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A Goldhirsch

Publications and source records attributed to A Goldhirsch.

At least 19 recordsLinked to original sources
PubMed2006

When can a second conservative approach be considered for ipsilateral breast tumour recurrence?

BACKGROUND: Mastectomy is considered the treatment of choice in patients with ipsilateral breast tumour recurrence (IBTR) after breast-conserving surgery (BCS). PATIENTS AND METHODS: One hundred and sixty-one patients with invasive IBTR who underwent a second conservative approach were retrospectively evaluated in order to describe prognosis, determine predictive factors of outcome and select the subset of patients with the best local control. RESULTS: Fifty-seven patients (35.4%) relapsed after IBTR. Thirty-four patients (21.1%) had further in-breast recurrences and four patients (2.5%) had skin relapses. Five years cumulative incidence of local relapse was 31.4%. Twenty-four patients (17.8%, 5 years cumulative incidence) died during the follow-up. At the multivariate analysis, recurrent tumour size >2 cm was found to affect local-disease-free survival [hazard ratio (HR): 2.8, 95% confidence interval (CI) 1.2-6.2], whereas Ki-67 >or=20% and time to relapse 48 months, eight (12.8%, 5 years cumulative incidence) had further local relapses. CONCLUSIONS: Some patients with IBTR might receive a second BCS, especially when a good local control can be estimated (small recurrent tumour, late relapse), also taking into account patients' preference.

Adult↗
PubMed2006

Breast cancer in Hodgkin's disease and non-Hodgkin's lymphoma survivors.

BACKGROUND: Better therapeutic approaches for patients with Hodgkin's disease (HD) and non-Hodgkin's lymphomas (NHL) resulted in high cure rates, at cost of serious late side effects. Second primary tumours are a major concern for long-term survivors, and breast cancer (BC) is the most common solid tumour among women treated for HD. MATERIALS AND METHODS: Fifty-three women treated for primary BC with previous history of malignant lymphoma were identified in our institution, 35 with HD (66%), 18 (34%) with NHL. A comparison group was randomly selected from our database matching for each patient with previous lymphoma, two patients with primary BC (rate 1 : 2) for age, stage (pathological tumour size [pT] status and nodal status), year of diagnosis, and estrogen and progesterone status (positive versus negative). The primary end points were disease-free survival (DFS) and overall survival (OS). RESULTS: The two groups of patients were compared for biological features: histopathological diagnosis, grading, lymphatic invasion, c-erbB2 overexpression, and Ki-67. Considering these variables, no significant differences were observed between the two groups with the exception of Ki-67, which was found higher in those with previous HD or NHL (65% versus 49%, respectively, P = 0.0526, borderline significant). Comparing the two groups for treatment approach, no differences were found for surgical and medical therapy (endocrine therapy and chemotherapy). However, regarding patients with node-positive disease (14 versus 35 patients), five patients in the lymphoma group (36%), compared with 24 (69%) in the matched group received anthracycline-based therapy (P = 0.0345). As expected, radiotherapy was used very differently in the two groups, with 36% of patients in the study group undergoing intraoperative radiotherapy with electrons versus 10% in the control group (P = 0.0001). Five-year DFS was 54.5% for the study cohort compared with 91% for controls (P < 0.0001). Five-year OS percentages were also statistically different (86.6% and 98.6%, respectively, P = 0.031). CONCLUSIONS: Previous history of malignant lymphoma is a negative prognostic factor for women diagnosed subsequently with BC. Some undertreatment of women with the latter might be hypothesised as the reason for the worse outcome. Influence of other variables, like previous exposure to cytotoxics, or some unknown biological features related to the previous disease and treatment, should still be investigated in the attempt to improve the dire outcome of these patients.

Adolescent↗
PubMed2006

First--select the target: better choice of adjuvant treatments for breast cancer patients.

St Gallen Expert Consensus meetings update evidence on treatment of early breast cancer every 2 years and interpret its significance for treatment of individual patients. Such interpretation is controversial. Clinical decisions cannot, however, be postponed, and the harms of failing to tailor treatment must be balanced against those of overinterpretation. Since the ninth meeting in January 2005, an extraordinary year of progress has significantly changed the landscape in breast cancer therapy. The panel in January recommended a fundamental change in selection of adjuvant systemic therapy, giving prime attention to endocrine responsiveness. Primarily, three categories were acknowledged: endocrine responsive in which the primary treatment should be endocrine, endocrine non-responsive in which endocrine therapy should not be used, and an intermediate group for which both endocrine and other therapies should be offered. Secondarily, three risk groups were defined: low, intermediate, and high, slightly modifying the previous classification. In June 2005, three trials, supported in December by a fourth, demonstrated the additional contribution of targeted therapy with trastuzumab in appropriately selected patients. Reports from several trials strengthened the evidence supporting the inclusion of taxanes, though controversy persists concerning their use in endocrine-responsive disease. This commentary midway between St Gallen meetings, therefore, emphasizes how new information influences algorithms for selecting adjuvant therapy in a rapidly changing environment.

