionpharma, Gilead, Seagen, Astra Zeneca, Exact Science and consultant from Dompè Farnaceutica outside the submitted work. Matteo Lambertini reports advisory role for Roche, Lilly, Novartis, Astrazeneca, Pfizer, Seagen, Gilead, MSD and Exact Sciences and speaker honoraria from Roche, Lilly, Novartis, Pfizer, Sandoz, Libbs, Daiichi Sankyo, Knight and Takeda, Travel Grants from Gilead and Daiichi Sankyo, and research support (to the Institution) from Gilead outside the submitted work. Lucia Del Mastro reports grants or contracts from Eli Lilly, Novartis, Roche, Daiichi Sankyo, and Seagan; honoraria from Roche, Novartis, Pfizer, Eli Lilly, AstraZeneca, MSD, Seagen, Gilead, Pierre Fabre, Eisai, Exact Sciences, and Ipsen; support for attending meetings or travel from Roche, Pfizer, and Eisai; participation on a Data Safety Monitoring Board or Advisory Board from Novartis, Roche, Eli Lilly, Pfizer, Daiichi Sankyo, Exact Sciences, Gilead, Pierre Fabre, Eisai, and AstraZeneca outside the submitted work. Meredith M Regan reports consulting or advisory role for Ipsen (to the Institution), Tolmar, Bristol Myers Squibb, Debiopharm Group (to the Institution), TerSera, AstraZeneca and research funding from Pfizer (to the Institution), Ipsen (to the Institution), Novartis (to the Institution), Merck (to the Institution), AstraZeneca (to the Institution), Pierre Fabre (to the Institution), Bayer (to the Institution), Bristol Myers Squibb (to the Institution), Roche (to the Institution), TerSera (to the Institution), Debiopharm Group (to the Institution), BioTheranostics (to the Institution) and honoraria from Bristol Myers Squibb and Canadian Urological Association., (© 2024 The Author(s).)

Competing Interests: Declaration of Competing Interest CG has received grants from Italian Ministry of Health and BMS and Honoraria for presentations or lectures from AstraZeneca, BMS, Lilly, MSD, Roche, Sanofi, Takeda, Thermo Fisher; ML has received personal fees (advisory role and/or speaker honoraria) from Roche, Takeda, Sandoz, Eli Lilly, Pfizer, AstraZeneca, Novartis Exact Sciences and Ipsen; LDM has reported consulting fees from Roche, Novartis, MSD, Pfizer, Ipsen, AstraZeneca, Genomic Health, Eli Lilly, Seattle Genetics, Eisai, Pierre Fabre, and Daiichi Sankyo, speaker Honoraria from Roche, Novartis, Eli Lilly and MSD, travel grants from Roche, Pfizer and Celgene; FS has reported Honoraria for presentations or lectures from Sanofi Genzyme, Roche, BMS, Novartis, Merk, Sun Pharma, MSD, Pierre Fabre and for advisory board for Novartis, Philogen, SunPharma, MSD.

Introduction: The addition of taxanes to anthracycline-based chemotherapy is considered standard of care in the treatment of breast cancer. However, there are insufficient data regarding the safety of taxanes during pregnancy. The aim of this study was to describe the incidence of obstetric and neonatal adverse events associated with the use of taxane-containing chemotherapy regimens for the treatment of breast cancer during pregnancy., Methods: This is a multicenter, international cohort study of breast cancer patients treated with taxanes during pregnancy. A descriptive analysis was undertaken to synthetize available data., Results: A total of 103 patients were included, most of whom were treated with paclitaxel and anthracyclines given in sequence during gestation (90.1%). The median gestational age at taxane initiation was 28 weeks (range = 12-37 weeks). Grade 3-4 adverse events were reported in 7 of 103 (6.8%) patients. The most common reported obstetric complications were intrauterine growth restriction (n = 8 of 94, 8.5%) and preterm premature rupture of membranes (n = 5 of 94, 5.3%). The live birth rate was 92 of 94 (97.9%), and the median gestational age at delivery was 37 weeks (range = 32-40 weeks). Admission to an intensive care unit was reported in 14 of 88 (15.9%) neonates, and 17 of 70 (24.3%) live births resulted in small for gestational age neonates. Congenital malformations were reported in 2 of 93 (2.2%)., Conclusion: Obstetric and neonatal outcomes after taxane exposure during pregnancy were generally favorable and did not seem to differ from those reported in the literature with standard anthracycline-based regimens. This study supports the use of taxanes during gestation when clinically indicated., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The COVID-19 pandemic poses a significant challenge for individuals with compromised immune systems, such as patients with cancer, as they face a heightened susceptibility