Publications by authors named "Maria Grazia Razeti"

10 Publications

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Knowledge, Practice, and Attitudes of Physicians in Low- and Middle-Income Countries on Fertility and Pregnancy-Related Issues in Young Women With Breast Cancer.

JCO Glob Oncol 2022 Jan;8:e2100153

Department of Medical Oncology, U.O. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy.

Purpose: Fertility and pregnancy-related issues are highly relevant for young (≤ 40 years) patients with breast cancer. Limited evidence exists on knowledge, practice, and attitudes of physicians from low- and middle-income countries (LMICs) regarding these issues.

Methods: A 19-item questionnaire adapted from an international survey exploring issues about fertility preservation and pregnancy after breast cancer was sent by e-mail between November 2019 and January 2020 to physicians from LMICs involved in breast cancer care. Descriptive analyses were performed.

Results: A total of 288 physicians from Asia, Africa, America, and Europe completed the survey. Median age was 38 years. Responders were mainly medical oncologists (44.4%) working in an academic setting (46.9%). Among responders, 40.2% and 53.8% reported having never consulted the available international guidelines on fertility preservation and pregnancy after breast cancer, respectively. 25.0%, 19.1%, and 24.3% of responders answered to be not at all knowledgeable about embryo, oocyte, or ovarian tissue cryopreservation, respectively; 29.2%, 23.6%, and 31.3% declared that embryo, oocyte, and ovarian tissue cryopreservation were not available in their countries, respectively. 57.6% of responders disagreed or were neutral on the statement that controlled ovarian stimulation can be considered safe in patients with breast cancer. 49.7% and 58.6% of responders agreed or were neutral on the statement that pregnancy in breast cancer survivors may increase the risk of recurrence overall or only in those with hormone receptor-positive disease, respectively.

Conclusion: This survey showed suboptimal knowledge, practice, and attitudes of physicians from LMICs on fertility preservation and pregnancy after treatment completion in young women with breast cancer. Increasing awareness and education on these aspects are needed to improve adherence to available guidelines and to promote patients' oncofertility counseling.
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http://dx.doi.org/10.1200/GO.21.00153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8769103PMC
January 2022

De novo Metastatic Breast Cancer Arising in Young Women: Review of the Current Evidence.

Clin Breast Cancer 2022 Jan 8;22(1):78-87. Epub 2021 Oct 8.

Department of Medical Oncology, U.O. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genoa, Italy; Department of Internal Medicine and Medical Specialties (DIMI), School of Medicine, University of Genoa, Genoa, Italy. Electronic address:

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.
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http://dx.doi.org/10.1016/j.clbc.2021.10.001DOI Listing
January 2022

Safety of systemic hormone replacement therapy in breast cancer survivors: a systematic review and meta-analysis.

Breast Cancer Res Treat 2022 Jan 3;191(2):269-275. Epub 2021 Nov 3.

Medical Oncology 2, IRCCS Ospedale Policlinico San Martino, Genova, Italy.

Purpose: 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.

Methods: 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.

Results: 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).

Conclusion: 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.
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http://dx.doi.org/10.1007/s10549-021-06436-9DOI Listing
January 2022

The PREgnancy and FERtility (PREFER) Study Investigating the Need for Ovarian Function and/or Fertility Preservation Strategies in Premenopausal Women With Early Breast Cancer.

Front Oncol 2021 3;11:690320. Epub 2021 Jun 3.

Department of Internal Medicine and Medical Sciences (DiMI), School of Medicine, University of Genova, Genova, Italy.

Background: Offering ovarian function and/or fertility preservation strategies in premenopausal women with newly diagnosed breast cancer candidates to undergo chemotherapy is standard of care. However, few data are available on uptake and main reasons for refusing these options.

Methods: The PREFER study (NCT02895165) is an observational, prospective study enrolling premenopausal women with early breast cancer, aged between 18 and 45 years, candidates to receive (neo)adjuvant chemotherapy. Primary objective is to collect information on acceptance rates and reasons for refusal of the proposed strategies for ovarian function and/or fertility preservation available in Italy.

Results: At the study coordinating center, 223 patients were recruited between November 2012 and December 2020. Median age was 38 years (range 24 - 45 years) with 159 patients (71.3%) diagnosed at ≤40 years. Temporary ovarian suppression with gonadotropin-releasing hormone agonists (GnRHa) was accepted by 58 out of 64 (90.6%) patients aged 41-45 years and by 151 out of 159 (95.0%) of those aged ≤40 years. Among patients aged ≤40 years, 57 (35.8%) accepted to access the fertility unit to receive a complete oncofertility counseling and 29 (18.2%) accepted to undergo a cryopreservation technique. Main reasons for refusal were fear of delaying the initiation of antineoplastic treatments and contraindications to the procedure or lack of interest in future childbearing. Patients with hormone-receptor positive breast cancer had a tendency for a higher acceptance rates of ovarian function and/or fertility preservation strategies than those with hormone-receptor negative disease.

Conclusions: More than 90% of premenopausal women with early breast cancer, and particularly those with hormone receptor-positive disease, were concerned about the potential risk of chemotherapy-induced premature ovarian insufficiency and/or infertility and accepted GnRHa administration. Less than 1 out of 5 women aged ≤40 years accepted to undergo cryopreservation strategies.
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http://dx.doi.org/10.3389/fonc.2021.690320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210666PMC
June 2021

Comparing the Gonadotoxicity of Multiple Breast Cancer Regimens: Important Understanding for Managing Breast Cancer in Pre-Menopausal Women.

Breast Cancer (Dove Med Press) 2021 24;13:341-351. Epub 2021 May 24.

Department of Medical Oncology, U.O.C Clinica Di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy.

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.
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http://dx.doi.org/10.2147/BCTT.S274283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164347PMC
May 2021

Trastuzumab emtansine (T-DM1) as adjuvant treatment of HER2-positive early breast cancer: safety and efficacy.

Expert Rev Anticancer Ther 2021 03 17;21(3):241-250. Epub 2020 Dec 17.

Department of Medical Oncology, U.O.C. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy.

: 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.: 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.: 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.
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http://dx.doi.org/10.1080/14737140.2021.1857243DOI Listing
March 2021

Gender-specific aspects related to type of fertility preservation strategies and access to fertility care.

ESMO Open 2020 10;5(Suppl 4):e000771

Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genova, Liguria, Italy; Department of Medical Oncology, U.O.C Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy. Electronic address:

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 .
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http://dx.doi.org/10.1136/esmoopen-2020-000771DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594356PMC
October 2020

Burning Questions in the Oncofertility Counseling of Young Breast Cancer Patients.

Breast Cancer (Auckl) 2020 4;14:1178223420954179. Epub 2020 Sep 4.

Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genova, Italy.

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.
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http://dx.doi.org/10.1177/1178223420954179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476336PMC
September 2020

Current State of the Art in the Adjuvant Systemic Treatment of Premenopausal Patients With Early Breast Cancer.

Clin Med Insights Oncol 2020 29;14:1179554920931816. Epub 2020 Jun 29.

Department of Medical Oncology, U.O.C Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy.

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.
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http://dx.doi.org/10.1177/1179554920931816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325453PMC
June 2020

Implementing the hub and spoke model for the oncofertility units.

Breast 2019 12 4;48:100. Epub 2019 Sep 4.

Department of Medical Oncology, U.O.C. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy; Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genova, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.breast.2019.09.002DOI Listing
December 2019
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