Publications by authors named "Piero Fregatti"

27 Publications

  • Page 1 of 1

Breast Cancer Surgery in the COVID-19 Pandemic: Validation of a Preventive Program for Patients and Health Care Workers.

In Vivo 2021 Jan-Feb;35(1):635-639

Department of Surgical Sciences and Integrated Diagnostic (DISC), School of Medicine, University of Genoa, Genoa, Italy.

Background/aim: The perspective validation of a selective approach in patients undergoing breast cancer surgery was performed in order to assess whether patients as well as Health Care Workers (HCWs) were exposed to any undue risk of COVD-19 infection.

Patients And Methods: From March 9 to June 9 2020, 207 patients were phone-triaged by a dedicated Breast Care Nurse; a patient-tailored program was adopted with the aim of avoiding hospitalization of SARS-CoV-2 symptomatic patients, with a careful prioritization of surgical procedures according to specific disease features.

Results: Two hundred and three out of 207 patients underwent operation; seven patients were temporarily excluded because they tested positive at phone triage (n=3), or in-hospital triage (n=3); another asymptomatic patient with negative NP swab tested IgM Ab-positive so that surgery was re-scheduled two weeks later. Four patients had no surgery; one of them was reconsidered for neoadjuvant chemotherapy (NAC) after testing positive at phone triage; three patients were excluded because they were already hospitalized for COVID-19. Overall, mean in-hospital stay was 2.2 days (±SD, 0.7) and, after hospital discharge, no patient required readmission.

Conclusion: This preventive program avoided any COVID-19 infection among patients and HCWs, so that an elective breast cancer surgical procedure can be safely and timely pursued without affecting the oncologic outcome.
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http://dx.doi.org/10.21873/invivo.12302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880727PMC
January 2021

Update on the Management of Breast Cancer during Pregnancy.

Cancers (Basel) 2020 Dec 3;12(12). Epub 2020 Dec 3.

Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, 16132 Genova, Italy.

The diagnosis of breast cancer during pregnancy represents a challenging situation for the patient, her caregivers and physicians. Pregnancy adds complexity to oncological treatment planning, as many therapies can be potentially dangerous to the fetus. Therefore, a multidisciplinary approach is needed to offer a proper care for obtaining the best possible outcomes for the mother and the future child. Breast surgery is feasible throughout the pregnancy while radiotherapy should be postponed after delivery. Administration of chemotherapy is considered safe and can be given during the second and third trimesters, while it is contraindicated in the first trimester due to the high risk of fetal malformations. Endocrine therapy and targeted agents are not recommended during the whole pregnancy period; however, limited data are available on the use of the majority of new anticancer drugs in this context. The aim of the current review is to provide an update on the current state of art about the management of women diagnosed with breast cancer during pregnancy.
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http://dx.doi.org/10.3390/cancers12123616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761659PMC
December 2020

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

Expert Rev Anticancer Ther 2021 Mar 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

Clinical outcomes of patients with breast cancer relapsing after (neo)adjuvant trastuzumab and receiving trastuzumab rechallenge or lapatinib-based therapy: a multicentre retrospective cohort study.

ESMO Open 2020 08;5(4)

U.O.S.D. Breast Unit, IRCCS Ospedale Policlinico San Martino, Genova, Italy

Background: In the prepertuzumab era, we evaluated the clinical outcomes of patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer who underwent first-line trastuzumab-based or lapatinib-based therapy according to prior exposure to (neo)adjuvant trastuzumab.

Materials And Methods: In this multicentre retrospective cohort study conducted in 14 Italian centres of the Gruppo Italiano Mammella, consecutive patients undergoing first-line trastuzumab or lapatinib-based therapy were included. Analyses were performed according to the type of first-line therapy for metastatic disease (trastuzumab or lapatinib). Dichotomous clinical outcomes were analysed using logistic regression and time-to-event outcomes using Cox proportional hazard models controlling for relevant demographic, clinicopathological and therapy characteristics.

Results: Out of 450 patients included in the study, 416 (92%) received trastuzumab and 34 (7.5%) lapatinib. As compared with the trastuzumab cohort, more patients in the lapatinib cohort had a trastuzumab-free interval <1 month (37% vs 13.9%; p=0.017) and brain metastasis as first site of relapse (38.2% vs 9.4%; p<0.001). Among the 128 patients who relapsed after prior (neo)adjuvant trastuzumab, 101 (78.9%) received first-line trastuzumab and 27 (21.1%) first-line lapatinib. The following outcomes were observed with first-line lapatinib or trastuzumab, respectively: overall response rate 45.5% vs 61.3% (p=0.184), clinical benefit rate 68.2% vs 72.5% (p=0.691), median progression-free survival (PFS) 11.4 vs 12.0 months (p=0.814) and median overall survival (OS) 34.7 vs 48.2 months (p=0.722). In patients with brain metastasis as first site of relapse, median PFS was 12.2 vs 9.9 months (p=0.093) and median OS 33.7 vs 28.5 months (p=0.280), respectively.

