Fertility preservation strategies for breast cancer patients.
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Antineoplastic Agents↗
Biomedical subjects
Marco Venturini
Publications and source records attributed to Marco Venturini.
Infertility and pregnancy after breast cancer: current knowledge and future perspectives.
Fertility impairment induced by adjuvant treatments and potential risk associated with pregnancy, are major concerns of young pre-menopausal patients with early breast cancer. Although current evidences suggest that pregnancy does not negatively affect prognosis, a low rate (3-8%) of pregnancy after breast cancer has been reported. Among the potential causes of such a low rate there are a high chance of spontaneous abortions (25%) as well as the fertility impairment induced by adjuvant treatments. No standard strategy to preserve fertility in breast cancer patients is available so far. Experimental approaches include cryopreservation strategies, and use of gonadotropin-releasing hormone (GnRH) agonists to render germinal epithelium quiescent and less sensitive to the chemotherapy cytotoxicity. Here, we reviewed current knowledge about incidence and risks of pregnancy after breast cancer, risks of ovarian failure after adjuvant treatments and experimental strategies aiming to preserve ovarian function and fertility in young breast cancer patients.
Adult↗
Outcome of patients with HER2-positive advanced breast cancer progressing during trastuzumab-based therapy.
We sought to describe patterns of treatment and clinical outcome in patients with HER2-positive advanced breast cancer progressing on trastuzumab-based therapy. One hundred eighty-four consecutive HER2-positive advanced breast cancer patients received trastuzumab-based therapy between September 1999 and September 2004. Patients were followed up until death or May 2005. For patients progressing on trastuzumab-based therapy, we calculated the response rate (RR) to the first post-progression treatment, overall survival (OS) from the first administration of trastuzumab, time to second progression (TT-SP), and post-progression survival (PPS), according to treatment. At the time of this analysis, 132 patients had progressed on trastuzumab-based therapy, and 89 had died. Of the progressing patients, 21 experienced rapid progression and could not receive additional anticancer treatments;40 patients continued trastuzumab either alone (12 patients with isolated central nervous system progression), with chemotherapy (23 patients), or with endocrine therapy (5 patients); and 71 stopped trastuzumab and received chemotherapy (61 patients) or endocrine therapy (10 patients) as the first post-progression treatment. Excluding patients with rapid progression, clinical outcomes were similar whether trastuzumab was continued or not, in terms of RR (18% and 27%, respectively), OS (31 and 30 months, respectively), TT-SP (6 and 7 months, respectively), and PPS (21 and 19 months, respectively). The clinical outcome of patients with HER2-positive advanced breast cancer progressing during trastuzumab-based therapy might not be influenced by continuing trastuzumab. The optimal therapeutic strategy in this setting of patients needs evaluation in randomized trials.
Adult↗
Dose-dense adjuvant chemotherapy in early breast cancer patients: results from a randomized trial.