Antineoplastic Agents, Hormonal↗
PubMed2006

Clinical benefit of fulvestrant in postmenopausal women with advanced breast cancer and primary or acquired resistance to aromatase inhibitors: final results of phase II Swiss Group for Clinical Cancer Research Trial (SAKK 21/00).

BACKGROUND: The aim of this study was to evaluate the efficacy and tolerability of fulvestrant, an estrogen receptor antagonist, in postmenopausal women with hormone-responsive tumors progressing after aromatase inhibitor (AI) treatment. PATIENTS AND METHODS: This is a phase II, open, multicenter, noncomparative study. Two patient groups were prospectively considered: group A (n=70) with AI-responsive disease and group B (n=20) with AI-resistant disease. Fulvestrant 250 mg was administered as intramuscular injection every 28 (+/-3) days. RESULTS: All patients were pretreated with AI and 84% also with tamoxifen or toremifene; 67% had bone metastases and 45% liver metastases. Fulvestrant administration was well tolerated and yielded a clinical benefit (CB; defined as objective response or stable disease [SD] for >or=24 weeks) in 28% (90% confidence interval [CI] 19% to 39%) of patients in group A and 37% (90% CI 19% to 58%) of patients in group B. Median time to progression (TTP) was 3.6 (95% CI 3.0 to 4.8) months in group A and 3.4 (95% CI 2.5 to 6.7) months in group B. CONCLUSIONS: Overall, 30% of patients who had progressed following prior AI treatment gained CB with fulvestrant, thereby delaying indication to start chemotherapy. Prior response to an AI did not appear to be predictive for benefit with fulvestrant.

Adult↗
PubMed2006

Bisphosphonates and jaw osteonecrosis in patients with advanced breast cancer.

BACKGROUND: In recent years, several cases of mandibular necrosis associated with long-term use of bisphosphonates have been reported. The estimated incidence varies from 1% to 4.6%. PATIENTS AND METHODS: We conducted an observational study with the aim of determining the incidence of jaw osteonecrosis in advanced breast cancer patients with bone metastases under bisphosphonate treatment and to identify subjects at higher risk of developing this complication evaluating preclinical signs. We considered two groups of patients. All the patients complaining of odontostomatological symptoms underwent maxillary CT scan and maxillo-surgeon clinical examination. Asymptomatic patients were asked to perform a standard orthopantomography (OPT). RESULTS: From February 2005 to October 2005, we observed five patients with jaw bone necrosis (6%). Diagnosis was radiological and clinical. In two patients a confirmatory biopsy was performed. In the same time interval, OPTs were collected from 76 asymptomatic patients. Three OPTs revealed radiological features of suspicious mandibular necrosis. Maxillary CT scan confirmed the presence of an osteolityc area with signs of periosteal reaction. All the three patients were referred to maxillo-surgeon and two out of three patients underwent mandibular biopsy, but histopathological results were not conclusive. CONCLUSIONS: In our experience, the incidence of jaw bone necrosis in breast cancer patients seems to be higher than in other reports (6%). Radiological features of suspicious jaw necrosis were observed in three asymptomatic patients. We do not know how these findings should be considered. Anyway, standard OPT is a simple procedure, and may allow identification of periodontal conditions that in some way can predispose to the development of this uncommon event.

Adult↗
PubMed2006

Role of endocrine responsiveness and adjuvant therapy in very young women (below 35 years) with operable breast cancer and node negative disease.

