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Loss of muscle mass is associated with negative clinical outcome in breast cancer (BC) patients. Therefore, the aim of the study is to evaluate if there is pectoralis muscle area (PMA) depletion, reflecting loss of muscle mass, in breast cancer patients of reproductive age (≤ 45 years) undergoing neoadjuvant chemotherapy (NAC) and to correlate PMA with clinical and histopathological data.This monocentric study, approved by our institutional review board, enrolled a total of 52 consecutive patients (mean age 37 ± 4.96 years) with histologically proven primary breast cancer between January 2019 and September 2021, treated with NAC and in whom tumor response and PMA were assessed with breast MRI. Two radiologists calculated PMA before and after NAC independently and blindly on axial 3D FLASH pre-contrast T1-weighted images. Wilcoxon-Mann-Whitney U test compared median values and percentage changes of pectoralis muscle area at the beginning and at the end of NAC (158 ± 25.5 days). Multivariate regression analysis on ΔPMA (difference between PMA pre-NAC and PMA post-NAC) was done according to clinical and histopathological data. Inter-reader and intra-reader agreement was estimated with K statistics.Pre-NAC PMA mean value was larger than post-NAC PMA mean value (9.6 ± 2.6 cmPMA variation in BC young patients, directly estimated on breast MRI, could be a potential tool to monitor body composition during NAC with potential implications in improving outcome.

Symptoms of treatment-induced menopause negatively affect quality of life and adherence to endocrine therapy of breast cancer (BC) survivors. Nevertheless, the use of systemic hormone replacement therapy (HRT) to mitigate these symptoms may be associated with an increased risk of disease recurrence in these patients. This systematic review and meta-analysis aimed to assess the safety of systemic HRT on risk of disease recurrence in BC survivors. A systematic search of PubMed up to April 20, 2021 was conducted to identify randomized controlled trials (RCTs) that investigated the risk of disease recurrence with the use of HRT in BC survivors. A random-effect model was applied to calculate the risk of recurrence, reported as pooled hazard ratio (HR) with 95% confidence intervals (CI). A subgroup analysis was performed to estimate the risk of recurrence according to hormone receptor status. Four RCTs were included in the meta-analysis (n = 4050 patients). Overall, 2022 patients were randomized to receive HRT (estrogen/progestogen combination or tibolone) and 2023 to the control group with placebo or no HRT. HRT significantly increased the risk of BC recurrence compared to placebo (HR 1.46, 95% CI 1.12–1.91, p = 0.006). At the subgroup analysis, the risk of BC recurrence with the use of HRT was significantly increased in patients with hormone receptor-positive disease (HR 1.8, 95% CI 1.15–2.82, p = 0.010) but not in those with hormone receptor-negative tumors (HR 1.19, 95% CI 0.80–1.77, p = 0.390). Use of HRT was associated with a detrimental prognostic effect in BC survivors, particularly in those with hormone receptor-positive disease. Alternative interventions to mitigate menopause-related symptoms should be proposed.

Background: Controlled ovarian stimulation (COS) for oocyte/embryo cryopreservation before starting chemotherapy is standard of care for young women with breast cancer wishing to preserve fertility. However, some oncologists remain concerned on the safety of COS, particularly in patients with hormone-sensitive tumors. Moreover, limited evidence exists on the safety of assisted reproductive technologies (ART) in breast cancer survivors after completion of anticancer treatments. Material and methods: A systematic literature review with no date restriction up to June 30, 2021 was conducted to identify studies reporting results of oncological outcomes in breast cancer patients and survivors who underwent COS or other ART compared to patients and survivors who did not access these techniques. From each included study, recurrence ratio, event-free survival (EFS) and mortality rate were extracted. Pooled relative risks (RRs) and hazard ratios (HRs) with 95% confidence intervals (CI) were calculated using the random effects models. Results: Out of 15 included studies (n=4,643), 11 reported outcomes of patients who underwent COS for fertility preservation before starting chemotherapy, and 4 of survivors who underwent ART following anticancer treatment completion. Compared to women who did not receive fertility preservation at diagnosis (n=2,386), those who underwent COS (n=1,594) had reduced risk of recurrence (RR 0.58, 95% CI 0.46-0.73) or mortality (RR 0.54, 95% CI 0.38-0.76). No detrimental effect of COS on EFS was observed (HR 0.76, 95% CI 0.55-1.06). A similar trend of better outcomes in terms of EFS was observed in women with hormone-receptor positive disease who underwent COS (HR 0.36, 95% CI 0.20-0.65).Compared to women not exposed to ART following completion of anticancer treatments (n=540), those exposed to ART (n=123) showed a tendency for better outcomes in terms of recurrence ratio (RR 0.34, 95% CI 0.17-0.70) and EFS (HR 0.43, 95% CI 0.17-1.11). Conclusions: Despite including mostly retrospective studies, this meta-analysis suggests that accessing COS at diagnosis, also in hormone receptor-positive disease, or ART following treatment completion is not associated with detrimental prognostic effect in young women with breast cancer. These results are important to reassure patients and oncologists on the safety of these procedures to increase the chances of future conception. Citation Format: Luca Arecco, Eva Blondeaux, Marco Bruzzone, Marcello Ceppi, Maria Maddalena Latocca, Andrea Boutros, Camilla Marrocco, Maria Grazia Razeti, Maurizio Cosso, Stefano Spinaci, Margherita Condorelli, Claudia Massarotti, Lucia Del Mastro, Isabelle Demeestere, Matteo Lambertini. Safety of assisted reproductive technologies before and after anticancer treatments in young women with breast cancer: A systematic review and meta-analysis [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD5-07.