to severe infections compared to the general population. Such severe infections substantially increase the risk of morbidity and mortality among these patients. Notable risk factors for mortality include advanced age (> 70 years), current or past smoking history, advanced disease stage, the use of cytotoxic chemotherapy, and an Eastern Cooperative Oncology Group (ECOG) score of 2 or higher. Multiple types of vaccines have been developed and implemented, demonstrating remarkable efficacy in preventing infections. However, there have been observable reductions in their ability to elicit an immune response, particularly among individuals with hematological malignancies. The situation becomes more challenging due to the emergence of viral variants of concern (VOCs). Despite the increase in neutralizing antibody levels after vaccination, they remain lower in response to these evolving variants. The need for booster vaccinations has become apparent, particularly for this vulnerable population, due to the suboptimal immune response and waning of immunity post-vaccination. Examining and comprehending how the immune system reacts to various vaccination regimens for SARS-CoV-2 and its VOCs in cancer patients is crucial for designing clinical and public health strategies. This review aims to provide an updated overview of the effectiveness of COVID-19 vaccines in cancer patients, including those undergoing treatments such as hematopoietic stem cell transplantation (HCT) or chimeric antigen receptor (CAR) T cell therapy, by exploring the extent of both humoral and cellular immune responses to COVID-19 vaccination. Furthermore, it outlines risk factors and potential biomarkers that are associated with severe SARS-CoV-2 infection and vaccine responses, and offers suggestions for improving SARS-CoV-2 protection in cancer patients., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Matteo Lambertini reports advisory role for Roche, Lilly, Novartis, Astrazeneca, Pfizer, Seagen, Gilead, MSD and Exact Sciences and speaker honoraria from Roche, Lilly, Novartis, Pfizer, Sandoz, Libbs, Daiichi Sankyo, Knight and Takeda, Travel Grants from Gilead and Daiichi Sankyo, and research support (to the Institution) from Gilead outside the submitted work. Cinzia Solinas reports on travel grants from Ipsen and Eli Lilly. All other authors have no conflict of interest to declare related to the present topic., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Novel systemic therapies for breast cancer are being rapidly implemented into clinical practice. These drugs often have different mechanisms of action and side-effect profiles compared with traditional chemotherapy. Underpinning practice-changing clinical trials focused on the systemic therapies under investigation, thus there are sparse data available on radiotherapy. Integration of these new systemic therapies with radiotherapy is therefore challenging. Given this rapid, transformative change in breast cancer multimodal management, the multidisciplinary community must unite to ensure optimal, safe, and equitable treatment for all patients. The aim of this collaborative group of radiation, clinical, and medical oncologists, basic and translational scientists, and patient advocates was to: scope, synthesise, and summarise the literature on integrating novel drugs with radiotherapy for breast cancer; produce consensus statements on drug-radiotherapy integration, where specific evidence is lacking; and make best-practice recommendations for recording of radiotherapy data and quality assurance for subsequent studies testing novel drugs., Competing Interests: Declaration of interests IMe declares participation in advisory boards supported by Eli Lilly, Novartis, Pfizer, Pierre Fabre, SeaGen, Daiichi Sankyo, and AstraZeneca. CB declares honoraria from Eli Lilly, and participation in advisory boards supported by Eli Lilly, Novartis, Pfizer, and Amgen. ML received honoraria from or participated in advisory boards for Roche, Novartis, Eli Lilly, Pfizer, AstraZeneca, Daiichi Sankyo, Gilead, SeaGen, Merck Sharp and Dohme, Exact Sciences, Takeda, Ipsen, Sandoz, Libbs, and Knight; received a travel grant from Gilead; and received research support for their institution from Gilead. EdA declares honoraria from or participation in advisory boards for Roche, Genentech, Novartis, SeaGen, Zodiac, Libbs, Pierre Fabre, Eli Lilly, and AstraZeneca. JC declares consulting or advisor roles supported by Roche, Celgene, Cellestia, AstraZeneca, SeaGen, Daiichi