Background
Follow‐up examinations are commonly performed after primary treatment for women with breast cancer. They are used to detect recurrences at an early (asymptomatic) stage. This is an update ...of a Cochrane review first published in 2000.
Objectives
To assess the effectiveness of different policies of follow‐up for distant metastases on mortality, morbidity and quality of life in women treated for stage I, II or III breast cancer.
Search methods
For this 2014 review update, we searched the Cochrane Breast Cancer Group's Specialised Register (4 July 2014), MEDLINE (4 July 2014), Embase (4 July 2014), CENTRAL (2014, Issue 3), the World Health Organization (WHO) International Clinical Trials Registry Platform (4 July 2014) and ClinicalTrials.gov (4 July 2014). References from retrieved articles were also checked.
Selection criteria
All randomised controlled trials (RCTs) assessing the effectiveness of different policies of follow‐up after primary treatment were reviewed for inclusion.
Data collection and analysis
Two review authors independently assessed trials for eligibility for inclusion in the review and risk of bias. Data were pooled in an individual patient data meta‐analysis for the two RCTs testing the effectiveness of different follow‐up schemes. Subgroup analyses were conducted by age, tumour size and lymph node status.
Main results
Since 2000, one new trial has been published; the updated review now includes five RCTs involving 4023 women with breast cancer (clinical stage I, II or III).
Two trials involving 2563 women compared follow‐up based on clinical visits and mammography with a more intensive scheme including radiological and laboratory tests. After pooling the data, no significant differences in overall survival (hazard ratio (HR) 0.98, 95% confidence interval (CI) 0.84 to 1.15, two studies, 2563 participants, high‐quality evidence), or disease‐free survival (HR 0.84, 95% CI 0.71 to 1.00, two studies, 2563 participants, low‐quality evidence) emerged. No differences in overall survival and disease‐free survival emerged in subgroup analyses according to patient age, tumour size and lymph node status before primary treatment. In 1999, 10‐year follow‐up data became available for one trial of these trials, and no significant differences in overall survival were found. No difference was noted in quality of life measures (one study, 639 participants, high‐quality evidence).
The new included trial, together with a previously included trial involving 1264 women compared follow‐up performed by a hospital‐based specialist versus follow‐up performed by general practitioners. No significant differences were noted in overall survival (HR 1.07, 95% CI 0.64 to 1.78, one study, 968 participants, moderate‐quality evidence), time to detection of recurrence (HR 1.06, 95% CI 0.76 to 1.47, two studies, 1264 participants, moderate‐quality evidence), and quality of life (one study, 356 participants, high‐quality evidence). Patient satisfaction was greater among patients treated by general practitioners. One RCT involving 196 women compared regularly scheduled follow‐up visits versus less frequent visits restricted to the time of mammography. No significant differences emerged in interim use of telephone and frequency of general practitioners's consultations.
Authors' conclusions
This updated review of RCTs conducted almost 20 years ago suggests that follow‐up programs based on regular physical examinations and yearly mammography alone are as effective as more intensive approaches based on regular performance of laboratory and instrumental tests in terms of timeliness of recurrence detection, overall survival and quality of life.
In two RCTs, follow‐up care performed by trained and not trained general practitioners working in an organised practice setting had comparable effectiveness to that delivered by hospital‐based specialists in terms of overall survival, recurrence detection, and quality of life.
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.
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).
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).
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.
Fertility and pregnancy issues are of key importance for young breast cancer patients. Despite several advances in the field, there are still multiple unmet needs and barriers in discussing and ...dealing with these concerns. To address the significant challenges related to fertility and pregnancy issues, the PREgnancy and FERtility (PREFER) study was developed as a national comprehensive program aiming to optimize care and improve knowledge around these topics.