Valentino Martelli,1,2 Maria Maddalena Latocca,1,2 Tommaso Ruelle,1,2 Marta Perachino,1,2 Luca Arecco,1,2 Kristi Beshiri,1,2 Maria Grazia Razeti,1,2 Marco Tagliamento,1,2 Maurizio Cosso,3 Piero Fregatti,4,5 Matteo Lambertini1,2 1Department of Medical Oncology, U.O.C Clinica Di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy; 2Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genova, Italy; 3Department of Radiology, IRCCS Ospedale Policlinico San Martino, Genova, Italy; 4U.O.C. Clinica Di Chirurgia Senologica, Department of Surgery, IRCCS Ospedale Policlinico San Martino, Genova, Italy; 5Department of Integrated Diagnostic Surgical Sciences, School of Medicine, University of Genova, Genova, ItalyCorrespondence: Matteo LambertiniIRCCS Ospedale Policlinico San Martino, University of Genova, Largo Rosanna Benzi 10, Genova, 16132, ItalyTel +39 010 555 4254Fax + 39 010 555 6536Email matteo.lambertini@unige.itAbstract: Over the last several decades, improvements in breast cancer treatment have contributed to increased cure rates for women diagnosed with this malignancy. Consequently, great importance should be paid to the long-term side effects of systemic therapies. For young women (defined as per guideline ≤ 40 years at diagnosis) who undergo chemotherapy, one of the most impactful side effects on their quality of life is premature ovarian insufficiency (POI) leading to fertility-related problems and the side effects of early menopause. Regimens, type, and doses of chemotherapy, as well as the age of patients and their ovarian reserve at the time of treatment are major risk factors for treatment-induced POI. For these reasons, childbearing desire and preservation of ovarian function and/or fertility should be discussed with all premenopausal patients before planning the treatments. This manuscript summarizes the available fertility preservation techniques in breast cancer patients, the risk of treatment-induced POI with different anticancer treatments, and the possible procedures to prevent it. A special focus is paid to the role of oncofertility counseling, as a central part of the visit in this setting, during which the patient should receive all the information about the potential consequences of the disease and of the proposed treatment on her future life.Keywords: breast cancer, fertility, young patient, oncofertility, premature ovarian insufficiency, anti-Mullerian hormone

Women with metastatic breast cancer remains a heterogeneous group of patients with different prognostic outcomes and therapeutic needs. Young women with de novo metastatic breast cancer (dnMBC) represent a peculiar population with respect to tumor biology, prognosis, clinical management and survivorship issues. Overall, these patients are able to attain long-term survival with a proper management of both primary tumor and distant metastases. On the other hand, they are also at higher risk of experiencing a deterioration in their quality of life (QoL) due to primary cancer-related side effects. Young women are also likely to harbor germline pathogenic variants in cancer predisposition genes which could affect treatment decisions and have a direct impact on the lives of patients' relatives. The loco-regional management of the primary tumor represents another thorny subject, as the surgical approach has shown controversial effects on the survival and the QoL of these patients. This review aims to provide an update on these issues to better inform the clinical management of dnMBC in young women.

Introduction: The prognosis of patients with HER2-positive early breast cancer has radically improved after the introduction of (neo)adjuvant anti-HER2 targeted therapy. Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate combining the anticancer properties of the anti-HER2 agent trastuzumab and the antineoplastic cytotoxic drug DM1. After demonstrating to be an effective and safe treatment for patients with HER2-positive advanced breast cancer, the development of T-DM1 has moved to the early setting.Areas covered: The aim of this review is to explore the current role of T-DM1 in the treatment landscape of HER2-positive early breast cancer, focusing specifically on the efficacy and safety data available in the adjuvant setting.Expert opinion: T-DM1 is an effective and safe treatment option in the adjuvant setting for patients with HER2-positive breast cancer without pathologic complete response after standard neoadjuvant chemotherapy plus anti-HER2 targeted therapy. With the availability of more effective anti-HER2 targeted agents, including T-DM1, there is an urgent need for more chemotherapy de-escalation research efforts in the early setting.