Conclusions: In patients with HER2-positive breast cancer relapsing after prior (neo)adjuvant trastuzumab, first-line treatment with trastuzumab or lapatinib was not associated with a significant difference in the clinical outcomes. A non-significant trend favouring the use of lapatinib was observed in patients with brain metastasis as the first site of relapse.
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http://dx.doi.org/10.1136/esmoopen-2020-000719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7437709PMC
August 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

Effect of dose-dense adjuvant chemotherapy in hormone receptor positive/HER2-negative early breast cancer patients according to immunohistochemically defined luminal subtype: an exploratory analysis of the GIM2 trial.

Eur J Cancer 2020 09 4;136:43-51. Epub 2020 Jul 4.

Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Viale Benedetto XV, 10, 16132, Genoa, GE, Italy; Breast Unit, IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132, Genoa, GE, Italy. Electronic address:

Background: Luminal A-like and luminal B-like subtypes have different sensitivity to (neo)adjuvant chemotherapy, but their role in predicting dose-dense (DD) efficacy in the high-risk setting is unknown. In this exploratory analysis of the Gruppo Italiano Mammella 2 (GIM2) trial, we investigated DD efficacy according to luminal-like subtypes.

Methods: Patients with node-positive early breast cancer were randomised to receive either DD or standard-interval (SI) anthracycline-based chemotherapy followed by paclitaxel. In our analysis, luminal A-like cohort was identified as having a Ki67 < 20% and a progesterone receptor (PgR) ≥ 20%; luminal B-like cohort as having a Ki67 ≥ 20% and/or a PgR < 20%.

Results: Out of 2003 patients enrolled in the GIM2 trial, 412 had luminal A-like and 638 luminal B-like breast cancer. After a median follow-up of 7.9 years, disease-free survival (DFS) was 80.8% (95% confidence interval [CI] 76.4-84.5) and 70.5% (66.5-74.2) in luminal A-like and luminal B-like cohorts; overall survival (OS) was 91.6% (88.2-94.1) and 85.1% (81.7-87.9), respectively. We found no significant interaction between treatment and luminal subtype (interaction p = 0.603 and 0.535 for DFS and OS, respectively). When DD efficacy was investigated separately in each cohort, luminal-B like cohort appeared to benefit more from the DD schedule both in terms of DFS (unadjusted hazard ratio [HR] 0.72 [95% CI 0.54-0.96]) and OS (unadjusted HR 0.61 [95% CI 0.40-0.94]), compared with the luminal A-like cohort (unadjusted HR for DFS 0.89 [95% CI 0.59-1.33]; unadjusted HR for OS 0.83 [95% CI 0.45-1.54]).

Conclusions: No significant interaction between luminal-like subtype and treatment was observed. Patients in the luminal B-like cohort seemed to benefit more from DD schedule.
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http://dx.doi.org/10.1016/j.ejca.2020.05.007DOI Listing
September 2020

Breast Cancer Surgery During the COVID-19 Pandemic: An Observational Clinical Study of the Breast Surgery Clinic at Ospedale Policlinico San Martino - Genoa, Italy.

In Vivo 2020 Jun;34(3 Suppl):1667-1673

Department Surgical Sciences and Integrated Diagnostic (DISC), School of Medicine, University of Genoa, Genoa, Italy.

Background: COVID-19 pandemic required a marked re-allocation of healthcare resources, including at Breast Units. A patient-tailored program was developed to assess its efficacy regarding prevention of COVID-19 infection among patients with breast cancer undergoing surgery and healthcare workers (HCWs).

Patients And Methods: From March 9th to April 9th 2020, 91 patients were selected for elective surgery by means of: i) Pre-hospital screening aimed at avoiding hospitalization of symptomatic or suspicious COVID-19 patients, and ii) prioritisation of surgical procedure according to specific disease features.

Results: Eighty-five patients (93.4%) were fit for surgery, while five patients (5.5%) were temporarily excluded through 'telephone triage'; another two patients were excluded at in-hospital triage. A total of 71 out of 85 patients (83.5%) were diagnosed with invasive cancer, most of whom were undergoing breast-conserving surgery (61 out of 85 patients, 71.8%). The mean in-hospital stay was 2.2 days (SD=0.7 days). After hospital discharge, no patient needed re-admission due to post-operative complications; moreover, no COVID-19 infection among patients or HCWs was detected.

Conclusion: Safe breast cancer surgery was accomplished for both patients and HCWs by means of a careful preoperative selection of patients and in-hospital preventative measures. This screening program can be transferred to high-volume Breast Units and it may be useful in implementing European Community recommendations for prevention of COVID-19 infection.
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http://dx.doi.org/10.21873/invivo.11959DOI Listing
June 2020

Tumor-to-nipple Distance Should Not Preclude Nipple-sparing Mastectomy in Breast Cancer Patients. Personal Experience and Literature Review.

Anticancer Res 2020 Jun;40(6):3543-3550

Department of Surgical Sciences and Integrated Diagnostic (DISC), School of Medicine, University of Genoa, Genoa, Italy.