The PREFER study is a prospective cohort study conducted across several Italian institution affiliated with the Gruppo Italiano Mammella (GIM) group evaluating patterns of care and clinical outcomes of young breast cancer patients dealing with fertility and pregnancy issues. It is composed of two distinctive studies: PREFER-FERTILITY and PREFER-PREGNANCY. The PREFER-FERTILITY study is enrolling premenopausal patients aged 18-45 years, diagnosed with non-metastatic breast cancer, who are candidates to (neo)adjuvant chemotherapy and not previously exposed to anticancer therapies. The primary objective is to obtain and centralize data about patients' preferences and choices towards the available fertility preserving procedures. The success and safety of these strategies and the hormonal changes during chemotherapy and study follow-up are secondary objectives. The PREFER-PREGNANCY study is enrolling survivors achieving a pregnancy after prior history of breast cancer and patients diagnosed with pregnancy-associated breast cancer (PABC). The primary objectives are to obtain and centralize data about the management and clinical outcomes of these women. Patients' survival outcomes, and the fetal, obstetrical and paediatric care of their children are secondary objectives. For both studies, the initial planned recruitment period is 5 years and patients will remain in active follow-up for up to 15 years. The PREFER-FERTILITY study was first activated in November 2012, and the PREFER-PREGNANCY study in May 2013.
The PREFER study is expected to support and improve oncofertility counseling in Italy, to explore the real need of fertility preserving procedures, and to acquire prospectively more robust data on the efficacy and safety of the available strategies for fertility preservation, on the management of breast cancer survivors achieving a pregnancy and of women with PABC (including the possible short- and long-term complications in their children).
ClinicalTrials.gov identifier: NCT02895165 (Retrospectively registered in August 2016).
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Approximately 5–10% of unselected breast cancer (BC) patients retain a hereditary predisposition related to a germline mutation in BRCA1/2 genes. The poly-ADP ribose polymerase (PARP)-inhibitors ...olaparib and talazoparib have been granted marketing authorization by both FDA and EMA for adults with BRCA1/2 germline mutations and HER2-negative (HER2-) advanced BC based on the results from the phase III OlympiAd and EMBRACA trials.
The panel of the Italian Association of Medical Oncology (AIOM) Clinical Practice Guidelines on Breast Cancer addressed two critical clinical questions, adopting the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach and the Evidence to Decision framework (EtD), to develop recommendations on the use of PARP-inhibitors, with respect to single-agent chemotherapy, in patients with BRCA-related triple-negative (clinical question 1) and hormone receptor-positive (HR+)/HER2- (clinical question 2) advanced BC.
Two studies were eligible (OlympiAd and EMBRACA). For both clinical questions, the Panel judged the benefit/harm balance probably in favor of the intervention, given the favorable impact in terms of PFS, ORR, and QoL at an acceptable cost in terms of toxicity; the overall certainty of the evidence was low. The panel's final recommendations were conditional in favor of PARP-inhibitors over single-agent chemotherapy in both HR+/HER2-and triple-negative BC. Finally, the Panel identified and discussed areas of uncertainty calling for further exploration.
The Panel of AIOM BC Clinical Practice Guideline provided clinical recommendations on the use of PARP-inhibitors, with respect to single-agent chemotherapy, in patients with BRCA-related HER2-advanced BC by adopting the GRADE methodology.
•Use of PARP-inhibitors in BRCA-related HER2-advanced BC has been addressed by the Italian Association of Medical Oncology.•The Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach has been adopted.•HR+/HER2-and triple-negative BC subtypes have been addressed in two separate clinical questions.•Germline BRCA testing in HER2-advanced BC has a predictive value, being indicated independently from familial criteria.
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.
In the absence of identified therapeutic targets, chemotherapy is the main systemic treatment option for triple-negative breast cancer (TNBC). The achievement of a pathological complete response ...(pCR) after neoadjuvant chemotherapy leads to good outcome, whereas patients not achieving a pCR are at high risk of relapse. Various trials have evaluated the inclusion of platinum in neoadjuvant chemotherapy regimens for TNBC, leading to non-univocal results. The panel of the Italian Association of Medical Oncology (AIOM) Guidelines on Breast Cancer developed a clinical recommendation on the addition of platinum to anthracycline/taxane-based neoadjuvant chemotherapy for TNBC by using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology and the Evidence to Decision framework (EtD). Five studies were eligible. The panel identified the following outcomes of benefit: pCR (critical), disease/event-free survival (DFS/EFS, critical), and overall survival (OS, critical). The panel identified febrile neutropenia (critical), serious adverse events (critical), anemia grade 3-4 (important), thrombocytopenia grade 3-4 (important) as outcomes of harms. The probability of pCR was higher in the platinum-based chemotherapy group versus control group (RR = 1.45, 95%CI 1.28-1.64); however, no impact on long-term outcome was observed. Neoadjuvant treatment regimens containing platinum resulted in a non-significant increase in the risk of febrile neutropenia and in a significant increase in the risk serious adverse events, G3-G4 anemia and G3-G4 thrombocytopenia: 11.3% versus 0.8%, RR = 15.66 (95%CI 6.38-38.44). The panel judged uncertain/favorable the benefit/harms balance. The panel's final recommendation was conditional in favor of the inclusion of platinum in anthracycline/taxane-based neoadjuvant regimens for TNBC.
