Patterns of care at the end of life: a retrospective study of Italian patients with advanced breast cancer.

OBJECTIVES: To better understand the type of care offered to Italian patients with advanced breast cancer at the End-of-Life (EoL), we conducted a retrospective observational study. EoL was defined as the period of six months before death. METHODS: One hundred and twenty-one patients with advanced breast cancer (ABC) treated at IRCCS San Martino Policlinic Hospital who died between 2017 and 2021 were included. Data about patient, disease, and treatment characteristics from breast cancer diagnosis to death, along with information about comorbidities, medications, imaging, specialist evaluations, hospitalization, palliative care and home care, hospice admissions, and site of death were collected. RESULTS: 98.3% of the patients received at least one line of active treatment at EoL; 52.8% were hospitalized during the selected period. Palliative (13.9%), psychological (7.4%), and nutritional evaluations (8.2%) were underutilized. Palliative home care was provided to 52% of the patients. Most of the patients died at home (66.1%) and fewer than one out of five (18.2%) died at the hospital. Among the patients who died at home, 27.3% had no palliative support. CONCLUSIONS: Our findings indicate that palliative care in EoL breast cancer patients is still inadequate. Only a minority of patients had psychological and nutritional support While low nutritional support may be explained by the fact that typical symptoms of ABC do not involve the gastrointestinal tract, the lack of psychological support suggests that significant barriers still exist. Data on the site of death are encouraging, indicating that EoL management is increasingly home centered in Italy.

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

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.

Italian survey on managing immune checkpoint inhibitors in oncology during COVID-19 outbreak.

BACKGROUND: During COVID-19 outbreak, oncological care has been reorganized. Patients with cancer have been reported to experience a more severe COVID-19 syndrome; moreover, there are concerns of a potential interference between immune checkpoint inhibitors (ICIs) and SARS-CoV-2 pathogenesis. MATERIALS AND METHODS: Between 6 and 16 May 2020, a 22-item survey was sent to Italian physicians involved in administering ICIs. It aimed at exploring the perception about SARS-CoV-2-related risks in cancer patients receiving ICIs, and the attitudes towards their management. RESULTS: The 104 respondents had a median age of 35.5 years, 58.7% were females and 71.2% worked in Northern Italy. 47.1% of respondents argued a synergism between ICIs and SARS-CoV-2 pathogenesis leading to worse outcomes, but 97.1% would not deny an ICI only for the risk of infection. During COVID-19 outbreak, to reduce hospital visits, 55.8% and 30.8% opted for the highest labelled dose of each ICI and/or, among different ICIs for the same indication, for the one with the longer interval between cycles, respectively. 53.8% of respondents suggested testing for SARS-CoV-2 every cancer patient candidate to ICIs. 71.2% declared to manage patients with onset of dyspnoea and cough as infected by SARS-CoV-2 until otherwise proven; however, 96.2% did not reduce the use of steroids to manage immune-related toxicities. The administration of ICIs in specific situations for different cancer types has not been drastically conditioned. CONCLUSIONS: These results highlight the uncertainties around the perception of a potential interference between ICIs and COVID-19, supporting the need of focused studies on this topic.

Adjuvant treatment in hormone receptor-positive early breast cancer: New approaches of endocrine therapy.

Breast cancer is the most common cancer in women, and luminal breast cancer is the predominant subtype, characterized by the presence of estrogen receptors and/or progesterone receptors in tumor cells. Adjuvant endocrine therapy is the pivotal approach in the management of luminal early breast cancer. Hence, new therapeutic approaches have been studied during the last few years, especially in patients with high risk of recurrence.Here we provide a summary of the most recent clinical trials evaluating adjuvant treatment in hormone-receptors-positive early breast cancer. First, the main cornerstone is related to the role of extended endocrine treatment, which has been widely investigated to access a benefit in disease-free survival and overall survival (only the GIM4 trial has positive feedback about survival) and to tailor the treatment according to patient compliance. The results highlighted an advantage in extending the use of endocrine treatment for at least seven full years, considering aromatase inhibitors as principal drugs. Second, the shift of CDK4/6 inhibitors (CDK4/6i) from advanced to early setting reported positive outcomes, with favorable results from MonarchE and NATALEE trials, using Abemaciclib and Ribociclib respectively, even if non-negligible toxicities have been reported. Last, the use of PARP inhibitors for BRCA1/2 mutated patients has been evaluated in the OlympiA trial (Olaparib), observing a comparable benefit between hormone-receptors-positive and triple-negative early breast cancer.However, more data are still required to better select patients that could benefit more from CDK4/6i considering side effects too, and sequential treatments are still not codified.

Practices and views about palliative care at the end of life: A survey of oncologists from the Italian region of Liguria.

INTRODUCTION: We conducted an online survey to investigate oncologists' clinical practices and views on palliative care at the end of life in the Italian region of Liguria. METHODS: The survey included 29 items divided into three sections: participant characteristics (n=6), hospital resources and practices (n=11), participant practices and views (n=12). RESULTS: Twenty-one of the 41 medical oncologists invited completed the survey (51%). Although almost all reported the presence of palliative medicine physicians at their hospitals (90%), nearly half (48%) stated that palliative medicine physicians were not responsible for managing cancer patients at end of life, and 21% reported routine participation of palliative medicine physicians in multidisciplinary meetings. Thirty-eight percent of the respondents stated they never consulted psychologists regarding end of life patient care, and 43% reported they rarely did. Notably, a substantial proportion of participants stated that they administered active treatments to patients with six months life expectancy. Regarding integration between oncology and palliative medicine, an equal proportion felt it had been fully (48%) or partially achieved (48%) at their hospitals. CONCLUSIONS: Participants seemed fairly satisfied with the level of integration between oncology and palliative medicine at their hospitals, which contrasts with other findings regarding, for instance, the scant participation of palliative medicine physicians in multidisciplinary meetings. Exploring the impact of the novel regional clinical healthcare pathway for palliative care on practices at hospitals in Liguria will be crucial to ensure that cancer patients at end of life receive quality care.