Background/aim: A retrospective study was performed in 246 breast cancer patients to define whether tumor-to-nipple distance (TND) assessment by breast MRI may select patients eligible to nipple-sparing mastectomy (NSM) as compared to permanent section assessment of retroareolar margin.

Patients And Methods: Pre- and post-operative parameters including imaging data, histology of the primary tumor, biologic prognostic factors, and adjuvant regimens were retrieved; patients with close/positive retroareolar margins underwent nipple or NAC excision. The primary endpoint was loco-regional recurrence (LRR).

Results: Patients with TND ≤2 cm had a significantly higher rate of invasive ductal carcinoma (p<0.003) and excision margins less than 2 mm (p<0.000). Eleven retroareolar specimens were positive at definitive pathology; final re-excision specimen examination showed residual disease in seven patients (63.6%). At a median follow-up of 31 to 33 months, no NAC recurrence did occur; disease-free survival was more than 96%, and LRR was homogeneously distributed among TND subgroups.

Conclusion: Therapeutic NSM is a safe procedure independently of TND assessed at preoperative breast MRI. Permanent section assessment of retroareolar tissue is more accurate and cost-effective than frozen section. Furthermore, delayed nipple and/or NAC excision did not impair local disease control.
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http://dx.doi.org/10.21873/anticanres.14343DOI Listing
June 2020

Circulating Tumor DNA Using Tagged Targeted Deep Sequencing to Assess Minimal Residual Disease in Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy.

J Oncol 2020 22;2020:8132507. Epub 2020 Jan 22.

Department of Internal Medicine, University of Genoa, 16132 Genoa, Italy.

In breast cancer patients undergoing neoadjuvant chemotherapy before surgery, there is an unmet need for noninvasive predictive biomarkers of response. The analysis of circulating tumor DNA (ctDNA) in particular has been the object of several reports, but few of them have studied the applicability of tagged targeted deep sequencing (tTDS) to clinical practice and its performance compared with droplet digital PCR (ddPCR). Here, we present the first results from an ongoing study involving a prospectively accrued, monocentric cohort of patients affected by invasive breast cancer, undergoing neoadjuvant chemotherapy followed by surgery with curative intent as per clinical practice. A pretreatment tumor biopsy and plasma samples were collected before and during treatment, after surgery, and every six months henceforth or until relapse, whichever came first. Pretreatment biopsies were sequenced with a 409-gene massive parallel sequencing (MPS) panel, allowing the identification of target mutations and their research in plasma by tTDS and ddPCR as a complementary approach. Using tTDS, we demonstrated the presence of at least one deleterious mutation in all the relapsed cases we studied ( = 4), with an average lead time of six months before clinical relapse. The association with ddPCR was suboptimal, and only one relapsed patient could be identified with such method. tTDS shows potential as an early noninvasive method for the detection of MRD in BC patients.
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http://dx.doi.org/10.1155/2020/8132507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196957PMC
January 2020

Moving trastuzumab emtansine (T-DM1) to the early setting of breast cancer treatment.

Ann Palliat Med 2020 Mar 18;9(2):512-516. Epub 2020 Mar 18.

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; Breast Unit, IRCCS Ospedale Policlinico San Martino, Genova, Italy.

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http://dx.doi.org/10.21037/apm.2020.01.09DOI Listing
March 2020

Dose-dense adjuvant chemotherapy in early breast cancer patients: 15-year results of the Phase 3 Mammella InterGruppo (MIG)-1 study.

Br J Cancer 2020 May 31;122(11):1611-1617. Epub 2020 Mar 31.

Department of Medical Oncology U.O. Oncologia Medica 2, IRCCS Ospedale Policlinico San Martino, Largo R. Benzi 10, 16132, Genova, Italy.

Background: Adjuvant chemotherapy is the standard of care in high-risk early breast cancer patients. Dose-dense should be the preferred schedule of administration. However, its long-term benefit is unknown.

Methods: In the Italian multicentre Phase 3 randomised MIG-1 trial, node-positive and high-risk node- negative breast cancer patients were randomised to receive six cycles of adjuvant fluorouracil, epirubicin and cyclophosphamide regimen administered every 3 (FEC21) or 2 (FEC14) weeks. The primary endpoint was overall survival (OS), and the secondary endpoint was event-free survival (EFS).

Results: From 1992 to 1997, 1214 patients were included. Median follow-up was 15.8 years. In all, 15-year OS was 71% and 68% in the FEC14 and FEC21 groups, respectively (HR = 0.89; p = 0.25). In all, 15-year EFS was 47% and 43% in the FEC14 and FEC21 groups, respectively (HR = 0.87; p = 0.18). In a pre-planned subgroup analysis, among patients with hormone receptor-negative tumours, 15-year OS was 70% and 65% in the FEC14 and FEC21 groups, respectively (HR = 0.73; 95% CI: 0.51-1.06); 15-year EFS was 58% and 43% in the FEC14 and FEC21 groups, respectively (HR = 0.70; 95% CI: 0.51-0.96).