BACKGROUND: To determine whether a dose-dense regimen improves outcome in early breast cancer patients, we compared outcomes with the same fluorouracil, epirubicin, and cyclophosphamide (FEC) chemotherapeutic regimen administered every 3 weeks (FEC21) or administered every 2 weeks (FEC14 including support with filgrastim, a granulocyte colony-stimulating factor) in a multicenter phase III randomized trial. METHODS: A total of 1214 patients with early-stage breast cancer were randomly assigned to receive six cycles of FEC14 (604 patients) or of FEC21 (610 patients). Study endpoints were overall survival and event-free survival. Associations were assessed by multivariable analysis with adjustment for age; tumor size; grade; proliferative rate; and menopausal, lymph node, estrogen receptor, and progesterone receptor status. All statistical tests were two-sided. RESULTS: Patients in the FEC14 arm had fewer dose reductions or treatment delays or discontinuation (26%) than those in the FEC21 arm (33%) (difference = 7%, 95% confidence interval [CI] = 2% to 12%; P = .008). FEC14 therapy, compared with FEC21 therapy, was associated with more asthenia (36% versus 29%, difference = 7%, 95% CI = 2% to 12%; P = .01), bone pain (33% versus 4%, difference = 29%, 95% CI = 25% to 33%; P < .001), anemia (38% versus 19%, difference = 19%, 95% CI = 14% to 24%; P < .001), and thrombocytopenia (8% versus 2%, difference = 6%, 95% CI = 4% to 9%; P < .001), but with less leukopenia (12% versus 45%, difference = 33%, 95% CI = 28% to 37%; P < .001). No acute myelogenous leukemia or myelodysplastic syndrome was observed. At a median follow-up of 10.4 years, no statistically significant difference in the hazard of death (hazard ratio [HR] = 0.87, 95% CI = 0.67 to 1.13) or recurrence (HR = 0.88, 95% CI = 0.71 to 1.08) was found between FEC14 and FEC21 groups after adjustment by multivariable analysis. Although the study was underpowered for subset analysis, we found no evidence that the effect of the treatment type was associated with any of the potential prognostic factors. CONCLUSION: Our results support the long-term safety of FEC14 chemotherapy as an adjuvant treatment of breast cancer. However, this therapy was not associated with improved outcome, but because of the limited statistical power of our study, we cannot rule out a modest improvement in outcome associated with FEC14 therapy.
Adult↗
HER2 expression and efficacy of dose-dense anthracycline-containing adjuvant chemotherapy in breast cancer patients.
No data are available on the role of HER2 overexpression in predicting the efficacy of dose-dense anthracycline-containing adjuvant chemotherapy in breast cancer patients. We retrospectively evaluated this role in patients enrolled in a phase III study comparing standard FEC21 (5-fluorouracil, epirubicin, and cyclophosphamide, administered every 3 weeks) vs dose-dense FEC14 (the same regimen repeated every 2 weeks). HER2 status was determined for 731 of 1214 patients. Statistical analyses were performed to test for interaction between treatment and HER2 status with respect to event-free survival (EFS) and overall survival (OS); EFS and OS were compared within each HER2 subgroup and within each treatment arm. Median follow-up was 6.7 years. Among FEC21-treated patients, both EFS (HR=2.07; 95% CI 1.27-3.38) and OS (HR=2.47; 95% CI 1.34-4.57) were significantly worse in HER2 + patients than in HER2 - patients. Among FEC14-treated patients, differences in either EFS (HR=1.21; 95% CI 0.65-2.24) or OS (HR=1.85; 95% CI 0.88-3.89) between HER2 + and HER2 - patients were not statistically significant. Interaction analysis suggested that the use of dose-dense FEC14 might remove the negative prognostic effect of HER2 overexpression on EFS and OS. Our data suggest a potential role of HER-2 overexpression in predicting the efficacy of dose-dense epirubicin-containing chemotherapy and the need to confirm this hypothesis in future prospective studies.
Antibiotics, Antineoplastic↗
Objective response to chemotherapy as a potential surrogate end point of survival in metastatic breast cancer patients.
PURPOSE: To assess the validity of objective response to chemotherapy as a surrogate end point for survival in metastatic breast cancer. PATIENTS AND METHODS: We carried out a meta-analysis on individual data from 2,126 metastatic breast cancer patients who were enrolled onto 10 randomized trials comparing standard versus intensified epirubicin-containing chemotherapy. RESULTS: The intensified chemotherapy was associated with a significantly higher tumor response rate compared with standard chemotherapy (pooled odds ratio for nonresponse, 0.60; 95% CI, 0.51 to 0.72). The intensified regimens also led to better (although not significant) survival (pooled odds ratio, 0.94; 95% CI, 0.86 to 1.04; P = .22). Tumor response was a highly significant predictor of survival (P < .0001). When tumor response was introduced in the Cox model, the hazard ratio in favor of experimental treatment changed from 0.94 to 1.005 (95% CI, 0.91 to 1.11; P = .92), indicating that no residual effect of the experimental treatment on survival was present once tumor response was adjusted for. This suggests that the overall survival benefit of intensified epirubicin was a result of the increase in response rate. The median survival time of patients with complete response and partial response was 28.8 months (95% CI, 25.4 to 45.3 months) and 21.3 months (95% CI, 19.2 to 22.4 months), respectively; whereas, the median survival time of patients with no response was 14.6 months (95% CI, 13.9 to 15.4 months). CONCLUSION: These results support the hypothesis that the achievement of an objective response to chemotherapy in metastatic breast cancer is associated with a true survival benefit. The potential role of objective response as a surrogate end point for survival in chemotherapy trials of metastatic breast cancer warrants further investigation.