Sankyo, Erytech, Athenex, Polyphor, Eli Lilly, Merck Sharp and Dohme, GSK, Leuko, Bioasis, Clovis Oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Gemoab, Gilead, Menarini, Zymeworks, Reveal Genomics, and Expres2ion Biotechnologies. NH declares honoraria for lectures or consulting from AstraZeneca, Daiichi Sankyo, Gilead, Eli Lilly, Merck Sharp and Dohme, Novartis, Pierre Fabre, Pfizer, Roche, Sanofi, Sandoz, and SeaGen. HSR declares institutional research support from Astellas Pharma, AstraZeneca, Daiichi Sankyo, F Hoffmann-La Roche, Genentech, Gilead Sciences, GSK, Eli Lilly, Merck & Co, Novartis Pharmaceuticals Corporation, OBI Pharma, Pfizer, Pionyr Immunotherapeutics, Sermonix Pharmaceuticals, Taiho Oncology, and Veru. GC reports personal fees for consulting, advisory roles, and speakers’ bureau from Roche, Genentech, Novartis, Pfizer, Eli Lilly, Foundation Medicine, Samsung, and Daiichi Sankyo; honoraria from Ellipses Pharma; and fees for travel and accommodations from Roche, Genentech, and Pfizer. LV declares participation in advisory boards from Daiichi Sankyo and Pfizer. ME declares participation in advisory boards supported by Pfizer and Novartis, and lecture fees supported by AstraZeneca. TS declares participation in advisory boards supported by Bristol Myers Squibb, Merck Sharp and Dohme, Novartis, and Pierre Fabre; and lecture fees supported by Astellas, AstraZeneca, and Bristol Myers Squibb. GM declares consultancy honoraria from Roche, Novartis, AstraZeneca, Pfizer, Jensen, Eli Lilly, and Sanofi. LDM declares consulting fees from Roche, Novartis, Eli Lilly, Merck Sharp and Dohme, Daiichi Sankyo, SeaGen, Gilead, Eisai, Pierre Fabre, AstraZeneca, Stemline Menarini, Exact Sciences, Agendia, GSK, and Pfizer. MM declares consulting fees from Cedilla Therapeutics and PharmEnable, and research support from PharmaMar, Eli Lilly, Pfizer, and Circle Pharma. SP-S declares consulting fees from Pfizer, Novartis, Eli Lilly, AstraZeneca, Gilead, Merck, Sharp and Dohme, and Roche. BP declares consulting fees from Astra Zeneca, SeaGen, Gilead, Eli Lilly, Merck Sharp and Dohme, Daiichi Sankyo, and Pierre Fabre. CS declares consulting fees from AstraZeneca, Daiichi Sankyo, Eisai Europe, Gilead, Novartis, Pharmalex, Pfizer, Phillips Health Works, Pierre Fabre, PintPharma, Puma Biotechnology, Roche Farma, SeaGen, Solti, Synthon Biopharmaceuticals, and Zymeworks. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Sexual concerns are a major unaddressed need among survivors of breast cancer (BC) with significant negative effects on quality of life. We longitudinally analyzed sexual health over time, using patient-reported outcomes., Methods: Patients with stage I-III BC prospectively included from the CANcer TOxicity cohort (CANTO) provided data at diagnosis, then 1, 2, and 4 years afterward. Sexual concerns outcomes included poor body image (score ≤91/100), poor sexual functioning (≤16/100), poor sexual enjoyment (≤66/100), and sexual inactivity (EORTC QLQ-B23). Multivariate generalized estimating equation models assessed associations with sexual concerns after diagnosis, adjusting for age, sociodemographic, tumor, treatment, and clinical characteristics., Results: Nearly 78.1% among 7895 patients reported at least one sexual concern between diagnosis and 4 years' follow-up. Over time, the proportion of patients reporting sexual concerns either increased or remained constant with diagnosis. Less than half (46%, range 11.4-57) of the patients with sexual concerns reported the use of supportive care strategies, including gynecological or psychological consultations (range 11.4-57.4). Factors consistently associated with sexual concerns up to 4 years after diagnosis included already reporting the same concern at diagnosis [odds ratio (OR) poor body image 3.48 [95% confidence interval (CI) 3.11-3.89]; OR sexual inactivity 9.94 (95% CI 8.84-11.18), OR poor sexual function 9.75 (95% CI 8.67-10.95), OR poor sexual enjoyment 3.96 (95% CI 3.34-4.69)], endocrine therapy use [OR poor body image 1.15 (95% CI 1.01-1.31); OR sexual inactivity 1.19 (95% CI 1.02-1.39), OR poor sexual function 1.17 (95% CI 1.01-1.37), OR poor sexual enjoyment 1.23 (95% CI 1.00-1.53)], and depression [OR poor body image 2.00 (95% CI 1.72-2.34); OR sexual inactivity 1.66 (95% CI 1.40-1.97), OR poor sexual function 1.69 (95% CI 1.43-2.00), OR poor sexual enjoyment 1.94 (95% CI 1.50-2.51)]. Outcome-specific associations were also identified., Conclusions: Sexual concerns seem frequent, persistent, and insufficiently