Conclusions: Updated results from the MIG-1 study are numerically in favour of dose-dense chemotherapy, and suggest a long-term benefit of this approach in high-risk early breast cancer patients.
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http://dx.doi.org/10.1038/s41416-020-0816-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7251109PMC
May 2020

The Role of Sentinel Lymph Node Biopsy in Patients With B5c Breast Cancer Diagnosis.

In Vivo 2020 Jan-Feb;34(1):355-359

School of Medicine, University of Genoa, Genoa, Italy.

Background/aim: The histopathological assessment of the B5c category may sometimes be hampered by simple artifacts that may lead to over- or underestimation of that particular breast cancer so that its management is still controversial, especially with regard to the decision to proceed immediately to sentinel lymph node (SLN) biopsy. Hence, a retrospective study was performed in 174 patients undergoing breast-conserving surgery with a preoperative diagnosis of B5c in order to assess the usefulness of axillary node staging by means of SLN biopsy.

Patients And Methods: Pre- and post-operative parameters including imaging data, histology of the primary tumor and SLN biopsy, biological prognostic factors, type of operation, and adjuvant regimens were computed.

Results: Invasive carcinoma and carcinoma in situ were diagnosed in 46 (26.5%) and 128 patients (73.5%), respectively. Preoperative tumor size was significantly related to post-operative diagnosis of invasive carcinoma (p=0.020), retaining its predictive value at logistic regression analysis (p=0.046). Post-operative predictive factors of invasion were represented by tumor stage (p=0.008) and grading (p=0.008).

Conclusion: B5c preoperative diagnosis in patients undergoing breast conservative surgery would suggest an immediate wide local excision avoiding any further preoperative histologic assessment. Conversely, one-stage SLN biopsy might be suggested for patients eligible to mastectomy, similar to patients with carcinoma in situ, although its impact on the therapeutic and prognostic assessment seems negligible.
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http://dx.doi.org/10.21873/invivo.11781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6984094PMC
June 2020

Experiences of patients with Poland syndrome of diagnosis and care in Italy: a pilot survey.

Orphanet J Rare Dis 2019 11 21;14(1):269. Epub 2019 Nov 21.

Department of Health Science (DISSAL), University of Genoa, Genoa, Italy.

Background: Poland Syndrome (PS) is a rare congenital malformation involving functional and aesthetic impairments. Early diagnosis and timely therapeutic approaches play an important role in improving the quality of life of patients and kindred. This study aims to explore healthcare experiences of the diagnosis of patients affected by PS and to investigate the factors associated with diagnostic delay in Italy.

Results: Seventy-two patients affected by PS were asked to fill in a self- administered questionnaire on: a) diagnostic path; b) perceived quality of care received after diagnosis; c) knowledge of the rights and the socio-economic hardships related to their disease; d) evaluation of the integration of various professional skills involved in the diagnostic and therapeutic approach; e) perception of the social support provided by the Italian Association of Poland Syndrome (AISP). The average age at diagnosis was around 14 years; diagnosis was made at birth in only 31.58% of cases. Although typical symptomatology had appeared on average at an early age (4 months), only 23 patients (40.35%) received an early diagnosis (within the first year of life). Just over half of the patients (n = 30) were diagnosed in their region of origin, while 27 were diagnosed elsewhere. Furthermore, 12.28% were self-diagnoses. Among the patients who were diagnosed outside their region, 15 (88.24%) stated they had foregone some visits or treatments owing to costs and/or organizational issues.

Conclusions: An analysis of the patients' experiences highlights several gaps and a lack of homogeneity in the diagnostic and therapeutic follow-up of PS patients in Italy. A specific national diagnostic and therapeutic path is essential to guarantee patients complete and appropriate health services, compliant with the ethical principles of non-discrimination, justice and empathy. Implementation of an effective information and research network and empowerment of patients' associations are necessary conditions to encourage clinical collaboration and improve the quality of life of people living with rare diseases.
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http://dx.doi.org/10.1186/s13023-019-1253-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6873522PMC
November 2019

Development of a predictor of one-year mortality in older patients with cancer by geriatric and oncologic parameters.

J Geriatr Oncol 2020 05 6;11(4):610-616. Epub 2019 Nov 6.

Department of Internal Medicine and Medical Specialties (DiMI), University of Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Genoa, Italy. Electronic address:

Objectives: More than 60% of the new cancer diagnoses are currently made in older adults, a highly heterogeneous population. Reliable and time-saving tools to define older adults' prognosis are needed to inform the oncologist's decisions in routine clinical practice. We sought to define a multi-domain classification tool for the prediction of all-cause one-year mortality in a cohort of older adults with solid tumors.

Materials And Methods: We conducted a single-centre, prospective study of patients with solid cancer aged 65 or older and with G8 score ≤ 14. All patients underwent a comprehensive geriatric assessment (CGA) before starting their surgical or medical treatment. One-year mortality was recorded. A CGA-based prediction tool of one-year mortality was developed and subsequently validated in two independent training and testing cohorts with a 70/30 split, respectively.