BACKGROUND: There is limited knowledge about prognosis, and treatment effects in young women with node-negative disease. PATIENTS AND METHODS: We evaluated biological features, treatment recommendations and prognosis for 841 premenopausal patients with pT1-3, pN0 and M0, operated from 1997 to 2001. RESULTS: Patients below 35 years (101, 12%) were more likely to have tumors > 2 cm (35.6% versus 24.2%, P = 0.002), grade 3 (48.5% versus 31.9%, P = 0.009) and with elevated Ki-67 expression (62.4% versus 50.7%, P = 0.002). At the multivariate analysis a statistically significant difference in disease-free survival (DFS, HR 4.44; 95% CI 2.53 to 7.78, P < 0.0001), risk of distant metastases (DDFS) (HR 3.23; 95% CI 1.32 to 7.94, P = 0.011) and overall survival (OS) (HR 2.89; 95% CI 1.06 to 7.87, P = 0.038) was observed for younger versus older patients and in the subgroup with endocrine responsive tumors (DFS, HR 5.17, 95% CI 2.72-9.83, P = < 0.0001; DDFS, 3.76, 95% CI 1.33-10.6, P = 0.013; OS, 4.71, 95% CI 1.09-20.4, P = 0.039 ). CONCLUSIONS: Compared with less young, very young patients with endocrine responsive and node-negative breast cancer have a worse prognosis. Tailored treatments should be explored in this cohort of patients.

Adult↗
PubMed2006

Identifying breast cancer patients at risk for Central Nervous System (CNS) metastases in trials of the International Breast Cancer Study Group (IBCSG).

BACKGROUND: We sought to determine whether a high-risk group could be defined among patients with operable breast cancer in whom a search of occult central nervous system (CNS) metastases was justified. PATIENTS AND METHODS: We evaluated data from 9524 women with early breast cancer (42% node-negative) who were randomized in International Breast Cancer Study Group clinical trials between 1978 and 1999, and treated without anthracyclines, taxanes, or trastuzumab. We identified patients whose site of first event was CNS and those who had a CNS event at any time. RESULTS: Median follow-up was 13 years. The 10-year incidence (10-yr) of CNS relapse was 5.2% (1.3% as first recurrence). Factors predictive of CNS as first recurrence included: node-positive disease (10-yr = 2.2% for > 3 N+), estrogen receptor-negative (2.3%), tumor size > 2 cm (1.7%), tumor grade 3 (2.0%), < 35 years old (2.2%), HER2-positive (2.7%), and estrogen receptor-negative and node-positive (2.6%). The risk of subsequent CNS recurrence was elevated in patients experiencing lung metastases (10-yr = 16.4%). CONCLUSION: Based on this large cohort we were able to define risk factors for CNS metastases, but could not define a group at sufficient risk to justify routine screening for occult CNS metastases.

Breast Neoplasms↗
PubMed2005

Metronomic low-dose oral cyclophosphamide and methotrexate plus or minus thalidomide in metastatic breast cancer: antitumor activity and biological effects.

BACKGROUND: We previously demonstrated efficacy and impact on serum vascular endothelial growth factor (VEGF) for metronomic cyclophosphamide (C) and methotrexate (M) in patients with breast cancer. New metronomic schedules were investigated. PATIENTS AND METHODS: Patients with advanced breast cancer were randomized to receive oral C (50 mg daily) and M (2.5 mg twice daily on days 1 and 4) (arm A) or the same regimen plus thalidomide (200 mg daily) (arm B). RESULTS: The mean VEGF level decreased from 378.9 (+/-274.4) pg/ml at baseline to 305.9 (+/-203.6) pg/ml at 2 months (P<0.001), with similar change with respect to baseline in both arms. In 171 evaluable patients we observed three complete remissions (CR) in both arms A and B, 15 partial remission (PR) in arm A and seven in arm B, for an overall response of 20.9% [95% confidence interval (CI) 12.9% to 31%] in arm A and 11.8% (95% CI 5.8% to 20.6%) in arm B. The clinical benefit (CR+PR+SD>or=24 weeks) was 41.5% for both arms. Toxicity was generally mild. Higher neurological toxicity (2% versus 60%; P<0.0001) and constipation (8% versus 51%; P<0.0001) was observed in arm B. CONCLUSIONS: Metronomic low-dose CM induced a drop in VEGF, and was effective and minimally toxic. The addition of thalidomide did not improve results.

Administration, Oral↗
PubMed2005

Dose-finding and pharmacokinetic study of an all-oral combination regimen of oral vinorelbine and capecitabine for patients with metastatic breast cancer.