Psychometric properties of patient-reported outcomes Common Terminology Criteria for adverse events (PRO-CTCAE®) in breast cancer patients: The prospective observational multicenter VIP study.

Patients' self-reporting is increasingly considered essential to measure quality-of-life and treatment-related side-effects. However, if multiple patient-reported instruments are used, redundancy may represent an overload for patients. Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE) are a tool allowing direct patients' reporting of side-effects. We tested psychometric properties of a selected list of PRO-CTCAE items, in a cohort of 303 breast cancer patients, using validated instruments for quality of life assessment as anchors. The analysis of convergent validity with HADS (Hospital Anxiety and Depression Scale) and EORTC BR-23 sub-scales, and the analysis of responsiveness with the PGIC (Patients Global Impression of Change) score supported that a selected list of PRO-CTCAE symptoms might represent a standardized, agile tool for both research and practice settings to reduce patient burden without missing relevant information on patient perceptions. Among patients using digital devices, those with a higher education levels required shorter time to fulfil questionnaires. In conclusion, a selected list of PRO-CTCAE items can be considered as a standardized, agile tool for capturing crucial domains of side-effects and quality of life in patients with breast cancer. The study is registered on clinicaltrials.gov (NCT04416672).

Evolving treatments and outcomes in HER2-Positive metastatic breast cancer: Data from the GIM14/BIOMETA study.

BACKGROUND: Treatment for HER2-positive (+) metastatic breast cancer has improved in the last decade. We analyzed treatment changes over time and their impact on patients outcomes in a real-world dataset. METHODS: Data from 637 HER2+ patients with metastatic breast cancer enrolled in the multicenter Italian GIM14/BIOMETA study were retrieved. Progression-free survival (PFS) over time was evaluated according to the type of anti-HER2 therapy, disease onset (de novo vs. relapsing), metastatic site, and year of treatment (2000-2013 vs. 2014-2020). RESULTS: Median follow-up was 64.4 months. Overall, for first-line therapies, mPFS was 16.5 vs 19.5 months for patients treated in 2000-2013 vs 2014-2020 (HR: 0.78, 95% CI:0.65-0.94, P = 0.008). mPFS improved over time in all patients except for those with brain metastasis. Interestingly mPFS was 17.4 vs13.4 months (HR, 1.49; 95% CI, 1.13-1.98, P = 0.005) in 2000-2013 and 24.4 vs 20.9 months (HR 1.04; 95% CI 0.78-1.40 p = 0.77) in 2014-2020 in pts without vs with liver metastases. For second line therapies, the overall median PFS was 9.6 months (95% CI, 8.31-10.97) and did not change over time. CONCLUSION: Median first-line PFS improved since 2014, mainly due to the introduction of pertuzumab. The outcome of patients with liver metastases appears to have improved in recent years. Patients with brain metastases had the worst PFS, which also did not improve over time.

"No Ink on Tumor" in Breast-Conserving Surgery after Neoadjuvant Chemotherapy.

Background/Aim: Patients with Stage I-II breast cancer undergoing breast-conserving surgery after neoadjuvant chemotherapy (BCS-NAC) were retrospectively assessed in order to evaluate the extent of a safe excision margin. Materials and Methods: Between 2003 and 2020, 151 patients underwent risk-adapted BCS-NAC; margin involvement was always assessed at definitive histology. Patients with complete pathological response (pCR) were classified as the RX group, whereas those with residual disease and negative margins were stratified as R0 < 1 mm (margin < 1 mm) and R0 > 1 mm (margin > 1 mm). Results: Totals of 29 (19.2%), 64 (42.4%), and 58 patients (38.4%) were included in the R0 < 1 mm, R0 > 1 mm, and RX groups, respectively, and 2 patients with margin involvement had a mastectomy. Ten instances of local recurrence (6.6%) occurred, with no statistically significant difference in local recurrence-free survival (LRFS) between the three groups. A statistically significant advantage of disease-free survival (p = 0.002) and overall survival (p = 0.010) was observed in patients with pCR. Conclusions: BCS-NAC was increased, especially in HER-2-positive and triple-negative tumors; risk-adapted BCS should be preferably pursued to highlight the cosmetic benefit of NAC. The similar rate of LRFS in the three groups of patients suggests a shift toward the "no ink on tumor" paradigm for patients undergoing BCS-NAC.

How to Protect Ovarian Function before and during Chemotherapy?

A significant number of women receive a cancer diagnosis before their age of natural menopause. Among these patients, the most frequent neoplasms are breast cancer, gynecological, and hematological malignancies. Premature ovarian insufficiency and infertility are among the most feared short- to long-term consequences of anticancer treatments in premenopausal patients. Both patient- and treatment-related characteristics are key factors in influencing the risk of gonadotoxicity with the use of chemotherapy. The cryopreservation of oocytes/embryos is a standard strategy for fertility preservations offered to young women interested in future family planning, but it does not allow gonadal function protection during chemotherapy. Ovarian suppression with gonadotropin-releasing hormone agonist (GnRHa) during chemotherapy is now recommended as an option to reduce the risk of gonadotoxicity in order to avoid the negative consequences of premature ovarian insufficiency in premenopausal women receiving cytotoxic therapy, including those not interested in fertility preservation. This review summarizes the risk of treatment-induced gonadotoxicity in premenopausal patients and the evidence available on the protective role of administering GnRHa during chemotherapy to preserve ovarian function.

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

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.

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

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.