Antineoplastic Agents↗
Use of granulocyte colony-stimulating factor: a survey among Italian medical oncologists.
In October 2003, the Italian Association of Medical Oncology (AIOM) published its own guidelines on the use of granulocyte colony-stimulating factor (G-CSF). The present survey was conducted during the same period with the aim of collecting data on the current use of G-CSF to provide a starting point for future evaluations of the implementation of AIOM guidelines. From October 2003 to January 2004, 1591 AIOM members were asked to complete a questionnaire based on specific clinical scenarios, regarding the use of G-CSF for primary and secondary prophylaxis and treatment of neutropenia. The rate of response was 22%. For primary prophylaxis, the majority of physicians avoid using G-CSF, with no difference in cases of adjuvant, curative or palliative chemotherapy (CT). In fact, 67.2% to 74.9% would 'rarely or never' use G-CSF in the proposed clinical scenarios. In chemosensitive tumors, rather than reducing CT doses, 55.7% would use G-CSF as a secondary prophylaxis after afebrile neutropenia (AN), and 68.8% after febrile neutropenia (FN). In elderly patients experiencing FN, 35.7% would reduce the adjuvant CT doses and 23.1% would change the regimen. Most oncologists would use G-CSF to treat neutropenia, and the median duration of G-CSF treatment is less than 1 week and would depend on neutrophil count. Our survey shows that Italian oncologists are particularly oriented towards the use of G-CSF in clinical practice to maintain the CT dose intensity, and are sensitive to the prevention and treatment of not only FN, but also AN. Finally, Italian medical oncologists appear to be very cautious in introducing G-CSF when treating elderly patients.
Data Collection↗
Concomitant versus sequential administration of epirubicin and paclitaxel as first-line therapy in metastatic breast carcinoma: results for the Gruppo Oncologico Nord Ovest randomized trial.
BACKGROUND: The authors performed a randomized trial comprising patients with metastatic breast carcinoma (MBC). They used a noninferiority design to evaluate whether the results of sequential administration of epirubicin and paclitaxel were not markedly worse than the concomitant administration in terms of objective response rates (ORRs). Toxicity profile, quality of life (QOL), and pharmacoeconomic evaluations were evaluated as well. METHODS: In the current study, 202 patients with MBC were randomized to receive either the combination of epirubicin at a dose of 90 mg/m2 plus paclitaxel at a dose of 200 mg/m2 for 8 cycles (concomitant arm, n = 108) or epirubicin at a dose of 120 mg/m2 for 4 cycles followed by paclitaxel at a dose of 250 mg/m2 over 3 hours for 4 cycles every 21 days (sequential arm, n = 94). RESULTS: The authors rejected the null hypothesis that the sequential treatment is less active than the standard concomitant regimen (ORRs: concomitant = 58.5%, sequential = 57.6%). The median progression-free and overall survival periods were 11.0 months (95% confidence interval [95% CI], 9.7-12.3) and 20.0 months (95% CI, 17.2-22.6), respectively, in the concomitant arm and 10.8 months (95% CI, 7.9-13.6) and 26 months (95% CI, 18.1-33.8), respectively, in the sequential arm (P = not significant). Patients who received the sequential regimen experienced a higher incidence of Grade 3/4 (according to the World Health Organization grading system) neutropenia (62.2% of courses vs. 50.62%; P = 0.003) and Grade > or = 2 neuropathy (45.5% vs. 30.4% of patients; P = 0.03), whereas 6 patients who received the concomitant regimen developed Grade II cardiotoxicity according to New York Heart Association criteria. QOL analyses failed to provide clear differences. CONCLUSIONS: The sequential administration of epirubicin and paclitaxel at full doses was found to be as active as their association. Therefore, both the sequential and the combined administration were acceptable options.