Results: 162 patients were enrolled. Mean patient age was 78 ± 5.5 years. Forty-three percent of the patients were men. Colorectal and breast cancer were the most common diagnoses. The clinical variables selected for the development of the new classifier (MetaGENUA®) were: mini-nutritional assessment (MNA), instrumental day life activities (IADL), Cumulative Illness Rating Scale (CIRS), geriatric depression scale (GDS), age, and cancer stage. In our independent validation cohort, MetaGENUA® showed high specificity (0.86) and AUC = 0.71 (95% CI = 0.55-0.87).

Conclusions: MetaGENUA® predicts one-year mortality in older patients with cancer with high specificity. As such, MetaGENUA® is predicted to reveal as a useful tool to guide the oncologist's decisions in clinical practice.
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http://dx.doi.org/10.1016/j.jgo.2019.10.018DOI Listing
May 2020

Simultaneous Integrated Boost in Once-weekly Hypofractionated Radiotherapy for Breast Cancer in the Elderly: Preliminary Evidence.

In Vivo 2019 Nov-Dec;33(6):1985-1992

Department of Radiation Oncology, IRCCS Policlinico San Martino, Genoa, Italy.

Aim: To evaluate once-weekly hypofractionated radiotherapy in elderly patients affected by early breast cancer, reporting acute and late toxicity profiles, and treatment feasibility.

Patients And Methods: Fifty patients were treated with a hypofractionated regimen: 28.5±2.5 Gy in five fractions at one fraction weekly. Simultaneous integrated boost (SIB) to the tumor bed in high-risk cases.

Inclusion Criteria: patients over 70 years old, pT1-2, N0-1a. Acute and late toxicities were assessed based on Radiation Therapy Oncology Group.

Results: The median follow-up was 20 months and the median patient age was 79 years. SIB was added for 22 patients (44%). Grade 3-4 acute cutaneous toxicities were not observed; grade 2 toxicity occurred only in four patients (8%). Late subcutaneous tissue toxicity consisted of grade 2 fibrosis in two patients (4%), grade 1 in five (10%) and grade 0 in 41(85%).

Conclusion: Limiting fraction numbers with a safer profile may improve the management of breast cancer for the elderly.
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http://dx.doi.org/10.21873/invivo.11694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6899087PMC
March 2020

Integrated Treatment With Stapled Haemorrhoidopexy and Proctonorm® of Haemorrhoidal Disease.

In Vivo 2019 Sep-Oct;33(5):1671-1675

Breast Surgery Unit, Azienda Sanitaria Locale 3, Genoa, Italy.

Background/aim: This retrospective study was performed in patients undergoing Stapled Haemorrhoidopexy (SH) who were post-operatively treated with Proctonorm® with the aim of assessing its effect on early and late haemorrhoidal-related symptoms.

Patients And Methods: Forty-six males and 54 females received Proctonorm® (one tablet twice daily for 14 days) and Ketoprofene R (200 mg, one tablet twice daily, as requested).

Results: "Early Complication Score" (0-12) two days after surgery was 2.02±1.03; pain VAS (Visual Analogue Scale) (0-10) was 1.21±0.89, and the number of anti-inflammatory tablets was 4.24±1.06. At 40-day post-operative assessment, seven patients had post-operative complications with "Late Complication Score" (0-20) of 0.34±0.68. At six-month follow-up, a high index of patient satisfaction (VAS=9.39±0.24) was self-reported with 75% reduction in CSS (Constipation Scoring System) (1.95±2.58) compared to preoperative scores; "Late Complication Score" was 0.

Conclusion: The specific target activity of Proctonorm® at the microcircular level may be effective in patients undergoing SH in order to reduce the inflammatory response of residual haemorrhoids while waiting for stable resolution of symptoms within one or two weeks.
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http://dx.doi.org/10.21873/invivo.11654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6755022PMC
February 2020

Correction to: Schlafen-11 expression is associated with immune signatures and basal-like phenotype in breast cancer.

Breast Cancer Res Treat 2019 10;177(3):773

Department of Internal Medicine (DiMI), University of Genoa and Ospedale Policlinico San Martino, Viale Benedetto XV, 6, 16132, Genoa, Italy.

In the original publication of the article, the funding information was incorrectly published. The corrected funding statement is given in this correction article.
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http://dx.doi.org/10.1007/s10549-019-05348-zDOI Listing
October 2019

Schlafen-11 expression is associated with immune signatures and basal-like phenotype in breast cancer.

Breast Cancer Res Treat 2019 Sep 20;177(2):335-343. Epub 2019 Jun 20.

Department of Internal Medicine (DiMI), University of Genoa and Ospedale Policlinico San Martino, Viale Benedetto XV, 6, 16132, Genoa, Italy.

Purpose: Breast cancer (BC) is a heterogeneous disorder, with variable response to systemic chemotherapy. Likewise, BC shows highly complex immune activation patterns, only in part reflecting classical histopathological subtyping. Schlafen-11 (SLFN11) is a nuclear protein we independently described as causal factor of sensitivity to DNA damaging agents (DDA) in cancer cell line models. SLFN11 has been reported as a predictive biomarker for DDA and PARP inhibitors in human neoplasms. SLFN11 has been implicated in several immune processes such as thymocyte maturation and antiviral response through the activation of interferon signaling pathway, suggesting its potential relevance as a link between immunity and cancer. In the present work, we investigated the transcriptional landscape of SLFN11, its potential prognostic value, and the clinico-pathological associations with its variability in BC.