addressed. Pretreatment concerns, endocrine therapy, and emotional distress are commonly associated factors. A proactive evaluation of sexual health across the care continuum is needed, to promptly identify patients suitable for multidisciplinary counseling, referral, and supportive interventions., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: To date, studies have not provided definitive answers regarding whether previous immune checkpoint inhibitor (ICI) treatment alters outcomes for cancer patients with COVID-19., Methods: The OnCovid registry (NCT04393974) was searched from February 27, 2020, to January 31, 2022, for patients who received systemic anti-cancer therapy in the 4 weeks before laboratory-confirmed COVID-19 diagnosis. Propensity-score matching using country, vaccination status, primary tumor type, sex, age, comorbidity burden, tumor stage, and remission status investigated differences in predefined clinical outcomes comparing those who had or had not received ICIs., Results: Of 3523 patients screened, 137 ICI-only and 1378 non-ICI met inclusion criteria. Before matching, ICI patients were older, male, enrolled at centers in Italy, and had histories of smoking, thoracic cancers, advanced cancer stages, and active malignancies (P ≤0.02). After matching, there were 120 ICI and 322 non-ICI patients. ICI patients had no differences (odds ratio: 95% CI) in presenting COVID-19 symptoms (0.69: 0.37-1.28), receipt of COVID-specific therapy (0.88: 0.54-1.41), 14-day (0.95: 0.56-1.61), or 28-day (0.79: 0.48-1.29) mortalities. However, ICI patients required less COVID-19-related hospitalization (0.37: 0.21-0.67) and oxygen therapy (0.51: 0.31-0.83) and developed fewer complications (0.57: 0.36-0.92)., Conclusion: In this propensity-score matched analysis, previous ICI therapy did not worsen and potentially improved COVID-19 outcomes in patients with cancer., Competing Interests: Declarations of competing interest Alessio Cortellini received consulting fees from MSD, BMS, AstraZeneca, Roche; and speakers’ fees from AstraZeneca, MSD, Novartis, and Eisai. Matteo Lambertini acted as a consultant for Roche, Novartis, Lilly, AstraZeneca, Exact Sciences, MSD, Pfizer, and Seagen and received speaker honoraria from Roche, Novartis, Lilly, Pfizer, Takeda, Ipsen and Sandoz outside the submitted work. Alessandra Gennari has declared consulting/advisory role for Roche, MSD, Eli Lilly, Pierre Fabre, Eisai, and Daichii Sankyo; speakers bureau for Eisai, Novartis, Eli Lilly, Roche, Teva, Gentili, Pfizer, Astra Zeneca, Celgene, and Daichii Sankyo; research funds: Eisai, Eli Lilly, and Roche. CMV has received travel grants and other honoraria from BMS, MSD, Novartis, and Roche. Joan Brunet has declared consulting/advisory role for MSD and Astra Zenec, and support for attending meetings and/or travel for GSK. Josep Tabernero reports personal financial interest in the form of scientific consultancy role for Array Biopharma, AstraZeneca, Bayer, Boehringer Ingelheim, Chugai, Daiichi Sankyo, F. Hoffmann-La Roche Ltd, Genentech Inc, HalioDX SAS, Hutchison MediPharma International, Ikena Oncology, Inspirna Inc, IQVIA, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Ona Therapeutics, Orion Biotechnology, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Scandion Oncology, Scorpion Therapeutics, Seattle Genetics, Servier, Sotio Biotech, Taiho, Tessa Therapeutics and TheraMyc. Stocks: Oniria Therapeutics and also educational collaboration with Imedex/HMP, Medscape Education, MJH Life Sciences, PeerView Institute for Medical Education, and Physicians Education Resource (PER). Lorenza Rimassa reports receiving consulting fees from AstraZeneca, Basilea, Bayer, BMS, Eisai, Exelixis, Genenta, Hengrui, Incyte, Ipsen, IQVIA, Lilly, MSD, Nerviano Medical Sciences, Roche, Servier, Taiho Oncology, Zymeworks; lecture fees from AstraZeneca, Bayer, Eisai, Gilead, Incyte, Ipsen, Lilly, Merck Serono, Roche, Sanofi, Servier; travel expenses from AstraZeneca; and institutional research funding from Agios, AstraZeneca, BeiGene, Eisai, Exelixis, Fibrogen, Incyte, Ipsen, Lilly, MSD, Nerviano Medical Sciences, Roche, Zymeworks. David J Pinato received lecture fees from ViiV Healthcare, Bayer Healthcare, BMS, Roche, Eisai, Falk Foundation, travel expenses from BMS and Bayer Healthcare; consulting fees for Mina Therapeutics, Eisai, Roche, DaVolterra, and Astra Zeneca; research funding (to institution) from MSD and BMS. All remaining authors have declared no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)