Summary Luteinising hormone releasing hormone agonists (LH-RHa) induce ovarian suppression in premenopausal women that is usually reversible on cessation of therapy. They act by binding to pituitary ...LH-RH receptors, resulting in down regulation of receptors and subsequent suppression of luteinising hormone and estradiol. LH-RHa are effective in the treatment of advanced breast cancer in premenopausal women but their role as adjuvant treatment of early breast cancer is still controversial. Approximately 60% of tumors in premenopausal women are hormone sensitive and these patients are candidates for hormonal treatment. Tamoxifen for 5 years is considered the standard endocrine therapy for all premenopausal women with hormone sensitive breast cancer. There is no definitive evidence of additional benefit associated with the use of LH-RHa administered as an alternative or in addition to tamoxifene. In this review we discuss available data on the role of LH-RHa alone or in combination with tamoxifen; on the role of LH-RHa in combination with aromatase inhibitors; and on the potential role of LH-RHa as a strategy to preserve ovarian function during adjuvant chemotherapy.
Abstract Background The role of temporary ovarian suppression with gonadotropin-releasing hormone analogues (GnRHa) in the prevention of chemotherapy-induced premature ovarian failure (POF) is still ...controversial. We conducted a systematic review and meta-analysis of randomized trials evaluating the efficacy of GnRHa, given before and during chemotherapy, in the prevention of POF in premenopausal cancer patients. Methods Studies were retrieved by searching PubMed, Web of Knowledge database and the proceedings of major conferences. We calculated Odds Ratios (OR) and 95% confidence intervals (CIs) for POF from each trial and obtained pooled estimates through the random effects model as suggested by DerSimonian and Laird. Results Nine studies were included in the meta-analysis with 225 events of POF occurring in 765 analyzed patients. The pooled OR estimate indicates a highly significant reduction in the risk of POF (OR = 0.43; 95% CI: 0.22–0.84; p = 0.013) in patients receiving GnRHa. There was statistically significant heterogeneity among studies ( I2 = 55.8%; p = 0.012). There was no evidence of publication bias. Subgroups analyses showed that the protective effect of GnRHa against POF was similar in subgroups of patients defined by age and timing of POF assessment, while it was present in breast cancer but unclear in ovarian cancer and lymphoma patients. Conclusions Our pooled analysis of randomized studies shows that the temporary ovarian suppression induced by GnRHa significantly reduces the risk of chemotherapy-induced POF in young cancer patients.