Methods: We assessed SLFN11 determinants in a gene expression meta-set of 5061 breast cancer patients annotated with clinical data and multigene signatures.

Results: We found that 537 transcripts are highly correlated with SLFN11, identifying "immune response", "lymphocyte activation", and "T cell activation" as top Gene Ontology processes. We established a strong association of SLFN11 with stromal signatures of basal-like phenotype and response to chemotherapy in estrogen receptor negative (ER-) BC. We identified a distinct subgroup of patients, characterized by high SLFN11 levels, ER- status, basal-like phenotype, immune activation, and younger age. Finally, we observed an independent positive predictive role for SLFN11 in BC.

Conclusions: Our findings are suggestive of a relevant role for SLFN11 in BC and its immune and molecular variability.
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http://dx.doi.org/10.1007/s10549-019-05313-wDOI Listing
September 2019

No Ink on Ductal Carcinoma : A Single Centre Experience.

Anticancer Res 2019 Jan;39(1):459-466

Breast Surgery Unit, Ospedale Policlinico San Martino, Genoa, Italy.

Background/aim: A retrospective analysis of 388 patients with pure ductal carcinoma in situ (DCIS) was performed in order to test the correlation of clearance margin of resection and other host-, tumor- and treatment-related factors with ipsilateral breast tumor recurrence (IBTR).

Materials And Methods: The pathological analysis was performed according to a standardized protocol: positive margins had DCIS at the inked margin; close margins had tumor between 0.1 to 0.9 mm, or 1 to 1.9 mm, and negative margins were ≥2 mm.

Results: At a median follow-up of 90 months there were 26 IBTR (10 invasive and 16 DCIS). Both in univariate and multivariate analysis a significant difference was observed in IBTR by comparing positive versus close/negative margins of excision (p=0.05) and the number of re-operations (p=0.000). Moreover, the actuarial IBTR rates were significantly different in patients with a positive compared to close/negative margins (log-rank test, p=0.042) while the stratification by the margin width (0.1-0.9 mm; 1.0-1.9 mm; ≥2 mm) was not significant (log-rank test, p=0.243).

Conclusion: The policy of "no ink on the tumor" can be translated from invasive to DCIS, because the actuarial IBTR rates were significantly different only in patients with a positive, compared to close/negative margins.
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http://dx.doi.org/10.21873/anticanres.13134DOI Listing
January 2019

Tumor Size-driven Dose of Intraoperative Radiotherapy for Breast Cancer: 18 Gy 21 Gy.

Anticancer Res 2018 Sep;38(9):5475-5479

Department of Radiation Oncology, IRCCS Policlinico San Martino and University, Genoa, Italy.

Aim: To test whether a reduced total single dose of 18 Gy of intraoperative radiotherapy with electrons (IORT) may be tailored to safely treat patients in comparison with the standard dose of 21 Gy. (NCT01276938).

Patients And Methods: From October 2009 to December 2011, 199 females affected by breast cancer were treated with conservative surgery and IORT with two different exclusive doses, 18 or 21 Gy.

Results: The median follow-up was 91 months (16-104 months). Sixty-five patients (pT1a\b, pN0\mic, pMx, G1-G3) received 18 Gy and 134 patients (pT1c\2, pN0\mic, pMx, G1-G3) received 21 Gy. No significant difference in local recurrence-free survival or overall survival was detected in the 18 Gy-treated arm versus that treated with 21 Gy: 96.9% vs. 96.3%, p=0.72, and 96.9% vs. 95.5%, p=0.82, respectively at 5 years.

Conclusion: The lower dose of 18 Gy achieved excellent results in terms of local toxicity and local control in early breast cancer.
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http://dx.doi.org/10.21873/anticanres.12880DOI Listing
September 2018

Vacuum assisted breast biopsy (VAB) excision of subcentimeter microcalcifications as an alternative to open biopsy for atypical ductal hyperplasia.

Br J Radiol 2018 May 23;91(1085):20180003. Epub 2018 Feb 23.

1 Department of Radiology, University of Genoa , Genoa , Italy.

Objective: Atypical ductal hyperplasia (ADH) is a proliferative lesion associated with a variable increased risk of breast malignancy, but the management of the patients is still not completely defined, with mandatory surgical excision in most cases. To report the results of the conservative management with mammographic checks of patients with ADH diagnosed by vacuum assisted breast biopsy (VAB), without residual calcifications.

Methods: The authors accessed the institutional database of radiological, surgical and pathological anatomy. Inclusion criteria were: ADH diagnosed by VAB on a single group of microcalcifications, without residual post-procedure; follow-up at least of 12 months. Exclusion criteria were the presence of personal history of breast cancer or other high-risk lesions; association with other synchronous lesions, both more and less advanced proliferative lesions.