Adult↗
Sentinel lymph node biopsy in breast cancer patients: the medical oncology perspective.
Recent data indicates that the sentinel lymph node biopsy (SLNB) is a possible alternative to axillary lymph node dissection (ALND) in early breast cancer patients, with minimal risk of complications. From the medical oncologist's point of view, the impact of SLNB on the management of patients should consider if SLNB is useful to choose adjuvant treatment, if it is adequate to provide local control, and what is the significance of lymph node micrometastases on treatment and staging. Lymph node involvement has always been recognised as the most important prognostic factor in early-stage breast cancer, even if many other parameters have been evaluated in recent years. However, the lack of knowledge of nodal status in patients with false-negative SLNB seems to result in an undertreatment in a very low percentage of patients. Adjuvant chemotherapy and hormonal therapy with tamoxifen are associated with an absolute reduction of the risk of recurrence and death both in node-positive and in node-negative patients, then if patients are treated with modern adjuvant systemic therapy, any effect associated with false negative SLN should be minimised. The impact of axillary treatment on survival is still controversial, but in recent times axillary lymph node positivity is considered as an indicator for high risk of systemic diffusion of the disease rather than a possible origin of systemic metastases. The significance of occult sentinel lymph node metastases detected by immunohistochemistry (IHC) or molecular biology on prognosis is still uncertain. The new version of the staging system of breast cancer has recognised the need for a standard diagnostic approach and of a nomenclature system which also takes SLNB into account.
Axilla↗
Capecitabine in combination with docetaxel and epirubicin in patients with previously untreated, advanced breast carcinoma.
BACKGROUND: The objective of this study was to evaluate the activity and safety of oral capecitabine in combination with docetaxel and epirubicin (TEX) as first-line treatment for patients with locally advanced/metastatic breast carcinoma. METHODS: This open-label, Phase II study was conducted at six Italian centers. Treatment consisted of epirubicin, 75 mg/m(2) (intravenous bolus), and docetaxel, 75 mg/m(2) (1-hour infusion), both administered on Day 1, plus oral capecitabine, 1000 mg/m(2) twice daily, on Days 1-14 of each 3-week treatment cycle. RESULTS: A total of 67 patients received 392 cycles of treatment, with a median of 6 cycles in patients with Stage III disease (n = 34 patients) and a median of 8 cycles in patients with Stage IV disease (n = 33 patients). The objective response rate was 82%, including complete responses in 21% of patients. A greater proportion of patients with Stage III disease achieved tumor responses compared with patients who had Stage IV disease (97% vs. 67%, respectively). Among 34 patients with Stage III disease, pathologic complete responses were confirmed in 10 patients (29%). TEX chemotherapy demonstrated an acceptable safety profile. There was a low incidence of Grade 3 adverse events, and Grade 4 adverse events were particularly rare (4%). The most common Grade 3-4 adverse event was febrile neutropenia, which occurred in 16% of patients. CONCLUSIONS: TEX combination therapy has important antitumor activity and an acceptable safety profile in this setting. A large, randomized, Phase III trial is ongoing to compare TEX chemotherapy with an epirubicin plus docetaxel regimen in patients with untreated, advanced breast carcinoma.
Adult↗
Herceptin in elderly patients.
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Age Factors↗
[New therapeutic prospects with capecitabin in breast carcinoma].
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Antimetabolites, Antineoplastic↗