CONTEXT Premenopausal patients with breast cancer are at high risk of premature ovarian failure induced by systemic treatments, but no standard strategies for preventing this adverse effect are yet ...available. OBJECTIVE To determine the effect of the temporary ovarian suppression obtained by administering the gonadotropin-releasing hormone analogue triptorelin during chemotherapy on the incidence of early menopause in young patients with breast cancer undergoing adjuvant or neoadjuvant chemotherapy. DESIGN, SETTING, AND PATIENTS The PROMISE-GIM6 (Prevention of Menopause Induced by Chemotherapy: A Study in Early Breast Cancer Patients–Gruppo Italiano Mammella 6) study, a parallel, randomized, open-label, phase 3 superiority trial, was conducted at 16 sites in Italy and enrolled 281 patients between October 2003 and January 2008. The patients were premenopausal women with stage I through III breast cancer who were candidates for adjuvant or neoadjuvant chemotherapy. Assuming a 60% rate of early menopause in the group treated with chemotherapy alone, it was estimated that 280 patients had to be enrolled to detect a 20% absolute reduction in early menopause in the group treated with chemotherapy plus triptorelin. The intention-to-treat analysis was performed by including all randomized patients and using imputed values for missing data. INTERVENTIONS Before beginning chemotherapy, patients were randomly allocated to receive chemotherapy alone or combined with triptorelin. Triptorelin was administered intramuscularly at a dose of 3.75 mg at least 1 week before the start of chemotherapy and then every 4 weeks for the duration of chemotherapy. MAIN OUTCOME MEASURE Incidence of early menopause (defined as no resumption of menstrual activity and postmenopausal levels of follicle-stimulating hormone and estradiol 1 year after the last cycle of chemotherapy). RESULTS The clinical and tumor characteristics of the 133 patients randomized to chemotherapy alone and the 148 patients randomized to chemotherapy plus triptorelin were similar. Twelve months after the last cycle of chemotherapy (last follow-up, August 18, 2009), the rate of early menopause was 25.9% in the chemotherapy-alone group and 8.9% in the chemotherapy plus triptorelin group, an absolute difference of −17% (95% confidence interval, −26% to −7.9%; P < .001). The odds ratio for treatment-related early menopause was 0.28 (95% confidence interval, 0.14 to 0.59; P < .001). CONCLUSION The use of triptorelin-induced temporary ovarian suppression during chemotherapy in premenopausal patients with early-stage breast cancer reduced the occurrence of chemotherapy-induced early menopause. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00311636
IMPORTANCE: Whether the administration of luteinizing hormone–releasing hormone analogues (LHRHa) during chemotherapy is a reliable strategy to preserve ovarian function is controversial owing to ...both the lack of data on long-term ovarian function and pregnancies and the safety concerns about the potential negative interactions between endocrine therapy and chemotherapy. OBJECTIVE: To evaluate long-term results of LHRHa-induced ovarian suppression during breast cancer chemotherapy. DESIGN, SETTING, AND PARTICIPANTS: Parallel, randomized, open-label, phase 3 superiority trial conducted at 16 Italian sites. Between October 2003 and January 2008, 281 premenopausal women with stage I to III hormone receptor–positive or hormone receptor–negative breast cancer were enrolled. Last annual follow-up was June 3, 2014. INTERVENTIONS: Patients were randomized to receive adjuvant or neoadjuvant chemotherapy alone (control group) or chemotherapy plus triptorelin (LHRHa group). MAIN OUTCOMES AND MEASURES: The primary planned end point was incidence of chemotherapy-induced early menopause. Post hoc end points were long-term ovarian function (evaluated by yearly assessment of menstrual activity and defined as resumed by the occurrence of at least 1 menstrual cycle), pregnancies, and disease-free survival (DFS). RESULTS: A total of 281 women (median age, 39 range, 24-45 years) were randomized. Median follow-up was 7.3 years (interquartile range, 6.3-8.2 years). The 5-year cumulative incidence estimate of menstrual resumption was 72.6% (95% CI, 65.7%-80.3%) among the 148 patients in the LHRHa group and 64.0% (95% CI, 56.2%-72.8%) among the 133 patients in the control group (hazard ratio HR, 1.28 95% CI, 0.98-1.68; P = .07; age-adjusted HR, 1.48 95% CI, 1.12-1.95; P = .006). Eight pregnancies (5-year cumulative incidence estimate of pregnancy, 2.1% 95% CI, 0.7%-6.3%) occurred in the LHRHa group and 3 (5-year cumulative incidence estimate of pregnancy, 1.6% 95% CI, 0.4%-6.2%) in the control group (HR, 2.56 95% CI, 0.68-9.60; P = .14; age-adjusted HR, 2.40 95% CI, 0.62-9.22; P = .20). Five-year DFS was 80.5% (95% CI, 73.1%-86.1%) in the LHRHa group and 83.7% (95% CI, 76.1%-89.1%) in the control group (LHRHa vs control: HR, 1.17 95% CI, 0.72-1.92; P = .52). CONCLUSIONS AND RELEVANCE: Among premenopausal women with either hormone receptor–positive or hormone receptor–negative breast cancer, concurrent administration of triptorelin and chemotherapy, compared with chemotherapy alone, was associated with higher long-term probability of ovarian function recovery, without a statistically significant difference in pregnancy rate. There was no statistically significant difference in DFS for women assigned to triptorelin and those assigned to chemotherapy alone, although study power was limited. TRIAL REGISTRATION: clinicaltrials.gov Identifier:NCT00311636
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