Results: The 65 included patients were all females, with age range of 40-79 years (mean 54 years). The maximum diameter range of the groups of microcalcifications was 4-11 mm (mean 6.2 mm), all classified as BI-RADS 4b (Breast Imaging Reporting and Data System 4b) and defined as fine pleomorphic in 29 cases (45%) or amorphous in 36 cases (55%). The range of follow-up length was 12-156 months (mean 67 months). Only one patients developed new microcalcifications, in the same breast, 48 months after and 15 mm from the first VAB, interpreted as low-grade ductal carcinoma in situ (DCIS) at surgical excision.

Conclusion: These results could justify the conservative management, in a selected group of patients, being the malignancy rate lower than 2%, considered in the literature as the "probably benign" definition. Advances in knowledge: Increasing the length of follow-up of selected patients conservatively managed can improve the management of ADH cases.
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http://dx.doi.org/10.1259/bjr.20180003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6190792PMC
May 2018

Her2 assessment using quantitative reverse transcriptase polymerase chain reaction reliably identifies Her2 overexpression without amplification in breast cancer cases.

J Transl Med 2017 05 1;15(1):91. Epub 2017 May 1.

Department of Internal Medicine (Di.M.I.), University of Genoa and IRCCS AOU San Martino-IST, Viale Benedetto XV, 6, 16132, Genoa, Italy.

Background: Immunohistochemistry (IHC) and fluorescent-in situ hybridization (FISH) are standard methods to assess human epidermal growth factor receptor 2 (HER2) status in breast cancer (BC) patients. Real-time quantitative polymerase-chain-reaction (qRT-PCR) is able to detect HER2 overexpression. Here we compared FISH, IHC, quantitative PCR (qPCR), and qRT-PCR to determine the concordance rates and evaluate their relative roles in HER2 determination.

Patients And Methods: We determined HER2 status in 153 BC patients, using IHC, FISH, Q-PCR and qRT-PCR. In discordant cases, we directly measured HER2 protein levels using Western blotting.

Results: The overall agreement (OA) between FISH and Q-PCR was 94.1, with a k value of 0.87. Assuming FISH as the standard reference, Q-PCR showed an 86.1% sensitivity and a 99.0% specificity with a global accuracy of 91.6%. OA between FISH and qRT-PCR was 90.8% with a k value of 0.81. Of interest, the disagreement between FISH and qRT-PCR was mostly restricted to equivocal cases. HER2 protein analysis suggested that qRT-PCR correlates better than FISH with HER2 protein levels, particularly where FISH fails to provide conclusive results.

Significance: qRT-PCR may outperform FISH in identifying patients overexpressing HER2 protein. Q-PCR cannot be used for HER2 status assessment, due to its suboptimal level of agreement with FISH. Both FISH and Q-PCR may be less accurate than qRT-PCR as surrogates of HER2 protein determination.
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http://dx.doi.org/10.1186/s12967-017-1195-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5412048PMC
May 2017

Tumescent Anesthesia in Skin- and Nipple-sparing Mastectomy: Results of a Prospective Clinical Study.

Anticancer Res 2017 01;37(1):349-352

Breast Surgery, Breast Unit, University of Genoa, School of Medicine, San Martino Hospital and National Cancer Institute, Genoa, Italy.

Background: The tumescent mastectomy technique has been used to facilitate dissection of subcutaneous tissue and mammary gland in order to reduce intraoperative bleeding and speed the operation.

Patients And Methods: A prospective clinical study was performed on 30 female patients undergoing immediate breast reconstructions after skin-sparing mastectomy (SSM) or nipple-sparing mastectomy (NSM) in order to assess early postoperative complications, pain, and final esthetic outcome of skin flaps related to tumescent anesthesia (TA).

Results: TA significantly speeded-up the operative procedure (131±49.99 vs. 180.5±67.15 min; p=0.03) achieving less skin damage compared to patients who did not have TA (p=0.045); moreover, no significant difference occurred with regard to the length of in-hospital stay and overall lymphatic drainage.

Conclusion: The length of the operation as well as the final cosmetic outcome of skin flaps was significantly improved due to TA, with no appreciable side-effects.
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http://dx.doi.org/10.21873/anticanres.11328DOI Listing
January 2017

Axillary ultrasound and Fine-Needle Aspiration Cytology in the preoperative staging of axillary node metastasis in breast cancer patients.

Breast 2016 Dec 10;30:146-150. Epub 2016 Oct 10.

Breast Unit, IRCCS "San Martino-IST", Genoa, Italy.

Objective: A prospective observational clinical study was undertaken to assess the accuracy of preoperative Axillary Ultrasound (AUS) plus Fine-Needle Aspiration Cytology (FNAC) as well as and its clinical utility, that is the capacity of the information supplied by the test to guide the clinical decision-making.

Materials And Methods: from January 2013 to August 2015, 400 female patients with pT1-3 cN0 operable breast cancer underwent AUS with FNAC at the Breast Unit of the "IRCCS San Martino-IST" in Genoa (Italy).