PURPOSE: A phase I study was performed to determine the maximal tolerated dose, recommended doses (RDs), safety and efficacy of oral vinorelbine when combined with capecitabine in an all-oral chemotherapy regimen in patients with metastatic breast cancer (MBC), with pharmacokinetic blood sampling to investigate potential drug-drug interactions. PATIENTS AND METHODS: Forty-four patients with MBC received as first- or second-line chemotherapy, oral vinorelbine at a dose of 60 or 80 mg/m2 on days 1 and 8 (and 15) with escalating doses of capecitabine from 1650 to 2500 mg/m2/day days 1-14 every 3 or 4 weeks. Three schedules were tested: day 1, day 8 and weekly regimens of oral vinorelbine with a 14-day course of capecitabine every 3 weeks; and a days 1 and 8 regimen of oral vinorelbine with a 14-day course of capecitabine every 4 weeks. RESULTS: With oral vinorelbine at 60 mg/m2, the RDs were established as oral vinorelbine 60 mg/m2 on days 1 and 8 plus capecitabine 2250 mg/m2/day days 1-14 and oral vinorelbine 60 mg/m2/week plus capecitabine 2000 mg/m2/day days 1-14. With oral vinorelbine at 80 mg/m2, the RD was oral vinorelbine 80 mg/m2 on days 1 and 8 plus capecitabine 2000 mg/m2/day days 1-14. Neutropenia was the main dose-limiting toxicity of the combination; it was reported in 40 patients (90.9%), with grade 3 in 14 patients (31.8%) and 6.2% of cycles, and grade 4 in 12 patients (27.3%) and 4.3% of cycles. Complications were rare with only three patients experiencing febrile neutropenia (one episode each). The most frequent non-haematological toxicity was gastrointestinal; however, the incidence of grade 3 was low, with no episode of grade 4. Hand-foot syndrome was reported in 14 patients (31.8%) and 22.6% of cycles, with grade 2 in two patients (4.5%) and 1.2% of cycles (two episodes each). No episode of grade 3 was observed. Objective responses were reported in 18 patients (three complete responses and 15 partial responses), yielding a response rate of 40.9% in the intention-to-treat population according to the investigator assessment. Results from the pharmacokinetic study demonstrated the absence of mutual pharmacokinetic interactions when both drugs were co-administered. CONCLUSIONS: The combination of oral vinorelbine and capecitabine is safe and easy to administer in an outpatient setting. This all-oral combination chemotherapy may offer a good alternative to the intravenous route for patients with MBC. Based on these promising results, a phase II study has started using oral vinorelbine 60 mg/m2/week with capecitabine 2000 mg/m2/day days 1-14 every 3 weeks as first-line chemotherapy in patients with MBC.

Administration, Oral↗
PubMed2005

Breast cancer vaccines: a clinical reality or fairy tale?

The characterization of tumor antigens recognized by immune effector cells has opened the perspective of developing therapeutic vaccines in the field of breast cancer. The potential advantages of the vaccines are: (i) the induction of a robust immune response against tumors that are spontaneously weekly immunogenic; (ii) the tumor specificity for some antigens; (iii) the good tolerance and safety profile and (iv) the long-term immune memory, critical to prevent efficiently tumor recurrence. Most trials evaluating breast cancer vaccines have been carried out in patients with extended metastatic breast cancer, characterized by aggressive tumors, resistant to standard cytotoxic treatments, so that clinical efficacy was difficult to achieve. However, some significant immune responses against tumor antigens induced upon vaccinations were recorded. The aim of this review is to analyze the activity of vaccination strategies in current clinical trials. Data of clinical activity have been observed by using vaccines targeting HER2/neu protein, human telomerase reverse transcriptase, carcinoembryonic antigen and carbohydrate antigen given after stem cell rescue. The review discusses possible future directions for vaccine development and applications in the adjuvant setting.

Antigens, Neoplasm↗
PubMed2005

Meeting highlights: international expert consensus on the primary therapy of early breast cancer 2005.

The ninth St Gallen (Switzerland) expert consensus meeting in January 2005 made a fundamental change in the algorithm for selection of adjuvant systemic therapy for early breast cancer. Rather than the earlier approach commencing with risk assessment, the Panel affirmed that the first consideration was endocrine responsiveness. Three categories were acknowledged: endocrine responsive, endocrine non-responsive and tumors of uncertain endocrine responsiveness. The three categories were further divided according to menopausal status. Only then did the Panel divide patients into low-, intermediate- and high-risk categories. It agreed that axillary lymph node involvement did not automatically define high risk. Intermediate risk included both node-negative disease (if some features of the primary tumor indicated elevated risk) and patients with one to three involved lymph nodes without additional high-risk features such as HER 2/neu gene overexpression. The Panel recommended that patients be offered chemotherapy for endocrine non-responsive disease; endocrine therapy as the primary therapy for endocrine responsive disease, adding chemotherapy for some intermediate- and all high-risk groups in this category; and both chemotherapy and endocrine therapy for all patients in the uncertain endocrine response category except those in the low-risk group.