Survivorship is an area of paramount importance to be addressed as early as possible after cancer diagnosis by all health care providers. On this regard, cancer care in young patients often poses several age-related considerations among which fertility and pregnancy-related issues have a crucial role. According to the available guidelines on the topic, all patients with cancer diagnosed during their reproductive years should be provided a proper oncofertility counselling before starting anticancer treatments. This is an important step in order to inform patients about the potential treatment-induced gonadotoxicity and the available strategies for fertility preservation so that they can be referred as early as possible to fertility specialists if potentially interested in these options. In this manuscript, we aim to provide an up to date overview on the available efficacy and safety data with the main strategies for fertility preservation in male and female cancer patients in order to help optimising the oncofertility counselling performed by healthcare providers involved in cancer care and dealing with young patients. In male patients with cancer, sperm cryopreservation is the standard technique for fertility preservation. Oocyte/embryo cryopreservation, ovarian tissue cryopreservation and temporary ovarian suppression with luteinising hormone-releasing hormone agonists during chemotherapy are the main options in female patients with cancer. A multidisciplinary management building a strong network between fertility and oncology/haematology units is crucial to properly address fertility care in all young patients with cancer, at both diagnosis and during oncologic follow-up. Discussing fertility and pregnancy-related issues with young patients with cancer has to be considered mandatory nowadays keeping in mind that returning to a normal life (including the possibility to have a family and to live with as few side effects as possible) should be considered an important ambition in cancer care in the 21st century.

The improved prognosis of breast cancer patients makes survivorship issues an area of crucial importance. In this regard, an increased attention is needed toward the development of potential anticancer treatment-related long-term side-effects, including gonadal failure and infertility in young women. Therefore, fertility preservation and family planning are crucial issues to be addressed in all young women of reproductive age with newly diagnosed cancer. Despite a growing availability of data on the efficacy and safety of fertility preservation options and the fact that conceiving after prior history of breast cancer has become more accepted over time, there are still several gray zones in this field so that many physicians remain uncomfortable to deal with these topics. The purpose of this review is to answer some of the most controversial questions frequently asked by patients during their oncofertility counseling, in order to provide a detailed and up-to-date overview on the evidence available in this field to physicians involved in the care of young women with breast cancer.

Breast cancer is the most frequent malignancy diagnosed in premenopausal women. In this age group, breast tumors tend to be diagnosed at more advanced stages and to harbor more aggressive biological features. In addition, specific age-related issues including genetic counseling, fertility preservation, impact on social and couple relationships, working life, and management of long-term side effects should be considered highly relevant when managing early breast cancer in premenopausal women. Therefore, the care of these patients is particularly complex and a multidisciplinary approach is mandatory. The present review summarizes the current state of art in the adjuvant systemic treatment of premenopausal women with early breast cancer focusing on the optimal chemotherapy, endocrine therapy, and targeted therapy approaches in this specific patient population.

12067 Background: Improvements in breast cancer (BC) care have led to increased survival of patients; hence, more attention to long-term treatment-related adverse events and quality of life (QoL) is required. Symptoms of spontaneous and treatment-induced menopause significantly affect the QoL and adherence to endocrine therapy among BC survivors, with potential negative implications on outcome. Use of systemic hormone replacement therapy (HRT) to mitigate menopause-associated symptoms is not recommended to reduce the burden of these side effects being historically associated with an increased risk of disease recurrence. This systematic review and metanalysis aimed to estimate the effect of HRT on risk of disease recurrence in BC survivors. Methods: A systematic search of Pubmed and Embase libraries up to January 15, 2021, was conducted in order to identify randomized controlled trials (RCTs) investigating the risk of disease recurrence with the use of HRT in BC survivors. We used the random-effect model to calculate the overall risk of recurrence, reported as pooled hazard ratio (HR) with 95% confidence intervals (CI). Moreover, we performed a subgroup analysis to estimate the risk of recurrence according to hormone receptor status. The Higgins I2 index was computed to assess the heterogeneity between studies. The likelihood of publication bias was assessed by Egger’s test. Results: Four RCTs were found and three were included in the metanalysis (n = 3.973 patients); one study (n = 100 patients) was excluded due to the impossibility to extract the HR for disease recurrence. Overall, 1.990 patients were randomized to receive HRT (estrogen-progesteron combination or tibolone), while 1.983 patients were included in control groups (placebo or no HRT). As compared to control group, HRT significantly increased the risk of BC recurrence (HR 1.49, 95% CI 1.15-1.93, p = 0.002). The heterogeneity between the studies was low (39%, p = 0.194), and no publication bias was found ( p = 0.537). Two studies reported the HR according to hormone receptor status. At the subgroups analysis, the risk of BC recurrence with the use of HRT was significantly increased in hormone receptor-positive patients (HR 1.8, 95% CI 1.15-2.82, p = 0.010) but not in those with hormone receptor-negative tumors (HR 1.25, 95% CI 0.83-1.88, p = 0.290). Conclusions: Use of HRT significantly increases the risk of recurrence in BC survivors, particularly in those with hormone receptor-positive disease. Therefore, this approach remains contraindicated in this setting. Alternative interventions to mitigate menopause-related symptoms should be proposed to these patients.