Results: 127 out of 400 patients (31.7%) had axillary lymph node metastases; in 69 out of 127 node-positive patients (54.3%) AUS detected at least one abnormal lymph node, and in 56 out of 127 patients (44.1%) the abnormal sonographic pattern of the lymph node was coupled with a positive FNAC finding. No false-positive finding by both AUS-alone or combined AUS/FNAC was observed. AUS-alone had sensitivity of 54.3% (69/127), specificity of 100% (273/273), PPV of 100% (69/69), NPV of 82.5% (273/331), and accuracy of 85.5% (342/400). Combined AUS/FNAC had sensitivity of 44.1% (56/127), specificity of 100% (273/273), PPV of 100% (56/56), NPV of 79.4% (273/344), and accuracy of 82.2% (329/400).

Conclusions: AUS-alone or combined AUS/FNAC had a high accuracy rate coupled with a more than satisfactory efficiency due to their low costs and easy access for the preoperative staging of the axilla. Notably, AUS-alone might be suggested for the preoperative staging of patients with early stage breast cancer because FNAC did not increased the specificity but reduced the sensitivity of the technique. Patients with negative findings might undergo either SLNB or close observation while waiting for the definitive results of ongoing SOUND randomized clinical trial.
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http://dx.doi.org/10.1016/j.breast.2016.09.009DOI Listing
December 2016

Implant-Based Breast Reconstruction Using a Polyester Mesh (Surgimesh-PET): A Retrospective Single-Center Study.

Plast Reconstr Surg 2016 Jun;137(6):931e-939e

Genoa, Italy.

Background: Although the introduction of acellular dermal matrices is considered one of the most important advancements in alloplastic breast reconstruction, costs and local policy limit their use in Italy. The purpose of this study was to assess short-term outcomes following Surgimesh-PET-based breast reconstruction.

Methods: A single-center, retrospective, case-control study was performed from January 1, 2012, to December 31, 2013, by enrolling 206 breast reconstructions performed in 196 patients after oncologic (n = 200) or prophylactic (n = 6) mastectomy. Group A included 63 patients who underwent 70 immediate Surgimesh-PET-assisted breast reconstructions, and group B included 133 patients who underwent 136 standard breast reconstructions.

Results: No significant differences between groups occurred for early postoperative complications (p = 0.610), major complications that required surgical revision (p = 0.887), volume (p = 0.498) or width of the prosthesis (p = 0.201), skin-sparing mastectomy (p = 0.315), or axillary surgery (p = 0.265). Multivariate logistic regression showed that prior radiotherapy was the only significant variable for early postoperative complications in both whole series (p = 0.011) and group B (p = 0.046), whereas body mass index greater than 25 was an independent predictor in group A (p = 0.041). Prior radiotherapy was the only variable that reached statistical significance in the multivariate model for major complications in the whole series (p = 0.005).

Conclusions: Short-term outcomes of Surgimesh-PET-based alloplastic breast reconstruction are promising. Further studies are needed to evaluate the long-term results of this surgical approach.

Clinical Question/level Of Evidence: Therapeutic, III.
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http://dx.doi.org/10.1097/PRS.0000000000002180DOI Listing
June 2016

Clinical decision-making in atypical and suspicious categories in fine-needle aspiration cytology of the breast.

Anticancer Res 2015 Apr;35(4):2369-74

Breast Surgery, IRCCS "A.O.U. San Martino-IST" Genoa, Genoa, Italy.

Background: Fine-needle aspiration cytology (FNAC) is a simple and reliable technique to assess breast lesions, although a definitive differential diagnosis (benignity vs. cancer) is achieved approximately in 60-70% of cases because an inadequate (C1), atypical (C3) or suspicious (C4) category is otherwise reported.

Patients And Methods: A retrospective analysis of 763 cases with C3 or C4 reports was performed to define their positive predictive value (PPV), as well as the practical implications of clinical and imaging findings as for clinical decision-making. FNACs were collected from January 2003 to September 2012 at the Breast Unit of IRCCS "A.O.U. San Martino-IST" Genoa, with each being received later to definitive histology. The PPV for cancer of C3/C4 categories were computed to measure the accuracy of FNAC; moreover, the PPV was also stratified according to clinical, mammography and sonography data alone or by their combination.

Results: The PPV of C3 and C4 was 21.1% (80/380) and 84.1 % (322/383), respectively. Within each C3/C4 category, a significant direct correlation (p<0.001) between the suspicion index of clinical, mammography and sonography data and cancer detection rate was always observed. The PPV of C3/C4 stratified by the combination of clinical and imaging findings showed satisfactory values in the C3 category only when there was an agreement between clinical and imaging findings, whereas the PPV of the C4 category was always remarkably high (ranging from 92.3% to 100%).

Conclusion: the diagnostic work-up in C4 reports or in patients with a C3 report but with an high suspicion index at clinical or imaging examination should be preferably implemented by means of a core biopsy to optimize the therapeutic planning; given a C3 report with dubious clinical and/or imaging findings, an excisional biopsy (or in alternative vacuum-assisted breast biopsy with complete removal of the nodule) should be preferably performed in order to reach a definitive histological dia gnosis with no further delay.
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April 2015