Antineoplastic Agents, Hormonal↗
PubMed2005

Dose-finding study of weekly docetaxel, anthracyclines plus fluoropyrimidines as first-line treatment in advanced breast cancer.

BACKGROUND: The efficacy and safety of prolonged fluoropyrimidines, either intravenously or orally, prompted their integration with taxanes and anthracyclines in the treatment of advanced breast cancer (ABC). We conducted three subsequent dose-finding studies on first-line chemotherapy in ABC with anthracyclines, either epirubicin (E) or doxorubicin (A), and docetaxel (T), both given on days 1 and 8 every 3 weeks, plus continuous infusion (CI) 5-fluorouracil (F) or capecitabine (X). PATIENTS AND METHODS: Sixty-two patients (37% dominant visceral disease, 48% locally advanced disease, 45% two or more sites involved), received different doses of T (60--80 mg/m(2)), A (40--50 mg/m(2)) or E (60--90 mg/m(2)) and X (1,650 and 2,000 mg/m(2)), or CI F at a fixed daily dose of 200 mg/m(2). Cardiac function was monitored at baseline and then every four cycles by echocardiography. RESULTS: The median number of cycles per patient with all regimens was four (range one to eight). Haematological and gastrointestinal toxicity defined the maximum tolerated doses, at T-80/E-90 mg/m(2) with TEF, T-70/A50/X-2,000 mg/m(2) with TAX and T-70/E-80/X-1,650 mg/m(2) with TEX. Two patients treated with TEF developed transient cardiac toxicity (dilatative cardiomyopathy and coronary subtotal stenosis requiring stenting) after cumulative E doses of 400 mg and 1,100 mg/m(2), respectively. Fifty-nine patients were evaluable for response; the overall response rates (ORR) were comparable between regimens (54% with TEF, 71% with TAX and 86% with TEX), with an 81% ORR in 31 patients with locally advanced disease. CONCLUSIONS: The addition of fluoropyrimidines to weekly, intermittent ET is well tolerated and active in ABC.

Adult↗
PubMed2005

Are all high-grade breast cancers with no steroid receptor hormone expression alike? The special case of the medullary phenotype.

BACKGROUND: Medullary carcinoma (MC) of the breast is associated with favorable prognosis compared with other histological types, despite high nuclear grade, fast proliferation and lack of steroid hormone receptor expression. We retrospectively evaluated the clinical relevance of selected immunohistochemical features of tumors in three cohorts of patients with typical medullary (MC), 'atypical' medullary (AMC) or ductal (DC) breast carcinoma. PATIENTS AND METHODS: Evaluation was performed on node-negative tumor specimens from 40 patients who had either MC (12 patients), AMC (nine patients) or DC (19 patients), treated in a single institution. All had no hormonal receptor, Ki-67 > or =30%, G3, expansive pattern of growth and peritumoral lymphocytic infiltration. In addition, p27, p21 and HER2/neu overexpression, p53, cyclin E and E-cadherin expression, presence of apoptotic cells, stromal tenascin (TN), and type of immune cell infiltration (CD3- and CD68-positive cells) were assessed. RESULTS: No difference in expression of HER2/neu, p21, p27, p53, number of apoptotic cells and CD68-positive cells was detected. Lower levels of stromal TN expression were found in MC compared with DC (P=0.0007), but differences between MC and AMC were not significant (P=0.27). A higher proportion of intratumoral CD3-positive cells was seen in MC than in AMC (P=0.046). No differences were seen between MC and DC (P=0.73). With a median follow-up of 67 months, three patients with DC had relapsed in distant sites, while one patient with AMC had a second primary. Two patients with MC had reappearance of DC in the breast. CONCLUSIONS: The three distinct disease types, selected by having similar high proliferation, had similar expression of cell cycle regulators. The lower expression of TN and massive infiltration of T lymphocytes might both indicate a special interaction between tumor cells and microenvironment, important features for conferring improved prognosis through negligible invasive and metastatic potential to MC. In our series, however, patients with a previous MC are not free from the risk of developing a subsequent DC. Finally, defining AMC as a distinct entity from DC is not justified.

Adult↗